HRP941020A2 - Thrombopoietin - Google Patents
Thrombopoietin Download PDFInfo
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- HRP941020A2 HRP941020A2 HR08/348,658A HRP941020A HRP941020A2 HR P941020 A2 HRP941020 A2 HR P941020A2 HR P941020 A HRP941020 A HR P941020A HR P941020 A2 HRP941020 A2 HR P941020A2
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- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
- Vehicle Body Suspensions (AREA)
- Information Transfer Systems (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17655394A | 1994-01-03 | 1994-01-03 | |
US18560794A | 1994-01-21 | 1994-01-21 | |
US08/196,689 US8357513B1 (en) | 1994-01-03 | 1994-02-15 | Nucleic acids encoding mpl ligand (thrombopoietin) and fragments thereof |
US22326394A | 1994-04-04 | 1994-04-04 | |
US08/249,376 US8192955B1 (en) | 1994-01-03 | 1994-05-25 | Nucleic acids encoding MPL ligand (thrombopoietin), variants, and fragments thereof |
US34865894A | 1994-12-02 | 1994-12-02 | |
US08/348,657 US6660256B1 (en) | 1994-01-03 | 1994-12-02 | Porcine mpl ligand |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP941020A2 true HRP941020A2 (en) | 1997-04-30 |
Family
ID=27569151
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR08/348,658A HRP941020A2 (en) | 1994-01-03 | 1994-12-27 | Thrombopoietin |
Country Status (28)
Country | Link |
---|---|
EP (1) | EP0738323A1 (lv) |
JP (2) | JPH09508262A (lv) |
CN (1) | CN1134539C (lv) |
AU (1) | AU704266B2 (lv) |
BG (1) | BG63639B1 (lv) |
CA (1) | CA2178482C (lv) |
CZ (1) | CZ296130B6 (lv) |
DK (1) | DK149194A (lv) |
ES (1) | ES2114786B1 (lv) |
FI (1) | FI121573B (lv) |
FR (1) | FR2714670B1 (lv) |
GB (1) | GB2285446B (lv) |
HR (1) | HRP941020A2 (lv) |
HU (1) | HUT75657A (lv) |
IE (1) | IE72517B1 (lv) |
IL (1) | IL112184A (lv) |
IT (1) | IT1283770B1 (lv) |
LU (1) | LU88573A1 (lv) |
LV (1) | LV11632B (lv) |
NL (1) | NL9500010A (lv) |
NO (1) | NO326903B1 (lv) |
NZ (1) | NZ278726A (lv) |
PT (1) | PT101627B (lv) |
RO (1) | RO117110B1 (lv) |
SG (1) | SG47030A1 (lv) |
SI (1) | SI9420079A (lv) |
SK (1) | SK282265B6 (lv) |
WO (1) | WO1995018858A1 (lv) |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6270989B1 (en) | 1991-11-05 | 2001-08-07 | Transkaryotic Therapies, Inc. | Protein production and delivery |
US5968502A (en) | 1991-11-05 | 1999-10-19 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
WO1995021920A1 (en) * | 1994-02-14 | 1995-08-17 | Zymogenetics, Inc. | Hematopoietic protein and materials and methods for making it |
US5795569A (en) * | 1994-03-31 | 1998-08-18 | Amgen Inc. | Mono-pegylated proteins that stimulate megakaryocyte growth and differentiation |
KR100203824B1 (ko) * | 1994-03-31 | 1999-06-15 | 스티븐 엠. 오드리 | 거핵구 성장 및 분화를 자극하기 위한 조성물 및방법 |
US5986049A (en) * | 1994-12-30 | 1999-11-16 | Zymogenetics, Inc. | Purified thrombopoietin and method of making it |
TW387940B (en) * | 1995-01-17 | 2000-04-21 | Kirin Brewery | Anti-tpo monodonal antibody |
US6254870B1 (en) | 1995-02-03 | 2001-07-03 | G. D. Searle & Co. | Thrombopoietin: IL-3 fusion protein |
AU691410B2 (en) * | 1995-02-15 | 1998-05-14 | Amgen, Inc. | MPL ligand analogs |
US5696250A (en) | 1995-02-15 | 1997-12-09 | Amgen Inc. | DNA encoding megakaryocyte growth and development factor analogs |
US5989538A (en) * | 1995-02-15 | 1999-11-23 | Amgen Inc. | Mpl ligand analogs |
TW434021B (en) * | 1995-03-15 | 2001-05-16 | Kirin Brewery | Methods for preventing adsorption of thrombopoietin (TPO), and stable TPO-containing compositions |
TW434020B (en) * | 1995-03-15 | 2001-05-16 | Kirin Brewery | Methods for preventing adsorption of thrombopoietin (TPO), and stable top-containing compositions |
ZA964382B (en) * | 1995-06-06 | 1997-12-01 | Genentech Inc | Lymphotoxin and thrombopoietin for use in the treatment of cancer. |
US6251864B1 (en) | 1995-06-07 | 2001-06-26 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
US5869451A (en) * | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
PL188795B1 (pl) * | 1995-06-07 | 2005-04-29 | Glaxo Group Ltd | Związek wiążący się z receptorem trombopoetyny, kompozycja farmaceutyczna i zastosowanie związku wiążącego się z receptorem trombopoetyny |
TW497972B (en) * | 1995-06-08 | 2002-08-11 | Kirin Brewery | Stable thrombopoietin (TPO)-containing lyophilized compositions |
US6066318A (en) | 1995-10-05 | 2000-05-23 | G.D. Searle & Co. | Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors |
US6031071A (en) * | 1996-01-24 | 2000-02-29 | Biophage, Inc. | Methods of generating novel peptides |
US5879673A (en) * | 1996-01-25 | 1999-03-09 | Genentech, Inc. | Administration of thrombopoietin on a single day only |
US7091311B2 (en) | 1996-06-07 | 2006-08-15 | Smithkline Beecham Corporation | Peptides and compounds that bind to a receptor |
AU728881B2 (en) * | 1996-08-13 | 2001-01-18 | Zymogenetics Inc. | Expression vectors, cells, and methods for preparing thrombopoietin polypeptides |
WO1998052598A1 (en) * | 1997-05-21 | 1998-11-26 | Genentech, Inc. | Novel administration of thrombopoietin |
US5980893A (en) * | 1997-07-17 | 1999-11-09 | Beth Israel Deaconess Medical Center, Inc. | Agonist murine monoclonal antibody as a stimulant for megakaryocytopoiesis |
US6342220B1 (en) | 1997-08-25 | 2002-01-29 | Genentech, Inc. | Agonist antibodies |
US20030228666A1 (en) | 1998-06-30 | 2003-12-11 | Daewoong Pharmaceutical Co., Ltd. | Novel human thrombopoietin mutein |
KR20000006549A (ko) * | 1998-06-30 | 2000-01-25 | 윤재승 | 생체내혈소판증식효능이향상된신규한트롬보포이에틴유도체 |
US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
JP3820105B2 (ja) | 1998-10-23 | 2006-09-13 | キリン−アムジエン・インコーポレーテツド | Mp1受容体に結合し血小板生成活性を有する二量体トロンボポエチンペプチド模倣体 |
CY2010012I2 (el) * | 2000-05-25 | 2020-05-29 | Novartis Ag | Μιμητικα θρομβοποιητινης |
UY26317A1 (es) * | 2000-08-30 | 2000-10-31 | Alfonso Cayota Carlos Pritsch | Sistema de produccion de trombopoyetina humana por celulas de mamiferos en cultivo |
US6673580B2 (en) | 2000-10-27 | 2004-01-06 | Genentech, Inc. | Identification and modification of immunodominant epitopes in polypeptides |
US7332474B2 (en) | 2001-10-11 | 2008-02-19 | Amgen Inc. | Peptides and related compounds having thrombopoietic activity |
EP1994824A1 (en) | 2001-11-15 | 2008-11-26 | Kirin Pharma Kabushiki Kaisha | Chimeric non-human animal |
KR100467750B1 (ko) * | 2001-11-29 | 2005-01-24 | 씨제이 주식회사 | 생체내 에리스로포이에틴 활성이 증진된 융합단백질 |
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 |
US8067367B2 (en) | 2002-09-18 | 2011-11-29 | Janssen Pharmaceutica, N.V. | Methods of increasing platelet and hematopoietic stem cell production |
HUE032370T2 (en) | 2003-08-28 | 2017-09-28 | 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 |
WO2005116231A1 (en) * | 2004-05-18 | 2005-12-08 | Intrexon Corporation | Methods for dynamic vector assembly of dna cloning vector plasmids |
EP1773400A2 (en) | 2004-07-08 | 2007-04-18 | Amgen Inc. | Therapeutic peptides |
US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
US9012605B2 (en) | 2006-01-23 | 2015-04-21 | Amgen Inc. | Crystalline polypeptides |
WO2007098547A1 (en) * | 2006-03-01 | 2007-09-07 | Apollo Life Sciences Limited | A molecule and chimeric molecules thereof |
US7981425B2 (en) | 2006-06-19 | 2011-07-19 | Amgen Inc. | Thrombopoietic compounds |
EP2044197B8 (en) | 2006-07-24 | 2018-03-07 | The University Of Queensland | Method of producing a population of cells |
TW200902708A (en) | 2007-04-23 | 2009-01-16 | Wyeth Corp | Methods of protein production using anti-senescence compounds |
MX2009012609A (es) | 2007-05-22 | 2009-12-07 | Amgen Inc | Composiciones y metodos para producir proteinas de fusion bioactivas. |
WO2010085086A2 (ko) | 2009-01-20 | 2010-07-29 | 한올바이오파마 주식회사 | 변형된 인간 트롬보포이에틴 폴리펩타이드 절편 및 그의 제조방법 |
WO2014089478A1 (en) * | 2012-12-07 | 2014-06-12 | University Of Tennessee Research Foundation | Methods of numerical analysis for platelet disorders and computer-readable media and systems for performing the same |
EP2934555B1 (en) | 2012-12-21 | 2021-09-22 | Astellas Institute for Regenerative Medicine | Methods for production of platelets from pluripotent stem cells |
CN103555760B (zh) * | 2013-10-18 | 2015-05-20 | 江苏康禾生物制药有限公司 | 一种重组人血小板生成素的制备方法及其制剂 |
SG11201804902UA (en) * | 2015-12-21 | 2018-07-30 | Brainon Inc | A composition for improving memory, learning ability, and cognitive ability |
GB201700621D0 (en) | 2017-01-13 | 2017-03-01 | Guest Ryan Dominic | Method,device and kit for the aseptic isolation,enrichment and stabilsation of cells from mammalian solid tissue |
US20230212565A1 (en) * | 2019-09-20 | 2023-07-06 | Ractigen Therapeutics | Nucleic acid molecule for treating thrombocytopenia and application thereof |
CA3164986A1 (en) | 2019-12-20 | 2021-06-24 | Instil Bio (Uk) Limited | Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5260417A (en) | 1989-04-03 | 1993-11-09 | Genetics Institute, Inc. | Megakaryocyte growth promoting activity protein |
WO1990012877A1 (en) * | 1989-04-19 | 1990-11-01 | Cetus Corporation | Multifunctional m-csf proteins and genes encoding therefor |
US5223408A (en) * | 1991-07-11 | 1993-06-29 | Genentech, Inc. | Method for making variant secreted proteins with altered properties |
ES2160591T3 (es) * | 1991-12-06 | 2001-11-16 | Genentech Inc | Celulas transformadas por convertasas prohormonales. |
IL139335A (en) | 1994-01-03 | 2005-08-31 | Genentech Inc | Mpl ligand polypeptides, nucleic acids encoding them, vectors and host cells comprising such nucleic acids, processes for producing such polypeptides pharmaceutical compositions containing them and use thereof in the preparation of medicaments for treating thrombocytopenia |
-
1994
- 1994-12-21 GB GB9425831A patent/GB2285446B/en not_active Expired - Lifetime
- 1994-12-21 SG SG1996003050A patent/SG47030A1/en unknown
- 1994-12-27 HR HR08/348,658A patent/HRP941020A2/hr not_active Application Discontinuation
- 1994-12-28 SK SK875-96A patent/SK282265B6/sk not_active IP Right Cessation
- 1994-12-28 HU HU9601805A patent/HUT75657A/hu not_active Application Discontinuation
- 1994-12-28 WO PCT/US1994/014553 patent/WO1995018858A1/en active IP Right Grant
- 1994-12-28 CZ CZ0192296A patent/CZ296130B6/cs not_active IP Right Cessation
- 1994-12-28 AU AU15146/95A patent/AU704266B2/en not_active Expired
- 1994-12-28 CA CA2178482A patent/CA2178482C/en not_active Expired - Lifetime
- 1994-12-28 RO RO96-01347A patent/RO117110B1/ro unknown
- 1994-12-28 DK DK149194A patent/DK149194A/da not_active Application Discontinuation
- 1994-12-28 SI SI9420079A patent/SI9420079A/sl unknown
- 1994-12-28 EP EP95906653A patent/EP0738323A1/en not_active Withdrawn
- 1994-12-28 JP JP7518499A patent/JPH09508262A/ja active Pending
- 1994-12-28 CN CNB941947513A patent/CN1134539C/zh not_active Expired - Lifetime
- 1994-12-28 NZ NZ278726A patent/NZ278726A/en not_active IP Right Cessation
- 1994-12-29 IL IL11218494A patent/IL112184A/en not_active IP Right Cessation
- 1994-12-30 PT PT101627A patent/PT101627B/pt not_active IP Right Cessation
- 1994-12-30 ES ES09402681A patent/ES2114786B1/es not_active Expired - Fee Related
-
1995
- 1995-01-02 FR FR9500007A patent/FR2714670B1/fr not_active Expired - Lifetime
- 1995-01-02 IT IT95TO000002A patent/IT1283770B1/it active IP Right Grant
- 1995-01-03 NL NL9500010A patent/NL9500010A/nl active Search and Examination
- 1995-01-03 LU LU88573A patent/LU88573A1/de unknown
- 1995-01-03 IE IE950002A patent/IE72517B1/en not_active IP Right Cessation
-
1996
- 1996-07-02 NO NO19962783A patent/NO326903B1/no not_active IP Right Cessation
- 1996-07-02 FI FI962723A patent/FI121573B/fi not_active IP Right Cessation
- 1996-07-02 BG BG100693A patent/BG63639B1/bg unknown
- 1996-07-24 LV LVP-96-315A patent/LV11632B/xx unknown
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1997
- 1997-03-27 JP JP9074906A patent/JPH10113186A/ja active Pending
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