Antibodies Against A Cancer-Associated Epitope of Variant HNRNPG and Uses Thereof

Abstract

The present application provides the amino acid and nucleic acid sequences of heavy chain and light chain complementarity determining regions of a cancer specific antibody. In addition, the application provides cancer specific antibodies and immunoconjugates comprising the cancer specific antibody attached to a toxin or label, and methods and uses thereof. The application also relates to diagnostic methods and kits using the cancer specific antibodies disclosed herein. Further, the application provides novel cancer-associated epitopes and antigens, and uses thereof.

1 - 91 . (canceled) 
     
     
         92 : As isolated variable region selected from the group consisting of:
 an isolated light chain variable region comprising the light chain complementarity determining regions of SEQ ID NOS:7, 8 and/or 9, or a variant thereof and an isolated heavy chain variable region comprising the heavy chain complementarity determining regions of SEQ ID NOS:10, 11 and/or 12, or a variant thereof.   
     
     
         93 : The variable region according to  claim 94  wherein the isolated light chain variable region comprises the amino acid sequence of SEQ ID NO:16, or a variant thereof and the isolated heavy chain variable region comprises the amino acid sequence of SEQ ID NO:14, or a variant thereof. 
     
     
         94 : An isolated nucleic acid sequence encoding a variable region of  claim 94 . 
     
     
         95 : The nucleic acid sequence of  claim 94  comprising the light chain variable region of SEQ ID NO:15, or a variant thereof or the heavy chain variable region of SEQ ID NO:13, or a variant thereof. 
     
     
         96 : A binding protein comprising the light chain complementarity determining regions comprising the amino acid sequences defined by SEQ ID NOS: 7, 8 and/or 9 and the heavy chain complementarity determining regions comprising the amino acid sequence defined by SEQ ID NOS: 10, 11 and/or 12, or a variant thereof. 
     
     
         97 : The binding protein of  claim 96  comprising the light chain variable region of SEQ ID NO:16, or a variant thereof and/or the heavy chain variable region of SEQ ID NO:14, or a variant thereof. 
     
     
         98 : The binding protein of  claim 96 , wherein the binding protein binds to prostate stem cell antigen (SEQ ID NO:17), variant HnRNPG, variant HnRNPG having the amino acid sequence of SEQ ID NO:71, variant HnRNPG having the amino acid sequence of SEQ ID NO:113 with one or more amino acid substitutions at positions 216, 218, 219 and/or 222, or a polypeptide comprising the amino acid sequence of SEQ ID NO:23, SEQ ID NO:41, SEQ ID NO: 111, or SEQ ID NO:112. 
     
     
         99 : A binding protein capable of binding an antigen on or in a cancer cell wherein the binding protein can be identified by a competition binding assay comprising:
 (1) a binding protein according to  claim 96 , preferably an antibody or antibody fragment (Ab1); and   (2) an antigen or epitope comprising the amino acid sequence of SEQ ID NO: 17, 71, 23, 41, 111 or 112;   wherein one or more concentrations of a test binding protein is tested for its ability to compete with Ab1 for binding to the antigen or epitope.   
     
     
         100 : The binding protein of  claim 96 , wherein the binding protein is an antibody or an antibody fragment. 
     
     
         101 : The binding protein of  claim 100 , wherein the antibody fragment is a Fab, Fab′, F(ab′) 2 , scFv, dsFv, ds-scFv, dimers, minibodies, diabodies, or multimers thereof or bispecific antibody fragments. 
     
     
         102 : An isolated nucleic acid sequence encoding the binding protein according to  claim 96 . 
     
     
         103 : An immunoconjugate comprising (1) a binding protein according to  claim 96  that binds to an antigen on a cancer cell attached to (2) a cancer therapeutic. 
     
     
         104 : The immunoconjugate of  claim 103 , wherein the cancer therapeutic is a cytotoxin. 
     
     
         105 : The immunoconjugate according to  claim 104 , wherein the cytotoxin is selected from the group consisting of gelonin, bouganin, saporin, ricin, ricin A chain, bryodin, diphtheria, restrictocin and  Pseudomonas  exotoxin A or variants thereof. 
     
     
         106 : The immunoconjugate according to  claim 103 , comprising the amino acid sequence of SEQ ID NO:49 or SEQ ID NO:51. 
     
     
         107 : An isolated nucleic acid sequence encoding the immunoconjugate according to  claim 103 . 
     
     
         108 : The isolated nucleic acid sequence according to  claim 107 , comprising the nucleic acid sequence of SEQ ID NO:48 or SEQ ID NO:50. 
     
     
         109 : A composition comprising the immunoconjugate according to  claim 103  with a pharmaceutically acceptable excipient, carrier, buffer or stabilizer. 
     
     
         110 : A method of treating or preventing cancer comprising administering an effective amount of the immunoconjugate according to  claim 103 . 
     
     
         111 : The method according to  claim 110  additionally comprising the use of one or more further cancer therapeutic agent for the manufacture of a medicament for simultaneous, separate or sequential treatment or prevention of cancer. 
     
     
         112 : A kit for treating or preventing cancer comprising an effective amount of the immunoconjugate of  claim 103 , and directions for the use thereof to treat or prevent the cancer. 
     
     
         113 : A method of detecting or monitoring cancer in a subject comprising the steps of:
 (1) contacting a test sample taken from said subject with the binding protein of  claim 96  and that binds specifically to an antigen on or in the cancer cell to produce a binding protein-antigen complex;   (2) measuring the amount of binding protein-antigen complex in the test sample; and   (3) comparing the amount of binding protein-antigen complex in the test sample to a control.   
     
     
         114 : A kit for diagnosing cancer comprising the binding proteins of  claim 96  that binds to an antigen on or in the cancer cell and instructions for the use thereof. 
     
     
         115 : A diagnostic agent comprising (1) a binding protein according to  claim 96  that binds to an antigen on or in a cancer cell attached to (2) a label that produces a detectable signal, directly or indirectly. 
     
     
         116 : The diagnostic agent of  claim 115 , wherein the label is a radioisotype, a fluorescent compound, a chemiluminescent compound, an enzyme, an imaging agent or a metal ion. 
     
     
         117 : A kit comprising the diagnostic agent of  claim 115  and instructions for the use thereof. 
     
     
         118 : A recombinant expression vector comprising the nucleic acid molecule of  claim 105 . 
     
     
         119 : A host cell comprising the recombinant expression vector of  claim 118 . 
     
     
         120 : An isolated polypeptide, comprising the amino acid sequence of SEQ ID NO:23, SEQ ID NO:41, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113 with one or more amino acid substitutions at positions 216, 218, 219 and/or 222, or SEQ ID NO:71, or a variant thereof. 
     
     
         121 : An isolated nucleic acid sequence encoding the isolated polypeptide of claim  120 . 
     
     
         122 : A recombinant expression vector comprising the nucleic acid sequence of  claim 121 . 
     
     
         123 : A method of detecting or monitoring cancer in a subject having or suspected of having cancer, comprising detecting the isolated polypeptide according to  claim 120  on or in a cell in the sample, wherein cancer is indicated, if the isolated polypeptide is detected on or in the cell. 
     
     
         124 : A pharmaceutical composition comprising an effective amount of the isolated polypeptide according to  claim 120  or fragment thereof in admixture with a suitable diluent or carrier.