CA2355874A1 - Inhibiteurs de l'integrine $g(a)v$g(b)6 - Google Patents
Inhibiteurs de l'integrine $g(a)v$g(b)6 Download PDFInfo
- Publication number
- CA2355874A1 CA2355874A1 CA002355874A CA2355874A CA2355874A1 CA 2355874 A1 CA2355874 A1 CA 2355874A1 CA 002355874 A CA002355874 A CA 002355874A CA 2355874 A CA2355874 A CA 2355874A CA 2355874 A1 CA2355874 A1 CA 2355874A1
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- CA
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- Prior art keywords
- arg
- leu
- asp
- peptide
- thr
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- C07K7/04—Linear peptides containing only normal peptide links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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Abstract
L'invention concerne de nouveaux peptides biologiquement efficaces comme ligands de l'intégrine .alpha.¿v?.beta.¿6?. Ces peptides présentent tous un motif commun, à savoir - Asp Leu Xaa Xaa Leu - ou, sous une forme préférée, - Arg Xaa Asp Leu Xaa Xaa Arg -, où Xaa désigne un reste aminoacide quelconque. Les peptides selon l'invention peuvent être utilisés comme inhibiteurs efficaces du récepteur de l'intégrine .alpha.¿v?.beta.¿6? et, par conséquent, pour le traitement de différentes maladies et de différents états pathologiques.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19858857 | 1998-12-19 | ||
| DE19858857.7 | 1998-12-19 | ||
| PCT/EP1999/009842 WO2000037487A1 (fr) | 1998-12-19 | 1999-12-11 | INHIBITEURS DE L'INTEGRINE $G(a)v$G(b)¿6? |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2355874A1 true CA2355874A1 (fr) | 2000-06-29 |
Family
ID=7891834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002355874A Abandoned CA2355874A1 (fr) | 1998-12-19 | 1999-12-11 | Inhibiteurs de l'integrine $g(a)v$g(b)6 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1140989A1 (fr) |
| JP (1) | JP2002533064A (fr) |
| CN (1) | CN1335853A (fr) |
| AR (1) | AR022395A1 (fr) |
| BR (1) | BR9916323A (fr) |
| CA (1) | CA2355874A1 (fr) |
| CZ (1) | CZ20012212A3 (fr) |
| NO (1) | NO20013013D0 (fr) |
| WO (1) | WO2000037487A1 (fr) |
| ZA (1) | ZA200105929B (fr) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8383593B2 (en) | 2005-10-03 | 2013-02-26 | Cancer Research Technology Limited | αvβ6 peptide ligands and their uses |
| USRE44681E1 (en) | 2006-07-10 | 2013-12-31 | Biogen Idec Ma Inc. | Compositions and methods for inhibiting growth of SMAD4-deficient cancers |
| US8992924B2 (en) | 2005-07-08 | 2015-03-31 | Biogen Idec Ma Inc. | Anti-ανβ6 antibodies and uses thereof |
| US9745376B2 (en) | 2002-03-13 | 2017-08-29 | Biogen Ma Inc. | Anti-ανβ6 antibodies |
| US10035860B2 (en) | 2013-03-15 | 2018-07-31 | Biogen Ma Inc. | Anti-alpha V beta 6 antibodies and uses thereof |
| US10035859B2 (en) | 2013-03-15 | 2018-07-31 | Biogen Ma Inc. | Anti-alpha V beta 6 antibodies and uses thereof |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19929410A1 (de) * | 1999-06-26 | 2000-12-28 | Merck Patent Gmbh | Inhibitoren des Integrins avß6 |
| DE19933173A1 (de) * | 1999-07-15 | 2001-01-18 | Merck Patent Gmbh | Cyclische Peptidderivate als Inhibitoren des Integrins alpha¶v¶beta¶6¶ |
| US7759302B2 (en) * | 2003-02-06 | 2010-07-20 | Merck Patent Gmbh | Peptidic sulfonamides |
| KR20090039739A (ko) | 2006-08-03 | 2009-04-22 | 아스트라제네카 아베 | αVβ6에 대해 작용하는 항체 및 그의 용도 |
| AU2007354317A1 (en) * | 2006-10-19 | 2008-12-04 | Biogen Idec Ma Inc. | Treatment and prevention of chronic asthma using antagonists of integrin alphaVbeta6 |
| WO2009093251A2 (fr) * | 2008-01-24 | 2009-07-30 | Gavish-Galilee Bio Applications Ltd | Vaccin contenant un réovirus basé sur une séquence de protéine sigma c |
| KR101510941B1 (ko) * | 2012-07-03 | 2015-04-10 | 일양약품주식회사 | 신규한 펩타이드 및 이의 용도 |
| SG11201907820SA (en) | 2017-02-28 | 2019-09-27 | Morphic Therapeutic Inc | Inhibitors of (alpha-v)(beta-6) integrin |
| US11046685B2 (en) | 2017-02-28 | 2021-06-29 | Morphic Therapeutic, Inc. | Inhibitors of (α-v)(β-6) integrin |
| CA3109534A1 (fr) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | Inhibition de l'integrine .alpha.v .beta.6 |
| UY38352A (es) | 2018-08-29 | 2020-03-31 | Morphic Therapeutic Inc | Inhibidores de integrina alfavbeta6 |
| EP3843727A4 (fr) | 2018-08-29 | 2022-08-17 | Morphic Therapeutic, Inc. | Inhibiteurs de l'intégrine (alpha-v)(bêta-6) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ219515A (en) * | 1987-02-10 | 1989-09-27 | Wellcome Found | Fusion proteins comprising influenza virus ha and a nonnatural antigenic epitope |
-
1999
- 1999-12-11 JP JP2000589556A patent/JP2002533064A/ja active Pending
- 1999-12-11 EP EP99963507A patent/EP1140989A1/fr not_active Withdrawn
- 1999-12-11 CA CA002355874A patent/CA2355874A1/fr not_active Abandoned
- 1999-12-11 CN CN99814760A patent/CN1335853A/zh active Pending
- 1999-12-11 BR BR9916323-3A patent/BR9916323A/pt not_active IP Right Cessation
- 1999-12-11 CZ CZ20012212A patent/CZ20012212A3/cs unknown
- 1999-12-11 WO PCT/EP1999/009842 patent/WO2000037487A1/fr not_active Ceased
- 1999-12-17 AR ARP990106525A patent/AR022395A1/es not_active Application Discontinuation
-
2001
- 2001-06-18 NO NO20013013A patent/NO20013013D0/no not_active Application Discontinuation
- 2001-07-18 ZA ZA200105929A patent/ZA200105929B/en unknown
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9745376B2 (en) | 2002-03-13 | 2017-08-29 | Biogen Ma Inc. | Anti-ανβ6 antibodies |
| US8992924B2 (en) | 2005-07-08 | 2015-03-31 | Biogen Idec Ma Inc. | Anti-ανβ6 antibodies and uses thereof |
| US8383593B2 (en) | 2005-10-03 | 2013-02-26 | Cancer Research Technology Limited | αvβ6 peptide ligands and their uses |
| US8927501B2 (en) | 2005-10-03 | 2015-01-06 | Cancer Research Technology Limited | αvβ6 peptide ligands and their uses |
| US9650416B2 (en) | 2005-10-03 | 2017-05-16 | Cancer Research Technology Limited | αvβ6 peptide ligands and their uses |
| USRE44681E1 (en) | 2006-07-10 | 2013-12-31 | Biogen Idec Ma Inc. | Compositions and methods for inhibiting growth of SMAD4-deficient cancers |
| US10035860B2 (en) | 2013-03-15 | 2018-07-31 | Biogen Ma Inc. | Anti-alpha V beta 6 antibodies and uses thereof |
| US10035859B2 (en) | 2013-03-15 | 2018-07-31 | Biogen Ma Inc. | Anti-alpha V beta 6 antibodies and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000037487A8 (fr) | 2001-03-29 |
| BR9916323A (pt) | 2001-10-30 |
| CZ20012212A3 (cs) | 2001-09-12 |
| NO20013013L (no) | 2001-06-18 |
| ZA200105929B (en) | 2003-03-18 |
| NO20013013D0 (no) | 2001-06-18 |
| EP1140989A1 (fr) | 2001-10-10 |
| AR022395A1 (es) | 2002-09-04 |
| WO2000037487A1 (fr) | 2000-06-29 |
| JP2002533064A (ja) | 2002-10-08 |
| CN1335853A (zh) | 2002-02-13 |
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