Diagnostic assays and kits for detection of folate receptor 1

Abstract

The invention generally relates to antibodies that bind to human folate receptor 1 and diagnostic assays for folate receptor 1-based therapies. Methods of using the antibodies to monitor therapy are further provided.

1 - 50 . (canceled) 
     
     
         51 . An antibody or antigen-binding fragment thereof that specifically binds to FOLR1, wherein said antibody or antigen-binding fragment thereof competitively inhibits binding to FOLR1 of an antibody selected from the group consisting of:
 (a) an antibody comprising the polypeptide of SEQ ID NO:25 and the polypeptide of SEQ ID NO: 29;   (b) an antibody comprising the polypeptide of SEQ ID NO:26 and the polypeptide of SEQ ID N0:30;   (c) an antibody comprising the polypeptide of SEQ ID NO:27 and the polypeptide of SEQ ID NO:31; and   (d) an antibody comprising the polypeptide of SEQ ID NO:28 and the polypeptide of SEQ ID NO:32.   
     
     
         52 - 72 . (canceled) 
     
     
         73 . A nucleic acid molecule encoding the antibody, antigen-binding fragment thereof of  claim 51 . 
     
     
         74 - 155 . (canceled) 
     
     
         156 . A method of treating cancer in a human patient comprising administering to the human patient an active agent comprising a maytansinoid conjugated to an antibody or antigen-binding fragment thereof that specifically binds to folate receptor 1 (FOLR1) , wherein the human patient has FOLR1 protein levels that were measured using a detection antibody or antigen-binding fragment thereof comprising variable heavy chain CDR amino acid sequences VH-CDR1, VH-CDR2, and VH-CDR3, and variable light chain CDR amino acid sequences VL-CDR1, VL-CDR2, and VL-CDR3 selected from the group consisting of:
 (a) SEQ ID NOs: 1, 2, and 3 and SEQ ID NOs: 13, 14, and 15, respectively;   (b) SEQ ID NOs: 4, 5, and 6 and SEQ ID NOs: 16, 17, and 18, respectively;   (c) SEQ ID NOs: 7, 8, and 9 and SEQ ID NOs: 19, 20, and 21, respectively; and   (d) SEQ ID NOs: 10, 11, and 12 and SEQ ID NOs: 22, 23, and 24, respectively, and   wherein the antibody or antigen-binding fragment thereof of the active agent comprises VH-CDR1, VH-CDR2, and VH-CDR3, and VL-CDR1, VL-CDR2, and VL-CDR3 comprising GYFMN (SEQ ID NO:50); RIHPYDGDTFYNQKFQG (SEQ ID NO:51), YDGSRAMDY (SEQ ID NO:52); KASQSVSFAGTSLMH (SEQ ID NO:53); RASNLEA (SEQ ID NO:54); and QQSREYPYT (SEQ ID NO:55), respectively.   
     
     
         157 - 162 . (canceled) 
     
     
         163 . The method of  claim 156 , wherein the detection antibody or antigen-binding fragment thereof comprises variable heavy chain CDR amino acid sequences VH-CDR1, VH-CDR2, and VH-CDR3 of SEQ ID NOs: 1, 2, and 3, respectively, and variable light chain CDR amino acid sequences VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID NOs: 13, 14, and 15, respectively. 
     
     
         164 . The method of  claim 156 , wherein the detection antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO:25 and a variable light chain (VL) comprising the amino acid sequence of SEQ ID NO:29. 
     
     
         165 . The method of  claim 156 , wherein the detection antibody or antigen-binding fragment thereof comprises variable heavy chain (VH) and variable light chain (VL) amino acid sequences comprises amino acid sequences selected from the group consisting of:
 (a) SEQ ID NO:25 and SEQ ID NO:29, respectively;   (b) SEQ ID NO:26 and SEQ ID NO:30, respectively;   (c) SEQ ID NO:27 and SEQ ID NO:31, respectively; and   (d) SEQ ID NO:28 and SEQ ID NO:32, respectively.   
     
     
         166 . The method of  claim 156 , wherein the antibody or antigen-binding fragment thereof of the active agent comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:48. 
     
     
         167 . The method of  claim 156 , wherein the maytansinoid is N(2′)-deacetyl-N(2′)-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4). 
     
     
         168 . The method of  claim 166 , wherein the maytansinoid is N(2′)-deacetyl-N(2′)-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4). 
     
     
         169 . The method of  claim 156 , wherein the active agent comprises N(2′)-deacetyl-N(2′)-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4) conjugated to an anti-FOLR1 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:48 via a N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB) linker. 
     
     
         170 . The method of  claim 156 , wherein the cancer is ovarian cancer, cancer of the peritoneum, or cancer of the fallopian tubes. 
     
     
         171 . The method of  claim 170 , wherein the cancer is ovarian cancer. 
     
     
         172 . The method of  claim 171 , wherein the ovarian cancer is platinum resistant or platinum refractory. 
     
     
         173 . The method of  claim 170 , wherein the cancer is cancer of the peritoneum. 
     
     
         174 . The method of  claim 170 , wherein the cancer is cancer of the fallopian tubes. 
     
     
         175 . The method of  claim 164 , wherein the active agent comprises N(2′)-deacetyl-N(2′)-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4) conjugated to an anti-FOLR1 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:46 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:48 via a N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB) linker. 
     
     
         176 . The method of  claim 175 , wherein the cancer is ovarian cancer, cancer of the peritoneum, or cancer of the fallopian tubes. 
     
     
         177 . The method of  claim 156 , wherein the patient’s FOLR1 protein levels were measured by an immunohistochemical assay or flow cytometry. 
     
     
         178 . The method of  claim 156 , wherein the patient’s FOLR1 protein levels were measured using an enzyme linked immunosorbent assay (ELISA). 
     
     
         179 . The method of  claim 175 , wherein the antibody of the active agent is an IgG1 antibody.