Antibodies Against T Cell Immunoglobulin Domain and Mucin Domain 1 (TIM-1) Antigen and Uses Thereof

Abstract

The invention described herein is related to antibodies directed to the antigen TIM-1 and uses of such antibodies. In particular, there are provided fully human monoclonal antibodies directed to the antigen TIM-1. Isolated polynucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions (FR's) and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.

What is claimed is: 
     
         1 . An isolated human antibody, or binding fragment thereof, that specifically binds to T cell, immunoglobulin domain and mucin domain 1 (TIM-1). 
     
     
         2 . The antibody of  claim 1 , wherein said TIM-1 comprises the amino acid sequence shown in SEQ ID NO:54. 
     
     
         3 . The antibody of  claim 1 , wherein said TIM-1 comprises the amino acid sequence of SEQ ID NO:87. 
     
     
         4 . The antibody of  claim 1 , wherein said antibody is a monoclonal antibody. 
     
     
         5 . The antibody of  claim 1 , wherein said binding fragment comprises a Fab, Fab′, F(ab′) 2 , or Fv fragment of said antibody. 
     
     
         6 . The antibody of  claim 1 , wherein said antibody is a single chain antibody. 
     
     
         7 . The antibody, or binding fragment, of  claim 1 , wherein said antibody or binding fragment is associated with a pharmaceutically acceptable carrier or diluent. 
     
     
         8 . The antibody, or binding fragment of  claim 1 , wherein the antibody or binding fragment is conjugated to a therapeutic agent. 
     
     
         9 . The antibody, or binding fragment of  claim 8 , wherein the therapeutic agent is a toxin. 
     
     
         10 . The antibody or binding fragment of  claim 8 , wherein the therapeutic agent is a radioactive isotope. 
     
     
         11 . The antibody or binding fragment of  claim 8 , wherein the therapeutic agent is a chemotherapeutic agent. 
     
     
         12 . A hybridoma cell line producing the antibody, or binding fragment, of  claim 1 . 
     
     
         13 . A transformed cell comprising a gene encoding the antibody, or binding fragment, of  claim 1 . 
     
     
         14 . The transformed cell of  claim 13 , wherein the cell is a Chinese hamster ovary (CHO) cell. 
     
     
         15 . A method of inhibiting cell proliferation associated with the expression of TIM-1, comprising treating cells expressing TIM-1 with an effective amount of the antibody of  claim 1 . 
     
     
         16 . A method of effectively treating renal cancer comprising:
 identifying an animal in need of treatment for renal cancer;   administering to said animal a therapeutically effective dose of the antibody of  claim 1 .   
     
     
         17 . A method of effectively treating ovarian cancer comprising:
 identifying an animal in need of treatment for ovarian cancer;   administering to said animal a therapeutically effective dose of the antibody of  claim 1 .   
     
     
         18 . An article of manufacture comprising a container, a composition contained therein, and a package insert or label indicating that the composition can be used to treat cancer characterized by the overexpression of TIM-1, wherein the composition comprises the antibody, or binding fragment, of  claim 1 . 
     
     
         19 . An assay kit for the detection of TIM-1 in mammalian tissues or cells in order to screen for lung, colon, gastric, kidney, renal, prostate or ovarian carcinomas, the TIM-1 being an antigen expressed by lung, colon, gastric, kidney, renal, prostate or ovarian carcinomas, the kit comprising the antibody of  claim 1  and means for indicating the reaction of the antibody with the antigen, if present. 
     
     
         20 . The assay kit of  claim 19 , wherein the antibody is labeled. 
     
     
         21 . The assay kit of  claim 19 , wherein the antibody is an unlabeled first antibody and the means for indicating the reaction comprises a labeled second antibody that is anti-immunoglobulin. 
     
     
         22 . The assay kit of  claim 21 , wherein the antibody that binds the antigen is labeled with a marker selected from the group consisting of a fluorochrome, an enzyme, a radionuclide and a radiopaque material. 
     
     
         23 . The assay kit of  claim 22 , wherein the second antibody is labeled with a marker selected from the group consisting of a fluorochrome, an enzyme, a radionuclide and a radiopaque material.