Title:
COMPOSITIONS AND METHODS FOR CANCER TREATMENT BY SELECTIVELY INHIBITING VEGF
Document Type and Number:
WIPO Patent Application WO2000064946
Kind Code:
A3
Abstract:
Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.
Inventors:
THORPE PHILIP E
BREKKEN ROLF A
BREKKEN ROLF A
Application Number:
PCT/US2000/011367
Publication Date:
February 15, 2001
Filing Date:
April 28, 2000
Export Citation:
Assignee:
UNIV TEXAS (US)
International Classes:
A61K39/395; A61K45/00; A61K47/48; A61P9/10; A61P27/02; A61P35/00; A61P43/00; C12N15/02; C07K5/103; C07K14/52; C07K16/22; C07K16/24; C07K16/30; C12N5/02; C12N5/10; C12P21/08; (IPC1-7): C07K16/28; A61K39/395; C12N5/20; C12N15/13; G01N33/577; A61K38/18; A61P35/00
Foreign References:
| US5877289A | 1999-03-02 | |||
| US5855866A | 1999-01-05 |
Other References:
BREKKEN ROLF A ET AL: "Vascular endothelial growth factor as a marker of tumor endothelium.", CANCER RESEARCH, vol. 58, no. 9, 1 May 1998 (1998-05-01), pages 1952 - 1959, XP000918910, ISSN: 0008-5472
MULLER YVES A ET AL: "Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 94, no. 14, 1997, 1997, pages 7192 - 7197, XP000918906, ISSN: 0027-8424
ORTEGA NATHALIE ET AL: "Signal relays in the VEGF system.", FRONTIERS IN BIOSCIENCE, vol. 4, 1 February 1999 (1999-02-01), pages D141 - 152, XP000940560
WITTE LARRY ET AL: "Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy.", CANCER AND METASTASIS REVIEWS, vol. 17, no. 2, June 1998 (1998-06-01), pages 155 - 161, XP000940443, ISSN: 0167-7659
HAISMA H J ET AL: "ANALYSIS OF A CONJUGATE BETWEEN ANTI-CARCINOEMBRYONIC ANTIGEN MONOCLONAL ANTIBODY AND ALKALINE PHOSPHATASE FOR SPECIFIC ACTIVATION OF THE PRODRUG ETOPOSIDE PHOSPHATE", CANCER IMMUNOLOGY IMMUNOTHERAPY, vol. 34, no. 5, 1992, pages 343 - 348, XP000918911, ISSN: 0340-7004
DEONARAIN M P ET AL: "Targeting enzymes for cancer therapy: Old enzymes in new roles.", BRITISH JOURNAL OF CANCER, vol. 70, no. 5, 1994, pages 786 - 794, XP000654784, ISSN: 0007-0920
GIORGIO NICK A ET AL: "Ellipticine conjugated to anti VEGFR2 monoclonal antibodies as reagents for targeting angiogenesis.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, no. 41, March 2000 (2000-03-01), 91st Annual Meeting of the American Association for Cancer Research.;San Francisco, California, USA; April 01-05, 2000, March, 2000, pages 387, XP000918901, ISSN: 0197-016X
HUBER J ET AL: "Vascular endothelial growth factor receptor (VEGFR-2) antibody therapy combined with conventional chemotherapy inhibits growth of established tumors in mice.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, no. 41, March 2000 (2000-03-01), 91st Annual Meeting of the American Association for Cancer Research.;San Francisco, California, USA; April 01-05, 2000, March, 2000, pages 567, XP000918903, ISSN: 0197-016X
MULLER YVES A ET AL: "Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 94, no. 14, 1997, 1997, pages 7192 - 7197, XP000918906, ISSN: 0027-8424
ORTEGA NATHALIE ET AL: "Signal relays in the VEGF system.", FRONTIERS IN BIOSCIENCE, vol. 4, 1 February 1999 (1999-02-01), pages D141 - 152, XP000940560
WITTE LARRY ET AL: "Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy.", CANCER AND METASTASIS REVIEWS, vol. 17, no. 2, June 1998 (1998-06-01), pages 155 - 161, XP000940443, ISSN: 0167-7659
HAISMA H J ET AL: "ANALYSIS OF A CONJUGATE BETWEEN ANTI-CARCINOEMBRYONIC ANTIGEN MONOCLONAL ANTIBODY AND ALKALINE PHOSPHATASE FOR SPECIFIC ACTIVATION OF THE PRODRUG ETOPOSIDE PHOSPHATE", CANCER IMMUNOLOGY IMMUNOTHERAPY, vol. 34, no. 5, 1992, pages 343 - 348, XP000918911, ISSN: 0340-7004
DEONARAIN M P ET AL: "Targeting enzymes for cancer therapy: Old enzymes in new roles.", BRITISH JOURNAL OF CANCER, vol. 70, no. 5, 1994, pages 786 - 794, XP000654784, ISSN: 0007-0920
GIORGIO NICK A ET AL: "Ellipticine conjugated to anti VEGFR2 monoclonal antibodies as reagents for targeting angiogenesis.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, no. 41, March 2000 (2000-03-01), 91st Annual Meeting of the American Association for Cancer Research.;San Francisco, California, USA; April 01-05, 2000, March, 2000, pages 387, XP000918901, ISSN: 0197-016X
HUBER J ET AL: "Vascular endothelial growth factor receptor (VEGFR-2) antibody therapy combined with conventional chemotherapy inhibits growth of established tumors in mice.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, no. 41, March 2000 (2000-03-01), 91st Annual Meeting of the American Association for Cancer Research.;San Francisco, California, USA; April 01-05, 2000, March, 2000, pages 567, XP000918903, ISSN: 0197-016X
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