CA2475595C - Method of reducing and preventing uvb-induced immunosuppression - Google Patents
Method of reducing and preventing uvb-induced immunosuppression Download PDFInfo
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- CA2475595C CA2475595C CA2475595A CA2475595A CA2475595C CA 2475595 C CA2475595 C CA 2475595C CA 2475595 A CA2475595 A CA 2475595A CA 2475595 A CA2475595 A CA 2475595A CA 2475595 C CA2475595 C CA 2475595C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
Abstract
Methods of preventing and/or treating UV-induced immunosuppression by administration of immune response modifier compounds are disclosed herein. Suitable immune response modifier compounds include agonists of one or more TLRs.
Description
METHOD OF REDUCING AND PREVENTING UVB-INDUCED
IMMUNOSUPPRESSION
Background of the Invention Human skin is an organ that protects the body from the influences of the external environment. A portion of that protective function is provided by an immune system specific to the skin - the so-called skin immune system - that protects the body from potentially harmful environmental influences including pathogens and transformed skin cells. The skin immune system may provide a localized response known as contact hypersensitivity (CHS), a systemic response known as delayed type hypersensitivity (DTH), or both.
Exposing skin to ultraviolet radiation of the sun, particularly UV-B
radiation, may damage certain types of cells involved in the skin immune system. Such damage may at least partially suppress function of the skin immune system and, therefore, may result in UV-induced immunosuppression.
Langerhans cells are dendritic-like elements of the skin immune system that may function to present antigens to Thl-lymphocytes. Langerhans cells may be particularly affected by exposure to UV radiation. Exposure to UV radiation can cause changes in Langerhans cells that may contribute to UV-induced immunosuppression. For example, exposure to UV radiation may impair the ability of Langerhans cells to present antigens.
Cytokines are known to be involved in the development of contact hypersensitivity (CHS) and the suppression of contact hypersensitivity by UV radiation. For example, interleukin (IL)-10 is a cytokine produced by keratinocytes after the keratinocytes are exposed to UV radiation. IL-10 impairs Langerhans cell function and suppresses CHS.
Also, IL-12 promotes a Thl-lymphocyte immune response and is involved in the induction of CHS. IL-12 can reduce the immunosuppressive effects of UV radiation.
Furthermore, administration of IL-12 prior to UV treatment may counteract UV-induced systemic suppression of delayed type hypersensitivity (DTH).
Ectoin and ectoin derivatives may be used for the prophylaxis or treatment of UV-induced immunosuppression. Such compounds may be incorporated into compositions for topical administration.
Summary of the Invention In one aspect, the present invention provides a method of reducing UV-induced immunosuppression that includes administering to a treatment area an immune response modifier compound in an amount effective to inhibit UV-induced immunosuppression.
In certain embodiments, the immune response modifier compound can be an agonist of at least one Toll-like receptor (TLR). For example, in some embodiments, the immune response modifier compound can include an imidazoquinoline amine, an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an oxazoloquinoline amine, an imidazotetrahydronaphthyridine amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine. In certain embodiments, the immune response modifier compound is administered via a topical application vehicle such as a cream, a gel, a spray, an ointment, a lotion, a solution, a suspension, an emulsion, a paste, a powder, or an oil.
In another aspect, the present invention provides a method of treating UV-induced immunosuppression that includes. administering to -a treatment area an immune response modifier compound in an amount effective to inhibit UV-induced immunosuppression.
In certain embodiments, the immune response modifier compound can be an agonist of at least one Toll-like receptor (TLR). For example, in some embodiments, the immune response modifier compound can include an imidazoquinoline amine, an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an imidazotetrahydronaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.
In certain embodiments, the immune response modifier compound is administered via a topical application vehicle such as a cream, a gel, a spray, an ointment, a lotion, a solution, a suspension, an emulsion, a paste, a powder, or an oil.
In another aspect, the present invention provides a use of an immune response modifier compound for reducing UV-induced immunosuppression on a treatment area wherein the immune response modifier compound is an agonist of at least one toll-like receptor (TLR).
In another aspect, the present invention also provides a use of an immune response modifier compound for reducing UV-induced immunosuppression on a treatment area wherein the immune response modifier compound is an agonist of at least one toll-like receptor (TLR), wherein the use of the immune response modifier compound occurs prior to exposure of the treatment area to UV irradiation.
In another aspect, the present invention also provides a use of an immune response modifier for treating UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR.
In another aspect, the present invention also provides a use of an immune response modifier for preventing UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR, wherein the use of the immune response modifier compound occurs prior to exposure of the treatment area to UV irradiation.
In another aspect, the invention provides a use of an immune response modifier in the manufacture of a medicament for treating UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR.
In another aspect, the invention provides a use of an immune response modifier in the manufacture of a medicament for preventing UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR, wherein the immune response modifier compound is adapted to be administered to a treatment area prior to exposure of said treatment area to UV
irradiation.
2a Various other features and advantages of the present invention should become readily apparent with reference to the following detailed description, examples, claims and appended drawings. In several places throughout the specification, guidance is provided through lists of examples. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.
2b Brief Description of the Drawings Fig. 1 is a summary of the protocol for testing the contact hypersensitivity of mice treated with IRM before exposure to UV-B radiation;
Fig. 2 is a bar graph summarizing the contact hypersensitivity of mice treated with IRM before exposure to UV-B radiation;
Fig. 3 is a summary of the protocol for testing the contact hypersensitivity of mice treated with IRM after exposure to UV-B radiation;
Fig. 4 is a bar graph summarizing the contact hypersensitivity of mice treated with IRM after exposure to UV-B radiation.
Detailed Description of Illustrative Embodiments of the Invention Immune response modifiers ("IRMs") include compounds that possess potent immunostimulating activity including but not limited to antiviral and antitumor activity.
Certain IRMs effect their immunostimulatory activity by inducing the production and secretion of cytokines such as, e.g., Type I interferons, TNF-a, IL-1, IL-6, IL-8, IL-10, IL-12, MIP- 1, and MCP- 1. Certain IRMs are small organic molecules such as those disclosed in, for example, U.S. Patent Nos. 4,689,338; 4,929,624; 5,266,575; 5,268,376;
5,352,784;
5,389,640; 5,482,936; 5,494,916; 6,110,929; 6,194,425; 4,988,815; 5,175,296;
5,367,076;
5,395,937; 5,693,811; 5,741,908; 5,238,944; 5,939,090; 6,039,969; 6,083,505;
6,245,776;
6,331,539; and 6,376,669; and PCT Publications WO 00/76505; WO 00/76518; WO
02/46188, WO 02/ 46189; WO 02/46190; WO 02/46191; WO 02/46192; WO 02/46193;
and WO 02/46194.
Additional small molecule IRMs include purine derivatives (such as those described in U.S. Patent Nos. 6,376,501 and 6,028,076), small heterocyclic compounds (such as those described in U.S. Patent No. 6,329,381), and amide derivatives (such as those described in U.S. Patent No. 6,069,149).
Other IRMs include large biological molecules such as oligonucleotide sequences.
Some IRM oligonucleotide sequences contain cytosine-guanine dinucleotides (CpG) and are described, for example, in U.S. Patent Nos. 6,1994,388; 6,207,646;
6,239,116;
6,339,068; and 6,406,705. Some CpG-containing oligonucleotides can include synthetic immunomodulatory structural motifs such as those described, for example, in U.S. Pat.
IMMUNOSUPPRESSION
Background of the Invention Human skin is an organ that protects the body from the influences of the external environment. A portion of that protective function is provided by an immune system specific to the skin - the so-called skin immune system - that protects the body from potentially harmful environmental influences including pathogens and transformed skin cells. The skin immune system may provide a localized response known as contact hypersensitivity (CHS), a systemic response known as delayed type hypersensitivity (DTH), or both.
Exposing skin to ultraviolet radiation of the sun, particularly UV-B
radiation, may damage certain types of cells involved in the skin immune system. Such damage may at least partially suppress function of the skin immune system and, therefore, may result in UV-induced immunosuppression.
Langerhans cells are dendritic-like elements of the skin immune system that may function to present antigens to Thl-lymphocytes. Langerhans cells may be particularly affected by exposure to UV radiation. Exposure to UV radiation can cause changes in Langerhans cells that may contribute to UV-induced immunosuppression. For example, exposure to UV radiation may impair the ability of Langerhans cells to present antigens.
Cytokines are known to be involved in the development of contact hypersensitivity (CHS) and the suppression of contact hypersensitivity by UV radiation. For example, interleukin (IL)-10 is a cytokine produced by keratinocytes after the keratinocytes are exposed to UV radiation. IL-10 impairs Langerhans cell function and suppresses CHS.
Also, IL-12 promotes a Thl-lymphocyte immune response and is involved in the induction of CHS. IL-12 can reduce the immunosuppressive effects of UV radiation.
Furthermore, administration of IL-12 prior to UV treatment may counteract UV-induced systemic suppression of delayed type hypersensitivity (DTH).
Ectoin and ectoin derivatives may be used for the prophylaxis or treatment of UV-induced immunosuppression. Such compounds may be incorporated into compositions for topical administration.
Summary of the Invention In one aspect, the present invention provides a method of reducing UV-induced immunosuppression that includes administering to a treatment area an immune response modifier compound in an amount effective to inhibit UV-induced immunosuppression.
In certain embodiments, the immune response modifier compound can be an agonist of at least one Toll-like receptor (TLR). For example, in some embodiments, the immune response modifier compound can include an imidazoquinoline amine, an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an oxazoloquinoline amine, an imidazotetrahydronaphthyridine amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine. In certain embodiments, the immune response modifier compound is administered via a topical application vehicle such as a cream, a gel, a spray, an ointment, a lotion, a solution, a suspension, an emulsion, a paste, a powder, or an oil.
In another aspect, the present invention provides a method of treating UV-induced immunosuppression that includes. administering to -a treatment area an immune response modifier compound in an amount effective to inhibit UV-induced immunosuppression.
In certain embodiments, the immune response modifier compound can be an agonist of at least one Toll-like receptor (TLR). For example, in some embodiments, the immune response modifier compound can include an imidazoquinoline amine, an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an imidazotetrahydronaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.
In certain embodiments, the immune response modifier compound is administered via a topical application vehicle such as a cream, a gel, a spray, an ointment, a lotion, a solution, a suspension, an emulsion, a paste, a powder, or an oil.
In another aspect, the present invention provides a use of an immune response modifier compound for reducing UV-induced immunosuppression on a treatment area wherein the immune response modifier compound is an agonist of at least one toll-like receptor (TLR).
In another aspect, the present invention also provides a use of an immune response modifier compound for reducing UV-induced immunosuppression on a treatment area wherein the immune response modifier compound is an agonist of at least one toll-like receptor (TLR), wherein the use of the immune response modifier compound occurs prior to exposure of the treatment area to UV irradiation.
In another aspect, the present invention also provides a use of an immune response modifier for treating UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR.
In another aspect, the present invention also provides a use of an immune response modifier for preventing UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR, wherein the use of the immune response modifier compound occurs prior to exposure of the treatment area to UV irradiation.
In another aspect, the invention provides a use of an immune response modifier in the manufacture of a medicament for treating UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR.
In another aspect, the invention provides a use of an immune response modifier in the manufacture of a medicament for preventing UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR, wherein the immune response modifier compound is adapted to be administered to a treatment area prior to exposure of said treatment area to UV
irradiation.
2a Various other features and advantages of the present invention should become readily apparent with reference to the following detailed description, examples, claims and appended drawings. In several places throughout the specification, guidance is provided through lists of examples. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.
2b Brief Description of the Drawings Fig. 1 is a summary of the protocol for testing the contact hypersensitivity of mice treated with IRM before exposure to UV-B radiation;
Fig. 2 is a bar graph summarizing the contact hypersensitivity of mice treated with IRM before exposure to UV-B radiation;
Fig. 3 is a summary of the protocol for testing the contact hypersensitivity of mice treated with IRM after exposure to UV-B radiation;
Fig. 4 is a bar graph summarizing the contact hypersensitivity of mice treated with IRM after exposure to UV-B radiation.
Detailed Description of Illustrative Embodiments of the Invention Immune response modifiers ("IRMs") include compounds that possess potent immunostimulating activity including but not limited to antiviral and antitumor activity.
Certain IRMs effect their immunostimulatory activity by inducing the production and secretion of cytokines such as, e.g., Type I interferons, TNF-a, IL-1, IL-6, IL-8, IL-10, IL-12, MIP- 1, and MCP- 1. Certain IRMs are small organic molecules such as those disclosed in, for example, U.S. Patent Nos. 4,689,338; 4,929,624; 5,266,575; 5,268,376;
5,352,784;
5,389,640; 5,482,936; 5,494,916; 6,110,929; 6,194,425; 4,988,815; 5,175,296;
5,367,076;
5,395,937; 5,693,811; 5,741,908; 5,238,944; 5,939,090; 6,039,969; 6,083,505;
6,245,776;
6,331,539; and 6,376,669; and PCT Publications WO 00/76505; WO 00/76518; WO
02/46188, WO 02/ 46189; WO 02/46190; WO 02/46191; WO 02/46192; WO 02/46193;
and WO 02/46194.
Additional small molecule IRMs include purine derivatives (such as those described in U.S. Patent Nos. 6,376,501 and 6,028,076), small heterocyclic compounds (such as those described in U.S. Patent No. 6,329,381), and amide derivatives (such as those described in U.S. Patent No. 6,069,149).
Other IRMs include large biological molecules such as oligonucleotide sequences.
Some IRM oligonucleotide sequences contain cytosine-guanine dinucleotides (CpG) and are described, for example, in U.S. Patent Nos. 6,1994,388; 6,207,646;
6,239,116;
6,339,068; and 6,406,705. Some CpG-containing oligonucleotides can include synthetic immunomodulatory structural motifs such as those described, for example, in U.S. Pat.
Nos. 6,426,334 and 6,476,000. Other IRM nucleotide sequences lack CpG and are described, for example, in International Patent Publication No. WO 00/75304.
Certain IRMs can function as Toll-like receptor (TLR) agonists, i.e., their immunomodulating influence is exerted through a TLR-mediated cellular pathway.
For example, some small molecule IRMs have been identified as agonists of one or more of TLRs 2, 4, 6, 7, and 8; and CpG has been identified as an agonist of TLR 9. In many cases, activating a TLR-mediated pathway results in gene transcription (e.g., cytokine or co-stimulatory marker expression) by activating NF--KB regardless of the particular TLR
that is activated.
Certain IRM compounds may be useful for the treatment of Th2-mediated diseases because they inhibit the Th2 immune response, suppress IL-4/IL-5 cytokine induction and eosinophilia, and enhance Thl immune response. IRM compounds that act as an agonist of at least one TLR have been shown to be particularly useful in this regard.
Some IRM
compounds have been found to have pharmacological effects on Langerhans cells as well.
Human Langerhans cells are .known to be derived from myeloid dendritic cells that express TLR8.
Therefore, the present invention provides for methods of reducing (including preventing) and/or treating UV-induced immunosuppression by administering one or more IRM compounds. In certain embodiments of the present invention, UV-induced immunosuppression may be reduced by prophylactic administration of an IRM
compound to a portion of the skin (e.g., topical application) before the skin is exposed to UV
radiation. In an alternative embodiment, UV-induced immunosuppression may be therapeutically treated by administration of an IRM compound to a portion of the skin (e.g., topical application) that has already been exposed to UV radiation. In yet other alternative embodiments, prophylactically reducing or therapeutically treating UV-induced immunosuppression may be accomplished by administering one or more IRM
compounds systemically.
In certain embodiments, the IRM compound includes an agonist of at least one TLR. In particular embodiments, the IRM compound can be an agonist of TLR7, TLR8, or TLR9. For example, the IRM compound can be an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an imidazotetrahydronaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, a thiazolonaphthyridine amine, or an imidazoquinoline amines including but not limited to 4-amino-2-ethoxymethyl-a,a-dimethyl-lH-imidazo[4,5-c]quinolin-1-ethanol, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, a 1,2-bridged imidazoquinoline amine, a sulfonamido-substituted imidazoquinoline amine; a urea-substituted imidazoquinoline amine; or a heteroaryl ether-substituted imidazoquinoline amine. The IRM may induce the production of one or more cytokines including but not limited to Type I interferons.
The IRM compound may be incorporated into a composition for topical administration. Suitable types of compositions include, but are not limited to, ointments, gels, foams, creams, lotions, solutions, suspensions, emulsions, pastes, powders, soaps, surfactant-containing cleaning preparations, solid sticks (e.g., wax- or petroleum-based sticks), oils and sprays. In particular exemplary embodiments, the IRM
compound may be incorporated into, for example, a sunscreen, a skin lotion, a skin moisturizer, or cosmetic.
Alternatively, the IRM compound may be incorporated into any vehicle suitable for systemic delivery. Typical systemic delivery routes include but are not limited to injection (e.g., intravenous, subcutaneous, intraperitoneal, intradermal), inhalation, ingestion, transdermal, or transmucosal delivery.
The particular amount of IRM compound necessary to (1) prophylactically reduce or prevent, or (2) therapeutically treat UV-induced immunosuppression in a subject may depend, at least in part, on one or more factors. Such factors include but are not limited to the particular IRM compound being administered, the state of the subject's immune system (e.g., suppressed, compromised, stimulated); the subject's past and expected UV
exposure; the route of administering the IRM; and the desired result (i.e., prophylactic reduction or prevention, or therapeutic treatment). Accordingly it is not practical to set forth generally the amount that constitutes an effective amount of IRM
compound. Those of ordinary skill in the art, however, can readily determine the appropriate amount with due consideration of such factors.
Examples The following examples have been selected merely to further illustrate features, advantages, and other details of the invention. It is to be expressly understood, however, that while the examples serve this purpose, the particular materials and amounts used as well as other conditions and details are not to be construed in a matter that would unduly limit the scope of this invention. Unless otherwise indicated, all percentages and ratios are by weight.
Example 1 - Contact Hypersensitivity in Mice Treated with IRM Before Exposure to UV-B Radiation Figure 1 summarizes the protocol used for testing the contact hypersensitivity of mice treated with immune response modifier compound 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (IRM) before exposure to UV-B radiation.
A topical cream including either a) 5% IRM (treated), or b) no IRM (vehicle-treated) was applied to a shaved portion of the abdomen of UVB-susceptible mice. The cream was applied for two consecutive days beginning five days before sensitization (Day -5 and Day -4).
The mice were exposed to either a) UV-B radiation, 70 mJ/cm from FS-20 light bulbs (National Biological Corp., Twinsburg, OH) equipped with a cellulose acetate filter to provide predominantly UV-B output, or b) sham radiation for four consecutive days beginning at three days prior to sensitization (Day -3 through Day 0).
The mice were sensitized for two consecutive days beginning at Day 0 (Day 0 and Day 1) with 25 L of 0.5% dinitrofluorobenzene (DNFB, Sigma Chemical Co., St.
Louis, MO) applied to the shaved portion of the abdomen.
On Day 5 after sensitization, the mice were challenged with DNFB on the pinna of the ear.
On Day 6 after sensitization, the extent to which the thickness of the ear pinna changed was measured in both the treated and untreated mice.
Three experiments were performed according to the protocol summarized in Figure 1. The results of each of the three experiments and the average of all three experiments are provided in Figure 2.
Example 2 - Contact Hypersensitivity in Mice Treated with IRM After Exposure to UV-B Radiation Figure 3 summarizes the protocol used for testing the contact hypersensitivity of mice treated with immune response modifier compound 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (IRM) after exposure to UV-B radiation.
The mice were exposed to either a) UV-B radiation, 70 mJ/cm from FS-20 light bulbs (National Biological Corp., Twinsburg, OH) equipped with a cellulose acetate filter to provide predominantly UV-B output, or b) sham radiation for four consecutive days beginning at four days prior to sensitization (Day -4 through Day -1).
A topical cream including either a) 5% IRM (treated), or b) no IRM (vehicle-treated) was applied to a shaved portion of the abdomen of UVB-susceptible mice. The cream was applied for two consecutive days beginning one day before sensitization (Day -1 and Day 0).
The mice were sensitized for two consecutive days beginning at Day 0 (Day 0 and Day 1) with 25 L of 0.5% dinitrofluorobenzene (DNFB, Sigma Chemical Co., St.
Louis, MO) applied to the shaved portion of the abdomen.
On Day 5 after sensitization, the mice were challenged with DNFB on the pinna of the ear.
On Day 6 after' sensitization, the extent to which the thickness of the ear pinna changed was measured in both the treated and untreated mice.
Two experiments were performed according to the protocol summarized in Figure 3. The results of those two experiments are shown in Figure 4.
Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows.
Certain IRMs can function as Toll-like receptor (TLR) agonists, i.e., their immunomodulating influence is exerted through a TLR-mediated cellular pathway.
For example, some small molecule IRMs have been identified as agonists of one or more of TLRs 2, 4, 6, 7, and 8; and CpG has been identified as an agonist of TLR 9. In many cases, activating a TLR-mediated pathway results in gene transcription (e.g., cytokine or co-stimulatory marker expression) by activating NF--KB regardless of the particular TLR
that is activated.
Certain IRM compounds may be useful for the treatment of Th2-mediated diseases because they inhibit the Th2 immune response, suppress IL-4/IL-5 cytokine induction and eosinophilia, and enhance Thl immune response. IRM compounds that act as an agonist of at least one TLR have been shown to be particularly useful in this regard.
Some IRM
compounds have been found to have pharmacological effects on Langerhans cells as well.
Human Langerhans cells are .known to be derived from myeloid dendritic cells that express TLR8.
Therefore, the present invention provides for methods of reducing (including preventing) and/or treating UV-induced immunosuppression by administering one or more IRM compounds. In certain embodiments of the present invention, UV-induced immunosuppression may be reduced by prophylactic administration of an IRM
compound to a portion of the skin (e.g., topical application) before the skin is exposed to UV
radiation. In an alternative embodiment, UV-induced immunosuppression may be therapeutically treated by administration of an IRM compound to a portion of the skin (e.g., topical application) that has already been exposed to UV radiation. In yet other alternative embodiments, prophylactically reducing or therapeutically treating UV-induced immunosuppression may be accomplished by administering one or more IRM
compounds systemically.
In certain embodiments, the IRM compound includes an agonist of at least one TLR. In particular embodiments, the IRM compound can be an agonist of TLR7, TLR8, or TLR9. For example, the IRM compound can be an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an imidazotetrahydronaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, a thiazolonaphthyridine amine, or an imidazoquinoline amines including but not limited to 4-amino-2-ethoxymethyl-a,a-dimethyl-lH-imidazo[4,5-c]quinolin-1-ethanol, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, a 1,2-bridged imidazoquinoline amine, a sulfonamido-substituted imidazoquinoline amine; a urea-substituted imidazoquinoline amine; or a heteroaryl ether-substituted imidazoquinoline amine. The IRM may induce the production of one or more cytokines including but not limited to Type I interferons.
The IRM compound may be incorporated into a composition for topical administration. Suitable types of compositions include, but are not limited to, ointments, gels, foams, creams, lotions, solutions, suspensions, emulsions, pastes, powders, soaps, surfactant-containing cleaning preparations, solid sticks (e.g., wax- or petroleum-based sticks), oils and sprays. In particular exemplary embodiments, the IRM
compound may be incorporated into, for example, a sunscreen, a skin lotion, a skin moisturizer, or cosmetic.
Alternatively, the IRM compound may be incorporated into any vehicle suitable for systemic delivery. Typical systemic delivery routes include but are not limited to injection (e.g., intravenous, subcutaneous, intraperitoneal, intradermal), inhalation, ingestion, transdermal, or transmucosal delivery.
The particular amount of IRM compound necessary to (1) prophylactically reduce or prevent, or (2) therapeutically treat UV-induced immunosuppression in a subject may depend, at least in part, on one or more factors. Such factors include but are not limited to the particular IRM compound being administered, the state of the subject's immune system (e.g., suppressed, compromised, stimulated); the subject's past and expected UV
exposure; the route of administering the IRM; and the desired result (i.e., prophylactic reduction or prevention, or therapeutic treatment). Accordingly it is not practical to set forth generally the amount that constitutes an effective amount of IRM
compound. Those of ordinary skill in the art, however, can readily determine the appropriate amount with due consideration of such factors.
Examples The following examples have been selected merely to further illustrate features, advantages, and other details of the invention. It is to be expressly understood, however, that while the examples serve this purpose, the particular materials and amounts used as well as other conditions and details are not to be construed in a matter that would unduly limit the scope of this invention. Unless otherwise indicated, all percentages and ratios are by weight.
Example 1 - Contact Hypersensitivity in Mice Treated with IRM Before Exposure to UV-B Radiation Figure 1 summarizes the protocol used for testing the contact hypersensitivity of mice treated with immune response modifier compound 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (IRM) before exposure to UV-B radiation.
A topical cream including either a) 5% IRM (treated), or b) no IRM (vehicle-treated) was applied to a shaved portion of the abdomen of UVB-susceptible mice. The cream was applied for two consecutive days beginning five days before sensitization (Day -5 and Day -4).
The mice were exposed to either a) UV-B radiation, 70 mJ/cm from FS-20 light bulbs (National Biological Corp., Twinsburg, OH) equipped with a cellulose acetate filter to provide predominantly UV-B output, or b) sham radiation for four consecutive days beginning at three days prior to sensitization (Day -3 through Day 0).
The mice were sensitized for two consecutive days beginning at Day 0 (Day 0 and Day 1) with 25 L of 0.5% dinitrofluorobenzene (DNFB, Sigma Chemical Co., St.
Louis, MO) applied to the shaved portion of the abdomen.
On Day 5 after sensitization, the mice were challenged with DNFB on the pinna of the ear.
On Day 6 after sensitization, the extent to which the thickness of the ear pinna changed was measured in both the treated and untreated mice.
Three experiments were performed according to the protocol summarized in Figure 1. The results of each of the three experiments and the average of all three experiments are provided in Figure 2.
Example 2 - Contact Hypersensitivity in Mice Treated with IRM After Exposure to UV-B Radiation Figure 3 summarizes the protocol used for testing the contact hypersensitivity of mice treated with immune response modifier compound 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (IRM) after exposure to UV-B radiation.
The mice were exposed to either a) UV-B radiation, 70 mJ/cm from FS-20 light bulbs (National Biological Corp., Twinsburg, OH) equipped with a cellulose acetate filter to provide predominantly UV-B output, or b) sham radiation for four consecutive days beginning at four days prior to sensitization (Day -4 through Day -1).
A topical cream including either a) 5% IRM (treated), or b) no IRM (vehicle-treated) was applied to a shaved portion of the abdomen of UVB-susceptible mice. The cream was applied for two consecutive days beginning one day before sensitization (Day -1 and Day 0).
The mice were sensitized for two consecutive days beginning at Day 0 (Day 0 and Day 1) with 25 L of 0.5% dinitrofluorobenzene (DNFB, Sigma Chemical Co., St.
Louis, MO) applied to the shaved portion of the abdomen.
On Day 5 after sensitization, the mice were challenged with DNFB on the pinna of the ear.
On Day 6 after' sensitization, the extent to which the thickness of the ear pinna changed was measured in both the treated and untreated mice.
Two experiments were performed according to the protocol summarized in Figure 3. The results of those two experiments are shown in Figure 4.
Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows.
Claims (13)
1. Use of an immune response modifier compound for reducing UV-induced immunosuppression on a treatment area wherein the immune response modifier compound is an agonist of at least one toll-like receptor (TLR), wherein the use of the immune response modifier compound occurs prior to exposure of the treatment area to UV irradiation.
2. The use of claim 1, wherein the immune response modifier compound is an agonist of TLR7, TLR8, or TLR9.
3. The use of claim 1, wherein the immune response modifier compound comprises an imidazoquinoline amine, an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an imidazotetrahydronaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.
4. The use of claim 1, wherein the immune response modifier compound is adapted to be administered via a topical application vehicle.
5. The use of claim 4, wherein the topical application vehicle comprises a cream, a gel, a spray, an ointment, a lotion, a solution, a suspension, an emulsion, a paste, a powder, or an oil.
6. The use of claim 4, wherein the immune response modifier compound is adapted to be administered via a sunscreen, a skin lotion, a skin moisturizer, a cosmetic, a soap, a spray, a foam, a gel, or a surfactant-containing cleaning preparation.
7. Use of an immune response modifier for preventing UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR, wherein the use of the immune response modifier compound occurs prior to exposure of the treatment area to UV irradiation.
8. The use of claim 7, wherein the immune response modifier compound is an agonist of TLR7, TLR8, or TLR9.
9. The use of claim 7, wherein the immune response modifier compound comprises an imidazoquinoline amine, an imidazopyridine amine, a 6,7-fused cycloalkylimidazopyridine amine, a 1,2-bridged imidazoquinoline amine, an imidazonaphthyridine amine, an imidazotetrahydronaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.
10. The use of claim 7, wherein the immune response modifier compound is adapted to be administered via a topical application vehicle.
11. The use of claim 10, wherein the topical application vehicle comprises a cream, a gel, a spray, an ointment, a lotion, a solution, a suspension, an emulsion, a paste, a powder, or an oil.
12. The use of claim 10, wherein the immune response modifier compound is adapted to be administered via a sunscreen, a skin lotion, a skin moisturizer, a cosmetic, a soap, a spray, a foam, a gel, or a surfactant-containing cleaning preparation.
13. Use of an immune response modifier in the manufacture of a medicament for preventing UV-induced immunosuppression, wherein the immune response modifier compound is an agonist of at least one TLR, wherein the immune response modifier compound is adapted to be administered to a treatment area prior to exposure of said treatment area to UV irradiation.
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Families Citing this family (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA67760C2 (en) * | 1997-12-11 | 2004-07-15 | Міннесота Майнінг Енд Мануфакчурінг Компані | Imidazonaphthyridines and use thereof to induce the biosynthesis of cytokines |
| US6756382B2 (en) * | 1999-06-10 | 2004-06-29 | 3M Innovative Properties Company | Amide substituted imidazoquinolines |
| US6573273B1 (en) * | 1999-06-10 | 2003-06-03 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| US6331539B1 (en) * | 1999-06-10 | 2001-12-18 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| JP3436512B2 (en) * | 1999-12-28 | 2003-08-11 | 株式会社デンソー | Accelerator device |
| UA75622C2 (en) | 2000-12-08 | 2006-05-15 | 3M Innovative Properties Co | Aryl ether substituted imidazoquinolines, pharmaceutical composition based thereon |
| US6545016B1 (en) | 2000-12-08 | 2003-04-08 | 3M Innovative Properties Company | Amide substituted imidazopyridines |
| US6664265B2 (en) | 2000-12-08 | 2003-12-16 | 3M Innovative Properties Company | Amido ether substituted imidazoquinolines |
| JP2008531580A (en) * | 2000-12-08 | 2008-08-14 | スリーエム イノベイティブ プロパティズ カンパニー | Compositions and methods for targeted delivery of immune response modifiers |
| US6660735B2 (en) * | 2000-12-08 | 2003-12-09 | 3M Innovative Properties Company | Urea substituted imidazoquinoline ethers |
| US6664264B2 (en) * | 2000-12-08 | 2003-12-16 | 3M Innovative Properties Company | Thioether substituted imidazoquinolines |
| US6545017B1 (en) * | 2000-12-08 | 2003-04-08 | 3M Innovative Properties Company | Urea substituted imidazopyridines |
| US6525064B1 (en) | 2000-12-08 | 2003-02-25 | 3M Innovative Properties Company | Sulfonamido substituted imidazopyridines |
| US6667312B2 (en) * | 2000-12-08 | 2003-12-23 | 3M Innovative Properties Company | Thioether substituted imidazoquinolines |
| US7226928B2 (en) * | 2001-06-15 | 2007-06-05 | 3M Innovative Properties Company | Methods for the treatment of periodontal disease |
| US6677349B1 (en) * | 2001-12-21 | 2004-01-13 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| JP2005518433A (en) * | 2002-02-22 | 2005-06-23 | スリーエム イノベイティブ プロパティズ カンパニー | Methods for reducing and treating UVB-induced immunosuppression |
| JP2005538057A (en) | 2002-06-07 | 2005-12-15 | スリーエム イノベイティブ プロパティズ カンパニー | Ether-substituted imidazopyridine |
| AU2003299863B2 (en) | 2002-08-15 | 2009-09-24 | 3M Innovative Properties Company | Immunostimulatory compositions and methods of stimulating an immune response |
| AU2003301052A1 (en) | 2002-12-20 | 2004-07-22 | 3M Innovative Properties Company | Aryl / hetaryl substituted imidazoquinolines |
| AU2004218349A1 (en) * | 2003-03-04 | 2004-09-16 | 3M Innovative Properties Company | Prophylactic treatment of UV-induced epidermal neoplasia |
| US7163947B2 (en) * | 2003-03-07 | 2007-01-16 | 3M Innovative Properties Company | 1-Amino 1H-imidazoquinolines |
| CA2517655A1 (en) * | 2003-03-07 | 2004-09-23 | 3M Innovative Properties Company | 1-amino 1h-imidazoquinolines |
| MXPA05009694A (en) * | 2003-03-13 | 2005-10-20 | 3M Innovative Properties Co | Methods of improving skin quality. |
| WO2004080293A2 (en) * | 2003-03-13 | 2004-09-23 | 3M Innovative Properties Company | Methods for diagnosing skin lesions |
| WO2004087049A2 (en) * | 2003-03-25 | 2004-10-14 | 3M Innovative Properties Company | Selective activation of cellular activities mediated through a common toll-like receptor |
| AU2004244962A1 (en) * | 2003-04-10 | 2004-12-16 | 3M Innovative Properties Company | Delivery of immune response modifier compounds using metal-containing particulate support materials |
| US20040265351A1 (en) * | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| WO2004110991A2 (en) * | 2003-06-06 | 2004-12-23 | 3M Innovative Properties Company | PROCESS FOR IMIDAZO[4,5-c]PYRIDIN-4-AMINES |
| WO2004110992A2 (en) * | 2003-06-06 | 2004-12-23 | 3M Innovative Properties Company | Process for imidazo[4,5-c] pyridin-4-amines |
| WO2005016273A2 (en) * | 2003-08-05 | 2005-02-24 | 3M Innovative Properties Company | Infection prophylaxis using immune response modifier compounds |
| 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 |
| PL1653959T3 (en) * | 2003-08-14 | 2015-10-30 | 3M Innovative Properties Co | Lipid-modified immune response modifiers |
| EP1660122A4 (en) * | 2003-08-25 | 2007-10-24 | 3M Innovative Properties Co | Immunostimulatory combinations and treatments |
| AU2004268616B2 (en) | 2003-08-25 | 2010-10-07 | 3M Innovative Properties Company | Delivery of immune response modifier compounds |
| EP1658076B1 (en) * | 2003-08-27 | 2013-03-06 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted imidazoquinolines |
| AU2004270201A1 (en) * | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for CD5+ B cell lymphoma |
| EP1664342A4 (en) * | 2003-09-17 | 2007-12-26 | 3M Innovative Properties Co | Selective modulation of tlr gene expression |
| AU2004315876B2 (en) | 2003-10-03 | 2011-05-26 | 3M Innovative Properties Company | Pyrazolopyridines and analogs thereof |
| BRPI0414856A (en) | 2003-10-03 | 2006-11-21 | 3M Innovative Properties Co | alkoxy-substituted imidazoquinolines |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| 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 |
| WO2005048945A2 (en) * | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Hydroxylamine substituted imidazo ring compounds |
| US8778963B2 (en) * | 2003-11-25 | 2014-07-15 | 3M Innovative Properties Company | Hydroxylamine and oxime substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines |
| US8691837B2 (en) | 2003-11-25 | 2014-04-08 | 3M Innovative Properties Company | Substituted imidazo ring systems and methods |
| US8940755B2 (en) * | 2003-12-02 | 2015-01-27 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
| AU2004315771A1 (en) * | 2003-12-04 | 2005-08-25 | 3M Innovative Properties Company | Sulfone substituted imidazo ring ethers |
| WO2005066172A1 (en) * | 2003-12-29 | 2005-07-21 | 3M Innovative Properties Company | Piperazine, [1,4]diazepane, [1,4]diazocane, and [1,5]diazocane fused imidazo ring compounds |
| WO2005066170A1 (en) | 2003-12-29 | 2005-07-21 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
| EP1699398A4 (en) * | 2003-12-30 | 2007-10-17 | 3M Innovative Properties Co | Enhancement of immune responses |
| US8735421B2 (en) | 2003-12-30 | 2014-05-27 | 3M Innovative Properties Company | Imidazoquinolinyl sulfonamides |
| CA2559607C (en) * | 2004-03-15 | 2013-02-19 | 3M Innovative Properties Company | Immune response modifier formulations and methods |
| WO2005094531A2 (en) | 2004-03-24 | 2005-10-13 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
| JP2008505857A (en) * | 2004-04-28 | 2008-02-28 | スリーエム イノベイティブ プロパティズ カンパニー | Compositions and methods for mucosal vaccination |
| US20050267145A1 (en) * | 2004-05-28 | 2005-12-01 | Merrill Bryon A | Treatment for lung cancer |
| US20080015184A1 (en) * | 2004-06-14 | 2008-01-17 | 3M Innovative Properties Company | Urea Substituted Imidazopyridines, Imidazoquinolines, and Imidazonaphthyridines |
| WO2005123080A2 (en) | 2004-06-15 | 2005-12-29 | 3M Innovative Properties Company | Nitrogen-containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
| EP1765348B1 (en) * | 2004-06-18 | 2016-08-03 | 3M Innovative Properties Company | Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines |
| WO2006009826A1 (en) | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
| WO2006065280A2 (en) | 2004-06-18 | 2006-06-22 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and methods |
| US8541438B2 (en) | 2004-06-18 | 2013-09-24 | 3M Innovative Properties Company | Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines |
| WO2006038923A2 (en) | 2004-06-18 | 2006-04-13 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
| US20070259881A1 (en) * | 2004-06-18 | 2007-11-08 | Dellaria Joseph F Jr | Substituted Imidazo Ring Systems and Methods |
| EP1786450A4 (en) * | 2004-08-27 | 2009-11-11 | 3M Innovative Properties Co | Hiv immunostimulatory compositions |
| CA2578741C (en) * | 2004-09-02 | 2014-01-14 | 3M Innovative Properties Company | 1-alkoxy 1h-imidazo ring systems and methods |
| CA2578975A1 (en) | 2004-09-02 | 2006-03-16 | 3M Innovative Properties Company | 2-amino 1h imidazo ring systems and methods |
| WO2006042254A2 (en) * | 2004-10-08 | 2006-04-20 | 3M Innovative Properties Company | Adjuvant for dna vaccines |
| WO2006074003A2 (en) * | 2004-12-30 | 2006-07-13 | 3M Innovative Properties Company | CHIRAL FUSED [1,2]IMIDAZO[4,5-c] RING COMPOUNDS |
| ES2538498T3 (en) * | 2004-12-30 | 2015-06-22 | Meda Ab | Use of Imiquimod for the treatment of skin metastases from a breast cancer tumor |
| US8436176B2 (en) * | 2004-12-30 | 2013-05-07 | Medicis Pharmaceutical Corporation | Process for preparing 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine |
| CA2592897A1 (en) * | 2004-12-30 | 2006-07-13 | Takeda Pharmaceutical Company Limited | 1-(2-methylpropyl)-1h-imidazo[4,5-c][1,5]naphthyridin-4-amine ethanesulfonate and 1-(2-methylpropyl)-1h-imidazo[4,5-c][1,5]naphthyridin-4-amine methanesulfonate |
| CA2594674C (en) | 2004-12-30 | 2016-05-17 | 3M Innovative Properties Company | Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds |
| KR101415864B1 (en) | 2005-01-28 | 2014-07-09 | 갈렌바이오 인코포레이티드 | Immunologically active compositions |
| US9248127B2 (en) | 2005-02-04 | 2016-02-02 | 3M Innovative Properties Company | Aqueous gel formulations containing immune response modifiers |
| CA2602083A1 (en) | 2005-02-09 | 2006-08-09 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted thiazolo(4,5-c) ring compounds and methods |
| AU2006212765B2 (en) | 2005-02-09 | 2012-02-02 | 3M Innovative Properties Company | Alkyloxy substituted thiazoloquinolines and thiazolonaphthyridines |
| US8658666B2 (en) * | 2005-02-11 | 2014-02-25 | 3M Innovative Properties Company | Substituted imidazoquinolines and imidazonaphthyridines |
| US7968563B2 (en) | 2005-02-11 | 2011-06-28 | 3M Innovative Properties Company | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
| CA2598695A1 (en) * | 2005-02-23 | 2006-09-21 | Coley Pharmaceutical Group, Inc. | Hydroxyalkyl substituted imidazoquinolines |
| EP1850849A2 (en) * | 2005-02-23 | 2007-11-07 | Coley Pharmaceutical Group, Inc. | Method of preferentially inducing the biosynthesis of interferon |
| CA2598639A1 (en) | 2005-02-23 | 2006-08-31 | Coley Pharmaceutical Group, Inc. | Hydroxyalkyl substituted imidazonaphthyridines |
| US8158794B2 (en) * | 2005-02-23 | 2012-04-17 | 3M Innovative Properties Company | Hydroxyalkyl substituted imidazoquinoline compounds and methods |
| AU2006223148A1 (en) | 2005-03-14 | 2006-09-21 | 3M Innovative Properties Company | Method of treating actinic keratosis |
| 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 |
| JP2008539252A (en) * | 2005-04-25 | 2008-11-13 | スリーエム イノベイティブ プロパティズ カンパニー | Immune activation composition |
| US8476292B2 (en) * | 2005-09-09 | 2013-07-02 | 3M Innovative Properties Company | Amide and carbamate derivatives of N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c] quinolin-1-Yl]-1,1-dimethylethyl}methanesulfonamide and methods |
| ZA200803029B (en) * | 2005-09-09 | 2009-02-25 | Coley Pharm Group Inc | Amide and carbamate derivatives of alkyl substituted /V-[4-(4-amino-1H-imidazo[4,5-c] quinolin-1-yl)butyl] methane-sulfonamides and methods |
| EP1948173B1 (en) | 2005-11-04 | 2013-07-17 | 3M Innovative Properties Company | Hydroxy and alkoxy substituted 1h-imidazoquinolines and methods |
| EP3085373A1 (en) | 2006-02-22 | 2016-10-26 | 3M Innovative Properties Company | Immune response modifier conjugates |
| WO2007106854A2 (en) * | 2006-03-15 | 2007-09-20 | Coley Pharmaceutical Group, Inc. | Hydroxy and alkoxy substituted 1h-imidazonaphthyridines and methods |
| US7906506B2 (en) | 2006-07-12 | 2011-03-15 | 3M Innovative Properties Company | Substituted chiral fused [1,2] imidazo [4,5-c] ring compounds and methods |
| EP2046121B1 (en) * | 2006-07-14 | 2012-08-22 | Stiefel Research Australia Pty Ltd | Fatty acid pharmaceutical foam |
| US8178539B2 (en) * | 2006-09-06 | 2012-05-15 | 3M Innovative Properties Company | Substituted 3,4,6,7-tetrahydro-5H-1,2a,4a,8-tetraazacyclopenta[cd]phenalenes and methods |
| US20080149123A1 (en) * | 2006-12-22 | 2008-06-26 | Mckay William D | Particulate material dispensing hairbrush with combination bristles |
| HUE033901T2 (en) | 2010-08-17 | 2018-01-29 | 3M Innovative Properties Co | Lipidated immune response modifier compound compositions, formulations, and methods |
| JP6460789B2 (en) | 2011-06-03 | 2019-01-30 | スリーエム イノベイティブ プロパティズ カンパニー | Heterobifunctional linker having polyethylene glycol segment and immune response modulating complex prepared from the linker |
| CA2838023C (en) | 2011-06-03 | 2019-08-13 | 3M Innovative Properties Company | Hydrazino 1h-imidazoquinolin-4-amines and conjugates made therefrom |
| EP3532505A4 (en) | 2016-10-25 | 2019-12-25 | Urogen Pharma Ltd. | Immunomodulating treatments of body cavities |
| US11306083B2 (en) | 2017-12-20 | 2022-04-19 | 3M Innovative Properties Company | Amide substituted imidazo[4,5-C]quinoline compounds with a branched chain linking group for use as an immune response modifier |
Family Cites Families (107)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL73534A (en) | 1983-11-18 | 1990-12-23 | Riker Laboratories Inc | 1h-imidazo(4,5-c)quinoline-4-amines,their preparation and pharmaceutical compositions containing certain such compounds |
| ZA848968B (en) | 1983-11-18 | 1986-06-25 | Riker Laboratories Inc | 1h-imidazo(4,5-c)quinolines and 1h-imidazo(4,5-c)quinolin-4-amines |
| US4894366A (en) * | 1984-12-03 | 1990-01-16 | Fujisawa Pharmaceutical Company, Ltd. | Tricyclo compounds, a process for their production and a pharmaceutical composition containing the same |
| US4689348A (en) * | 1984-08-17 | 1987-08-25 | Dow Chemical Company | Cyanoguanidines useful as animal growth promoting agents |
| US5382579A (en) * | 1988-10-31 | 1995-01-17 | Eisai Co., Ltd. | Triazolo-1,4-diazepine derivatives and their use in pharmaceuticals |
| US5238944A (en) | 1988-12-15 | 1993-08-24 | Riker Laboratories, Inc. | Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine |
| US5756747A (en) | 1989-02-27 | 1998-05-26 | Riker Laboratories, Inc. | 1H-imidazo 4,5-c!quinolin-4-amines |
| US4929624A (en) | 1989-03-23 | 1990-05-29 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo(4,5-c)quinolin-4-amines |
| US5037986A (en) | 1989-03-23 | 1991-08-06 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo[4,5-c]quinolin-4-amines |
| US4988815A (en) | 1989-10-26 | 1991-01-29 | Riker Laboratories, Inc. | 3-Amino or 3-nitro quinoline compounds which are intermediates in preparing 1H-imidazo[4,5-c]quinolines |
| DK0553202T3 (en) | 1990-10-05 | 1995-07-03 | Minnesota Mining & Mfg | Process for the preparation of imidazo (4,5-c) quinoline-4-amines |
| US5175296A (en) | 1991-03-01 | 1992-12-29 | Minnesota Mining And Manufacturing Company | Imidazo[4,5-c]quinolin-4-amines and processes for their preparation |
| US5389640A (en) | 1991-03-01 | 1995-02-14 | Minnesota Mining And Manufacturing Company | 1-substituted, 2-substituted 1H-imidazo[4,5-c]quinolin-4-amines |
| US5268376A (en) | 1991-09-04 | 1993-12-07 | Minnesota Mining And Manufacturing Company | 1-substituted 1H-imidazo[4,5-c]quinolin-4-amines |
| US5266575A (en) | 1991-11-06 | 1993-11-30 | Minnesota Mining And Manufacturing Company | 2-ethyl 1H-imidazo[4,5-ciquinolin-4-amines |
| IL105325A (en) | 1992-04-16 | 1996-11-14 | Minnesota Mining & Mfg | Immunogen/vaccine adjuvant composition |
| US5395937A (en) | 1993-01-29 | 1995-03-07 | Minnesota Mining And Manufacturing Company | Process for preparing quinoline amines |
| US5346501A (en) * | 1993-02-05 | 1994-09-13 | Ethicon, Inc. | Laparoscopic absorbable anastomosic fastener and means for applying |
| EP0622681B1 (en) | 1993-04-27 | 1997-10-01 | Agfa-Gevaert N.V. | Process for incorporation of a water-insoluble substance into a hydrophilic layer |
| US5352784A (en) | 1993-07-15 | 1994-10-04 | Minnesota Mining And Manufacturing Company | Fused cycloalkylimidazopyridines |
| CZ288182B6 (en) | 1993-07-15 | 2001-05-16 | Minnesota Mining & Mfg | Imidazo[4,5-c]pyridine-4-amines and pharmaceutical preparations based thereon |
| CN1046725C (en) * | 1994-06-20 | 1999-11-24 | 武田药品工业株式会社 | Condensed imidazole compounds, their production and use |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5482936A (en) | 1995-01-12 | 1996-01-09 | Minnesota Mining And Manufacturing Company | Imidazo[4,5-C]quinoline amines |
| US5741908A (en) | 1996-06-21 | 1998-04-21 | Minnesota Mining And Manufacturing Company | Process for reparing imidazoquinolinamines |
| US5693811A (en) | 1996-06-21 | 1997-12-02 | Minnesota Mining And Manufacturing Company | Process for preparing tetrahdroimidazoquinolinamines |
| EP0882727B9 (en) | 1996-07-03 | 2005-06-15 | Sumitomo Pharmaceuticals Company, Limited | Novel purine derivatives |
| US6387938B1 (en) | 1996-07-05 | 2002-05-14 | Mochida Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
| CA2268957C (en) | 1996-10-25 | 2008-04-29 | Minnesota Mining And Manufacturing Company | Immune response modifier compounds for treatment of th2 mediated and related diseases |
| US5939090A (en) | 1996-12-03 | 1999-08-17 | 3M Innovative Properties Company | Gel formulations for topical drug delivery |
| EP0894797A4 (en) | 1997-01-09 | 2001-08-16 | Terumo Corp | Novel amide derivatives and intermediates for the synthesis thereof |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| JPH10298181A (en) * | 1997-04-25 | 1998-11-10 | Sumitomo Pharmaceut Co Ltd | Type 2 helper t cell selective immune response inhibitor |
| US6426334B1 (en) | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
| US6303347B1 (en) | 1997-05-08 | 2001-10-16 | Corixa Corporation | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| US6113918A (en) | 1997-05-08 | 2000-09-05 | Ribi Immunochem Research, Inc. | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
| EP1003531B1 (en) | 1997-05-20 | 2007-08-22 | Ottawa Health Research Institute | Processes for preparing nucleic acid constructs |
| ES2205573T3 (en) | 1997-11-28 | 2004-05-01 | Sumitomo Pharmaceuticals Company, Limited | NEW HETEROCICLIC COMPOUNDS. |
| UA67760C2 (en) | 1997-12-11 | 2004-07-15 | Міннесота Майнінг Енд Мануфакчурінг Компані | Imidazonaphthyridines and use thereof to induce the biosynthesis of cytokines |
| TW572758B (en) | 1997-12-22 | 2004-01-21 | Sumitomo Pharma | Type 2 helper T cell-selective immune response inhibitors comprising purine derivatives |
| AUPP112497A0 (en) * | 1997-12-24 | 1998-01-22 | Novogen Research Pty Ltd | Compositions and method for protecting skin from UV induced immunosupression and skin damage |
| FR2775622A1 (en) | 1998-03-03 | 1999-09-03 | Atochem Elf Sa | SUPPORTED BIMETALLIC CATALYZER BASED ON PLATINUM OR SILVER, ITS MANUFACTURING PROCESS AND ITS USE FOR ELECTROCHEMICAL CELLS |
| US6110929A (en) | 1998-07-28 | 2000-08-29 | 3M Innovative Properties Company | Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs thereof |
| JP2000119271A (en) | 1998-08-12 | 2000-04-25 | Hokuriku Seiyaku Co Ltd | 1h-imidazopyridine derivative |
| US20020058674A1 (en) | 1999-01-08 | 2002-05-16 | Hedenstrom John C. | Systems and methods for treating a mucosal surface |
| CN1555264A (en) | 1999-01-08 | 2004-12-15 | 3M | Formulations for treatment of mucosal associated conditions with an immune response modifier |
| US6558951B1 (en) * | 1999-02-11 | 2003-05-06 | 3M Innovative Properties Company | Maturation of dendritic cells with immune response modifying compounds |
| JP2000247884A (en) * | 1999-03-01 | 2000-09-12 | Sumitomo Pharmaceut Co Ltd | Arachidonic acid-induced skin disease-treating agent |
| US6573273B1 (en) | 1999-06-10 | 2003-06-03 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| US6451810B1 (en) | 1999-06-10 | 2002-09-17 | 3M Innovative Properties Company | Amide substituted imidazoquinolines |
| US6541485B1 (en) | 1999-06-10 | 2003-04-01 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| US6756382B2 (en) | 1999-06-10 | 2004-06-29 | 3M Innovative Properties Company | Amide substituted imidazoquinolines |
| US6331539B1 (en) | 1999-06-10 | 2001-12-18 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| WO2001012804A2 (en) | 1999-08-13 | 2001-02-22 | Hybridon, Inc. | MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES |
| US6147086A (en) * | 1999-09-01 | 2000-11-14 | Brenman; Steven A. | Method employing imiquimod cream for treatment of topical sarcoidosis on equine |
| US6376669B1 (en) | 1999-11-05 | 2002-04-23 | 3M Innovative Properties Company | Dye labeled imidazoquinoline compounds |
| AUPQ515000A0 (en) * | 2000-01-19 | 2000-02-10 | Grigg, Geoffrey Walter | Treatment of uv induced immunosuppression |
| US20040023870A1 (en) | 2000-01-21 | 2004-02-05 | Douglas Dedera | Methods of therapy and diagnosis using targeting of cells that express toll-like receptor proteins |
| GB0001704D0 (en) | 2000-01-25 | 2000-03-15 | Glaxo Group Ltd | Protein |
| CA2403553A1 (en) | 2000-03-17 | 2001-09-27 | David Johnson | Novel amphipathic aldehydes and their use as adjuvants and immunoeffectors |
| DE10014631A1 (en) * | 2000-03-24 | 2001-09-27 | Merck Patent Gmbh | Treating or preventing UV-induced immunosuppression, using ectoine or its derivatives, is useful in topical care or make-up cosmetic compositions for maintaining the barrier effect of the skin |
| EP1300418A1 (en) * | 2001-10-04 | 2003-04-09 | Erasmus Universiteit Rotterdam | Gene regulation by oligopeptides |
| US6894060B2 (en) | 2000-03-30 | 2005-05-17 | 3M Innovative Properties Company | Method for the treatment of dermal lesions caused by envenomation |
| US20020055517A1 (en) | 2000-09-15 | 2002-05-09 | 3M Innovative Properties Company | Methods for delaying recurrence of herpes virus symptoms |
| US20030134283A1 (en) * | 2000-10-03 | 2003-07-17 | Peterson David P. | Genes regulated in dendritic cell differentiation |
| US6664260B2 (en) | 2000-12-08 | 2003-12-16 | 3M Innovative Properties Company | Heterocyclic ether substituted imidazoquinolines |
| US6667312B2 (en) | 2000-12-08 | 2003-12-23 | 3M Innovative Properties Company | Thioether substituted imidazoquinolines |
| US6660735B2 (en) | 2000-12-08 | 2003-12-09 | 3M Innovative Properties Company | Urea substituted imidazoquinoline ethers |
| US6664265B2 (en) | 2000-12-08 | 2003-12-16 | 3M Innovative Properties Company | Amido ether substituted imidazoquinolines |
| US6545017B1 (en) | 2000-12-08 | 2003-04-08 | 3M Innovative Properties Company | Urea substituted imidazopyridines |
| UA75622C2 (en) | 2000-12-08 | 2006-05-15 | 3M Innovative Properties Co | Aryl ether substituted imidazoquinolines, pharmaceutical composition based thereon |
| US6545016B1 (en) | 2000-12-08 | 2003-04-08 | 3M Innovative Properties Company | Amide substituted imidazopyridines |
| US6660747B2 (en) | 2000-12-08 | 2003-12-09 | 3M Innovative Properties Company | Amido ether substituted imidazoquinolines |
| US6677348B2 (en) | 2000-12-08 | 2004-01-13 | 3M Innovative Properties Company | Aryl ether substituted imidazoquinolines |
| US6677347B2 (en) | 2000-12-08 | 2004-01-13 | 3M Innovative Properties Company | Sulfonamido ether substituted imidazoquinolines |
| EP1360486A2 (en) | 2000-12-08 | 2003-11-12 | 3M Innovative Properties Company | Screening method for identifying compounds that selectively induce interferon alpha |
| US6525064B1 (en) | 2000-12-08 | 2003-02-25 | 3M Innovative Properties Company | Sulfonamido substituted imidazopyridines |
| US6664264B2 (en) | 2000-12-08 | 2003-12-16 | 3M Innovative Properties Company | Thioether substituted imidazoquinolines |
| ATE350010T1 (en) * | 2001-02-23 | 2007-01-15 | Richter Chem Lab | COMPOSITION FOR TOPICAL USE |
| US20030129605A1 (en) * | 2001-05-04 | 2003-07-10 | Dong Yu | Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosophonate linkages |
| US20030133913A1 (en) | 2001-08-30 | 2003-07-17 | 3M Innovative Properties Company | Methods of maturing plasmacytoid dendritic cells using immune response modifier molecules |
| AU2002360278A1 (en) * | 2001-10-12 | 2003-11-11 | Coley Pharmaceutical Gmbh | Methods and products for enhancing immune responses using imidazoquinoline compounds |
| DK1719511T3 (en) * | 2001-11-16 | 2009-04-14 | Coley Pharm Group Inc | N- [4- (4-amino-2-ethyl-1H-imidazo [4,5-c] quinolin-1-yl) butyl] methanesulfonamide, a pharmaceutical composition comprising the same, and use thereof |
| CN101033242A (en) | 2001-11-27 | 2007-09-12 | 安那迪斯药品股份有限公司 | Antenna system for a level measurement apparatus |
| ES2312659T3 (en) * | 2001-11-29 | 2009-03-01 | 3M Innovative Properties Company | PHARMACEUTICAL FORMULATIONS THAT INCLUDE A MODIFIER OF THE IMMUNE RESPONSE. |
| US6677349B1 (en) | 2001-12-21 | 2004-01-13 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| US6525028B1 (en) | 2002-02-04 | 2003-02-25 | Corixa Corporation | Immunoeffector compounds |
| JP2005518433A (en) | 2002-02-22 | 2005-06-23 | スリーエム イノベイティブ プロパティズ カンパニー | Methods for reducing and treating UVB-induced immunosuppression |
| AU2003233519A1 (en) | 2002-05-29 | 2003-12-19 | 3M Innovative Properties Company | Process for imidazo(4,5-c)pyridin-4-amines |
| JP2005538057A (en) | 2002-06-07 | 2005-12-15 | スリーエム イノベイティブ プロパティズ カンパニー | Ether-substituted imidazopyridine |
| AU2003299863B2 (en) | 2002-08-15 | 2009-09-24 | 3M Innovative Properties Company | Immunostimulatory compositions and methods of stimulating an immune response |
| AU2003299082A1 (en) | 2002-09-26 | 2004-04-19 | 3M Innovative Properties Company | 1h-imidazo dimers |
| AU2003287316A1 (en) | 2002-12-11 | 2004-06-30 | 3M Innovative Properties Company | Assays relating to toll-like receptor activity |
| AU2003301052A1 (en) | 2002-12-20 | 2004-07-22 | 3M Innovative Properties Company | Aryl / hetaryl substituted imidazoquinolines |
| US7387271B2 (en) | 2002-12-30 | 2008-06-17 | 3M Innovative Properties Company | Immunostimulatory combinations |
| WO2004071459A2 (en) | 2003-02-13 | 2004-08-26 | 3M Innovative Properties Company | Methods and compositions related to irm compounds and toll-like receptor 8 |
| US7485432B2 (en) | 2003-02-27 | 2009-02-03 | 3M Innovative Properties Company | Selective modulation of TLR-mediated biological activity |
| AU2004218349A1 (en) | 2003-03-04 | 2004-09-16 | 3M Innovative Properties Company | Prophylactic treatment of UV-induced epidermal neoplasia |
| CA2517655A1 (en) | 2003-03-07 | 2004-09-23 | 3M Innovative Properties Company | 1-amino 1h-imidazoquinolines |
| CA2518445A1 (en) | 2003-03-13 | 2004-09-23 | 3M Innovative Properties Company | Method of tattoo removal |
| WO2004080293A2 (en) | 2003-03-13 | 2004-09-23 | 3M Innovative Properties Company | Methods for diagnosing skin lesions |
| MXPA05009694A (en) | 2003-03-13 | 2005-10-20 | 3M Innovative Properties Co | Methods of improving skin quality. |
| US20040192585A1 (en) | 2003-03-25 | 2004-09-30 | 3M Innovative Properties Company | Treatment for basal cell carcinoma |
| WO2004087049A2 (en) | 2003-03-25 | 2004-10-14 | 3M Innovative Properties Company | Selective activation of cellular activities mediated through a common toll-like receptor |
| AU2004244962A1 (en) | 2003-04-10 | 2004-12-16 | 3M Innovative Properties Company | Delivery of immune response modifier compounds using metal-containing particulate support materials |
| EP1617845A4 (en) * | 2003-04-28 | 2006-09-20 | 3M Innovative Properties Co | Compositions and methods for induction of opioid receptors |
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- 2003-02-20 JP JP2003570773A patent/JP2005518433A/en active Pending
- 2003-02-20 PT PT37091717T patent/PT1478327E/en unknown
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| US20060142235A1 (en) | 2006-06-29 |
| DK1478327T3 (en) | 2015-07-27 |
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| BR0307788A (en) | 2006-04-04 |
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| JP2005518433A (en) | 2005-06-23 |
| ZA200407605B (en) | 2006-06-28 |
| EP1478327B1 (en) | 2015-04-29 |
| AU2003213125B2 (en) | 2008-02-21 |
| NZ534566A (en) | 2007-02-23 |
| US20030161797A1 (en) | 2003-08-28 |
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| MXPA04008023A (en) | 2004-11-26 |
| AU2003213125A1 (en) | 2003-09-09 |
| WO2003072026A3 (en) | 2003-12-24 |
| ES2541132T3 (en) | 2015-07-16 |
| EP1478327A4 (en) | 2007-07-04 |
| US7030129B2 (en) | 2006-04-18 |
| SI1478327T1 (en) | 2015-08-31 |
| PT1478327E (en) | 2015-08-04 |
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