JP2002502359A - 内皮細胞増殖阻害剤およびその使用法 - Google Patents
内皮細胞増殖阻害剤およびその使用法Info
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- JP2002502359A JP2002502359A JP52383197A JP52383197A JP2002502359A JP 2002502359 A JP2002502359 A JP 2002502359A JP 52383197 A JP52383197 A JP 52383197A JP 52383197 A JP52383197 A JP 52383197A JP 2002502359 A JP2002502359 A JP 2002502359A
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- C07K7/04—Linear peptides containing only normal peptide links
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- C—CHEMISTRY; METALLURGY
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
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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
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- C07K14/745—Blood coagulation or fibrinolysis factors
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.プラスミノーゲン分子のクリングル5ペプチドをコードするアミノ酸配列 を有し、且つ約14kDの分子量を有する単離されたタンパク質。 2.タンパク質が約80のアミノ酸を含む請求の範囲第1項に記載のタンパク 質。 3.プラスミノーゲンがヒトプラスミノーゲンである請求の範囲第1項に記載 のタンパク質。 4.タンパク質がヒトプラスミノーゲン分子の約462のアミノ酸から始まり 約80のアミノ酸に伸びるヒトプラスミノーゲン分子に対応したアミノ酸配列を 有する請求の範囲第1項に記載のタンパク質。 5.タンパク質が内皮細胞増殖阻害能を有する請求の範囲第1項に記載のタン パク質。 6.プラスミノーゲン分子のクリングル5ペプチドをコードするアミノ酸配列 を有し、且つ約14kDの分子量を有するタンパク質を内皮細胞に対し有効な量 投与することを含む、内皮細胞の増殖を阻害する方法。 7.タンパク質が約80のアミノ酸を含む請求の範囲第6項に記載の方法。 8.プラスミノーゲンがヒトプラスミノーゲンである請求の範囲第6項に記載 の方法。 9.タンパク質がヒトプラスミノーゲンの約462のアミノ酸から始まり約8 0のアミノ酸に伸びるヒトプラスミノーゲン分子に対応したアミノ酸配列を有す る請求の範囲第6項に記載の方法。 10.個体に、プラスミノーゲン分子のクリングル5ペプチドをコードするア ミノ酸配列を有し、且つ約14kDの分子量を有するタンパク質を有効な量投与 することを含む、血管形成により仲介された疾患を有する個体を治療する方法。 11.タンパク質が約80のアミノ酸からなる請求の範囲第10項に記載の方 法。 12.プラスミノーゲンがヒトプラスミノーゲンである請求の範囲第10項に 記載の方法。 13.タンパク質がヒトプラスミノーゲン分子の462のアミノ酸から始まり 約80のアミノ酸に伸びるヒトプラスミノーゲンタンパク質に対応するアミノ酸 配列を有する請求の範囲第10項に記載の方法。 14.タンパク質が内皮細胞増殖阻害能を有する請求の範囲第10項に記載の 方法。 15.血管形成により仲介された疾患がガンである請求の範囲第10項に記載 の方法。 16.ガンが固体腫瘍である請求の範囲第15項に記載の方法。 17.プラスミノーゲン分子のクリングル5ペプチドをコードするアミノ酸配 列を有し、且つ約14kDの分子量を有するタンパク質を含む医薬組成物。 18.タンパク質が約80のアミノ酸からなる請求の範囲第17項に記載の医 薬組成物。 19.プラスミノーゲンがヒトプラスミノーゲンである請求の範囲第17項に 記載の医薬組成物。 20.タンパク質がヒトプラスミノーゲン分子の約462のアミノ酸から始ま り約80のアミノ酸に伸びるヒトプラスミノーゲン分子に対応するアミノ酸配列 を有する請求の範囲第17項に記載の医薬組成物。 21.タンパク質が内皮細胞増殖阻害能を有する請求の範囲第17項に記載の 医薬組成物。 22.プラスミノーゲン分子のクリングル5ペプチドをコードするアミノ酸配 列を有し、且つ約14kDの分子量を有するタンパク質に特異的に結合可能な単 離した抗体。 23.タンパク質が約80のアミノ酸を含む請求の範囲第22項に記載の抗体 。 24.プラスミノーゲンがヒトプラスミノーゲンである請求の範囲第22項に 記載の抗体。 25.タンパク質がヒトプラスミノーゲン分子の約462のアミノ酸から始ま り約80のアミノ酸に伸びるヒトプラスミノーゲン分子に対応するアミノ酸配列 を有する請求の範囲第22項に記載の抗体。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US851995P | 1995-12-13 | 1995-12-13 | |
US60/008,519 | 1995-12-13 | ||
US08/763,528 US5854221A (en) | 1996-12-12 | 1996-12-12 | Endothelial cell proliferation inhibitor and method of use |
US08/763,528 | 1996-12-12 | ||
PCT/US1996/020447 WO1997023500A1 (en) | 1995-12-13 | 1996-12-13 | Endothelial cell proliferation inhibitor and method of use |
Publications (2)
Publication Number | Publication Date |
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JP2002502359A true JP2002502359A (ja) | 2002-01-22 |
JP3684371B2 JP3684371B2 (ja) | 2005-08-17 |
Family
ID=26678280
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP52383197A Expired - Fee Related JP3684371B2 (ja) | 1995-12-13 | 1996-12-13 | 内皮細胞増殖阻害剤およびその使用法 |
Country Status (20)
Country | Link |
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US (1) | US20010016644A1 (ja) |
EP (1) | EP0869970B1 (ja) |
JP (1) | JP3684371B2 (ja) |
KR (1) | KR100477280B1 (ja) |
CN (1) | CN1554444A (ja) |
AT (1) | ATE262537T1 (ja) |
AU (1) | AU710612B2 (ja) |
BR (1) | BR9612115A (ja) |
CA (1) | CA2240296C (ja) |
CZ (1) | CZ298612B6 (ja) |
DE (1) | DE69631972T2 (ja) |
DK (1) | DK0869970T3 (ja) |
ES (1) | ES2217340T3 (ja) |
HK (1) | HK1017692A1 (ja) |
HU (1) | HUP9900979A3 (ja) |
NO (1) | NO321775B1 (ja) |
NZ (1) | NZ330537A (ja) |
PL (1) | PL188719B1 (ja) |
PT (1) | PT869970E (ja) |
WO (1) | WO1997023500A1 (ja) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997023500A1 (en) * | 1995-12-13 | 1997-07-03 | The Children's Medical Center Corporation | Endothelial cell proliferation inhibitor and method of use |
US6699838B1 (en) | 1996-05-03 | 2004-03-02 | Abbott Laboratories | Antiangiogenic peptides |
WO1997041824A2 (en) * | 1996-05-03 | 1997-11-13 | Abbott Laboratories | Antiangiogenic peptides derived from plasminogen |
US5801146A (en) * | 1996-05-03 | 1998-09-01 | Abbott Laboratories | Compound and method for inhibiting angiogenesis |
US5801012A (en) | 1996-09-17 | 1998-09-01 | Northwestern University | Methods and compositions for generating angiostatin |
WO1999000420A1 (en) * | 1997-06-26 | 1999-01-07 | Karolinska Innovations Ab | Kringle domains 1-5 of plasminogen, capable of modulating angiogenesis in vivo |
WO1999026480A1 (en) * | 1997-11-20 | 1999-06-03 | Genetix Pharmaceuticals, Inc. | Anti-angiogenic gene therapy vectors and their use in treating angiogenesis-related diseases |
US6632961B1 (en) | 1998-05-22 | 2003-10-14 | Abbott Laboratories | Antiangiogenic drug to treat cancer, arthritis and retinopathy |
DE60006100T2 (de) | 1999-05-17 | 2004-07-01 | Conjuchem, Inc., Montreal | Lang wirkende insulinotrope peptide |
US7144854B1 (en) | 1999-09-10 | 2006-12-05 | Conjuchem, Inc. | Long lasting anti-angiogenic peptides |
JP4209086B2 (ja) * | 1999-05-17 | 2009-01-14 | コンジュケム バイオテクノロジーズ インコーポレイテッド | 長期持続性抗新脈管形成ペプチド |
CA2394167A1 (en) * | 1999-12-15 | 2001-06-21 | Entremed, Inc. | Compositions and methods for inhibiting endothelial cell proliferation |
AU8591901A (en) | 2000-09-05 | 2002-03-22 | Karolinska Innovations Ab | Materials and methods relating to endothelial cell growth inhibitors |
AU2002239414A1 (en) * | 2000-11-02 | 2002-05-27 | Bristol-Myers Squibb Company | Modified plasminogen related peptide fragments and their use as angiogenesis inhibitors |
WO2005072341A2 (en) * | 2004-01-21 | 2005-08-11 | Fujirebio America, Inc. | Detection of mesothelin-/megakaryocyte potentiating factor-related peptides in peritoneal fluid for assessment of the peritoneum and the peritoneal cavity |
CN100355458C (zh) * | 2005-03-16 | 2007-12-19 | 北京大学 | 人增殖抑制基因-腺病毒表达载体的应用 |
WO2010138631A1 (en) | 2009-05-26 | 2010-12-02 | Biolex Therapeutics, Inc. | Compositions and methods for production of aglycosylated plasminogen |
CN103060265B (zh) * | 2013-01-23 | 2014-12-03 | 山东大学 | 老年大鼠脑血管内皮细胞原代培养方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4929444A (en) * | 1985-05-28 | 1990-05-29 | Burroughs Wellcome Co. | Low pH pharmaceutical formulation containing t-PA |
US5149533A (en) * | 1987-06-04 | 1992-09-22 | Zymogenetics, Inc. | Modified t-PA with kringle-/replaced by another kringle |
US5302390A (en) * | 1987-07-01 | 1994-04-12 | Beecham Group Plc | Hybrid proteins of human plasminogen and human t-PA, pharmaceutical compositions and methods of treatment |
HUT64977A (en) * | 1992-07-30 | 1994-03-28 | Yeda Res & Dev | Synthetical peptone derivatives of vitronectine and pharmaceutical preparaties containing them |
CN1309833C (zh) * | 1994-04-26 | 2007-04-11 | 儿童医学中心公司 | 血管生成抑制素及其在制备药物中的用途 |
JPH09512426A (ja) * | 1994-04-26 | 1997-12-16 | ファルマシア・アンド・アップジョン・カンパニー | 好中球の接着および移動の遮断に有用なMac−1 I−ドメイン蛋白質 |
CA2219081C (en) * | 1995-04-26 | 2004-02-24 | The Children's Medical Center Corporation | Angiostatin fragments and aggregate angiostatin and methods of use |
WO1997023500A1 (en) * | 1995-12-13 | 1997-07-03 | The Children's Medical Center Corporation | Endothelial cell proliferation inhibitor and method of use |
-
1996
- 1996-12-13 WO PCT/US1996/020447 patent/WO1997023500A1/en active IP Right Grant
- 1996-12-13 PT PT96945635T patent/PT869970E/pt unknown
- 1996-12-13 NZ NZ330537A patent/NZ330537A/en not_active IP Right Cessation
- 1996-12-13 AT AT96945635T patent/ATE262537T1/de active
- 1996-12-13 CA CA002240296A patent/CA2240296C/en not_active Expired - Fee Related
- 1996-12-13 CZ CZ0182898A patent/CZ298612B6/cs not_active IP Right Cessation
- 1996-12-13 DE DE69631972T patent/DE69631972T2/de not_active Expired - Lifetime
- 1996-12-13 JP JP52383197A patent/JP3684371B2/ja not_active Expired - Fee Related
- 1996-12-13 ES ES96945635T patent/ES2217340T3/es not_active Expired - Lifetime
- 1996-12-13 AU AU16870/97A patent/AU710612B2/en not_active Ceased
- 1996-12-13 HU HU9900979A patent/HUP9900979A3/hu unknown
- 1996-12-13 KR KR10-1998-0704447A patent/KR100477280B1/ko not_active IP Right Cessation
- 1996-12-13 BR BR9612115A patent/BR9612115A/pt not_active Application Discontinuation
- 1996-12-13 CN CNA2004100432779A patent/CN1554444A/zh active Pending
- 1996-12-13 EP EP96945635A patent/EP0869970B1/en not_active Expired - Lifetime
- 1996-12-13 PL PL96327200A patent/PL188719B1/pl unknown
- 1996-12-13 DK DK96945635T patent/DK0869970T3/da active
-
1998
- 1998-06-12 NO NO19982715A patent/NO321775B1/no not_active IP Right Cessation
-
1999
- 1999-06-23 HK HK99102688.5A patent/HK1017692A1/xx not_active IP Right Cessation
-
2000
- 2000-12-29 US US09/753,064 patent/US20010016644A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
HUP9900979A3 (en) | 2001-10-29 |
HUP9900979A2 (hu) | 1999-07-28 |
NO982715L (no) | 1998-08-12 |
NO982715D0 (no) | 1998-06-12 |
CA2240296A1 (en) | 1997-07-03 |
ATE262537T1 (de) | 2004-04-15 |
JP3684371B2 (ja) | 2005-08-17 |
PL188719B1 (pl) | 2005-04-29 |
AU1687097A (en) | 1997-07-17 |
BR9612115A (pt) | 1999-02-17 |
DK0869970T3 (da) | 2004-07-05 |
ES2217340T3 (es) | 2004-11-01 |
CZ182898A3 (cs) | 1998-10-14 |
NO321775B1 (no) | 2006-07-03 |
KR19990072126A (ko) | 1999-09-27 |
CA2240296C (en) | 2004-05-04 |
US20010016644A1 (en) | 2001-08-23 |
EP0869970B1 (en) | 2004-03-24 |
DE69631972D1 (de) | 2004-04-29 |
PL327200A1 (en) | 1998-11-23 |
NZ330537A (en) | 2001-06-29 |
DE69631972T2 (de) | 2005-01-05 |
WO1997023500A1 (en) | 1997-07-03 |
EP0869970A1 (en) | 1998-10-14 |
EP0869970A4 (en) | 2002-01-30 |
HK1017692A1 (en) | 1999-11-26 |
AU710612B2 (en) | 1999-09-23 |
KR100477280B1 (ko) | 2005-07-18 |
CN1554444A (zh) | 2004-12-15 |
PT869970E (pt) | 2004-08-31 |
CZ298612B6 (cs) | 2007-11-21 |
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