US20050049215A1 - Immunostimulatory nucleic acid molecules - Google Patents
Immunostimulatory nucleic acid molecules Download PDFInfo
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- US20050049215A1 US20050049215A1 US10/888,449 US88844904A US2005049215A1 US 20050049215 A1 US20050049215 A1 US 20050049215A1 US 88844904 A US88844904 A US 88844904A US 2005049215 A1 US2005049215 A1 US 2005049215A1
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Definitions
- oligonucleotides Like DNA, oligodeoxyribonucleotides (ODNs) are able to enter cells in a saturable, sequence independent, and temperature and energy dependent fashion (reviewed in Jaroszewski, J. W., and J. S. Cohen. 1991.
- Lymphocyte ODN uptake has been shown to be regulated by cell activation.
- Spleen cells stimulated with the B cell mitogen LPS had dramatically enhanced ODN uptake in the B cell population, while spleen cells treated with the T cell mitogen Con A showed enhanced ODN uptake by T but not B cells (Krieg, A. M., F. Gmelig-Meyling, M. F. Gourley, W. J. Kisch, L. A. Chrisey, and A. D. Steinberg. 1991. “Uptake of oligodeoxyribonucleotides by lymphoid cells is heterogeneous and inducible”. Antisense Research and Development 1:161).
- poly (I,C) which is a potent inducer of IFN production as well as a macrophage activator and inducer of NK activity
- I,C a potent inducer of IFN production as well as a macrophage activator and inducer of NK activity
- Guanine ribonucleotides substituted at the C8 position with either a bromine or a thiol group are B cell mitogens and may replace “B cell differentiation factors” (Feldbush, T. L., and Z. K. Ballas. 1985. “Lymphokine-like activity of 8-mercaptoguanosine: induction of T and B cell differentiation”. J. Immunol. 134:3204; and Goodman, M. G. 1986. “Mechanism of synergy between T cell signals and C8-substituted guanine nucleosides in humoral immunity: B lymphotropic cytokines induce responsiveness to 8-mercaptoguanosine”. J. Immunol. 136:3335).
- 8-mercaptoguanosine and 8-bromoguanosine also can substitute for the cytokine requirement for the generation of MHC restricted CTL (Feldbush, T. L., 1985. cited supra), augment murine NK activity (Koo, G. C., M. E. Jewell, C. L. Manyak, N. H. Sigal, and L. S. Wicker. 1988. “Activation of murine natural killer cells and macrophages by 8-bromoguanosine”. J. Immunol. 140:3249), and synergize with IL-2 in inducing murine LAK generation (Thompson, R. A., and Z. K. Ballas. 1990. “Lymphokine-activated killer (LAK) cells.
- CREB cAMP response element binding protein
- ATF activating transcription factor
- CREB/ATF family of transcription factors is a ubiquitously expressed class of transcription factors of which 11 members have so far been cloned (reviewed in de Groot, R. P., and P. Sassone-Corsi: “Hormonal control of gene expression: Multiplicity and versatility of cyclic adenosine 3′,5′-monophosphate-responsive nuclear regulators”. Mol. Endocrin. 7:145, 1993; Lee, K. A. W., and N. Masson: “Transcriptional regulation by CREB and its relatives”. Biochim. Biophys. Acta 1174:221, 1993.).
- bZip basic region/leucine zipper
- All cells appear to express one or more CREB/ATF proteins, but the members expressed and the regulation of mRNA splicing appear to be tissue-specific. Differential splicing of activation domains can determine whether a particular CREB/ATF protein will be a transcriptional inhibitor or activator. Many CREB/ATF proteins activate viral transcription, but some splicing variants which lack the activation domain are inhibitory.
- CREB/ATF proteins can bind DNA as homo- or hetero-dimers through the cAMP response element, the CRE, the consensus form of which is the umethylated sequence TGACGTC (binding is abolished if the CpG is methylated) (Iguchi-Ariga, S. M. M., and W. Schaffner: “CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation”. Genes & Develop. 3:612, 1989.).
- CREB/ATF proteins appear to regulate the expression of multiple genes through the CRE including immunologically important genes such as fos, jun B, Rb-1, IL-6, IL-1 (Tsukada, J., K. Saito, W. R. Waterman, A. C. Webb, and P. E. Auron: “Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 ⁇ gene”. Mol. Cell.
- Ehrlich “Binding of AP-1/CREB proteins and of MDBP to contiguous sites downstream of the human TGF-B1 gene”. Biochim. Biophys. Acta 1219:55, 1994.), TGF- ⁇ 2, class II MHC (Cox, P. M., and C. R. Goding: “An ATF/CREB binding motif is required for aberrant constitutive expression of the MHC class II DRa promoter and activation by SV40 T-antigen”. Nucl. Acids Res. 20:4881, 1992.), E-selectin, GM-CSF, CD-8 ⁇ , the germline Ig ⁇ constant region gene, the TCR V ⁇ gene, and the proliferating cell nuclear antigen (Huang, D., P. M.
- Activation of CREB through the cyclic AMP pathway requires protein kinase A (PKA), which phosphorylates CREB 341 on ser 133 and allows it to bind to a recently cloned protein, CBP (Kwok, R. P. S., J. R. Lundblad, J. C. Chrivia, J. P. Richards, H. P. Bachinger, R. G. Brennan, S. G. E. Roberts, M. R. Green, and R. H. Goodman: “Nuclear protein CBP is a coactivator for the transcription factor CREB”. Nature 370:223, 1994; Arias, J., A. S. Alberts, P. Brindle, F. X.
- PKA protein kinase A
- CBP basal transcription factor
- TFIIB basal transcription factor
- CREB also has been reported to interact with dTAFII 110, a TATA binding protein-associated factor whose binding may regulate transcription (Ferreri, K., G. Gill, and M. Montminy: “The cAMP-regulated transcription factor CREB interacts with a component of the TFIID complex”. Proc. Natl. Acad. Sci. USA 91:1210, 1994.).
- CREB/ATF proteins can specifically bind multiple other nuclear factors (Hoeffler, J. P., J. W. Lustbader, and C. -Y. Chen: “Identification of multiple nuclear factors that interact with cyclic adenosine 3′,5′-monophosphate response element-binding protein and activating transcription factor-2 by protein-protein interactions”. Mol. Endocrinol. 5:256, 1991) but the biologic significance of most of these interactions is unknown.
- CREB is normally thought to bind DNA either as a homodimer or as a heterodimer with several other proteins.
- CREB monomers constitutively activate transcription Krajewski, W., and K. A. W. Lee: “A monomeric derivative of the cellular transcription factor CREB functions as a constitutive activator”. Mol. Cell. Biol. 14:7204, 1994.).
- cytomegalovirus immediate early promoter one of the strongest known mammalian promoters, contains eleven copies of the CRE which are essential for promoter function (Chang, Y. -N., S. Crawford, J. Stall, D. R. Rawlins, K. -T. Jeang, and G. S. Hayward: “The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements”. J. Virol.
- HTLV-1 Human T lymphotropic virus-I
- oligonucleotides do not include a GCG trinucleotide sequence at or near the 5′ and/or 3′ terminals and/or the consensus mitogenic CpG motif is not a palindrome.
- Prolonged immunostimulation can be obtained using stabilized oligonucleotides, particularly phosphorothioate stabilized oligonucleotides.
- the invention features useful therapies, which are based on the immunostimulatory activity of the nucleic acid molecules.
- the immunostimulatory nucleic acid molecules can be used to treat, prevent or ameliorate an immune system deficiency (e.g., a tumor or cancer or a viral, fungal, bacterial or parasitic infection in a subject).
- an immune system deficiency e.g., a tumor or cancer or a viral, fungal, bacterial or parasitic infection in a subject.
- immunostimulatory nucleic acid molecules can be administered to stimulate a subject's response to a vaccine.
- the instant claimed nucleic acid molecules can be administered to treat or prevent the symptoms of asthma.
- the instant claimed nucleic acid molecules can be administered in conjunction with a particular allergen to a subject as a type of desensitization therapy to treat or prevent the occurrence of an allergic reaction.
- immunostimulatory nucleic acid molecules to induce leukemic cells to enter the cell cycle supports the use of immunostimulatory nucleic acid molecules in treating leukemia by increasing the sensitivity of chronic leukemia cells and then administering conventional ablative chemotherapy, or combining the immunostimulatory nucleic acid molecules with another immunotherapy.
- FIG. 1A -C are graphs plotting dose-dependent IL-6 production in response to various DNA sequences in T cell depleted spleen cell cultures.
- ODN phosphodiester oligodeoxynucleotide
- SEQ ID NO:1 ATGGAAGGTCCAGTGTTCTC 3′
- CpG ODN 5′ ATCGACCTACGTGCGTTCTC 3′
- SEQ ID NO:3 5′ TCCATAACGTTCCTGATGCT 3′
- FIG. 2 is a graph plotting IL-6 production induced by CpG DNA in vivo as determined 1-8 hrs after injection. Data represent the mean from duplicate analyses of sera from two mice. BALB/c mice (two mice/group) were injected iv. with 100 ill of PBS ( ⁇ ) or 200 ⁇ g of CpG phosphorothioate ODN 5′ TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) ( ⁇ ) or non-CpG phosphorothioate ODN 5′ TCCATGAGCTTCCTGAGTCT 3′ (SEQ ID NO:8) ( ⁇ ).
- FIG. 3 is an autoradiograph showing IL-6 mRNA expression as determined by reverse transcription polymerase chain reaction in liver, spleen, and thymus at various time periods after in vivo stimulation of BALB/c mice (two mice/group) injected iv with 100 ⁇ l of PBS, 200 ⁇ g of CpG phosphorothioate ODN 5′ TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) or non-CpG phosphorothioate ODN 5′ TCCATGAGCTTCCTGAGTCT 3′ (SEQ ID NO:8).
- FIG. 4A is a graph plotting dose-dependent inhibition of CpG-induced IgM production by anti-IL-6.
- Splenic B-cells from DBA/2 mice were stimulated with CpG ODN 5′ TCCAAGACGTTCCTGATGCT 3′ (SEQ ID NO:9) in the presence of the indicated concentrations of neutralizing anti-IL-6 ( ⁇ ) or isotype control Ab ( ⁇ ) and IgM levels in culture supernatants determined by ELISA.
- ⁇ neutralizing anti-IL-6
- ⁇ isotype control Ab
- IgM levels in culture supernatants determined by ELISA.
- the anti-IL-6 Ab had no effect on IgM secretion ( ⁇ ).
- FIG. 4B is a graph plotting the stimulation index of CpG-induced splenic B cells cultured with anti-IL-6 and CpG S-ODN 5′ TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) ( ⁇ ) or anti-IL-6 antibody only ( ⁇ ). Data present the mean ⁇ standard deviation of triplicates.
- FIG. 5 is a bar graph plotting chloramphenicol acetyltransferase (CAT) activity in WEHI-231 cells transfected with a promoter-less CAT construct (pCAT), positive control plasmid (RSV), or IL-6 promoter-CAT construct alone or cultured with CpG 5′ TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) or non-CpG 5′ TCCATGAGCTTCCTGAGTCT 3′ (SEQ ID NO:8) phosphorothioate ODN at the indicated concentrations. Data present the mean of triplicates.
- FIG. 6 is a schematic overview of the immune effects of the immunostimulatory unmethylated CpG containing nucleic acids, which can directly activate both B cells and monocytic cells (including macrophages and dendritic cells) as shown.
- the immunostimulatory oligonucleotides do not directly activate purified NK cells, but render them competent to respond to IL-12 with a marked increase in their IFN- ⁇ production.
- the immunostimulatory nucleic acids promote a Th1 type immune response. No direct activation of proliferation of cytokine secretion by highly purified T cells has been found. However, the induction of Th1 cytokine secretion by the immunostimulatory oligonucleotides promotes the development of a cytotoxic lymphocyte response.
- FIG. 7 is an autoradiograph showing NF ⁇ B mRNA induction in monocytes treated with E. coli (EC) DNA (containing unmethylated CpG motifs), control (CT) DNA (containing no unmethylated CpG motifs) and lipopolysaccharide (LPS) at various measured times, 15 and 30 minutes after contact.
- E. coli E. coli
- CT control
- LPS lipopolysaccharide
- FIG. 8A shows the results from a flow cytometry study using mouse B cells with the dihydrorhodamine 123 dye to determine levels of reactive oxygen species.
- the dye only sample in Panel A of the figure shows the background level of cells positive for the dye at 28.6%.
- This level of reactive oxygen species was greatly increased to 80% in the cells treated for 20 minutes with PMA and ionomycin, a positive control (Panel B).
- the cells treated with the CpG oligo (TCCATGACGTTCCTGACGTT SEQ ID NO:10) also showed an increase in the level of reactive oxygen species such that more than 50% of the cells became positive (Panel D).
- FIG. 8B shows the results from a flow cytometry study using mouse B cells in the presence of chloroquine with the dihydrorhodamine 123 dye to determine levels of reactive oxygen species. Chloroquine slightly lowers the background level of reactive oxygen species in the cells such that the untreated cells in Panel A have only 4.3% that are positive. Chloroquine completely abolishes the induction of reactive oxygen species in the cells treated with CpG DNA (Panel B) but does not reduce the level of reactive oxygen species in the cells treated with PMA and ionomycin (Panel E).
- FIG. 9 is a graph plotting lung lavage cell count over time.
- the graph shows that when the mice are initially injected with Schistosoma mansoni eggs “egg”, which induces a Th2 immune response, and subsequently inhale Schistosoma mansoni egg antigen “SEA” (open circle), many inflammatory cells are present in the lungs.
- SEA Schistosoma mansoni egg antigen
Abstract
Description
- This application is a divisional of co-pending U.S. patent application Ser. No. 08/738,652, filed Oct. 30, 1996, which is a continuation-in-part of U.S. patent application Ser. No. 08/386,063, filed Feb. 7, 1995, now issued as U.S. Pat. No. 6,194,388, which is a continuation-in-part of U.S. patent application Ser. No. 08/276,358, filed Jul. 15, 1994, now abandoned.
- The work resulting in this invention was supported in part by National Institute of Health Grant No. R29-AR42556-01. The U.S. Government may therefore be entitled to certain rights in the invention.
- DNA binds to cell membranes and is internalized In the 1970's, several investigators reported the binding of high molecular weight DNA to cell membranes (Lerner, R. A., W. Meinke, and D. A. Goldstein. 1971. “Membrane-associated DNA in the cytoplasm of diploid human lymphocytes”. Proc. Natl. Acad. Sci. USA 68:1212; Agrawal, S. K., R. W. Wagner, P. K. McAllister, and B. Rosenberg. 1975. “Cell-surface-associated nucleic acid in tumorigenic cells made visible with platinum-pyrimidine complexes by electron microscopy”. Proc. Natl. Acad. Sci. USA 72:928). In 1985, Bennett et al. presented the first evidence that DNA binding to lymphocytes is similar to a ligand receptor interaction: binding is saturable, competitive, and leads to DNA endocytosis and degradation into oligonucleotides (Bennett, R. M., G. T. Gabor, and M. M. Merritt. 1985. “DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA”. J. Clin. Invest. 76:2182). Like DNA, oligodeoxyribonucleotides (ODNs) are able to enter cells in a saturable, sequence independent, and temperature and energy dependent fashion (reviewed in Jaroszewski, J. W., and J. S. Cohen. 1991. “Cellular uptake of antisense oligodeoxynucleotides”. Advanced Drug Delivery Reviews 6:235; Akhtar, S., Y. Shoji, and R. L. Juliano. 1992. “Pharmaceutical aspects of the biological stability and membrane transport characteristics of antisense oligonucleotides”. In: Gene Regulation: Biology of Antisense RNA and DNA. R. P. Erickson, and J. G. Izant, eds. Raven Press, Ltd. New York, pp. 133; and Zhao, Q., T. Waldschmidt, E. Fisher, C. J. Herrera, and A. M. Krieg., 1994. “Stage specific oligonucleotide uptake in murine bone marrow B cell precursors”. Blood, 84:3660). No receptor for DNA or ODN uptake has yet been cloned, and it is not yet clear whether ODN binding and cell uptake occurs through the same or a different mechanism from that of high molecular weight DNA.
- Lymphocyte ODN uptake has been shown to be regulated by cell activation. Spleen cells stimulated with the B cell mitogen LPS had dramatically enhanced ODN uptake in the B cell population, while spleen cells treated with the T cell mitogen Con A showed enhanced ODN uptake by T but not B cells (Krieg, A. M., F. Gmelig-Meyling, M. F. Gourley, W. J. Kisch, L. A. Chrisey, and A. D. Steinberg. 1991. “Uptake of oligodeoxyribonucleotides by lymphoid cells is heterogeneous and inducible”. Antisense Research and Development 1:161).
- Immune Effects of Nucleic Acids
- Several polynucleotides have been extensively evaluated as biological response modifiers. Perhaps the best example is poly (I,C) which is a potent inducer of IFN production as well as a macrophage activator and inducer of NK activity (Talmadge, J. E., J. Adams, H. Phillips, M. Collins, B. Lenz, M. Schneider, E. Schlick, R. Ruffmann, R. H. Wiltrout, and M. A. Chirigos. 1985. “Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose”. Cancer Res. 45:1058; Wiltrout, R. H., R. R. Salup, T. A. Twilley, and J. E. Talmadge. 1985. “Immunomodulation of natural killer activity by polyribonucleotides”. J. Biol. Resp. Mod. 4:512; Krown, S. E. 1986. “Interferons and interferon inducers in cancer treatment”. Sem. Oncol. 13:207; and Ewel, C. H., S. J. Urba, W. C. Kopp, J. W. Smith II, R. G. Steis, J. L. Rossio, D. L. Longo, M. J. Jones, W. G. Alvord, C. M. Pinsky, J. M. Beveridge, K. L. McNitt, and S. P. Creekmore. 1992. “Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin-2 in patients with cancer: clinical and immunological effects”. Canc. Res. 52:3005). It appears that this murine NK activation may be due solely to induction of IFN-β secretion (Ishikawa, R., and C. A. Biron. 1993. “IFN induction and associated changes in splenic leukocyte distribution”. J. Immunol. 150:3713). This activation was specific for the ribose sugar since deoxyribose was ineffective. Its potent in vitro antitumor activity led to several clinical trials using poly (I,C) complexed with poly-L-lysine and carboxymethylcellulose (to reduce degradation by RNAse) (Talmadge, J. E., et al., 1985. cited supra; Wiltrout, R. H., et al., 1985. cited supra); Krown, S. E., 1986. cited supra); and Ewel, C. H., et al., 1992. cited supra). Unfortunately, toxic side effects have thus far prevented poly (I,C) from becoming a useful therapeutic agent.
- Guanine ribonucleotides substituted at the C8 position with either a bromine or a thiol group are B cell mitogens and may replace “B cell differentiation factors” (Feldbush, T. L., and Z. K. Ballas. 1985. “Lymphokine-like activity of 8-mercaptoguanosine: induction of T and B cell differentiation”. J. Immunol. 134:3204; and Goodman, M. G. 1986. “Mechanism of synergy between T cell signals and C8-substituted guanine nucleosides in humoral immunity: B lymphotropic cytokines induce responsiveness to 8-mercaptoguanosine”. J. Immunol. 136:3335). 8-mercaptoguanosine and 8-bromoguanosine also can substitute for the cytokine requirement for the generation of MHC restricted CTL (Feldbush, T. L., 1985. cited supra), augment murine NK activity (Koo, G. C., M. E. Jewell, C. L. Manyak, N. H. Sigal, and L. S. Wicker. 1988. “Activation of murine natural killer cells and macrophages by 8-bromoguanosine”. J. Immunol. 140:3249), and synergize with IL-2 in inducing murine LAK generation (Thompson, R. A., and Z. K. Ballas. 1990. “Lymphokine-activated killer (LAK) cells. V. 8-Mercaptoguanosine as an IL-2-sparing agent in LAK generation”. J. Immunol. 145:3524). The NK and LAK augmenting activities of these C8-substituted guanosines appear to be due to their induction of IFN (Thompson, R. A., et al. 1990. cited supra). Recently, a 5′ triphosphorylated thymidine produced by a mycobacterium was found to be mitogenic for a subset of human γδ T cells (Constant, P., F. Davodeau, M. -A. Peyrat, Y. Poquet, G. Puzo, M. Bonneville, and J. -J. Foumie. 1994. “Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands” Science 264:267). This report indicated the possibility that the immune system may have evolved ways to preferentially respond to microbial nucleic acids.
- Several observations suggest that certain DNA structures may also have the potential to activate lymphocytes. For example, Bell et al. reported that nucleosomal protein-DNA complexes (but not naked DNA) in spleen cell supernatants caused B cell proliferation and immunoglobulin secretion (Bell, D. A., B. Morrison, and P. VandenBygaart. 1990. “Immunogenic DNA-related factors”. J. Clin. Invest. 85:1487). In other cases, naked DNA has been reported to have immune effects. For example, Messina et al. have recently reported that 260 to 800 bp fragments of poly (dG)·(dC) and poly (dG·dC) were mitogenic for B cells (Messina, J. P., G. S. Gilkeson, and D. S. Pisetsky. 1993. “The influence of DNA structure on the in vitro stimulation of murine lymphocytes by natural and synthetic polynucleotide antigens”. Cell. Immunol. 147:148). Tokunaga, et al. have reported that dG·dC induces IFN-γ and NK activity (Tokunaga, S. Yamamoto, and K. Namba. 1988. “A synthetic single-stranded DNA, poly(dG,dC), induces interferon-α/β and -γ, augments natural killer activity, and suppresses tumor growth” Jpn. J Cancer Res. 79:682). Aside from such artificial homopolymer sequences, Pisetsky et al. reported that pure mammalian DNA has no detectable immune effects, but that DNA from certain bacteria induces B cell activation and immunoglobulin secretion (Messina, J. P., G. S. Gilkeson, and D. S. Pisetsky. 1991. “Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA”. J. Immunol. 147:1759). Assuming that these data did not result from some unusual contaminant, these studies suggested that a particular structure or other characteristic of bacterial DNA renders it capable of triggering B cell activation. Investigations of mycobacterial DNA sequences have demonstrated that ODN which contain certain palindrome sequences can activate NK cells (Yamamoto, S., T. Yamamoto, T. Kataoka, E. Kuramoto, O. Yano, and T. Tokunaga. 1992. “Unique palindromic sequences in synthetic oligonucleotides are required to induce INF and augment INF-mediated natural killer activity”. J. Immunol. 148:4072; Kuramoto, E., O. Yano, Y. Kimura, M. Baba, T. Makino, S. Yamamoto, T. Yamamoto, T. Kataoka, and T. Tokunaga. 1992. “Oligonucleotide sequences required for natural killer cell activation”. Jpn. J. Cancer Res. 83:1128).
- Several phosphorothioate modified ODN have been reported to induce in vitro or in vivo B cell stimulation (Tanaka, T., C. C. Chu, and W. E. Paul. 1992. “An antisense oligonucleotide complementary to a sequence in Iγ2b increases γ2b germline transcripts, stimulates B cell DNA synthesis, and inhibits immunoglobulin secretion”. J. Exp. Med. 175:597; Branda, R. F., A. L. Moore, L. Mathews, J. J. McCormack, and G. Zon. 1993. “Immune stimulation by an antisense oligomer complementary to the rev gene of HIV-1”. Biochem. Pharmacol. 45:2037; McIntyre, K. W., K. Lombard-Gillooly, J. R. Perez, C. Kunsch, U. M. Sarmiento, J. D. Larigan, K. T. Landreth, and R. Narayanan. 1993. “A sense phosphorothioate oligonucleotide directed to the initiation codon of transcription factor NFκB T65 causes sequence-specific immune stimulation”. Antisense Res. Develop. 3:309; and Pisetsky, D. S., and C. F. Reich. 1993. “Stimulation of murine lymphocyte proliferation by a phosphorothioate oligonucleotide with antisense activity for herpes simplex virus”. Life Sciences 54:101). These reports do not suggest a common structural motif or sequence element in these ODN that might explain their effects.
- The CREB/ATF Family of Transcription Factors and Their Role in Replication
- The cAMP response element binding protein (CREB) and activating transcription factor (ATF) or CREB/ATF family of transcription factors is a ubiquitously expressed class of transcription factors of which 11 members have so far been cloned (reviewed in de Groot, R. P., and P. Sassone-Corsi: “Hormonal control of gene expression: Multiplicity and versatility of
cyclic adenosine 3′,5′-monophosphate-responsive nuclear regulators”. Mol. Endocrin. 7:145, 1993; Lee, K. A. W., and N. Masson: “Transcriptional regulation by CREB and its relatives”. Biochim. Biophys. Acta 1174:221, 1993.). They all belong to the basic region/leucine zipper (bZip) class of proteins. All cells appear to express one or more CREB/ATF proteins, but the members expressed and the regulation of mRNA splicing appear to be tissue-specific. Differential splicing of activation domains can determine whether a particular CREB/ATF protein will be a transcriptional inhibitor or activator. Many CREB/ATF proteins activate viral transcription, but some splicing variants which lack the activation domain are inhibitory. CREB/ATF proteins can bind DNA as homo- or hetero-dimers through the cAMP response element, the CRE, the consensus form of which is the umethylated sequence TGACGTC (binding is abolished if the CpG is methylated) (Iguchi-Ariga, S. M. M., and W. Schaffner: “CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation”. Genes & Develop. 3:612, 1989.). - The transcriptional activity of the CRE is increased during B cell activation (Xie, H. T. C. Chiles, and T. L. Rothstein: “Induction of CREB activity via the surface Ig receptor of B cells”. J. Immunol. 151:880, 1993.). CREB/ATF proteins appear to regulate the expression of multiple genes through the CRE including immunologically important genes such as fos, jun B, Rb-1, IL-6, IL-1 (Tsukada, J., K. Saito, W. R. Waterman, A. C. Webb, and P. E. Auron: “Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1β gene”. Mol. Cell. Biol. 14:7285, 1994; Gray, G. D., O. M. Hernandez, D. Hebel, M. Root, J. M. Pow-Sang, and E. Wickstrom: “Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice”. Cancer Res. 53:577, 1993), IFN-β (Du, W., and T. Maniatis: “An ATF/CREB binding site protein is required for virus induction of the human interferon B gene”. Proc. Natl. Acad. Sci. USA 89:2150, 1992), TGF-β1 (Asiedu, C. K., L. Scott, R. K. Assoian, M. Ehrlich: “Binding of AP-1/CREB proteins and of MDBP to contiguous sites downstream of the human TGF-B1 gene”. Biochim. Biophys. Acta 1219:55, 1994.), TGF-β2, class II MHC (Cox, P. M., and C. R. Goding: “An ATF/CREB binding motif is required for aberrant constitutive expression of the MHC class II DRa promoter and activation by SV40 T-antigen”. Nucl. Acids Res. 20:4881, 1992.), E-selectin, GM-CSF, CD-8α, the germline Igα constant region gene, the TCR Vβ gene, and the proliferating cell nuclear antigen (Huang, D., P. M. Shipman-Appasamy, D. J. Orten, S. H. Hinrichs, and M. B. Prystowsky: “Promoter activity of the proliferating-cell nuclear antigen gene is associated with inducible CRE-binding proteins in interleukin 2-stimulated T lymphocytes”. Mol. Cell. Biol. 14:4233, 1994.). In addition to activation through the cAMP pathway, CREB can also mediate transcriptional responses to changes in intracellular Ca++ concentration (Sheng, M., G. McFadden, and M. E. Greenberg: “Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB”. Neuron 4:571, 1990).
- The role of protein-protein interactions in transcriptional activation by CREB/ATF proteins appears to be extremely important. There are several published studies reporting direct or indirect interactions between NFκB proteins and CREB/ATF proteins (Whitley, et. al., (1994) Mol. & Cell. Biol. 14:6464; Cogswell, et al., (1994) J. Immun. 153:712; Hines, et al., (1993) Oncogene 8:3189; and Du, et al., (1993) Cell 74:887. Activation of CREB through the cyclic AMP pathway requires protein kinase A (PKA), which phosphorylates CREB341 on ser133 and allows it to bind to a recently cloned protein, CBP (Kwok, R. P. S., J. R. Lundblad, J. C. Chrivia, J. P. Richards, H. P. Bachinger, R. G. Brennan, S. G. E. Roberts, M. R. Green, and R. H. Goodman: “Nuclear protein CBP is a coactivator for the transcription factor CREB”. Nature 370:223, 1994; Arias, J., A. S. Alberts, P. Brindle, F. X. Claret, T. Smea, M. Karin, J. Feramisco, and M. Montminy: “Activation of cAMP and mitogen responsive genes relies on a common nuclear factor”. Nature 370:226, 1994.). CBP in turn interacts with the basal transcription factor TFIIB causing increased transcription. CREB also has been reported to interact with
dTAFII 110, a TATA binding protein-associated factor whose binding may regulate transcription (Ferreri, K., G. Gill, and M. Montminy: “The cAMP-regulated transcription factor CREB interacts with a component of the TFIID complex”. Proc. Natl. Acad. Sci. USA 91:1210, 1994.). In addition to these interactions, CREB/ATF proteins can specifically bind multiple other nuclear factors (Hoeffler, J. P., J. W. Lustbader, and C. -Y. Chen: “Identification of multiple nuclear factors that interact withcyclic adenosine 3′,5′-monophosphate response element-binding protein and activating transcription factor-2 by protein-protein interactions”. Mol. Endocrinol. 5:256, 1991) but the biologic significance of most of these interactions is unknown. CREB is normally thought to bind DNA either as a homodimer or as a heterodimer with several other proteins. Surprisingly, CREB monomers constitutively activate transcription (Krajewski, W., and K. A. W. Lee: “A monomeric derivative of the cellular transcription factor CREB functions as a constitutive activator”. Mol. Cell. Biol. 14:7204, 1994.). - Aside from their critical role in regulating cellular transcription, it has recently been shown that CREB/ATF proteins are subverted by some infectious viruses and retroviruses, which require them for viral replication. For example, the cytomegalovirus immediate early promoter, one of the strongest known mammalian promoters, contains eleven copies of the CRE which are essential for promoter function (Chang, Y. -N., S. Crawford, J. Stall, D. R. Rawlins, K. -T. Jeang, and G. S. Hayward: “The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements”. J. Virol. 64:264, 1990). At least some of the transcriptional activating effects of the adenovirus E1A protein, which induces many promoters, are due to its binding to the DNA binding domain of the CREB/ATF protein, ATF-2, which mediates E1A inducible transcription activation (Liu, F., and M. R. Green: “Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains”. Nature 368:520, 1994). It has also been suggested that E1A binds to the CREB-binding protein, CBP (Arany, Z., W. R. Sellers, D. M. Livingston, and R. Eckner: “E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators”. Cell 77:799, 1994). Human T lymphotropic virus-I (HTLV-1), the retrovirus which causes human T cell leukemia and tropical spastic paresis, also requires CREB/ATF proteins for replication. In this case, the retrovirus produces a protein, Tax, oligonucleotides do not include a GCG trinucleotide sequence at or near the 5′ and/or 3′ terminals and/or the consensus mitogenic CpG motif is not a palindrome. Prolonged immunostimulation can be obtained using stabilized oligonucleotides, particularly phosphorothioate stabilized oligonucleotides.
- In a second aspect, the invention features useful therapies, which are based on the immunostimulatory activity of the nucleic acid molecules. For example, the immunostimulatory nucleic acid molecules can be used to treat, prevent or ameliorate an immune system deficiency (e.g., a tumor or cancer or a viral, fungal, bacterial or parasitic infection in a subject). In addition, immunostimulatory nucleic acid molecules can be administered to stimulate a subject's response to a vaccine.
- Further, by redirecting a subject's immune response from Th2 to Th1, the instant claimed nucleic acid molecules can be administered to treat or prevent the symptoms of asthma. In addition, the instant claimed nucleic acid molecules can be administered in conjunction with a particular allergen to a subject as a type of desensitization therapy to treat or prevent the occurrence of an allergic reaction.
- Further, the ability of immunostimulatory nucleic acid molecules to induce leukemic cells to enter the cell cycle supports the use of immunostimulatory nucleic acid molecules in treating leukemia by increasing the sensitivity of chronic leukemia cells and then administering conventional ablative chemotherapy, or combining the immunostimulatory nucleic acid molecules with another immunotherapy.
- Other features and advantages of the invention will become more apparent from the following detailed description and claims.
-
FIG. 1A -C are graphs plotting dose-dependent IL-6 production in response to various DNA sequences in T cell depleted spleen cell cultures. A. E. coli DNA (●) and calf thymus DNA (▪) sequences and LPS (at 10× the concentration of E. coli and calf thymus DNA) (♦). B. Control phosphodiester oligodeoxynucleotide (ODN) 5′ATGGAAGGTCCAGTGTTCTC3′ (SEQ ID NO:1) (▪) and two phosphodiester CpG ODN5′ATCGACCTACGTGCGTTCTC3′ (SEQ ID NO:2) (♦) and 5′TCCATAACGTTCCTGATGCT3′ (SEQ ID NO:3) (●). C. Control phosphorothioate ODN5′GCTAGATGTTAGCGT3′ (SEQ ID NO:4) (▪) and two phosphorothioate CpG ODN5′GAGAACGTCGACCTTCGAT3′ (SEQ ID NO:5) (♦) and 5′GCATGACGTTGAGCT3′ (SEQ ID NO:6) (●). Data present the mean±standard deviation of triplicates. -
FIG. 2 is a graph plotting IL-6 production induced by CpG DNA in vivo as determined 1-8 hrs after injection. Data represent the mean from duplicate analyses of sera from two mice. BALB/c mice (two mice/group) were injected iv. with 100 ill of PBS (□) or 200 μg ofCpG phosphorothioate ODN 5′TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) (ζ) ornon-CpG phosphorothioate ODN 5′TCCATGAGCTTCCTGAGTCT 3′ (SEQ ID NO:8) (♦). -
FIG. 3 is an autoradiograph showing IL-6 mRNA expression as determined by reverse transcription polymerase chain reaction in liver, spleen, and thymus at various time periods after in vivo stimulation of BALB/c mice (two mice/group) injected iv with 100 μl of PBS, 200 μg ofCpG phosphorothioate ODN 5′TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) ornon-CpG phosphorothioate ODN 5′TCCATGAGCTTCCTGAGTCT 3′ (SEQ ID NO:8). -
FIG. 4A is a graph plotting dose-dependent inhibition of CpG-induced IgM production by anti-IL-6. Splenic B-cells from DBA/2 mice were stimulated with CpG ODN5′TCCAAGACGTTCCTGATGCT3′ (SEQ ID NO:9) in the presence of the indicated concentrations of neutralizing anti-IL-6 (♦) or isotype control Ab (●) and IgM levels in culture supernatants determined by ELISA. In the absence of CpG ODN, the anti-IL-6 Ab had no effect on IgM secretion (▪). -
FIG. 4B is a graph plotting the stimulation index of CpG-induced splenic B cells cultured with anti-IL-6 and CpG S-ODN 5′TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) (♦) or anti-IL-6 antibody only (▪). Data present the mean±standard deviation of triplicates. -
FIG. 5 is a bar graph plotting chloramphenicol acetyltransferase (CAT) activity in WEHI-231 cells transfected with a promoter-less CAT construct (pCAT), positive control plasmid (RSV), or IL-6 promoter-CAT construct alone or cultured withCpG 5′TCCATGACGTTCCTGATGCT 3′ (SEQ ID NO:7) or non-CpG 5′TCCATGAGCTTCCTGAGTCT 3′ (SEQ ID NO:8) phosphorothioate ODN at the indicated concentrations. Data present the mean of triplicates. -
FIG. 6 is a schematic overview of the immune effects of the immunostimulatory unmethylated CpG containing nucleic acids, which can directly activate both B cells and monocytic cells (including macrophages and dendritic cells) as shown. The immunostimulatory oligonucleotides do not directly activate purified NK cells, but render them competent to respond to IL-12 with a marked increase in their IFN-γ production. By inducing IL-12 production and the subsequent increased IFN-γ secretion by NK cells, the immunostimulatory nucleic acids promote a Th1 type immune response. No direct activation of proliferation of cytokine secretion by highly purified T cells has been found. However, the induction of Th1 cytokine secretion by the immunostimulatory oligonucleotides promotes the development of a cytotoxic lymphocyte response. -
FIG. 7 is an autoradiograph showing NFκB mRNA induction in monocytes treated with E. coli (EC) DNA (containing unmethylated CpG motifs), control (CT) DNA (containing no unmethylated CpG motifs) and lipopolysaccharide (LPS) at various measured times, 15 and 30 minutes after contact. -
FIG. 8A shows the results from a flow cytometry study using mouse B cells with the dihydrorhodamine 123 dye to determine levels of reactive oxygen species. The dye only sample in Panel A of the figure shows the background level of cells positive for the dye at 28.6%. This level of reactive oxygen species was greatly increased to 80% in the cells treated for 20 minutes with PMA and ionomycin, a positive control (Panel B). The cells treated with the CpG oligo (TCCATGACGTTCCTGACGTT SEQ ID NO:10) also showed an increase in the level of reactive oxygen species such that more than 50% of the cells became positive (Panel D). However, cells treated with an oligonucleotide with the identical sequence except that the CpGs were switched (TCCATGAGCTTCCTGAGTGCT SEQ ID NO:11) did not show this significant increase in the level of reactive oxygen species (Panel E). -
FIG. 8B shows the results from a flow cytometry study using mouse B cells in the presence of chloroquine with the dihydrorhodamine 123 dye to determine levels of reactive oxygen species. Chloroquine slightly lowers the background level of reactive oxygen species in the cells such that the untreated cells in Panel A have only 4.3% that are positive. Chloroquine completely abolishes the induction of reactive oxygen species in the cells treated with CpG DNA (Panel B) but does not reduce the level of reactive oxygen species in the cells treated with PMA and ionomycin (Panel E). -
FIG. 9 is a graph plotting lung lavage cell count over time. The graph shows that when the mice are initially injected with Schistosoma mansoni eggs “egg”, which induces a Th2 immune response, and subsequently inhale Schistosoma mansoni egg antigen “SEA” (open circle), many inflammatory cells are present in the lungs. However, when the mice are initially given CpG oligo (SEQ ID NO:10) along with egg, the
Claims (16)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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US10/888,449 US20050049215A1 (en) | 1994-07-15 | 2004-07-09 | Immunostimulatory nucleic acid molecules |
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US27635894A | 1994-07-15 | 1994-07-15 | |
US08/386,063 US6194388B1 (en) | 1994-07-15 | 1995-02-07 | Immunomodulatory oligonucleotides |
US08/738,652 US6207646B1 (en) | 1994-07-15 | 1996-10-30 | Immunostimulatory nucleic acid molecules |
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US6423493B1 (en) * | 1998-10-26 | 2002-07-23 | Board Of Regents The University Of Texas System | Combinatorial selection of oligonucleotide aptamers |
CA2357413A1 (en) * | 1998-12-22 | 2000-06-29 | Panacea Pharmaceuticals, Llc | Sensitizing agents for the treatment of skin lesions |
US6558951B1 (en) * | 1999-02-11 | 2003-05-06 | 3M Innovative Properties Company | Maturation of dendritic cells with immune response modifying compounds |
ES2242604T3 (en) | 1999-02-26 | 2005-11-16 | Chiron Corporation | MICROEMULSIONS WITH MACROPARTICLES AND ADSORBID MICROPARTICLES. |
EP1154790B1 (en) * | 1999-02-26 | 2004-10-20 | Chiron S.r.l. | Enhancement of bactericidal activity of neisseria antigens with oligonucleotides containing cg motifs |
GB2348132B (en) * | 1999-03-02 | 2004-08-04 | Nedaa Abdul-Ghani Nasif | Asthma/allergy therapy that targets t-lymphocytes and/or eosinophils |
FR2790955B1 (en) * | 1999-03-19 | 2003-01-17 | Assist Publ Hopitaux De Paris | USE OF STABILIZED OLIGONUCLEOTIDES AS ANTI-TUMOR ACTIVE INGREDIENT |
US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
WO2000061151A2 (en) | 1999-04-12 | 2000-10-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
US6562801B1 (en) | 1999-04-15 | 2003-05-13 | Board Of Regents, The University Of Texas System | PpGpp and pppGpp as immunomodulatory agents |
US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
GB9908885D0 (en) * | 1999-04-19 | 1999-06-16 | Smithkline Beecham Biolog | Vccine |
HU229255B1 (en) | 1999-04-19 | 2013-10-28 | Smithkline Beecham Biolog | Vaccines |
AU762857B2 (en) * | 1999-04-20 | 2003-07-10 | Smithkline Beecham Biologicals (Sa) | Vaccine |
WO2001000232A2 (en) * | 1999-06-29 | 2001-01-04 | Smithkline Beecham Biologicals S.A. | Use of cpg as an adjuvant for hiv vaccine |
US20050002958A1 (en) * | 1999-06-29 | 2005-01-06 | Smithkline Beecham Biologicals Sa | Vaccines |
US6514948B1 (en) | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
FR2795963A1 (en) * | 1999-07-08 | 2001-01-12 | Pasteur Merieux Serums Vacc | New polynucleotides are useful as vaccines for humans |
DE19935756A1 (en) | 1999-07-27 | 2001-02-08 | Mologen Forschungs Entwicklung | Covalently closed nucleic acid molecule for immune stimulation |
US20050226890A1 (en) * | 1999-08-12 | 2005-10-13 | Cohen David I | Tat-based vaccine compositions and methods of making and using same |
PT1200580E (en) * | 1999-08-13 | 2005-03-31 | Hybridon Inc | MODULATION OF IMMUNITARY STIMULATION MEASURED BY OLIGONUCLEOTIDES CPG THROUGH POSITIONAL MODIFICATION OF NUCLEOSIDOS |
ATE419869T1 (en) * | 1999-08-19 | 2009-01-15 | Dynavax Tech Corp | METHOD FOR MODULATING AN IMMUNE RESPONSE USING IMMUNSTIMULATIVE SEQUENCES AND COMPOSITIONS THEREOF |
US20050249794A1 (en) * | 1999-08-27 | 2005-11-10 | Semple Sean C | Compositions for stimulating cytokine secretion and inducing an immune response |
CA2382611A1 (en) * | 1999-08-27 | 2001-03-08 | Inex Pharmaceuticals Corp. | Compositions for stimulating cytokine secretion and inducing an immune response |
EP1688147A1 (en) * | 1999-09-27 | 2006-08-09 | Coley Pharmaceutical Group, Inc. | Methods Related to Immunostimulatory Nucleic Acid-Induced Interferon |
IL148844A0 (en) * | 1999-09-27 | 2002-09-12 | Coley Pharm Group Inc | Methods related to immunostimulatory nucleic acid-induced interferon |
ES2559317T3 (en) | 1999-10-29 | 2016-02-11 | Glaxosmithkline Biologicals Sa | Neisseria antigenic peptides |
US7223398B1 (en) | 1999-11-15 | 2007-05-29 | Dynavax Technologies Corporation | Immunomodulatory compositions containing an immunostimulatory sequence linked to antigen and methods of use thereof |
ATE378348T1 (en) * | 2000-01-14 | 2007-11-15 | Us Health | OLIGODEOXYNUCLEOTIDES AND THEIR USE FOR INDUCING AN IMMUNE RESPONSE |
AU3108001A (en) * | 2000-01-20 | 2001-12-24 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for inducing a th2 immune response |
WO2001055341A2 (en) * | 2000-01-31 | 2001-08-02 | The Regents Of The University Of California | Immunomodulatory polynucleotides in treatment of an infection by an intracellular pathogen |
US20030130217A1 (en) * | 2000-02-23 | 2003-07-10 | Eyal Raz | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
CA2399550A1 (en) * | 2000-02-23 | 2001-08-30 | The Regents Of The University Of California | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
WO2001062092A1 (en) * | 2000-02-25 | 2001-08-30 | Thomas Jefferson University | Formulations and methods for using the same to elicit an immune response |
US7157437B2 (en) | 2000-03-10 | 2007-01-02 | Dynavax Technologies Corporation | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
US20020098199A1 (en) | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences |
US20030129251A1 (en) | 2000-03-10 | 2003-07-10 | Gary Van Nest | Biodegradable immunomodulatory formulations and methods for use thereof |
US7129222B2 (en) * | 2000-03-10 | 2006-10-31 | Dynavax Technologies Corporation | Immunomodulatory formulations and methods for use thereof |
US20010046967A1 (en) | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
US20020142978A1 (en) * | 2000-04-07 | 2002-10-03 | Eyal Raz | Synergistic improvements to polynucleotide vaccines |
EP1278761B1 (en) * | 2000-05-01 | 2005-04-06 | Hybridon, Inc. | MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES |
US6696064B2 (en) * | 2000-06-20 | 2004-02-24 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of protecting vasculature from damage by diphtheria toxin-and pseudomonas toxin-based immunotoxins during therapy |
WO2001098206A1 (en) | 2000-06-22 | 2001-12-27 | Rxkinetix, Inc. | Delivery vehicle composition and methods for delivering antigens and other drugs |
JP5008244B2 (en) * | 2000-06-23 | 2012-08-22 | ワイス・ホールディングズ・コーポレイション | Assembly of wild-type and chimeric influenza virus-like particles (VLPs) |
WO2002002172A1 (en) * | 2000-06-30 | 2002-01-10 | Univ Jefferson | Dna palindrome - oligoguanylic acid compositions and uses thereof |
US20080044435A1 (en) * | 2004-03-16 | 2008-02-21 | Cohen David I | Tat-Based Tolerogen Compositions and Methods of Making and Using Same |
JP2005503320A (en) * | 2000-08-25 | 2005-02-03 | イエダ・リサーチ・アンド・デベロツプメント・カンパニー・リミテツド | Methods for treating or preventing autoimmune diseases with CpG-containing polynucleotides |
AU9475001A (en) * | 2000-09-26 | 2002-04-08 | Hybridon Inc | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
CA2881568C (en) | 2000-10-27 | 2019-09-24 | Novartis Vaccines And Diagnostics, Inc. | Nucleic acids and proteins from streptococcus groups a & b |
US6677347B2 (en) * | 2000-12-08 | 2004-01-13 | 3M Innovative Properties Company | Sulfonamido ether substituted imidazoquinolines |
WO2006091720A2 (en) * | 2000-12-08 | 2006-08-31 | 3M Innovative Properties Company | Compositions and methods for targeted delivery of immune response modifiers |
WO2002052002A2 (en) * | 2000-12-27 | 2002-07-04 | Dynavax Technologies Corporation | Immunomodulatory polynucleotides and methods of using the same |
CA2434573A1 (en) * | 2001-01-12 | 2002-07-18 | Amato Pharmaceutical Products, Ltd. | Agent for protection against microorganism infection |
US7264810B2 (en) * | 2001-01-19 | 2007-09-04 | Cytos Biotechnology Ag | Molecular antigen array |
DE10290185D2 (en) * | 2001-01-31 | 2004-04-15 | Mologen Forschungs Entwicklung | tumor vaccine |
US20030050268A1 (en) * | 2001-03-29 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid for treatment of non-allergic inflammatory diseases |
WO2002083859A2 (en) * | 2001-04-13 | 2002-10-24 | Wyeth | Surface proteins of streptococcus pyogenes |
US20070128229A1 (en) * | 2002-04-12 | 2007-06-07 | Wyeth | Surface proteins of Streptococcus pyogenes |
KR20080081201A (en) | 2001-04-16 | 2008-09-08 | 와이어쓰 홀딩스 코포레이션 | Novel streptococcus pneumoniae open reading frames encoding polypeptide antigens and a composition comprising the same |
US7034140B2 (en) * | 2001-04-24 | 2006-04-25 | E.I. Du Pont De Nemours And Company | Genes involved in isoprenoid compound production |
WO2002094845A2 (en) | 2001-05-21 | 2002-11-28 | Intercell Ag | Method for stabilising of nucleic acids |
US6818787B2 (en) * | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
GB0115176D0 (en) | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
ES2487645T3 (en) * | 2001-06-21 | 2014-08-22 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of use thereof |
US7785610B2 (en) * | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
US20030138458A1 (en) * | 2001-06-29 | 2003-07-24 | Michael Houghton | HCV E1E2 vaccine compositions |
GB0118249D0 (en) | 2001-07-26 | 2001-09-19 | Chiron Spa | Histidine vaccines |
GB0121591D0 (en) | 2001-09-06 | 2001-10-24 | Chiron Spa | Hybrid and tandem expression of neisserial proteins |
US7666674B2 (en) | 2001-07-27 | 2010-02-23 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo |
US20030148316A1 (en) * | 2001-08-01 | 2003-08-07 | Lipford Grayson B. | Methods and compositions relating to plasmacytoid dendritic cells |
WO2003025119A2 (en) * | 2001-08-03 | 2003-03-27 | Medarex, Inc. | Compositions comprising immunostimulatory oligonucleotides and uses thereof to enhance fc receptor-mediated immunotherapies |
EP1420829A4 (en) * | 2001-08-07 | 2006-05-17 | Dynavax Tech Corp | Immunomodulatory compositions, formulations, and methods for use thereof |
WO2003020884A2 (en) * | 2001-08-14 | 2003-03-13 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Method for rapid generation of mature dendritic cells |
JP4319908B2 (en) | 2001-08-24 | 2009-08-26 | ユニバーシティ オブ ビクトリア イノベーション アンド ディベロップメント コーポレーション | Proaerolysin containing a protease activating sequence and methods of use for the treatment of prostate cancer |
WO2003020889A2 (en) * | 2001-08-30 | 2003-03-13 | 3M Innovative Properties Company | Methods of maturing plasmacytoid dendritic cells using immune response modifier molecules |
JP2005501917A (en) * | 2001-09-07 | 2005-01-20 | ザ トラスティーズ オブ ボストン ユニバーシティ | Methods and compositions for treating immune complex related diseases |
EP1425040A2 (en) * | 2001-09-14 | 2004-06-09 | Cytos Biotechnology AG | In vivo activation of antigen presenting cells for enhancement of immune responses induced by virus like particles |
AU2002339224B2 (en) * | 2001-09-14 | 2008-10-09 | Kuros Us Llc | Packaging of immunostimulatory substances into virus-like particles: method of preparation and use |
WO2003027313A2 (en) | 2001-09-24 | 2003-04-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SUPPRESSORS OF CpG OLIGONUCLEOTIDES AND METHODS OF USE |
US20030119774A1 (en) * | 2001-09-25 | 2003-06-26 | Marianna Foldvari | Compositions and methods for stimulating an immune response |
AR045702A1 (en) | 2001-10-03 | 2005-11-09 | Chiron Corp | COMPOSITIONS OF ASSISTANTS. |
EP1451581A4 (en) * | 2001-10-05 | 2006-01-11 | Coley Pharm Gmbh | Toll-like receptor 3 signaling agonists and antagonists |
WO2003030656A2 (en) | 2001-10-06 | 2003-04-17 | Merial Limited | Methods and compositions for promoting growth and innate immunity in young animals |
US20050238660A1 (en) * | 2001-10-06 | 2005-10-27 | Babiuk Lorne A | Cpg formulations and related methods |
MX339524B (en) | 2001-10-11 | 2016-05-30 | Wyeth Corp | Novel immunogenic compositions for the prevention and treatment of meningococcal disease. |
US7276489B2 (en) * | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
WO2003039595A2 (en) * | 2001-11-07 | 2003-05-15 | Inex Pharmaceuticals Corporation | Mucosal adjuvants comprising an oligonucleotide and a cationic lipid |
US20050085433A1 (en) * | 2001-11-09 | 2005-04-21 | Claudia Breidenstein | Cellular vaccines comprising adjuvants |
US7179798B2 (en) * | 2001-11-16 | 2007-02-20 | Russell R. Roby | Methods and compositions for the treatment of pain and other hormone-allergy-related symptoms using dilute hormone solutions |
US20040014779A1 (en) * | 2001-11-16 | 2004-01-22 | 3M Innovative Properties Company | Methods and compositions related to IRM compounds and toll-like recptor pathways |
US20050250716A1 (en) * | 2001-12-07 | 2005-11-10 | Intercell Ag | Immunostimulatory oligodeoxynucleotides |
US7615227B2 (en) * | 2001-12-20 | 2009-11-10 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce angiogenesis |
CA2365732A1 (en) * | 2001-12-20 | 2003-06-20 | Ibm Canada Limited-Ibm Canada Limitee | Testing measurements |
US8466116B2 (en) | 2001-12-20 | 2013-06-18 | The Unites States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce epithelial cell growth |
CA2471092A1 (en) * | 2001-12-21 | 2003-07-10 | Antigenics Inc. | Compositions comprising immunoreactive reagents and saponins, and methods of use thereof |
JP2005526497A (en) * | 2002-02-04 | 2005-09-08 | ビオミラ,インコーポレーテッド | Immunostimulatory, covalently lipidated oligonucleotide |
US8088388B2 (en) * | 2002-02-14 | 2012-01-03 | United Biomedical, Inc. | Stabilized synthetic immunogen delivery system |
JP4646516B2 (en) | 2002-02-20 | 2011-03-09 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | Fine particles with adsorbed polypeptide-containing molecules |
PT1478327E (en) * | 2002-02-22 | 2015-08-04 | Meda Ab | Method of reducing and treating uvb-induced immunosuppression |
US6923958B2 (en) * | 2002-03-02 | 2005-08-02 | The Scripps Research Institute | DNA vaccines encoding CEA and a CD40 ligand and methods of use thereof |
CA2479187A1 (en) * | 2002-03-15 | 2003-09-25 | Astral, Inc. | Immunostimulatory double stranded rna and methods of inducing, enhancing or modulating the immune response |
EP2258712A3 (en) | 2002-03-15 | 2011-05-04 | Multicell Immunotherapeutics, Inc. | Compositions and Methods to Initiate or Enhance Antibody and Major-histocompatibility Class I or Class II-restricted T Cell Responses by Using Immunomodulatory, Non-coding RNA Motifs |
NZ535754A (en) * | 2002-03-15 | 2007-01-26 | Wyeth Corp | Mutants of the P4 protein of nontypable haemophilus influenzae with reduced enzymatic activity |
US20030224013A1 (en) * | 2002-04-19 | 2003-12-04 | Cole Garry T. | Methods for protection against Coccidioides spp. infection using Coccidioides spp. urea amidohydrolase (Ure) protein |
US20040009943A1 (en) * | 2002-05-10 | 2004-01-15 | Inex Pharmaceuticals Corporation | Pathogen vaccines and methods for using the same |
US20040009944A1 (en) * | 2002-05-10 | 2004-01-15 | Inex Pharmaceuticals Corporation | Methylated immunostimulatory oligonucleotides and methods of using the same |
US20040013649A1 (en) * | 2002-05-10 | 2004-01-22 | Inex Pharmaceuticals Corporation | Cancer vaccines and methods of using the same |
US9045727B2 (en) | 2002-05-17 | 2015-06-02 | Emory University | Virus-like particles, methods of preparation, and immunogenic compositions |
US20060088909A1 (en) * | 2002-05-17 | 2006-04-27 | Compans Richard W | Virus-like particles, methods of preparation, and immunogenic compositions |
KR100456681B1 (en) * | 2002-05-22 | 2004-11-10 | 주식회사 대웅 | Immnune-stimulating and controlling Composition comprising bacterial chromosomal DNA fragments and detoxified lipopolysaccharides |
CA2388049A1 (en) | 2002-05-30 | 2003-11-30 | Immunotech S.A. | Immunostimulatory oligonucleotides and uses thereof |
US20040009949A1 (en) * | 2002-06-05 | 2004-01-15 | Coley Pharmaceutical Group, Inc. | Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory CpG nucleic acids |
BR0311995A (en) * | 2002-06-20 | 2005-04-05 | Cytos Biotechnology Ag | Virus-like particles packaged for use as adjuvants: Method of preparation and use |
CN1678188B (en) * | 2002-07-03 | 2012-10-10 | 科勒制药集团有限公司 | Nucleic acid compositions for stimulating immune responses |
AU2003255969A1 (en) * | 2002-07-17 | 2004-02-02 | Coley Pharmaceutical Gmbh | Use of cpg nucleic acids in prion-disease |
US20060270620A1 (en) * | 2002-07-23 | 2006-11-30 | University Of South Florida | Method of Enhancing Therapeutic Effect of Nucleic Acids |
EP1523557A2 (en) | 2002-07-24 | 2005-04-20 | Intercell AG | Antigens encoded by alternative reading frame from pathogenic viruses |
EP1575504A4 (en) | 2002-08-01 | 2009-11-04 | Us Gov Health & Human Serv | Method of treating inflammatory arthropathies with suppressors of cpg oligonucleotides |
DK1545597T3 (en) | 2002-08-15 | 2011-01-31 | 3M Innovative Properties Co | Immune Stimulating Compositions and Methods for Stimulating an Immune Response |
US7785608B2 (en) * | 2002-08-30 | 2010-08-31 | Wyeth Holdings Corporation | Immunogenic compositions for the prevention and treatment of meningococcal disease |
GB0220194D0 (en) | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
US7595303B1 (en) * | 2002-09-05 | 2009-09-29 | University Of South Florida | Genetic adjuvants for immunotherapy |
US20050196382A1 (en) * | 2002-09-13 | 2005-09-08 | Replicor, Inc. | Antiviral oligonucleotides targeting viral families |
EP1537418A2 (en) | 2002-09-13 | 2005-06-08 | Intercell AG | Method for isolating hepatitis c virus peptides |
EP1537208A1 (en) * | 2002-09-13 | 2005-06-08 | Replicor, Inc. | Non-sequence complementary antiviral oligonucleotides |
US8263091B2 (en) * | 2002-09-18 | 2012-09-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides |
US7301554B2 (en) * | 2002-09-20 | 2007-11-27 | Ricoh Company, Ltd. | Light scanning device, scanning line adjusting method, scanning line adjusting control method, image forming apparatus, and image forming method |
AU2003268737A1 (en) * | 2002-10-02 | 2004-04-23 | Mochida Pharmaceutical Co., Ltd. | Novel method of constructing monoclonal antibody |
US8043622B2 (en) | 2002-10-08 | 2011-10-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides |
BRPI0315228A8 (en) | 2002-10-11 | 2018-04-03 | Chiron Srl | Polypeptide vaccines for broad protection against hypervirulent meningococcal strains |
CA2503457A1 (en) * | 2002-10-25 | 2004-05-06 | University Of Connecticut Health Center | Apparatus and method for immunotherapy of a cancer through controlled cell lysis |
AU2003304107B2 (en) * | 2002-11-01 | 2008-05-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of preventing infections from bioterrorism agents with immunostimulatory CpG oligonucleotides |
WO2004044139A2 (en) * | 2002-11-05 | 2004-05-27 | Isis Parmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
WO2004046177A2 (en) | 2002-11-15 | 2004-06-03 | Chiron Srl | Unexpected surface proteins in neisseria meningitidis |
US8039443B2 (en) * | 2002-11-21 | 2011-10-18 | Archemix Corporation | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
US10100316B2 (en) * | 2002-11-21 | 2018-10-16 | Archemix Llc | Aptamers comprising CPG motifs |
EP2298360A3 (en) * | 2002-11-21 | 2011-07-13 | Bayhill Therapeutics, Inc. | Methods and immune modulatory nucleic acid compositions for preventing and treating disease |
US8853376B2 (en) | 2002-11-21 | 2014-10-07 | Archemix Llc | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
US20050124565A1 (en) * | 2002-11-21 | 2005-06-09 | Diener John L. | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
GB0227346D0 (en) | 2002-11-22 | 2002-12-31 | Chiron Spa | 741 |
AU2003287316A1 (en) * | 2002-12-11 | 2004-06-30 | 3M Innovative Properties Company | Assays relating to toll-like receptor activity |
WO2004052293A2 (en) * | 2002-12-11 | 2004-06-24 | Hawaii Biotech, Inc. | Recombinant vaccine against flavivirus infection |
WO2004053057A2 (en) * | 2002-12-11 | 2004-06-24 | 3M Innovative Properties Company | Gene expression systems and recombinant cell lines |
US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
AU2003302743B2 (en) * | 2002-12-23 | 2008-09-04 | Dynavax Technologies Corporation | Branched immunomodulatory compounds and methods of using the same |
ATE544772T1 (en) | 2002-12-23 | 2012-02-15 | Dynavax Tech Corp | IMMUNO-STIMULATING SEQUENCE OLIGONUCLEOTIDES AND METHOD OF USE THEREOF |
CA2511512C (en) | 2002-12-27 | 2013-10-29 | Chiron Corporation | Immunogenic compositions containing phospholipid |
EP2572714A1 (en) | 2002-12-30 | 2013-03-27 | 3M Innovative Properties Company | Immunostimulatory Combinations |
PT1587537E (en) | 2003-01-30 | 2012-05-30 | Novartis Ag | Injectable vaccines against multiple meningococcal serogroups |
US7354907B2 (en) * | 2003-02-07 | 2008-04-08 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
EP1592302A4 (en) * | 2003-02-13 | 2007-04-25 | 3M Innovative Properties Co | Methods and compositions related to irm compounds and toll-like receptor 8 |
ATE491463T1 (en) | 2003-02-20 | 2011-01-15 | Univ Connecticut Health Ct | METHOD FOR PRODUCING ALPHA (2) MACROGLOBULIN-ANTIGEN MOLECULE COMPLEXES |
GB2398783A (en) | 2003-02-26 | 2004-09-01 | Antonio Lanzavecchia | A method for producing immortalised human B memory lymphocytes |
WO2004075865A2 (en) * | 2003-02-27 | 2004-09-10 | 3M Innovative Properties Company | Selective modulation of tlr-mediated biological activity |
EP1601365A4 (en) | 2003-03-04 | 2009-11-11 | 3M Innovative Properties Co | Prophylactic treatment of uv-induced epidermal neoplasia |
CN100439386C (en) * | 2003-03-05 | 2008-12-03 | 长春华普生物技术有限公司 | Deoxyoligonucleotide containing CpG single strand for strengthening immunological effect of Protein vaccine |
ATE556711T1 (en) * | 2003-03-13 | 2012-05-15 | 3M Innovative Properties Co | METHOD FOR IMPROVING SKIN QUALITY |
WO2004080292A2 (en) | 2003-03-13 | 2004-09-23 | 3M Innovative Properties Company | Method of tattoo removal |
ES2562456T3 (en) | 2003-03-24 | 2016-03-04 | Valneva Austria Gmbh | Use of an adjuvant that induces a Th1 immune response to improve immune responses |
US20040192585A1 (en) | 2003-03-25 | 2004-09-30 | 3M Innovative Properties Company | Treatment for basal cell carcinoma |
CA2520181A1 (en) * | 2003-03-26 | 2004-10-14 | Astral Inc. | Selected rna motifs to include cell death and/or apoptosis |
US20060210588A1 (en) * | 2003-03-26 | 2006-09-21 | Cytos Biotechnology Ag | Hiv-peptide-carrier-conjugates |
AU2004224761A1 (en) | 2003-03-26 | 2004-10-07 | Cytos Biotechnology Ag | HIV-peptide-carrier-conjugates |
US7537767B2 (en) | 2003-03-26 | 2009-05-26 | Cytis Biotechnology Ag | Melan-A- carrier conjugates |
AU2004226605A1 (en) * | 2003-04-02 | 2004-10-14 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations for topical application |
US20040265351A1 (en) * | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
EP1617871A4 (en) * | 2003-04-10 | 2010-10-06 | 3M Innovative Properties Co | Delivery of immune response modifier compounds using metal-containing particulate support materials |
US20060257852A1 (en) | 2003-04-10 | 2006-11-16 | Chiron Corporation | Severe acute respiratory syndrome coronavirus |
EP2623601B1 (en) | 2003-04-21 | 2015-02-18 | Archemix LLC | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
JP4673217B2 (en) * | 2003-04-23 | 2011-04-20 | 由紀夫 佐藤 | Methylated CpG polynucleotide |
US20050250106A1 (en) * | 2003-04-24 | 2005-11-10 | David Epstein | Gene knock-down by intracellular expression of aptamers |
AU2004233851B2 (en) * | 2003-04-25 | 2009-07-30 | Novartis Vaccines And Diagnostics, Inc. | Compositions comprising cationic microparticles and HCV E1E2 DNA and methods of use thereof |
EP1617845A4 (en) * | 2003-04-28 | 2006-09-20 | 3M Innovative Properties Co | Compositions and methods for induction of opioid receptors |
WO2004100965A1 (en) * | 2003-05-15 | 2004-11-25 | Japan Science And Technology Agency | Immunostimulant |
US8080642B2 (en) * | 2003-05-16 | 2011-12-20 | Vical Incorporated | Severe acute respiratory syndrome DNA compositions and methods of use |
ES2328697T5 (en) | 2003-06-02 | 2017-07-25 | Novartis Vaccines And Diagnostics, Inc. | Immunogenic compositions based on microparticles comprising adsorbed toxoid and an antigen containing a polysaccharide |
US7803386B2 (en) | 2003-06-05 | 2010-09-28 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Poly-gamma-glutamic conjugates for eliciting immune responses directed against bacilli |
ES2569927T3 (en) * | 2003-06-11 | 2016-05-13 | Idera Pharmaceuticals, Inc. | Stabilized immunomodulatory oligonucleotides |
KR20060031607A (en) * | 2003-07-10 | 2006-04-12 | 사이토스 바이오테크놀로지 아게 | Packaged virus-like particles |
US20080039533A1 (en) * | 2003-07-31 | 2008-02-14 | 3M Innovative Properties Company | Bioactive Compositions Comprising Triazines |
CA2534313C (en) * | 2003-08-05 | 2013-03-19 | 3M Innovative Properties Company | Formulations containing an immune response modifier |
JP2007502288A (en) * | 2003-08-12 | 2007-02-08 | スリーエム イノベイティブ プロパティズ カンパニー | Oxime-substituted imidazo-containing compounds |
US20050065136A1 (en) * | 2003-08-13 | 2005-03-24 | Roby Russell R. | Methods and compositions for the treatment of infertility using dilute hormone solutions |
US20060035242A1 (en) | 2004-08-13 | 2006-02-16 | Michelitsch Melissa D | Prion-specific peptide reagents |
WO2005020902A2 (en) * | 2003-08-21 | 2005-03-10 | Cytokine Pharmasciences, Inc. | Compositions and methods for treating and diagnosing irritable bowel syndrome |
WO2005020912A2 (en) * | 2003-08-25 | 2005-03-10 | 3M Innovative Properties Company | Delivery of immune response modifier compounds |
WO2005018574A2 (en) * | 2003-08-25 | 2005-03-03 | 3M Innovative Properties Company | Immunostimulatory combinations and treatments |
AU2004268625B2 (en) * | 2003-08-27 | 2011-03-31 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted imidazoquinolines |
EP1663222A4 (en) * | 2003-09-02 | 2008-05-21 | 3M Innovative Properties Co | Methods related to the treatment of mucosal associated conditions |
JP2007504269A (en) * | 2003-09-05 | 2007-03-01 | スリーエム イノベイティブ プロパティズ カンパニー | Method for treating CD5 + B cell lymphoma |
US8541002B2 (en) | 2003-09-12 | 2013-09-24 | Agenus Inc. | Vaccine for treatment and prevention of herpes simplex virus infection |
GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
ES2397923T3 (en) | 2003-10-02 | 2013-03-12 | Novartis Ag | Liquid vaccines for multiple meningococcal serogroups |
US20090075980A1 (en) * | 2003-10-03 | 2009-03-19 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and Analogs Thereof |
US7544697B2 (en) * | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
ES2544477T3 (en) * | 2003-10-03 | 2015-08-31 | 3M Innovative Properties Company | Alkoxy substituted imidazoquinolines |
WO2005034979A2 (en) * | 2003-10-11 | 2005-04-21 | Inex Pharmaceuticals Corporation | Methods and compositions for enhancing innate immunity and antibody dependent cellular cytotoxicity |
GB0323965D0 (en) * | 2003-10-13 | 2003-11-19 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
WO2005041891A2 (en) * | 2003-10-31 | 2005-05-12 | 3M Innovative Properties Company | Neutrophil activation by immune response modifier compounds |
CA2545774A1 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Oxime substituted imidazo ring compounds |
EP1682544A4 (en) * | 2003-11-14 | 2009-05-06 | 3M Innovative Properties Co | Hydroxylamine substituted imidazo ring compounds |
NZ547467A (en) * | 2003-11-25 | 2010-06-25 | 3M Innovative Properties Co | Substituted imidazo ring system and methods |
US20050287118A1 (en) * | 2003-11-26 | 2005-12-29 | Epitomics, Inc. | Bacterial plasmid with immunological adjuvant function and uses thereof |
US20050277127A1 (en) * | 2003-11-26 | 2005-12-15 | Epitomics, Inc. | High-throughput method of DNA immunogen preparation and immunization |
US20050226878A1 (en) * | 2003-12-02 | 2005-10-13 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
WO2005055932A2 (en) * | 2003-12-02 | 2005-06-23 | 3M Innovative Properties Company | Therapeutic combinations and methods including irm compounds |
US9090673B2 (en) | 2003-12-12 | 2015-07-28 | City Of Hope | Synthetic conjugate of CpG DNA and T-help/CTL peptide |
HUE026000T2 (en) | 2003-12-17 | 2016-04-28 | Wyeth Llc | Immunogenic peptide carrier conjugates and methods of producing same |
EP2336147B1 (en) | 2003-12-17 | 2014-04-30 | Janssen Alzheimer Immunotherapy | A beta immunogenic peptide carrier conjugates and methods of producing same |
JP4817599B2 (en) * | 2003-12-25 | 2011-11-16 | 独立行政法人科学技術振興機構 | Immune activity enhancer and method for enhancing immune activity using the same |
JP2007517035A (en) * | 2003-12-29 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
EP1699788A2 (en) * | 2003-12-30 | 2006-09-13 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl and imidazonaphthyridinyl sulfonamides |
EP1699398A4 (en) * | 2003-12-30 | 2007-10-17 | 3M Innovative Properties Co | Enhancement of immune responses |
KR100558851B1 (en) * | 2004-01-08 | 2006-03-10 | 학교법인연세대학교 | Modified CpG oligodeoxynucleotide with improved immunoregulatory function |
US7973016B2 (en) * | 2004-01-23 | 2011-07-05 | Joslin Diebetes Center | Methods of treating, reducing, or preventing autoimmune conditions |
US20050181035A1 (en) * | 2004-02-17 | 2005-08-18 | Dow Steven W. | Systemic immune activation method using non CpG nucleic acids |
WO2005080567A1 (en) * | 2004-02-20 | 2005-09-01 | Mologen Ag | Substituted, non-coding nucleic acid molecule used for the therapeutic and prophylactic immune stimulation in humans and higher animals |
US20060193821A1 (en) * | 2004-03-05 | 2006-08-31 | Diener John L | Aptamers to the human IL-12 cytokine family and their use as autoimmune disease therapeutics |
US8569474B2 (en) | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
JP5600375B2 (en) | 2004-03-09 | 2014-10-01 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | Influenza virus vaccine |
WO2005090968A1 (en) * | 2004-03-16 | 2005-09-29 | Inist Inc. | Tat-based immunomodulatory compositions and methods of their discovery and use |
US7820175B2 (en) | 2004-03-19 | 2010-10-26 | Herbal Spring, Llc | Herbal therapy for the treatment of food allergy |
US8697873B2 (en) * | 2004-03-24 | 2014-04-15 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
TWI235440B (en) * | 2004-03-31 | 2005-07-01 | Advanced Semiconductor Eng | Method for making leadless semiconductor package |
JP2007531746A (en) * | 2004-04-02 | 2007-11-08 | コーリー ファーマシューティカル グループ,インコーポレイテッド | Immunostimulatory nucleic acid for inducing an IL-10 response |
US20050260755A1 (en) * | 2004-04-06 | 2005-11-24 | Isis Pharmaceuticals, Inc. | Sequential delivery of oligomeric compounds |
WO2005105106A2 (en) * | 2004-04-21 | 2005-11-10 | Roby Russell R | Hormone treatment of macular degeneration |
US20050239758A1 (en) * | 2004-04-21 | 2005-10-27 | Roby Russell R | Hormone treatment of multiple sclerosis |
US7579450B2 (en) * | 2004-04-26 | 2009-08-25 | Archemix Corp. | Nucleic acid ligands specific to immunoglobulin E and their use as atopic disease therapeutics |
CN101426524A (en) * | 2004-04-28 | 2009-05-06 | 3M创新有限公司 | Compositions and methods for mucosal vaccination |
GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
PT1740217E (en) | 2004-04-30 | 2011-08-02 | Novartis Ag | Meningococcal conjugate vaccination |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
EP1751612B1 (en) * | 2004-05-06 | 2009-02-25 | The Government of the United States of America, as represented by the Secretary of the Department of Health and Human Services | Methods and compositions for the treatment of uveitis |
GB0410220D0 (en) | 2004-05-07 | 2004-06-09 | Kirkham Lea Ann | Mutant pneumolysin proteins |
GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
CN1296378C (en) * | 2004-05-17 | 2007-01-24 | 中国人民解放军第三军医大学 | CpG-N ODN gene sequence with high immunological activity CpG-S ODN and antagonism CpG-N ODN and use thereof |
EP1766094A4 (en) * | 2004-05-18 | 2009-11-25 | Vical Inc | Influenza virus vaccine composition and method of use |
WO2006078294A2 (en) | 2004-05-21 | 2006-07-27 | Novartis Vaccines And Diagnostics Inc. | Alphavirus vectors for respiratory pathogen vaccines |
MXPA06013448A (en) | 2004-05-21 | 2007-01-23 | Wyeth Corp | Altered fibronectin-binding protein of staphylococcus aureus. |
US20050267145A1 (en) * | 2004-05-28 | 2005-12-01 | Merrill Bryon A | Treatment for lung cancer |
DK1765310T3 (en) | 2004-05-28 | 2016-01-11 | Oryxe | MIXING for transdermal delivery of LAV AND HØJMOLEKYLVÆGTFORBINDELSER |
US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
AU2005326144A1 (en) * | 2004-06-08 | 2006-08-03 | Coley Pharmaceutical Gmbh | Abasic oligonucleotide as carrier platform for antigen and immunostimulatory agonist and antagonist |
WO2005123080A2 (en) * | 2004-06-15 | 2005-12-29 | 3M Innovative Properties Company | Nitrogen-containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
TW200613554A (en) | 2004-06-17 | 2006-05-01 | Wyeth Corp | Plasmid having three complete transcriptional units and immunogenic compositions for inducing an immune response to HIV |
WO2006009832A1 (en) * | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Substituted imidazo ring systems and methods |
WO2006065280A2 (en) * | 2004-06-18 | 2006-06-22 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and methods |
US8026366B2 (en) * | 2004-06-18 | 2011-09-27 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
WO2006038923A2 (en) * | 2004-06-18 | 2006-04-13 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
US7482158B2 (en) * | 2004-07-01 | 2009-01-27 | Mathison Brian H | Composite polynucleic acid therapeutics |
JP2008506789A (en) * | 2004-07-18 | 2008-03-06 | シーエスエル、リミテッド | Immunostimulatory complex and oligonucleotide formulation for inducing enhanced interferon-gamma response |
US20060025390A1 (en) * | 2004-07-28 | 2006-02-02 | Roby Russell R | Treatment of hormone allergy and related symptoms and disorders |
EP2612679A1 (en) | 2004-07-29 | 2013-07-10 | Novartis Vaccines and Diagnostics, Inc. | Immunogenic compositions for gram positive bacteria such as streptococcus agalactiae |
ES2534288T3 (en) | 2004-08-03 | 2015-04-21 | Innate Pharma | Therapeutic compositions against cancer that target 4Ig-B7-H3 |
US20060045886A1 (en) * | 2004-08-27 | 2006-03-02 | Kedl Ross M | HIV immunostimulatory compositions |
WO2006026760A2 (en) * | 2004-09-02 | 2006-03-09 | 3M Innovative Properties Company | 1-amino imidazo-containing compounds and methods |
US7884086B2 (en) * | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
PT1791858E (en) | 2004-09-24 | 2010-07-26 | Intercell Ag | Modified vp1-capsid protein of parvovirus b19 |
JP2008000001A (en) * | 2004-09-30 | 2008-01-10 | Osaka Univ | Immune stimulating oligonucleotide and use in pharmaceutical |
KR101376889B1 (en) | 2004-10-06 | 2014-03-25 | 메디뮨 엘엘씨 | Refrigerator-temperature stable influenza vaccine compositions |
AU2005294129B2 (en) | 2004-10-08 | 2010-12-23 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Modulation of replicative fitness by using less frequently used synonymous codons |
US20070243215A1 (en) * | 2004-10-08 | 2007-10-18 | Miller Richard L | Adjuvant for Dna Vaccines |
WO2007001423A2 (en) | 2004-10-21 | 2007-01-04 | Wyeth | Immunogenic compositions of staphylococcus epidermidis polypeptide and polynucleotide antigens |
GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
EP2436391A3 (en) | 2004-11-02 | 2012-07-04 | Archemix LLC | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
US7332324B2 (en) | 2004-12-03 | 2008-02-19 | University Of Toledo | Attenuated vaccine useful for immunizations against Coccidioides spp. infections |
WO2006063072A2 (en) * | 2004-12-08 | 2006-06-15 | 3M Innovative Properties Company | Immunomodulatory compositions, combinations and methods |
WO2006065751A2 (en) * | 2004-12-13 | 2006-06-22 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Cpg oligonucleotide prodrugs, compositions thereof and associated therapeutic methods |
WO2006073760A2 (en) | 2004-12-17 | 2006-07-13 | Dana-Farber Cancer Institute, Inc. | Regulation of mink in thymocytes and t lymphocytes |
CA2592922A1 (en) * | 2004-12-29 | 2006-07-06 | Mannkind Corporation | Methods to trigger, maintain and manipulate immune responses by targeted administration of biological response modifiers into lymphoid organs |
US8034938B2 (en) | 2004-12-30 | 2011-10-11 | 3M Innovative Properties Company | Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds |
WO2006071997A2 (en) | 2004-12-30 | 2006-07-06 | 3M Innovative Properties Company | Treatment for cutaneous metastases |
ES2392647T3 (en) * | 2004-12-30 | 2012-12-12 | 3M Innovative Properties Company | Chiral tetracyclic compounds that induce interferon biosynthesis |
LT2682126T (en) | 2005-01-27 | 2017-02-27 | Children`s Hospital & Research Center at Oakland | GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by Neisseria meningitidis |
JP4836145B2 (en) * | 2005-01-28 | 2011-12-14 | クウォン,ヒュン−ジョ | Oligonucleotide derived from mycobacteria for immune function stimulation, immune disease treatment, atopic dermatitis treatment and / or normal immune cell protection |
GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
WO2006084251A2 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune reponse modifiers |
US7968563B2 (en) | 2005-02-11 | 2011-06-28 | 3M Innovative Properties Company | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
US8062644B2 (en) | 2005-02-18 | 2011-11-22 | Novartis Vaccines & Diagnostics Srl. | Immunogens from uropathogenic Escherichia coli |
PL2351772T3 (en) | 2005-02-18 | 2017-01-31 | Glaxosmithkline Biologicals Sa | Proteins and nucleic acids from meningitis/sepsis-associated Escherichia coli |
JP2008531722A (en) | 2005-03-04 | 2008-08-14 | ダイナバックス テクノロジーズ コーポレイション | Composition comprising a structurally stable conjugate molecule |
US8101345B1 (en) | 2005-03-25 | 2012-01-24 | Isis Pharmaceuticals, Inc. | Proinflammatory nucleic acids |
AU2006232375A1 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | 1-substituted pyrazolo (3,4-c) ring compounds as modulators of cytokine biosynthesis for the treatment of viral infections and neoplastic diseases |
EP1869043A2 (en) | 2005-04-01 | 2007-12-26 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
CN113198013B (en) | 2005-04-08 | 2024-02-20 | 惠氏有限责任公司 | Multivalent pneumococcal polysaccharide-protein conjugate composition |
JP2008535862A (en) * | 2005-04-08 | 2008-09-04 | キメリクス,インコーポレイテッド | Compounds, compositions and methods for the treatment of poxvirus infections |
WO2006110656A2 (en) * | 2005-04-08 | 2006-10-19 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of viral infections and other medical disorders |
US7709001B2 (en) | 2005-04-08 | 2010-05-04 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
CA2604683C (en) | 2005-04-12 | 2019-04-30 | Duke University | Method of inducing neutralizing antibodies to human immunodeficiency virus |
EP2329843A3 (en) | 2005-04-18 | 2011-09-14 | Novartis Vaccines and Diagnostics, Inc. | Expressing Hepatitis B Virus surface antigen for vaccine preparation |
US20080193474A1 (en) * | 2005-04-25 | 2008-08-14 | Griesgraber George W | Immunostimulatory Compositions |
US20090075342A1 (en) * | 2005-04-26 | 2009-03-19 | Sharon Cload | Metabolic profile directed aptamer medicinal chemistry |
CN101238145B (en) | 2005-06-14 | 2013-04-24 | 普罗陶克斯有限公司 | Use of modified pore-forming proteins in preparing medicine for treating or preventing benign prostatic hyperplasia |
MX2007016561A (en) | 2005-06-30 | 2008-03-10 | Archemix Corp | Materials and methods for the generation of fully 2'-modified nucleic acid transcripts. |
US8101385B2 (en) | 2005-06-30 | 2012-01-24 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
ES2450593T3 (en) | 2005-07-01 | 2014-03-25 | Index Pharmaceuticals Ab | Immunostimulant method |
PL2179737T3 (en) | 2005-07-01 | 2014-01-31 | Index Pharmaceuticals Ab | Modulating responsiveness to steroids |
WO2007008904A2 (en) * | 2005-07-08 | 2007-01-18 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Targeting poly-gamma-glutamic acid to treat staphylococcus epidermidis and related infections |
EP2614709A1 (en) | 2005-07-18 | 2013-07-17 | Novartis AG | Small animal model for HCV replication |
WO2007012285A1 (en) * | 2005-07-28 | 2007-02-01 | Changchun Huapu Biotechnology Co., Ltd. | Viral infection resistent single strand deoxynucleosides |
WO2007041190A2 (en) * | 2005-09-30 | 2007-04-12 | The University Of Iowa Research Foundation | Polymer-based delivery system for immunotherapy of cancer |
WO2007047749A1 (en) | 2005-10-18 | 2007-04-26 | Novartis Vaccines And Diagnostics Inc. | Mucosal and systemic immunizations with alphavirus replicon particles |
CA2625969A1 (en) | 2005-10-28 | 2007-05-03 | Index Pharmaceuticals Ab | Composition and method for the prevention, treatment and/or alleviation of an inflammatory disease |
PT2368572T (en) | 2005-11-04 | 2020-06-16 | Seqirus Uk Ltd | Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture |
AU2006310339B2 (en) | 2005-11-04 | 2013-01-10 | Novartis Ag | Influenza vaccines including combinations of particulate adjuvants and immunopotentiators |
EP1951302A2 (en) | 2005-11-04 | 2008-08-06 | Novartis Vaccines and Diagnostics S.r.l. | Influenza vaccine with reduced amount of oil-in-water emulsion as adjuvant |
CN102755645A (en) | 2005-11-04 | 2012-10-31 | 诺华疫苗和诊断有限公司 | Influenza vaccines with reduced amount of emulsion adjuvant |
CN102864152B (en) * | 2005-11-07 | 2015-11-18 | 艾德拉药物股份有限公司 | Comprise the immunostimulatory properties of the compound based on oligonucleotide of modified immunostimulating dinucleotides |
JP5215865B2 (en) | 2005-11-22 | 2013-06-19 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス インコーポレイテッド | Norovirus and sapovirus antigens |
GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
US20070184068A1 (en) | 2005-12-14 | 2007-08-09 | Cytos Biotechnology Ag | Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity |
WO2007085969A2 (en) | 2006-01-27 | 2007-08-02 | Novartis Vaccines And Diagnostics Gmbh & Co Kg | Influenza vaccines containing hemagglutinin and matrix proteins |
EP1988896A4 (en) * | 2006-02-22 | 2011-07-27 | 3M Innovative Properties Co | Immune response modifier conjugates |
BRPI0708912B8 (en) | 2006-03-14 | 2021-07-27 | Univ Oregon Health & Science | in vitro methods for detecting mycobacterium tuberculosis and cd8 expressing t cells that specifically recognize seq id no: 11 in an individual |
ES2388556T3 (en) * | 2006-03-23 | 2012-10-16 | Novartis Ag | Immunopotentiating compounds |
EP2357184B1 (en) | 2006-03-23 | 2015-02-25 | Novartis AG | Imidazoquinoxaline compounds as immunomodulators |
CA2646349A1 (en) | 2006-03-24 | 2007-10-04 | Novartis Vaccines And Diagnostics Gmbh & Co Kg | Storage of influenza vaccines without refrigeration |
WO2007126825A2 (en) | 2006-03-31 | 2007-11-08 | Novartis Ag | Combined mucosal and parenteral immunization against hiv |
WO2007119815A1 (en) | 2006-04-14 | 2007-10-25 | Kyowa Hakko Kirin Co., Ltd. | Toll-like receptor 9 agonists |
TW200806315A (en) | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
CN101460620B (en) | 2006-05-31 | 2012-02-15 | 东丽株式会社 | Immunostimulatory oligonucleotide and pharmaceutical application thereof |
ATE522541T1 (en) | 2006-06-09 | 2011-09-15 | Novartis Ag | BACTERIAL ADHESIN CONFORMERS |
SG172696A1 (en) | 2006-06-12 | 2011-07-28 | Cytos Biotechnology Ag | Processes for packaging oligonucleotides into virus-like particles of rna bacteriophages |
BRPI0713711A2 (en) | 2006-06-20 | 2012-10-30 | Transgene Sa | recombinant viral vaccine, vaccination kit, and method for using at least one compound |
US8153116B2 (en) | 2006-07-11 | 2012-04-10 | University Of Connecticut | Use of conditional plasmodium strains lacking an essential gene in malaria vaccination |
WO2008094183A2 (en) * | 2006-07-11 | 2008-08-07 | University Of Connecticut | Use of conditional plasmodium strains lacking nutrient transporters in malaria vaccination |
WO2008008432A2 (en) * | 2006-07-12 | 2008-01-17 | Coley Pharmaceutical Group, Inc. | Substituted chiral fused( 1,2) imidazo (4,5-c) ring compounds and methods |
GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
EP2586790A3 (en) | 2006-08-16 | 2013-08-14 | Novartis AG | Immunogens from uropathogenic Escherichia coli |
ES2536401T3 (en) | 2006-09-11 | 2015-05-25 | Novartis Ag | Making vaccines against influenza viruses without using eggs |
DE102006050655A1 (en) * | 2006-10-24 | 2008-04-30 | Halmon Beheer B.V. | Pharmaceutical composition useful for treating allergic diseases comprises RNA and an allergen |
US20100144846A1 (en) * | 2006-10-26 | 2010-06-10 | Coley Pharmaceutical Gmbh | Oligoribonucleotides and uses thereof |
EP3564674B1 (en) | 2006-11-01 | 2021-08-25 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US8252757B2 (en) * | 2006-11-09 | 2012-08-28 | Dynavax Technologies Corporation | Long term disease modification using immunostimulatory oligonucleotides |
WO2008140571A2 (en) * | 2006-11-15 | 2008-11-20 | Functional Genetics, Inc. | Methods and compositions for treating influenza |
EP2679240A1 (en) | 2006-12-06 | 2014-01-01 | Novartis AG | Vaccines including antigen from four strains of influenza virus |
AR064642A1 (en) | 2006-12-22 | 2009-04-15 | Wyeth Corp | POLINUCLEOTIDE VECTOR THAT INCLUDES IT RECOMBINATING CELL THAT UNDERSTANDS THE VECTOR POLYPEPTIDE, ANTIBODY, COMPOSITION THAT UNDERSTANDS THE POLINUCLEOTIDE, VECTOR, RECOMBINATING CELL POLYPEPTIDE OR ANTIBODY, USE OF THE COMPOSITION AND A COMPOSITION AND A METHOD |
US20080149123A1 (en) | 2006-12-22 | 2008-06-26 | Mckay William D | Particulate material dispensing hairbrush with combination bristles |
GB0700562D0 (en) | 2007-01-11 | 2007-02-21 | Novartis Vaccines & Diagnostic | Modified Saccharides |
JP5596980B2 (en) | 2007-02-28 | 2014-10-01 | アメリカ合衆国 | Brachyury polypeptides and methods of use |
CA2683752A1 (en) * | 2007-04-13 | 2008-10-23 | Duke University | Method of inducing neutralizing antibodies to human immunodeficiency virus |
US8518903B2 (en) | 2007-04-19 | 2013-08-27 | University of Pittsburgh—of the Commonwealth System of Higher Education | Use of toll-like receptor-9 agonists |
EP2377952A1 (en) | 2007-04-26 | 2011-10-19 | Ludwig Institute For Cancer Research | Methods for diagnosing and treating astrocytomas |
MX2009012482A (en) * | 2007-05-17 | 2009-12-02 | Coley Pharm Group Inc | Class a oligonucleotides with immunostimulatory potency. |
DK2170353T3 (en) * | 2007-05-18 | 2015-07-27 | Adiutide Pharmaceuticals Gmbh | The phosphate-modified oligonucleotide analogs with immunostimulatory activity |
CA2687178C (en) * | 2007-05-23 | 2014-02-04 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
TW200911304A (en) * | 2007-05-24 | 2009-03-16 | Glaxosmithkline Biolog Sa | Lyophillised antigen composition |
WO2009001217A2 (en) | 2007-06-27 | 2008-12-31 | Novartis Ag | Low-additive influenza vaccines |
GB0713880D0 (en) * | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
US7879812B2 (en) | 2007-08-06 | 2011-02-01 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides and methods of use therefor |
CN101835487A (en) * | 2007-08-21 | 2010-09-15 | 戴纳瓦克斯技术公司 | Composition and methods of making and using influenza proteins |
WO2009034473A2 (en) | 2007-09-12 | 2009-03-19 | Novartis Ag | Gas57 mutant antigens and gas57 antibodies |
CN101820908A (en) * | 2007-10-09 | 2010-09-01 | 科利制药公司 | The immune stimulatory oligonucleotide analogs that comprises modified sugar moieties |
US20110014231A1 (en) * | 2007-11-05 | 2011-01-20 | Mor Research Applications Ltd | Anti-measles cancer immunotherapy |
WO2010008411A1 (en) | 2007-11-09 | 2010-01-21 | The Salk Institute For Biological Studies | Use of tam receptor inhibitors as immunoenhancers and tam activators as immunosuppressors |
GB0810305D0 (en) | 2008-06-05 | 2008-07-09 | Novartis Ag | Influenza vaccination |
WO2009076158A1 (en) | 2007-12-07 | 2009-06-18 | Novartis Ag | Compositions for inducing immune responses |
GB0818453D0 (en) | 2008-10-08 | 2008-11-12 | Novartis Ag | Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom |
EP2235046B1 (en) | 2007-12-21 | 2012-08-01 | Novartis AG | Mutant forms of streptolysin o |
PE20091104A1 (en) * | 2007-12-21 | 2009-07-18 | Wyeth Corp | GENETICALLY MODIFIED ATTENUATED VESICULAR STOMATITIS VIRUS, COMPOSITIONS AND METHODS OF USE OF THE SAME |
CN102670628B (en) * | 2008-01-25 | 2015-11-25 | 奇默里克斯公司 | The method for the treatment of viral infection |
DK2176408T5 (en) * | 2008-01-31 | 2015-12-14 | Curevac Gmbh | Nucleic acids comprising FORMULA (NuGiXmGnNv) a AND DERIVATIVES AS IMMUNE STIMULATING AGENTS / ADJUVANTS. |
ES2532946T3 (en) | 2008-02-21 | 2015-04-06 | Novartis Ag | Meningococcal PUfH polypeptides |
US9511131B2 (en) | 2008-03-10 | 2016-12-06 | Children's Hospital & Research Center Oakland | Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use |
EP3459563A1 (en) | 2008-03-18 | 2019-03-27 | Seqirus UK Limited | Improvements in preparation of influenza virus vaccine antigens |
US8815817B2 (en) * | 2008-05-15 | 2014-08-26 | Dynavax Technologies Corporation | Long term disease modification using immunostimulatory oligonucleotides |
US8222225B2 (en) | 2008-05-21 | 2012-07-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating pneumoconiosis with oligodeoxynucleotides |
US8703490B2 (en) | 2008-06-05 | 2014-04-22 | Ventana Medical Systems, Inc. | Compositions comprising nanomaterials and method for using such compositions for histochemical processes |
MX2010014358A (en) | 2008-06-20 | 2011-07-04 | Wyeth Llc | Compositions and methods of use of orf1358 from beta-hemolytic streptococcal strains. |
CA2960734C (en) | 2008-06-27 | 2021-08-24 | Zoetis Services Llc | Adjuvants containing saponins, sterols and quaternary amines |
TWI351288B (en) * | 2008-07-04 | 2011-11-01 | Univ Nat Pingtung Sci & Tech | Cpg dna adjuvant in avian vaccines |
US20110136897A1 (en) * | 2008-08-14 | 2011-06-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Toll-like receptor 9 agonists for the treatment of anxiety-related disorders and inflammatory disorders |
EP3301116A1 (en) | 2008-08-25 | 2018-04-04 | Dana Farber Cancer Institute, Inc. | Conserved influenza hemagglutinin epitope and antibodies thereto |
EP2331127A2 (en) | 2008-09-18 | 2011-06-15 | Novartis AG | Vaccine adjuvant combinations |
EP2385371B1 (en) | 2008-09-22 | 2014-10-22 | Oregon Health and Science University | Methods for detecting a mycobacterium tuberculosis infection |
HUE028497T2 (en) * | 2008-10-16 | 2016-12-28 | The Univ Of Saskatchewan | Combination adjuvant formulation |
US8691502B2 (en) | 2008-10-31 | 2014-04-08 | Tremrx, Inc. | T-cell vaccination with viral vectors via mechanical epidermal disruption |
JP2012508174A (en) * | 2008-11-05 | 2012-04-05 | ワイス・エルエルシー | Multi-component immunogenic composition for preventing β-hemolytic streptococci (BHS) disease |
EP2346529B1 (en) | 2008-11-12 | 2016-02-10 | Theraclone Sciences, Inc. | Human m2e peptide immunogens |
RU2015151857A (en) | 2008-12-02 | 2019-01-15 | Уэйв Лайф Сайенсес Джапан, Инк. | METHOD FOR SYNTHESIS OF NUCLEIC ACIDS MODIFIED BY PHOSPHOR ATOMIC |
PE20142330A1 (en) | 2008-12-09 | 2015-01-14 | Pfizer Vaccines Llc | IGE CH3 PEPTIDE VACCINE |
CN102333538B (en) | 2008-12-09 | 2014-01-15 | 科勒制药集团有限公司 | Immunostimulatory oligonucleotides |
US8552165B2 (en) * | 2008-12-09 | 2013-10-08 | Heather Davis | Immunostimulatory oligonucleotides |
BRPI1005670A8 (en) | 2009-01-05 | 2017-12-26 | Epitogenesis Inc | adjuvant compositions and processes of use. |
US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
CN103897045A (en) | 2009-01-12 | 2014-07-02 | 诺华股份有限公司 | Cna_b domain antigens in vaccines against gram positive bacteria |
WO2010099472A2 (en) | 2009-02-27 | 2010-09-02 | The U.S.A. Of America, As Represented By The Secretary, Department Of Health And Human Services | Spanx-b polypeptides and their use |
EP2403526B1 (en) | 2009-03-06 | 2019-05-15 | GlaxoSmithKline Biologicals SA | Chlamydia antigens |
WO2010111292A1 (en) | 2009-03-23 | 2010-09-30 | Nanirx, Inc. | Treatment of cancer with immunostimulatory hiv tat derivative polypeptides |
SI2411048T1 (en) | 2009-03-24 | 2020-08-31 | Glaxosmithkline Biologicals Sa | Adjuvanting meningococcal factor h binding protein |
US9402917B2 (en) | 2009-04-03 | 2016-08-02 | Duke University | Methods for the induction of broadly anti-HIV-1 neutralizing antibody responses employing liposome-MPER peptide compositions |
WO2010115118A2 (en) | 2009-04-03 | 2010-10-07 | Antigenics, Inc. | Methods for preparing and using multichaperone-antigen complexes |
MX363222B (en) | 2009-04-14 | 2019-03-15 | Novartis Ag | Compositions for immunising against staphylococcus aerus. |
KR20120022984A (en) * | 2009-04-21 | 2012-03-12 | 셀렉타 바이오사이언시즈, 인크. | Immunonanotherapeutics providing a th1-biased response |
CA2757620C (en) | 2009-04-30 | 2016-04-26 | Coley Pharmaceutical Group, Inc. | Pneumococcal vaccine and uses thereof |
EA201791383A1 (en) | 2009-05-27 | 2018-06-29 | Селекта Байосайенсиз, Инк. | NANOSEELS HAVE COMPONENTS WITH DIFFERENT RELEASE RATES |
CN102802665B (en) | 2009-06-15 | 2015-11-25 | 新加坡国立大学 | Influenza vaccines, compositions and using method |
TW201544119A (en) | 2009-06-22 | 2015-12-01 | Wyeth Llc | Compositions and methods for preparing staphylococcus aureus serotype 5 and 8 capsular polysaccharide conjugate immunogenic compositions |
PE20110023A1 (en) | 2009-06-22 | 2011-01-31 | Wyeth Llc | IMMUNOGENIC COMPOSITIONS OF STAPHYLOCOCCUS AUREUS ANTIGENS |
RU2612521C2 (en) | 2009-07-06 | 2017-03-09 | Онтории, Инк. | Novel prodrugs of nucleic acids and their application methods |
TW201116294A (en) | 2009-07-15 | 2011-05-16 | Novartis Ag | RSV F protein compositions and methods for making same |
PT2464658E (en) | 2009-07-16 | 2015-01-14 | Novartis Ag | Detoxified escherichia coli immunogens |
KR101346197B1 (en) | 2009-07-17 | 2014-02-06 | 한림대학교 산학협력단 | Immunostimulatory Compositions Comprising Liposome―Encapsulated Oligonucleotides and Epitopes |
US8614200B2 (en) | 2009-07-21 | 2013-12-24 | Chimerix, Inc. | Compounds, compositions and methods for treating ocular conditions |
MX2012001194A (en) | 2009-07-30 | 2012-03-07 | Pfizer Vaccines Llc | Antigenic tau peptides and uses thereof. |
US20110033515A1 (en) * | 2009-08-04 | 2011-02-10 | Rst Implanted Cell Technology | Tissue contacting material |
IN2012DN01984A (en) * | 2009-08-18 | 2015-07-24 | Baxter Int | |
US8598327B2 (en) | 2009-08-18 | 2013-12-03 | Baxter International Inc. | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
CN107617110A (en) | 2009-08-26 | 2018-01-23 | 西莱克塔生物科技公司 | The composition of inducing T cell auxiliary |
US8858958B2 (en) | 2009-08-27 | 2014-10-14 | Novartis Ag | Adjuvant comprising aluminum, oligonucleotide and polycation |
CN102596240B (en) | 2009-08-27 | 2015-02-04 | 诺华股份有限公司 | Hybrid polypeptides including meningococcal fHBP sequences |
WO2011026111A1 (en) | 2009-08-31 | 2011-03-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Oral delivery of a vaccine to the large intestine to induce mucosal immunity |
NO2473605T3 (en) | 2009-09-03 | 2018-09-08 | ||
JP2013504556A (en) | 2009-09-10 | 2013-02-07 | ノバルティス アーゲー | Combination vaccine for respiratory tract disease |
GB0917002D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Improved shigella blebs |
GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
CN102596254B (en) | 2009-09-30 | 2016-10-19 | 诺华股份有限公司 | Staphylococcus aureus 5 type and the coupling of CP8 |
CA2776004A1 (en) | 2009-09-30 | 2011-04-07 | Novartis Ag | Expression of meningococcal fhbp polypeptides |
CN102782138A (en) | 2009-10-07 | 2012-11-14 | Uvic工业合伙公司 | Vaccines comprising heat-sensitive transgenes |
WO2011047340A1 (en) | 2009-10-16 | 2011-04-21 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Insertion of foreign genes in rubella virus and their stable expression in a live, attenuated viral vaccine |
GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
WO2011051893A1 (en) | 2009-10-27 | 2011-05-05 | Novartis Ag | Modified meningococcal fhbp polypeptides |
GB0919690D0 (en) | 2009-11-10 | 2009-12-23 | Guy S And St Thomas S Nhs Foun | compositions for immunising against staphylococcus aureus |
EP3360566B1 (en) | 2009-11-20 | 2019-12-25 | Oregon Health&Science University | Methods for detecting a mycobacterium tuberculosis infection |
SG10201408505SA (en) | 2009-12-22 | 2015-02-27 | Celldex Therapeutics Inc | Vaccine compositions |
AU2011216243B2 (en) | 2010-02-12 | 2015-07-09 | Chimerix, Inc. | Nucleoside phosphonate salts |
GB201003333D0 (en) | 2010-02-26 | 2010-04-14 | Novartis Ag | Immunogenic proteins and compositions |
US8685416B2 (en) | 2010-03-02 | 2014-04-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Compositions and methods for the treatment of cancer |
EP2542670A2 (en) | 2010-03-05 | 2013-01-09 | President and Fellows of Harvard College | Induced dendritic cell compositions and uses thereof |
WO2011112599A2 (en) | 2010-03-12 | 2011-09-15 | The United States Of America, As Represented By The Secretary. Department Of Health & Human Services | Immunogenic pote peptides and methods of use |
WO2012020326A1 (en) | 2010-03-18 | 2012-02-16 | Novartis Ag | Adjuvanted vaccines for serogroup b meningococcus |
AU2011238670B2 (en) | 2010-03-30 | 2015-04-23 | Children's Hospital & Research Center Oakland | Factor H binding proteins (FHBP) with altered properties and methods of use thereof |
GB201005625D0 (en) | 2010-04-01 | 2010-05-19 | Novartis Ag | Immunogenic proteins and compositions |
EP2556151A1 (en) | 2010-04-07 | 2013-02-13 | Novartis AG | Method for generating a parvovirus b19 virus-like particle |
CA2796314A1 (en) | 2010-04-13 | 2011-10-20 | Novartis Ag | Benzonapthyridine compositions and uses thereof |
AU2011248620B2 (en) | 2010-04-26 | 2015-11-26 | Chimerix, Inc. | Methods of treating retroviral infections and related dosage regimes |
PT2772265T (en) | 2010-05-14 | 2018-04-20 | Univ Oregon Health & Science | Recombinant hcmv and rhcmv vectors and uses thereof |
NO2575876T3 (en) | 2010-05-26 | 2018-05-05 | ||
WO2011149564A1 (en) | 2010-05-28 | 2011-12-01 | Tetris Online, Inc. | Interactive hybrid asynchronous computer game infrastructure |
DK2575878T3 (en) | 2010-05-28 | 2018-08-13 | Zoetis Belgium S A | VACCINES INCLUDING CHOLESTEROL AND CPG AS THE ONLY ADJUVENT CARRIER MOLECULES |
AU2011261185A1 (en) | 2010-06-03 | 2013-01-10 | Pharmacyclics, Inc. | The use of inhibitors of Bruton's tyrosine kinase (Btk) |
CA2799747C (en) | 2010-06-04 | 2016-10-18 | Wyeth Llc | Vaccine formulations comprising 2-phenoxyethanol |
WO2011154878A1 (en) | 2010-06-07 | 2011-12-15 | Pfizer Vaccines Llc | Ige ch3 peptide vaccine |
GB201009861D0 (en) | 2010-06-11 | 2010-07-21 | Novartis Ag | OMV vaccines |
US10478483B2 (en) | 2010-06-25 | 2019-11-19 | Glaxosmithkline Biologicals Sa | Combinations of meningococcal factor H binding proteins |
JP2013533745A (en) | 2010-07-06 | 2013-08-29 | ノバルティス アーゲー | Immunogenic compositions and methods derived from norovirus |
US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
EP2608805B1 (en) | 2010-08-23 | 2017-07-05 | Wyeth LLC | STABLE FORMULATIONS OF NEISSERIA MENINGITIDIS rLP2086 ANTIGENS |
EP2613806B2 (en) | 2010-09-10 | 2022-10-26 | Wyeth LLC | Non-lipidated variants of neisseria meningitidis orf2086 antigens |
EP3431100B1 (en) | 2010-09-14 | 2021-09-08 | University of Pittsburgh- Of the Commonwealth System of Higher Education | Computationally optimized broadly reactive antigens for influenza |
GB201101665D0 (en) | 2011-01-31 | 2011-03-16 | Novartis Ag | Immunogenic compositions |
US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
US9072760B2 (en) | 2010-09-24 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
US10668092B2 (en) | 2010-09-24 | 2020-06-02 | The John Hopkins University | Compositions and methods for treatment of inflammatory disorders |
GB201017519D0 (en) | 2010-10-15 | 2010-12-01 | Novartis Vaccines Inst For Global Health S R L | Vaccines |
EP2640190A4 (en) | 2010-11-05 | 2016-05-11 | Selecta Biosciences Inc | Modified nicotinic compounds and related methods |
WO2012072769A1 (en) | 2010-12-01 | 2012-06-07 | Novartis Ag | Pneumococcal rrgb epitopes and clade combinations |
EP2468866A1 (en) * | 2010-12-21 | 2012-06-27 | Index Pharmaceuticals AB | Biologically active oligonucleotides capable of modulating the immune system |
WO2012088425A2 (en) | 2010-12-22 | 2012-06-28 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease |
PL2654785T3 (en) | 2010-12-22 | 2019-09-30 | Bayer Intellectual Property Gmbh | Enhanced immune response in bovine species |
AU2011346535B2 (en) | 2010-12-22 | 2015-09-24 | Wyeth Llc | Stable immunogenic compositions of Staphylococcus aureus antigens |
GB201021867D0 (en) | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
US20130315959A1 (en) | 2010-12-24 | 2013-11-28 | Novartis Ag | Compounds |
EP2471926A3 (en) | 2010-12-30 | 2012-07-11 | Intervet International BV | Immunostimulatory oligodeoxynucleotides |
US10342862B2 (en) | 2011-01-26 | 2019-07-09 | Glaxosmithkline Biologicals, Sa | RSV immunization regimen |
WO2012109675A1 (en) | 2011-02-11 | 2012-08-16 | Baxter International Inc. | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
US20140004142A1 (en) | 2011-03-02 | 2014-01-02 | Pfizer Inc. | Pcsk9 vaccine |
EA027236B1 (en) | 2011-04-08 | 2017-07-31 | Иммьюн Дизайн Корп. | Immunogenic compositions and methods of using the compositions for inducing humoral and cellular immune responses |
US9452212B2 (en) | 2011-04-14 | 2016-09-27 | Dynavax Technologies Corporation | Methods and compositions for eliciting an immune response against hepatitis B virus |
WO2012149307A2 (en) | 2011-04-27 | 2012-11-01 | Immune Design Corp. | Synthetic long peptide (slp)-based vaccines |
LT3275892T (en) | 2011-05-13 | 2020-04-10 | Glaxosmithkline Biologicals S.A. | Pre-fusion rsv f antigens |
FR2975600B1 (en) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | AGENTS FOR THE TREATMENT OF TUMORS |
EP2714908B1 (en) * | 2011-05-26 | 2018-04-18 | Intervet International B.V. | Immunostimulatory oligodeoxynucleotides |
KR102052215B1 (en) | 2011-06-01 | 2019-12-04 | 야누스 바이오테라퓨틱스, 인크. | Novel immune system modulators |
EP2713737B1 (en) | 2011-06-01 | 2016-04-20 | Janus Biotherapeutics, Inc. | Novel immune system modulators |
MX355623B (en) | 2011-06-03 | 2018-04-25 | 3M Innovative Properties Co | Hydrazino 1h-imidazoquinolin-4-amines and conjugates made therefrom. |
US9475804B2 (en) | 2011-06-03 | 2016-10-25 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
KR102033185B1 (en) | 2011-06-17 | 2019-10-16 | 유니버시티 오브 테네시 리서치 파운데이션 | Group a streptococcus multivalent vaccine |
US9580475B2 (en) | 2011-06-20 | 2017-02-28 | University of Pittsburgh—of the Commonwealth System of Higher Education | Computationally optimized broadly reactive antigens for H1N1 influenza |
ITMI20111182A1 (en) | 2011-06-28 | 2012-12-29 | Canio Buonavoglia | VACCINE FOR CORONAVIRUS CANINO |
JP2014522842A (en) | 2011-07-06 | 2014-09-08 | ノバルティス アーゲー | Immunogenic combination compositions and uses thereof |
EP2729168A2 (en) | 2011-07-06 | 2014-05-14 | Novartis AG | Immunogenic compositions and uses thereof |
WO2013007703A1 (en) * | 2011-07-08 | 2013-01-17 | Universität Zürich | CLASS A CpG OLIGONUCLEOTIDES FOR PREVENTION OF VIRAL INFECTION IN CATS |
WO2013009564A1 (en) | 2011-07-08 | 2013-01-17 | Novartis Ag | Tyrosine ligation process |
MX347361B (en) | 2011-07-19 | 2017-04-12 | Wave Life Sciences Ltd | Methods for the synthesis of functionalized nucleic acids. |
US20130023736A1 (en) | 2011-07-21 | 2013-01-24 | Stanley Dale Harpstead | Systems for drug delivery and monitoring |
ES2687129T3 (en) | 2011-07-25 | 2018-10-23 | Glaxosmithkline Biologicals Sa | Compositions and methods to evaluate the functional immunogenicity of parvovirus vaccines |
EP2736537A4 (en) | 2011-07-29 | 2015-04-15 | Selecta Biosciences Inc | Synthetic nanocarriers that generate humoral and cytotoxic t lymphocyte (ctl) immune responses |
GB201114923D0 (en) | 2011-08-30 | 2011-10-12 | Novartis Ag | Immunogenic proteins and compositions |
US20140348865A1 (en) | 2011-09-12 | 2014-11-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Ser. | Immunogens based on an hiv-1 v1v2 site-of-vulnerability |
WO2013038385A2 (en) | 2011-09-14 | 2013-03-21 | Novartis Ag | Escherichia coli vaccine combination |
TR201909110T4 (en) | 2011-09-14 | 2019-07-22 | Glaxosmithkline Biologicals Sa | Methods for making saccharide-protein glycoconjugates. |
WO2013049535A2 (en) | 2011-09-30 | 2013-04-04 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Influenza vaccine |
US9873694B2 (en) | 2011-10-04 | 2018-01-23 | Janus Biotherapeutics, Inc. | Imidazole quinoline-based immune system modulators |
US20140286983A1 (en) | 2011-10-20 | 2014-09-25 | The Government of the USA as represented by the Secretaryof the Dept. of Health and Human Services | Dengue virus e-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes |
WO2013068949A1 (en) | 2011-11-07 | 2013-05-16 | Novartis Ag | Carrier molecule comprising a spr0096 and a spr2021 antigen |
BR112014013876A2 (en) | 2011-12-08 | 2019-09-24 | Novartis Ag | clostridium difficile toxin-based vaccine |
EA201491081A1 (en) | 2012-01-16 | 2016-11-30 | Элизабет Маккенна | COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISEASES AND LIVER DISORDERS |
US20140086849A1 (en) | 2012-09-21 | 2014-03-27 | Elizabeth McKenna | Naturally-Occurring CpG Oligonucleotide Compositions and Therapeutic Applications Thereof |
WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
CN104136456A (en) | 2012-02-07 | 2014-11-05 | 高等教育联邦系统-匹兹堡大学 | Computationally optimized broadly reactive antigens for h3n2, h2n2, and b influenza viruses |
IN2014DN05695A (en) | 2012-02-13 | 2015-05-15 | Univ Pittsburgh | |
JP2015509713A (en) | 2012-02-24 | 2015-04-02 | ノバルティス アーゲー | Pili protein and composition |
SA115360586B1 (en) | 2012-03-09 | 2017-04-12 | فايزر انك | Neisseria meningitidis compositions and methods thereof |
US8986710B2 (en) | 2012-03-09 | 2015-03-24 | Pfizer Inc. | Neisseria meningitidis compositions and methods thereof |
WO2013142808A1 (en) | 2012-03-23 | 2013-09-26 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pathogenic phlebovirus isolates and compositions and methods of use |
EP2841098A4 (en) | 2012-04-23 | 2016-03-02 | Allertein Therapeutics Llc | Nanoparticles for treatment of allergy |
US10279026B2 (en) | 2012-04-26 | 2019-05-07 | Glaxosmithkline Biologicals Sa | Antigens and antigen combinations |
RU2727476C2 (en) | 2012-04-26 | 2020-07-21 | Новартис Аг | Antigens and antigen compositions |
WO2013162828A1 (en) | 2012-04-27 | 2013-10-31 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Use of cpg oligonucleotides co-formulated with an antibiotic to accelarate wound healing |
NZ701324A (en) | 2012-05-04 | 2016-09-30 | Pfizer | Prostate-associated antigens and vaccine-based immunotherapy regimens |
AU2013265336A1 (en) | 2012-05-22 | 2014-12-04 | Novartis Ag | Meningococcus serogroup X conjugate |
US9409956B2 (en) | 2012-05-23 | 2016-08-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Salmonella typhi Ty21a expressing Yersinia pestis F1-V fusion protein and uses thereof |
CN104428008B (en) | 2012-05-24 | 2020-10-09 | 美国政府(由卫生和人类服务部的部长所代表) | Multivalent meningococcal conjugates and methods of making conjugates |
US9687542B2 (en) | 2012-06-19 | 2017-06-27 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Rift valley fever virus replicon particles and use thereof |
EP2861834B1 (en) | 2012-06-19 | 2021-04-14 | Volvo Lastvagnar AB | A device for controlling a gas flow, an exhaust aftertreatment system and a system for propelling a vehicle |
KR102057217B1 (en) | 2012-06-20 | 2020-01-22 | 에스케이바이오사이언스 주식회사 | Multivalent pneumococcal polysaccharide-protein conjugate composition |
JP2015522580A (en) | 2012-07-06 | 2015-08-06 | ノバルティス アーゲー | Immunological compositions and uses thereof |
US9982257B2 (en) | 2012-07-13 | 2018-05-29 | Wave Life Sciences Ltd. | Chiral control |
JP6246121B2 (en) * | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | Chiral nucleic acid adjuvant |
US9598458B2 (en) | 2012-07-13 | 2017-03-21 | Wave Life Sciences Japan, Inc. | Asymmetric auxiliary group |
WO2014015091A2 (en) | 2012-07-19 | 2014-01-23 | Zoetis Llc | Bovine influenza virus compositions |
CN104704129A (en) | 2012-07-24 | 2015-06-10 | 药品循环公司 | Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (BTK) |
AU2013295770A1 (en) | 2012-07-27 | 2015-01-29 | Zoetis Services Llc | Tick toxin compositions |
SI2885007T1 (en) | 2012-08-16 | 2018-12-31 | Pfizer Inc. | Glycoconjugation processes and compositions |
US10973892B2 (en) | 2012-09-04 | 2021-04-13 | Bavarian Nordic A/S | Methods and compositions for enhancing vaccine immune responses |
WO2014043518A1 (en) | 2012-09-14 | 2014-03-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Brachyury protein, non-poxvirus non-yeast vectors encoding brachyury protein, and their use |
WO2014043535A1 (en) | 2012-09-14 | 2014-03-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Compositions for the treatment of cancer |
RU2662970C2 (en) | 2012-09-18 | 2018-07-31 | Новартис Аг | Outer membrane vesicles |
US9562066B2 (en) * | 2012-09-25 | 2017-02-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Oral therapy of necrotizing enterocolitis |
US9855325B2 (en) | 2012-10-03 | 2018-01-02 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
KR20150080592A (en) | 2012-11-02 | 2015-07-09 | 파마시클릭스, 인코포레이티드 | Tec family kinase inhibitor adjuvant therapy |
WO2014074785A1 (en) | 2012-11-08 | 2014-05-15 | Ludwig Institute For Cancer Research Ltd. | Methods of predicting outcome and treating breast cancer |
KR20140075201A (en) | 2012-12-11 | 2014-06-19 | 에스케이케미칼주식회사 | Multivalent pneumococcal polysaccharide-protein conjugate composition |
KR20140075196A (en) | 2012-12-11 | 2014-06-19 | 에스케이케미칼주식회사 | Multivalent pneumococcal polysaccharide-protein conjugate composition |
TWI465241B (en) | 2012-12-19 | 2014-12-21 | Ind Tech Res Inst | Use of an extract of juniperus chinensis or lignan for manufacturing a medicament for inhibiting angiogenesis |
CN104870463B (en) | 2012-12-20 | 2018-09-28 | 辉瑞公司 | Sugared conjugation methods |
EP2948469A4 (en) | 2013-01-23 | 2016-11-02 | Univ Leland Stanford Junior | Stabilized hepatitis b core polypeptide |
US11576958B2 (en) | 2013-02-07 | 2023-02-14 | Children's Medical Center Corporation | Protein antigens that provide protection against pneumococcal colonization and/or disease |
EP2964665B1 (en) | 2013-03-08 | 2018-08-01 | Pfizer Inc | Immunogenic fusion polypeptides |
KR20150127206A (en) | 2013-03-14 | 2015-11-16 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | Nanoparticle-based compositions |
CA2907098A1 (en) | 2013-03-15 | 2014-09-25 | Zoetis Services Llc | Cross-protection of bovines against b. trehalosi infection by a multi-valent vaccine |
DE102013004595A1 (en) | 2013-03-15 | 2014-09-18 | Emergent Product Development Germany Gmbh | RSV vaccines |
WO2014165679A1 (en) | 2013-04-03 | 2014-10-09 | Allertein Therapeutics, Llc | Novel nanoparticle compositions |
EP2986717A1 (en) | 2013-04-19 | 2016-02-24 | The Regents of The University of California | Lone star virus |
AR095882A1 (en) | 2013-04-22 | 2015-11-18 | Hoffmann La Roche | ANTIBODY COMBINATION THERAPY AGAINST HUMAN CSF-1R WITH A TLR9 AGONIST |
CN103550783A (en) * | 2013-04-27 | 2014-02-05 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Nucleic acid drug targeting delivery system and preparation method thereof |
WO2015132619A1 (en) | 2013-05-15 | 2015-09-11 | The Governors Of The University Of Alberta | E1e2 hcv vaccines and methods of use |
WO2014201245A1 (en) | 2013-06-12 | 2014-12-18 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Tlr-9 agonist with tlr-7 and/or tlr-8 agonist for treating tumors |
TWI535451B (en) * | 2013-07-19 | 2016-06-01 | 財團法人國家衛生研究院 | Cpg-oligodeoxynucleotide, immunogenic composition comprising the same, and use of preparation of medicament for treatment in stimulating immune response |
CA2919268C (en) | 2013-07-25 | 2023-09-05 | Exicure, Inc. | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
EP3632458A1 (en) | 2013-07-26 | 2020-04-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of bacterial infections |
EP3041502A2 (en) | 2013-09-08 | 2016-07-13 | Pfizer Inc. | Neisseria meningitidis compositions and methods thereof |
AR097584A1 (en) | 2013-09-12 | 2016-03-23 | Hoffmann La Roche | ANTIBODY COMBINATION THERAPY AGAINST HUMAN CSF-1R AND ANTIBODIES AGAINST HUMAN PD-L1 |
CA3005608C (en) | 2013-09-19 | 2020-06-30 | Zoetis Services Llc | Water-in-oil emulsions comprising immunostimulatory oligonucleotides |
US10076567B2 (en) | 2013-09-27 | 2018-09-18 | Duke University | MPER-liposome conjugates and uses thereof |
US10010606B2 (en) | 2013-09-30 | 2018-07-03 | Los Alamos National Security, Llc | Mosaic conserved region HIV immunogenic polypeptides |
EP3052127A1 (en) | 2013-10-04 | 2016-08-10 | PIN Pharma, Inc. | Immunostimulatory hiv tat derivative polypeptides for use in cancer treatment |
JP2016535989A (en) | 2013-11-01 | 2016-11-24 | ファイザー・インク | Vector for expressing prostate-related antigen |
EP2870974A1 (en) | 2013-11-08 | 2015-05-13 | Novartis AG | Salmonella conjugate vaccines |
HUE056105T2 (en) | 2013-11-28 | 2022-01-28 | Bavarian Nordic As | Compositions and methods for inducing an enhanced immune response using poxvirus vectors |
CN112107693B (en) * | 2013-12-03 | 2023-05-26 | 西北大学 | Liposome particles, method for preparing said liposome particles and use thereof |
JP6758185B2 (en) | 2013-12-13 | 2020-09-23 | ザ ユナイテッド ステイツ オブ アメリカ, アズ リプレゼンテッド バイ ザ セクレタリー, デパートメント オブ ヘルス アンド ヒューマン サービシーズ | Multiepitope TARP peptide vaccine and its use |
US11708411B2 (en) | 2013-12-20 | 2023-07-25 | Wake Forest University Health Sciences | Methods and compositions for increasing protective antibody levels induced by pneumococcal polysaccharide vaccines |
EP3095460A4 (en) * | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
JPWO2015108048A1 (en) * | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | Chiral nucleic acid adjuvant and antitumor agent having antitumor activity |
JPWO2015108047A1 (en) * | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | Chiral nucleic acid adjuvant having immunity induction activity and immunity induction activator |
CA2936712A1 (en) | 2014-01-16 | 2015-07-23 | Meena | Chiral design |
DK3096783T3 (en) | 2014-01-21 | 2021-08-02 | Pfizer | Streptococcus pneumoniae capsule polysaccharides and conjugates thereof |
US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
IL296681A (en) | 2014-01-21 | 2022-11-01 | Pfizer | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
SG11201605883UA (en) | 2014-01-21 | 2016-08-30 | Immune Design Corp | Compositions for use in the treatment of allergic conditions |
DK3583947T3 (en) | 2014-01-21 | 2023-11-06 | Pfizer | Streptococcus pneumoniae capsular polysaccharides and conjugates thereof |
WO2016130569A1 (en) | 2015-02-09 | 2016-08-18 | Mj Biologics, Inc. | A composition comprising pedv antigens and methods for making and using the composition |
WO2015123291A1 (en) | 2014-02-11 | 2015-08-20 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Pcsk9 vaccine and methods of using the same |
US10668164B2 (en) | 2014-02-14 | 2020-06-02 | Pfizer Inc. | Immunogenic glycoprotein conjugates |
GB2523187A (en) | 2014-02-18 | 2015-08-19 | Mologen Ag | Covalently closed non-coding immunomodulatory DNA construct |
WO2015130584A2 (en) | 2014-02-25 | 2015-09-03 | Merck Sharp & Dohme Corp. | Lipid nanoparticle vaccine adjuvants and antigen delivery systems |
PE20170404A1 (en) | 2014-02-28 | 2017-05-14 | Bayer Animal Health Gmbh | IMMUNOSTIMULATORY PLASMIDS |
CN106535930A (en) | 2014-03-11 | 2017-03-22 | 明尼苏达大学董事会 | Porcine epidemic diarrhea virus vaccines and methods of use thereof |
EP3119910A4 (en) | 2014-03-20 | 2018-02-21 | Pharmacyclics LLC | Phospholipase c gamma 2 and resistance associated mutations |
SI3122378T1 (en) | 2014-03-26 | 2020-03-31 | Glaxosmithkline Biologicals S.A. | Mutant staphylococcal antigens |
US9549914B2 (en) | 2014-04-03 | 2017-01-24 | The Johns Hopkins University | Treatment of human cytomegalovirus by modulating Wnt |
EP3134104B1 (en) | 2014-04-25 | 2018-12-26 | Tria Bioscience Corp. | Synthetic hapten carrier compositions and methods |
RU2016150941A (en) * | 2014-05-23 | 2018-06-26 | Грегори КОЧОН | COATING METHOD AND MATERIALS |
CA2986096A1 (en) | 2014-05-30 | 2015-12-03 | Sanofi Pasteur Inc. | Expression and conformational analysis of engineered influenza hemagglutinin |
PL3164113T3 (en) | 2014-06-04 | 2019-09-30 | Exicure, Inc. | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
WO2015200728A1 (en) | 2014-06-25 | 2015-12-30 | Selecta Biosciences, Inc. | Methods and compositions for treatment with synthetic nanocarriers and immune checkpoint inhibitors |
EP3169352A1 (en) | 2014-07-15 | 2017-05-24 | Immune Design Corp. | Prime-boost regimens with a tlr4 agonist adjuvant and a lentiviral vector |
EP3398948A3 (en) | 2014-08-22 | 2018-12-05 | Janus Biotherapeutics, Inc. | 2,4,6,7-tetrasubstituted pteridine compounds and methods of synthesis and use thereof |
MX2017004448A (en) | 2014-10-06 | 2017-10-23 | Exicure Inc | Anti-tnf compounds. |
US20160129097A1 (en) * | 2014-11-06 | 2016-05-12 | Jeremy Delk | Method of processing a veterinary tumor vaccine and a veterinary tumor vaccine processing kit |
CA2968531A1 (en) | 2014-11-21 | 2016-05-26 | Northwestern University | The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
US20180256630A1 (en) * | 2014-12-26 | 2018-09-13 | National Institutes Of Biomedical Innovation, Health And Nutrition | Use of nucleic acid-polysaccharide complexes having immunopotentiating activity as anti-tumor drug |
WO2016109310A1 (en) | 2014-12-31 | 2016-07-07 | Checkmate Pharmaceuticals, Llc | Combination tumor immunotherapy |
SI3244917T1 (en) | 2015-01-15 | 2023-07-31 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
KR102382773B1 (en) | 2015-01-16 | 2022-04-04 | 조에티스 서비시즈 엘엘씨 | Foot-and-mouth disease vaccine |
CA3014427A1 (en) | 2015-02-13 | 2016-08-18 | Icahn School Of Medicine At Mount Sinai | Rna containing compositions and methods of their use |
BR112017017460A2 (en) | 2015-02-19 | 2018-04-10 | Pfizer Inc. | neisseria meningitidis compositions and methods thereof |
DK3268380T3 (en) | 2015-03-12 | 2019-02-18 | Zoetis Services Llc | PYOLYSIS METHODS AND COMPOSITIONS |
WO2016178123A1 (en) | 2015-05-04 | 2016-11-10 | Pfizer Inc. | Group b streptococcus polysaccharide-protein conjugates, methods for producing conjugates, immunogenic compositions comprising conjugates, and uses thereof |
WO2016180852A1 (en) | 2015-05-12 | 2016-11-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for preparing antigen-specific t cells from an umbilical cord blood sample |
EP3294324A1 (en) | 2015-05-13 | 2018-03-21 | Agenus Inc. | Vaccines for treatment and prevention of cancer |
WO2016183371A1 (en) | 2015-05-13 | 2016-11-17 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Methods for the treatment or prevention of ischemic tissue damage |
AU2016270979B2 (en) | 2015-06-02 | 2020-11-12 | Sanofi Pasteur Inc. | Engineered influenza antigenic polypeptides and immunogenic compositions thereof |
WO2016200787A2 (en) | 2015-06-09 | 2016-12-15 | The Board Of Regents Of The University Of Oklahoma | Compositions and treatments for haemophilus influenzae |
JP6886410B2 (en) | 2015-06-10 | 2021-06-16 | ザ ユナイテッド ステイツ オブ アメリカ, アズ リプレゼンテッド バイ ザ セクレタリー, デパートメント オブ ヘルス アンド ヒューマン サービシーズ | Process for preparation and purification of nucleic acid-containing compositions |
JP2018524323A (en) | 2015-06-26 | 2018-08-30 | セキラス ユーケー リミテッド | Antigen matched influenza vaccine |
US10449212B2 (en) | 2015-07-09 | 2019-10-22 | National Institute For Materials Science | Immunostimulating oligonucleotide complex |
RU2721128C2 (en) | 2015-07-21 | 2020-05-18 | Пфайзер Инк. | Immunogenic compositions containing conjugated antigens of the capsular saccharide, kits containing these compositions and use thereof |
TW201718001A (en) | 2015-07-31 | 2017-06-01 | 拜耳動物保健有限公司 | Enhanced immune response in porcine species |
HUE060545T2 (en) | 2015-08-14 | 2023-03-28 | Zoetis Services Llc | Mycoplasma bovis compositions |
WO2017040885A1 (en) | 2015-09-03 | 2017-03-09 | The Board Of Regents Of The University Of Oklahoma | Peptide inhibitors of clostridium difficile tcdb toxin |
LU92821B1 (en) | 2015-09-09 | 2017-03-20 | Mologen Ag | Combination comprising immunostimulatory oligonucleotides |
CN108024914A (en) | 2015-09-17 | 2018-05-11 | Jrx生物技术有限公司 | Improve the method for the aquation or wetting action of skin |
GB2542425A (en) | 2015-09-21 | 2017-03-22 | Mologen Ag | Means for the treatment of HIV |
WO2017059280A1 (en) | 2015-10-02 | 2017-04-06 | The University Of North Carolina At Chapel Hill | Novel pan-tam inhibitors and mer/axl dual inhibitors |
US10548970B2 (en) | 2015-10-05 | 2020-02-04 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Human rotavirus G9P[6] strain and use as a vaccine |
WO2017075570A1 (en) | 2015-10-30 | 2017-05-04 | The United States Of America, As Represented By Secretary, Department Of Health And Human Sevices | Compositions and methods for the treatment of her2-expressing solid tumors |
WO2017085586A1 (en) | 2015-11-20 | 2017-05-26 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
CA3006779A1 (en) | 2015-12-09 | 2017-06-15 | Admedus Vaccines Pty Ltd | Immunomodulating composition for treatment |
EP3402878A1 (en) | 2016-01-11 | 2018-11-21 | Zoetis Services LLC | Novel cross protective vaccine compositions for porcine epidemic diarrhea virus |
PL3407910T3 (en) | 2016-01-29 | 2022-08-16 | Bavarian Nordic A/S | Recombinant modified vaccinia virus ankara (mva) equine encephalitis virus vaccine |
WO2017189448A1 (en) | 2016-04-25 | 2017-11-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bivalent immunogenic conjugate for malaria and typhoid |
WO2017192874A1 (en) | 2016-05-04 | 2017-11-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Albumin-binding immunomodulatory compositions and methods of use thereof |
WO2017201390A1 (en) | 2016-05-19 | 2017-11-23 | The Regents Of The University Of Michigan | Novel adjuvant compositions |
WO2017210215A1 (en) | 2016-05-31 | 2017-12-07 | The Government Of The United States Of America As Represented By The Secretary Of The Army | Zika virus vaccine and methods of production |
CA3026096A1 (en) | 2016-06-02 | 2017-12-07 | Sanofi Pasteur Inc. | Engineered influenza antigenic polypeptides and immunogenic compositions thereof |
MA45159A (en) | 2016-06-03 | 2019-04-10 | Sanofi Pasteur Inc | MODIFIED INFLUENZA HEMAGGLUTININ POLYPEPTIDES |
US10947277B2 (en) | 2016-06-13 | 2021-03-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Nucleic acids encoding zika virus-like particles and their use in zika virus vaccines and diagnostic assays |
WO2017220753A1 (en) | 2016-06-22 | 2017-12-28 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Pneumococcal polysaccharide-protein conjugate composition |
EP3269385A1 (en) | 2016-07-12 | 2018-01-17 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Pneumococcal polysaccharide-protein conjugate composition |
WO2018009604A1 (en) | 2016-07-08 | 2018-01-11 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric dengue/zika viruses live-attenuated zika virus vaccines |
WO2018009603A1 (en) | 2016-07-08 | 2018-01-11 | The United State of America, as represented by the Secretary, Department of Health and Human Service | Chimeric west nile/zika viruses and methods of use |
WO2018027123A1 (en) | 2016-08-05 | 2018-02-08 | Sanofi Pasteur, Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US11241489B2 (en) | 2016-08-05 | 2022-02-08 | Sanofi Pasteur Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US10182146B2 (en) * | 2016-08-22 | 2019-01-15 | Nice Ltd. | System and method for dynamic redundant call recording |
US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
EP3504239A1 (en) | 2016-08-25 | 2019-07-03 | H. Hoffnabb-La Roche Ag | Intermittent dosing of an anti-csf-1r antibody in combination with macrophage activating agent |
US10172933B2 (en) | 2016-10-31 | 2019-01-08 | The United States Of America, As Represented By The Secretary Of Agriculture | Mosaic vaccines for serotype a foot-and-mouth disease virus |
US10751402B2 (en) | 2016-11-09 | 2020-08-25 | Pfizer Inc. | Immunogenic compositions and uses thereof |
WO2018115051A1 (en) | 2016-12-22 | 2018-06-28 | F. Hoffmann-La Roche Ag | Treatment of tumors with an anti-csf-1r antibody in combination with an anti-pd-l1 antibody after failure of anti-pd-l1/pd1 treatment |
HRP20220573T1 (en) | 2017-01-20 | 2022-06-10 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
CN110225757A (en) | 2017-01-31 | 2019-09-10 | 默沙东公司 | By the method for S. pneumoniae serotypes 19F production capsular polysaccharide protein conjugate |
SG11201906519RA (en) | 2017-01-31 | 2019-08-27 | Pfizer | Neisseria meningitidis compositions and methods thereof |
AU2018214451B2 (en) | 2017-02-06 | 2022-02-03 | Meat & Livestock Australia Limited | Immunostimulating compositions and uses therefore |
GB201703529D0 (en) | 2017-03-06 | 2017-04-19 | Cambridge Entpr Ltd | Vaccine composition |
WO2018183666A1 (en) | 2017-03-31 | 2018-10-04 | Boston Medical Center Corporation | Methods and compositions using highly converved pneumococcal surface proteins |
WO2018201090A1 (en) | 2017-04-28 | 2018-11-01 | Exicure, Inc. | Synthesis of spherical nucleic acids using lipophilic moieties |
CA3066915A1 (en) | 2017-06-11 | 2018-12-20 | Molecular Express, Inc. | Methods and compositions for substance use disorder vaccine formulations and uses thereof |
WO2018237221A1 (en) | 2017-06-23 | 2018-12-27 | Nosocomial Vaccine Corporation | Immunogenic compositions |
BR112020001255A2 (en) | 2017-07-21 | 2020-07-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | immunogenic compositions of neisseria meningitidis |
JP7438102B2 (en) | 2017-09-07 | 2024-02-26 | メルク・シャープ・アンド・ドーム・エルエルシー | Pneumococcal polysaccharide and its use in immunogenic polysaccharide-carrier protein conjugates |
AU2018330494A1 (en) | 2017-09-08 | 2020-03-26 | Mina Therapeutics Limited | HNF4a saRNA compositions and methods of use |
WO2019066571A2 (en) | 2017-09-28 | 2019-04-04 | 연세대학교 산학협력단 | Method for producing myeloid-derived suppressor cells, myeloid-derived suppressor cells produced thereby, and uses thereof |
US11235046B2 (en) | 2017-11-04 | 2022-02-01 | Nevada Research & Innovation Corporation | Immunogenic conjugates and methods of use thereof |
CA3084436A1 (en) | 2017-12-06 | 2019-07-18 | Merck Sharp & Dohme Corp. | Compositions comprising streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof |
WO2019126197A1 (en) | 2017-12-18 | 2019-06-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bacterial polysaccharide-conjugated carrier proteins and use thereof |
CN111741767A (en) | 2017-12-19 | 2020-10-02 | 麻省理工学院 | Antigen-adjuvant coupling agents and methods of use |
CN111629751A (en) | 2018-01-22 | 2020-09-04 | 美国政府(由卫生和人类服务部的部长所代表) | Broad spectrum protective inactivated influenza virus vaccines |
CA3034912A1 (en) | 2018-02-28 | 2019-08-28 | Pfizer Inc. | Il-15 variants and uses thereof |
WO2019169332A1 (en) * | 2018-03-02 | 2019-09-06 | Elicio Therapeutics Inc. | Compounds including a mutant kras sequence and a lipid and uses thereof |
US11633471B2 (en) | 2018-03-06 | 2023-04-25 | Unm Rainforest Innovations | Compositions and methods for reducing serum triglycerides |
JP7329529B2 (en) | 2018-03-28 | 2023-08-18 | サノフィ パスツール インコーポレイテッド | Methods of Producing Broadly Protective Vaccine Compositions Containing Hemagglutinin |
CN112512565A (en) | 2018-04-03 | 2021-03-16 | 赛诺菲 | Antigenic influenza-ferritin polypeptides |
MX2020010199A (en) | 2018-04-03 | 2021-01-08 | Sanofi Sa | Antigenic respiratory syncytial virus polypeptides. |
EP3773698A1 (en) | 2018-04-03 | 2021-02-17 | Sanofi | Ferritin proteins |
CN112584858A (en) | 2018-04-03 | 2021-03-30 | 赛诺菲 | Antigenic OSPA polypeptides |
CN112512566A (en) | 2018-04-03 | 2021-03-16 | 赛诺菲 | Antigenic epstein-barr virus polypeptides |
US11434292B2 (en) | 2018-05-23 | 2022-09-06 | Pfizer Inc. | Antibodies specific for CD3 and uses thereof |
MX2020012607A (en) | 2018-05-23 | 2021-01-29 | Pfizer | Antibodies specific for gucy2c and uses thereof. |
EP3574915A1 (en) | 2018-05-29 | 2019-12-04 | Neovacs | Immunogenic product comprising il-4 and/or il-13 for treating disorders associated with aberrant il-4 and/or il 13 expression or activity |
CN110004150B (en) * | 2018-08-01 | 2023-03-10 | 中国农业科学院兰州兽医研究所 | CpG oligonucleotide sequence with immune enhancement activity and application thereof |
US11260119B2 (en) | 2018-08-24 | 2022-03-01 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
KR20210124205A (en) | 2018-12-04 | 2021-10-14 | 더 락커펠러 유니버시티 | HIV Vaccine Immunogen |
EP3894547A1 (en) | 2018-12-12 | 2021-10-20 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Recombinant mumps virus vaccine expressing genotype g fusion and hemagglutinin-neuraminidase proteins |
WO2020121159A1 (en) | 2018-12-12 | 2020-06-18 | Pfizer Inc. | Immunogenic multiple hetero-antigen polysaccharide-protein conjugates and uses thereof |
US20220023410A1 (en) | 2018-12-14 | 2022-01-27 | University Of Georgia Research Foundation, Inc. | Crimean-congo hemorrhagic fever virus replicon particles and use thereof |
CN113453708A (en) | 2018-12-19 | 2021-09-28 | 默沙东公司 | Compositions comprising streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof |
US20220370606A1 (en) | 2018-12-21 | 2022-11-24 | Pfizer Inc. | Combination Treatments Of Cancer Comprising A TLR Agonist |
EP3946446A1 (en) | 2019-04-02 | 2022-02-09 | Sanofi | Antigenic multimeric respiratory syncytial virus polypeptides |
WO2020208502A1 (en) | 2019-04-10 | 2020-10-15 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
US20220241321A1 (en) * | 2019-05-10 | 2022-08-04 | Microbio (Shanghai) Co., Ltd. | Dimeric cpg oligonucleotides for use in modulating immune responses |
CA3143198A1 (en) * | 2019-06-14 | 2020-12-17 | G Tech Bio Llc | Activated lymphocytic cells and methods of using the same to treat cancer and infectious conditions |
US20220280636A1 (en) | 2019-07-19 | 2022-09-08 | Merck Sharp & Dohme Corp. | Antigenic glycoprotein e polypeptides, compositions, and methods of use thereof |
EP4003411A1 (en) | 2019-07-30 | 2022-06-01 | Phibro Animal Health Corporation | A composition for mucosal administration to avians |
MX2022001241A (en) | 2019-07-31 | 2022-04-20 | Sanofi Pasteur Inc | Multivalent pneumococcal polysaccharide-protein conjugate compositions and methods of using the same. |
JP2022545181A (en) | 2019-08-30 | 2022-10-26 | ユニバーシティ オブ ロチェスター | Septin inhibitors for cancer therapy |
CN110646557A (en) * | 2019-10-12 | 2020-01-03 | 北京航空航天大学 | Urine metabolic marker of glioblastoma patient carrying IDH gene mutation and application thereof |
JP2021087420A (en) | 2019-11-01 | 2021-06-10 | ファイザー・インク | Escherichia coli compositions and methods thereof |
BR112022010228A2 (en) | 2019-12-17 | 2022-09-06 | Us Health | ATTENUATED LIVE LEISHMANIA PARASITE VACCINES WITH INCREASED SAFETY CHARACTERISTICS |
BR112022009723A2 (en) | 2019-12-17 | 2022-08-09 | Pfizer | SPECIFIC ANTIBODIES TO CD47, PD-L1, AND USES THEREOF |
WO2021154745A1 (en) | 2020-01-27 | 2021-08-05 | Oregon State University | Gonorrhea subunit vaccine |
WO2021163448A2 (en) | 2020-02-13 | 2021-08-19 | The Board Of Trustees Of The University Of Illinois | Vaccine and methods for detecting and preventing filariasis |
IL295632A (en) | 2020-02-23 | 2022-10-01 | Pfizer | Escherichia coli compositions and methods thereof |
JP2023515829A (en) | 2020-02-28 | 2023-04-14 | サノフィ パスツール インコーポレイテッド | High-dose influenza vaccine for pediatric subjects |
US11213482B1 (en) | 2020-03-05 | 2022-01-04 | University of Pittsburgh—Of the Commonwealth System of Higher Educat | SARS-CoV-2 subunit vaccine and microneedle array delivery system |
WO2021211279A1 (en) | 2020-04-17 | 2021-10-21 | Regents Of The University Of Minnesota | SARS-CoV-2 SPIKE RECEPTOR BINDING DOMAIN AND COMPOSITIONS AND METHODS THEREOF |
EP3900739A1 (en) | 2020-04-21 | 2021-10-27 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Synthetic streptococcus pneumoniae saccharide conjugates to conserved membrane protein |
CA3178252A1 (en) | 2020-05-11 | 2021-11-18 | Erytech Pharma | Red cell extracellular vesicles (rcevs) containing cargoes and methods of use and production thereof |
CN116323668A (en) | 2020-07-17 | 2023-06-23 | 辉瑞公司 | Therapeutic antibodies and uses thereof |
JP2023538736A (en) | 2020-08-26 | 2023-09-11 | ファイザー・インク | Group B streptococcal polysaccharide-protein conjugates, methods for producing the conjugates, immunogenic compositions comprising the conjugates, and uses thereof |
AU2021343290A1 (en) | 2020-09-17 | 2023-04-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Immunogenic product comprising an IgE fragment for treating IgE-mediated inflammatory disorders |
JP2023542528A (en) | 2020-09-24 | 2023-10-10 | フレッド ハッチンソン キャンサー センター | Immunotherapy targeting SOX2 antigen |
WO2022066973A1 (en) | 2020-09-24 | 2022-03-31 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting pbk or oip5 antigens |
TW202227467A (en) | 2020-10-27 | 2022-07-16 | 美商輝瑞大藥廠 | Escherichia coli compositions and methods thereof |
CA3200602A1 (en) | 2020-11-04 | 2022-05-12 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
WO2022101745A2 (en) | 2020-11-10 | 2022-05-19 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
US20220202923A1 (en) | 2020-12-23 | 2022-06-30 | Pfizer Inc. | E. coli fimh mutants and uses thereof |
WO2022147373A1 (en) | 2020-12-31 | 2022-07-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibody-guided pcsk9-mimicking immunogens lacking 9-residue sequence overlap with human proteins |
WO2022169835A1 (en) | 2021-02-03 | 2022-08-11 | The Board Of Trustees Of The University Of Illinois | Vaccine and methods for preventing filariasis and dirofilariasis |
TW202306969A (en) | 2021-05-28 | 2023-02-16 | 美商輝瑞大藥廠 | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
BR112023023671A2 (en) | 2021-05-28 | 2024-02-06 | Pfizer | IMMUNOGENIC COMPOSITIONS COMPRISING CONJUGATED CAPSULAR SACHARIDE ANTIGENS AND USES THEREOF |
WO2022261251A1 (en) | 2021-06-08 | 2022-12-15 | Glyde Bio Inc. | Immunogenic compositions comprising tumour-associated antigen |
EP4104830A1 (en) | 2021-06-16 | 2022-12-21 | Burghardt Wittig | Sequential innate and adaptive immune modulation for cancer treatment |
WO2023288263A1 (en) | 2021-07-16 | 2023-01-19 | The Board Of Trustees Of The University Of Illinois | Universal vaccine for influenza virus based on tetrameric m2 protein incorporated into nanodiscs |
WO2023018817A1 (en) | 2021-08-11 | 2023-02-16 | Sanofi Pasteur Inc. | Truncated influenza neuraminidase and methods of using the same |
WO2023059857A1 (en) | 2021-10-08 | 2023-04-13 | Sanofi Pasteur Inc. | Multivalent influenza vaccines |
WO2023079507A1 (en) | 2021-11-05 | 2023-05-11 | Sanofi | Respiratory syncytial virus rna vaccine |
WO2023081798A1 (en) | 2021-11-05 | 2023-05-11 | Sanofi Pasteur Inc. | Multivalent influenza vaccines comprising recombinant hemagglutinin and neuraminidase and methods of using the same |
WO2023079113A1 (en) | 2021-11-05 | 2023-05-11 | Sanofi | Hybrid multivalent influenza vaccines comprising hemagglutinin and neuraminidase and methods of using the same |
US20230310571A1 (en) | 2021-11-30 | 2023-10-05 | Sanofi Pasteur Inc. | Human metapneumovirus vaccines |
WO2023102388A1 (en) | 2021-11-30 | 2023-06-08 | Sanofi Pasteur Inc. | Human metapneumovirus viral vector-based vaccines |
WO2023111262A1 (en) | 2021-12-17 | 2023-06-22 | Sanofi | Lyme disease rna vaccine |
WO2023135515A1 (en) | 2022-01-13 | 2023-07-20 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2023144206A1 (en) | 2022-01-27 | 2023-08-03 | Sanofi Pasteur | Modified vero cells and methods of using the same for virus production |
WO2023161817A1 (en) | 2022-02-25 | 2023-08-31 | Pfizer Inc. | Methods for incorporating azido groups in bacterial capsular polysaccharides |
WO2023177579A1 (en) | 2022-03-14 | 2023-09-21 | Sanofi Pasteur Inc. | Machine-learning techniques in protein design for vaccine generation |
WO2023201109A1 (en) | 2022-04-15 | 2023-10-19 | Yale University | Exatecan formulation |
WO2023214082A2 (en) | 2022-05-06 | 2023-11-09 | Sanofi | Signal sequences for nucleic acid vaccines |
WO2023218322A1 (en) | 2022-05-11 | 2023-11-16 | Pfizer Inc. | Process for producing of vaccine formulations with preservatives |
WO2024003239A1 (en) | 2022-06-29 | 2024-01-04 | Bavarian Nordic A/S | RECOMBINANT MODIFIED saRNA (VRP) AND VACCINIA VIRUS ANKARA (MVA) PRIME-BOOST REGIMEN |
Citations (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4452775A (en) * | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
US4981684A (en) * | 1989-10-24 | 1991-01-01 | Coopers Animal Health Limited | Formation of adjuvant complexes |
US5023243A (en) * | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US5178860A (en) * | 1989-09-01 | 1993-01-12 | Coopers Animal Health Limited | Adjuvant complexes and vaccine made therefrom |
US5514577A (en) * | 1990-02-26 | 1996-05-07 | Isis Pharmaceuticals, Inc. | Oligonucleotide therapies for modulating the effects of herpes viruses |
US5527899A (en) * | 1989-10-23 | 1996-06-18 | Gilead Sciences, Inc. | Oligonucleotides with inverted polarity |
US5594122A (en) * | 1993-06-23 | 1997-01-14 | Genesys Pharma Inc. | Antisense oligonucleotides targeted against human immunodeficiency virus |
US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US5705385A (en) * | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
US5723335A (en) * | 1994-03-25 | 1998-03-03 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
US5728518A (en) * | 1994-01-12 | 1998-03-17 | The Immune Response Corporation | Antiviral poly-and oligonucleotides |
US5736152A (en) * | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
US5753613A (en) * | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
US5766920A (en) * | 1982-08-11 | 1998-06-16 | Cellcor, Inc. | Ex vivo activation of immune cells |
US5858987A (en) * | 1995-05-05 | 1999-01-12 | Mitotix, Inc. | E6AP antisense constructs and methods of use |
US6027732A (en) * | 1996-02-21 | 2000-02-22 | Morein; Bror | Iscom or iscom-matrix comprising hydrophobic receptor molecules for antigenic substances |
US6027726A (en) * | 1994-09-30 | 2000-02-22 | Inex Phamaceuticals Corp. | Glycosylated protein-liposome conjugates and methods for their preparation |
US6030954A (en) * | 1991-09-05 | 2000-02-29 | University Of Connecticut | Targeted delivery of poly- or oligonucleotides to cells |
US6030955A (en) * | 1996-03-21 | 2000-02-29 | The Trustees Of Columbia University In The City Of New York And Imclone Systems, Inc. | Methods of affecting intracellular phosphorylation of tyrosine using phosphorothioate oligonucleotides, and antiangiogenic and antiproliferative uses thereof |
US6031086A (en) * | 1994-03-18 | 2000-02-29 | The Regents Of The University Of California | Antisense oligonucleitide containing compositions and method of forming duplexes |
US6174872B1 (en) * | 1996-10-04 | 2001-01-16 | The Regents Of The University Of California | Method for treating allergic lung disease |
US6184369B1 (en) * | 1993-04-23 | 2001-02-06 | Aronex Pharmaceuticals, Inc. | Anti-viral guanosine-rich oligonucleotides |
US6191257B1 (en) * | 1993-04-27 | 2001-02-20 | Baylor College Of Medicine | Natural or recombinant DNA binding proteins as carriers for gene transfer or gene therapy |
US6194388B1 (en) * | 1994-07-15 | 2001-02-27 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US6214806B1 (en) * | 1997-02-28 | 2001-04-10 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CPC dinucleotide in the treatment of LPS-associated disorders |
US6218371B1 (en) * | 1998-04-03 | 2001-04-17 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
US6221882B1 (en) * | 1997-07-03 | 2001-04-24 | University Of Iowa Research Foundation | Methods for inhibiting immunostimulatory DNA associated responses |
US6225292B1 (en) * | 1997-06-06 | 2001-05-01 | The Regents Of The University Of California | Inhibitors of DNA immunostimulatory sequence activity |
US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US6339068B1 (en) * | 1997-05-20 | 2002-01-15 | University Of Iowa Research Foundation | Vectors and methods for immunization or therapeutic protocols |
US6348312B1 (en) * | 1993-11-12 | 2002-02-19 | Hoescht Aktiengesellschaft | Stabilized oligonucleotides and their use |
US20020055477A1 (en) * | 2000-03-10 | 2002-05-09 | Nest Gary Van | Immunomodulatory formulations and methods for use thereof |
US6503533B1 (en) * | 1994-07-28 | 2003-01-07 | Georgetown University | Antisense ogligonucleotides against Hepatitis B viral replication |
US20030022852A1 (en) * | 2000-03-10 | 2003-01-30 | Nest Gary Van | Biodegradable immunomodulatory formulations and methods for use thereof |
US20030026801A1 (en) * | 2000-06-22 | 2003-02-06 | George Weiner | Methods for enhancing antibody-induced cell lysis and treating cancer |
US20030029783A1 (en) * | 2001-07-13 | 2003-02-13 | Donald Hubbard H. | Aerobic treatment plant with filter pipe |
US20030050263A1 (en) * | 1994-07-15 | 2003-03-13 | The University Of Iowa Research Foundation | Methods and products for treating HIV infection |
US20030049266A1 (en) * | 2000-12-27 | 2003-03-13 | Fearon Karen L. | Immunomodulatory polynucleotides and methods of using the same |
US20030050268A1 (en) * | 2001-03-29 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid for treatment of non-allergic inflammatory diseases |
US20030055014A1 (en) * | 2000-12-14 | 2003-03-20 | Bratzler Robert L. | Inhibition of angiogenesis by nucleic acids |
US20030078223A1 (en) * | 1996-01-30 | 2003-04-24 | Eyal Raz | Compositions and methods for modulating an immune response |
US20030091599A1 (en) * | 1997-03-10 | 2003-05-15 | Coley Pharmaceutical Gmbh | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US20030092663A1 (en) * | 1997-09-05 | 2003-05-15 | Eyal Raz | Immunization-free methods for treating antigen-stimulated inflammation in a mammalian host and shifting the host's antigen immune responsiveness to a Th1 phenotype |
US20030100527A1 (en) * | 1994-07-15 | 2003-05-29 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
US20040006034A1 (en) * | 1998-06-05 | 2004-01-08 | Eyal Raz | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
US20040009949A1 (en) * | 2002-06-05 | 2004-01-15 | Coley Pharmaceutical Group, Inc. | Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory CpG nucleic acids |
US20040030118A1 (en) * | 1998-05-14 | 2004-02-12 | Hermann Wagner | Methods for regulating hematopoiesis using CpG-oligonucleotides |
US20040053882A1 (en) * | 2000-05-18 | 2004-03-18 | Smith Mark Peart | Combination chemotherapy |
US20040067902A9 (en) * | 2000-02-03 | 2004-04-08 | Bratzler Robert L. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
US20040067905A1 (en) * | 2002-07-03 | 2004-04-08 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
US20040087534A1 (en) * | 1994-07-15 | 2004-05-06 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20040092472A1 (en) * | 2002-07-03 | 2004-05-13 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US20050054601A1 (en) * | 1997-01-23 | 2005-03-10 | Coley Pharmaceutical Gmbh | Pharmaceutical composition comprising a polynucleotide and optionally an antigen especially for vaccination |
US20050059619A1 (en) * | 2002-08-19 | 2005-03-17 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids |
US20050101557A1 (en) * | 1994-07-15 | 2005-05-12 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20050100983A1 (en) * | 2003-11-06 | 2005-05-12 | Coley Pharmaceutical Gmbh | Cell-free methods for identifying compounds that affect toll-like receptor 9 (TLR9) signaling |
US20060003962A1 (en) * | 2002-10-29 | 2006-01-05 | Coley Pharmaceutical Group, Ltd. | Methods and products related to treatment and prevention of hepatitis C virus infection |
US20060019923A1 (en) * | 2004-07-18 | 2006-01-26 | Coley Pharmaceutical Group, Ltd. | Methods and compositions for inducing innate immune responses |
US20060019916A1 (en) * | 2004-04-02 | 2006-01-26 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for inducing IL-10 responses |
US7157437B2 (en) * | 2000-03-10 | 2007-01-02 | Dynavax Technologies Corporation | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
US20070006010A1 (en) * | 2005-06-30 | 2007-01-04 | Paul Wallner | Synchronous signal generator |
US20070066554A1 (en) * | 1999-09-25 | 2007-03-22 | Coley Pharmaceutical Gmbh | Immunostimulatory nucleic acids |
US7214380B1 (en) * | 1998-06-23 | 2007-05-08 | The Board Of Trustees Of The Leland Stanford Junior University | Adjuvant therapy |
Family Cites Families (459)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2003A (en) * | 1841-03-12 | Improvement in horizontal windivhlls | ||
US2005A (en) * | 1841-03-16 | Improvement in the manner of constructing molds for casting butt-hinges | ||
US2002A (en) * | 1841-03-12 | Tor and planter for plowing | ||
US2010A (en) * | 1841-03-18 | Machine foe | ||
US2004A (en) * | 1841-03-12 | Improvement in the manner of constructing and propelling steam-vessels | ||
US3521637A (en) * | 1967-11-28 | 1970-07-28 | Nelson J Waterbury | Tampon or similar sanitary napkin containing vitamin a |
US3627874A (en) | 1969-07-16 | 1971-12-14 | Merck & Co Inc | Vaccine preparation |
US3761585A (en) | 1971-04-05 | 1973-09-25 | Beecham Group Ltd | Vaccines containing modified allergenic material |
US3906092A (en) | 1971-11-26 | 1975-09-16 | Merck & Co Inc | Stimulation of antibody response |
DE2643213C2 (en) * | 1976-09-25 | 1985-02-21 | Bayer Ag, 5090 Leverkusen | Process for attenuating or inactivating microorganisms |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
EP0092574B1 (en) | 1981-10-23 | 1992-04-29 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and methods of making same |
ES8301593A1 (en) | 1981-11-16 | 1983-01-01 | Union Ind Y Agro Ganader S A U | Nucleotide enriched humanized milk and process for its preparation |
SE8205892D0 (en) | 1982-10-18 | 1982-10-18 | Bror Morein | IMMUNOGENT MEMBRANE PROTEIN COMPLEX, SET FOR PREPARATION AND USE THEREOF |
SE8405493D0 (en) | 1984-11-01 | 1984-11-01 | Bror Morein | IMMUNOGENT COMPLEX AND KITCHEN FOR PREPARING IT AND USING IT AS IMMUNOSTIMENTING AGENTS |
US5308626A (en) * | 1985-06-28 | 1994-05-03 | Toni N. Mariani | Lymphokine activated effector cells for antibody-dependent cellular cytotoxicity (ADCC) treatment of cancer and other diseases |
ES2039229T3 (en) | 1986-01-14 | 1993-09-16 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezondheid En Cultuur | PROCEDURE FOR THE PREPARATION OF IMMUNOGENIC COMPLEXES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPLEXES. |
US5194428A (en) | 1986-05-23 | 1993-03-16 | Worcester Foundation For Experimental Biology | Inhibition of influenza virus replication by oligonucleotide phosphorothioates |
US4806463A (en) | 1986-05-23 | 1989-02-21 | Worcester Foundation For Experimental Biology | Inhibition of HTLV-III by exogenous oligonucleotides |
US5059519A (en) | 1986-07-01 | 1991-10-22 | University Of Massachusetts Medical School | Oligonucleotide probes for the determination of the proclivity for development of autoimmune diseases |
US5075109A (en) * | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
ES2007350A6 (en) | 1987-05-29 | 1989-06-16 | Ganadera Union Ind Agro | Food products enriched with nucleosides and/or nucleotides and preparation thereof. |
CA1339596C (en) | 1987-08-07 | 1997-12-23 | New England Medical Center Hospitals, Inc. | Viral expression inhibitors |
US5004810A (en) | 1988-09-30 | 1991-04-02 | Schering Corporation | Antiviral oligomers |
NZ230747A (en) | 1988-09-30 | 1992-05-26 | Bror Morein | Immunomodulating matrix comprising a complex of at least one lipid and at least one saponin; certain glycosylated triterpenoid saponins derived from quillaja saponaria molina |
US5087617A (en) * | 1989-02-15 | 1992-02-11 | Board Of Regents, The University Of Texas System | Methods and compositions for treatment of cancer using oligonucleotides |
US5112605A (en) * | 1989-03-17 | 1992-05-12 | Genentech, Inc. | Temporal gamma-interferon administration for allergies |
US5693622A (en) | 1989-03-21 | 1997-12-02 | Vical Incorporated | Expression of exogenous polynucleotide sequences cardiac muscle of a mammal |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5629158A (en) * | 1989-03-22 | 1997-05-13 | Cemu Bitecknik Ab | Solid phase diagnosis of medical conditions |
US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
US5399346A (en) * | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
US5676954A (en) | 1989-11-03 | 1997-10-14 | Vanderbilt University | Method of in vivo delivery of functioning foreign genes |
US5786189A (en) | 1989-11-29 | 1998-07-28 | Smithkline Beecham Biologicals (S.A.) | Vaccine |
US5457189A (en) | 1989-12-04 | 1995-10-10 | Isis Pharmaceuticals | Antisense oligonucleotide inhibition of papillomavirus |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5514788A (en) * | 1993-05-17 | 1996-05-07 | Isis Pharmaceuticals, Inc. | Oligonucleotide modulation of cell adhesion |
US5248670A (en) | 1990-02-26 | 1993-09-28 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides for inhibiting herpesviruses |
US5166195A (en) | 1990-05-11 | 1992-11-24 | Isis Pharmaceuticals, Inc. | Antisense inhibitors of the human immunodeficiency virus phosphorothioate oligonucleotides |
EP1493825A3 (en) | 1990-06-11 | 2005-02-09 | Gilead Sciences, Inc. | Method for producing nucleic acid ligands |
EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
US5245022A (en) * | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
ATE154947T1 (en) | 1990-08-16 | 1997-07-15 | Isis Pharmaceuticals Inc | OLIGONUCLEOTIDES FOR MODULATING THE EFFECTS OF CYTOMEGALOVIRUS INFECTIONS |
US6042838A (en) | 1991-02-15 | 2000-03-28 | Uab Research Foundation | immunogenic compositions for mucosal administration of pneumococcal surface protein A (PspA) |
JP3507486B2 (en) * | 1991-03-15 | 2004-03-15 | アムジエン・インコーポレーテツド | Intrapulmonary administration of granulocyte colony-stimulating factor |
US5683985A (en) | 1991-04-18 | 1997-11-04 | The Salk Institute For Biological Studies | Oligonucleotide decoys and methods relating thereto |
US5498410A (en) * | 1991-04-22 | 1996-03-12 | Gleich; Gerald J. | Method for the treatment of eosinophil-associated conditions with anionic polymers |
US5681555A (en) | 1991-04-22 | 1997-10-28 | Gleich; Gerald J. | Method for the treatment of bronchial asthma by parenteral administration of anionic polymers |
WO1994008003A1 (en) | 1991-06-14 | 1994-04-14 | Isis Pharmaceuticals, Inc. | ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE |
CA2110040A1 (en) | 1991-05-31 | 1992-12-10 | Lyle J. Arnold, Jr. | Compositions and delivery systems for transdermal administration of neutral oligomers |
US5582986A (en) | 1991-06-14 | 1996-12-10 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide inhibition of the ras gene |
US5576302A (en) | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
CA2123611A1 (en) | 1991-11-15 | 1993-05-27 | Alan M. Gewirtz | Treatment of melanoma with antisense oligonucleotides to c-myb proto-oncogene |
WO1993010138A1 (en) | 1991-11-18 | 1993-05-27 | Tanox Biosystems, Inc. | Anti-sense oligonucleotides for isotype-specific suppression of immunoglobulin production |
US5858784A (en) * | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
WO1993015207A2 (en) | 1992-02-04 | 1993-08-05 | Viagene, Inc. | Hepatitis therapeutics |
US5643578A (en) * | 1992-03-23 | 1997-07-01 | University Of Massachusetts Medical Center | Immunization by inoculation of DNA transcription unit |
US6498147B2 (en) | 1992-05-22 | 2002-12-24 | The Scripps Research Institute | Suppression of nuclear factor-κb dependent processes using oligonucleotides |
IL105914A0 (en) | 1992-06-04 | 1993-10-20 | Univ California | Methods and compositions for in vivo gene therapy |
US5726518A (en) * | 1992-07-22 | 1998-03-10 | Nikon Corporation | Supporting device of relative moving element of vibration actuator or vibration motor |
US5585479A (en) | 1992-07-24 | 1996-12-17 | The United States Of America As Represented By The Secretary Of The Navy | Antisense oligonucleotides directed against human ELAM-I RNA |
DE69316369D1 (en) | 1992-07-27 | 1998-02-19 | Hybridon Inc | Oligonukleotid alkylphosphonothiate |
US6107062A (en) * | 1992-07-30 | 2000-08-22 | Inpax, Inc. | Antisense viruses and antisense-ribozyme viruses |
WO1994004196A1 (en) | 1992-08-14 | 1994-03-03 | Imperial Cancer Research Technology Limited | Tumour therapy |
US5429199A (en) * | 1992-08-26 | 1995-07-04 | Kennametal Inc. | Cutting bit and cutting insert |
HUT72400A (en) | 1992-10-05 | 1996-04-29 | Hybridon Inc | Therapeutic anti-hiv oligonucleotide, pharmaceutical compositions containing them and methods for use of compositions |
US5593972A (en) * | 1993-01-26 | 1997-01-14 | The Wistar Institute | Genetic immunization |
EP0692972B2 (en) * | 1993-04-02 | 2012-03-21 | AntiCancer, Inc. | Method for delivering beneficial compositions to hair follicles |
WO1994029461A1 (en) | 1993-06-11 | 1994-12-22 | Commonwealth Scientific And Industrial Research Organisation | Method for specific silencing of genes by dna methylation |
CA2166889C (en) | 1993-07-19 | 2001-09-11 | Todd C. Peterson | Oligonucleotides with activity against human immunodeficiency virus |
US6004534A (en) | 1993-07-23 | 1999-12-21 | Massachusetts Institute Of Technology | Targeted polymerized liposomes for improved drug delivery |
US6605708B1 (en) | 1993-07-28 | 2003-08-12 | Hybridon, Inc. | Building blocks with carbamate internucleoside linkages and oligonucleotides derived therefrom |
US5830877A (en) | 1993-08-26 | 1998-11-03 | The Regents Of The University Of California | Method, compositions and devices for administration of naked polynucleotides which encode antigens and immunostimulatory |
US5679647A (en) | 1993-08-26 | 1997-10-21 | The Regents Of The University Of California | Methods and devices for immunizing a host against tumor-associated antigens through administration of naked polynucleotides which encode tumor-associated antigenic peptides |
US20030109469A1 (en) | 1993-08-26 | 2003-06-12 | Carson Dennis A. | Recombinant gene expression vectors and methods for use of same to enhance the immune response of a host to an antigen |
AU705889B2 (en) | 1993-08-26 | 1999-06-03 | Regents Of The University Of California, The | Method, compositions and devices for administration of naked polynucleotides which encode antigens and immunostimulatory peptides |
US5804566A (en) | 1993-08-26 | 1998-09-08 | The Regents Of The University Of California | Methods and devices for immunizing a host through administration of naked polynucleotides with encode allergenic peptides |
US5985847A (en) | 1993-08-26 | 1999-11-16 | The Regents Of The University Of California | Devices for administration of naked polynucleotides which encode biologically active peptides |
FR2711670B1 (en) * | 1993-10-22 | 1996-01-12 | Pasteur Institut | Nucleotide vector, composition containing it and vaccine for immunization against hepatitis. |
EP0736093B1 (en) | 1993-12-23 | 2003-03-19 | BIOGNOSTIK GESELLSCHAFT FÜR BIOMOLEKULARE DIAGNOSTIK mbH | ANTISENSE NUCLEIC ACIDS FOR THE PREVENTION AND TREATMENT OF DISORDERS IN WHICH EXPRESSION OF c-erbB-2 PLAYS A ROLL |
US5712384A (en) | 1994-01-05 | 1998-01-27 | Gene Shears Pty Ltd. | Ribozymes targeting retroviral packaging sequence expression constructs and recombinant retroviruses containing such constructs |
US5646126A (en) | 1994-02-28 | 1997-07-08 | Epoch Pharmaceuticals | Sterol modified oligonucleotide duplexes having anticancer activity |
CA2190121A1 (en) | 1994-03-15 | 1995-09-21 | Edith Mathiowitz | Polymeric gene delivery system |
US5451569A (en) | 1994-04-19 | 1995-09-19 | Hong Kong University Of Science And Technology R & D Corporation Limited | Pulmonary drug delivery system |
US5696248A (en) | 1994-06-15 | 1997-12-09 | Hoechst Aktiengesellschaft | 3'-modified oligonucleotide derivatives |
US5741516A (en) | 1994-06-20 | 1998-04-21 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
US5543152A (en) | 1994-06-20 | 1996-08-06 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
JPH10502820A (en) | 1994-07-18 | 1998-03-17 | ユニバーシティ・オブ・ノース・カロライナ・アット・チャペル・ヒル | Oligonucleoside compounds and methods for inhibiting tumor growth, invasion and metastasis |
ATE219660T1 (en) * | 1994-09-30 | 2002-07-15 | Inex Pharmaceuticals Corp | AGENT FOR INTRODUCING POLYANIONIC MATERIALS INTO CELLS |
WO1996012008A1 (en) | 1994-10-13 | 1996-04-25 | Merck & Co., Inc. | Synthesis of methylase-resistant genes |
US6630455B1 (en) | 1995-01-13 | 2003-10-07 | Vanderbilt University | Methods for inducing mucosal immune responses |
US5795587A (en) * | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
US6008202A (en) * | 1995-01-23 | 1999-12-28 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
US5674483A (en) * | 1995-01-31 | 1997-10-07 | National Jewish Medical And Research Center | Treatment for diseases involving inflammation |
DE19502912A1 (en) | 1995-01-31 | 1996-08-01 | Hoechst Ag | G-Cap Stabilized Oligonucleotides |
WO1996024380A1 (en) | 1995-02-09 | 1996-08-15 | Icn Pharmaceuticals, Inc. | Methods and compositions for regulation of cd28 expression |
US5932556A (en) | 1995-09-17 | 1999-08-03 | Tam; Robert C | Methods and compositions for regulation of CD28 expression |
GB9505438D0 (en) | 1995-03-17 | 1995-05-03 | Sod Conseils Rech Applic | Antisense oligonucleotides |
US5703057A (en) | 1995-04-07 | 1997-12-30 | Board Of Regents The University Of Texas System | Expression library immunization |
CA2192674C (en) | 1995-04-13 | 2001-02-13 | John Mcmichael | Methods for treating respiratory disease |
US6096721A (en) * | 1995-04-13 | 2000-08-01 | Milkhaus Laboratory, Inc. | Method for treating mucositis by sublingual administration of DNA |
UA56132C2 (en) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Vaccine composition (variants), method for stabilizing qs21 providing resistance against hydrolysis (variants), method for manufacturing vaccine |
CA2220433C (en) | 1995-05-11 | 2010-02-16 | Applied Research Systems Ars Holding N.V. | Il-6 activity inhibitor |
US5955059A (en) * | 1995-06-06 | 1999-09-21 | Trustees Of Boston University | Use of locally applied DNA fragments |
US6025339A (en) * | 1995-06-07 | 2000-02-15 | East Carolina University | Composition, kit and method for treatment of disorders associated with bronchoconstriction and lung inflammation |
US5830878A (en) | 1995-06-07 | 1998-11-03 | Megabios Corporation | Cationic lipid: DNA complexes for gene targeting |
US7034007B1 (en) * | 1995-06-07 | 2006-04-25 | East Carolina University | Low adenosine anti-sense oligonucleotide, compositions, kit & method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) & surfactant depletion |
US6040296A (en) * | 1995-06-07 | 2000-03-21 | East Carolina University | Specific antisense oligonucleotide composition & method for treatment of disorders associated with bronchoconstriction and lung inflammation |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
EP1489184A1 (en) | 1995-06-07 | 2004-12-22 | Inex Pharmaceutical Corp. | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
US5994315A (en) | 1995-06-07 | 1999-11-30 | East Carolina University | Low adenosine agent, composition, kit and method for treatment of airway disease |
WO1997000957A1 (en) | 1995-06-23 | 1997-01-09 | President And Fellows Of Harvard College | Transcriptional regulation of genes encoding vascular endothelial growth factor receptors |
US5985662A (en) | 1995-07-13 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of hepatitis B virus replication |
CA2227287A1 (en) | 1995-07-21 | 1997-02-06 | Brown University Research Foundation | A method for gene therapy using nucleic acid loaded polymeric microparticles |
US6248720B1 (en) * | 1996-07-03 | 2001-06-19 | Brown University Research Foundation | Method for gene therapy using nucleic acid loaded polymeric microparticles |
US5968909A (en) | 1995-08-04 | 1999-10-19 | Hybridon, Inc. | Method of modulating gene expression with reduced immunostimulatory response |
US6667293B1 (en) * | 1995-09-12 | 2003-12-23 | Hybridon, Inc. | Use of cyclodextrins to modulate gene expression with reduced immunostimulatory response |
CZ97798A3 (en) | 1995-10-04 | 1999-02-17 | Immunex Corporation | Use of flt3 ligand, vaccine adjuvans, expansion media, preparation and cell population and method |
US5780448A (en) * | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
WO1997028259A1 (en) | 1996-01-30 | 1997-08-07 | The Regents Of The University Of California | Gene expression vectors which generate an antigen specific immune response and methods of using the same |
SE9600647D0 (en) | 1996-02-21 | 1996-02-21 | Bror Morein | New use |
US5994316A (en) | 1996-02-21 | 1999-11-30 | The Immune Response Corporation | Method of preparing polynucleotide-carrier complexes for delivery to cells |
US5843770A (en) | 1996-03-11 | 1998-12-01 | The Immune Response Corporation | Antisense constructs directed against viral post-transcriptional regulatory sequences |
US6620805B1 (en) | 1996-03-14 | 2003-09-16 | Yale University | Delivery of nucleic acids by porphyrins |
US6121247A (en) | 1996-03-29 | 2000-09-19 | The Johns Hopkins University | Therapy for allergic diseases |
US6184037B1 (en) | 1996-05-17 | 2001-02-06 | Genemedicine, Inc. | Chitosan related compositions and methods for delivery of nucleic acids and oligonucleotides into a cell |
JP2002514047A (en) | 1996-07-10 | 2002-05-14 | イミュネックス・コーポレーション | How to activate dendritic cells |
DE69736692T2 (en) | 1996-07-16 | 2007-06-14 | Archibald James Mixson | Cationic vehicle: DNA complexes and their use in gene therapy |
US5854418A (en) | 1996-07-25 | 1998-12-29 | The Trustees Of Columbia University In The City Of New York | Kaposi's sarcoma-associated herpesvirus (KSHV) viral macrophage inflammatory protein-1α II (vMIP-1α II) and uses thereof |
US5856462A (en) | 1996-09-10 | 1999-01-05 | Hybridon Incorporated | Oligonucleotides having modified CpG dinucleosides |
DE19637223A1 (en) * | 1996-09-13 | 1998-04-09 | Beiersdorf Ag | Removable, self-adhesive device |
ES2241042T3 (en) * | 1996-10-11 | 2005-10-16 | The Regents Of The University Of California | IMMUNO STIMULATOR POLINUCLEOTIDE CONJUGATES / IMMUNOMODULATOR MOLECULA. |
US6562345B1 (en) * | 1996-11-12 | 2003-05-13 | City Of Hope | Immuno-reactive peptide CTL epitopes of human cytomegalovirus |
US6797276B1 (en) * | 1996-11-14 | 2004-09-28 | The United States Of America As Represented By The Secretary Of The Army | Use of penetration enhancers and barrier disruption agents to enhance the transcutaneous immune response |
US20060002949A1 (en) * | 1996-11-14 | 2006-01-05 | Army Govt. Of The Usa, As Rep. By Secretary Of The Office Of The Command Judge Advocate, Hq Usamrmc. | Transcutaneous immunization without heterologous adjuvant |
US20060002959A1 (en) * | 1996-11-14 | 2006-01-05 | Government Of The United States | Skin-sctive adjuvants for transcutaneous immuization |
SE9604296D0 (en) | 1996-11-22 | 1996-11-22 | Astra Ab | New pharmaceutical formulation of polypeptides |
HU0000769A (en) | 1996-12-27 | 2000-07-28 | G-rich oligo aptamers and methods of modulating an immune response | |
FR2757876B1 (en) | 1996-12-27 | 1999-04-09 | Biovector Therapeutics Sa | CONJUGATES OF A PARTICULATE VECTOR AND OLIGONUCLEOTIDES, THEIR PREPARATION METHOD AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
US20030064945A1 (en) * | 1997-01-31 | 2003-04-03 | Saghir Akhtar | Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptors |
GB9702021D0 (en) | 1997-01-31 | 1997-03-19 | Imperial College | Medicaments |
US7517952B1 (en) * | 1997-02-25 | 2009-04-14 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
CA2283557A1 (en) * | 1997-03-10 | 1998-09-17 | Heather L. Davis | Use of nucleic acids containing unmethylated cpg dinucleotide as an adjuvant |
US5965542A (en) | 1997-03-18 | 1999-10-12 | Inex Pharmaceuticals Corp. | Use of temperature to control the size of cationic liposome/plasmid DNA complexes |
US6426334B1 (en) | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
US6835395B1 (en) | 1997-05-14 | 2004-12-28 | The University Of British Columbia | Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles |
US20030104044A1 (en) * | 1997-05-14 | 2003-06-05 | Semple Sean C. | Compositions for stimulating cytokine secretion and inducing an immune response |
DE69841002D1 (en) * | 1997-05-14 | 2009-09-03 | Univ British Columbia | Highly effective encapsulation of nucleic acids in lipid vesicles |
JP2001526688A (en) | 1997-05-19 | 2001-12-18 | メルク エンド カンパニー インコーポレーテッド | Oligonucleotide adjuvant |
US6589940B1 (en) | 1997-06-06 | 2003-07-08 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
AU8428998A (en) | 1997-07-24 | 1999-02-16 | Inex Pharmaceuticals Corporation | Preparation of lipid-nucleic acid particles using a solvent extraction and direct hydration method |
US5877309A (en) * | 1997-08-13 | 1999-03-02 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides against JNK |
WO1999009154A2 (en) | 1997-08-19 | 1999-02-25 | Hybridon, Inc. | Novel hiv-specific synthetic oligonucleotides and methods of their use |
US6749856B1 (en) | 1997-09-11 | 2004-06-15 | The United States Of America, As Represented By The Department Of Health And Human Services | Mucosal cytotoxic T lymphocyte responses |
NZ504894A (en) * | 1997-12-02 | 2002-12-20 | Powderject Vaccines Inc | Crystalline vaccine and adjuvant compositions jointly and separately administered to animals using a transdermal or transmucosally delivery technique |
AU1656799A (en) | 1997-12-12 | 1999-07-05 | Inex Pharmaceuticals Corp. | Cationic drugs encapsulated in anionic liposomes |
US7393630B2 (en) * | 1997-12-16 | 2008-07-01 | Novartis Vaccines And Diagnostics, Inc. | Use of microparticles combined with submicron oil-in-water emulsions |
DE69834133D1 (en) | 1997-12-23 | 2006-05-18 | Inex Pharmaceuticals Corp | NYLON Oligomers |
US20050031638A1 (en) * | 1997-12-24 | 2005-02-10 | Smithkline Beecham Biologicals S.A. | Vaccine |
GB9727262D0 (en) | 1997-12-24 | 1998-02-25 | Smithkline Beecham Biolog | Vaccine |
JPH11209289A (en) * | 1998-01-22 | 1999-08-03 | Taisho Pharmaceut Co Ltd | Mucosal immunity inducer |
BR9908278A (en) | 1998-02-25 | 2002-01-02 | Iomai Corp | Use of agents to improve penetration and break through skin barriers, improve the immune transcutaneous response induced by the adp ribosylation ethoxine |
CN1159348C (en) * | 1998-03-12 | 2004-07-28 | 卢西特国际英国有限公司 | Polymer composition |
NZ506603A (en) | 1998-04-09 | 2002-10-25 | Smithkline Beecham Biolog S | Adjuvant compositions comprising polyoxyethylene ether or polyoxyethylene ester |
DE69932164D1 (en) | 1998-04-28 | 2006-08-10 | Inex Pharmaceuticals Corp | POLYANIONIC POLYMERS WITH IMPROVED FUSOGENICITY |
JP2002513763A (en) | 1998-05-06 | 2002-05-14 | ユニバーシティ オブ アイオワ リサーチ ファウンデーション | Methods for preventing and treating parasitic infections and related diseases using CPG oligonucleotides |
DK1077722T3 (en) | 1998-05-22 | 2006-11-27 | Ottawa Health Research Inst | Methods and products for the induction of mucosa immunity |
US6881561B1 (en) | 1998-05-27 | 2005-04-19 | Cheil Jedang Corporation | Endonuclease of immune cell, process for producing the same and immune adjuvant using the same |
US6248329B1 (en) * | 1998-06-01 | 2001-06-19 | Ramaswamy Chandrashekar | Parasitic helminth cuticlin nucleic acid molecules and uses thereof |
US6562798B1 (en) * | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
JP4627369B2 (en) | 1998-06-10 | 2011-02-09 | バイオグノスティック ゲゼルシャフト フュア バイオモレキュラー ダイアグノスティック ミット ベシュレンクテル ハフツング | How to stimulate the immune system |
US6693086B1 (en) * | 1998-06-25 | 2004-02-17 | National Jewish Medical And Research Center | Systemic immune activation method using nucleic acid-lipid complexes |
US20030022854A1 (en) * | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
US20040247662A1 (en) | 1998-06-25 | 2004-12-09 | Dow Steven W. | Systemic immune activation method using nucleic acid-lipid complexes |
ATE237312T1 (en) | 1998-07-20 | 2003-05-15 | Protiva Biotherapeutics Inc | NUCLEIC ACID COMPLEXES ENCAPSULATED IN LIPOSOMES |
EP1100807A1 (en) | 1998-07-27 | 2001-05-23 | University Of Iowa Research Foundation | STEREOISOMERS OF CpG OLIGONUCLEOTIDES AND RELATED METHODS |
GB9817052D0 (en) | 1998-08-05 | 1998-09-30 | Smithkline Beecham Biolog | Vaccine |
EP0979869A1 (en) | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
US20010034330A1 (en) | 1998-08-10 | 2001-10-25 | Charlotte Kensil | Innate immunity-stimulating compositions of CpG and saponin and methods thereof |
ATE315405T1 (en) | 1998-08-10 | 2006-02-15 | Antigenics Inc | CPG COMPOSITIONS, SAPONIN ADJUVANTS AND METHODS OF USE THEREOF |
DE69943392D1 (en) * | 1998-08-20 | 2011-06-09 | Du Pont | GENES FOR FATTY ACID MODIFYING ENZYMES OF PLANTS AND ASSOCIATED EDUCATION OF CONJUGATED DOUBLE BINDINGS |
EP1108017A2 (en) | 1998-09-03 | 2001-06-20 | Coley Pharmaceutical GmbH | G-motif oligonucleotides and uses thereof |
US20020065236A1 (en) | 1998-09-09 | 2002-05-30 | Yew Nelson S. | CpG reduced plasmids and viral vectors |
FR2783170B1 (en) * | 1998-09-11 | 2004-07-16 | Pasteur Merieux Serums Vacc | IMMUNOSTIMULATING EMULSION |
ATE326239T1 (en) | 1998-09-18 | 2006-06-15 | Dynavax Tech Corp | METHODS FOR TREATING IG-E ASSOCIATED DISEASES AND COMPOSITIONS FOR USE IN SUCH METHODS |
EP1671646A3 (en) | 1998-09-18 | 2007-08-29 | Dynavax Technologies Corporation | Methods of treating IgE-associated disorders and compositions for use therein |
WO2000020039A1 (en) | 1998-10-05 | 2000-04-13 | The Regents Of The University Of California | Methods and adjuvants for stimulating mucosal immunity |
AU6425999A (en) | 1998-10-09 | 2000-05-01 | Dynavax Technologies Corporation | Anti hiv compositions comprising immunostimulatory polynucleotides and hiv antigens |
DE69935606T9 (en) | 1998-10-16 | 2021-03-11 | Glaxosmithkline Biologicals S.A. | ADJUVANCE SYSTEMS AND VACCINE |
AUPP807399A0 (en) | 1999-01-08 | 1999-02-04 | Csl Limited | Improved immunogenic lhrh composition and methods relating thereto |
EP1165773A4 (en) | 1999-02-02 | 2005-01-05 | Biocache Pharmaceuticals Inc | Advanced antigen presentation platform |
US6887464B1 (en) | 1999-02-02 | 2005-05-03 | Biocache Pharmaceuticals, Inc. | Advanced antigen presentation platform |
WO2000045849A2 (en) | 1999-02-05 | 2000-08-10 | Genzyme Corporation | Use of cationic lipids to generate anti-tumor immunity |
US6207819B1 (en) | 1999-02-12 | 2001-03-27 | Isis Pharmaceuticals, Inc. | Compounds, processes and intermediates for synthesis of mixed backbone oligomeric compounds |
AU3760100A (en) * | 1999-03-16 | 2000-10-04 | Panacea Pharmaceuticals, Llc | Immunostimulatory nucleic acids and antigens |
FR2790955B1 (en) | 1999-03-19 | 2003-01-17 | Assist Publ Hopitaux De Paris | USE OF STABILIZED OLIGONUCLEOTIDES AS ANTI-TUMOR ACTIVE INGREDIENT |
NZ513841A (en) | 1999-03-19 | 2001-09-28 | Smithkline Beecham Biolog S | Vaccine against Streptococcus pneumoniae |
US6625426B2 (en) * | 1999-03-22 | 2003-09-23 | Ronald Baratono | Combined rear view mirror and telephone |
US6977245B2 (en) * | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
WO2000061151A2 (en) | 1999-04-12 | 2000-10-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
AU4642600A (en) | 1999-04-15 | 2000-11-02 | Regents Of The University Of California, The | Methods and compositions for use in potentiating antigen presentation by antigenpresenting cells |
US6558670B1 (en) * | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
HU229255B1 (en) | 1999-04-19 | 2013-10-28 | Smithkline Beecham Biolog | Vaccines |
WO2000067023A1 (en) | 1999-04-29 | 2000-11-09 | Coley Pharmaceutical Gmbh | Screening for immunostimulatory dna functional modifyers |
US6737066B1 (en) * | 1999-05-06 | 2004-05-18 | The Immune Response Corporation | HIV immunogenic compositions and methods |
CA2372960C (en) | 1999-05-06 | 2006-03-28 | The Immune Response Corporation | Hiv immunogenic compositions and methods |
CA2376634A1 (en) | 1999-06-08 | 2000-12-14 | Aventis Pasteur | Immunostimulant oligonucleotide |
CA2412345A1 (en) | 1999-06-16 | 2000-12-21 | University Of Iowa Research Foundation | Antagonism of immunostimulatory cpg-oligonucleotides by 4-aminoquinolines and other weak bases |
GB9915204D0 (en) | 1999-06-29 | 1999-09-01 | Smithkline Beecham Biolog | Vaccine |
US20050002958A1 (en) * | 1999-06-29 | 2005-01-06 | Smithkline Beecham Biologicals Sa | Vaccines |
WO2001000232A2 (en) | 1999-06-29 | 2001-01-04 | Smithkline Beecham Biologicals S.A. | Use of cpg as an adjuvant for hiv vaccine |
US6514948B1 (en) * | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
FR2795963A1 (en) * | 1999-07-08 | 2001-01-12 | Pasteur Merieux Serums Vacc | New polynucleotides are useful as vaccines for humans |
DE19935756A1 (en) * | 1999-07-27 | 2001-02-08 | Mologen Forschungs Entwicklung | Covalently closed nucleic acid molecule for immune stimulation |
PT1200580E (en) | 1999-08-13 | 2005-03-31 | Hybridon Inc | MODULATION OF IMMUNITARY STIMULATION MEASURED BY OLIGONUCLEOTIDES CPG THROUGH POSITIONAL MODIFICATION OF NUCLEOSIDOS |
ATE419869T1 (en) | 1999-08-19 | 2009-01-15 | Dynavax Tech Corp | METHOD FOR MODULATING AN IMMUNE RESPONSE USING IMMUNSTIMULATIVE SEQUENCES AND COMPOSITIONS THEREOF |
US20050249794A1 (en) | 1999-08-27 | 2005-11-10 | Semple Sean C | Compositions for stimulating cytokine secretion and inducing an immune response |
US6395678B1 (en) * | 1999-09-01 | 2002-05-28 | Aero-Terra-Aqua Technologies Corporation | Bead and process for removing dissolved metal contaminants |
GB9921147D0 (en) | 1999-09-07 | 1999-11-10 | Smithkline Beecham Biolog | Novel composition |
GB9921146D0 (en) | 1999-09-07 | 1999-11-10 | Smithkline Beecham Biolog | Novel composition |
IL148844A0 (en) * | 1999-09-27 | 2002-09-12 | Coley Pharm Group Inc | Methods related to immunostimulatory nucleic acid-induced interferon |
US6949520B1 (en) | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
JP2003512826A (en) * | 1999-10-27 | 2003-04-08 | カイロン コーポレイション | Activation of HCV-specific T cells |
US7223398B1 (en) | 1999-11-15 | 2007-05-29 | Dynavax Technologies Corporation | Immunomodulatory compositions containing an immunostimulatory sequence linked to antigen and methods of use thereof |
WO2001037869A1 (en) | 1999-11-19 | 2001-05-31 | Csl Limited | Vaccine compositions |
AU4139801A (en) * | 1999-12-06 | 2001-06-12 | Board Of Trustees Of The University Of Arkansas, The | Controlled delivery of antigens |
AU2593701A (en) | 1999-12-21 | 2001-07-03 | Regents Of The University Of California, The | Method for preventing an anaphylactic reaction |
WO2001051083A2 (en) | 2000-01-13 | 2001-07-19 | Antigenics Inc. | Innate immunity-stimulating compositions of cpg and saponin and methods thereof |
ATE378348T1 (en) * | 2000-01-14 | 2007-11-15 | Us Health | OLIGODEOXYNUCLEOTIDES AND THEIR USE FOR INDUCING AN IMMUNE RESPONSE |
AU3108001A (en) * | 2000-01-20 | 2001-12-24 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for inducing a th2 immune response |
US6852705B2 (en) * | 2000-01-21 | 2005-02-08 | Merial | DNA vaccines for farm animals, in particular bovines and porcines |
WO2001055370A2 (en) | 2000-01-26 | 2001-08-02 | Hybridon, Inc. | MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES |
AT409085B (en) | 2000-01-28 | 2002-05-27 | Cistem Biotechnologies Gmbh | PHARMACEUTICAL COMPOSITION FOR IMMUNULATING AND PRODUCING VACCINES |
WO2001055341A2 (en) | 2000-01-31 | 2001-08-02 | The Regents Of The University Of California | Immunomodulatory polynucleotides in treatment of an infection by an intracellular pathogen |
KR100808348B1 (en) | 2000-01-31 | 2008-02-27 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | Vaccine for the prophylactic or therapeutic immunization against hiv |
FR2805265B1 (en) | 2000-02-18 | 2002-04-12 | Aventis Pasteur | IMMUNOSTIMULATING OLIGONUCLEOTIDES |
US20030130217A1 (en) * | 2000-02-23 | 2003-07-10 | Eyal Raz | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
CA2399550A1 (en) | 2000-02-23 | 2001-08-30 | The Regents Of The University Of California | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
WO2001062275A1 (en) | 2000-02-24 | 2001-08-30 | The Board Of Trustees Of The Leland Stanford Junior University | Adjuvant treatment by in vivo activation of dendritic cells |
US20020156033A1 (en) * | 2000-03-03 | 2002-10-24 | Bratzler Robert L. | Immunostimulatory nucleic acids and cancer medicament combination therapy for the treatment of cancer |
US20040131628A1 (en) * | 2000-03-08 | 2004-07-08 | Bratzler Robert L. | Nucleic acids for the treatment of disorders associated with microorganisms |
US20020098199A1 (en) | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences |
US20020028784A1 (en) * | 2000-03-10 | 2002-03-07 | Nest Gary Van | Methods of preventing and treating viral infections using immunomodulatory polynucleotide sequences |
US6851845B2 (en) * | 2000-03-10 | 2005-02-08 | The Maitland Company, Inc. | Method and apparatus for processing waste material |
US20010046967A1 (en) | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
US20020107212A1 (en) | 2000-03-10 | 2002-08-08 | Nest Gary Van | Methods of reducing papillomavirus infection using immunomodulatory polynucleotide sequences |
CA2404041A1 (en) | 2000-03-28 | 2001-10-04 | The Regents Of The University Of California | Methods for increasing a cytotoxic t lymphocyte response in vivo |
US8246945B2 (en) * | 2000-04-06 | 2012-08-21 | University Of Arkansas | Methods and reagents for decreasing clinical reaction to allergy |
US20020142978A1 (en) | 2000-04-07 | 2002-10-03 | Eyal Raz | Synergistic improvements to polynucleotide vaccines |
US7524826B2 (en) | 2000-04-14 | 2009-04-28 | Mcmaster University And Hamilton Health Sciences Corporation | Method of inhibiting the generation of active thrombin on the surface of a cell within an atherosclerotic plaque |
US6321873B1 (en) * | 2000-04-21 | 2001-11-27 | Tra-Lor-Mate, Inc. | Ladder mounting system |
EP1278761B1 (en) | 2000-05-01 | 2005-04-06 | Hybridon, Inc. | MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES |
US6893821B2 (en) * | 2000-05-05 | 2005-05-17 | The Regents Of The University Of California | Agents that modulate DNA-PK activity and methods of use thereof |
WO2001085751A1 (en) | 2000-05-09 | 2001-11-15 | Reliable Biopharmaceutical, Inc. | Polymeric compounds useful as prodrugs |
EP1280521B1 (en) | 2000-05-12 | 2005-07-20 | Pharmacia & Upjohn Company LLC | Vaccine composition, method of preparing the same, and method of vaccinating vertebrates |
US6339630B1 (en) * | 2000-05-18 | 2002-01-15 | The United States Of America As Represented By The United States Department Of Energy | Sealed drive screw operator |
EP1292331A2 (en) | 2000-06-07 | 2003-03-19 | Biosynexus Incorporated | Immunostimulatory rna/dna hybrid molecules |
US20020165178A1 (en) * | 2000-06-28 | 2002-11-07 | Christian Schetter | Immunostimulatory nucleic acids for the treatment of anemia, thrombocytopenia, and neutropenia |
JP5511117B2 (en) | 2000-07-27 | 2014-06-04 | チルドレンズ ホスピタル アンド リサーチ センター アット オークランド | Vaccine for broad protection against diseases caused by Neisseria meningitidis |
WO2002009748A1 (en) | 2000-07-31 | 2002-02-07 | Yale University | Innate immune system-directed vaccines |
US20020198165A1 (en) * | 2000-08-01 | 2002-12-26 | Bratzler Robert L. | Nucleic acids for the prevention and treatment of gastric ulcers |
ES2299520T3 (en) | 2000-09-01 | 2008-06-01 | Epigenomics Ag | PROCEDURE FOR THE DETERMINATION OF THE DEGREE OF METHYLATION OF CERTAIN CITOSINES IN GENOMIC DNA IN THE SEQUENTIAL CONTEXT 5'-CPG-3 '. |
WO2002018631A2 (en) * | 2000-09-01 | 2002-03-07 | Epigenomics Ag | Diagnosis of illnesses or predisposition to certain illnesses |
US20020091097A1 (en) * | 2000-09-07 | 2002-07-11 | Bratzler Robert L. | Nucleic acids for the prevention and treatment of sexually transmitted diseases |
EP1366077B1 (en) * | 2000-09-15 | 2011-05-25 | Coley Pharmaceutical GmbH | PROCESS FOR HIGH THROUGHPUT SCREENING OF CpG-BASED IMMUNO-AGONIST/ANTAGONIST |
GB0023008D0 (en) | 2000-09-20 | 2000-11-01 | Glaxo Group Ltd | Improvements in vaccination |
US6787524B2 (en) * | 2000-09-22 | 2004-09-07 | Tanox, Inc. | CpG oligonucleotides and related compounds for enhancing ADCC induced by anti-IgE antibodies |
AU9475001A (en) | 2000-09-26 | 2002-04-08 | Hybridon Inc | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
SE0003538D0 (en) * | 2000-09-29 | 2000-09-29 | Isconova Ab | New immunogenic complex |
US7537772B1 (en) * | 2000-10-02 | 2009-05-26 | Emergent Product Development Gaithersburg Inc. | Chlamydia protein, gene sequence and the uses thereof |
FR2814958B1 (en) | 2000-10-06 | 2003-03-07 | Aventis Pasteur | VACCINE COMPOSITION |
GB0025577D0 (en) * | 2000-10-18 | 2000-12-06 | Smithkline Beecham Biolog | Vaccine |
ES2377077T3 (en) * | 2000-10-18 | 2012-03-22 | Glaxosmithkline Biologicals S.A. | Vaccines comprising the MAGE antigen bound to a protein D fragment |
JP2004512383A (en) | 2000-11-02 | 2004-04-22 | アイネックス ファーマシューティカルズ コーポレイション | Therapeutic oligonucleotides with reduced toxicity |
US20020110840A1 (en) * | 2000-12-08 | 2002-08-15 | 3M Innovative Properties Company | Screening method for identifying compounds that selectively induce interferon alpha |
ES2307568T3 (en) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | CPG TYPE NUCLEIC ACIDS AND SAME USE METHODS. |
US7337306B2 (en) * | 2000-12-29 | 2008-02-26 | Stmicroelectronics, Inc. | Executing conditional branch instructions in a data processor having a clustered architecture |
US7713942B2 (en) | 2001-04-04 | 2010-05-11 | Nordic Vaccine Technology A/S | Cage-like microparticle complexes comprising sterols and saponins for delivery of polynucleotides |
US7176296B2 (en) | 2001-04-30 | 2007-02-13 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
US7105495B2 (en) | 2001-04-30 | 2006-09-12 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
US20030129605A1 (en) | 2001-05-04 | 2003-07-10 | Dong Yu | Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosophonate linkages |
WO2004030608A2 (en) * | 2001-06-05 | 2004-04-15 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
JP2005509591A (en) | 2001-06-15 | 2005-04-14 | リバファーム・インコーポレイテッド | Nucleoside vaccine adjuvant |
ES2487645T3 (en) | 2001-06-21 | 2014-08-22 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of use thereof |
US7785610B2 (en) | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
US20040132677A1 (en) | 2001-06-21 | 2004-07-08 | Fearon Karen L. | Chimeric immunomodulatory compounds and methods of using the same-IV |
WO2003000232A2 (en) | 2001-06-25 | 2003-01-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method for preparation of vesicles loaded with immunostimulator y oligodeoxynucleotides |
US20030003970A1 (en) | 2001-06-28 | 2003-01-02 | Alan Johnson | Portable communications device |
US20030138458A1 (en) | 2001-06-29 | 2003-07-24 | Michael Houghton | HCV E1E2 vaccine compositions |
WO2003040308A2 (en) | 2001-07-27 | 2003-05-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of sterically stabilized cationic liposomes to efficiently deliver cpg oligonucleotides in vivo |
US7666674B2 (en) | 2001-07-27 | 2010-02-23 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo |
US20030148316A1 (en) * | 2001-08-01 | 2003-08-07 | Lipford Grayson B. | Methods and compositions relating to plasmacytoid dendritic cells |
EP1420829A4 (en) * | 2001-08-07 | 2006-05-17 | Dynavax Tech Corp | Immunomodulatory compositions, formulations, and methods for use thereof |
JP2005510462A (en) | 2001-08-10 | 2005-04-21 | ダイナバックス テクノロジーズ コーポレイション | Production of immunomodulating oligonucleotides and methods of use thereof |
WO2003020884A2 (en) * | 2001-08-14 | 2003-03-13 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Method for rapid generation of mature dendritic cells |
DE60229422D1 (en) * | 2001-08-17 | 2008-11-27 | Coley Pharm Gmbh | COMBINATION MOTIF IMMUNOSTIMULATING OLIGONUCLEOTIDES WITH IMPROVED EFFECT |
WO2003020889A2 (en) | 2001-08-30 | 2003-03-13 | 3M Innovative Properties Company | Methods of maturing plasmacytoid dendritic cells using immune response modifier molecules |
WO2003027313A2 (en) * | 2001-09-24 | 2003-04-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SUPPRESSORS OF CpG OLIGONUCLEOTIDES AND METHODS OF USE |
US20030119774A1 (en) * | 2001-09-25 | 2003-06-26 | Marianna Foldvari | Compositions and methods for stimulating an immune response |
DE60234782D1 (en) | 2001-09-28 | 2010-01-28 | Purdue Research Foundation | TREATMENT PROCEDURE WITH LIGAND IMMUNOGENIC CONJUGATES |
EP1451581A4 (en) * | 2001-10-05 | 2006-01-11 | Coley Pharm Gmbh | Toll-like receptor 3 signaling agonists and antagonists |
WO2003030656A2 (en) | 2001-10-06 | 2003-04-17 | Merial Limited | Methods and compositions for promoting growth and innate immunity in young animals |
US20050238660A1 (en) | 2001-10-06 | 2005-10-27 | Babiuk Lorne A | Cpg formulations and related methods |
WO2003094836A2 (en) * | 2001-10-12 | 2003-11-20 | University Of Iowa Research Foundation | Methods and products for enhancing immune responses using imidazoquinoline compounds |
US7276489B2 (en) | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
WO2003035836A2 (en) | 2001-10-24 | 2003-05-01 | Hybridon Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
WO2003039595A2 (en) | 2001-11-07 | 2003-05-15 | Inex Pharmaceuticals Corporation | Mucosal adjuvants comprising an oligonucleotide and a cationic lipid |
US20040014779A1 (en) | 2001-11-16 | 2004-01-22 | 3M Innovative Properties Company | Methods and compositions related to IRM compounds and toll-like recptor pathways |
TW200303759A (en) * | 2001-11-27 | 2003-09-16 | Schering Corp | Methods for treating cancer |
EP1455833A1 (en) * | 2001-12-04 | 2004-09-15 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE DEPARTMENT OF HEALTH & HUMAN SERVICES | Chimeric molecule for the treatment of th2-like cytokine mediated disorders |
DE10161755B4 (en) * | 2001-12-15 | 2005-12-15 | Infineon Technologies Ag | Contact pin for testing microelectronic components with spherical contacts |
US7615227B2 (en) * | 2001-12-20 | 2009-11-10 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce angiogenesis |
US8466116B2 (en) * | 2001-12-20 | 2013-06-18 | The Unites States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce epithelial cell growth |
CA2471092A1 (en) | 2001-12-21 | 2003-07-10 | Antigenics Inc. | Compositions comprising immunoreactive reagents and saponins, and methods of use thereof |
JP2005526497A (en) | 2002-02-04 | 2005-09-08 | ビオミラ,インコーポレーテッド | Immunostimulatory, covalently lipidated oligonucleotide |
US8088388B2 (en) | 2002-02-14 | 2012-01-03 | United Biomedical, Inc. | Stabilized synthetic immunogen delivery system |
US20030232443A1 (en) | 2002-06-18 | 2003-12-18 | Isis Pharmaceuticals Inc. | Antisense modulation of centromere protein B expression |
WO2003086280A2 (en) * | 2002-04-04 | 2003-10-23 | Coley Pharmaceutical Gmbh | Immunostimulatory g,u-containing oligoribonucleotides |
EP1496925A4 (en) * | 2002-04-11 | 2007-05-30 | Zymogenetics Inc | Use of interleukin-24 to treat ovarian cancer |
JP2006515266A (en) * | 2002-04-22 | 2006-05-25 | バイオニケ ライフ サイエンシーズ インコーポレイテッド | Oligonucleotide compositions and their use for modulating immune responses |
US6948271B2 (en) * | 2002-05-06 | 2005-09-27 | Innovative Supply, Inc. | Identification and tracking system for deceased bodies |
EP1502012A4 (en) * | 2002-05-08 | 2009-07-01 | Btu Int | Plasma-assisted engine exhaust treatment |
JP2005525414A (en) | 2002-05-10 | 2005-08-25 | イネックス ファーマシューティカルズ コーポレイション | Pathogen vaccine and method of use |
WO2003094963A2 (en) | 2002-05-10 | 2003-11-20 | Inex Pharmaceuticals Corporation | Methylated immunostimulatory oligonucleotides and methods of using the same |
US20040009944A1 (en) | 2002-05-10 | 2004-01-15 | Inex Pharmaceuticals Corporation | Methylated immunostimulatory oligonucleotides and methods of using the same |
EP1507850A1 (en) | 2002-05-28 | 2005-02-23 | MERCK PATENT GmbH | A method for generating antigen-presenting cells |
CA2388049A1 (en) | 2002-05-30 | 2003-11-30 | Immunotech S.A. | Immunostimulatory oligonucleotides and uses thereof |
US7807803B2 (en) * | 2002-07-03 | 2010-10-05 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US20040053880A1 (en) * | 2002-07-03 | 2004-03-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
AU2003267986A1 (en) * | 2002-07-03 | 2004-01-23 | Depuy Mitek, Inc. | Vaccines to induce mucosal immunity |
US7605138B2 (en) | 2002-07-03 | 2009-10-20 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
AU2003255969A1 (en) | 2002-07-17 | 2004-02-02 | Coley Pharmaceutical Gmbh | Use of cpg nucleic acids in prion-disease |
CN1468957A (en) | 2002-07-19 | 2004-01-21 | 中国人民解放军第二军医大学 | Plasmid used as human therapeutic vaccine adjuvant |
US20050209183A1 (en) | 2002-07-25 | 2005-09-22 | Phenion Gmbh & Co. Kg | Cosmetic or pharmaceutical preparations comprising nucleic acids based on non-methylated CPG motifs |
EP1393745A1 (en) | 2002-07-29 | 2004-03-03 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5'ends |
EP1575504A4 (en) * | 2002-08-01 | 2009-11-04 | Us Gov Health & Human Serv | Method of treating inflammatory arthropathies with suppressors of cpg oligonucleotides |
EP1551376A4 (en) | 2002-08-12 | 2010-10-06 | Dynavax Tech Corp | Immunomodulatory compositions, methods of making, and methods of use thereof |
US6928476B2 (en) * | 2002-08-23 | 2005-08-09 | Mirra, Inc. | Peer to peer remote data storage and collaboration |
US6744084B2 (en) * | 2002-08-29 | 2004-06-01 | Micro Technology, Inc. | Two-transistor pixel with buried reset channel and method of formation |
CN100536853C (en) * | 2002-09-13 | 2009-09-09 | 艾登尼科斯(开曼)有限公司 | Ss-l-2'-deoxynucleosides for the treatment of resistant HBV strains and combination therapies |
US6994870B2 (en) * | 2002-09-18 | 2006-02-07 | Jaw-Ji Tsai | Local nasal immunotherapy with allergen strip for allergic rhinitis |
US8263091B2 (en) * | 2002-09-18 | 2012-09-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides |
WO2004026888A2 (en) | 2002-09-19 | 2004-04-01 | Coley Pharmaceutical Gmbh | Toll-like receptor 9 (tlr9) from various mammalian species |
US6988995B2 (en) * | 2002-09-30 | 2006-01-24 | Carl Zeiss Meditec, Inc. | Method and system for detecting the effects of Alzheimer's disease in the human retina |
US8043622B2 (en) * | 2002-10-08 | 2011-10-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides |
WO2004041183A2 (en) | 2002-11-01 | 2004-05-21 | The Regents Of The University Of California | Methods of treating pulmonary fibrotic disorders |
AU2003304107B2 (en) * | 2002-11-01 | 2008-05-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of preventing infections from bioterrorism agents with immunostimulatory CpG oligonucleotides |
JP2006512927A (en) * | 2002-12-11 | 2006-04-20 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 5 'CPG nucleic acids and methods of use thereof |
KR100525321B1 (en) | 2002-12-13 | 2005-11-02 | 안웅식 | Pharmaceutical composition for prophylaxis and treatment of papillomavirus-derived diseases comprising papillomavirus antigen protein and CpG-oligodeoxynucleotide |
AU2003302743B2 (en) | 2002-12-23 | 2008-09-04 | Dynavax Technologies Corporation | Branched immunomodulatory compounds and methods of using the same |
ATE544772T1 (en) * | 2002-12-23 | 2012-02-15 | Dynavax Tech Corp | IMMUNO-STIMULATING SEQUENCE OLIGONUCLEOTIDES AND METHOD OF USE THEREOF |
EP1601789A4 (en) | 2003-01-16 | 2007-10-31 | Idera Pharmaceuticals Inc | Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides |
US7189781B2 (en) * | 2003-03-13 | 2007-03-13 | H.B. Fuller Licensing & Finance Inc. | Moisture curable, radiation curable sealant composition |
US20070041998A1 (en) | 2003-03-24 | 2007-02-22 | Intercell Ag | Use of alum and a th1 immune response inducing adjuvant for enhancing immune responses |
AU2004224761A1 (en) | 2003-03-26 | 2004-10-07 | Cytos Biotechnology Ag | HIV-peptide-carrier-conjugates |
AU2004226605A1 (en) | 2003-04-02 | 2004-10-14 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations for topical application |
WO2005016235A2 (en) * | 2003-04-14 | 2005-02-24 | The Regents Of The University Of California | Combined use of impdh inhibitors with toll-like receptor agonists |
WO2004094671A2 (en) | 2003-04-22 | 2004-11-04 | Coley Pharmaceutical Gmbh | Methods and products for identification and assessment of tlr ligands |
JP3887346B2 (en) * | 2003-04-28 | 2007-02-28 | 株式会社東芝 | Video signal processing apparatus, video signal processing method, and video display apparatus |
MXPA05012421A (en) | 2003-05-16 | 2006-02-22 | Hybridon Inc | Synergistic treatment of cancer using immunomers in conjunction with chemotherapeutic agents. |
EP1484336A1 (en) * | 2003-06-02 | 2004-12-08 | Pevion Biotech Ltd. | Methods for synthesizing conformationally constrained peptides, peptidometics and the use thereof as synthetic vaccines |
ES2569927T3 (en) | 2003-06-11 | 2016-05-13 | Idera Pharmaceuticals, Inc. | Stabilized immunomodulatory oligonucleotides |
WO2004110489A1 (en) * | 2003-06-13 | 2004-12-23 | Daiichi Asubio Pharma Co., Ltd. | MEDICINAL COMPOSITION FOR PREVENTING OR TREATING Th1 TYPE IMMUNOLOGICAL DISEASE |
EP2356999A1 (en) * | 2003-06-17 | 2011-08-17 | Mannkind Corporation | Compositions to elicit, enhance and sustain immune responses against MHC class I-restricted epitopes, for prophylactic or therapeutic purposes |
US7410975B2 (en) * | 2003-06-20 | 2008-08-12 | Coley Pharmaceutical Group, Inc. | Small molecule toll-like receptor (TLR) antagonists |
US20040265833A1 (en) | 2003-06-23 | 2004-12-30 | Cathy Lofton-Day | Methods and nucleic acids for the analysis of colorectal cell proliferative disorders |
KR20060031607A (en) | 2003-07-10 | 2006-04-12 | 사이토스 바이오테크놀로지 아게 | Packaged virus-like particles |
JP4734241B2 (en) | 2003-07-11 | 2011-07-27 | インターツェル・アクチェンゲゼルシャフト | HCV vaccine |
US20050013812A1 (en) | 2003-07-14 | 2005-01-20 | Dow Steven W. | Vaccines using pattern recognition receptor-ligand:lipid complexes |
WO2005009355A2 (en) | 2003-07-15 | 2005-02-03 | Hybridon, Inc. | Synergistic stimulation of the immune system using immunostimulatory oligonucleotides and/or immunomer compounds in conjunction with cytokines and/or chemotherapeutic agents or radiation therapy |
EP1646427A1 (en) * | 2003-07-22 | 2006-04-19 | Cytos Biotechnology AG | Cpg-packaged liposomes |
AU2004269379A1 (en) | 2003-08-28 | 2005-03-10 | The Immune Response Corporation | Immunogenic HIV compositions and related methods |
DE602004026891D1 (en) * | 2003-09-05 | 2010-06-10 | Anadys Pharmaceuticals Inc | TLR7 LIGANDS FOR THE TREATMENT OF HEPATITIS C |
US20070110714A1 (en) | 2003-09-08 | 2007-05-17 | Norio Hayashi | Medicinal composition for treatment of chronic hepatitis c |
GB0321615D0 (en) * | 2003-09-15 | 2003-10-15 | Glaxo Group Ltd | Improvements in vaccination |
WO2005027920A1 (en) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | 2-alkylidene-19-nor-vitamin d derivatives for the treatment of rickets or vitamin d deficiency |
CA2536139A1 (en) * | 2003-09-25 | 2005-04-07 | Coley Pharmaceutical Group, Inc. | Nucleic acid-lipophilic conjugates |
WO2005034979A2 (en) | 2003-10-11 | 2005-04-21 | Inex Pharmaceuticals Corporation | Methods and compositions for enhancing innate immunity and antibody dependent cellular cytotoxicity |
US20050087538A1 (en) * | 2003-10-23 | 2005-04-28 | Wolfe Darrell R. | Iceless multiple can cooler |
US20050215501A1 (en) | 2003-10-24 | 2005-09-29 | Coley Pharmaceutical Group, Inc. | Methods and products for enhancing epitope spreading |
UA88457C2 (en) | 2003-10-30 | 2009-10-26 | Коли Фармасьютикал Гмбх | Immunostimulatory nucleic acid with enhanced immunostimulatory potency |
US20050239733A1 (en) | 2003-10-31 | 2005-10-27 | Coley Pharmaceutical Gmbh | Sequence requirements for inhibitory oligonucleotides |
JP4088246B2 (en) * | 2003-12-05 | 2008-05-21 | 富士通株式会社 | Ring network master setting method and apparatus |
CN101094594B (en) | 2003-12-08 | 2012-08-15 | 海布里顿公司 | Modulation of immunostimulatory properties by small oligonucleotide-based compounds |
US9090673B2 (en) | 2003-12-12 | 2015-07-28 | City Of Hope | Synthetic conjugate of CpG DNA and T-help/CTL peptide |
US20070172315A1 (en) * | 2003-12-18 | 2007-07-26 | Barrett Robert K | Method and Apparatus for Creating Soil or Rock Subsurface Support |
EP1550458A1 (en) | 2003-12-23 | 2005-07-06 | Vectron Therapeutics AG | Synergistic liposomal adjuvants |
KR100558851B1 (en) | 2004-01-08 | 2006-03-10 | 학교법인연세대학교 | Modified CpG oligodeoxynucleotide with improved immunoregulatory function |
AU2005213460A1 (en) * | 2004-02-06 | 2005-08-25 | Mayo Foundation For Medical Education And Research | Complexed polypeptide and adjuvant for improved vaccines |
US20050181035A1 (en) | 2004-02-17 | 2005-08-18 | Dow Steven W. | Systemic immune activation method using non CpG nucleic acids |
TW200533750A (en) | 2004-02-19 | 2005-10-16 | Coley Pharm Group Inc | Immunostimulatory viral RNA oligonucleotides |
WO2005080567A1 (en) | 2004-02-20 | 2005-09-01 | Mologen Ag | Substituted, non-coding nucleic acid molecule used for the therapeutic and prophylactic immune stimulation in humans and higher animals |
US20050266015A1 (en) | 2004-03-12 | 2005-12-01 | Hybridon, Inc. | Enhanced activity of HIV vaccine using a second generation immunomodulatory oligonucleotide |
US7303881B2 (en) * | 2004-04-30 | 2007-12-04 | Pds Biotechnology Corporation | Antigen delivery compositions and methods of use |
WO2005115449A1 (en) * | 2004-05-28 | 2005-12-08 | Alk-Abelló A/S | Method of treating allergy and infection by eliciting an iga antibody response |
US8399025B2 (en) * | 2004-06-04 | 2013-03-19 | Board Of Regents, The University Of Texas System | Polyamine modified particles |
AU2005326144A1 (en) | 2004-06-08 | 2006-08-03 | Coley Pharmaceutical Gmbh | Abasic oligonucleotide as carrier platform for antigen and immunostimulatory agonist and antagonist |
US7756043B1 (en) * | 2004-06-09 | 2010-07-13 | Sprint Communications Company L.P. | Method for identifying high traffic origin-destination node pairs in a packet based network |
US7498425B2 (en) | 2004-06-15 | 2009-03-03 | Idera Pharmaceuticals, Inc. | Immunostimulatory oligonucleotide multimers |
CA2570786C (en) | 2004-06-15 | 2013-05-28 | Idera Pharmaceuticals, Inc. | Modified cpg-containing oligonucleotide multimers in immune stimulation |
EP1766610A1 (en) * | 2004-06-25 | 2007-03-28 | TC Electronic A/S | Method of evaluating perception intensity of an audio signal and a method of controlling an input audio signal on the basis of the evaluation |
US7534449B2 (en) * | 2004-07-01 | 2009-05-19 | Yale University | Targeted and high density drug loaded polymeric materials |
JP2008506789A (en) | 2004-07-18 | 2008-03-06 | シーエスエル、リミテッド | Immunostimulatory complex and oligonucleotide formulation for inducing enhanced interferon-gamma response |
WO2006015560A1 (en) | 2004-08-09 | 2006-02-16 | Mologen Ag | Immunomodulating agent used in conjunction with chemotherapy |
US20060058261A1 (en) * | 2004-09-15 | 2006-03-16 | Andre Aube | Chitin derivatives for hyperlipidemia |
MY159370A (en) | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
KR100721928B1 (en) * | 2004-11-05 | 2007-05-28 | 주식회사 바이오씨에스 | Pharmaceutical composition for treating or preventing dermatitis comprising CpG oligodeoxynucleotide |
US20060105979A1 (en) | 2004-11-08 | 2006-05-18 | Hybridon, Inc. | Synergistic inhibition of VEGF and modulation of the immune response |
CA2594382A1 (en) | 2005-01-07 | 2006-07-13 | Alk-Abello A/S | Method of preventive treatment of allergy by oromucosal administration of an allergy vaccine |
BRPI0617254A2 (en) * | 2005-01-12 | 2011-07-19 | Cancer Rec Tech Ltd | Single-stranded oligonucleotide, pharmaceutical composition, methods for stimulating tlr7 activity in a tlr7-expressing cell, for stimulating tlr8 activity in a tlr8-expressing cell, and for stimulating an immune response in a patient |
JP2008531018A (en) * | 2005-02-24 | 2008-08-14 | コーリー ファーマシューティカル グループ,インコーポレイテッド | Immunostimulatory oligonucleotide |
SG161260A1 (en) | 2005-04-08 | 2010-05-27 | Coley Pharm Group Inc | Methods for treating infectious disease exacerbated asthma |
US20060241076A1 (en) | 2005-04-26 | 2006-10-26 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
US20090117132A1 (en) * | 2005-07-07 | 2009-05-07 | Pfizer, Inc. | Anti-Ctla-4 Antibody and Cpg-Motif-Containing Synthetic Oligodeoxynucleotide Combination Therapy for Cancer Treatment |
WO2007027718A1 (en) * | 2005-08-31 | 2007-03-08 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Methods of altering an immune response induced by cpg oligodeoxynucleotides |
BRPI0616235A2 (en) | 2005-09-16 | 2011-06-14 | Coley Pharm Gmbh | phosphodiester main chain immunostimulatory monofilamentated ribonucleic acid |
KR20080047463A (en) | 2005-09-16 | 2008-05-28 | 콜리 파마슈티칼 게엠베하 | Modulation of immunostimulatory properties of short interfering ribonucleic acid (sirna) by nucleotide modification |
WO2007038720A2 (en) | 2005-09-27 | 2007-04-05 | Coley Pharmaceutical Gmbh | Modulation of tlr-mediated immune responses using adaptor oligonucleotides |
US20070093439A1 (en) | 2005-10-25 | 2007-04-26 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
CA2625969A1 (en) * | 2005-10-28 | 2007-05-03 | Index Pharmaceuticals Ab | Composition and method for the prevention, treatment and/or alleviation of an inflammatory disease |
US20070243209A1 (en) * | 2005-10-28 | 2007-10-18 | Health Research, Inc. | Compositions and methods for prevention and treatment of fungal diseases |
AU2006310339B2 (en) | 2005-11-04 | 2013-01-10 | Novartis Ag | Influenza vaccines including combinations of particulate adjuvants and immunopotentiators |
CN102755645A (en) | 2005-11-04 | 2012-10-31 | 诺华疫苗和诊断有限公司 | Influenza vaccines with reduced amount of emulsion adjuvant |
US7470674B2 (en) | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
US7776834B2 (en) | 2005-11-07 | 2010-08-17 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
MX2008006004A (en) | 2005-11-07 | 2008-10-01 | Idera Pharmaceuticals Inc | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides. |
CA2628306C (en) | 2005-11-07 | 2014-06-17 | Sudhir Agrawal | Immunostimulatory oligonucleotide-based compounds with glycerol-linked dinucleotides and modified guanosines at cpg and uses thereof |
AU2006318464B2 (en) * | 2005-11-25 | 2011-02-17 | Zoetis Belgium Sa | Immunostimulatory oligoribonucleotides |
JP2009521218A (en) | 2005-12-20 | 2009-06-04 | イデラ ファーマシューティカルズ インコーポレイテッド | Immunostimulatory action of palindromic immune modulatory oligonucleotides (IMO (TM)) containing palindromic segments of different lengths |
EP2405002B1 (en) * | 2006-02-15 | 2014-09-24 | AdiuTide Pharmaceuticals GmbH | Compositions and methods for oligonucleotide formulations |
DE102006007433A1 (en) | 2006-02-17 | 2007-08-23 | Curevac Gmbh | Immunostimulant adjuvant useful in vaccines against cancer or infectious diseases comprises a lipid-modified nucleic acid |
WO2008019018A2 (en) * | 2006-08-03 | 2008-02-14 | William Soo Hoo | Bioactive molecular matrix and methods of use in the treatment of disease |
US20080124366A1 (en) * | 2006-08-06 | 2008-05-29 | Ohlfest John R | Methods and Compositions for Treating Tumors |
WO2008019486A1 (en) * | 2006-08-16 | 2008-02-21 | Protiva Biotherapeutics, Inc. | Nucleic acid modulation of toll-like receptor-mediated immune stimulation |
US8027888B2 (en) | 2006-08-31 | 2011-09-27 | Experian Interactive Innovation Center, Llc | Online credit card prescreen systems and methods |
WO2008033432A2 (en) | 2006-09-12 | 2008-03-20 | Coley Pharmaceutical Group, Inc. | Immune modulation by chemically modified ribonucleosides and oligoribonucleotides |
CN101516396B (en) * | 2006-09-26 | 2013-10-09 | 传染性疾病研究院 | Vaccine composition containing synthetic adjuvant |
US20090181078A1 (en) * | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
PT2078080E (en) | 2006-09-27 | 2015-09-18 | Coley Pharm Gmbh | Cpg oligonucleotide analogs containing hydrophobic t analogs with enhanced immunostimulatory activity |
EP2068912A2 (en) | 2006-09-27 | 2009-06-17 | Coley Pharmaceutical Group, Inc. | Compositions of tlr ligands and antivirals |
US20100144846A1 (en) * | 2006-10-26 | 2010-06-10 | Coley Pharmaceutical Gmbh | Oligoribonucleotides and uses thereof |
WO2008057529A2 (en) * | 2006-11-06 | 2008-05-15 | Coley Pharmaceutical Group, Inc. | Peptide-based vaccine compositions to endogenous cholesteryl ester transfer protein (cetp) |
KR20090095626A (en) * | 2006-12-04 | 2009-09-09 | 더 보드 오브 트러스티즈 오브 더 유니버시티 오브 일리노이 | COMPOSITIONS AND METHODS TO TREAT CANCER WITH CpG RICH DNA AND CUPREDOXINS |
US8057804B2 (en) * | 2006-12-28 | 2011-11-15 | The Trustees Of The University Of Pennsylvania | Herpes simplex virus combined subunit vaccines and methods of use thereof |
EP2591800A1 (en) * | 2006-12-28 | 2013-05-15 | The Trustees of The University of Pennsylvania | Herpes simplex virus combined subunit vaccines and methods of use thereof |
AR066405A1 (en) * | 2007-04-20 | 2009-08-19 | Glaxosmithkline Biolog Sa | VACCINE |
MX2009012482A (en) | 2007-05-17 | 2009-12-02 | Coley Pharm Group Inc | Class a oligonucleotides with immunostimulatory potency. |
JP2010536335A (en) * | 2007-08-13 | 2010-12-02 | ファイザー・インク | Combinatorial motif immunostimulatory oligonucleotides with improved activity |
CN101835487A (en) * | 2007-08-21 | 2010-09-15 | 戴纳瓦克斯技术公司 | Composition and methods of making and using influenza proteins |
EP2185160B1 (en) * | 2007-08-31 | 2019-02-13 | Neurimmune Holding AG | Method of providing patient specific immune response in amyloidoses and protein aggregation disorders |
US7892567B2 (en) * | 2007-10-01 | 2011-02-22 | Board Of Regents, The University Of Texas System | Methods and compositions for immunization against chlamydial infection and disease |
CN101820908A (en) | 2007-10-09 | 2010-09-01 | 科利制药公司 | The immune stimulatory oligonucleotide analogs that comprises modified sugar moieties |
TW200932274A (en) * | 2007-12-18 | 2009-08-01 | Alcon Res Ltd | Interfering RNA delivery system and uses thereof |
US7720322B2 (en) * | 2008-06-30 | 2010-05-18 | Intuitive Surgical, Inc. | Fiber optic shape sensor |
TWI351288B (en) * | 2008-07-04 | 2011-11-01 | Univ Nat Pingtung Sci & Tech | Cpg dna adjuvant in avian vaccines |
US20100166782A1 (en) * | 2008-07-25 | 2010-07-01 | Martha Karen Newell | Clip inhibitors and methods of modulating immune function |
US8053422B2 (en) * | 2008-12-04 | 2011-11-08 | The United States Of America As Represented By The Department Of Health And Human Services | Anti-cancer oligodeoxynucleotides |
-
1996
- 1996-10-30 US US08/738,652 patent/US6207646B1/en not_active Expired - Lifetime
-
1997
- 1997-10-30 WO PCT/US1997/019791 patent/WO1998018810A1/en active IP Right Grant
- 1997-10-30 DE DE69736331T patent/DE69736331T2/en not_active Revoked
- 1997-10-30 EP EP10186177.1A patent/EP2360252B8/en not_active Expired - Lifetime
- 1997-10-30 EP EP97947311A patent/EP0948510B1/en not_active Revoked
- 1997-10-30 AU AU52424/98A patent/AU5242498A/en not_active Abandoned
- 1997-10-30 NZ NZ335397A patent/NZ335397A/en not_active IP Right Cessation
- 1997-10-30 PT PT97947311T patent/PT948510E/en unknown
- 1997-10-30 CN CNA2007101300520A patent/CN101265285A/en active Pending
- 1997-10-30 CN CNB971993521A patent/CN100338086C/en not_active Expired - Lifetime
- 1997-10-30 ES ES10186177.1T patent/ES2624859T3/en not_active Expired - Lifetime
- 1997-10-30 CA CA2270345A patent/CA2270345C/en not_active Expired - Lifetime
- 1997-10-30 EP EP06115792A patent/EP1714969A3/en not_active Withdrawn
- 1997-10-30 EP EP06115801A patent/EP1746159A3/en not_active Withdrawn
- 1997-10-30 EP EP10186108A patent/EP2322615A1/en not_active Withdrawn
- 1997-10-30 JP JP52078498A patent/JP2001503267A/en active Pending
- 1997-10-30 AT AT97947311T patent/ATE332966T1/en active
- 1997-10-30 DK DK97947311T patent/DK0948510T3/en active
- 1997-10-30 ES ES97947311T patent/ES2268736T3/en not_active Expired - Lifetime
- 1997-10-30 KR KR1019997003873A patent/KR100689942B1/en not_active IP Right Cessation
-
2001
- 2001-03-27 US US09/818,918 patent/US20030050261A1/en not_active Abandoned
- 2001-12-14 AU AU97249/01A patent/AU775185B2/en not_active Expired
-
2003
- 2003-03-03 JP JP2003056446A patent/JP2003286174A/en not_active Withdrawn
- 2003-05-09 US US10/435,656 patent/US20050277604A1/en not_active Abandoned
- 2003-07-03 US US10/613,916 patent/US20050070491A1/en not_active Abandoned
- 2003-09-10 JP JP2003319045A patent/JP2004041224A/en not_active Withdrawn
- 2003-10-03 US US10/679,710 patent/US20040147468A1/en not_active Abandoned
- 2003-12-22 US US10/743,625 patent/US20040132685A1/en not_active Abandoned
-
2004
- 2004-01-30 US US10/769,282 patent/US7674777B2/en not_active Expired - Fee Related
- 2004-04-02 US US10/817,165 patent/US20040198688A1/en not_active Abandoned
- 2004-04-23 US US10/831,647 patent/US7402572B2/en not_active Expired - Fee Related
- 2004-05-17 US US10/847,642 patent/US20050004061A1/en not_active Abandoned
- 2004-06-24 US US10/877,407 patent/US20040229835A1/en not_active Abandoned
- 2004-07-02 US US10/884,852 patent/US20050059625A1/en not_active Abandoned
- 2004-07-09 US US10/888,449 patent/US20050049215A1/en not_active Abandoned
- 2004-07-09 US US10/888,785 patent/US7517861B2/en not_active Expired - Fee Related
- 2004-07-16 US US10/894,657 patent/US20050054602A1/en not_active Abandoned
- 2004-07-16 US US10/894,862 patent/US8058249B2/en not_active Expired - Fee Related
- 2004-08-26 US US10/928,762 patent/US20050123523A1/en not_active Abandoned
- 2004-10-01 US US10/956,494 patent/US7879810B2/en not_active Expired - Fee Related
- 2004-10-01 US US10/956,745 patent/US20050239732A1/en not_active Abandoned
- 2004-10-13 AU AU2004218696A patent/AU2004218696B2/en not_active Expired
- 2004-10-22 US US10/972,301 patent/US20050215500A1/en not_active Abandoned
- 2004-11-12 US US10/987,146 patent/US20050148537A1/en not_active Abandoned
-
2005
- 2005-01-07 US US11/031,460 patent/US8158592B2/en not_active Expired - Fee Related
- 2005-01-14 US US11/036,527 patent/US7723022B2/en not_active Expired - Fee Related
- 2005-02-25 US US11/067,587 patent/US8129351B2/en not_active Expired - Fee Related
- 2005-05-23 US US11/134,918 patent/US20050267064A1/en not_active Abandoned
- 2005-12-07 US US11/296,572 patent/US20060089326A1/en not_active Abandoned
-
2006
- 2006-08-11 US US11/503,483 patent/US7723500B2/en not_active Expired - Fee Related
- 2006-09-22 US US11/526,197 patent/US20070078104A1/en not_active Abandoned
- 2006-11-10 US US11/598,207 patent/US8258106B2/en not_active Expired - Fee Related
-
2007
- 2007-06-05 US US11/810,353 patent/US20080026011A1/en not_active Abandoned
-
2008
- 2008-07-25 JP JP2008192729A patent/JP5082063B2/en not_active Expired - Lifetime
- 2008-10-09 US US12/248,493 patent/US20090202575A1/en not_active Abandoned
-
2009
- 2009-03-25 US US12/383,824 patent/US7888327B2/en not_active Expired - Fee Related
-
2010
- 2010-03-10 JP JP2010053784A patent/JP2010150280A/en active Pending
Patent Citations (98)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5023243A (en) * | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US5766920A (en) * | 1982-08-11 | 1998-06-16 | Cellcor, Inc. | Ex vivo activation of immune cells |
US4452775A (en) * | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
US5178860A (en) * | 1989-09-01 | 1993-01-12 | Coopers Animal Health Limited | Adjuvant complexes and vaccine made therefrom |
US5527899A (en) * | 1989-10-23 | 1996-06-18 | Gilead Sciences, Inc. | Oligonucleotides with inverted polarity |
US4981684A (en) * | 1989-10-24 | 1991-01-01 | Coopers Animal Health Limited | Formation of adjuvant complexes |
US5514577A (en) * | 1990-02-26 | 1996-05-07 | Isis Pharmaceuticals, Inc. | Oligonucleotide therapies for modulating the effects of herpes viruses |
US6030954A (en) * | 1991-09-05 | 2000-02-29 | University Of Connecticut | Targeted delivery of poly- or oligonucleotides to cells |
US6184369B1 (en) * | 1993-04-23 | 2001-02-06 | Aronex Pharmaceuticals, Inc. | Anti-viral guanosine-rich oligonucleotides |
US6191257B1 (en) * | 1993-04-27 | 2001-02-20 | Baylor College Of Medicine | Natural or recombinant DNA binding proteins as carriers for gene transfer or gene therapy |
US5594122A (en) * | 1993-06-23 | 1997-01-14 | Genesys Pharma Inc. | Antisense oligonucleotides targeted against human immunodeficiency virus |
US20030027782A1 (en) * | 1993-08-26 | 2003-02-06 | Carson Dennis A. | Method for treating allergic lung disease |
US6348312B1 (en) * | 1993-11-12 | 2002-02-19 | Hoescht Aktiengesellschaft | Stabilized oligonucleotides and their use |
US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US5728518A (en) * | 1994-01-12 | 1998-03-17 | The Immune Response Corporation | Antiviral poly-and oligonucleotides |
US6031086A (en) * | 1994-03-18 | 2000-02-29 | The Regents Of The University Of California | Antisense oligonucleitide containing compositions and method of forming duplexes |
US20050075302A1 (en) * | 1994-03-25 | 2005-04-07 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
US5723335A (en) * | 1994-03-25 | 1998-03-03 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
US20050070491A1 (en) * | 1994-07-15 | 2005-03-31 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20060003955A1 (en) * | 1994-07-15 | 2006-01-05 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US7223741B2 (en) * | 1994-07-15 | 2007-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20070078104A1 (en) * | 1994-07-15 | 2007-04-05 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US6194388B1 (en) * | 1994-07-15 | 2001-02-27 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20070065467A1 (en) * | 1994-07-15 | 2007-03-22 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
US20070066553A1 (en) * | 1994-07-15 | 2007-03-22 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20070009482A9 (en) * | 1994-07-15 | 2007-01-11 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20070010470A9 (en) * | 1994-07-15 | 2007-01-11 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20060094683A1 (en) * | 1994-07-15 | 2006-05-04 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20060089326A1 (en) * | 1994-07-15 | 2006-04-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20060058251A1 (en) * | 1994-07-15 | 2006-03-16 | University Of Iowa Research Foundation | Methods for treating and preventing infectious disease |
US20050101554A1 (en) * | 1994-07-15 | 2005-05-12 | University Of Iowa Research Foundation | Methods for treating and preventing infectious disease |
US20050101557A1 (en) * | 1994-07-15 | 2005-05-12 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20050059625A1 (en) * | 1994-07-15 | 2005-03-17 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20050054602A1 (en) * | 1994-07-15 | 2005-03-10 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20050049216A1 (en) * | 1994-07-15 | 2005-03-03 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20050037403A1 (en) * | 1994-07-15 | 2005-02-17 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20050037985A1 (en) * | 1994-07-15 | 2005-02-17 | Krieg Arthur M. | Methods and products for treating HIV infection |
US20030050263A1 (en) * | 1994-07-15 | 2003-03-13 | The University Of Iowa Research Foundation | Methods and products for treating HIV infection |
US20050032736A1 (en) * | 1994-07-15 | 2005-02-10 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20050009774A1 (en) * | 1994-07-15 | 2005-01-13 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20030050261A1 (en) * | 1994-07-15 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid molecules |
US20050004062A1 (en) * | 1994-07-15 | 2005-01-06 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20050004061A1 (en) * | 1994-07-15 | 2005-01-06 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20040087538A1 (en) * | 1994-07-15 | 2004-05-06 | University Of Iowa Research Foundation | Methods of treating cancer using immunostimulatory oligonucleotides |
US20040087534A1 (en) * | 1994-07-15 | 2004-05-06 | University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US20030100527A1 (en) * | 1994-07-15 | 2003-05-29 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
US6503533B1 (en) * | 1994-07-28 | 2003-01-07 | Georgetown University | Antisense ogligonucleotides against Hepatitis B viral replication |
US6027726A (en) * | 1994-09-30 | 2000-02-22 | Inex Phamaceuticals Corp. | Glycosylated protein-liposome conjugates and methods for their preparation |
US5753613A (en) * | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
US5858987A (en) * | 1995-05-05 | 1999-01-12 | Mitotix, Inc. | E6AP antisense constructs and methods of use |
US5705385A (en) * | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
US5736152A (en) * | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
US20030078223A1 (en) * | 1996-01-30 | 2003-04-24 | Eyal Raz | Compositions and methods for modulating an immune response |
US6027732A (en) * | 1996-02-21 | 2000-02-22 | Morein; Bror | Iscom or iscom-matrix comprising hydrophobic receptor molecules for antigenic substances |
US6030955A (en) * | 1996-03-21 | 2000-02-29 | The Trustees Of Columbia University In The City Of New York And Imclone Systems, Inc. | Methods of affecting intracellular phosphorylation of tyrosine using phosphorothioate oligonucleotides, and antiangiogenic and antiproliferative uses thereof |
US6174872B1 (en) * | 1996-10-04 | 2001-01-16 | The Regents Of The University Of California | Method for treating allergic lung disease |
US7001890B1 (en) * | 1997-01-23 | 2006-02-21 | Coley Pharmaceutical Gmbh | Pharmaceutical compositions comprising a polynucleotide and optionally an antigen especially for vaccination |
US20050054601A1 (en) * | 1997-01-23 | 2005-03-10 | Coley Pharmaceutical Gmbh | Pharmaceutical composition comprising a polynucleotide and optionally an antigen especially for vaccination |
US6214806B1 (en) * | 1997-02-28 | 2001-04-10 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CPC dinucleotide in the treatment of LPS-associated disorders |
US20030091599A1 (en) * | 1997-03-10 | 2003-05-15 | Coley Pharmaceutical Gmbh | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US20050043529A1 (en) * | 1997-03-10 | 2005-02-24 | Coley Pharmaceutical Gmbh | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US6339068B1 (en) * | 1997-05-20 | 2002-01-15 | University Of Iowa Research Foundation | Vectors and methods for immunization or therapeutic protocols |
US20050032734A1 (en) * | 1997-05-20 | 2005-02-10 | Krieg Arthur M. | Vectors and methods for immunization or therapeutic protocols |
US6225292B1 (en) * | 1997-06-06 | 2001-05-01 | The Regents Of The University Of California | Inhibitors of DNA immunostimulatory sequence activity |
US6521637B2 (en) * | 1997-07-03 | 2003-02-18 | University Of Iowa Research Foundation | Methods for inhibiting immunostimulatory DNA associated responses |
US6221882B1 (en) * | 1997-07-03 | 2001-04-24 | University Of Iowa Research Foundation | Methods for inhibiting immunostimulatory DNA associated responses |
US20030092663A1 (en) * | 1997-09-05 | 2003-05-15 | Eyal Raz | Immunization-free methods for treating antigen-stimulated inflammation in a mammalian host and shifting the host's antigen immune responsiveness to a Th1 phenotype |
US6218371B1 (en) * | 1998-04-03 | 2001-04-17 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
US20020064515A1 (en) * | 1998-04-03 | 2002-05-30 | Krieg Arthur M. | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
US20040030118A1 (en) * | 1998-05-14 | 2004-02-12 | Hermann Wagner | Methods for regulating hematopoiesis using CpG-oligonucleotides |
US20040006034A1 (en) * | 1998-06-05 | 2004-01-08 | Eyal Raz | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
US7214380B1 (en) * | 1998-06-23 | 2007-05-08 | The Board Of Trustees Of The Leland Stanford Junior University | Adjuvant therapy |
US20070066554A1 (en) * | 1999-09-25 | 2007-03-22 | Coley Pharmaceutical Gmbh | Immunostimulatory nucleic acids |
US20070037767A1 (en) * | 2000-02-03 | 2007-02-15 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
US20040067902A9 (en) * | 2000-02-03 | 2004-04-08 | Bratzler Robert L. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
US20030059773A1 (en) * | 2000-03-10 | 2003-03-27 | Gary Van Nest | Immunomodulatory formulations and methods for use thereof |
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