Compositions and methods for predicting response to napi2b-targeted therapy

Abstract

This disclosure provides reagents and methods of predicting the responsiveness of a patient to NaPi2b-targeted antibody-drug conjugates (e.g., NaPi2b-targeted antibody-polymer-drug conjugates).

What is claimed is: 
     
         1 . A method of predicting the responsiveness of a cancer patient to treatment with a NaPi2b-targeted antibody drug conjugate comprising:
 a. detecting whether NaPi2b is present in a tumor sample obtained from the patient by contacting the tumor sample with the chimeric anti-NaPi2b antibody of  claim 30 ;   b. detecting binding between NaPi2b in the tumor sample and the chimeric antibody;   c. predicting that the patient with be responsive to treatment when the presence of NaPi2b in the tumor sample is is higher than a predetermined quantitative or semi quantitative cut-off score; and   d. administering the NaPi2b-targeted antibody drug conjugate to a subject predicted to be responsive:
 wherein the NaPi2b-targeted antibody conjugate comprises the NaPi2b-targeted antibody, XMT-1535 comprising a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence GYTFTGYNIH (SEQ ID NO: 3), a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence AIYPGNGDTSYKQKFRG (SEQ ID NO: 4), a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GETARATFAY (SEQ ID NO: 5), a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence SASQDIGNFLN (SEQ ID NO: 6), a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence YTSSLYS (SEQ ID NO: 7), a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYSKLPLT (SEQ ID NO: 8). 
   
     
     
         2 - 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the antibody of the NaPi2b- targeted antibody drug conjugate comprises: a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence GYTFTGYNIH (SEQ ID NO: 3), a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence AIYPGNGDTSYKQKFRG (SEQ ID NO: 4), a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GETARATFAY (SEQ ID NO: 5), a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence SASQDIGNFLN (SEQ ID NO: 6), a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence YTSSLYS (SEQ ID NO: 7), a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYSKLPLT (SEQ ID NO: 8). 
     
     
         20 . The method of  claim 1 , wherein the NaPi2b-targeted antibody drug conjugate is:
                       wherein:   m is an integer from 1 to about 300,   m 1  is an integer from 1 to about 140,   m 2  is an integer from 1 to about 40,   m 3a  is an integer from 0 to about 17,   m 3b  is an integer from 1 to about 8;   the sum of m 3a  and m 3b  ranges from 1 and about 18; and   the sum of m, m 1 , m 2 , m 3a , and m 3b  ranges from 15 to about 300;   the terminal
                     
 denotes the attachment of one or more polymeric scaffolds to the NaPi2b-targeted antibody XMT-1535. 
   
     
     
         21 - 29 . (canceled) 
     
     
         30 . A chimeric antibody comprising: a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence GYTFTGYNIH (SEQ ID NO: 3), a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence AIYPGNGDTSYKQKFRG (SEQ ID NO: 4), a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GETARATFAY (SEQ ID NO: 5), a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence SASQDIGNFLN (SEQ ID NO: 6), a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence YTSSLYS (SEQ ID NO: 7), a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYSKLPLT (SEQ ID NO: 8). 
     
     
         31 . The chimeric antibody of  claim 30 , wherein the antibody comprises the variable heavy chain of SEQ ID No: 1 and the variable light chain of SEQ ID No:2. 
     
     
         32 . The chimeric antibody of  claim 30  or  31  wherein the constant region is a rabbit constant region. 
     
     
         33 . The chimeric antibody of any one of  claims 30-32  comprising a rabbit IgG1 heavy chain constant region and a rabbit kappa constant region light chain. 
     
     
         34 . The chimeric antibody of  claim 33 , wherein the wherein antibody comprise the heavy chain constant region of SEQ ID No: 11 and the light chain constant region of SEQ ID NO:12. 
     
     
         35 . A plasmid comprising the nucleic acid of SEQ ID NO: 17 and/or SEQ ID NO: 18. 
     
     
         36 . A cell comprising the plasmid of  claim 35 . 
     
     
         37 - 38 . (canceled)