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US 9,751,932 B2Granted
Anti-big-endothelin-1 (big-ET-1) antibodies and uses thereof
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLori C. Morton, Douglas MacDonald
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AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLori C. Morton, Douglas MacDonald
Estimating the term…
The present invention provides antibodies that bind big-endothelin-1 (“big-ET-1”), and methods of using same. According to certain embodiments of the invention, the antibodies specifically bind human big-ET-1 but do not bind human small-ET-1 (i.e., the active form of endothelin-1 that results from proteolytic cleavage of big-ET-1 by endothelin-converting enzyme-1 [ECE-1]). According to certain embodiments of the invention, the anti-big-ET-1 antibodies are capable of blocking cleavage of big-ET-1 by ECE-1. The antibodies of the invention are useful for the treatment of big-ET-1-related disorders, including hypertension disorders, fibrotic disorders, neurodegenerative disorders, retinal disorders, pain and cancers.
An isolated human antibody or antigen-binding fragment thereof that specifically binds human big-endothelin-1 (big-ET-1) (SEQ ID NO:434), and does not bind small-endothelin-1 (small-ET-1) (SEQ ID NO:435), wherein the antibody or antigen-binding fragment thereof blocks cleavage of big-ET-1 by endothelin-converting enzyme-1 (ECE-1) and comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence selected from the group consisting of SEQ ID NO:2, 18, 34, 50, 66, 146, 162, 194, 210, 226, 242, 258, 274, 290, 322, 338, 370, and 386, and the CDRs of a light chain variable region (LCVR) having the amino acid sequence selected from the group consisting of SEQ ID NO:10, 26, 42, 58, 74, 154, 170, 202, 218, 234, 250, 266, 282, 298, 330, 346, 378, and 394.
Dependencies are inferred from the claim text.