Bcma-binding antibodies and uses thereof

Abstract

Antibody species that bind B-Cell Maturation Antigen (BCMA) are provided as well as methods of depleting BCMA-expressing cells in a patient in need thereof, comprising administering a therapeutically effective amount of the antibody species or an entity comprising a BCMA binding fragment thereof. Methods of treating B cell-related disorders associated with BCMA expression in a patient in need thereof are provided, comprising administering to the patient a therapeutically effective amount of the antibody species or an entity comprising a BCMA binding fragment thereof.

1 .- 57 . (canceled) 
     
     
         58 . A method of recognizing BCMA +  cells comprising: 
       (i) subjecting cells to an antibody or BCMA-binding fragment thereof comprising:
 (A) heavy chain CDR1, CDR2 and CDR3 sequences:
 a. SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively; 
 b. SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12, respectively; 
 c. SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, respectively; 
 d. SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, respectively; 
 e. SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively; 
 f. SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively; 
 g. SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31, respectively; 
 h. SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, respectively; 
 i. SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37, respectively; 
 j. SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, respectively; 
 k. SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, respectively; 
 l. SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, respectively; 
 m. SEQ ID NO:51, SEQ ID NO:52 and SEQ ID NO:53, respectively; 
 n. SEQ ID NO:54, SEQ ID NO:55 and SEQ ID NO:56, respectively; or 
 o. SEQ ID NO:57, SEQ ID NO:58 and SEQ ID NO:59, respectively; and 
 
 (B) light chain CDR1, CDR2 or CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively; and, 
 
       (ii) recognizing cells to which the antibody binds. 
     
     
         59 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
 p. SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively; 
 q. SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively; or 
 r. SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, respectively. 
 
     
     
         60 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
 s. SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, respectively; 
 t. SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively; or 
 u. SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively. 
 
     
     
         61 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
 v. SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31, respectively; 
 w. SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, respectively; or 
 x. SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37, respectively. 
 
     
     
         62 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
 y. SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, respectively; 
 z. SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, respectively; or 
 aa. SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, respectively. 
 
     
     
         63 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a light chain comprising CDR1, CDR2 and CDR3 sequences SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4, respectively, and heavy chain CDR1, CDR2 and CDR3 sequences:
 bb. SEQ ID NO:51, SEQ ID NO:52 and SEQ ID NO:53, respectively; 
 cc. SEQ ID NO:54, SEQ ID NO:55 and SEQ ID NO:56, respectively; or 
 dd. SEQ ID NO:57, SEQ ID NO:58 and SEQ ID NO:59, respectively. 
 
     
     
         64 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a light chain variable SEQ ID NO:1. 
     
     
         65 . A method according to  claim 58  wherein the antibody or BCMA-binding fragment thereof comprises a heavy chain variable SEQ ID NO:6, SEQ ID NO:17, SEQ ID NO:28, SEQ ID NO:39, or SEQ ID NO:50. 
     
     
         66 . A method according to  claim 58  wherein the BCMA±cells are multiple myeloma cells. 
     
     
         67 . A method according to  claim 66  wherein the antibody exhibits BCMA-dependent, dose-responsive cell-binding.