Imclone Systems, Inc.

Imclone LLC

Daniel J Hicklin

Peter Bohlen

Yan Wu

Charles T Tackney

Fang Liao

Harlan W Waksal

Monoclonal antibodies that are specific for vascular endothelial growth factor receptor 1 (VEGFR-I). This invention also provides nucleotide sequences encoding and amino acid sequences comprising variable heavy and light chain immunoglobulin molecules, including sequences corresponding to the complementarity determining regions of CDR1, CDR2, and CDR3. The invention also provides methods for generation and expression of anti-VEGFR-I antibodies and methods of treating angiogenic-related disorders and reducing tumor growth by administering anti-VEGFR-I antibodies.

Antibodies against vascular endothelial growth factor receptor-1

The murine epitope sequence recognized by antibody E4B9 shares 100% homology with human VE-cadherin, so this antibody was examined to determine if it cross-reacts with human VIE-cadherin. Western-blot analysis of several VE-cadherin expressing human and murine ceH indicated that E4B9 indeed cross-reacts with human VE-cadherin (FIG.). This finding facilitates development of a 'humanized' E4B9 antibody and its success in the prectinical development since its anti-tumor activity can be tested extensively in several mouse models.

Antibody antagonists of VE-cadherin without adverse effects on vascular permeability

Methods and materials for producing hepatitis virus HBe antigenic proteins useful in immunoassays without the necessity of maintaining these proteins in denaturing environments are disclosed. Assay methods and materials utilizing these HBe proteins are also provided.

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Upper Montclair, NJ, United States of America

Daniel J Hicklin