DE69225978D1 - Verfahren zur herstellung und anwendung von multimeren hämoblobinen - Google Patents

Verfahren zur herstellung und anwendung von multimeren hämoblobinen

Info

Publication number
DE69225978D1
DE69225978D1 DE69225978T DE69225978T DE69225978D1 DE 69225978 D1 DE69225978 D1 DE 69225978D1 DE 69225978 T DE69225978 T DE 69225978T DE 69225978 T DE69225978 T DE 69225978T DE 69225978 D1 DE69225978 D1 DE 69225978D1
Authority
DE
Germany
Prior art keywords
multimeral
hemoblobines
production
cysteines
artificial
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
DE69225978T
Other languages
English (en)
Other versions
DE69225978T2 (de
Inventor
David Anderson
Anthony Mathews
Gary Stetler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter Biotech Technology SARL
Original Assignee
SOMATOGEN Inc BOULDER US
Somatogen Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by SOMATOGEN Inc BOULDER US, Somatogen Inc filed Critical SOMATOGEN Inc BOULDER US
Publication of DE69225978D1 publication Critical patent/DE69225978D1/de
Application granted granted Critical
Publication of DE69225978T2 publication Critical patent/DE69225978T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/795—Porphyrin- or corrin-ring-containing peptides
    • C07K14/805—Haemoglobins; Myoglobins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6445—Haemoglobin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/90—Fusion polypeptide containing a motif for post-translational modification
    • C07K2319/92—Fusion polypeptide containing a motif for post-translational modification containing an intein ("protein splicing")domain
DE69225978T 1991-11-08 1992-11-06 Verfahren zur herstellung und anwendung von multimeren hämoblobinen Expired - Fee Related DE69225978T2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/789,179 US5545727A (en) 1989-05-10 1991-11-08 DNA encoding fused di-alpha globins and production of pseudotetrameric hemoglobin
PCT/US1992/009752 WO1993009143A1 (en) 1991-11-08 1992-11-06 Production and use of multimeric hemoglobins

Publications (2)

Publication Number Publication Date
DE69225978D1 true DE69225978D1 (de) 1998-07-23
DE69225978T2 DE69225978T2 (de) 1999-02-11

Family

ID=25146814

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69225978T Expired - Fee Related DE69225978T2 (de) 1991-11-08 1992-11-06 Verfahren zur herstellung und anwendung von multimeren hämoblobinen

Country Status (13)

Country Link
US (7) US5545727A (de)
EP (2) EP0857489A3 (de)
JP (1) JPH07501059A (de)
AT (1) ATE167485T1 (de)
AU (1) AU672960B2 (de)
CA (1) CA2121889C (de)
DE (1) DE69225978T2 (de)
FI (1) FI942138A (de)
HU (1) HUT70309A (de)
IL (2) IL119656A0 (de)
NO (1) NO941703L (de)
SG (1) SG47882A1 (de)
WO (1) WO1993009143A1 (de)

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5449759A (en) * 1987-05-16 1995-09-12 Somatogen, Inc. Hemoglobins with intersubunit desulfide bonds
US6828125B1 (en) * 1989-05-10 2004-12-07 Baxter Biotech Technology, S.A.R.L. DNA encoding fused di-alpha globins and use thereof
US5599907A (en) * 1989-05-10 1997-02-04 Somatogen, Inc. Production and use of multimeric hemoglobins
US6150506A (en) * 1989-05-10 2000-11-21 Baxter Biotech Technology Sarl Modified hemoglobin-like compounds and methods of purifying same
US5844090A (en) * 1994-05-09 1998-12-01 Somatogen, Inc. Modified hemoglobin-like compounds
US5478806A (en) * 1989-11-22 1995-12-26 Enzon, Inc. Enhancement of antitumor therapy with hemoglobin-based conjugates
AU665599B2 (en) * 1991-11-08 1996-01-11 Hemosol Inc. Hemoglobins as drug delivery agents
US5939391A (en) * 1993-03-31 1999-08-17 Pro-Neuron, Inc. Hemoglobin alpha chain peptide fragments useful for inhibiting stem cell proliferation
US6610654B2 (en) 1993-03-31 2003-08-26 Wellstat Therapeutics Corporation Inhibitor of stem cell proliferation and uses thereof
WO1994022915A1 (en) 1993-03-31 1994-10-13 Pro-Neuron, Inc. Inhibitor of stem cell proliferation and uses thereof
IS4198A (is) * 1993-08-13 1995-02-14 Somatogen, Inc Meðferð vegna aukaverkana sem tengjast gjöf á utanfrumublóðrauða
US5631219A (en) * 1994-03-08 1997-05-20 Somatogen, Inc. Method of stimulating hematopoiesis with hemoglobin
US6242417B1 (en) 1994-03-08 2001-06-05 Somatogen, Inc. Stabilized compositions containing hemoglobin
WO1997023631A2 (en) * 1995-12-22 1997-07-03 Somatogen, Inc. Globins containing binding domains
US6218513B1 (en) 1995-12-22 2001-04-17 Baxter Biotech Technology Sarl Globins containing binding domains
US5861483A (en) * 1996-04-03 1999-01-19 Pro-Neuron, Inc. Inhibitor of stem cell proliferation and uses thereof
JP2000516455A (ja) 1996-08-02 2000-12-12 バクスター バイオテック テクノロジー エス．アー．エール．エル． ヘモグロビンにおけるβダイマー形成を制御する方法
AU4652797A (en) * 1996-09-27 1998-04-17 Board Of Trustees Of The University Of Illinois, The Oxygen-binding heme proteins incorporating circularly-permuted globins
CA2268278A1 (en) * 1996-10-18 1998-04-30 Somatogen, Inc. Methods of reducing the levels of protoporphyrin ix in recombinant hemoglobin preparations
AU735459B2 (en) 1997-01-30 2001-07-12 University Of Virginia Patent Foundation Cysteine-depleted peptides recognized by A3-restricted cytotoxic lymphocytes, and uses therefor
US6054427A (en) * 1997-02-28 2000-04-25 The Regents Of The University Of California Methods and compositions for optimization of oxygen transport by cell-free systems
US5814601A (en) * 1997-02-28 1998-09-29 The Regents Of The University Of California Methods and compositions for optimization of oxygen transport by cell-free systems
JP4512673B2 (ja) 1997-05-02 2010-07-28 バクスター バイオテク テクノロジー エス． アー． アール． エル． 増大した可溶性発現および／または低下した一酸化窒素の排出を伴うヘモグロビン変異体
EP1950298A3 (de) 1997-05-02 2008-12-24 Baxter Biotech Technology S.A.R.L. Hämoglobinmutanten mit erhöhtem Löslichkeitswert und/oder reduzierter Stickoxidspülung
US6780892B1 (en) 1998-10-01 2004-08-24 Temple University—Of the Commonwealth System of Higher Education Polymeric hemoglobin mutants
AU6504199A (en) * 1998-10-01 2000-04-17 Temple University - Of The Commonwealth System Of Higher Education Polymeric hemoglobin mutants
US8128922B2 (en) * 1999-10-20 2012-03-06 Johns Hopkins University Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen
EP2292657A1 (de) 1999-11-12 2011-03-09 Baxter Biotech Technology S.A.R.L. Hämoglobinzusammensetzungen mit verringerten Nebenwirkungen
US7164035B2 (en) * 2000-01-07 2007-01-16 Newsome David A Zinc-monocysteine complex and method of using zinc-cysteine complexes
JP5087201B2 (ja) * 2000-08-03 2012-12-05 ジョンズ・ホプキンス・ユニバーシティ 抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン
US6645767B1 (en) * 2000-10-03 2003-11-11 Carnegie Mellon University Cells engineered to contain genes of interest without expressed bacterial sequences and materials and methods therefor
US8008459B2 (en) * 2001-01-25 2011-08-30 Evolva Sa Concatemers of differentially expressed multiple genes
EP1363660A4 (de) * 2001-02-01 2006-06-21 Univ Johns Hopkins "überlegene molekulare vakzine auf basis selbstreplizierender rna, suizid-dna oder nacktem dna-vektor, zur verknüpfung von antigen mit polypeptid zur förderung der antigenpräsentation"
MXPA03008022A (es) * 2001-03-09 2003-12-04 Genentech Inc Proceso para la produccion de polipeptidos.
US20040133468A1 (en) * 2002-04-12 2004-07-08 Varghese Kivin G. Method and system for providing interactive adversing cross reference to related application
US7238777B2 (en) * 2001-10-16 2007-07-03 Asahi Kasei Kabushiki Kaisha Agents for adsorption and bridging for adenovirus
JPWO2003040025A1 (ja) 2001-11-08 2005-03-03 松下電器産業株式会社 微粒子膜およびその製造方法
US20050164915A1 (en) * 2002-04-01 2005-07-28 Sangart, Inc. Compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin
US20030153491A1 (en) * 2002-01-11 2003-08-14 Winslow Robert M. Methods and compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin
JP3912206B2 (ja) * 2002-07-05 2007-05-09 株式会社日立製作所 筒内直接燃料噴射装置用燃料ポンプ
JP5253708B2 (ja) * 2002-07-22 2013-07-31 エムビーエー ポリマーズ， インコーポレイテッド 静電分離の媒介
US7998705B2 (en) * 2002-08-06 2011-08-16 FUJIFILM Diosynth Biotechnologies U.S.A., Inc Increased dynamic binding capacity in ion exchange chromatography by addition of polyethylene glycol
CA2509260C (en) 2002-12-31 2012-10-02 Nektar Therapeutics Al, Corporation Maleamic acid polymer derivatives and their bioconjugates
WO2004098526A2 (en) * 2003-05-05 2004-11-18 Johns Hopkins University Anti-cancer dna vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein
SI1678314T1 (sl) 2003-10-22 2013-01-31 Keck Graduate Institute Metode za sintetiziranje heteromultimernih polipeptidov pri kvasovkah s strategijo razmnoĺ˝evanja haploidnih celic
WO2005074521A2 (en) * 2004-01-30 2005-08-18 The Trustees Of Columbia University In The City Of New York C-TERMINAL p53 PALINDROMIC PEPTIDE THAT INDUCES APOPTOSIS OF CELLS WITH ABERRANT p53 AND USES THEREOF
AU2005322960A1 (en) * 2005-01-06 2006-07-13 The Johns Hopkins University RNA interference that blocks expression of pro-apoptotic proteins potentiates immunity induced by DNA and transfected dendritic cell vaccines
WO2006081323A2 (en) * 2005-01-26 2006-08-03 The Johns Hopkins University Anti-cancer dna vaccine employing plasmids encoding mutant oncoprotein antigen and calreticulin
WO2006089206A2 (en) * 2005-02-16 2006-08-24 Massachusetts Institute Of Technology Methods to enhance carbon monoxide dehydrogenase activity and uses thereof
US8318474B1 (en) * 2005-05-23 2012-11-27 California Institute Of Technology Engineered yeast cells and uses thereof
WO2008024844A2 (en) * 2006-08-22 2008-02-28 The Johns Hopkins University Anticancer combination therapies
US9085638B2 (en) 2007-03-07 2015-07-21 The Johns Hopkins University DNA vaccine enhancement with MHC class II activators
US20080260765A1 (en) * 2007-03-15 2008-10-23 Johns Hopkins University HPV DNA Vaccines and Methods of Use Thereof
EP2190987B1 (de) * 2007-08-21 2012-11-14 MorphoSys AG Verfahren zur Formung von Disulphid-Bindungen
US20090285861A1 (en) * 2008-04-17 2009-11-19 Tzyy-Choou Wu Tumor cell-based cancer immunotherapeutic compositions and methods
EP2571991A1 (de) 2010-05-20 2013-03-27 Evolva SA Verfahren zur herstellung von isoprenoidverbindungen in hefe
US20130137645A1 (en) * 2010-07-19 2013-05-30 Mary S. Rosendahl Modified peptides and proteins
US9814759B2 (en) * 2014-07-02 2017-11-14 Cheer Global Ltd. Pharmaceutical composition comprising recombinant hemoglobin protein or subunit-based therapeutic agent for cancer targeting treatment
US10752672B1 (en) * 2019-02-01 2020-08-25 Cheer Global Limited Recombinant hemoglobins and methods of preparation and use thereof
CN112662677B (zh) * 2021-03-02 2022-12-02 天津师范大学 一组红裸须摇蚊Hb基因及其在水质生物监测中的应用
CN113087787B (zh) * 2021-05-19 2023-03-21 广西医科大学第二附属医院(广西医科大学第二临床医学院) 一种蚯蚓血红蛋白分离及纯化方法
WO2023102156A1 (en) 2021-12-03 2023-06-08 Wisconsin Alumni Research Foundation Mutant ace2 proteins and methods of using same
CN116203144B (zh) * 2022-05-11 2023-10-27 重庆医科大学附属儿童医院 测定血红蛋白中各型珠蛋白链比率的方法及其应用

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2449885C3 (de) * 1974-10-21 1980-04-30 Biotest-Serum-Institut Gmbh, 6000 Frankfurt Verfahren zur Herstellung von chemisch modifizierten haltbaren Hämoglobinpräparaten sowie das nach diesem Verfahren hergestellte modifizierte Hämoglobinpräparat
US4061736A (en) * 1975-02-02 1977-12-06 Alza Corporation Pharmaceutically acceptable intramolecularly cross-linked, stromal-free hemoglobin
US4001401A (en) * 1975-02-02 1977-01-04 Alza Corporation Blood substitute and blood plasma expander comprising polyhemoglobin
US4001200A (en) * 1975-02-27 1977-01-04 Alza Corporation Novel polymerized, cross-linked, stromal-free hemoglobin
US4053590A (en) * 1975-02-27 1977-10-11 Alza Corporation Compositions of matter comprising macromolecular hemoglobin
US4769326A (en) * 1980-02-29 1988-09-06 The Regents Of The University Of California Expression linkers
US4338397A (en) * 1980-04-11 1982-07-06 President And Fellows Of Harvard College Mature protein synthesis
US4551433A (en) * 1981-05-18 1985-11-05 Genentech, Inc. Microbial hybrid promoters
US4473496A (en) * 1981-09-14 1984-09-25 The United States Of America As Represented By The Secretary Of The Army Intramolecularly crosslinked hemoglobin
DE3144705C2 (de) * 1981-11-11 1983-12-08 Biotest-Serum-Institut Gmbh, 6000 Frankfurt Verfahren zur Herstellung eines lagerstabilen, vernetzten Hämoglobinpräparates mit hoher Sauerstoff-Transportkapazität, sowie das nach diesem Verfahren hergestellte Hämoglobinpräparat
US4599197A (en) * 1982-12-22 1986-07-08 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4511503A (en) * 1982-12-22 1985-04-16 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4620948A (en) * 1982-12-22 1986-11-04 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4512922A (en) * 1982-12-22 1985-04-23 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4713339A (en) * 1983-01-19 1987-12-15 Genentech, Inc. Polycistronic expression vector construction
US4529719A (en) * 1983-05-04 1985-07-16 Tye Ross W Modified crosslinked stroma-free tetrameric hemoglobin
US4840896A (en) * 1983-11-02 1989-06-20 Integrated Genetics, Inc. Heteropolymeric protein
US4738952A (en) * 1984-04-27 1988-04-19 Synthetic Blood Corporation Substitute for human blood and a method of making the same
GB8412517D0 (en) * 1984-05-16 1984-06-20 Nagai K Recombinant fusion proteins
US4600531A (en) * 1984-06-27 1986-07-15 University Of Iowa Research Foundation Production of alpha-alpha cross-linked hemoglobins in high yield
US4598064A (en) * 1984-06-27 1986-07-01 University Of Iowa Research Foundation Alpha-alpha cross-linked hemoglobins
US4542225A (en) * 1984-08-29 1985-09-17 Dana-Farber Cancer Institute, Inc. Acid-cleavable compound
US4774180A (en) * 1986-02-26 1988-09-27 Massachusetts Institute Of Technology Construction and application of polyproteins
US4584130A (en) * 1985-03-29 1986-04-22 University Of Maryland Intramolecularly cross-linked hemoglobin and method of preparation
DE3515252C2 (de) * 1985-04-27 1994-02-24 Roehm Gmbh Verfahren zur Immobilisierung gelöster Eiweißstoffe
DE3675588D1 (de) * 1985-06-19 1990-12-20 Ajinomoto Kk Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist.
US4826811A (en) * 1986-06-20 1989-05-02 Northfield Laboratories, Inc. Acellular red blood cell substitute
US4704692A (en) * 1986-09-02 1987-11-03 Ladner Robert C Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US4730936A (en) * 1986-10-10 1988-03-15 The United States Of America As Represented By The Secretary Of The Air Force Gas driven system for preparing large volumes of non-oxidized, pyridoxylated, polymerized stroma-free hemoglobin solution for use as a blood substitute
DE3636590A1 (de) * 1986-10-28 1988-05-26 Braun Melsungen Ag Blutersatzmittel
WO1988006601A1 (en) * 1987-03-02 1988-09-07 Genex Corporation Gene repressors
GB8710598D0 (en) * 1987-05-05 1987-06-10 Star Medical Diagnostics Ltd Hemoglobin based blood substitute
GB8711614D0 (en) 1987-05-16 1987-06-24 Medical Res Council Proteins
US5049493A (en) * 1987-10-23 1991-09-17 California Institute Of Technology Enhancement of cell growth by expression of a cloned hemoglobin gene
EP0319206A3 (de) * 1987-11-30 1990-04-18 Berlex Laboratories, Inc. Gen-Vermehrung
IL87708A (en) * 1988-09-08 1994-04-12 Technion Inst For Research And Hemoglobin-based blood substitute possessing a colloid oncotic pressure substantially similar to human blood and method for the preparation thereof
NL8901174A (nl) * 1989-05-10 1990-12-03 Het Hoofd Van De Afdeling Mili Hemoglobine-preparaat en gebruik daarvan.
ES2093640T3 (es) * 1989-05-10 1997-01-01 Somatogen Inc Produccion de hemoglobina y sus analogos mediante bacterias y levadura.
US5173426A (en) * 1989-10-06 1992-12-22 Yale University DNAs encoding genetically engineered low oxygen affinity mutants of human hemoglobin
JPH07504645A (ja) * 1990-04-16 1995-05-25 アペックス　バイオサイエンス　インコーポレーテッド 酵母での組換えヘモグロビンの発現
DE69132763D1 (de) * 1990-12-20 2001-11-15 Univ Alabama Res Foundation Bi Transgenes, vernetztes hämoglobin
US5250665A (en) * 1991-05-31 1993-10-05 The University Of Toronto Innovations Foundation Specifically β-β cross-linked hemoglobins and method of preparation

Also Published As

Publication number Publication date
NO941703L (no) 1994-07-04
US5801019A (en) 1998-09-01
JPH07501059A (ja) 1995-02-02
EP0857489A3 (de) 1998-09-30
CA2121889A1 (en) 1993-05-13
IL119657A0 (en) 1997-02-18
HU9401338D0 (en) 1994-08-29
ATE167485T1 (de) 1998-07-15
EP0857489A2 (de) 1998-08-12
US5844088A (en) 1998-12-01
FI942138A0 (fi) 1994-05-09
IL119656A0 (en) 1997-02-18
AU672960B2 (en) 1996-10-24
FI942138A (fi) 1994-06-29
US5744329A (en) 1998-04-28
US6274331B1 (en) 2001-08-14
NO941703D0 (no) 1994-05-06
EP0611376B1 (de) 1998-06-17
WO1993009143A1 (en) 1993-05-13
EP0611376A1 (de) 1994-08-24
HUT70309A (en) 1995-09-28
CA2121889C (en) 2001-08-21
US5798227A (en) 1998-08-25
AU3133793A (en) 1993-06-07
SG47882A1 (en) 1998-04-17
US5844089A (en) 1998-12-01
US5545727A (en) 1996-08-13
DE69225978T2 (de) 1999-02-11

Similar Documents

Publication Publication Date Title
ATE167485T1 (de) Verfahren zur herstellung und anwendung von multimeren hämoblobinen
DE3382190D1 (de) Immunogener protein- oder peptidkomplex, verfahren zur herstellung dieses komplexes und seine verwendung als immunstimulans und als impfstoff.
DE69233204D1 (de) Verfahren und materialien zur herstellung von modifizierten variablen antikörperdomänen und ihre therapeutische verwendung
DE68928934T2 (de) Verfahren zur herstellung von menschlicher dnase
DE68904986T2 (de) Verfahren zur herstellung von 1,1,1-trifluor-2,2-dichlorethan.
DE69526861T2 (de) Linse zur korrektur von fehlsichtigkeiten aus polyersterharz mit hohem brechungsindex, erhöhter optischer uniformität und/oder verbesserter einfärbbarkeit
DE68907258D1 (de) Verfahren zur herstellung von perfluorierten copolymeren.
ATE131876T1 (de) Verfahren zur herstellung von proteinen durch verwendung von cks-fusionsproteinen
ATE167232T1 (de) Protein mit knochenbildungs-eigenschaften und verfahren zu seiner herstellung
DE69325452D1 (de) Verfahren zur herstellung von (s)-3-amino-1-substituiert-pirrolidine
DE58902137D1 (de) Verfahren zur herstellung von caprolacton.
DE68911680D1 (de) Verfahren zur herstellung von copolyarylensulfiden mit verwendung eines sauerstoffhaltigen gases.
KR910003095A (ko) 사람의 단백질 c변이체 및 이의 제조방법
DK313389D0 (da) Fremgangsmaade til opdraet af fisk og apparat til anvendelse derved
DE68900211D1 (de) Verfahren zur herstellung von 4,4'-dihydroxydiphenylmethan.
ATE125298T1 (de) Verfahren zur herstellung von motilinähnlichen polypeptiden und seine expression.
DE58902242D1 (de) Verfahren zur herstellung von thymol.
AT364813B (de) Verfahren zur herstellung von alpha-aryl-alpha, alpha-di(omega-aminoalkyl)acetamiden mit disubstituierter aminogruppe
DE3861262D1 (de) Verfahren zur herstellung von polysulfurierten olefin-zusammensetzungen mit hohem schwefel-und sehr niedrigem chlorgehalt.
DE68901559D1 (de) Verfahren und mittel zur augenanaesthesie unter verwendung von rodocain.
DE68905264T2 (de) Verfahren zur herstellung von proteoliposomen und verfahren zur herstellung von riesenproteoliposomen.
DE58903321D1 (de) Substituierte bisacyloxynaphtacene und verfahren zur herstellung von tetrathiotetracenen.
DE68917520T2 (de) Verfahren und Systeme zur Herstellung von HIV-Antigenen.
DE68902379T2 (de) Verfahren zur herstellung von verbessertem proteinhydrolysat.
DE58902422D1 (de) Verfahren zur herstellung von ethylen/acrylnitril-copolymerisaten, neue ethylen/acrylnitril-copolymerisate und ihre verwendung.

Legal Events

Date Code Title Description
8364 No opposition during term of opposition
8327 Change in the person/name/address of the patent owner

Owner name: BAXTER BIOTECH TECHNOLOGY S.A.R.L., NEUCHATEL, CH

8339 Ceased/non-payment of the annual fee