KR900004801B1 - 중합체 접합된 단백질, 상기 단백질이 용해되어 있는 약제학적 조성물 및 상기 조성물의 제조방법 - Google Patents
중합체 접합된 단백질, 상기 단백질이 용해되어 있는 약제학적 조성물 및 상기 조성물의 제조방법 Download PDFInfo
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- KR900004801B1 KR900004801B1 KR1019860005125A KR860005125A KR900004801B1 KR 900004801 B1 KR900004801 B1 KR 900004801B1 KR 1019860005125 A KR1019860005125 A KR 1019860005125A KR 860005125 A KR860005125 A KR 860005125A KR 900004801 B1 KR900004801 B1 KR 900004801B1
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- 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
- A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A—HUMAN NECESSITIES
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- 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
- A61K47/68—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6817—Toxins
- A61K47/6819—Plant toxins
- A61K47/6825—Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin
- A61K47/6827—Ricin A
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- Bioinformatics & Cheminformatics (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74995585A | 1985-06-26 | 1985-06-26 | |
| US749955 | 1985-06-26 | ||
| US749,955 | 1985-06-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR870000423A KR870000423A (ko) | 1987-02-18 |
| KR900004801B1 true KR900004801B1 (ko) | 1990-07-06 |
Family
ID=25015921
Family Applications (1)
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| KR1019860005125A Expired KR900004801B1 (ko) | 1985-06-26 | 1986-06-26 | 중합체 접합된 단백질, 상기 단백질이 용해되어 있는 약제학적 조성물 및 상기 조성물의 제조방법 |
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| WO (1) | WO1987000056A1 (enExample) |
| ZA (1) | ZA864766B (enExample) |
Families Citing this family (183)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| CA1283046C (en) * | 1986-05-29 | 1991-04-16 | Nandini Katre | Tumor necrosis factor formulation |
| US4745180A (en) * | 1986-06-27 | 1988-05-17 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using heparin fragments |
| US5004605A (en) * | 1987-12-10 | 1991-04-02 | Cetus Corporation | Low pH pharmaceutical compositions of recombinant β-interferon |
| US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| IE62463B1 (en) * | 1988-07-07 | 1995-02-08 | Res Dev Foundation | Immunoconjugates for cancer diagnosis and therapy |
| US5091176A (en) * | 1988-11-02 | 1992-02-25 | W. R. Grace & Co.-Conn. | Polymer-modified peptide drugs having enhanced biological and pharmacological activities |
| CA2006596C (en) * | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
| US6166183A (en) * | 1992-11-30 | 2000-12-26 | Kirin-Amgen, Inc. | Chemically-modified G-CSF |
| US4902502A (en) * | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| WO1990015628A1 (en) * | 1989-06-14 | 1990-12-27 | Cetus Corporation | Polymer/antibiotic conjugate |
| KR920703114A (ko) * | 1989-07-14 | 1992-12-17 | 원본미기재 | 접합체 백신을 위한 시토킨 및 호르몬 운반체 |
| IL95031A (en) | 1989-07-18 | 2007-03-08 | Amgen Inc | Method for the production of a human recombinant tumor necrosis factor inhibitor |
| WO1991001758A1 (en) * | 1989-08-07 | 1991-02-21 | Debiopharm S.A. | Biologically active drug polymer derivatives |
| US5393735A (en) * | 1990-08-09 | 1995-02-28 | Rohm And Haas Company | Herbicidal glutarimides |
| US5552391A (en) * | 1990-01-16 | 1996-09-03 | La Jolla Pharmaceutical Company | Chemically-defined non-polymeric valency platform molecules and conjugates thereof |
| JPH04218000A (ja) * | 1990-02-13 | 1992-08-07 | Kirin Amgen Inc | 修飾ポリペプチド |
| FR2658519B1 (fr) * | 1990-02-19 | 1995-07-07 | Serbio | Substrats peptidiques pour identification du facteur xa. |
| FR2658521B1 (fr) * | 1990-02-19 | 1994-01-21 | Serbioo | Bipeptides symetriques comportant un reste polyalkyleneglycol, procede de preparation et utilisation dans le dosage des proteases. |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| US5312903A (en) * | 1990-06-01 | 1994-05-17 | E. I. Du Pont De Nemours And Company | Lysine-glycosylated recombinant interleukin-2 |
| IE912365A1 (en) * | 1990-07-23 | 1992-01-29 | Zeneca Ltd | Continuous release pharmaceutical compositions |
| US5229366A (en) * | 1990-10-23 | 1993-07-20 | Fuji Photo Film Co., Ltd. | Peptide-containing polyethylene glycol derivatives and application thereof |
| US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| KR100361933B1 (ko) | 1993-09-08 | 2003-02-14 | 라 졸라 파마슈티칼 컴파니 | 화학적으로정의된비중합성결합가플랫폼분자및그것의콘주게이트 |
| ATE359830T1 (de) * | 1993-09-08 | 2007-05-15 | Jolla Pharma | Chemisch definierten nicht-polymer wertigen plattformmolokülen und ihren konjugaten |
| US5880131A (en) * | 1993-10-20 | 1999-03-09 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| US5446090A (en) * | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| US5629384A (en) * | 1994-05-17 | 1997-05-13 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
| US20030053982A1 (en) | 1994-09-26 | 2003-03-20 | Kinstler Olaf B. | N-terminally chemically modified protein compositions and methods |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| ATE452136T1 (de) * | 1995-05-04 | 2010-01-15 | Gilead Sciences Inc | Nukleinsäureligand-komplexe |
| US8071737B2 (en) | 1995-05-04 | 2011-12-06 | Glead Sciences, Inc. | Nucleic acid ligand complexes |
| US5874409A (en) | 1995-06-07 | 1999-02-23 | La Jolla Pharmaceutical Company | APL immunoreactive peptides, conjugates thereof and methods of treatment for APL antibody-mediated pathologies |
| WO1997009989A1 (en) * | 1995-09-14 | 1997-03-20 | Lxr Biotechnology Inc. | Compositions with anti-apoptotic activity, containing a mixture of phospholipids |
| TW517067B (en) | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
| TW555765B (en) | 1996-07-09 | 2003-10-01 | Amgen Inc | Low molecular weight soluble tumor necrosis factor type-I and type-II proteins |
| CN1168495C (zh) * | 1997-01-15 | 2004-09-29 | 凤凰药理学公司 | 被修饰的肿瘤坏死因子 |
| US6321909B1 (en) | 1997-02-13 | 2001-11-27 | Sky High, Llc | System for storing polyethylene glycol solutions |
| JP4574007B2 (ja) * | 1998-04-28 | 2010-11-04 | メルク・セローノ・ソシエテ・アノニム | ポリオール−ifn−ベータ複体 |
| US6858210B1 (en) | 1998-06-09 | 2005-02-22 | La Jolla Pharmaceutical Co. | Therapeutic and diagnostic domain 1 β2GPI polypeptides and methods of using same |
| US6783965B1 (en) | 2000-02-10 | 2004-08-31 | Mountain View Pharmaceuticals, Inc. | Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates |
| ATE498409T1 (de) | 1998-08-06 | 2011-03-15 | Mountain View Pharmaceuticals | Peg-uricase konjugate und verwendung davon |
| MXPA01003790A (es) | 1998-10-16 | 2002-09-18 | Biogen Inc | Proteinas de fusion beta - interferon y sus usos. |
| HU229888B1 (en) * | 1998-10-16 | 2014-11-28 | Biogen Idec Ma Inc Cambridge | Polymer conjugates of interferon betha-1a and uses |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| US6458953B1 (en) | 1998-12-09 | 2002-10-01 | La Jolla Pharmaceutical Company | Valency platform molecules comprising carbamate linkages |
| US6399578B1 (en) | 1998-12-09 | 2002-06-04 | La Jolla Pharmaceutical Company | Conjugates comprising galactose α1,3 galactosyl epitopes and methods of using same |
| US7431921B2 (en) | 1999-08-27 | 2008-10-07 | Maxygen Aps | Interferon beta-like molecules |
| BR0013638A (pt) * | 1999-08-27 | 2002-05-14 | Maxygen Aps | Novas moléculas semelhantes a interferon beta |
| US6531122B1 (en) | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
| US7144574B2 (en) | 1999-08-27 | 2006-12-05 | Maxygen Aps | Interferon β variants and conjugates |
| TR200101086A3 (enExample) * | 1999-10-15 | 2001-08-21 | ||
| PL356007A1 (en) | 1999-11-12 | 2004-05-31 | Maxygen Holdings Ltd | Interferon gamma conjugates |
| US7230081B1 (en) | 1999-11-12 | 2007-06-12 | Maxygen Holdings, Ltd. | Interferon gamma conjugates |
| AR027509A1 (es) | 2000-01-10 | 2003-04-02 | Maxygen Aps | Conjugados g-csf |
| JP2003521930A (ja) | 2000-02-11 | 2003-07-22 | マキシゲン・エイピーエス | 第VII因子または第VIIa因子様分子 |
| CA2414076A1 (en) | 2000-06-08 | 2001-12-13 | La Jolla Pharmaceutical Company | Multivalent platform molecules comprising high molecular weight polyethylene oxide |
| ZA200305980B (en) | 2001-02-12 | 2007-01-31 | Res Dev Foundation | Modified proteins, designer toxins, and methods of making thereof |
| ATE432288T1 (de) | 2001-02-27 | 2009-06-15 | Maxygen Aps | Neue interferon-beta-ähnliche moleküle |
| US7038015B2 (en) | 2001-04-06 | 2006-05-02 | Maxygen Holdings, Ltd. | Interferon gamma polypeptide variants |
| US6958388B2 (en) | 2001-04-06 | 2005-10-25 | Maxygen, Aps | Interferon gamma polypeptide variants |
| WO2003000278A1 (en) * | 2001-06-22 | 2003-01-03 | Kyowa Hakko Kogyo Co., Ltd. | Ointments |
| EP1414471B1 (en) | 2001-07-17 | 2012-06-13 | Research Development Foundation | Therapeutic agents comprising pro-apoptotic proteins |
| JP2005507870A (ja) | 2001-08-13 | 2005-03-24 | ユニバーシティ・オブ・サザン・カリフォルニア | 低毒性のインターロイキン−2突然変異体 |
| US7125843B2 (en) | 2001-10-19 | 2006-10-24 | Neose Technologies, Inc. | Glycoconjugates including more than one peptide |
| US7265084B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| US7399613B2 (en) | 2001-10-10 | 2008-07-15 | Neose Technologies, Inc. | Sialic acid nucleotide sugars |
| ES2411007T3 (es) | 2001-10-10 | 2013-07-04 | Novo Nordisk A/S | Remodelación y glicoconjugación de péptidos |
| US7297511B2 (en) | 2001-10-10 | 2007-11-20 | Neose Technologies, Inc. | Interferon alpha: remodeling and glycoconjugation of interferon alpha |
| US7179617B2 (en) | 2001-10-10 | 2007-02-20 | Neose Technologies, Inc. | Factor IX: remolding and glycoconjugation of Factor IX |
| US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
| US7696163B2 (en) | 2001-10-10 | 2010-04-13 | Novo Nordisk A/S | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7226903B2 (en) | 2001-10-10 | 2007-06-05 | Neose Technologies, Inc. | Interferon beta: remodeling and glycoconjugation of interferon beta |
| US7265085B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycoconjugation methods and proteins/peptides produced by the methods |
| US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7795210B2 (en) | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| US7439043B2 (en) | 2001-10-10 | 2008-10-21 | Neose Technologies, Inc. | Galactosyl nucleotide sugars |
| US7473680B2 (en) | 2001-11-28 | 2009-01-06 | Neose Technologies, Inc. | Remodeling and glycoconjugation of peptides |
| CA2753899C (en) | 2002-01-18 | 2014-03-25 | Biogen Idec Ma Inc. | Polyalkylene glycol with moiety for conjugating biologically active compounds |
| PT1517710E (pt) | 2002-06-21 | 2011-07-08 | Novo Nordisk Healthcare Ag | Glicoformas do factor vii peguilado |
| US7524931B2 (en) | 2002-07-03 | 2009-04-28 | Maxygen Holdings Ltd. | Full-length interferon gamma polypeptide variants |
| CN102319437B (zh) | 2002-12-26 | 2017-10-13 | 山景医药公司 | 具有增强的生物学效用的干扰素‑β的聚合物缀合物 |
| CA2519092C (en) | 2003-03-14 | 2014-08-05 | Neose Technologies, Inc. | Branched water-soluble polymers and their conjugates |
| US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
| EP1613261A4 (en) | 2003-04-09 | 2011-01-26 | Novo Nordisk As | INTRA-CELLULAR FORMATION OF PEPTIDE CONJUGATES |
| PL1615945T3 (pl) | 2003-04-09 | 2012-03-30 | Ratiopharm Gmbh | Sposoby glikopegylacji i białka/peptydy wytwarzane tymi sposobami |
| US9005625B2 (en) | 2003-07-25 | 2015-04-14 | Novo Nordisk A/S | Antibody toxin conjugates |
| DK1668031T3 (da) * | 2003-08-07 | 2008-06-30 | Zymogenetics Inc | Homogene præparater af IL-29 |
| PL1666496T3 (pl) * | 2003-08-25 | 2014-08-29 | Toray Industries | Kompozyt interferonu beta |
| CN102516386A (zh) | 2003-10-10 | 2012-06-27 | 诺沃挪第克公司 | Il-21衍生物 |
| EP2633866A3 (en) | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
| KR20060120141A (ko) | 2003-11-24 | 2006-11-24 | 네오스 테크놀로지스, 인크. | 글리코페질화 에리트로포이에틴 |
| US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
| WO2005074546A2 (en) | 2004-02-02 | 2005-08-18 | Ambrx, Inc. | Modified human growth hormone polypeptides and their uses |
| CA2565414A1 (en) | 2004-05-04 | 2005-11-24 | Novo Nordisk Health Care Ag | O-linked glycoforms of polypeptides and method to manufacture them |
| NZ582684A (en) | 2004-06-18 | 2011-05-27 | Ambrx Inc | Use of an antibody or binding fragment thereof comprising a non naturally encoded amino acid coupled to a linker |
| EP1771066A2 (en) | 2004-07-13 | 2007-04-11 | Neose Technologies, Inc. | Branched peg remodeling and glycosylation of glucagon-like peptide-1 glp-1 |
| JP2008507280A (ja) | 2004-07-21 | 2008-03-13 | アンブレツクス・インコーポレイテツド | 非天然コードアミノ酸を用いた生合成ポリペプチド |
| US8268967B2 (en) | 2004-09-10 | 2012-09-18 | Novo Nordisk A/S | Glycopegylated interferon α |
| DK2586456T3 (en) | 2004-10-29 | 2016-03-21 | Ratiopharm Gmbh | Conversion and glycopegylation of fibroblast growth factor (FGF) |
| KR20070090023A (ko) | 2004-12-22 | 2007-09-04 | 암브룩스, 인코포레이티드 | 변형 인간 성장 호르몬 |
| WO2006074467A2 (en) | 2005-01-10 | 2006-07-13 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
| US20070154992A1 (en) | 2005-04-08 | 2007-07-05 | Neose Technologies, Inc. | Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants |
| NZ562292A (en) | 2005-04-11 | 2009-11-27 | Savient Pharmaceuticals Inc | Variant forms of urate oxidase and use thereof |
| JP5216580B2 (ja) | 2005-05-25 | 2013-06-19 | ノヴォ ノルディスク アー/エス | グリコペグ化第ix因子 |
| ES2553160T3 (es) | 2005-06-17 | 2015-12-04 | Novo Nordisk Health Care Ag | Reducción y derivatización selectivas de proteínas Factor VII transformadas por ingeniería que comprenden al menos una cisteína no nativa |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| WO2007056191A2 (en) | 2005-11-03 | 2007-05-18 | Neose Technologies, Inc. | Nucleotide sugar purification using membranes |
| EP1951890A4 (en) | 2005-11-16 | 2009-06-24 | Ambrx Inc | PROCESSES AND COMPOSITIONS WITH NON-NATURAL AMINO ACIDS |
| RU2304586C1 (ru) * | 2006-03-27 | 2007-08-20 | Михаил Николаевич Смирнов | Препарат интерлейкина-2 и способ его получения |
| RU2322452C2 (ru) * | 2006-03-27 | 2008-04-20 | Михаил Николаевич Смирнов | Иммуномодулирующая композиция |
| EP2213733A3 (en) | 2006-05-24 | 2010-12-29 | Novo Nordisk Health Care AG | Factor IX analogues having prolonged in vivo half life |
| CN101516388B (zh) | 2006-07-21 | 2012-10-31 | 诺和诺德公司 | 通过o-联糖基化序列的肽的糖基化 |
| CN104193815A (zh) | 2006-09-08 | 2014-12-10 | Ambrx公司 | 经修饰的人类血浆多肽或Fc骨架和其用途 |
| WO2008031612A1 (en) * | 2006-09-15 | 2008-03-20 | Creabilis Therapeutics S.P.A. | Polymer conjugates of box-a of hmgb1 and box-a variants of hmgb1 |
| EP2054521A4 (en) | 2006-10-03 | 2012-12-19 | Novo Nordisk As | PROCESS FOR CLEANING POLYPEPTIDE CONJUGATES |
| KR20140012199A (ko) | 2007-03-30 | 2014-01-29 | 암브룩스, 인코포레이티드 | 변형된 fgf-21 폴리펩티드 및 그 용도 |
| JP2010523582A (ja) | 2007-04-03 | 2010-07-15 | バイオジェネリクス アクチェンゲゼルシャフト | グリコpeg化g−csfを用いた治療方法 |
| WO2008154639A2 (en) | 2007-06-12 | 2008-12-18 | Neose Technologies, Inc. | Improved process for the production of nucleotide sugars |
| NZ583276A (en) | 2007-08-27 | 2012-06-29 | Biogenerix Ag | Liquid formulations of granulocyte colony stimulating factor and polymer conjugates |
| EP2930182A1 (en) | 2007-11-20 | 2015-10-14 | Ambrx, Inc. | Modified insulin polypeptides and their uses |
| JP2011510005A (ja) * | 2008-01-18 | 2011-03-31 | ダウ グローバル テクノロジーズ インコーポレイティド | メトキシポリエチレングリコールを用いる難溶性活性物質の水溶解度増強方法 |
| NZ601868A (en) | 2008-01-22 | 2014-05-30 | Araim Pharmaceuticals Inc | Tissue protective peptides and peptide analogs for preventing and treating diseases and disorders associated with tissue damage |
| EP3103880A1 (en) | 2008-02-08 | 2016-12-14 | Ambrx, Inc. | Modified leptin polypeptides and their uses |
| RU2573587C2 (ru) | 2008-02-27 | 2016-01-20 | Ново Нордиск А/С | Конъюгированные молекулы фактора viii |
| JP5592355B2 (ja) | 2008-05-13 | 2014-09-17 | アドヴァンスト リキッド ロジック インコーポレイテッド | 液滴アクチュエータ装置、システム、および方法 |
| AU2009274076C1 (en) | 2008-07-23 | 2014-04-17 | Ambrx, Inc. | Modified bovine G-CSF polypeptides and their uses |
| US9121024B2 (en) | 2008-09-26 | 2015-09-01 | Ambrx, Inc. | Non-natural amino acid replication-dependent microorganisms and vaccines |
| PL2342223T3 (pl) | 2008-09-26 | 2017-09-29 | Ambrx, Inc. | Zmodyfikowane polipeptydy zwierzęcej erytropoetyny i ich zastosowania |
| KR101861547B1 (ko) | 2009-06-25 | 2018-07-02 | 크레알타 파마슈티칼스 엘엘씨 | 페길화된 유리카아제 치료 중에 혈청 요산을 모니터링하여 주입 반응의 위험성 및 반응의 항체매개 상실을 예측하는 방법 및 키트 |
| WO2011087810A1 (en) | 2009-12-21 | 2011-07-21 | Ambrx, Inc. | Modified porcine somatotropin polypeptides and their uses |
| BR112012015461A2 (pt) | 2009-12-21 | 2017-01-10 | Ambrx Inc | polipeptídeos de somatotropina boviina modificados e seus usos |
| EP2542569B1 (en) | 2010-03-05 | 2020-09-16 | Omeros Corporation | Chimeric inhibitor molecules of complement activation |
| EP2569331A1 (en) | 2010-05-10 | 2013-03-20 | Perseid Therapeutics LLC | Polypeptide inhibitors of vla4 |
| ES2742296T3 (es) | 2010-08-17 | 2020-02-13 | Ambrx Inc | Polipéptidos de relaxina modificados y sus usos |
| US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
| TWI480288B (zh) | 2010-09-23 | 2015-04-11 | Lilly Co Eli | 牛顆粒細胞群落刺激因子及其變體之調配物 |
| KR20200070407A (ko) * | 2010-11-12 | 2020-06-17 | 넥타르 테라퓨틱스 | Il-2 부분 및 중합체의 접합체 |
| EP2673294B1 (en) | 2011-02-10 | 2016-04-27 | Roche Glycart AG | Mutant interleukin-2 polypeptides |
| AU2012280474A1 (en) | 2011-07-01 | 2014-01-16 | Bayer Intellectual Property Gmbh | Relaxin fusion polypeptides and uses thereof |
| CN104136038A (zh) | 2012-02-29 | 2014-11-05 | 东丽株式会社 | 体腔积液抑制剂 |
| WO2013156488A2 (en) | 2012-04-16 | 2013-10-24 | Leverton Licence Holdings Limited | Optimised subcutaneous therapeutic agents |
| WO2013177187A2 (en) * | 2012-05-22 | 2013-11-28 | Massachusetts Institute Of Technology | Synergistic tumor treatment with extended-pk il-2 and therapeutic agents |
| DK2859017T3 (da) | 2012-06-08 | 2019-05-13 | Sutro Biopharma Inc | Antistoffer omfattrende stedsspecifikke ikke-naturlige aminosyrerester, fremgangsmåder til fremstilling heraf og fremgangsmåder til anvendelse heraf |
| ES2611788T3 (es) | 2012-06-26 | 2017-05-10 | Sutro Biopharma, Inc. | Proteínas de Fc modificadas que comprenden residuos de aminoácidos no naturales específicos del sitio, conjugados de las mismas, métodos para su preparación y métodos para su uso |
| EP3584255B1 (en) | 2012-08-31 | 2022-02-16 | Sutro Biopharma, Inc. | Modified amino acids comprising an azido group |
| US20150017120A1 (en) * | 2013-06-13 | 2015-01-15 | Massachusetts Institute Of Technology | Synergistic tumor treatment with extended-pk il-2 and adoptive cell therapy |
| ES2865473T3 (es) | 2013-07-10 | 2021-10-15 | Sutro Biopharma Inc | Anticuerpos que comprenden múltiples residuos de aminoácidos no naturales sitio-específicos, métodos para su preparación y métodos de uso |
| WO2015054658A1 (en) | 2013-10-11 | 2015-04-16 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
| CN107108710B (zh) | 2014-10-24 | 2022-02-15 | 百时美施贵宝公司 | 修饰的fgf-21多肽及其用途 |
| MA47290A (fr) | 2015-10-08 | 2019-11-27 | Nektar Therapeutics | Combinaison d'un agoniste sélectif de l'il-2rbeta et d'un agoniste de l'il-15 à action prolongée |
| CN109310741A (zh) | 2016-04-29 | 2019-02-05 | 阿拉伊姆药品公司 | 用于预防和治疗与组织损伤相关的疾病和障碍的组织保护肽 |
| US20200237881A1 (en) | 2019-01-30 | 2020-07-30 | Horizon Pharma Rheumatology Llc | Reducing immunogenicity to pegloticase |
| EP3538135A4 (en) | 2016-11-11 | 2020-07-29 | Horizon Pharma Rheumatology LLC | POLYTHERAPIES OF PREDNISONE AND URICASE MOLECULES AND THEIR USES |
| KR102670432B1 (ko) | 2017-02-08 | 2024-05-28 | 브리스톨-마이어스 스큅 컴퍼니 | 약동학적 인핸서를 포함하는 변형된 렐락신 폴리펩티드 및 그의 용도 |
| EP3606947B1 (en) | 2017-04-03 | 2022-12-21 | F. Hoffmann-La Roche AG | Immunoconjugates of il-2 with an anti-pd-1 and tim-3 bispecific antibody |
| MX2019011770A (es) | 2017-04-03 | 2020-01-09 | Hoffmann La Roche | Inmunoconjugados de un anticuerpo anti-pd-1 con un mutante il-2 o con il-15. |
| AU2018394189B2 (en) * | 2017-12-27 | 2023-12-21 | Kyowa Kirin Co., Ltd. | IL-2 variant |
| JP7441826B2 (ja) | 2018-09-11 | 2024-03-01 | アンブルックス,インコーポレイテッド | インターロイキン-2ポリペプチド抱合物およびその使用 |
| WO2020082057A1 (en) | 2018-10-19 | 2020-04-23 | Ambrx, Inc. | Interleukin-10 polypeptide conjugates, dimers thereof, and their uses |
| WO2020158690A1 (ja) | 2019-01-28 | 2020-08-06 | 東レ株式会社 | 肝細胞増殖因子又はその活性断片のポリエチレングリコール修飾体 |
| JPWO2020158691A1 (ja) | 2019-01-28 | 2021-12-02 | 東レ株式会社 | 肝細胞増殖因子又はその活性断片のポリエチレングリコール修飾体 |
| CN119455003A (zh) | 2019-02-12 | 2025-02-18 | Ambrx公司 | 包含抗体-tlr激动剂缀合物的组合物、方法和用途 |
| JP2022538139A (ja) | 2019-07-02 | 2022-08-31 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | 変異体インターロイキン-2及び抗cd8抗体を含む免疫複合体 |
| IL321567A (en) * | 2019-12-13 | 2025-08-01 | Synthekine Inc | Il-2 orthologs and methods of use |
| CN115243726B (zh) | 2020-03-11 | 2025-07-15 | 北京泰德制药股份有限公司 | 白介素-2多肽偶联物及其使用方法 |
| CN115485028A (zh) | 2020-04-15 | 2022-12-16 | 豪夫迈·罗氏有限公司 | 免疫缀合物 |
| KR20230010240A (ko) | 2020-05-11 | 2023-01-18 | 에프. 호프만-라 로슈 아게 | 변형된 pbmc 및 면역접합체를 이용한 병용 요법 |
| AU2021327396A1 (en) | 2020-08-20 | 2023-03-23 | Ambrx, Inc. | Antibody-TLR agonist conjugates, methods and uses thereof |
| CA3197740A1 (en) | 2020-12-04 | 2022-06-09 | F. Hoffman-La Roche Ag | Ph-dependent mutant interleukin-2 polypeptides |
| WO2022148853A1 (en) | 2021-01-11 | 2022-07-14 | F. Hoffmann-La Roche Ag | Immunoconjugates |
| MX2023011480A (es) | 2021-04-03 | 2023-12-06 | Ambrx Inc | Conjugados anticuerpo anti-her2-fármaco y usos de estos. |
| WO2023052541A1 (en) | 2021-09-30 | 2023-04-06 | Imcheck Therapeutics | Combination of an anti-btn3a activating antibody and an il-2 agonist for use in therapy |
| JP2024537096A (ja) | 2021-10-14 | 2024-10-10 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | がんの治療のための代替的なPD1-IL7vイムノコンジュゲート |
| AU2022362681A1 (en) | 2021-10-14 | 2024-04-04 | F. Hoffmann-La Roche Ag | New interleukin-7 immunoconjugates |
| CN120676957A (zh) | 2023-01-20 | 2025-09-19 | 豪夫迈·罗氏有限公司 | 重组Fc结构域-IL2变体多肽以及与膜锚定抗原结合多肽的组合疗法 |
| US12269875B2 (en) | 2023-08-03 | 2025-04-08 | Jeff R. Peterson | Gout flare prevention methods using IL-1BETA blockers |
| WO2025163581A1 (en) | 2024-02-01 | 2025-08-07 | Astrazeneca Ab | Cd8-binding cytokine engagers and methods of use thereof |
| WO2025202147A1 (en) | 2024-03-27 | 2025-10-02 | F. Hoffmann-La Roche Ag | Interleukin-7 immunoconjugates |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS54157816A (en) * | 1978-05-27 | 1979-12-13 | Unitika Ltd | Fixing of bioactive substance to solid surface |
| US4414147A (en) * | 1981-04-17 | 1983-11-08 | Massachusetts Institute Of Technology | Methods of decreasing the hydrophobicity of fibroblast and other interferons |
| EP0098110B1 (en) * | 1982-06-24 | 1989-10-18 | NIHON CHEMICAL RESEARCH KABUSHIKI KAISHA also known as JAPAN CHEMICAL RESEARCH CO., LTD | Long-acting composition |
| WO1985003934A1 (fr) * | 1984-03-06 | 1985-09-12 | Takeda Chemical Industries, Ltd. | Proteine modifiee chimiquement et son procede de preparation |
| DE3572982D1 (en) * | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
-
1986
- 1986-06-06 DE DE8686903990T patent/DE3676670D1/de not_active Expired - Lifetime
- 1986-06-06 JP JP61503399A patent/JP2524586B2/ja not_active Expired - Lifetime
- 1986-06-06 WO PCT/US1986/001252 patent/WO1987000056A1/en not_active Ceased
- 1986-06-06 EP EP86903990A patent/EP0229108B1/en not_active Expired - Lifetime
- 1986-06-12 CA CA000511466A patent/CA1291708C/en not_active Expired - Lifetime
- 1986-06-20 NZ NZ216618A patent/NZ216618A/xx unknown
- 1986-06-23 IN IN464/CAL/86A patent/IN163200B/en unknown
- 1986-06-24 PH PH33934A patent/PH25004A/en unknown
- 1986-06-24 PT PT82834A patent/PT82834B/pt unknown
- 1986-06-25 GR GR861641A patent/GR861641B/el unknown
- 1986-06-25 IE IE170686A patent/IE59406B1/en not_active IP Right Cessation
- 1986-06-25 IL IL79235A patent/IL79235A/xx not_active IP Right Cessation
- 1986-06-26 KR KR1019860005125A patent/KR900004801B1/ko not_active Expired
- 1986-06-26 ZA ZA864766A patent/ZA864766B/xx unknown
- 1986-06-26 MX MX002938A patent/MX174442B/es unknown
-
1987
- 1987-02-25 DK DK097987A patent/DK169874B1/da not_active IP Right Cessation
- 1987-02-25 FI FI870809A patent/FI93424C/fi not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DK97987A (da) | 1987-02-25 |
| KR870000423A (ko) | 1987-02-18 |
| FI870809A0 (fi) | 1987-02-25 |
| MX174442B (es) | 1994-05-17 |
| DK169874B1 (da) | 1995-03-20 |
| PT82834A (en) | 1986-07-01 |
| CA1291708C (en) | 1991-11-05 |
| WO1987000056A1 (en) | 1987-01-15 |
| FI870809L (fi) | 1987-02-25 |
| IE861706L (en) | 1986-12-26 |
| IE59406B1 (en) | 1994-02-23 |
| IL79235A0 (en) | 1986-09-30 |
| FI93424B (fi) | 1994-12-30 |
| DE3676670D1 (de) | 1991-02-07 |
| PH25004A (en) | 1991-01-28 |
| NZ216618A (en) | 1989-05-29 |
| DK97987D0 (da) | 1987-02-25 |
| JP2524586B2 (ja) | 1996-08-14 |
| FI93424C (fi) | 1995-04-10 |
| JPS62503171A (ja) | 1987-12-17 |
| EP0229108B1 (en) | 1990-12-27 |
| IN163200B (enExample) | 1988-08-20 |
| ZA864766B (en) | 1988-02-24 |
| GR861641B (en) | 1986-09-12 |
| IL79235A (en) | 1991-01-31 |
| EP0229108A1 (en) | 1987-07-22 |
| PT82834B (pt) | 1988-12-15 |
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