Anti-bcma heavy chain-only antibodies

Abstract

Anti-BCMA heavy chain-only antibodies (UniAb) and disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat B-cell disorders characterized by the expression of BCMA.

1 . A heavy chain-only antibody binding to human B-Cell Maturation Antigen (BCMA) comprising a heavy chain variable region comprising:
 (a) a CDR1 sequence of SEQ ID NO:1;   (b) a CDR2 sequence of SEQ ID NO:8; and   (c) a CDR3 sequence of SEQ ID NO:14.   
     
     
         2 . The heavy chain-only antibody of  claim 1 , wherein said CDR1, CDR2, and CDR3 sequences are present in a human framework. 
     
     
         3 . The heavy chain-only antibody of  claim 1  further comprising a heavy chain constant region sequence in the absence of a C H 1 sequence. 
     
     
         4 .- 6 . (canceled) 
     
     
         7 . The heavy chain-only antibody of  claim 1 , comprising a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:34. 
     
     
         8 . The heavy chain-only antibody of  claim 7  comprising a heavy chain variable region sequence comprising SEQ ID NO:34. 
     
     
         9 .- 12 . (canceled) 
     
     
         13 . A heavy chain-only antibody binding to human B-Cell Maturation Antigen (BCMA) comprising a heavy chain variable region comprising a heavy chain variable region comprising a CDR1 sequence of SEQ ID NO:1, a CDR2 sequence of SEQ ID NO:8, and a CDR3 sequence of SEQ ID NO:14
 in a human VH framework.   
     
     
         14 .- 21 . (canceled) 
     
     
         22 . A pharmaceutical composition comprising a heavy chain-only antibody of  claim 13 . 
     
     
         23 . A method for the treatment of a B-cell disorder characterized by the expression of BCMA comprising administering to a subject with said disorder an antibody of  claim 13 , optionally wherein the B-cell disorder is multiple myeloma or systemic lupus erythematosus. 
     
     
         24 .- 25 . (canceled) 
     
     
         26 . A polynucleotide encoding an antibody of  claim 13 . 
     
     
         27 . A vector comprising the polynucleotide of  claim 13 . 
     
     
         28 . A cell comprising the vector of  claim 27 . 
     
     
         29 . A method of producing a heavy chain-only antibody binding to human B-Cell Maturation Antigen (BCMA) comprising a heavy chain variable region comprising a heavy chain variable region comprising a CDR1 sequence of SEQ ID NO:1, a CDR2 sequence of SEQ ID NO:8, and a CDR3 sequence of SEQ ID NO:14 in a human VH framework, wherein the method comprises growing a cell according to  claim 28  under conditions permissive for expression of the protein, and isolating the antibody from the cells. 
     
     
         30 . A method of making the antibody of  claim 13  comprising immunizing a UniRat animal with BCMA and identifying BCMA-binding heavy chain sequences. 
     
     
         31 . A heavy chain-only antibody binding to human B-Cell Maturation Antigen (BCMA) comprising:
 (a) a heavy chain variable region comprising a heavy chain variable region comprising a CDR1 sequence of SEQ ID NO:1, a CDR2 sequence of SEQ ID NO:8, and a CDR3 sequence of SEQ ID NO:14 in a human VH framework, and   (b) a heavy chain constant region sequence in the absence of a C H 1 sequence.   
     
     
         32 . The heavy chain-only antibody of  claim 31 , which is multi-specific. 
     
     
         33 . The heavy chain-only antibody of  claim 32 , which is bispecific. 
     
     
         34 . The heavy chain-only antibody of  claim 32 , having binding affinity to an effector cell. 
     
     
         35 . The heavy chain-only antibody of  claim 32 , having binding affinity to a T-cell antigen. 
     
     
         36 . The heavy chain-only antibody of  claim 35 , having binding affinity to CD3. 
     
     
         37 . A pharmaceutical composition comprising a heavy chain-only antibody of  claim 31 . 
     
     
         38 . A method for the treatment of a B-cell disorder characterized by the expression of BCMA comprising administering to a subject with said disorder a pharmaceutical composition of  claim 22 , optionally wherein the B-cell disorder is multiple myeloma or systemic lupus erythematosus.