Title:
METHODS AND COMPOSITIONS USEFUL FOR TARGETING ACTIVATED VITRONECTIN RECEPTOR alpha v beta 3
Document Type and Number:
WIPO Patent Application WO2000034780
Kind Code:
A3
Abstract:
The present invention provides ligands which can selectively bind to activated alpha v beta 3 integrin. A novel monovalent ligand-mimetic (WOW-1 Fab) which includes a single alpha v integrin-binding domain from multivalent adenovirus penton base is provided. Further, the present invention describes particular compositions of activated alpha v beta 3-specific ligands, such as an antibody which immunoreacts preferentially with activated alpha v beta 3 integrin. The invention also describes methods using an activated alpha v beta 3-specific ligand for diagnostic detection of activated alpha v beta 3 integrin in tissues and for the targeted delivery of therapeutic agents to tissues containing activated alpha v beta 3 integrin.
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Inventors:
SHATTIL SANFORD JACK
NEMEROW GLEN ROBERT
HATO TAKAAKI
STUPACK DWAYNE GARRY
PAMPORI NISAR AHMAD
NEMEROW GLEN ROBERT
HATO TAKAAKI
STUPACK DWAYNE GARRY
PAMPORI NISAR AHMAD
Application Number:
PCT/EP1999/009460
Publication Date:
October 19, 2000
Filing Date:
December 03, 1999
Export Citation:
Assignee:
NOVARTIS AG (CH)
NOVARTIS ERFIND VERWALT GMBH (AT)
SCRIPPS RESEARCH INST (US)
NOVARTIS ERFIND VERWALT GMBH (AT)
SCRIPPS RESEARCH INST (US)
International Classes:
G01N33/566; A61K31/711; A61K35/76; A61K38/00; A61K39/395; A61K45/00; A61K48/00; A61P9/00; A61P27/00; A61P29/00; A61P35/00; C07K14/78; C07K16/28; C12N15/09; G01N33/53; G01N33/68; (IPC1-7): G01N33/68; C07K14/705; C07K16/28
Domestic Patent References:
| WO1994017832A1 | 1994-08-18 | |||
| WO1998033919A2 | 1998-08-06 | |||
| WO1993020229A1 | 1993-10-14 |
Other References:
FACCIO R. ET AL: "Activation of. alpha.( v ). beta. 3 integrin on human osteoclast-like cells stimulates adhesion and migration in response to osteopontin.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, (19 AUG 1998) 249/2 (522-525)., XP000919101
PAMPORI NISAR ET AL: "Mechanisms and consequences of affinity modulation of integrin alphaVbeta3 detected with a novel patch-engineered monovalent ligand.", JOURNAL OF BIOLOGICAL CHEMISTRY JULY 30, 1999, vol. 274, no. 31, 30 July 1999 (1999-07-30), pages 21609 - 21616, XP002140739, ISSN: 0021-9258
COLLER B S: "Potential non-glycoprotein IIb/IIIa effects of abciximab.", AMERICAN HEART JOURNAL, (1999 JUL) 138 (1 PT 2) S1-5. REF: 50, XP002140976
VARNER J A ET AL: "REVIEW: THE INTEGRIN ALPHAVBETA3: ANGIOGENESIS AND APOPTOSIS", CELL ADHESION AND COMMUNICATION,US,HARWOOD ACADEMIC PUBLISHERS, GMBH, YVERDON,, vol. 3, no. 4, 1995, pages 367 - 374, XP000857373, ISSN: 1061-5385
ABRAMS CHARLES ET AL: "Determinants of specificity of a baculovirus-expressed antibody Fab fragment that binds selectively to the activated form of integrin alpha-IIb-beta-3.", JOURNAL OF BIOLOGICAL CHEMISTRY 1994, vol. 269, no. 29, 1994, pages 18781 - 18788, XP000910264, ISSN: 0021-9258
SHATTIL SANFORD J ET AL: "Integrin signaling: The platelet paradigm.", BLOOD APRIL 15, 1998, vol. 91, no. 8, 15 April 1998 (1998-04-15), pages 2645 - 2657, XP000915915, ISSN: 0006-4971
MEHTA RAJ J ET AL: "Transmembrane-truncated alphavbeta3 integrin retains high affinity for ligand binding: Evidence for an 'inside-out' suppressor?", BIOCHEMICAL JOURNAL MARCH 1, 1998, vol. 330, no. 2, 1 March 1998 (1998-03-01), pages 861 - 869, XP002140740, ISSN: 0264-6021
PAMPORI NISAR ET AL: "Mechanisms and consequences of affinity modulation of integrin alphaVbeta3 detected with a novel patch-engineered monovalent ligand.", JOURNAL OF BIOLOGICAL CHEMISTRY JULY 30, 1999, vol. 274, no. 31, 30 July 1999 (1999-07-30), pages 21609 - 21616, XP002140739, ISSN: 0021-9258
COLLER B S: "Potential non-glycoprotein IIb/IIIa effects of abciximab.", AMERICAN HEART JOURNAL, (1999 JUL) 138 (1 PT 2) S1-5. REF: 50, XP002140976
VARNER J A ET AL: "REVIEW: THE INTEGRIN ALPHAVBETA3: ANGIOGENESIS AND APOPTOSIS", CELL ADHESION AND COMMUNICATION,US,HARWOOD ACADEMIC PUBLISHERS, GMBH, YVERDON,, vol. 3, no. 4, 1995, pages 367 - 374, XP000857373, ISSN: 1061-5385
ABRAMS CHARLES ET AL: "Determinants of specificity of a baculovirus-expressed antibody Fab fragment that binds selectively to the activated form of integrin alpha-IIb-beta-3.", JOURNAL OF BIOLOGICAL CHEMISTRY 1994, vol. 269, no. 29, 1994, pages 18781 - 18788, XP000910264, ISSN: 0021-9258
SHATTIL SANFORD J ET AL: "Integrin signaling: The platelet paradigm.", BLOOD APRIL 15, 1998, vol. 91, no. 8, 15 April 1998 (1998-04-15), pages 2645 - 2657, XP000915915, ISSN: 0006-4971
MEHTA RAJ J ET AL: "Transmembrane-truncated alphavbeta3 integrin retains high affinity for ligand binding: Evidence for an 'inside-out' suppressor?", BIOCHEMICAL JOURNAL MARCH 1, 1998, vol. 330, no. 2, 1 March 1998 (1998-03-01), pages 861 - 869, XP002140740, ISSN: 0264-6021
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