Compositions and methods related to anti-cd19 antibody drug conjugates

Abstract

The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-CD19 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind CD19, as well as methods of making and using these anti-CD19 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications.

1 - 142 . (canceled) 
     
     
         143 . An antibody or antigen-binding fragment thereof that binds CD19, wherein the antibody or antigen binding thereof comprises a variable heavy chain complimentary determining region 1 (CDRH1), a variable heavy chain complimentary determining region 2 (CDRH2), a variable heavy chain complimentary determining region 3 (CDRH3), a variable light chain complimentary determining region 1 (CDRL1), a variable light chain complimentary determining region 2 (CDRL2), and a variable light chain complimentary determining region 3 (CDRL3); wherein,
 CDRH1 comprises the amino acid sequence of SEQ ID NO: 23 or 29;   CDRH2 comprises the amino acid sequence of SEQ ID NO: 24 or 30;   CDRH3 comprises the amino acid sequence of SEQ ID NO: 25, 26, 27, 28, or 31;   CDRL1 comprises the amino acid sequence of SEQ ID NO: 32, 37, 41, or 44,   CDRL2 comprises the amino acid sequence of AAS, GAS, DNN, or EVS;   CDRL3 comprises the amino acid sequence of SEQ ID NO: 34, 35, 36, 40, 43, or 46.   
     
     
         144 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody further comprises a combination of a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 2, 6, 12, 16, or 20, and a variable light chain comprising the amino acid sequence of SEQ ID NO: 4, 8, 10, 14, 18, or 22. 
     
     
         145 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody further comprises a combination of a variable heavy chain sequence and a variable light chain sequence selected from:
 (a) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 2 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 4;   (b) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 6, and a variable light chain comprising the amino acid sequence of SEQ ID NO: 8;   (c) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 6 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 10;   (d) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 12 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 14;   (e) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 16 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 18; and   (f) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 20 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 22.   
     
     
         146 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the anti-CD19 antibody is 5F5, 7F11, 9G8, F6, 7F1 or 10D8. 
     
     
         147 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the CD19 is human CD19. 
     
     
         148 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody is a monoclonal antibody, a domain antibody (dAb), a single chain antibody (scAb), a Fab fragment, a F(ab′) 2  fragment, a single chain variable fragment (scFv), a scFv-Fc fragment, a single domain heavy chain antibody, a single domain light chain antibody, a variant antibody, a multimeric antibody, or a bispecific antibody. 
     
     
         149 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody is a rabbit, mouse, chimeric, humanized or fully human monoclonal antibody. 
     
     
         150 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody is an IgG isotype. 
     
     
         151 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody is an IgG1 isotype. 
     
     
         152 . The antibody or antigen-binding fragment thereof of  claim 143 , wherein the antibody is conjugated to one or more chemical moieties, each comprising one or more active agents and a linker, wherein the linker links the antibody to the active agent(s).