Antibodies directed to her-3 and uses thereof

Abstract

The present invention relates to binding proteins that bind to HER-3 and polynucleotides encoding the same. Expression vectors and host cells comprising the same for the production of the binding protein of the invention are also provided. In addition, the invention provides compositions and methods for diagnosing and treating diseases associated with HER-3 mediated signal transduction and/or its ligand heregulin.

1 . An isolated binding protein that binds to HER-3, comprising: a heavy chain amino acid sequence that comprises at least one of the CDR's selected from the group consisting of (a) CDRH1's as shown in SEQ ID NOs:235-257; (b) CDRH2's as shown in SEQ ID NOs:258-282; and (c) CDRH3's as shown in SEQ ID NOs:283-317. 
     
     
         2 . An isolated binding protein that binds to HER-3, comprising: a light chain amino acid sequence that comprises at least one of the CDR's selected from the group consisting of: (d) CDRL1's as shown in SEQ ID NOs:318-342; (e) CDRL2's as shown in SEQ ID NOs:343-359; and (f CDRL3's as shown in SEQ ID NOs:360-388. 
     
     
         3 . The isolated binding protein of  claim 1 , wherein said binding protein comprises: a heavy chain amino acid sequence that comprises at least one of the CDR's selected from the group consisting of (a) CDRH1's as shown in SEQ ID NOs:235-257; (b) CDRH2's as shown in SEQ ID NOs:258-282; and (c) CDRH3's as shown in SEQ ID NOs:283-317, and a light chain amino acid sequence that comprises at least one of the CDR's selected from the group consisting of: (d) CDRL1's as shown in SEQ ID NOs:318-342; (e) CDRL2's as shown in SEQ ID NOs:343-359; and (f) CDRL3's as shown in SEQ ID NOs:360-388. 
     
     
         4 .- 5 . (canceled) 
     
     
         6 . The isolated binding protein of  claim 1 , comprising: a heavy chain amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 6, 10, 14, 18, 22, 26, 30, 34, 36, 40, 42, 46, 50, 54, 60, 62, 66, 70, 74, 78, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226 and 230. 
     
     
         7 . The isolated binding protein of  claim 2  comprising: a light chain amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, 24, 28, 32, 38, 44, 48, 52, 56, 58, 64, 68, 72, 76, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228 and 232. 
     
     
         8 .- 12 . (canceled) 
     
     
         13 . The isolated binding protein according to  claim 1  comprising the heavy chain amino acid sequence of SEQ ID NO:70 and the light chain amino acid sequence of SEQ ID NO:72. 
     
     
         14 . (canceled) 
     
     
         15 . The isolated binding protein of  claim 1 , wherein the binding protein is directed against the extracellular domain of HER-3. 
     
     
         16 .- 20 . (canceled) 
     
     
         21 . The isolated binding protein  claim 1  which is an antibody. 
     
     
         22 . The isolated binding protein of  claim 21 , wherein the antibody is a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a humanized antibody, a human antibody, a chimeric antibody, a multispecific antibody, or an antibody fragment thereof. 
     
     
         23 .- 24 . (canceled) 
     
     
         25 . The isolated binding protein of  claim 1 , wherein the binding protein is coupled to a labelling group. 
     
     
         26 . (canceled) 
     
     
         27 . The isolated binding protein of  claim 1 , wherein the binding protein is coupled to an effector group. 
     
     
         28 . The isolated binding protein of  claim 27 , wherein the effector group is a radioisotope or radionuclide, a toxin, or a therapeutic or chemotherapeutic group. 
     
     
         29 . (canceled) 
     
     
         30 . An isolated nucleic acid molecule encoding an binding protein of  claim 1 . 
     
     
         31 . (canceled) 
     
     
         32 . A vector comprising the nucleic acid molecule of  claim 30 . 
     
     
         33 . (canceled) 
     
     
         34 . A host cell transformed with the vector of  claim 32 . 
     
     
         35 . (canceled) 
     
     
         36 . A process for preparing the isolated binding protein of  claim 1 , comprising the step of isolating said binding protein from a host cell. 
     
     
         37 . (canceled) 
     
     
         38 . A pharmaceutical composition comprising as an active agent at least one isolated binding protein of  claim 1 , and a pharmaceutically acceptable carrier, diluent or adjuvant. 
     
     
         39 .- 40 . (canceled) 
     
     
         41 . A method for treating or preventing a disease associated with HER-3 in a patient, comprising administering a pharmaceutically effective amount of a pharmaceutical composition of  claim 38  to a subject in need thereof. 
     
     
         42 .- 44 . (canceled) 
     
     
         45 . A method for diagnosing a disease associated with HER-3, comprising: (a) contacting a sample with the binding protein of any one of  claims 1 - 26 , under conditions suitable to allow binding of said binding protein to HER-3; and (c) identifying binding of said binding protein to HER-3. 
     
     
         46 . The method of  claim 45 , wherein the disease is a hyperproliferative disease. 
     
     
         47 .- 52 . (canceled)