Cd19 binding agents and uses thereof

Abstract

This invention, inter alia, relates to CD19 binding agents and methods of using such CD19 binding agents for treating disease.

1 . A CD19 binding agent that specifically binds to human CD19, said binding agent comprising a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO:2 or SEQ ID NO:9; the binding agent binding to human CD19 with a dissociation constant of less than 10 −7  M. 
     
     
         2 . The CD19 binding agent of  claim 1  that specifically binds to human CD19 and comprises a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO:2 or SEQ ID NO:9; the binding agent binding to human CD19 with a dissociation constant of less than 10 −7 M and comprising CDR regions having the amino acid sequences set forth in SEQ ID NOS. 46, 47, and 48. 
     
     
         3 . The binding agent of  claim 1  further comprising a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO:17 or SEQ ID NO:26. 
     
     
         4 . The CD19 binding agent of  claim 1 , further comprising a human IgG constant region joined to the heavy chain variable region. 
     
     
         5 . The CD19 binding agent of  claim 4 , wherein the isotype of IgG constant region is IgG1, IgG2, or IgG1V1. 
     
     
         6 . The CD19 binding agent of  claim 3  further comprising a light chain constant domain joined to the light chain variable region. 
     
     
         7 . The CD19 binding agent of  claim 6 , wherein the light chain constant domain is a kappa constant domain. 
     
     
         8 - 17 . (canceled) 
     
     
         18 . A CD19 binding agent that specifically binds to human CD19, said binding agent comprising a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO:17 or SEQ ID NO:26, the binding agent binding to human CD19 with a dissociation constant of less than 10 −7  M. 
     
     
         19 . The CD19 binding agent of  claim 18  that specifically binds to human CD19, said binding agent comprising a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO:17 or SEQ ID NO:26, the binding agent binding to human CD19 with a dissociation constant of less than 10 −7 M and comprising CDR regions having the amino acid sequences set forth in SEQ ID NOS. 49, 50, and 51. 
     
     
         20 . The CD19 binding agent of  claim 1  that comprises a humanized antibody. 
     
     
         21 . The CD19 binding agent of  claim 18  that comprises a humanized antibody. 
     
     
         22 . A CD19 binding agent comprising a heavy chain variable region comprising the amino acid sequence set forth SEQ ID NO:9. 
     
     
         23 . The CD19 binding agent of  claim 22  wherein the CD19 binding agent further comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:24. 
     
     
         24 - 45 . (canceled) 
     
     
         46 . A pharmaceutical composition comprising the ligand-drug conjugate compound of claim  27 , and a pharmaceutically acceptable carrier or excipient. 
     
     
         47 . A pharmaceutical composition comprising the ligand-drug conjugate compound of claim  43 , and a pharmaceutically acceptable carrier or excipient. 
     
     
         48 . A method for treating a CD19-associated disorder in a mammalian subject comprising administering a pharmaceutical composition of  claim 46  in an amount effective to treat the disorder in the mammalian subject. 
     
     
         49 . The method of  claim 48  wherein the CD19-associated disorder is a CD19 expressing cancer. 
     
     
         50 - 76 . (canceled)