Heterodimeric antibodies that bind msln and cd3

Abstract

The present invention is directed to antibodies, including novel antigen binding domains and heterodimeric antibodies, that bind Mesothelin (MSLN).

1 . A heterodimeric antibody comprising:
 a) a first monomer comprising, from N-terminus to C-terminus, a VH1-CH1-linker 1-scFv-linker 2-CH2-CH3,   wherein VH1 is a first variable heavy domain, scFv is an anti-CD3 scFV, linker 1 and linker 2 are a first domain linker and second domain linker, respectively, and CH2-CH3 is a first Fc domain;   b) a second monomer comprising, from N-terminus to C-terminus, a VH2-CH1-hinge-CH2-CH3, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second Fc domain; and   c) a common light chain comprising a variable light domain and a light chain constant domain;   wherein the first variable heavy domain and the variable light domain form a first PSMA binding domain, and the second variable heavy domain and the variable light domain form a second PSMA binding domain.   
     
     
         2 . A heterodimeric antibody according to  claim 1 , wherein the first and second PSMA binding domains each comprise the variable heavy complementary determining regions 1-3 (vhCDR1-3) of PSMA-H variable heavy domain H1 ( FIG. 17 ); and the variable light complementary determining regions (vlCDR1-3) of a PSMA-H variable light domain selected from any one of the PSMA-H variable light domains L1 and L1.1-L1.84 ( FIGS. 17 and 18A-18E ). 
     
     
         3 . (canceled) 
     
     
         4 . A heterodimeric antibody according to  claim 1 , wherein the scFv comprises the vhCDR1-3 and the vlCDR1-3 of any of the following CD3 binding domains: H1.32_L1.47, H1.30_L1.47, H1.89_L1.47, H1.90_L1.47, H1.33_L1.47, H1.31_L1.47, L1.47_H1.30, L1.47_H1.30, L1.47_H1.32, L1.47_H1.89, L1.47_H1.90, L1.47_H1.33, and L1.47_H1.31 ( FIGS. 10A-10F ). 
     
     
         5 .- 22 . (canceled) 
     
     
         23 . A heterodimeric antibody according to  claim 1 , selected from the following heterodimeric antibodies: XENP31602, XENP31603, XENP31855, XENP32218, XENP32219, XENP32220, XENP32221, XENP32222, XENP32223, XENP32224, XENP32225, XENP32226, XENP34237, XENP34238, XENP34239, XENP34625, XENP34626, XENP34627, XENP34628, XENP31853, XENP31856, XENP33063, XENP33064, XENP33065, XENP33066, XENP33067, XENP33068, XENP33069, XENP33070, XENP33071, XENP34240, XENP34241, XENP34242, XENP34629, XENP34630, XENP34631, XENP34632, XENP31854, and XENP31857. 
     
     
         24 . A nucleic acid composition comprising:
 a) a first nucleic acid encoding the first monomer according to  claim 1 ;   b) a second nucleic acid encoding the second monomer according to  claim 1 ; and   c) a third nucleic acid encoding the light chain according to  claim 1 .   
     
     
         25 . An expression vector composition comprising:
 a) a first expression vector comprising the first nucleic acid according to  claim 1 ;   b) a second expression vector comprising the second nucleic acid according to  claim 24 ; and   c) a third expression vector comprising the third nucleic acid according to  claim 1 .   
     
     
         26 . A host cell transformed with the expression vector composition according to  claim 1 . 
     
     
         27 . (canceled) 
     
     
         28 . A heterodimeric antibody comprising:
 a) a first monomer comprising:
 i) an anti-CD3 scFv comprising a first variable heavy domain, an scFv linker and a first variable light domain; and 
 ii) a first Fc domain, wherein the scFv is covalently attached to the N-terminus of the first Fc domain using a domain linker; 
   b) a second monomer comprising a VH2-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy domain and CH2-CH3 is a second Fc domain; and   c) a light chain comprising a second variable light domain,   wherein the second variable heavy domain and the second variable light domain form an PSMA binding domain.   
     
     
         29 .- 53 . (canceled) 
     
     
         54 . A composition comprising a Prostate Specific Membrane Antigen (PSMA) binding domain comprising:
 a) a variable heavy domain comprising the variable heavy complementary determining regions 1-3 (vhCDR1-3) of PSMA-H variable heavy domain H1 ( FIG. 17 ); and   b) a variable light domain comprising the variable light complementary determining regions (vlCDR1-3) of a PSMA-H variable light domain selected from PSMA-H variable light domains L1 and L1.1-L1.84 ( FIGS. 17 and 18A-18E ).   
     
     
         55 .- 82 . (canceled)