CA2307142C - N-terminally chemically modified protein compositions and methods - Google Patents
N-terminally chemically modified protein compositions and methods Download PDFInfo
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- CA2307142C CA2307142C CA2307142A CA2307142A CA2307142C CA 2307142 C CA2307142 C CA 2307142C CA 2307142 A CA2307142 A CA 2307142A CA 2307142 A CA2307142 A CA 2307142A CA 2307142 C CA2307142 C CA 2307142C
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- Prior art keywords
- consensus interferon
- csf
- protein
- moiety
- pegylated
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- Expired - Lifetime
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Classifications
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- 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
- A61K47/56—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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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/56—IFN-alpha
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Molecular Biology (AREA)
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- Vascular Medicine (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002472085A CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/321,510 | 1994-10-12 | ||
| US08/321,510 US5824784A (en) | 1994-10-12 | 1994-10-12 | N-terminally chemically modified protein compositions and methods |
| CA002178752A CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002178752A Division CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002472085A Division CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Publications (2)
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| CA2307142A1 CA2307142A1 (en) | 1996-04-25 |
| CA2307142C true CA2307142C (en) | 2010-09-21 |
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| CA002178752A Expired - Lifetime CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
| CA2307142A Expired - Lifetime CA2307142C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
| CA002472085A Abandoned CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002178752A Expired - Lifetime CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002472085A Abandoned CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
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| EP (5) | EP0733067B1 (show.php) |
| JP (8) | JP3177251B2 (show.php) |
| KR (2) | KR100248111B1 (show.php) |
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| AT (2) | ATE179991T1 (show.php) |
| CA (3) | CA2178752C (show.php) |
| DE (3) | DE10299044I1 (show.php) |
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| NZ (1) | NZ281469A (show.php) |
| PT (1) | PT822199E (show.php) |
| WO (1) | WO1996011953A1 (show.php) |
| ZA (1) | ZA951008B (show.php) |
Families Citing this family (565)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2989002B2 (ja) * | 1988-12-22 | 1999-12-13 | キリン―アムジエン・インコーポレーテツド | 化学修飾顆粒球コロニー刺激因子 |
| US20020177688A1 (en) * | 1988-12-22 | 2002-11-28 | Kirin-Amgen, Inc., | Chemically-modified G-CSF |
| US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| DE69521880T2 (de) * | 1994-02-08 | 2002-01-03 | Amgen Inc., Thousand Oaks | Orales verabreichungssystem von chemischmodifizierten proteinen g-csf |
| US6001968A (en) | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
| US6429290B1 (en) | 1994-08-17 | 2002-08-06 | The Rockefeller University | OB polypeptides, modified forms and derivatives |
| 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 |
| CA2204726A1 (en) * | 1994-11-09 | 1996-12-27 | Robin E. Offord | Functionalized polymers for site-specific attachment |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US6008202A (en) * | 1995-01-23 | 1999-12-28 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| EP0858343B1 (en) | 1995-11-02 | 2004-03-31 | Schering Corporation | Continuous low-dose cytokine infusion therapy |
| US5908621A (en) * | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| TW517067B (en) | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
| AU736876B2 (en) | 1996-12-06 | 2001-08-02 | Amgen, Inc. | Combination therapy using an IL-1 inhibitor for treating IL-1 mediated diseases |
| JP2001508783A (ja) * | 1997-01-29 | 2001-07-03 | ポリマスク・ファーマシューティカルズ・パブリック・リミテッド・カンパニー | Peg化法 |
| WO1998055500A1 (en) | 1997-06-06 | 1998-12-10 | Kyowa Hakko Kogyo Co., Ltd. | Chemically modified polypeptides |
| ATE375363T1 (de) * | 1997-07-14 | 2007-10-15 | Bolder Biotechnology Inc | Derivate des wachstumshormons und verwandte proteine |
| US20080076706A1 (en) | 1997-07-14 | 2008-03-27 | Bolder Biotechnology, Inc. | Derivatives of Growth Hormone and Related Proteins, and Methods of Use Thereof |
| US6753165B1 (en) * | 1999-01-14 | 2004-06-22 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| US6017876A (en) * | 1997-08-15 | 2000-01-25 | Amgen Inc. | Chemical modification of granulocyte-colony stimulating factor (G-CSF) bioactivity |
| US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| US5981709A (en) * | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| PL193352B1 (pl) * | 1998-04-28 | 2007-02-28 | Applied Research Systems | Koniugat poliol-interferon ß, sposób jego wytwarzania i jego zastosowanie oraz kompozycja farmaceutyczna |
| TWI277424B (en) * | 1998-05-15 | 2007-04-01 | Schering Corp | Combination therapy for eradicating detectable NCV-RNA in antiviral treatment naive patients having chronic hepatitis C infection |
| NL1009601C2 (nl) * | 1998-07-09 | 2000-01-11 | Univ Utrecht | Verbinding welke de binding van een eiwit aan mestcellen kan remmen, toepassing van de verbinding voor de bereiding van een geneesmiddel, een farmaceutisch preparaat, een werkwijze voor het diagnostiseren van een ziekte en een selectiewerkwijze. |
| WO2000004041A2 (en) * | 1998-07-16 | 2000-01-27 | Hyseq, Inc. | Methods and molecules relating to cd39-like polypeptides |
| US6783965B1 (en) * | 2000-02-10 | 2004-08-31 | Mountain View Pharmaceuticals, Inc. | Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates |
| CA2338665C (en) * | 1998-08-06 | 2011-01-18 | Mountain View Pharmaceuticals, Inc. | Peg-urate oxidase conjugates and use thereof |
| US6420339B1 (en) * | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
| EP1121156B1 (en) * | 1998-10-16 | 2006-02-22 | Biogen Idec MA Inc. | Polymer conjugates of interferon beta- 1a and their uses |
| IL142350A0 (en) * | 1998-10-16 | 2002-03-10 | Biogen Inc | Interferon-beta fusion proteins and pharmaceutical compositions containing the same |
| US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
| US6835809B1 (en) * | 1998-10-23 | 2004-12-28 | Amgen Inc. | Thrombopoietic compounds |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| WO2000032772A2 (en) * | 1998-11-30 | 2000-06-08 | Eli Lilly And Company | Erythropoietic compounds |
| US8288126B2 (en) | 1999-01-14 | 2012-10-16 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| KR100731826B1 (ko) | 1999-01-14 | 2007-06-22 | 볼더 바이오테크놀로지 인코퍼레이티드 | 유리 시스테인 잔기를 함유하는 단백질의 제조 방법 |
| EP1369429A1 (en) * | 1999-01-29 | 2003-12-10 | F. Hoffmann-La Roche Ag | GCSF conjugates |
| DE60004172T2 (de) * | 1999-01-29 | 2004-04-22 | F. Hoffmann-La Roche Ag | Gcsf konjugate |
| AU2824700A (en) * | 1999-03-01 | 2000-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Chemically modified g-csf preparations |
| US6485718B1 (en) | 1999-04-13 | 2002-11-26 | Pharmacia Corporation | Site specific ligation of proteins to synthetic particles |
| US6924264B1 (en) * | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| US7160924B2 (en) * | 2002-07-19 | 2007-01-09 | The General Hospital Corporation | Protein conjugates with a water-soluble biocompatible, biodegradable polymer |
| US8106098B2 (en) * | 1999-08-09 | 2012-01-31 | The General Hospital Corporation | Protein conjugates with a water-soluble biocompatible, biodegradable polymer |
| US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US6348558B1 (en) | 1999-12-10 | 2002-02-19 | Shearwater Corporation | Hydrolytically degradable polymers and hydrogels made therefrom |
| US7074878B1 (en) * | 1999-12-10 | 2006-07-11 | Harris J Milton | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6831158B2 (en) * | 2000-01-10 | 2004-12-14 | Maxygen Holdings Ltd. | G-CSF conjugates |
| US6646110B2 (en) * | 2000-01-10 | 2003-11-11 | Maxygen Holdings Ltd. | G-CSF polypeptides and conjugates |
| WO2001051510A2 (en) | 2000-01-10 | 2001-07-19 | Maxygen Holdings Ltd | G-csf conjugates |
| US6555660B2 (en) * | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
| US7049761B2 (en) * | 2000-02-11 | 2006-05-23 | Altair Engineering, Inc. | Light tube and power supply circuit |
| NZ521257A (en) | 2000-02-11 | 2004-10-29 | Maxygen Aps | Factor VII or VIIa-like molecules |
| ES2220673T3 (es) | 2000-02-29 | 2004-12-16 | Pfizer Products Inc. | Factor estimulante de colonias de granulocitos estabilizado. |
| US20020064820A1 (en) * | 2000-03-13 | 2002-05-30 | Jean-Michel Dayer | Apo-A-I regulation of T-cell signaling |
| AU2001289307A1 (en) * | 2000-04-06 | 2001-10-23 | Pharmacia Corporation | Chemically-modified myelopoietin conjugates |
| US6586398B1 (en) * | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| CA2406390A1 (en) * | 2000-04-14 | 2001-10-25 | University Of South Carolina Research Foundation | Cloning, overexpression and therapeutic uses of bioactive histidine ammonia lyase |
| DK1290013T3 (da) | 2000-04-21 | 2006-06-26 | Amgen Inc | Apo-A1/All-peptidderivater |
| US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
| US20030211094A1 (en) * | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| US20050089970A1 (en) * | 2000-07-12 | 2005-04-28 | Bradburne James A. | Polymer-modified bioactive synthetic chemokines, and methods for their manufacture and use |
| CA2412279A1 (en) * | 2000-09-08 | 2002-03-14 | Gryphon Therapeutics, Inc. | "pseudo"-native chemical ligation |
| US7118737B2 (en) * | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| EP1324779B1 (en) | 2000-09-29 | 2011-07-20 | Schering Corporation | Pegylated interleukin-10 |
| US20040082765A1 (en) * | 2000-10-16 | 2004-04-29 | Teruo Nakamura | Peg-modified erythropoietin |
| US6706289B2 (en) * | 2000-10-31 | 2004-03-16 | Pr Pharmaceuticals, Inc. | Methods and compositions for enhanced delivery of bioactive molecules |
| EP1334127A1 (en) * | 2000-11-02 | 2003-08-13 | Maxygen Aps | Single-chain multimeric polypeptides |
| CN1321134C (zh) * | 2000-11-23 | 2007-06-13 | 赵剑 | 一种生物活性蛋白质的非均一制品及其制备方法 |
| RU2275207C2 (ru) * | 2000-12-14 | 2006-04-27 | Амилин Фармасьютикалз, Инк. | Способ снижения доступности питательного вещества, способ подавления аппетита |
| US7053150B2 (en) * | 2000-12-18 | 2006-05-30 | Nektar Therapeutics Al, Corporation | Segmented polymers and their conjugates |
| TW593427B (en) * | 2000-12-18 | 2004-06-21 | Nektar Therapeutics Al Corp | Synthesis of high molecular weight non-peptidic polymer derivatives |
| KR100645843B1 (ko) * | 2000-12-20 | 2006-11-14 | 에프. 호프만-라 로슈 아게 | 에리트로포이에틴 접합체 |
| US7442370B2 (en) | 2001-02-01 | 2008-10-28 | Biogen Idec Ma Inc. | Polymer conjugates of mutated neublastin |
| ATE399794T1 (de) * | 2001-02-06 | 2008-07-15 | Merck Patent Gmbh | Modifizierter granulozyten stimulierender factor (g-csf) mit verringerter immunogenität |
| EP1234583A1 (en) | 2001-02-23 | 2002-08-28 | F. Hoffmann-La Roche Ag | PEG-conjugates of HGF-NK4 |
| CZ20032526A3 (cs) | 2001-02-27 | 2003-12-17 | Maxygen Aps | Nové molekuly podobné interferonu beta |
| US7276580B2 (en) | 2001-03-12 | 2007-10-02 | Biogen Idec Ma Inc. | Neurotrophic factors |
| US7247618B2 (en) * | 2001-04-30 | 2007-07-24 | Tripathi Rajavashisth | Methods for inhibiting macrophage colony stimulating factor and c-FMS-dependent cell signaling |
| US20030203865A1 (en) * | 2001-04-30 | 2003-10-30 | Pierrot Harvie | Lipid-comprising drug delivery complexes and methods for their production |
| EA010435B1 (ru) | 2001-05-11 | 2008-08-29 | Амген, Инк. | Связывающиеся с tall-1 молекулы и их применение |
| US7229810B2 (en) * | 2001-06-28 | 2007-06-12 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates of proteinases |
| CA2452582C (en) * | 2001-07-11 | 2013-01-22 | Maxygen, Inc. | G-csf conjugates |
| US20040077835A1 (en) * | 2001-07-12 | 2004-04-22 | Robin Offord | Chemokine receptor modulators, production and use |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| EP1450838A4 (en) * | 2001-10-05 | 2005-09-28 | Intermune Inc | METHOD FOR THE TREATMENT OF HEPATITIS INFECTIONS WITH A MULTIPHASIC INTERFERON DELIVERY PROFILE |
| US6908963B2 (en) * | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| US7214660B2 (en) * | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
| US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| SI2939696T1 (sl) | 2001-10-18 | 2016-06-30 | Nektar Therapeutics | Polimerni konjugati opioidnih antagonistov |
| WO2003043651A1 (fr) * | 2001-11-19 | 2003-05-30 | Kyowa Hakko Kogyo Co., Ltd. | Medicament mobilisant les cellules souches totipotentes d'un tissu dans le sang peripherique |
| US20030171285A1 (en) * | 2001-11-20 | 2003-09-11 | Finn Rory F. | Chemically-modified human growth hormone conjugates |
| EP1453859A2 (en) * | 2001-11-20 | 2004-09-08 | Pharmacia Corporation | Chemically-modified human growth hormone conjugates |
| KR100480432B1 (ko) * | 2001-12-04 | 2005-04-06 | 선바이오(주) | G-csf와 폴리에틸렌글리콜 유도체의 배합체 |
| EP1461067A1 (en) * | 2001-12-07 | 2004-09-29 | Intermune, Inc. | Compositions and method for treating hepatitis virus infection |
| DE60323936D1 (de) * | 2002-01-14 | 2008-11-20 | Gen Hospital Corp | Bioabbaubare polyketale, verfahren zu ihrer herstellung sowie ihre verwendung |
| EE05509B1 (et) | 2002-01-18 | 2012-02-15 | Biogen@Idec@Ma@Inc | Aktiveeritud polalkleenglkoolpolmeer ja seda sisaldavad kompositsioonid |
| DE10209821A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
| US20030191056A1 (en) | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
| US20030199464A1 (en) * | 2002-04-23 | 2003-10-23 | Silviu Itescu | Regeneration of endogenous myocardial tissue by induction of neovascularization |
| ATE494002T1 (de) * | 2002-06-14 | 2011-01-15 | Amylin Pharmaceuticals Inc | Prävention und/oder behandlung von colitis ulcerosa mit pyy oder pyyä3-36ü |
| US20040002451A1 (en) * | 2002-06-20 | 2004-01-01 | Bruce Kerwin | Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing |
| CA2492803C (en) | 2002-07-19 | 2013-11-05 | The General Hospital Corporation | Oxime conjugates and methods for their formation and use |
| PL376536A1 (pl) | 2002-08-28 | 2006-01-09 | Immunex Corporation | Kompozycje i sposoby leczenia chorób układu sercowo-naczyniowego |
| PL375883A1 (en) * | 2002-09-09 | 2005-12-12 | Nektar Therapeutics Al, Corporation | Water-soluble polymer alkanals |
| US8129330B2 (en) | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| EP1549350B1 (en) | 2002-10-08 | 2008-09-24 | Fresenius Kabi Deutschland GmbH | Pharmaceutically active oligosaccharide conjugates |
| JP2004196770A (ja) * | 2002-10-24 | 2004-07-15 | Effector Cell Institute Inc | 樹状細胞前駆体の血中レベル上昇剤 |
| US20050075279A1 (en) * | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| US7314613B2 (en) | 2002-11-18 | 2008-01-01 | Maxygen, Inc. | Interferon-alpha polypeptides and conjugates |
| TWI281864B (en) * | 2002-11-20 | 2007-06-01 | Pharmacia Corp | N-terminally monopegylated human growth hormone conjugates and process for their preparation |
| CN1761680A (zh) | 2002-12-26 | 2006-04-19 | 武田药品工业株式会社 | 肿瘤迁移抑制素衍生物及其用途 |
| EP1667708B9 (en) * | 2002-12-26 | 2012-10-31 | Mountain View Pharmaceuticals, Inc. | POLYETHYLENE GLYCOL CONJUGATES OF INTERFERON-BETA-1b WITH ENHANCED IN VITRO BIOLOGICAL POTENCY |
| PL396711A1 (pl) * | 2002-12-26 | 2011-12-19 | Mountain View Pharmaceuticals, Inc. | Koniugaty polimerów z cytokinami, chemokinami, czynnikami wzrostu, hormonami polipeptydowymi i ich antagonistami, kompozycja farmaceutyczna i sposób zapobiegania, diagnozowania lub leczenia |
| EP1616003A4 (en) | 2002-12-30 | 2007-06-20 | Gryphon Therapeutics Inc | WATER-SOLUBLE THIOESTER AND SELENOESTER COMPOUNDS AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| US7803362B2 (en) * | 2003-01-24 | 2010-09-28 | Synageva Biopharma Corp. | Glycosylated interferon alpha |
| EP1597278A4 (en) * | 2003-02-26 | 2006-03-22 | Intermune Inc | COMPOSITIONS OF POLYETHYLENE GLYCOL-MODIFIED INTERFERON AND METHOD FOR THE APPLICATION THEREOF |
| US20070077225A1 (en) * | 2003-02-28 | 2007-04-05 | Blatt Lawrence M | Continuous delivery methods for treating hepatitis virus infection |
| US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
| SI1603541T2 (sl) | 2003-03-05 | 2013-04-30 | Halozyme, Inc. | Topen hialuronidazni glikoprotein (sHASEGP), postopek za pripravo le-tega, uporabe in farmacevtski sestavki, ki ga obsegajo |
| US7871607B2 (en) | 2003-03-05 | 2011-01-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases |
| CN102212019B (zh) | 2003-03-14 | 2015-05-27 | 蔚所番有限公司 | 支化水溶性聚合物及其缀合物 |
| US20060134736A1 (en) * | 2003-03-28 | 2006-06-22 | Jacobs John W | Human growth hormone conjugated with biocompatible polymer |
| MXPA05010411A (es) * | 2003-03-28 | 2006-05-31 | Biopolymed Inc | Material activo biologicamente conjugado con polimeros biocompatibles con el complejo 1:1, metodo de preparacion del mismo y composicion farmaceutica que lo contienen. |
| EP1610825A2 (en) | 2003-03-31 | 2006-01-04 | Xencor, Inc. | Methods for rational pegylation of proteins |
| US7610156B2 (en) | 2003-03-31 | 2009-10-27 | Xencor, Inc. | Methods for rational pegylation of proteins |
| US7642340B2 (en) | 2003-03-31 | 2010-01-05 | Xencor, Inc. | PEGylated TNF-α variant proteins |
| SG155777A1 (en) | 2003-04-09 | 2009-10-29 | Neose Technologies Inc | Glycopegylation methods and proteins/peptides produced by the methods |
| US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
| CN101514223B (zh) | 2003-04-11 | 2017-03-01 | 安特里阿比奥有限公司 | 位点特异性蛋白质偶联物的制备方法 |
| DE602004025799D1 (de) | 2003-04-15 | 2010-04-15 | Glaxosmithkline Llc | Humane il-18 substitutionsmutanten und deren konjugate |
| ATE433759T1 (de) | 2003-04-18 | 2009-07-15 | Biogen Idec Inc | Polymerkonjugiertes glycosiliertes neublastin |
| CA2525647A1 (en) | 2003-05-16 | 2005-02-24 | Intermune, Inc. | Synthetic chemokine receptor ligands and methods of use thereof |
| DE602004025949D1 (de) | 2003-07-22 | 2010-04-22 | Nektar Therapeutics | Verfahren zur herstellung von funktionalisierten polymeren aus polymeralkoholen |
| EP2133362B1 (en) | 2003-07-25 | 2012-04-18 | Amgen, Inc | Methods relating to LDCAM and CRTAM |
| WO2005012484A2 (en) | 2003-07-25 | 2005-02-10 | Neose Technologies, Inc. | Antibody-toxin conjugates |
| WO2005014655A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| US7691975B2 (en) * | 2003-08-25 | 2010-04-06 | Toray Industries, Inc. | Interferon-β complex |
| GB0320638D0 (en) | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| LT1675622T (lt) | 2003-09-17 | 2017-09-11 | Nektar Therapeutics | Daugiašakio polimero provaistai |
| ATE500264T1 (de) * | 2003-09-22 | 2011-03-15 | Boehringer Ingelheim Int | Makrozyklische peptide mit wirkung gegen das hepatitis-c-virus |
| EP2322569B1 (en) * | 2003-10-09 | 2020-08-26 | Ambrx, Inc. | Polymer derivatives for the selective modification of proteins |
| EP1675871A2 (en) | 2003-10-10 | 2006-07-05 | Xencor Inc. | Protein based tnf-alpha variants for the treatment of tnf-alpha related disorders |
| WO2005035565A1 (en) | 2003-10-10 | 2005-04-21 | Novo Nordisk A/S | Il-21 derivatives |
| RS20110578A3 (en) | 2003-10-14 | 2016-02-29 | F. Hoffmann-La Roche Ltd | MACROCYCLIC CARBOXYLIC ACIDS AND ACYLSULPHONAMIDES AS HCV REPLICATION INHIBITORS |
| EP2633866A3 (en) | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
| WO2005040758A2 (en) * | 2003-10-24 | 2005-05-06 | Intermune, Inc. | Use of pirfenidone in therapeutic regimens |
| US7220407B2 (en) * | 2003-10-27 | 2007-05-22 | Amgen Inc. | G-CSF therapy as an adjunct to reperfusion therapy in the treatment of acute myocardial infarction |
| US8637650B2 (en) | 2003-11-05 | 2014-01-28 | Genovoxx Gmbh | Macromolecular nucleotide compounds and methods for using the same |
| US8633157B2 (en) | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
| US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| WO2005053730A1 (ja) * | 2003-12-05 | 2005-06-16 | Kirin Beer Kabushiki Kaisha | 末期心不全治療剤 |
| WO2005067963A1 (en) * | 2003-12-23 | 2005-07-28 | Intermune, Inc. | Use of polyethylene glycol-modified interferon-alpha in therapeutic dosing regimens |
| GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
| CA2552892C (en) | 2004-01-08 | 2014-08-05 | Neose Technologies, Inc. | O-linked glycosylation of peptides |
| DE602005025855D1 (de) * | 2004-01-21 | 2011-02-24 | Boehringer Ingelheim Pharma | Makrocyclische peptide mit wirkung gegen das hepatitis-c-virus |
| MXPA06008496A (es) | 2004-02-02 | 2007-01-30 | Ambrx Inc | Polipeptidos de interferon humano modificados y sus usos. |
| US8076288B2 (en) * | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
| EP2335716A3 (en) * | 2004-02-11 | 2011-10-19 | Amylin Pharmaceuticals Inc. | Pancreatic polypeptide family motifs and polypeptides comprising the same |
| WO2006066024A2 (en) | 2004-12-13 | 2006-06-22 | Amylin Pharmaceuticals, Inc. | Pancreatic polypeptide family motifs, polypeptides and methods comprising the same |
| CA2555877C (en) | 2004-02-11 | 2015-11-24 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| JP2007526317A (ja) * | 2004-03-01 | 2007-09-13 | エンゾン ファーマスーティカルズ インコーポレイテッド | インターフェロン−ベータ・ポリマー結合体 |
| AU2005229001A1 (en) * | 2004-03-23 | 2005-10-13 | Amgen Inc. | Chemically modified protein compositions and methods |
| US8470315B2 (en) * | 2004-04-13 | 2013-06-25 | Quintessence Biosciences, Inc. | Non-natural ribonuclease conjugates as cytotoxic agents |
| EP1586334A1 (en) * | 2004-04-15 | 2005-10-19 | TRASTEC scpa | G-CSF conjugates with peg |
| MXPA06013412A (es) | 2004-05-19 | 2007-01-23 | Maxygen Inc | Polipeptidos de interferon-alfa y conjugados. |
| WO2005123113A2 (en) * | 2004-06-14 | 2005-12-29 | Intermune, Inc. | Interferon compositions and methods of use thereof |
| KR20070034512A (ko) | 2004-06-18 | 2007-03-28 | 암브룩스, 인코포레이티드 | 신규 항원-결합 폴리펩티드 및 이의 용도 |
| CN101863971A (zh) | 2004-06-25 | 2010-10-20 | 武田药品工业株式会社 | 转移素衍生物及其用途 |
| AU2005260664A1 (en) * | 2004-06-30 | 2006-01-12 | Egen Corporation | Pegylated interferon alpha-1b |
| US8143380B2 (en) * | 2004-07-08 | 2012-03-27 | Amgen Inc. | Therapeutic peptides |
| US20080300173A1 (en) | 2004-07-13 | 2008-12-04 | Defrees Shawn | Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1] |
| KR20070039593A (ko) | 2004-07-21 | 2007-04-12 | 암브룩스, 인코포레이티드 | 비천연적으로 코딩된 아미노산을 이용한 생합성 폴리펩티드 |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| US8722862B2 (en) | 2004-08-19 | 2014-05-13 | Biogen Idec Ma Inc. | Refolding transforming growth factor beta family proteins |
| DK1786454T3 (da) | 2004-08-19 | 2010-09-06 | Biogen Idec Inc | Neublastinvarianter |
| WO2006031811A2 (en) | 2004-09-10 | 2006-03-23 | Neose Technologies, Inc. | Glycopegylated interferon alpha |
| WO2006034455A2 (en) | 2004-09-23 | 2006-03-30 | Vasgene Therapeutics, Inc. | Polipeptide compounds for inhibiting angiogenesis and tumor growth |
| DK1797127T3 (en) | 2004-09-24 | 2017-10-02 | Amgen Inc | Modified Fc molecules |
| DK2586456T3 (en) * | 2004-10-29 | 2016-03-21 | Ratiopharm Gmbh | Conversion and glycopegylation of fibroblast growth factor (FGF) |
| US20060153799A1 (en) * | 2004-11-05 | 2006-07-13 | Northwestern University | Use of SCF and G-CSF in the treatment of cerebral ischemia and neurological disorders |
| US7736872B2 (en) * | 2004-12-22 | 2010-06-15 | Ambrx, Inc. | Compositions of aminoacyl-TRNA synthetase and uses thereof |
| EP1836316A4 (en) | 2004-12-22 | 2009-07-22 | Ambrx Inc | PROCESS FOR EXPRESSION AND CLEANING OF RECOMBINANT HUMAN GROWTH HORMONE |
| EP1833993A4 (en) | 2004-12-22 | 2009-07-22 | Ambrx Inc | HUMAN GROWTH HORMONE FORMULATIONS COMPRISING AN AMINO ACID CODED NON-NATURALLY |
| CA2594557C (en) | 2004-12-22 | 2016-04-26 | Ambrx, Inc. | Modified human growth hormone |
| EP1674113A1 (en) | 2004-12-22 | 2006-06-28 | F. Hoffmann-La Roche Ag | Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol) |
| DK1828224T3 (en) | 2004-12-22 | 2016-07-18 | Ambrx Inc | Compositions containing, methods including, AND USES OF NON-NATURAL AMINO ACIDS AND POLYPEPTIDES |
| ES2449195T3 (es) | 2005-01-10 | 2014-03-18 | Ratiopharm Gmbh | Factor estimulante de colonias de granulocitos glicopegilado |
| MX2007008982A (es) | 2005-01-25 | 2007-12-06 | Cell Therapeutics Inc | Conjugados de proteinas biologicamente activas que tienen una vida media modificada in vivo. |
| JPWO2006080171A1 (ja) * | 2005-01-31 | 2008-06-19 | 株式会社 エフェクター細胞研究所 | 免疫増強剤 |
| US7402730B1 (en) | 2005-02-03 | 2008-07-22 | Lexicon Pharmaceuticals, Inc. | Knockout animals manifesting hyperlipidemia |
| US8263545B2 (en) * | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| EP2390264A1 (en) | 2005-02-11 | 2011-11-30 | Amylin Pharmaceuticals Inc. | GIP analog and hybrid polypeptides with selectable propperties |
| WO2006094530A1 (en) * | 2005-03-11 | 2006-09-14 | Siegfried Ltd. | Di-polymer protein conjugates and processes for their preparation |
| WO2007010552A2 (en) * | 2005-03-17 | 2007-01-25 | Serum Institute Of India Limited | N- terminal peg conjugate of erythropoietin |
| KR20080003849A (ko) | 2005-03-31 | 2008-01-08 | 아밀린 파마슈티칼스, 인크. | 비만 및 섭식 장애의 조절, 예방 및 치료를 위한 조성물 및방법 |
| US20100092505A1 (en) | 2005-04-05 | 2010-04-15 | Elisabetta Bianchi | Method for Shielding Functional Sites or Epitopes on Proteins |
| 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 |
| HU229068B1 (hu) | 2005-04-11 | 2013-07-29 | Savient Pharmaceuticals | Urát oxidáz változatok és alkalmazásuk |
| US7833979B2 (en) | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
| US7619067B2 (en) | 2005-05-18 | 2009-11-17 | Maxygen, Inc. | Evolved interferon-alpha polypeptides |
| EP2975135A1 (en) | 2005-05-25 | 2016-01-20 | Novo Nordisk A/S | Glycopegylated factor IX |
| US20060286657A1 (en) * | 2005-06-01 | 2006-12-21 | Samuel Zalipsky | Novel bioconjugation reactions for acylating polyethylene glycol reagents |
| KR20080027291A (ko) * | 2005-06-01 | 2008-03-26 | 맥시겐 홀딩스 엘티디 | 피이지화된 지-씨에스에프 폴리펩타이드 및 그 제조방법 |
| WO2007009208A1 (en) * | 2005-06-02 | 2007-01-25 | Cangene Corporation | Poly(ethylene glocol) modified human gm-csf with increased biological activity |
| AU2006255122B2 (en) * | 2005-06-03 | 2010-10-21 | Ambrx, Inc. | Improved human interferon molecules and their uses |
| KR100694994B1 (ko) * | 2005-06-13 | 2007-03-14 | 씨제이 주식회사 | 사람 과립구 콜로니 형성인자 동종체 |
| MX2007015819A (es) * | 2005-06-13 | 2008-02-22 | Nastech Pharm Co | Suministro de derivados peptidicos a traves de la mucosa. |
| AR054778A1 (es) | 2005-06-17 | 2007-07-18 | Novartis Ag | Uso de sangliferina en hcv |
| US8633300B2 (en) | 2005-06-17 | 2014-01-21 | Novo Nordisk Healthcare Ag | Selective reduction and derivatization of engineered proteins comprising at least one non-native cysteine |
| US7695710B2 (en) * | 2005-06-20 | 2010-04-13 | Pepgen Corporation | Antitumor and antiviral combination therapies using low-toxicity, long-circulating human interferon-alpha analogs |
| WO2007002233A2 (en) * | 2005-06-20 | 2007-01-04 | Pepgen Corporation | Low-toxicity, long-circulating chimeras of human interferon- alpha analogs and interferon tau |
| EP1926768B1 (en) | 2005-07-18 | 2011-09-14 | Nektar Therapeutics | Branched functionalized polymers using branched polyol cores |
| KR100735784B1 (ko) * | 2005-07-20 | 2007-07-06 | 재단법인 목암생명공학연구소 | 인간 과립구콜로니자극인자 변이체 및 이의 화학적 접합물 |
| CN101263156A (zh) | 2005-07-25 | 2008-09-10 | 因特蒙公司 | C型肝炎病毒复制的新颖大环抑制剂 |
| WO2007015591A1 (en) * | 2005-08-02 | 2007-02-08 | Cheil Industries Inc. | Epoxy resin composition for packaging semiconductor device |
| JP2009503111A (ja) * | 2005-08-04 | 2009-01-29 | ネクター セラピューティックス エイエル,コーポレイション | G−csf部分および重合体の複合体 |
| EP2330124B1 (en) | 2005-08-11 | 2015-02-25 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| BRPI0614649A2 (pt) | 2005-08-11 | 2011-04-12 | Amylin Pharmaceuticals Inc | polipeptìdeos hìbridos com propriedades selecionáveis |
| US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
| DK1937824T3 (da) | 2005-08-18 | 2013-04-02 | Ambrx Inc | Sammensætninger af tRNA og anvendelser deraf |
| HUE045165T2 (hu) | 2005-08-19 | 2019-12-30 | Amylin Pharmaceuticals Llc | Exendin diabetes kezelésére és testtömeg csökkentésére |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| JP2009511595A (ja) | 2005-10-11 | 2009-03-19 | インターミューン・インコーポレーテッド | C型肝炎ウイルスの複製を阻害する化合物および方法 |
| WO2007047303A2 (en) * | 2005-10-12 | 2007-04-26 | Alvine Pharmaceuticals, Inc. | Pegylated glutenase polypeptides |
| KR20080074120A (ko) | 2005-10-13 | 2008-08-12 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 자가항체 양성 질환 환자의 치료에 유용한 방법 및 조성물 |
| CA2622210A1 (en) * | 2005-10-21 | 2007-04-26 | Avigenics, Inc. | Glycolated and glycosylated poultry derived therapeutic proteins |
| US20080171696A1 (en) * | 2005-10-21 | 2008-07-17 | Avigenics, Inc. | Pharmacodynamically enhanced therapeutic proteins |
| US8168592B2 (en) | 2005-10-21 | 2012-05-01 | Amgen Inc. | CGRP peptide antagonists and conjugates |
| WO2007056191A2 (en) | 2005-11-03 | 2007-05-18 | Neose Technologies, Inc. | Nucleotide sugar purification using membranes |
| US20090137736A1 (en) * | 2005-11-08 | 2009-05-28 | Ambrx, Inc. | Accelerants for the Modification of Non-Natural Amino Acids and Non-Natural Amino Acid Polypeptides |
| AR056806A1 (es) | 2005-11-14 | 2007-10-24 | Amgen Inc | Moleculas quimericas de anticuerpo rankl- pth/ pthrp |
| CN101454461A (zh) * | 2005-11-16 | 2009-06-10 | Ambrx公司 | 包括非天然氨基酸的方法和组合物 |
| CA2631491C (en) * | 2005-12-14 | 2015-02-24 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| US8404643B2 (en) | 2005-12-22 | 2013-03-26 | Takeda Pharmaceutical Company Limited | Metastin derivatives and use thereof |
| AU2006332340B2 (en) | 2005-12-30 | 2013-09-26 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Extended release of neuregulin for improved cardiac function |
| US8992905B2 (en) | 2006-01-12 | 2015-03-31 | Hokusan Co. Ltd. | Oral composition containing interferon-α |
| CN100475270C (zh) * | 2006-01-20 | 2009-04-08 | 清华大学 | 一种治疗肿瘤的药物及其应用 |
| EP1991577A2 (en) | 2006-01-31 | 2008-11-19 | Parkinson, John F. | Modulation of mdl-1 activity for treatment of inflammatory disease |
| WO2007098466A2 (en) | 2006-02-21 | 2007-08-30 | Nektar Therapeutics Al, Corporation | Segmented degradable polymers and conjugates made therefrom |
| TWI501774B (zh) | 2006-02-27 | 2015-10-01 | Biogen Idec Inc | 神經性病症之治療 |
| WO2007111661A2 (en) | 2006-03-20 | 2007-10-04 | Xoma Technology Ltd. | Human antibodies specific for gastrin materials and methods |
| US20090306349A1 (en) * | 2006-03-31 | 2009-12-10 | Rampak Corp | Binding partners with immunoglobulin domains modified to have extended half-life |
| UA100666C2 (uk) | 2006-04-11 | 2013-01-25 | Новартіс Аг | Інгібітори нсv/віл та їх застосування |
| US9283260B2 (en) | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
| WO2007133778A2 (en) * | 2006-05-12 | 2007-11-22 | Amylin Pharmaceuticals, Inc. | Methods to restore glycemic control |
| WO2007136752A2 (en) | 2006-05-19 | 2007-11-29 | Glycofi, Inc. | Erythropoietin compositions |
| KR20090013816A (ko) | 2006-05-24 | 2009-02-05 | 노보 노르디스크 헬스 케어 악티엔게젤샤프트 | 연장된 생체내 반감기를 갖는 인자 ⅸ 유사체 |
| US7981425B2 (en) | 2006-06-19 | 2011-07-19 | Amgen Inc. | Thrombopoietic compounds |
| US8840882B2 (en) * | 2006-06-23 | 2014-09-23 | Quintessence Biosciences, Inc. | Modified ribonucleases |
| ES2376396T3 (es) | 2006-06-26 | 2012-03-13 | Amgen Inc. | Método para tratar aterosclerosis. |
| EP2049151A4 (en) | 2006-07-17 | 2010-03-24 | Quintessence Biosciences Inc | METHOD AND COMPOSITIONS FOR THE TREATMENT OF CANCER |
| EP2049144B8 (en) | 2006-07-21 | 2015-02-18 | ratiopharm GmbH | Glycosylation of peptides via o-linked glycosylation sequences |
| EP2630972B1 (en) | 2006-07-25 | 2017-08-30 | Lipoxen Technologies Limited | N-terminal polysialylation |
| GB0615067D0 (en) * | 2006-07-28 | 2006-09-06 | Ttp Communications Ltd | Reconfigurable signal processing scheme |
| PT2054074E (pt) * | 2006-08-04 | 2014-11-07 | Prolong Pharmaceuticals Llc | Eritropoietina modificada |
| ITMI20061624A1 (it) * | 2006-08-11 | 2008-02-12 | Bioker Srl | Mono-coniugati sito-specifici di g-csf |
| US8497240B2 (en) | 2006-08-17 | 2013-07-30 | Amylin Pharmaceuticals, Llc | DPP-IV resistant GIP hybrid polypeptides with selectable properties |
| CL2007002502A1 (es) | 2006-08-31 | 2008-05-30 | Hoffmann La Roche | Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer. |
| KR101106795B1 (ko) * | 2006-08-31 | 2012-01-18 | 에프. 호프만-라 로슈 아게 | 인슐린-유사 성장 인자-i의 제조 방법 |
| AU2007292903B2 (en) | 2006-09-08 | 2012-03-29 | Ambrx, Inc. | Modified human plasma polypeptide or Fc scaffolds and their uses |
| JP5399906B2 (ja) * | 2006-09-08 | 2014-01-29 | アンブルックス,インコーポレイテッド | 脊椎動物細胞用のハイブリッドサプレッサーtrna |
| CN101511856B (zh) * | 2006-09-08 | 2016-01-20 | Ambrx公司 | 脊椎动物细胞中抑制因子trna的转录 |
| US7985783B2 (en) | 2006-09-21 | 2011-07-26 | The Regents Of The University Of California | Aldehyde tags, uses thereof in site-specific protein modification |
| WO2008054585A2 (en) | 2006-09-28 | 2008-05-08 | Schering Corporation | Use of pegylated il-10 to treat cancer |
| EP2054521A4 (en) | 2006-10-03 | 2012-12-19 | Novo Nordisk As | PROCESS FOR CLEANING POLYPEPTIDE CONJUGATES |
| CN101600448B (zh) * | 2006-10-04 | 2015-11-25 | 诺和诺德公司 | 甘油连接的peg化的糖和糖肽 |
| WO2008051383A2 (en) * | 2006-10-19 | 2008-05-02 | Amgen Inc. | Use of alcohol co-solvents to improve pegylation reaction yields |
| TWI404726B (zh) | 2006-10-25 | 2013-08-11 | Takeda Pharmaceutical | 腫瘤轉移抑制素衍生物及其用途 |
| US7803769B2 (en) | 2006-10-25 | 2010-09-28 | Amgen Inc. | OSK1 peptide analogs and pharmaceutical compositions |
| KR101079993B1 (ko) * | 2006-11-17 | 2011-11-04 | 동아제약주식회사 | 폴리에틸렌글리콜 과립구 콜로니 자극인자 접합체 |
| US8470332B2 (en) | 2006-11-22 | 2013-06-25 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR |
| WO2008073300A2 (en) | 2006-12-08 | 2008-06-19 | Lexicon Pharmaceuticals, Inc. | Monoclonal antibodies against angptl3 |
| EP2111228B1 (en) | 2007-02-02 | 2011-07-20 | Bristol-Myers Squibb Company | 10Fn3 domain for use in treating diseases associated with inappropriate angiogenesis |
| CN101245109B (zh) * | 2007-02-12 | 2011-12-14 | 杭州九源基因工程有限公司 | 一种聚乙二醇单修饰的重组人粒细胞集落刺激因子突变体及其制备方法 |
| DK2068909T3 (da) | 2007-03-30 | 2012-08-06 | Ambrx Inc | Modificerede FGF-21-polypeptider og anvendelse heraf |
| NZ580030A (en) | 2007-04-03 | 2012-06-29 | Biogenerix Ag | Methods of treatment using glycopegylated g-csf |
| JP2008266219A (ja) * | 2007-04-20 | 2008-11-06 | National Institute Of Advanced Industrial & Technology | リジン及びシステイン残基を含まないタンパク質 |
| US8329655B2 (en) | 2007-05-01 | 2012-12-11 | Biogen Idec Ma Inc. | Methods for increasing vascularization |
| CN103965347B (zh) | 2007-05-02 | 2017-07-18 | Ambrx公司 | 经修饰干扰素β多肽和其用途 |
| EP2162540A2 (en) | 2007-05-22 | 2010-03-17 | Amgen Inc. | Compositions and methods for producing bioactive fusion proteins |
| WO2008151258A2 (en) * | 2007-06-04 | 2008-12-11 | Neose Technologies, Inc. | O-linked glycosylation using n-acetylglucosaminyl transferases |
| CA2690611C (en) | 2007-06-12 | 2015-12-08 | Novo Nordisk A/S | Improved process for the production of nucleotide sugars |
| US20110159523A1 (en) * | 2007-06-27 | 2011-06-30 | Cedars-Sinai Medical Center | N-terminal specific chemical labeling for proteomics applications |
| PT2489731E (pt) | 2007-07-26 | 2014-09-15 | Amgen Inc | Enzimas aciltransferase de lecitina-colesterol modificadas |
| CN101352573B (zh) * | 2007-07-27 | 2011-02-09 | 杭州九源基因工程有限公司 | 聚乙二醇单修饰的重组人集落细胞刺激因子赖氨酸缺陷体 |
| EP2581441A1 (en) | 2007-08-09 | 2013-04-17 | Genzyme Corporation | Method of treating autoimmune disease with mesenchymal stem cells |
| CL2008002399A1 (es) * | 2007-08-16 | 2009-01-02 | Pharmaessentia Corp | Conjugado sustancialmente puro que posee una porcion polimerica, una porcion proteica (interferon alfa 2b) y un ligante alifatico de 1 a 10 atomos de carbono, util en el tratamiento de las hepatitis b o c. |
| DE202008017456U1 (de) | 2007-08-27 | 2009-08-27 | Biogenerix Ag | Flüssig-Formulierung von G-CSF-Konjugaten |
| US8207112B2 (en) | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
| US8758761B2 (en) * | 2007-09-30 | 2014-06-24 | University Of Florida Research Foundation, Inc. | Combination therapies for treating type 1 diabetes |
| JP2010540681A (ja) * | 2007-10-08 | 2010-12-24 | クインテッセンス バイオサイエンシズ,インコーポレーテッド | リボヌクレアーゼに基づく治療のための組成物及び方法 |
| CN101835496B (zh) | 2007-10-23 | 2015-11-25 | 尼克塔治疗公司 | 靶向羟基磷灰石的多臂聚合物以及由其制造的偶联物 |
| CA2703830A1 (en) * | 2007-11-20 | 2009-05-28 | Ambrx, Inc. | Modified insulin polypeptides and their uses |
| US20110124841A1 (en) * | 2007-12-13 | 2011-05-26 | Monthony James F | Polypeptides Modified by Protein Trans-Splicing Technology |
| EP2245456B1 (en) | 2007-12-27 | 2013-02-13 | Baxter International Inc. | Method and compositions for specifically detecting physiologically acceptable polymer molecules |
| EP2242505A4 (en) * | 2008-01-08 | 2012-03-07 | Biogenerix Ag | GLYCOCONJUGATION OF POLYPEPTIDES USING OLIGOSACCHARYLTRANSFERASES |
| US20100316702A1 (en) * | 2008-01-08 | 2010-12-16 | The Regents Of The University Of California | Compositions and methods for regulating erythropoeitin expression and ameliorating anemia and stimulating erythropoiesis |
| WO2009091994A2 (en) | 2008-01-18 | 2009-07-23 | Biomarin Pharmaceutical Inc. | Manufacture of active highly phosphorylated human lysosomal sulfatase enzymes and uses thereof |
| US20090183503A1 (en) * | 2008-01-18 | 2009-07-23 | Alberto Verdesi | Exhaust apparatus |
| EP2247743B1 (en) | 2008-02-08 | 2016-04-06 | Ambrx, Inc. | Modified leptin polypeptides and their uses |
| EP2248832B1 (en) | 2008-02-18 | 2014-09-03 | Jiangsu Hengrui Medicine Co., Ltd. | A g-csf conjugate modified by water-soluble polymer |
| WO2009108806A1 (en) | 2008-02-27 | 2009-09-03 | Novo Nordisk A/S | Conjugated factor viii molecules |
| TWI395593B (zh) | 2008-03-06 | 2013-05-11 | Halozyme Inc | 可活化的基質降解酵素之活體內暫時性控制 |
| ES2375606T3 (es) * | 2008-04-03 | 2012-03-02 | F. Hoffmann-La Roche Ag | Ensayo de factor de crecimiento tipo insulina pegilado. |
| CA2720306C (en) | 2008-04-03 | 2016-03-15 | Biosteed Gene Expression Tech. Co., Ltd. | Double-stranded polyethylene glycol modified growth hormone, preparation method and application thereof |
| KR20100135291A (ko) | 2008-04-14 | 2010-12-24 | 할로자임, 아이엔씨 | 히알루로난 관련 질환 및 상태 치료용 변형된 히알루로니다제 및 그 용도 |
| TWI394580B (zh) | 2008-04-28 | 2013-05-01 | Halozyme Inc | 超快起作用胰島素組成物 |
| ES2552646T3 (es) | 2008-05-21 | 2015-12-01 | Amylin Pharmaceuticals, Inc. | Exendinas para disminuir el colesterol y los triglicéridos |
| CN102099373A (zh) | 2008-05-22 | 2011-06-15 | 百时美施贵宝公司 | 基于纤连蛋白的多价支架结构域蛋白 |
| JOP20190083A1 (ar) | 2008-06-04 | 2017-06-16 | Amgen Inc | بولي ببتيدات اندماجية طافرة لـfgf21 واستخداماتها |
| GB0811743D0 (en) | 2008-06-26 | 2008-07-30 | Hemosol Biopharma Inc | Composition |
| WO2009158432A2 (en) | 2008-06-27 | 2009-12-30 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| WO2010011735A2 (en) | 2008-07-23 | 2010-01-28 | Ambrx, Inc. | Modified bovine g-csf polypeptides and their uses |
| ES2617657T3 (es) * | 2008-07-30 | 2017-06-19 | Takeda Pharmaceutical Company Limited | Derivado de metastina y uso del mismo |
| CN102131844B (zh) * | 2008-07-31 | 2016-03-02 | 药华医药股份有限公司 | 肽-聚合物缀合物 |
| WO2010019233A1 (en) | 2008-08-11 | 2010-02-18 | Nektar Therapeutics | Multi-arm polymeric alkanoate conjugates |
| WO2010030366A2 (en) * | 2008-09-11 | 2010-03-18 | Nektar Therapeutics | Polymeric alpha-hydroxy aldehyde and ketone reagents and conjugation method |
| MX346001B (es) | 2008-09-26 | 2017-03-01 | Ambrx Inc | Polipeptidos de eritropoyetina animal modificados y sus usos. |
| CA2738033C (en) | 2008-09-26 | 2019-11-26 | Ambrx, Inc. | Non-natural amino acid replication-dependent microorganisms and vaccines |
| US8029782B2 (en) | 2008-10-01 | 2011-10-04 | Quintessence Biosciences, Inc. | Therapeutic ribonucleases |
| CN102625811B (zh) | 2008-10-10 | 2016-09-21 | 安姆根有限公司 | Fgf21突变体及其用途 |
| WO2010045321A2 (en) | 2008-10-15 | 2010-04-22 | Baxter International Inc. | Pegylation of recombinant blood coagulation factors in the presence of bound antibodies |
| KR101929641B1 (ko) * | 2008-10-17 | 2018-12-14 | 박스알타 인코퍼레이티드 | 낮은 수준의 수용성 중합체를 포함하는 개질된 혈액 인자 |
| WO2010089756A2 (en) | 2008-10-20 | 2010-08-12 | Usv Limited | An improved process for pegylation of proteins |
| WO2010048184A2 (en) | 2008-10-21 | 2010-04-29 | Baxter International Inc. | Methods for determining active ingredients in pro-drug peg protein conjugates with releasable peg reagents (in vitro de-pegylation) |
| WO2010051335A1 (en) * | 2008-10-31 | 2010-05-06 | Amgen Inc. | Materials and methods relating to stem cell mobilization by multi-pegylated granulocyte colony stimulating factor |
| IT1392655B1 (it) | 2008-11-20 | 2012-03-16 | Bio Ker S R L | Site-specific monoconjugated insulinotropic glp-1 peptides. |
| TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之egfr/igfir結合分子 |
| JP5670913B2 (ja) | 2008-12-09 | 2015-02-18 | ハロザイム インコーポレイテッド | 延長された可溶性ph20ポリペプチドおよびその使用 |
| ES2430335T3 (es) | 2008-12-11 | 2013-11-20 | Baxter International Inc. | Detección de moléculas poliméricas fisiológicamente aceptables utilizando espectroscopia infrarroja cercana |
| HUE037936T2 (hu) | 2008-12-17 | 2018-09-28 | Merck Sharp & Dohme | Mono- és di-pegil IL-10 elõállítása és alkalmazása |
| US9636384B2 (en) | 2009-04-06 | 2017-05-02 | Mayo Foundation For Medical Education And Research | Methods for making polymeric nanoparticle-polypeptide complex |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| FI3248610T3 (fi) | 2009-05-05 | 2024-01-18 | Amgen Inc | Fgf21-mutantit ja niiden käyttö |
| MX2011011815A (es) | 2009-05-05 | 2012-01-27 | Amgen Inc | Mutantes fgf21 y usos de los mismos. |
| PL3175863T3 (pl) | 2009-05-20 | 2022-03-21 | Biomarin Pharmaceutical Inc. | Warianty peptydu natriuretycznego typu C |
| MX2011013903A (es) | 2009-06-17 | 2012-05-08 | Amgen Inc | Polipeptidos quimericos y usos de los mismos. |
| US20120237496A1 (en) | 2009-06-19 | 2012-09-20 | Joerg Birkenfeld | Protease variants |
| US9377454B2 (en) | 2009-06-25 | 2016-06-28 | Crealta Pharmaceuticals Llc | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy |
| US20110027229A1 (en) | 2009-07-31 | 2011-02-03 | Medtronic, Inc. | Continuous subcutaneous administration of interferon-alpha to hepatitis c infected patients |
| PT2477603E (pt) | 2009-09-17 | 2016-06-16 | Baxalta Inc | Co-formulação estável de hialuronidase e imunoglobulina e métodos para a sua utilização |
| US20120178914A1 (en) * | 2009-09-25 | 2012-07-12 | Vybion, Inc. | Polypeptide modification |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| CA2772945A1 (en) | 2009-09-25 | 2011-03-31 | Xoma Technology Ltd. | Screening methods |
| EP2494073B1 (de) | 2009-10-26 | 2017-11-29 | AGCT GmbH | Konjugate von nukleotiden und methoden zu deren anwendung |
| EA201200650A1 (ru) | 2009-10-30 | 2012-12-28 | Бёрингер Ингельхайм Интернациональ Гмбх | Курсы комбинированного лечения вируса гепатита с, включающие bi201335, интерферон-альфа и рибавирин |
| AU2010313456A1 (en) | 2009-10-30 | 2012-05-17 | Ntf Therapeutics, Inc. | Improved neurturin molecules |
| US20140066370A1 (en) | 2009-11-23 | 2014-03-06 | Amylin Pharmaceuticals, Llc | Polypeptide Conjugate |
| EP3778917A3 (en) | 2009-12-04 | 2021-06-09 | F. Hoffmann-La Roche AG | Multispecific antibodies, antibody analogs, compositions, and methods |
| UA109888C2 (uk) | 2009-12-07 | 2015-10-26 | ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ | |
| WO2011087808A1 (en) | 2009-12-21 | 2011-07-21 | Ambrx, Inc. | Modified bovine somatotropin polypeptides and their uses |
| CN107056929A (zh) | 2009-12-21 | 2017-08-18 | Ambrx 公司 | 经过修饰的猪促生长素多肽和其用途 |
| US20110152188A1 (en) * | 2009-12-23 | 2011-06-23 | Hanns-Christian Mahler | Pharmaceutical compositions of igf/i proteins |
| US20130040888A1 (en) | 2010-02-16 | 2013-02-14 | Novo Nordisk A/S | Factor VIII Molecules With Reduced VWF Binding |
| RU2573909C2 (ru) * | 2010-03-04 | 2016-01-27 | Пфенекс Инк. | Способ получения растворимого рекомбинантного белка интерферона без денатурирования |
| AU2011235210B2 (en) | 2010-04-01 | 2015-07-16 | Pfenex Inc. | Methods for G-CSF production in a Pseudomonas host cell |
| AU2011239689A1 (en) | 2010-04-15 | 2012-11-08 | Amgen Inc. | Human FGF receptor and beta-Klotho binding proteins |
| CN103118692A (zh) | 2010-04-26 | 2013-05-22 | Atyr医药公司 | 与半胱氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
| JP6294074B2 (ja) | 2010-04-27 | 2018-03-14 | エータイアー ファーマ, インコーポレイテッド | イソロイシルtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| US8993723B2 (en) | 2010-04-28 | 2015-03-31 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl-tRNA synthetases |
| CA2797374C (en) | 2010-04-29 | 2021-02-16 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of asparaginyl trna synthetases |
| US9034320B2 (en) | 2010-04-29 | 2015-05-19 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Valyl-tRNA synthetases |
| CN102234310B (zh) * | 2010-04-30 | 2017-02-08 | 杭州九源基因工程有限公司 | 一种聚乙二醇修饰蛋白的分离纯化方法 |
| JP6008840B2 (ja) | 2010-05-03 | 2016-10-19 | エータイアー ファーマ, インコーポレイテッド | フェニルアラニルαtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| US8961961B2 (en) | 2010-05-03 | 2015-02-24 | a Tyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related protein fragments of arginyl-tRNA synthetases |
| AU2011248230B2 (en) | 2010-05-03 | 2016-10-06 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of methionyl-tRNA synthetases |
| CN102985103A (zh) | 2010-05-04 | 2013-03-20 | Atyr医药公司 | 与p38多-tRNA合成酶复合物相关的治疗、诊断和抗体组合物的创新发现 |
| US20120135912A1 (en) | 2010-05-10 | 2012-05-31 | Perseid Therapeutics Llc | Polypeptide inhibitors of vla4 |
| JP6396656B2 (ja) | 2010-05-14 | 2018-09-26 | エータイアー ファーマ, インコーポレイテッド | フェニルアラニルβtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| JP6027965B2 (ja) | 2010-05-17 | 2016-11-16 | エータイアー ファーマ, インコーポレイテッド | ロイシルtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| MX2012013375A (es) | 2010-05-17 | 2013-04-11 | Cebix Inc | Peptido c pegilado. |
| EP3091028A1 (en) | 2010-05-26 | 2016-11-09 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
| EP2575856B1 (en) | 2010-05-27 | 2017-08-16 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-trna synthetases |
| WO2011153277A2 (en) | 2010-06-01 | 2011-12-08 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of lysyl-trna synthetases |
| CN102711871A (zh) | 2010-06-16 | 2012-10-03 | 麦德托尼克公司 | 用于稳定药物递送装置中的药物的阻尼系统 |
| CA2803093A1 (en) | 2010-06-24 | 2011-12-29 | Panmed Ltd. | Treatment of hepatitis c virus related diseases using hydroxychloroquine or a combination of hydroxychloroquine and an anti-viral agent |
| AU2011289831C1 (en) | 2010-07-12 | 2017-06-15 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-tRNA synthetases |
| US20130183280A1 (en) | 2010-07-15 | 2013-07-18 | Novo Nordisk A/S | Stabilized factor viii variants |
| ES2661089T3 (es) | 2010-07-20 | 2018-03-27 | Halozyme Inc. | Métodos de tratamiento o prevención de los efectos secundarios adversos asociados con la administración de un agente anti-hialuronano |
| AR082319A1 (es) | 2010-07-22 | 2012-11-28 | Biomarin Pharm Inc | Produccion de una n-acetilgalactosamina-6-sulfatasa humana activa altamente fosforilada y sus usos |
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| RU2446173C1 (ru) * | 2010-08-13 | 2012-03-27 | Зао "Биокад" | Новый функционально активный, высокоочищенный стабильный конъюгат гранулоцитарного колониестимулирующего фактора (г-ксф) с полиэтиленгликолем с пролонгированным биологическим действием, пригодный для медицинского применения, и иммунобиологическое средство на его основе |
| AU2011291943B2 (en) | 2010-08-17 | 2015-01-22 | Ambrx, Inc. | Modified relaxin polypeptides and their uses |
| US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
| JP5964304B2 (ja) | 2010-08-25 | 2016-08-03 | エータイアー ファーマ, インコーポレイテッド | チロシルtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| CN103209992A (zh) | 2010-09-15 | 2013-07-17 | 诺沃—诺迪斯克有限公司 | 具有减少的细胞摄取的因子viii变体 |
| 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 |
| EP3241558B1 (en) | 2010-09-28 | 2021-03-03 | Aegerion Pharmaceuticals, Inc. | Highly soluble leptins |
| AU2011311706B2 (en) | 2010-10-05 | 2015-11-12 | Debiopharm S.A. | New treatments of Hepatitis C virus infection |
| BR112013008510A2 (pt) | 2010-10-08 | 2016-07-05 | Novartis Ag | vitamina e formulações de inibidores de sulfamida ns3 |
| CN102453089B (zh) * | 2010-10-25 | 2014-06-04 | 北京凯因科技股份有限公司 | 重组集成干扰素变异体聚乙二醇偶联物的制备和应用 |
| CN103933577B (zh) * | 2010-10-25 | 2014-12-10 | 北京凯因科技股份有限公司 | 重组集成干扰素变异体聚乙二醇偶联物的制备和应用 |
| US9023791B2 (en) | 2010-11-19 | 2015-05-05 | Novartis Ag | Fibroblast growth factor 21 mutations |
| RU2013123793A (ru) | 2010-11-24 | 2014-12-27 | Лексикон Фармасьютикалз, Инк. | Антитела, связывающиеся с notum пектинацетилэстеразой |
| CA2818067A1 (en) | 2010-11-30 | 2012-06-07 | Novartis Ag | New treatments of hepatitis c virus infection |
| CN102485742A (zh) * | 2010-12-02 | 2012-06-06 | 山东新时代药业有限公司 | 一种聚乙二醇单修饰的重组人粒细胞集落刺激因子的制备及分离纯化方法 |
| US20140371258A1 (en) | 2010-12-17 | 2014-12-18 | Nektar Therapeutics | Water-Soluble Polymer Conjugates of Topotecan |
| JP5899241B2 (ja) | 2010-12-21 | 2016-04-06 | ネクター セラピューティクス | ペメトレキセドベースの化合物のマルチアームポリマープロドラッグコンジュゲート |
| WO2012088422A1 (en) | 2010-12-22 | 2012-06-28 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of taxane-based compounds |
| WO2012088445A1 (en) | 2010-12-22 | 2012-06-28 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of cabazitaxel-based compounds |
| EP2907504B1 (en) | 2011-02-08 | 2017-06-28 | Halozyme, Inc. | Composition and lipid formulation of a hyaluronan-degrading enzyme and the use thereof for treatment of benign prostatic hyperplasia |
| AP2013007173A0 (en) | 2011-03-16 | 2013-10-31 | Amgen Inc | Potent and selective inhibitors of NAV1.3 and NAV1.7 |
| JP2014509646A (ja) * | 2011-03-25 | 2014-04-21 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | ペグ化ヒトhdl粒子およびその製造方法 |
| MX2013011256A (es) | 2011-03-31 | 2013-10-17 | Novartis Ag | Alisporivir para el tratamiento de la infeccion por el virus de hepatitis c. |
| KR20140010097A (ko) | 2011-04-01 | 2014-01-23 | 노파르티스 아게 | B형 간염 바이러스 단독 감염 또는 델타 간염 바이러스와의 조합 감염 및 연관된 간 질환의 치료 |
| JP2014510772A (ja) | 2011-04-13 | 2014-05-01 | ノバルティス アーゲー | アリスポリビルを用いたc型肝炎ウイルス感染症の治療 |
| WO2012158678A1 (en) | 2011-05-17 | 2012-11-22 | Bristol-Myers Squibb Company | Methods for maintaining pegylation of polypeptides |
| KR102148982B1 (ko) | 2011-06-03 | 2020-08-27 | 조마 테크놀로지 리미티드 | Tgf-베타에 특이적인 항체 |
| US20130011378A1 (en) | 2011-06-17 | 2013-01-10 | Tzung-Horng Yang | Stable formulations of a hyaluronan-degrading enzyme |
| EA201400030A1 (ru) | 2011-06-17 | 2014-07-30 | Галозим, Инк. | Способ непрерывного подкожного введения инсулина с использованием фермента, разрушающего хиалуронан |
| RU2654231C2 (ru) | 2011-06-28 | 2018-05-17 | Алтернатив Инновейтив Текнолоджиз, Ллц | Способ применения белков теплового шока-70 (бтш70) для повышения выносливости и лечения бтш70-зависимых заболеваний (варианты) |
| MX2014000031A (es) | 2011-07-01 | 2014-07-09 | Bayer Ip Gmbh | Polipeptidos de fusion de relaxina y usos de los mismos. |
| PT2717917T (pt) | 2011-07-05 | 2016-07-27 | Bioasis Technologies Inc | Conjugados de anticorpos p97 |
| PT2729160T (pt) | 2011-07-08 | 2019-07-08 | Aegerion Pharmaceuticals Inc | Polipéptidos modificados com uma maior duração da ação e uma imunogenicidade reduzida |
| CN102952067A (zh) * | 2011-08-30 | 2013-03-06 | 苏州欣诺科生物科技有限公司 | 用于蛋白质n端聚乙二醇修饰的吡哆醛衍生物、制备方法及其应用 |
| AU2012301769B2 (en) | 2011-08-31 | 2016-05-19 | Amgen Inc. | FGF21 for use in treating type 1 diabetes |
| US20130071394A1 (en) | 2011-09-16 | 2013-03-21 | John K. Troyer | Compositions and combinations of organophosphorus bioscavengers and hyaluronan-degrading enzymes, and methods of use |
| TWI593708B (zh) | 2011-09-26 | 2017-08-01 | 諾華公司 | 治療代謝病症之融合蛋白質 |
| US9458214B2 (en) | 2011-09-26 | 2016-10-04 | Novartis Ag | Dual function fibroblast growth factor 21 proteins |
| EP2760461A1 (en) | 2011-09-27 | 2014-08-06 | Novartis AG | Alisporivr for treatment of hepatis c virus infection |
| RU2014114849A (ru) | 2011-10-14 | 2015-11-20 | Алтернатив Инновейтив Текнолоджиз Ллц | Устойчивые к деградации производные белков теплового шока-70 (бтш70) и способы их применения (варианты) |
| EA030440B1 (ru) | 2011-10-24 | 2018-08-31 | Галозим, Инк. | Сопровождающая диагностика для терапии антигиалуронановым агентом и способы ее применения |
| EP2771297B1 (en) | 2011-10-25 | 2017-12-13 | Corning Incorporated | Delamination resistant pharmaceuticals glass containers containing active pharmaceutical ingredients |
| US10350139B2 (en) | 2011-10-25 | 2019-07-16 | Corning Incorporated | Pharmaceutical glass packaging assuring pharmaceutical sterility |
| JP2015504038A (ja) | 2011-10-31 | 2015-02-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 低減した免疫原性を有するフィブロネクチン結合ドメイン |
| CN104220086A (zh) | 2011-11-17 | 2014-12-17 | 塞比克斯股份公司 | Peg化的c-肽 |
| RU2685867C2 (ru) | 2011-12-15 | 2019-04-23 | Алтернатив Инновейтив Текнолоджиз Ллц | Гибридные белки и белковые конъюгаты на основе белка теплового шока-70 (БТШ70) и способы их применения (варианты) |
| BR112014016195A2 (pt) | 2011-12-30 | 2020-10-27 | Halozyme, Inc. | variantes de polipeptídio ph20, formulações e usos das mesmas |
| DK2809350T3 (en) | 2012-01-30 | 2019-01-28 | Arecor Ltd | STABILIZED Aqueous Antibody Preparations |
| US8835387B2 (en) | 2012-02-16 | 2014-09-16 | Atyr Pharma, Inc. | Histidyl-tRNA synthetases for treating autoimmune and inflammatory diseases |
| SG10201700340WA (en) | 2012-02-27 | 2017-03-30 | Amunix Operating Inc | Xten conjugate compositions and methods of making same |
| AU2013226944B2 (en) | 2012-02-29 | 2017-03-23 | Toray Industries, Inc. | Inhibitory agent for body cavity fluid accumulation |
| AU2013230484B2 (en) | 2012-03-03 | 2017-04-27 | Immungene, Inc. | Engineered antibody-interferon mutant fusion molecules |
| JP2015509980A (ja) | 2012-03-14 | 2015-04-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Hcv−hiv同時感染患者集団のhcv感染症を治療するための併用療法 |
| WO2013143581A1 (en) | 2012-03-28 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Combination therapy for treating hcv infection in specific patient subgenotype sub-population |
| HK1206610A1 (en) | 2012-03-30 | 2016-01-15 | Sorrento Therapeutics, Inc. | Fully human antibodies that bind to vegfr2 |
| EA031986B1 (ru) | 2012-04-04 | 2019-03-29 | Галозим, Инк. | Способ и комбинация для лечения солидной раковой опухоли и набор, содержащий комбинацию |
| KR102163408B1 (ko) | 2012-05-31 | 2020-10-08 | 소렌토 쎄라퓨틱스, 인코포레이티드 | Pd-l1에 결합하는 항원 결합 단백질 |
| JP6498600B2 (ja) | 2012-06-08 | 2019-04-10 | ストロ バイオファーマ インコーポレーテッド | 部位特異的な非天然アミノ酸残基を含む抗体、その調製方法、及びその使用方法 |
| HK1208236A1 (en) | 2012-06-22 | 2016-02-26 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind ccr2 |
| US9732161B2 (en) | 2012-06-26 | 2017-08-15 | Sutro Biopharma, Inc. | Modified Fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use |
| WO2014022515A1 (en) | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| EP2890402B1 (en) | 2012-08-31 | 2019-04-17 | Sutro Biopharma, Inc. | Modified amino acids comprising an azido group |
| US9278124B2 (en) | 2012-10-16 | 2016-03-08 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| KR20150083121A (ko) | 2012-11-12 | 2015-07-16 | 레드우드 바이오사이언스 인코포레이티드 | 화합물, 및 컨쥬게이트의 제조방법 |
| US9310374B2 (en) | 2012-11-16 | 2016-04-12 | Redwood Bioscience, Inc. | Hydrazinyl-indole compounds and methods for producing a conjugate |
| JP2016505528A (ja) | 2012-11-16 | 2016-02-25 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | タンパク質の化学修飾のためのピクテ−スペングラーライゲーション |
| US20140205566A1 (en) | 2012-11-30 | 2014-07-24 | Novartis Ag | Cyclic nucleuoside derivatives and uses thereof |
| US9383357B2 (en) | 2012-12-07 | 2016-07-05 | Northwestern University | Biomarker for replicative senescence |
| JP6426107B2 (ja) | 2012-12-20 | 2018-11-21 | アムジエン・インコーポレーテツド | Apj受容体アゴニストおよびその使用 |
| CN103908660B (zh) * | 2013-01-05 | 2015-02-04 | 石药集团百克(山东)生物制药有限公司 | 一种聚乙二醇修饰的rhG-CSF药物组合物及其制备方法 |
| EP2951206A2 (en) | 2013-02-01 | 2015-12-09 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins |
| CN103113466B (zh) * | 2013-03-01 | 2015-06-03 | 中国科学院过程工程研究所 | 聚乙二醇修饰的重组人干扰素β-1b及制备方法 |
| UY35397A (es) | 2013-03-12 | 2014-10-31 | Amgen Inc | INHIBIDORES POTENTES Y SELECTIVOS DE NaV1.7 |
| ES2774549T3 (es) | 2013-03-13 | 2020-07-21 | Bioasis Technologies Inc | Fragmentos de P97 y usos de los mismos |
| RU2535002C2 (ru) * | 2013-04-04 | 2014-12-10 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт фармакологии" Сибирского отделения Российской академии медицинских наук | Средство коррекции отдаленных последствий нарушений сперматогенеза, вызванных цитостатическим воздействием |
| HK1215681A1 (zh) | 2013-04-18 | 2016-09-09 | Armo Biosciences, Inc. | 使用白细胞介素-10治疗疾病和病症的方法 |
| US9707155B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9717649B2 (en) | 2013-04-24 | 2017-08-01 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9717648B2 (en) | 2013-04-24 | 2017-08-01 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9603775B2 (en) | 2013-04-24 | 2017-03-28 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9839579B2 (en) | 2013-04-24 | 2017-12-12 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9700485B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9700486B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9707153B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9713572B2 (en) | 2013-04-24 | 2017-07-25 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9849066B2 (en) | 2013-04-24 | 2017-12-26 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9707154B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| EP3010527B1 (en) | 2013-06-17 | 2018-08-08 | Armo Biosciences, Inc. | Method for assessing protein identity and stability |
| TW201534726A (zh) | 2013-07-03 | 2015-09-16 | Halozyme Inc | 熱穩定ph20玻尿酸酶變異體及其用途 |
| ES2658039T3 (es) | 2013-07-10 | 2018-03-08 | Sutro Biopharma, Inc. | Anticuerpos que comprenden múltiples residuos de aminoácidos no naturales sitio-específicos, métodos para su preparación y métodos de uso |
| AU2014312190A1 (en) | 2013-08-28 | 2016-02-18 | Bioasis Technologies Inc. | CNS-targeted conjugates of antibodies |
| CA2920679A1 (en) | 2013-08-30 | 2015-03-05 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| AU2014330853A1 (en) | 2013-10-02 | 2016-02-25 | National Institutes Of Health | Insulin-like growth factor mimetics for use in therapy |
| 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 |
| US20160235810A1 (en) | 2013-10-18 | 2016-08-18 | Novartis Ag | Methods of treating diabetes and related disorders |
| EP3068425B1 (en) | 2013-11-11 | 2021-01-27 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| US20160296632A1 (en) | 2013-11-13 | 2016-10-13 | Aequus Biopharma, Inc. | Engineered glycoproteins and uses thereof |
| KR102320019B1 (ko) | 2013-11-27 | 2021-11-01 | 레드우드 바이오사이언스 인코포레이티드 | 히드라지닐-피롤로 화합물 및 콘쥬게이트 제조 방법 |
| UY35874A (es) | 2013-12-12 | 2015-07-31 | Novartis Ag | Un proceso para la preparación de una composición de proteínas pegiladas |
| WO2015130963A2 (en) | 2014-02-27 | 2015-09-03 | Xenetic Biosciences, Inc. | Compositions and methods for administering insulin or insulin-like protein to the brain |
| CN106573072A (zh) | 2014-06-02 | 2017-04-19 | 阿尔莫生物科技股份有限公司 | 降低血清胆固醇的方法 |
| JP6803236B2 (ja) | 2014-06-10 | 2020-12-23 | アムジェン インコーポレイテッド | アペリンポリペプチド |
| HUE055931T2 (hu) | 2014-06-12 | 2022-01-28 | Ra Pharmaceuticals Inc | A komplementaktivitás modulálása |
| MA40526A (fr) | 2014-08-22 | 2017-06-28 | Sorrento Therapeutics Inc | Protéines de fixation antigénique fixant le cxcr3 |
| TR201907471T4 (tr) | 2014-08-28 | 2019-06-21 | Halozyme Inc | Bir hiyalüronan ayrıştırıcı enzim ve bir bağışıklık kontrol noktası inhibitörüyle kombinasyon terapisi. |
| WO2016061286A2 (en) | 2014-10-14 | 2016-04-21 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
| CN107001438A (zh) | 2014-10-14 | 2017-08-01 | 阿尔莫生物科技股份有限公司 | 白细胞介素‑15组合物及其用途 |
| KR20170084033A (ko) | 2014-10-22 | 2017-07-19 | 아르모 바이오사이언시스 인코포레이티드 | 질환 및 장애를 치료하기 위해 인터루킨-10을 사용하는 방법 |
| EA036697B1 (ru) | 2014-10-24 | 2020-12-09 | Бристол-Майерс Сквибб Компани | Модифицированные полипептиды fgf-21 и их применение |
| FI3215193T3 (fi) | 2014-11-06 | 2023-12-28 | Pharmaessentia Corp | Pegyloidun interferonin annostusohjelma |
| US10046058B2 (en) * | 2014-12-02 | 2018-08-14 | Rezolute, Inc. | Use of hydrophobic organic acids to increase hydrophobicity of proteins and protein conjugates |
| CN104491843B (zh) * | 2015-01-23 | 2017-09-12 | 石药集团百克(山东)生物制药有限公司 | 一种聚乙二醇修饰的rhG‑CSF活性药物组合物 |
| PL3250230T3 (pl) | 2015-01-28 | 2022-02-14 | Ra Pharmaceuticals, Inc. | Modulatory aktywności dopełniacza |
| US10618970B2 (en) | 2015-02-03 | 2020-04-14 | Armo Biosciences, Inc. | Method of treating cancer with IL-10 and antibodies that induce ADCC |
| WO2016140983A1 (en) * | 2015-03-03 | 2016-09-09 | Avalon Biologics Limited | Compositions and methods for pegylated il-11 |
| EP3265491A1 (en) | 2015-03-03 | 2018-01-10 | Xoma (Us) Llc | Treatment of post-prandial hyperinsulinemia and hypoglycemia after bariatric surgery |
| CN108136001B (zh) | 2015-04-03 | 2022-07-29 | 佐马技术有限公司 | 使用TGF-β抑制剂和PD-1抑制剂治疗癌症 |
| US20180118799A1 (en) | 2015-04-13 | 2018-05-03 | National Institute Of Advanced Industrial Science And Technology | Cyclized cytokine and method for producing same |
| JP7245649B2 (ja) | 2015-05-01 | 2023-03-24 | アリスタ ファーマスーティカルス インク. | 眼疾患を治療するためのアディポネクチンペプチド模倣薬(関連出願の相互参照) |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| CA2986755A1 (en) | 2015-05-28 | 2016-12-01 | Armo Biosciences, Inc. | Pegylated interleukin-10 for use in treating cancer |
| HK1255271A1 (zh) | 2015-08-06 | 2019-08-09 | Xoma (Us) Llc | 针对胰岛素受体的抗体片段和其治疗低血糖的用途 |
| ES3039640T3 (en) | 2015-08-25 | 2025-10-23 | Armo Biosciences Inc | Methods of using interleukin-10 for treating diseases and disorders |
| AU2016324119B2 (en) * | 2015-09-18 | 2019-11-14 | Himuka AM Australia Pty Ltd. | Long-acting adrenomedullin derivative |
| AU2016332062A1 (en) | 2015-10-01 | 2018-04-26 | Amgen Inc. | Treatment of bile acid disorders |
| US10935276B2 (en) | 2015-10-20 | 2021-03-02 | Steven Michalski | Air mixing device |
| AU2016354009B2 (en) | 2015-11-09 | 2021-05-20 | R.P. Scherer Technologies, Llc | Anti-CD22 antibody-maytansine conjugates and methods of use thereof |
| CN108697766A (zh) | 2015-12-08 | 2018-10-23 | 生物马林药物股份有限公司 | C型钠尿肽变体在治疗骨关节炎中的用途 |
| ES2781551T3 (es) | 2015-12-16 | 2020-09-03 | Ra Pharmaceuticals Inc | Moduladores de la actividad del complemento |
| IL259658B2 (en) | 2016-01-08 | 2024-06-01 | Ascendis Pharma Growth Disorders As | Controlled-release cnp agonists with reduced side-effects |
| CN116333124A (zh) | 2016-01-29 | 2023-06-27 | 索伦托药业有限公司 | 与pd-l1结合的抗原结合蛋白 |
| KR102438354B1 (ko) | 2016-04-15 | 2022-08-31 | 베크만 컬터, 인코포레이티드 | 광활성 거대분자 및 그의 용도 |
| JP7148493B2 (ja) | 2016-08-01 | 2022-10-05 | ゾーマ (ユーエス) リミテッド ライアビリティ カンパニー | 副甲状腺ホルモン受容体1(pth1r)抗体およびその使用 |
| AU2017335771A1 (en) | 2016-09-28 | 2019-02-28 | Musc Foundation For Research Development | Antibodies that bind interleukin-2 and uses thereof |
| 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 |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| AU2017370692A1 (en) | 2016-12-07 | 2019-06-06 | Ra Pharmaceuticals, Inc. | Modulators of complement activity |
| US10533092B2 (en) | 2016-12-12 | 2020-01-14 | Becton, Dickinson And Company | Water-soluble polymeric dyes |
| KR102670432B1 (ko) | 2017-02-08 | 2024-05-28 | 브리스톨-마이어스 스큅 컴퍼니 | 약동학적 인핸서를 포함하는 변형된 렐락신 폴리펩티드 및 그의 용도 |
| KR102675270B1 (ko) | 2017-06-22 | 2024-06-17 | 버텍스 파마슈티칼스 인코포레이티드 | 변형된 막 유형 세린 프로테아제 1(mtsp-1) 폴리펩티드 및 사용 방법 |
| KR102020995B1 (ko) | 2017-10-30 | 2019-09-16 | 한국코러스 주식회사 | 콜로니자극인자와 폴리올이 접합된 접합물을 고수율로 제조하는 방법 |
| US11492493B2 (en) | 2017-12-26 | 2022-11-08 | Becton, Dickinson And Company | Deep ultraviolet-excitable water-solvated polymeric dyes |
| WO2019130344A1 (en) | 2017-12-27 | 2019-07-04 | Council Of Scientific And Industrial Research | A polypeptide exhibiting granulocyte-colony stimulating factor activity |
| JP2021517143A (ja) * | 2018-03-14 | 2021-07-15 | バ、ヨン | Peg化不凍タンパク質およびそれを作製する方法およびそれを使用する方法 |
| CN119220109A (zh) | 2018-03-30 | 2024-12-31 | 贝克顿·迪金森公司 | 含侧基发色团的水溶性聚合染料 |
| SG11202010430QA (en) | 2018-04-24 | 2020-11-27 | Amgen Inc | Method for making injectable pharmaceutical compositions |
| US20190351031A1 (en) | 2018-05-16 | 2019-11-21 | Halozyme, Inc. | Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20 |
| KR102167755B1 (ko) | 2018-05-23 | 2020-10-19 | 주식회사 큐어바이오 | 단편화된 grs 폴리펩타이드, 이의 변이체 및 이들의 용도 |
| EP3813867A1 (en) | 2018-07-22 | 2021-05-05 | Bioasis Technologies Inc. | Treatment of lymmphatic metastases |
| MX2021002575A (es) | 2018-09-11 | 2021-06-08 | Ambrx Inc | Conjugados de polipeptidos de interleucina-2 y sus usos. |
| WO2020082057A1 (en) | 2018-10-19 | 2020-04-23 | Ambrx, Inc. | Interleukin-10 polypeptide conjugates, dimers thereof, and their uses |
| JP7604376B2 (ja) | 2018-12-28 | 2024-12-23 | バーテックス ファーマシューティカルズ インコーポレイテッド | 改変ウロキナーゼ型プラスミノゲンアクティベータポリペプチドおよび使用方法 |
| US11613744B2 (en) | 2018-12-28 | 2023-03-28 | Vertex Pharmaceuticals Incorporated | Modified urokinase-type plasminogen activator polypeptides and methods of use |
| US12121566B2 (en) | 2019-01-30 | 2024-10-22 | Horizon Therapeutics Usa, Inc. | Methods for treating gout |
| KR20210136014A (ko) | 2019-02-12 | 2021-11-16 | 암브룩스, 인코포레이티드 | 항체-tlr 작용제 콘쥬게이트를 함유하는 조성물, 방법 및 이의 용도 |
| US10882954B2 (en) | 2019-04-11 | 2021-01-05 | Sunbio Inc. | Tertiary alkoxy polyethylene glycol and derivatives thereof |
| EP3955957A1 (en) | 2019-04-15 | 2022-02-23 | Qwixel Therapeutics LLC | Fusion protein composition(s) comprising targeted masked type i interferons (ifna and ifnb) and an antibody against tumor antigen, for use in the treatment of cancer |
| EP3955965A1 (en) | 2019-04-15 | 2022-02-23 | NOF Corporation | Conjugate of bio-related substance and block polymer, and block polymer derivative for obtaining said conjugate |
| 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 |
| AU2021240088A1 (en) | 2020-03-20 | 2022-10-06 | Amgen Inc. | Determination of free N-terminus of PEGFilgrastim using an acid protease |
| US20210355468A1 (en) | 2020-05-18 | 2021-11-18 | Bioasis Technologies, Inc. | Compositions and methods for treating lewy body dementia |
| US20210393787A1 (en) | 2020-06-17 | 2021-12-23 | Bioasis Technologies, Inc. | Compositions and methods for treating frontotemporal dementia |
| KR20230073200A (ko) | 2020-08-20 | 2023-05-25 | 암브룩스, 인코포레이티드 | 항체-tlr 작용제 접합체, 그 방법 및 용도 |
| US11602598B1 (en) | 2020-08-27 | 2023-03-14 | Fresenius Kabi Deutschland Gmbh | Prefilled syringe with pegfilgrastim having optimized dose and methods related thereto |
| CN112710826A (zh) * | 2020-11-17 | 2021-04-27 | 北京九强生物技术股份有限公司 | 一种提高试剂稳定性的包被和封闭方法 |
| US11952461B2 (en) | 2021-03-22 | 2024-04-09 | Sunbio, Inc. | Siloxy polyethylene glycol and derivatives thereof |
| KR20240004342A (ko) | 2021-04-03 | 2024-01-11 | 암브룩스, 인코포레이티드 | 항-her2 항체-약물 접합체 및 이의 용도 |
| CN113214328B (zh) * | 2021-05-08 | 2022-06-28 | 宁波经济技术开发区弘翔生化科技有限公司 | 一种双水相体系以及基于双水相体系的单糖分离方法 |
| EP4155349A1 (en) | 2021-09-24 | 2023-03-29 | Becton, Dickinson and Company | Water-soluble yellow green absorbing dyes |
| JP2025522834A (ja) | 2022-07-01 | 2025-07-17 | ベックマン コールター, インコーポレイテッド | ジヒドロフェナントレン誘導体からの新規な蛍光染料およびポリマー |
| WO2024044327A1 (en) | 2022-08-26 | 2024-02-29 | Beckman Coulter, Inc. | Dhnt monomers and polymer dyes with modified photophysical properties |
| EP4680677A1 (en) | 2023-03-17 | 2026-01-21 | Beckman Coulter, Inc. | Benzothienopyrrole cyanine dyes |
| US12269875B2 (en) | 2023-08-03 | 2025-04-08 | Jeff R. Peterson | Gout flare prevention methods using IL-1BETA blockers |
| WO2025064842A1 (en) | 2023-09-21 | 2025-03-27 | Beckman Coulter, Inc. | Dihydrophenanthrene (dhp) bridged dyes for use in flow cytometry |
| WO2025227129A2 (en) | 2024-04-25 | 2025-10-30 | Starrock Pharma Llc | Delivery vehicles comprising proglucagon derived polypeptides and anabolic polypeptides and uses thereof |
| US20250341516A1 (en) | 2024-05-01 | 2025-11-06 | BioLegend, Inc. | Compositions for use with multiple fluorophores and methods of using |
Family Cites Families (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1609546A (en) | 1925-11-19 | 1926-12-07 | Petroleum Rectifying Co | Process of separating water from emulsions |
| DE2047413C3 (de) | 1970-09-26 | 1980-05-29 | F. Hoffmann-La Roche & Co Ag, Basel (Schweiz) | Verfahren zur Herstellung von Peptiden in homogener Phase |
| US4002714A (en) * | 1972-08-14 | 1977-01-11 | Fumio Usui | Method for producing a tapered pipe of reinforced synthetic resin |
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4002531A (en) * | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| DE2930542A1 (de) | 1979-07-27 | 1981-02-12 | Hoechst Ag | Neue insulinderivate und verfahren zu ihrer herstellung |
| JPS57192435A (en) | 1981-05-20 | 1982-11-26 | Toyobo Co Ltd | Modified polypeptide |
| DE3139483C2 (de) | 1981-10-03 | 1985-06-13 | Dr.-Ing. Rudolf Hell Gmbh, 2300 Kiel | Verfahren und Schaltungsanordnung zur Kontraststeigerung |
| US6936694B1 (en) * | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| JPS58225025A (ja) * | 1982-06-24 | 1983-12-27 | Nippon Chem Res Kk | 効力持続性組成物 |
| DE3380726D1 (en) | 1982-06-24 | 1989-11-23 | Japan Chem Res | Long-acting composition |
| WO1985003934A1 (fr) | 1984-03-06 | 1985-09-12 | Takeda Chemical Industries, Ltd. | Proteine modifiee chimiquement et son procede de preparation |
| EP0154316B1 (en) * | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
| JPS61227526A (ja) | 1984-07-25 | 1986-10-09 | Chugai Pharmaceut Co Ltd | 新規なコロニー刺激因子 |
| JPS6142558A (ja) | 1984-08-06 | 1986-03-01 | Matsushita Electric Works Ltd | アミノ樹脂成形材料 |
| ATE65798T1 (de) | 1985-02-08 | 1991-08-15 | Chugai Pharmaceutical Co Ltd | Menschlicher granuloxcyt-koloniestimulierungsfaktor. |
| JPS62129298A (ja) | 1985-12-02 | 1987-06-11 | Chugai Pharmaceut Co Ltd | 新規ポリペプチド |
| US5532341A (en) | 1985-03-28 | 1996-07-02 | Sloan-Kettering Institute For Cancer Research | Human pluripotent hematopoietic colony stimulating factor |
| WO1987000056A1 (en) | 1985-06-26 | 1987-01-15 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| ES8800982A1 (es) | 1985-07-05 | 1987-12-01 | Takeda Chemical Industries Ltd | Un metodo para producir la enzima superoxido-dismutasa modificada con derivados de polietilenglicol y triazina. |
| JPS63500636A (ja) | 1985-08-23 | 1988-03-10 | 麒麟麦酒株式会社 | 多分化能性顆粒球コロニー刺激因子をコードするdna |
| US4810643A (en) * | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| JPH0657152B2 (ja) | 1985-09-17 | 1994-08-03 | 中外製薬株式会社 | Csf遺伝子類 |
| JP2514950B2 (ja) | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質,その製造法および中間体 |
| DK203187A (da) * | 1986-04-22 | 1987-10-23 | Immunex Corp | Human g-csf proteinekspression |
| US6673347B1 (en) | 1986-04-30 | 2004-01-06 | Gryphon Therapeutics | Polypeptide and protein derivatives and process for their preparation |
| CA1283046C (en) | 1986-05-29 | 1991-04-16 | Nandini Katre | Tumor necrosis factor formulation |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| JPS63126900A (ja) | 1986-06-26 | 1988-05-30 | Takeda Chem Ind Ltd | 化学修飾蛋白質 |
| JPS63152393A (ja) | 1986-07-03 | 1988-06-24 | Takeda Chem Ind Ltd | グリコシル誘導体 |
| GR871067B (en) | 1986-07-18 | 1987-11-19 | Chugai Pharmaceutical Co Ltd | Process for producing stable pharmaceutical preparation containing granulocyte colony stimulating factor |
| EP0256843A1 (en) | 1986-08-11 | 1988-02-24 | Cetus Corporation | Expression of g-csf and muteins thereof and their use |
| JPS6360938A (ja) | 1986-09-02 | 1988-03-17 | Meiji Milk Prod Co Ltd | 修飾組織型プラスミノ−ゲン活性化因子およびその製造方法 |
| US4894226A (en) | 1986-11-14 | 1990-01-16 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polyproline conjugation |
| US5362853A (en) | 1986-12-23 | 1994-11-08 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
| US5214132A (en) | 1986-12-23 | 1993-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
| DK174044B1 (da) * | 1986-12-23 | 2002-05-06 | Kyowa Hakko Kogyo Kk | Polypeptid afledt fra human granulocytkolonistimulerende faktor, og fremgangsmåde til fremstilling deraf, DNA kodende for nævnte polypeptid, rekombinant plasmid indeholdende nævnte DNA, og mikroorganismer indeholdende nævnte rekombinante plasmid....... |
| US5194592A (en) | 1986-12-23 | 1993-03-16 | Kyowa Hakko Kogyo Co. Ltd. | Monoclonal antibodies to novel polypeptide derivatives of human granulocyte colony stimulating factor |
| JPH086063B2 (ja) | 1987-07-22 | 1996-01-24 | 日本ペイント株式会社 | 親水性表面処理剤及び処理方法 |
| US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US4847325A (en) | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| CA1340810C (en) * | 1988-03-31 | 1999-11-02 | Motoo Yamasaki | Polypeptide derivatives of human granulocyte colony stimulating factor |
| JP2958019B2 (ja) | 1988-05-06 | 1999-10-06 | 住友製薬株式会社 | ポリエチレングリコール誘導体、修飾ペプチドおよびその製造方法 |
| JP2796388B2 (ja) * | 1988-05-13 | 1998-09-10 | アムジエン・インコーポレーテツド | G−csfの精製方法 |
| US5218092A (en) | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
| US5349052A (en) * | 1988-10-20 | 1994-09-20 | Royal Free Hospital School Of Medicine | Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor |
| GB8824591D0 (en) * | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Fractionation process |
| AU4660789A (en) | 1988-11-23 | 1990-06-12 | Genentech Inc. | Polypeptide derivatives |
| JP2989002B2 (ja) * | 1988-12-22 | 1999-12-13 | キリン―アムジエン・インコーポレーテツド | 化学修飾顆粒球コロニー刺激因子 |
| US6166183A (en) | 1992-11-30 | 2000-12-26 | Kirin-Amgen, Inc. | Chemically-modified G-CSF |
| EP0460101A4 (en) | 1989-02-24 | 1992-04-15 | Immunotherapeutics, Inc. | Immobilized cytokines |
| US5324844A (en) | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| EP0447523A4 (en) * | 1989-10-10 | 1991-11-27 | Amgen Inc. | Compositions and methods for treating or preventing infections in canine and feline animals |
| JP2978187B2 (ja) | 1989-11-02 | 1999-11-15 | 日本ケミカルリサーチ株式会社 | 修飾スーパーオキサイドディスムターゼの製造法 |
| JPH04218000A (ja) * | 1990-02-13 | 1992-08-07 | Kirin Amgen Inc | 修飾ポリペプチド |
| DE4009661C1 (show.php) | 1990-03-26 | 1991-03-07 | Aisa Automation Industrielle S.A., Vouvry, Ch | |
| GB9107846D0 (en) | 1990-04-30 | 1991-05-29 | Ici Plc | Polypeptides |
| DE4014750A1 (de) | 1990-05-08 | 1991-11-14 | Boehringer Mannheim Gmbh | Muteine des granulozyten-stimulierenden faktors (g-csf) |
| US5126324A (en) | 1990-06-07 | 1992-06-30 | Genentech, Inc. | Method of enhancing growth in patients using combination therapy |
| IE912365A1 (en) * | 1990-07-23 | 1992-01-29 | Zeneca Ltd | Continuous release pharmaceutical compositions |
| US5372808A (en) * | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
| DK0553294T3 (da) * | 1990-10-17 | 1999-08-23 | Amgen Inc | Fremstillingen af sammensætninger til behandlingen af celleproliferationssygdomme |
| US5252714A (en) * | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| US5124297A (en) | 1990-12-07 | 1992-06-23 | Amoco Corporation | Olefin polymerization and copolymerization catalyst |
| CH682636A5 (de) * | 1990-12-21 | 1993-10-29 | Bucher Guyer Ag Masch | Verfahren zum selektiven Entfernen von Zucker aus Getränken. |
| DE69230789T3 (de) | 1991-01-18 | 2007-10-31 | Amgen Inc., Thousand Oaks | Methoden zur behandlung von durch den tumor nekrose faktor ausgelösten krankheiten |
| DE4105480A1 (de) | 1991-02-21 | 1992-08-27 | Boehringer Mannheim Gmbh | Verbesserte aktivierung von rekombinanten proteinen |
| CA2288429C (en) | 1991-03-15 | 2006-04-25 | Synergen, Inc. | Pegylation of polypeptides |
| US5595732A (en) | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| AU2147192A (en) | 1991-06-28 | 1993-01-25 | Genentech Inc. | Method of stimulating immune response using growth hormone |
| US5281698A (en) | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
| US5197592A (en) * | 1991-08-05 | 1993-03-30 | Fmc Corporation | Wire frame idler roll support |
| NZ244778A (en) * | 1991-10-21 | 1994-03-25 | Ortho Pharma Corp | Peg imidates and protein derivatives thereof |
| US5589365A (en) * | 1991-11-29 | 1996-12-31 | Banyu Pharmaceutical Co., Ltd. | Process for producing glycosylated indolopyrrolocarbazole derivatives by culturing certain microorganisms |
| JP3235855B2 (ja) | 1991-12-19 | 2001-12-04 | 住友製薬株式会社 | 細胞接着活性ペプチド及びその高分子修飾体 |
| JP3387519B2 (ja) * | 1992-03-04 | 2003-03-17 | 株式会社日立製作所 | 情報記録再生方式及びデイスク状記録媒体 |
| FR2692736B1 (fr) | 1992-06-23 | 1996-12-20 | Thomson Csf | Filtre radioelectrique de forte et moyenne puissance. |
| US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| JPH08506095A (ja) | 1992-11-25 | 1996-07-02 | アムジェン ボールダー インコーポレイテッド | 改変インシュリン様成長因子 |
| US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| WO1995000162A1 (en) * | 1993-06-21 | 1995-01-05 | Enzon, Inc. | Site specific synthesis of conjugated peptides |
| US5589356A (en) | 1993-06-21 | 1996-12-31 | Vanderbilt University | Litigation of sidechain unprotected peptides via a masked glycoaldehyde ester and O,N-acyl rearrangement |
| US5481571A (en) | 1993-11-12 | 1996-01-02 | Pacific Communication Sciences, Inc. | Method and apparatus for switching between radio frequency circuits |
| KR100203824B1 (ko) * | 1994-03-31 | 1999-06-15 | 스티븐 엠. 오드리 | 거핵구 성장 및 분화를 자극하기 위한 조성물 및방법 |
| US5795569A (en) * | 1994-03-31 | 1998-08-18 | Amgen Inc. | Mono-pegylated proteins that stimulate megakaryocyte growth and differentiation |
| US5646113A (en) | 1994-04-07 | 1997-07-08 | Genentech, Inc. | Treatment of partial growth hormone insensitivity syndrome |
| US5935924A (en) | 1994-04-15 | 1999-08-10 | Genentech, Inc. | Treatment of congestive heart failure |
| US5661122A (en) | 1994-04-15 | 1997-08-26 | Genentech, Inc. | Treatment of congestive heart failure |
| CA2190752A1 (en) | 1994-05-24 | 1995-11-30 | George N. Cox | Modified insulin-like growth factors |
| US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| US5770577A (en) * | 1994-11-14 | 1998-06-23 | Amgen Inc. | BDNF and NT-3 polypeptides selectively linked to polyethylene glycol |
| JP3708151B2 (ja) | 1994-12-15 | 2005-10-19 | 協和醗酵工業株式会社 | Peg化したヒト顆粒球コロニー刺激因子の定量法 |
| US5672662A (en) | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| KR101441331B1 (ko) | 2013-07-19 | 2014-09-17 | 주식회사 슈프리마 | 광학식 지문 인식 장치 |
-
1994
- 1994-10-12 US US08/321,510 patent/US5824784A/en not_active Expired - Lifetime
-
1995
- 1995-02-08 EP EP95910233A patent/EP0733067B1/en not_active Expired - Lifetime
- 1995-02-08 CN CNB001309749A patent/CN1229388C/zh not_active Expired - Lifetime
- 1995-02-08 ES ES97117514T patent/ES2224197T3/es not_active Expired - Lifetime
- 1995-02-08 DE DE2002199044 patent/DE10299044I1/de active Pending
- 1995-02-08 CA CA002178752A patent/CA2178752C/en not_active Expired - Lifetime
- 1995-02-08 NZ NZ281469A patent/NZ281469A/en not_active IP Right Cessation
- 1995-02-08 AT AT95910233T patent/ATE179991T1/de active
- 1995-02-08 IL IL11258595A patent/IL112585A/xx not_active IP Right Cessation
- 1995-02-08 EP EP10180124A patent/EP2399930A1/en not_active Withdrawn
- 1995-02-08 MX MX9602259A patent/MX9602259A/es active IP Right Grant
- 1995-02-08 IL IL134754A patent/IL134754A/en not_active IP Right Cessation
- 1995-02-08 DE DE69533556T patent/DE69533556T2/de not_active Revoked
- 1995-02-08 CN CNA2005101137680A patent/CN1896103A/zh active Pending
- 1995-02-08 KR KR1019960703099A patent/KR100248111B1/ko not_active Expired - Lifetime
- 1995-02-08 WO PCT/US1995/001729 patent/WO1996011953A1/en not_active Ceased
- 1995-02-08 CA CA2307142A patent/CA2307142C/en not_active Expired - Lifetime
- 1995-02-08 JP JP51319196A patent/JP3177251B2/ja not_active Expired - Lifetime
- 1995-02-08 AT AT97117514T patent/ATE277078T1/de active
- 1995-02-08 EP EP04015640A patent/EP1564219A1/en not_active Withdrawn
- 1995-02-08 PT PT97117514T patent/PT822199E/pt unknown
- 1995-02-08 CN CN2008101276757A patent/CN101381409B/zh not_active Expired - Lifetime
- 1995-02-08 EP EP10183858A patent/EP2392594A1/en not_active Withdrawn
- 1995-02-08 CA CA002472085A patent/CA2472085A1/en not_active Abandoned
- 1995-02-08 ZA ZA951008A patent/ZA951008B/xx unknown
- 1995-02-08 DK DK95910233T patent/DK0733067T3/da active
- 1995-02-08 ES ES95910233T patent/ES2131811T3/es not_active Expired - Lifetime
- 1995-02-08 CN CN95191454A patent/CN1071760C/zh not_active Expired - Lifetime
- 1995-02-08 DE DE69509628T patent/DE69509628T2/de not_active Expired - Lifetime
- 1995-02-08 EP EP97117514A patent/EP0822199B1/en not_active Revoked
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1996
- 1996-07-22 JP JP19257696A patent/JP3177449B2/ja not_active Expired - Lifetime
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1997
- 1997-06-20 US US08/879,760 patent/US5985265A/en not_active Expired - Lifetime
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1999
- 1999-03-19 JP JP11076959A patent/JPH11310600A/ja active Pending
- 1999-06-16 GR GR990401601T patent/GR3030526T3/el unknown
- 1999-10-23 KR KR1019997009836A patent/KR100261030B1/ko not_active Expired - Lifetime
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2000
- 2000-02-27 IL IL13475400A patent/IL134754A0/xx unknown
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2001
- 2001-03-26 US US09/817,725 patent/US7090835B2/en not_active Expired - Fee Related
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2002
- 2002-10-01 JP JP2002288746A patent/JP2003155299A/ja not_active Withdrawn
- 2002-11-04 NL NL300106C patent/NL300106I2/nl unknown
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2003
- 2003-01-29 LU LU91006C patent/LU91006I2/fr unknown
- 2003-04-10 JP JP2003106520A patent/JP2003327600A/ja active Pending
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2005
- 2005-09-30 JP JP2005286189A patent/JP2006045243A/ja not_active Withdrawn
- 2005-09-30 JP JP2005286188A patent/JP2006077021A/ja not_active Withdrawn
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2006
- 2006-04-26 US US11/411,321 patent/US7662933B2/en not_active Expired - Fee Related
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2009
- 2009-12-16 US US12/639,398 patent/US8258262B2/en not_active Expired - Fee Related
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2010
- 2010-06-14 JP JP2010134726A patent/JP5350330B2/ja not_active Expired - Lifetime
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2012
- 2012-08-02 US US13/565,447 patent/US20120296072A1/en not_active Abandoned
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2013
- 2013-03-19 US US13/847,290 patent/US20130189219A1/en not_active Abandoned
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