Cd3 binding antibodies

Abstract

The present invention relates to human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

1 .- 38 . (canceled) 
     
     
         39 . A polynucleotide encoding a bispecific antibody, wherein the bispecific antibody comprises:
 (a) a first binding moiety specific for human CD3δε, wherein the first binding moiety comprises:
 (i) a first polypeptide subunit comprising a heavy chain variable (VH) domain comprising a CDR1 having an amino acid sequence of GFTFDDYA (SEQ ID NO:29), a CDR2 having an amino acid sequence of ISWNSGSI (SEQ ID NO:24), and a CDR3 having an amino acid sequence of AKDSRGYGDYRLGGAY (SEQ ID NO:41); and 
 (ii) a second polypeptide subunit comprising a light chain variable (VL) domain comprising a CDR1 having an amino acid sequence of QSVSSN (SEQ ID NO:35), a CDR2 having an amino acid sequence of GAS (SEQ ID NO:38), and a CDR3 having an amino acid sequence of QQYNNWPWT (SEQ ID NO:45); and 
   (b) a second binding moiety specific for human BCMA, wherein the second binding moiety comprises:
 (i) a third polypeptide subunit comprising a VH domain comprising a CDR1 having an amino acid sequence of GFTVSSYG (SEQ ID NO:36), a CDR2 having an amino acid sequence of IRGSDGST (SEQ ID NO:39), and a CDR3 having an amino acid sequence of AKQGENDGPFDH (SEQ ID NO:46). 
   
     
     
         40 . The polynucleotide of  claim 39 , wherein the CDR1, CDR2 and CDR3 sequences in the VH domain of the first polypeptide subunit are present in a human VH framework. 
     
     
         41 . The polynucleotide of  claim 39 , wherein the CDR1, CDR2 and CDR3 sequences in the VL domain of the second polypeptide subunit are present in a human VL framework. 
     
     
         42 . The polynucleotide of  claim 39 , wherein the CDR1, CDR2 and CDR3 sequences in the VH domain of the first polypeptide subunit are present in a human VH framework; and the CDR1, CDR2 and CDR3 sequences in the VL domain of the second polypeptide subunit are present in a human VL framework. 
     
     
         43 . The polynucleotide of  claim 39 , wherein the first polypeptide subunit comprises a VH domain having an amino acid sequence of SEQ ID NO:1. 
     
     
         44 . The polynucleotide of  claim 39 , wherein the second polypeptide subunit comprises a VL domain having an amino acid sequence of SEQ ID NO:19. 
     
     
         45 . The polynucleotide of  claim 39 , wherein the first polypeptide subunit comprises a VH domain having an amino acid sequence of SEQ ID NO:1 and the second polypeptide subunit comprises a VL domain having an amino acid sequence of SEQ ID NO:19. 
     
     
         46 . The polynucleotide of  claim 39 , wherein the third polypeptide subunit comprises a VH domain having an amino acid sequence of SEQ ID NO:21. 
     
     
         47 . The polynucleotide of  claim 39 , wherein the third polypeptide subunit has an amino acid sequence of SEQ ID NO:20. 
     
     
         48 . The polynucleotide of  claim 43 , wherein the third polypeptide subunit comprises a VH domain having an amino acid sequence of SEQ ID NO:21. 
     
     
         49 . The polynucleotide of  claim 43 , wherein the third polypeptide subunit has an amino acid sequence of SEQ ID NO:20. 
     
     
         50 . The polynucleotide of  claim 44 , wherein the third polypeptide subunit comprises a VH domain having an amino acid sequence of SEQ ID NO:21. 
     
     
         51 . The polynucleotide of  claim 44 , wherein the third polypeptide subunit has an amino acid sequence of SEQ ID NO:20. 
     
     
         52 . A polynucleotide encoding a bispecific antibody, wherein the bispecific antibody comprises:
 (a) a first binding moiety specific for human CD3δε, wherein the first binding moiety comprises a first polypeptide subunit comprising a VH domain having an amino acid sequence of SEQ ID NO:1 and a second polypeptide subunit comprising a VL domain having an amino acid sequence of SEQ ID NO:19; and   (b) a second binding moiety specific for human BCMA, wherein the second binding moiety comprises a third polypeptide subunit comprising a VH domain having an amino acid sequence of SEQ ID NO:21.   
     
     
         53 . The polynucleotide of  claim 52 , wherein the third polypeptide subunit comprises a first VH domain having an amino acid sequence of SEQ ID NO:21 and a second VH domain having an amino acid sequence of SEQ ID NO:21, wherein the first VH domain and the second VH domain are arranged in a tandem configuration. 
     
     
         54 . The polynucleotide of  claim 53 , wherein the first VH domain and the second VH domain of the third polypeptide subunit are arranged in a tandem configuration and joined by a linker. 
     
     
         55 . A polynucleotide encoding a bispecific antibody, wherein the bispecific antibody comprises:
 (a) a first binding moiety specific for human CD3δε, wherein the first binding moiety comprises a first polypeptide subunit comprising a VH domain having an amino acid sequence of SEQ ID NO:1 and a second polypeptide subunit comprising a VL domain having an amino acid sequence of SEQ ID NO:19; and   (b) a second binding moiety specific for human BCMA, wherein the second binding moiety comprises a third polypeptide subunit having an amino acid sequence of SEQ ID NO:20.   
     
     
         56 . A vector comprising the polynucleotide of  claim 39 . 
     
     
         57 . A cell comprising the vector of  claim 56 . 
     
     
         58 . A vector comprising the polynucleotide of  claim 52 . 
     
     
         59 . A cell comprising the vector of  claim 58 . 
     
     
         60 . A vector comprising the polynucleotide of  claim 55 . 
     
     
         61 . A cell comprising the vector of  claim 60 . 
     
     
         62 . A method for treating a disease or condition, comprising administering an effective dose of a bispecific antibody, wherein the bispecific antibody comprises:
 (a) a first binding moiety specific for human CD3δε, wherein the first binding moiety comprises:
 (i) a first polypeptide subunit comprising a heavy chain variable (VH) domain comprising a CDR1 having an amino acid sequence of GFTFDDYA (SEQ ID NO:29), a CDR2 having an amino acid sequence of ISWNSGSI (SEQ ID NO:24), and a CDR3 having an amino acid sequence of AKDSRGYGDYRLGGAY (SEQ ID NO:41); and 
 (ii) a second polypeptide subunit comprising a light chain variable (VL) domain comprising a CDR1 having an amino acid sequence of QSVSSN (SEQ ID NO:35), a CDR2 having an amino acid sequence of GAS (SEQ ID NO:38), and a CDR3 having an amino acid sequence of QQYNNWPWT (SEQ ID NO:45); and 
   (b) a second binding moiety specific for human BCMA, wherein the second binding moiety comprises:
 (i) a third polypeptide subunit comprising a VH domain comprising a CDR1 having an amino acid sequence of GFTVSSYG (SEQ ID NO:36), a CDR2 having an amino acid sequence of IRGSDGST (SEQ ID NO:39), and a CDR3 having an amino acid sequence of AKQGENDGPFDH (SEQ ID NO:46). 
   
     
     
         63 . The method of  claim 62 , wherein the CDR1, CDR2 and CDR3 sequences in the VH domain of the first polypeptide subunit are present in a human VH framework, and/or the CDR1, CDR2 and CDR3 sequences in the VL domain of the second polypeptide subunit are present in a human VL framework. 
     
     
         64 . The method of  claim 62 , wherein the first polypeptide subunit comprises a VH domain having an amino acid sequence of SEQ ID NO:1, and/or the second polypeptide subunit comprises a VL domain having an amino acid sequence of SEQ ID NO:19. 
     
     
         65 . The method of  claim 62 , wherein the third polypeptide subunit
 (a) comprises a VH domain having an amino acid sequence of SEQ ID NO:21, or   (b) has an amino acid sequence of SEQ ID NO:20.