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 - 9 . (canceled) 
     
     
         10 . A method of treating a patient having a FOLR1-mediated disease or disorder comprising:
 (a) administering to a patient having a FOLR1-mediated disease or disorder a fixed dose of an active agent comprising an antibody or antigen-binding fragment thereof that specifically binds to FOLR1;   (b) measuring the patient's FOLR1 protein level on circulating tumor cells using an antibody or antigen-binding fragment thereof that does not competitively inhibit the binding of the active agent to FOLR1; and   (c) increasing the amount and/or frequency of subsequent fixed doses if the FOLR1 protein level on the patient's circulating tumor cells is elevated relative to a reference FOLR1 protein level.   
     
     
         11 - 43 . (canceled) 
     
     
         44 . The method of  claim 10 , wherein the FOLR1 protein level is measured using an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof specifically binds to the same FOLR1 epitope as, or competitively inhibits the 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 NO: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.   
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 10 , wherein the FOLR1 protein level is measured using an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises amino acid sequences selected from the group consisting of:
 (a) SEQ ID NOs: 1, 2, and 3 and SEQ ID NOs: 13, 14, and 15;   (b) SEQ ID NOs: 4, 5, and 6 and SEQ ID NOs: 16, 17, and 18;   (c) SEQ ID NOs: 7, 8, and 9 and SEQ ID NOs: 19, 20, and 21;   (d) SEQ ID NOs: 10, 11, and 12 and SEQ ID NOs: 22, 23, and 24; and   (e) variants of (a) to (d) comprising 1, 2, 3, or 4 conservative amino acid substitutions.   
     
     
         47 - 49 . (canceled) 
     
     
         50 . An antibody or antigen-binding fragment thereof that specifically binds to the same FOLR1 epitope as, or competitively inhibits the 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 NO: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.   
     
     
         51 . (canceled) 
     
     
         52 . The antibody or antigen-binding fragment thereof of  claim 50 , wherein said antibody or antigen-binding fragment thereof comprises amino acid sequences selected from the group consisting of:
 (a) SEQ ID NOs: 1, 2, and 3 and SEQ ID NOs: 13, 14, and 15;   (b) SEQ ID NOs: 4, 5, and 6 and SEQ ID NOs: 16, 17, and 18;   (c) SEQ ID NOs: 7, 8, and 9 and SEQ ID NOs: 19, 20, and 21;   (d) SEQ ID NOs: 10, 11, and 12 and SEQ ID NOs: 22, 23, and 24; and   (e) variants of (a) to (d) comprising 1, 2, 3, or 4 conservative amino acid substitutions.   
     
     
         53 - 56 . (canceled) 
     
     
         57 . The antibody or antigen-binding fragment thereof of  claim 52 , wherein said antibody or antigen-binding fragment thereof is murine, non-human, humanized, chimeric, resurfaced, or human. 
     
     
         58 - 62 . (canceled) 
     
     
         63 . A polypeptide that specifically binds FOLR1, wherein said polypeptide comprises the sequences selected from the group consisting of:
 (a) SEQ ID NOs: 1, 2, and 3 and SEQ ID NOs: 13, 14, and 15;   (b) SEQ ID NOs: 4, 5, and 6 and SEQ ID NOs: 16, 17, and 18;   (c) SEQ ID NOs: 7, 8, and 9 and SEQ ID NOs: 19, 20, and 21;   (d) SEQ ID NOs: 10, 11, and 12 and SEQ ID NOs: 22, 23, and 24; and   (e) variants of (a) to (d) comprising 1, 2, 3, or 4 conservative amino acid substitutions.   
     
     
         64 - 72 . (canceled) 
     
     
         73 . A nucleic acid molecule encoding the antibody or antigen-binding fragment thereof of  claim 50 . 
     
     
         74 . A vector comprising the nucleic acid molecule of  claim 73 . 
     
     
         75 - 76 . (canceled) 
     
     
         77 . A method of detecting FOLR1 protein in a sample comprising contacting said sample with the antibody or antigen-binding fragment thereof of  claim 50 . 
     
     
         78 - 86 . (canceled) 
     
     
         87 . A cell producing the antibody or antigen-binding fragment thereof of  claim 50 . 
     
     
         88 - 90 . (canceled) 
     
     
         91 . A method of making an antibody or antigen-binding fragment thereof comprising (a) culturing the cell of  claim 87 ; and (b) isolating said antibody or antigen-binding fragment thereof from said cultured cell. 
     
     
         92 . An immunoassay kit for detecting FOLR1 protein in a sample, the kit comprising: (a) first reagent, wherein the first reagent is the antibody or antigen-binding fragment thereof of  claim 50 , and (b) a second reagent, wherein the second reagent is a detection reagent. 
     
     
         93 - 155 . (canceled) 
     
     
         156 . A method of treating cancer comprising administering an active agent comprising an antibody or antigen-binding fragment thereof that specifically binds to FOLR1 to a patient with elevated FOLR1 protein levels on circulating tumor cells relative to a reference FOLR1 protein level, wherein the patient's FOLR1 protein levels were measured using the antibody or antigen-binding fragment of  claim 50 . 
     
     
         157 - 162 . (canceled)