JP4897050B2 - 抗血管形成化合物 - Google Patents
抗血管形成化合物 Download PDFInfo
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- JP4897050B2 JP4897050B2 JP2009535878A JP2009535878A JP4897050B2 JP 4897050 B2 JP4897050 B2 JP 4897050B2 JP 2009535878 A JP2009535878 A JP 2009535878A JP 2009535878 A JP2009535878 A JP 2009535878A JP 4897050 B2 JP4897050 B2 JP 4897050B2
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- antibody
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
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| US86536006P | 2006-11-10 | 2006-11-10 | |
| US60/865,360 | 2006-11-10 | ||
| US93983007P | 2007-05-23 | 2007-05-23 | |
| US60/939,830 | 2007-05-23 | ||
| US94532907P | 2007-06-20 | 2007-06-20 | |
| US60/945,329 | 2007-06-20 | ||
| PCT/IE2007/000110 WO2008056346A2 (en) | 2006-11-10 | 2007-11-12 | Anti-angiogenic compounds |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011283619A Division JP2012121886A (ja) | 2006-11-10 | 2011-12-26 | 抗血管形成化合物 |
Publications (3)
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| JP2010509315A JP2010509315A (ja) | 2010-03-25 |
| JP2010509315A5 JP2010509315A5 (enExample) | 2010-12-16 |
| JP4897050B2 true JP4897050B2 (ja) | 2012-03-14 |
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| JP2009535878A Expired - Fee Related JP4897050B2 (ja) | 2006-11-10 | 2007-11-12 | 抗血管形成化合物 |
| JP2011283619A Ceased JP2012121886A (ja) | 2006-11-10 | 2011-12-26 | 抗血管形成化合物 |
Family Applications After (1)
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| JP2011283619A Ceased JP2012121886A (ja) | 2006-11-10 | 2011-12-26 | 抗血管形成化合物 |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US8288349B2 (enExample) |
| EP (2) | EP2089425B1 (enExample) |
| JP (2) | JP4897050B2 (enExample) |
| KR (2) | KR101309948B1 (enExample) |
| CN (1) | CN101611053B (enExample) |
| AT (1) | ATE520712T1 (enExample) |
| AU (1) | AU2007318912B2 (enExample) |
| BR (1) | BRPI0718591A2 (enExample) |
| CA (1) | CA2669207A1 (enExample) |
| DK (1) | DK2089425T3 (enExample) |
| IL (1) | IL198581A (enExample) |
| MX (1) | MX2009005045A (enExample) |
| MY (1) | MY146985A (enExample) |
| NO (1) | NO20092203L (enExample) |
| NZ (1) | NZ576751A (enExample) |
| PL (1) | PL2089425T3 (enExample) |
| PT (1) | PT2089425E (enExample) |
| WO (1) | WO2008056346A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012121886A (ja) * | 2006-11-10 | 2012-06-28 | Covx Technologies Ireland Ltd | 抗血管形成化合物 |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090098130A1 (en) * | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
| US8293714B2 (en) | 2008-05-05 | 2012-10-23 | Covx Technology Ireland, Ltd. | Anti-angiogenic compounds |
| WO2010036930A1 (en) * | 2008-09-26 | 2010-04-01 | Javad Parvizi | Methods and kits for detecting joint infection |
| SG186451A1 (en) * | 2010-07-12 | 2013-01-30 | Covx Technologies Ireland Ltd | Multifunctional antibody conjugates |
| SG190082A1 (en) | 2010-11-05 | 2013-06-28 | Covx Technologies Ireland Ltd | Anti-diabetic compounds |
| EP2726088B1 (en) | 2011-06-29 | 2019-01-02 | Amgen Inc. | Predictive biomarker of survival in the treatment of renal cell carcinoma |
| SG11201403324TA (en) * | 2011-12-20 | 2014-07-30 | Pfizer | Improved processes for preparing peptide conjugates and linkers |
| US20130323234A1 (en) * | 2012-01-09 | 2013-12-05 | Covx Technologies Ireland Limited | Mutant antibodies and conjugation thereof |
| WO2013148877A1 (en) | 2012-03-28 | 2013-10-03 | Amgen Inc. | Dr5 receptor agonist combinations |
| DK3007717T3 (da) | 2013-06-12 | 2019-01-02 | Pharis Biotec Gmbh | Peptider med antagonistiske aktiviteter mod naturlig cxcr4 |
| WO2015014376A1 (en) * | 2013-07-31 | 2015-02-05 | Biontech Ag | Diagnosis and therapy of cancer involving cancer stem cells |
| PT3057585T (pt) * | 2013-10-15 | 2020-10-21 | Seagen Inc | Fármaco-ligadores peguilados para farmacocinética melhorada de conjugados de fármaco-ligando |
| WO2016209972A1 (en) | 2015-06-26 | 2016-12-29 | Amgen Inc. | Biomarker of survival in the treatment of renal cell carcinoma with a vegfr inhibitor and an ang2 inhibitor |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| US11229708B2 (en) | 2015-12-04 | 2022-01-25 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| EP3433278A4 (en) | 2016-03-25 | 2019-11-06 | Seattle Genetics, Inc. | METHOD FOR THE PRODUCTION OF PEGYLATED ACTIVE LINKERS AND INTERMEDIATE PRODUCTS THEREOF |
| SG10201912034UA (en) | 2017-02-08 | 2020-02-27 | Bristol Myers Squibb Co | Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof |
| JP7527787B2 (ja) | 2017-03-24 | 2024-08-05 | シージェン インコーポレイテッド | グルクロニド薬物－リンカーの調製のためのプロセスおよびその中間体 |
| CA3061467A1 (en) | 2017-04-28 | 2019-10-24 | Ajinomoto Co., Inc. | Compound having affinity substance to soluble protein, cleavable portionand reactive group, or salt thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005514024A (ja) * | 2001-10-11 | 2005-05-19 | アムジエン・インコーポレーテツド | ヒトアンギオポエチン−２の特異的結合物質 |
| WO2006010057A2 (en) * | 2004-07-08 | 2006-01-26 | Amgen Inc. | Therapeutic peptides |
| WO2006036834A2 (en) * | 2004-09-24 | 2006-04-06 | Amgen Inc. | MODIFIED Fc MOLECULES |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719667A (en) | 1970-08-24 | 1973-03-06 | Lilly Co Eli | Epimerization of 6-acylamido and 6-imido penicillin sulfoxide esters |
| US3840556A (en) | 1971-05-28 | 1974-10-08 | Lilly Co Eli | Penicillin conversion by halogen electrophiles and anti-bacterials derived thereby |
| US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
| US5216132A (en) | 1990-01-12 | 1993-06-01 | Protein Design Labs, Inc. | Soluble t-cell antigen receptor chimeric antigens |
| ATE155482T1 (de) | 1990-04-06 | 1997-08-15 | Jolla Cancer Res Found | Verfahren und verbindung zur behandlung von thrombose |
| US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| US6080840A (en) | 1992-01-17 | 2000-06-27 | Slanetz; Alfred E. | Soluble T cell receptors |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US5981478A (en) | 1993-11-24 | 1999-11-09 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
| US5733757A (en) | 1995-12-15 | 1998-03-31 | The Scripps Research Institute | Aldolase catalytic antibody |
| US5739277A (en) | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
| DE19544393A1 (de) | 1995-11-15 | 1997-05-22 | Hoechst Schering Agrevo Gmbh | Synergistische herbizide Mischungen |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| US6326176B1 (en) * | 1997-12-18 | 2001-12-04 | The Scripps Research Institute | Aldol condensations by catalytic antibodies |
| AU1190101A (en) | 1999-09-27 | 2001-04-30 | Regents Of The University Of California, The | Engineering antibodies that bind irreversibly |
| US6294374B1 (en) * | 1999-10-08 | 2001-09-25 | The Scripps Research Institute | Use of catalytic antibodies for synthesizing epothilone |
| JP4303105B2 (ja) | 2001-06-28 | 2009-07-29 | ドマンティス リミテッド | 二重特異性リガンドとその利用 |
| US20030045477A1 (en) | 2001-07-26 | 2003-03-06 | Fortuna Haviv | Peptides having antiangiogenic activity |
| US7205275B2 (en) * | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
| KR20040058229A (ko) * | 2001-10-22 | 2004-07-03 | 더 스크립스 리서치 인스티튜트 | 항체 표적화 화합물 |
| US6737524B2 (en) * | 2002-03-25 | 2004-05-18 | Paul K. Smith | Activated polyethylene glycol compounds |
| CN1678634A (zh) | 2002-06-28 | 2005-10-05 | 多曼蒂斯有限公司 | 免疫球蛋白单个变体抗原结合区及其特异性构建体 |
| CA2511910A1 (en) | 2002-12-27 | 2004-07-15 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| BRPI0718591A2 (pt) * | 2006-11-10 | 2013-12-03 | Covx Technologies Ireland Ltd | Compostos antiangiogênicos. |
-
2007
- 2007-11-12 BR BRPI0718591-0A patent/BRPI0718591A2/pt not_active IP Right Cessation
- 2007-11-12 AT AT07827123T patent/ATE520712T1/de active
- 2007-11-12 CA CA002669207A patent/CA2669207A1/en not_active Abandoned
- 2007-11-12 WO PCT/IE2007/000110 patent/WO2008056346A2/en not_active Ceased
- 2007-11-12 DK DK07827123.6T patent/DK2089425T3/da active
- 2007-11-12 CN CN200780049649.0A patent/CN101611053B/zh not_active Expired - Fee Related
- 2007-11-12 NZ NZ576751A patent/NZ576751A/en not_active IP Right Cessation
- 2007-11-12 JP JP2009535878A patent/JP4897050B2/ja not_active Expired - Fee Related
- 2007-11-12 EP EP07827123A patent/EP2089425B1/en not_active Not-in-force
- 2007-11-12 AU AU2007318912A patent/AU2007318912B2/en not_active Ceased
- 2007-11-12 PL PL07827123T patent/PL2089425T3/pl unknown
- 2007-11-12 KR KR1020097011924A patent/KR101309948B1/ko not_active Expired - Fee Related
- 2007-11-12 KR KR1020127005049A patent/KR20120043028A/ko not_active Ceased
- 2007-11-12 MY MYPI20091889A patent/MY146985A/en unknown
- 2007-11-12 EP EP20110170480 patent/EP2368908A3/en not_active Withdrawn
- 2007-11-12 US US11/938,766 patent/US8288349B2/en not_active Expired - Fee Related
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2009
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2011
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2012
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2014
- 2014-10-31 US US14/530,444 patent/US20150057431A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005514024A (ja) * | 2001-10-11 | 2005-05-19 | アムジエン・インコーポレーテツド | ヒトアンギオポエチン−２の特異的結合物質 |
| WO2006010057A2 (en) * | 2004-07-08 | 2006-01-26 | Amgen Inc. | Therapeutic peptides |
| WO2006036834A2 (en) * | 2004-09-24 | 2006-04-06 | Amgen Inc. | MODIFIED Fc MOLECULES |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012121886A (ja) * | 2006-11-10 | 2012-06-28 | Covx Technologies Ireland Ltd | 抗血管形成化合物 |
Also Published As
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| US8912148B2 (en) | 2014-12-16 |
| CN101611053B (zh) | 2015-06-03 |
| IL198581A (en) | 2015-10-29 |
| WO2008056346A2 (en) | 2008-05-15 |
| PT2089425E (pt) | 2011-10-17 |
| WO2008056346B1 (en) | 2008-12-04 |
| DK2089425T3 (da) | 2011-10-10 |
| US20080166364A1 (en) | 2008-07-10 |
| EP2368908A2 (en) | 2011-09-28 |
| KR20120043028A (ko) | 2012-05-03 |
| JP2012121886A (ja) | 2012-06-28 |
| BRPI0718591A2 (pt) | 2013-12-03 |
| CN101611053A (zh) | 2009-12-23 |
| US8288349B2 (en) | 2012-10-16 |
| US20150057431A1 (en) | 2015-02-26 |
| CA2669207A1 (en) | 2008-05-15 |
| NZ576751A (en) | 2011-10-28 |
| ATE520712T1 (de) | 2011-09-15 |
| JP2010509315A (ja) | 2010-03-25 |
| AU2007318912B2 (en) | 2011-03-03 |
| MY146985A (en) | 2012-10-15 |
| MX2009005045A (es) | 2009-11-10 |
| EP2089425A2 (en) | 2009-08-19 |
| AU2007318912A1 (en) | 2008-05-15 |
| PL2089425T3 (pl) | 2012-02-29 |
| IL198581A0 (en) | 2011-08-01 |
| WO2008056346A3 (en) | 2008-10-23 |
| US20120301431A1 (en) | 2012-11-29 |
| EP2368908A3 (en) | 2011-10-12 |
| EP2089425B1 (en) | 2011-08-17 |
| NO20092203L (no) | 2009-08-10 |
| KR20090090331A (ko) | 2009-08-25 |
| KR101309948B1 (ko) | 2013-09-23 |
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