KR100668546B1 - 수용체에 결합하는 펩티드 및 화합물 - Google Patents
수용체에 결합하는 펩티드 및 화합물 Download PDFInfo
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- KR100668546B1 KR100668546B1 KR1020057005233A KR20057005233A KR100668546B1 KR 100668546 B1 KR100668546 B1 KR 100668546B1 KR 1020057005233 A KR1020057005233 A KR 1020057005233A KR 20057005233 A KR20057005233 A KR 20057005233A KR 100668546 B1 KR100668546 B1 KR 100668546B1
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- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
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- 238000001262 western blot Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- C07K14/524—Thrombopoietin, i.e. C-MPL ligand
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020067003807A KR100679576B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/764,640 US5869451A (en) | 1995-06-07 | 1996-12-11 | Peptides and compounds that bind to a receptor |
| US08/764,640 | 1996-12-11 | ||
| KR1019997005169A KR100625708B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019997005169A Division KR100625708B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020067003807A Division KR100679576B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20050042505A KR20050042505A (ko) | 2005-05-09 |
| KR100668546B1 true KR100668546B1 (ko) | 2007-01-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019997005169A Expired - Lifetime KR100625708B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
| KR1020067003807A Expired - Lifetime KR100679576B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
| KR1020057005233A Expired - Lifetime KR100668546B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019997005169A Expired - Lifetime KR100625708B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
| KR1020067003807A Expired - Lifetime KR100679576B1 (ko) | 1996-12-11 | 1997-12-09 | 수용체에 결합하는 펩티드 및 화합물 |
Country Status (24)
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| EP (3) | EP0948539B1 (enExample) |
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| AR (2) | AR010752A1 (enExample) |
| AT (1) | ATE420893T1 (enExample) |
| AU (1) | AU725731B2 (enExample) |
| BR (1) | BRPI9713914B1 (enExample) |
| CA (1) | CA2274149C (enExample) |
| CO (1) | CO5080768A1 (enExample) |
| DE (1) | DE69739219D1 (enExample) |
| ES (1) | ES2321038T3 (enExample) |
| HR (1) | HRP970683B1 (enExample) |
| MA (1) | MA26454A1 (enExample) |
| PA (1) | PA8442601A1 (enExample) |
| PE (1) | PE27599A1 (enExample) |
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| TN (1) | TNSN97201A1 (enExample) |
| TR (2) | TR200401638T2 (enExample) |
| TW (1) | TW515804B (enExample) |
| UY (1) | UY24805A1 (enExample) |
| WO (1) | WO1998025965A2 (enExample) |
| ZA (1) | ZA9711045B (enExample) |
Families Citing this family (124)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5869451A (en) * | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
| PT885242E (pt) * | 1995-06-07 | 2008-06-18 | Glaxo Group Ltd | Péptidos e compostos que se ligam a um receptor de trombopoietina |
| US6251864B1 (en) | 1995-06-07 | 2001-06-26 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
| US7091311B2 (en) | 1996-06-07 | 2006-08-15 | Smithkline Beecham Corporation | Peptides and compounds that bind to a receptor |
| US7083983B2 (en) * | 1996-07-05 | 2006-08-01 | Cancer Research Campaign Technology Limited | Inhibitors of the interaction between P53 and MDM2 |
| WO1999022732A1 (en) | 1997-10-31 | 1999-05-14 | Smithkline Beecham Corporation | Novel metal complexes |
| CA2308317A1 (en) | 1997-10-31 | 1999-05-14 | Smithkline Beecham Corporation | Novel metal complexes |
| JP2001521897A (ja) * | 1997-10-31 | 2001-11-13 | スミスクライン・ビーチャム・コーポレイション | 新規な金属錯体 |
| US7153655B2 (en) | 1998-06-16 | 2006-12-26 | Alligator Bioscience Ab | Method for in vitro molecular evolution of protein function involving the use of exonuclease enzyme and two populations of parent polynucleotide sequence |
| ATE348163T1 (de) * | 1998-10-23 | 2007-01-15 | Amgen Inc | Thrombopoietin substitute |
| US6660843B1 (en) * | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| US7488590B2 (en) * | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
| WO2001021163A2 (en) * | 1999-09-21 | 2001-03-29 | Emory University | Methods and compositions for treating platelet-related disorders using mpl pathway inhibitory agents |
| US7332275B2 (en) | 1999-10-13 | 2008-02-19 | Sequenom, Inc. | Methods for detecting methylated nucleotides |
| US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
| CA2387805C (en) | 1999-11-18 | 2012-08-28 | Corvas International, Inc. | Nucleic acids encoding endotheliases, endotheliases and uses thereof |
| TWI284639B (en) * | 2000-01-24 | 2007-08-01 | Shionogi & Co | A compound having thrombopoietin receptor agonistic effect |
| US7700341B2 (en) * | 2000-02-03 | 2010-04-20 | Dendreon Corporation | Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon |
| MXPA02010787A (es) * | 2000-05-03 | 2003-07-14 | Amgen Inc | Peptidos modificados como agentes terapeuticos. |
| US20050158838A1 (en) * | 2000-06-19 | 2005-07-21 | Dyax Corp., A Delaware Corporation | Novel enterokinase cleavage sequences |
| US20040253242A1 (en) * | 2000-12-05 | 2004-12-16 | Bowdish Katherine S. | Rationally designed antibodies |
| ES2258558T3 (es) * | 2000-12-05 | 2006-09-01 | Alexion Pharmaceuticals, Inc. | Anticuerpos diseñados racionalmente. |
| US7396917B2 (en) * | 2000-12-05 | 2008-07-08 | Alexion Pharmaceuticals, Inc. | Rationally designed antibodies |
| US6958213B2 (en) | 2000-12-12 | 2005-10-25 | Alligator Bioscience Ab | Method for in vitro molecular evolution of protein function |
| WO2002072786A2 (en) | 2001-03-13 | 2002-09-19 | Corvas International, Inc. | Nucleic acid molecules encoding a transmembrane serine protease 7, the encoded polypeptides and methods based thereon |
| JP2004535166A (ja) | 2001-03-22 | 2004-11-25 | デンドレオン・サンディエゴ・リミテッド・ライアビリティ・カンパニー | セリンプロテアーゼｃｖｓｐ１４をコードする核酸分子、コードされるポリペプチドおよびそれに基づく方法 |
| KR20030096292A (ko) | 2001-03-27 | 2003-12-24 | 덴드레온 샌 디에고 엘엘씨 | 트랜스막 세린 프로테아제 9를 암호화하는 핵산 분자,암호화된 폴리펩티드 및 이에 근거한 방법 |
| US7112430B2 (en) | 2001-05-14 | 2006-09-26 | Dendreon Corporation | Nucleic acid molecules encoding a transmembrane serine protease 10, the encoded polypeptides and methods based thereon |
| US7332474B2 (en) * | 2001-10-11 | 2008-02-19 | Amgen Inc. | Peptides and related compounds having thrombopoietic activity |
| AU2002357004A1 (en) * | 2001-11-20 | 2003-06-10 | Dendreon San Diego Llc | Nucleic acid molecules encoding serine protease 17, the encoded polypeptides and methods based thereon |
| 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 |
| AU2003228809A1 (en) | 2002-05-03 | 2003-11-17 | Sequenom, Inc. | Kinase anchor protein muteins, peptides thereof, and related methods |
| DK1504098T4 (da) | 2002-05-17 | 2011-05-23 | Alligator Bioscience Ab | Fremgangsmåde til molekyulær udvikling in vitro af proteinfunktion |
| CA2448513A1 (en) * | 2002-06-29 | 2003-12-29 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Isoflavone concentrates, as well as methods for their production |
| US20040028661A1 (en) * | 2002-08-07 | 2004-02-12 | Bartelmez Stephen H. | Expansion of cells using thrombopoietin and anti-transforming growth factor-beta |
| CA2495184A1 (en) | 2002-08-14 | 2004-02-26 | Nissan Chemical Industries, Ltd. | Thrombopoietin receptor activators and process for their production |
| US7598224B2 (en) * | 2002-08-20 | 2009-10-06 | Biosurface Engineering Technologies, Inc. | Dual chain synthetic heparin-binding growth factor analogs |
| US8227411B2 (en) * | 2002-08-20 | 2012-07-24 | BioSurface Engineering Technologies, Incle | FGF growth factor analogs |
| US7166574B2 (en) | 2002-08-20 | 2007-01-23 | Biosurface Engineering Technologies, Inc. | Synthetic heparin-binding growth factor analogs |
| US7981862B2 (en) | 2003-08-19 | 2011-07-19 | Biosurface Engineering Technologies, Inc. | Composition comprising BMP-2 amplifier/co-activator for enhancement of osteogenesis |
| KR20050093759A (ko) * | 2002-09-18 | 2005-09-23 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 혈소판 및 조혈 줄기세포의 생산을 증가시키는 방법 |
| TWI324593B (en) | 2002-10-09 | 2010-05-11 | Nissan Chemical Ind Ltd | Pyrazolone compounds and thrombopoietin receptor activator |
| EP1638587A4 (en) | 2003-02-14 | 2007-04-18 | Univ Missouri | RECIPROCAL PROCEDURES AND COMPOSITIONS CONCERNING PROTEASOMAL INTERFERENCE |
| NZ543905A (en) | 2003-05-12 | 2008-07-31 | Affymax Inc | Peptides that bind to the erythropoietin receptor |
| ATE478093T1 (de) * | 2003-05-12 | 2010-09-15 | Affymax Inc | Neue poly(ethylenglycol) modifizierte erythropoietinagonisten und deren verwendungen |
| NZ543934A (en) * | 2003-05-12 | 2008-06-30 | Affymax Inc | Novel spacer moiety for poly (ethylene glycol)-modified peptide-based compounds |
| NZ543935A (en) * | 2003-05-12 | 2008-06-30 | Affymax Inc | Peptides that bind to the erythropoietin receptor |
| CN103130739B (zh) * | 2003-08-12 | 2015-09-16 | 盐野义制药株式会社 | 具有血小板生成素受体激动作用的化合物 |
| EP1675606B1 (en) * | 2003-08-28 | 2017-04-05 | Janssen Pharmaceuticals, Inc. | Peptides and compounds that bind to thrombopoietin receptors |
| US7723295B2 (en) * | 2003-08-28 | 2010-05-25 | Ortho-Mcneil Pharmaceutical, Inc. | Peptides and compounds that bind to a receptor |
| ATE376556T1 (de) | 2003-12-31 | 2007-11-15 | Hoffmann La Roche | Verfahren zur peptidsynthese unter verwendung einer reduzierten menge an entschützungsmittel |
| US7414028B1 (en) * | 2004-02-04 | 2008-08-19 | Biosurface Engineering Technologies, Inc. | Growth factor analogs |
| US7528105B1 (en) | 2004-02-10 | 2009-05-05 | Biosurface Engineering Technologies | Heterodimeric chain synthetic heparin-binding growth factor analogs |
| US20060024347A1 (en) * | 2004-02-10 | 2006-02-02 | Biosurface Engineering Technologies, Inc. | Bioactive peptide coatings |
| US7671012B2 (en) | 2004-02-10 | 2010-03-02 | Biosurface Engineering Technologies, Inc. | Formulations and methods for delivery of growth factor analogs |
| US20080227696A1 (en) * | 2005-02-22 | 2008-09-18 | Biosurface Engineering Technologies, Inc. | Single branch heparin-binding growth factor analogs |
| EP1725576B1 (en) | 2004-02-20 | 2010-09-22 | Biosurface Engineering Technologies, Inc. | Positive modulator of bone morphogenic protein-2 |
| JP2008505928A (ja) * | 2004-07-08 | 2008-02-28 | アムジェン インコーポレーテッド | 治療用ペプチド |
| US20060210542A1 (en) * | 2004-08-16 | 2006-09-21 | Yurkow Edward J | Use of TPO mimetic compounds and pharmaceutical compositions in the treatment of anemia |
| DK1797127T3 (en) | 2004-09-24 | 2017-10-02 | Amgen Inc | Modified Fc molecules |
| US7589063B2 (en) | 2004-12-14 | 2009-09-15 | Aplagen Gmbh | Molecules which promote hematopoiesis |
| WO2006062685A2 (en) * | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
| WO2006060148A2 (en) * | 2004-11-11 | 2006-06-08 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
| TWI351954B (en) | 2004-12-08 | 2011-11-11 | Nissan Chemical Ind Ltd | Heterocyclic compounds and thrombopoietin receptor |
| JP4973192B2 (ja) | 2004-12-14 | 2012-07-11 | 日産化学工業株式会社 | アミド化合物及びトロンボポエチンレセプター活性化剤 |
| CA2600749C (en) | 2005-03-10 | 2014-04-15 | Nascacell Ip Gmbh | Dimeric or multimeric microproteins |
| WO2006094530A1 (en) * | 2005-03-11 | 2006-09-14 | Siegfried Ltd. | Di-polymer protein conjugates and processes for their preparation |
| US8324159B2 (en) * | 2005-06-03 | 2012-12-04 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
| US7919461B2 (en) | 2005-06-03 | 2011-04-05 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
| US7550433B2 (en) * | 2005-06-03 | 2009-06-23 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
| WO2006136450A2 (en) * | 2005-06-23 | 2006-12-28 | Aplagen Gmbh | Supravalent compounds |
| CA2609319C (en) | 2005-07-15 | 2014-02-04 | Nissan Chemical Industries, Ltd. | Thiophene compounds and thrombopoietin receptor activators |
| US7960425B2 (en) | 2005-07-20 | 2011-06-14 | Nissan Chemical Industries, Ltd. | Pyrazole compounds and thrombopoietin receptor activators |
| US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
| WO2007052808A1 (ja) | 2005-11-07 | 2007-05-10 | Nissan Chemical Industries, Ltd. | ヒドラジド化合物及びトロンボポエチンレセプター活性化剤 |
| US7879318B2 (en) | 2006-01-23 | 2011-02-01 | Mcw Research Foundation, Inc. | Method of reducing the effects of ischemia by administration of a thrombopoietin receptor ligand |
| US9012605B2 (en) | 2006-01-23 | 2015-04-21 | Amgen Inc. | Crystalline polypeptides |
| EP1986677A2 (en) * | 2006-01-25 | 2008-11-05 | Amgen Inc. | Thrombopoietic compounds |
| EP1834963A1 (en) * | 2006-03-13 | 2007-09-19 | Siegfried Ltd. | Di-polymer protein conjugates and processes for their preparation |
| EP2005185B1 (en) * | 2006-03-22 | 2010-10-20 | Viral Logic Systems Technology Corp. | Methods for identifying polypeptide targets |
| JO3324B1 (ar) | 2006-04-21 | 2019-03-13 | Amgen Inc | مركبات علاجية مجففة بالتبريد تتعلق بالعصارة الهضمية |
| WO2007133811A2 (en) * | 2006-05-15 | 2007-11-22 | Viral Logic Systems Technology Corp. | Cd47 related compositions and methods for treating immunological diseases and disorders |
| US8377448B2 (en) * | 2006-05-15 | 2013-02-19 | The Board Of Trustees Of The Leland Standford Junior University | CD47 related compositions and methods for treating immunological diseases and disorders |
| US7820172B1 (en) | 2006-06-01 | 2010-10-26 | Biosurface Engineering Technologies, Inc. | Laminin-derived multi-domain peptides |
| EP2025671A4 (en) | 2006-06-07 | 2011-04-06 | Nissan Chemical Ind Ltd | NITROGENIC HETEROCYCLIC COMPOUND AND THROMBOPOIETIN RECEPTOR ACTIVATOR |
| US7981425B2 (en) * | 2006-06-19 | 2011-07-19 | Amgen Inc. | Thrombopoietic compounds |
| WO2008051383A2 (en) * | 2006-10-19 | 2008-05-02 | Amgen Inc. | Use of alcohol co-solvents to improve pegylation reaction yields |
| JP2010520855A (ja) * | 2007-01-31 | 2010-06-17 | アフィーマックス・インコーポレイテッド | 修飾基をポリペプチドおよびその他の高分子に結合するための窒素ベースのリンカー |
| EP2738257A1 (en) | 2007-05-22 | 2014-06-04 | Amgen Inc. | Compositions and methods for producing bioactive fusion proteins |
| WO2008157824A2 (en) * | 2007-06-21 | 2008-12-24 | Conjuchem Biotechnologies Inc. | Thrombopoietin peptide conjugates |
| WO2009029682A1 (en) * | 2007-08-28 | 2009-03-05 | Rigel Pharmaceuticals, Inc. | Combination therapy with syk kinase inhibitor |
| US8183342B2 (en) * | 2007-11-06 | 2012-05-22 | Case Western Reserve University | Method of treating chemotherapy-induced thrombocytopenia |
| CN101481352A (zh) | 2008-01-10 | 2009-07-15 | 上海恒瑞医药有限公司 | 双环取代吡唑酮偶氮类衍生物、其制备方法及其在医药上的应用 |
| US9175078B2 (en) | 2008-01-25 | 2015-11-03 | Amgen Inc. | Ferroportin antibodies and methods of use |
| EP2620448A1 (en) | 2008-05-01 | 2013-07-31 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
| JP2012521360A (ja) | 2009-03-20 | 2012-09-13 | アムジエン・インコーポレーテツド | Ｋｖ１．３の選択的かつ強力なペプチド阻害剤 |
| WO2011012306A2 (en) | 2009-07-30 | 2011-02-03 | Aplagen Gmbh | Use of emps for antagonising epo-stimulatory effects on epo-responsive tumors while maintaining erythropoiesis |
| US8889732B2 (en) | 2009-10-23 | 2014-11-18 | Nissan Chemical Industries, Ltd. | Fused heterocyclic compounds and thrombopoietin receptor activators |
| WO2011098095A1 (en) | 2010-02-09 | 2011-08-18 | Aplagen Gmbh | Peptides binding the tpo receptor |
| EP2725034B1 (en) | 2010-09-22 | 2019-04-03 | Amgen Inc. | Carrier immunoglobulins with no specificity for human tissues and uses thereof |
| WO2014159242A1 (en) | 2013-03-14 | 2014-10-02 | Novartis Ag | Notch 3 mutants and uses thereof |
| US9308236B2 (en) | 2013-03-15 | 2016-04-12 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
| MX380553B (es) | 2014-09-11 | 2025-03-12 | Bristol Myers Squibb Co | Inhibidores macrocíclicos de las interacciones proteína/proteína de muerte programada 1 (pd-1)/pd-l1 y cd80(b7-1)/pd-l1. |
| US9732119B2 (en) | 2014-10-10 | 2017-08-15 | Bristol-Myers Squibb Company | Immunomodulators |
| US9856292B2 (en) | 2014-11-14 | 2018-01-02 | Bristol-Myers Squibb Company | Immunomodulators |
| WO2016079219A1 (en) | 2014-11-19 | 2016-05-26 | Koninklijke Philips N.V. | Diagnostic method employing hnl |
| US9861680B2 (en) | 2014-12-18 | 2018-01-09 | Bristol-Myers Squibb Company | Immunomodulators |
| US9944678B2 (en) | 2014-12-19 | 2018-04-17 | Bristol-Myers Squibb Company | Immunomodulators |
| US20160222060A1 (en) | 2015-02-04 | 2016-08-04 | Bristol-Myers Squibb Company | Immunomodulators |
| US9809625B2 (en) | 2015-03-18 | 2017-11-07 | Bristol-Myers Squibb Company | Immunomodulators |
| US10143746B2 (en) | 2016-03-04 | 2018-12-04 | Bristol-Myers Squibb Company | Immunomodulators |
| US10358463B2 (en) | 2016-04-05 | 2019-07-23 | Bristol-Myers Squibb Company | Immunomodulators |
| EA038019B1 (ru) | 2016-05-19 | 2021-06-23 | Бристол-Маерс Сквибб Компани | Иммуномодуляторы для пэт-визуализации |
| WO2018085750A2 (en) | 2016-11-07 | 2018-05-11 | Bristol-Myers Squibb Company | Immunomodulators |
| US11066445B2 (en) | 2017-06-23 | 2021-07-20 | Bristol-Myers Squibb Company | Immunomodulators acting as antagonists of PD-1 |
| JP7481252B2 (ja) * | 2017-07-26 | 2024-05-10 | ヤンセン ファーマシューティカ エヌ．ベー． | 標的放射線治療誘発性血管完全性を保護する方法 |
| JP7257393B2 (ja) | 2017-10-03 | 2023-04-13 | ブリストル－マイヤーズ スクイブ カンパニー | 免疫調節剤 |
| EP3914281A1 (en) | 2019-01-25 | 2021-12-01 | Janssen Pharmaceutica NV | Methods of enhancing protection against organ and vascular injury, hematopoietic recovery and survival in response to total body radiation/chemical exposure |
| CN113905754B (zh) | 2019-01-25 | 2025-03-11 | 詹森药业有限公司 | 减轻起疱剂和腐蚀性气体毒性作用的方法 |
| AU2020211412A1 (en) | 2019-01-25 | 2021-08-12 | Janssen Pharmaceutica Nv | Methods for mitigating liver injury and promoting liver hypertrophy, regeneration and cell engraftment in conjunction with radiation and/or radiomimetic treatments |
| JP2023510737A (ja) | 2020-01-06 | 2023-03-15 | ブリストル－マイヤーズ スクイブ カンパニー | 免疫調節剤 |
| KR20220161407A (ko) | 2020-03-30 | 2022-12-06 | 브리스톨-마이어스 스큅 컴퍼니 | 면역조정제 |
| EP4408984A1 (en) | 2021-10-01 | 2024-08-07 | Janssen Pharmaceutica NV | Methods of increasing progenitor cell production |
| WO2024095178A1 (en) | 2022-11-01 | 2024-05-10 | Janssen Pharmaceutica Nv | Thrombopoietin mimetic for use in the treatment of acute liver failure |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2046920B1 (enExample) | 1969-06-19 | 1974-05-03 | Citizen Watch Co Ltd | |
| US3940475A (en) | 1970-06-11 | 1976-02-24 | Biological Developments, Inc. | Radioimmune method of assaying quantitatively for a hapten |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| US4612132A (en) | 1984-07-20 | 1986-09-16 | Chevron Research Company | Modified succinimides |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US5198424A (en) * | 1989-03-08 | 1993-03-30 | Board Of Regents Of The University Of Oklahoma | Functionally active selectin-derived peptides |
| US5143854A (en) * | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5326558A (en) * | 1989-08-08 | 1994-07-05 | Genetics Institute, Inc. | Megakaryocytopoietic factor |
| IL96477A0 (en) * | 1989-12-01 | 1991-08-16 | Amgen Inc | Megakaryocyte production |
| US5571508A (en) * | 1989-12-18 | 1996-11-05 | Amrad Corporation Limited | Method for the treatment of thrombocytopenia and pharmaceutical compositions useful therefor |
| IT1241395B (it) * | 1990-04-02 | 1994-01-10 | Eniricerche Spa | Composti immunogenici,il procedimento per la loro sintesi e loro impiego per la preparazione di vaccini antimalaria |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| US5250732A (en) * | 1991-07-18 | 1993-10-05 | Genentech, Inc. | Ketamine analogues for treatment of thrombocytopenia |
| US5270170A (en) * | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| JPH07507806A (ja) * | 1992-06-11 | 1995-08-31 | アルカーメス コントロールド セラピューティクス，インコーポレイテッド | エリスロポエチン薬物送達システム |
| US5354934A (en) | 1993-02-04 | 1994-10-11 | Amgen Inc. | Pulmonary administration of erythropoietin |
| AU685506B2 (en) | 1993-08-25 | 1998-01-22 | Systemix, Inc. | Method for producing a highly enriched population of hematopoietic stem cells |
| AU8124694A (en) * | 1993-10-29 | 1995-05-22 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
| SG47030A1 (en) * | 1994-01-03 | 1998-03-20 | Genentech Inc | Thrombopoietin |
| WO1995021919A2 (en) * | 1994-02-14 | 1995-08-17 | Kirin Brewery Company, Limited | Protein having tpo activity |
| WO1995021626A1 (en) * | 1994-02-14 | 1995-08-17 | University Of Washington | Methods for stimulating erythropoiesis using thrombopoietin |
| EP0668352A1 (en) * | 1994-02-14 | 1995-08-23 | Kirin Brewery Company, Ltd. | Protein having TPO activity |
| CZ221496A3 (en) * | 1994-02-14 | 1997-07-16 | Zymogenetics Inc | Haematopoetic protein, materials and processes for preparing thereof |
| TW496870B (en) * | 1994-03-31 | 2002-08-01 | Amgen Inc | Compositions methods for stimulating megakaryocyte growth and differentiation |
| US5571686A (en) * | 1994-04-14 | 1996-11-05 | Massachusetts Institute Of Technology | Method of using megapoietin for prolonging the survival & viability of platlets |
| US5641655A (en) * | 1994-11-30 | 1997-06-24 | Zymogenetics, Inc. | Methods for producing thrombopoietin polypeptides using a mammalian tissue plasminogen activator secretory peptide |
| AU4163196A (en) * | 1994-11-30 | 1996-06-19 | Zymogenetics Inc. | Low molecular weight thrombopoietin |
| ES2276401T3 (es) * | 1995-04-26 | 2007-06-16 | Kyowa Hakko Kogyo Co., Ltd. | Proteinas de fusion g-csf tpo. |
| US5869451A (en) * | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
| PT885242E (pt) * | 1995-06-07 | 2008-06-18 | Glaxo Group Ltd | Péptidos e compostos que se ligam a um receptor de trombopoietina |
| KR102127408B1 (ko) | 2014-01-29 | 2020-06-29 | 삼성전자주식회사 | 항 Her3 scFv 단편 및 이를 포함하는 항 c-Met/항 Her3 이중 특이 항체 |
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