Erbb3 based methods and compositions for treating neoplasms

Abstract

The present invention relates to compositions and methods for treating neoplasms in mammals, particularly humans. More particularly, the present invention provides for methods for preventing, treating or delaying neoplasm in a mammal using an ErbB-3 protein, a nucleic acid encoding an ErbB-3 protein or a functional fragment thereof. The present invention also provides for an isolated nucleic acids encoding an extracellular domain of the ErbB-3 protein, or a functional fragment thereof, substantially purified extracellular domain of the ErbB-3 protein, or a functional fragment thereof and antibodies that bind to an epitope in an extracellular domain of the ErbB-3 protein, or a functional fragment thereof. The present invention further provides for pharmaceutical compositions and/or vaccines comprising the extracellular domain of the ErbB-3 protein, or a functional fragment thereof, or nucleic acids encoding and antibodies binding to such extracellular domain or functional fragments thereof.

1 - 28 . (canceled) 
     
     
         29 . An antibody which binds to an ErbB-3 protein, wherein the ErbB-3 protein is a fragment of the extracellular domain of ErbB-3 and comprises:
 a) the amino acid sequence set forth in SEQ ID NO:3; or;   b) amino acid residues 24-81 of the amino acid sequence set forth in SEQ ID NO: 14; or   c) amino acid residues 2-139 of the amino acid sequence set forth in SEQ ID NO:16   wherein the ErbB-3 protein is not the entire extracellular domain of ErbB-3.   
     
     
         30 . The antibody of  claim 29 , which is a polyclonal or monoclonal antibody. 
     
     
         31 . The antibody of  claim 29 , which is a human or humanized antibody. 
     
     
         32 - 43 . (canceled) 
     
     
         44 . The antibody of  claim 29 , further comprising administering an immune response potentiator to the mammal. 
     
     
         45 . The antibody of  claim 29 , wherein the antibody is co-administered with a pharmaceutically acceptable carrier or excipient. 
     
     
         46 . The antibody of  claim 29 , wherein the antibody is co-administered with an anti-neoplasm agent. 
     
     
         47 . The antibody of  claim 46 , wherein the anti-neoplasm agent is selected from the group consisting of an anti-angiogenic agent, an alkylating agent, an antimetabolite, a natural product, a platinum coordination complex, an anthracenedione, a substituted urea, a methylhydrazine derivative, an adrenocortical suppressant, a hormone, an antagonist, an oncogene inhibitor, a tumor suppressor gene or protein, an anti-oncogene antibody and an anti-oncogene antisense oligonucleotide. 
     
     
         48 . The antibody of  claim 46 , wherein the neoplasm to be treated is selected from the group consisting of adrenal gland, anus, auditory nerve, bile ducts, bladder, bone, brain, breast, bruccal, central nervous system, cervix, colon, ear, endometrium, esophagus, eye, eyelids, fallopian tube, gastrointestinal tract, head and neck, heart, kidney, larynx, liver, lung, mandible, mandibular condyle, maxilla, mouth, nasopharynx, nose, oral cavity, ovary, pancreas, parotid gland, penis, pinna, pituitary, prostate gland, rectum, retina, salivary glands, skin, small intestine, spinal cord, stomach, testes, thyroid, tonsil, urethra, uterus, vagina, vestibulocochlear nerve and vulva neoplasm. 
     
     
         49 . The antibody of  claim 46 , wherein the neoplasm to be treated is selected from the group consisting of breast, ovary, stomach, prostate, colon and lung cancer. 
     
     
         50 . The antibody of  claim 46 , wherein the neoplasm to be treated is breast cancer. 
     
     
         51 . The antibody of  claim 29 , wherein the antibody is administered by intracavernous injection, subcutaneous injection, intravenous injection, intramuscular injection, intradermal injection, oral administration or topical administration. 
     
     
         52 . The antibody of  claim 29 , wherein the antibody is administered by subcutaneous injection. 
     
     
         53 . The antibody of  claim 29 , wherein the antibody is administered to the neoplasm in situ. 
     
     
         53 . The antibody of  claim 44 , wherein the immune response potentiator is administered to the neoplasm in situ. 
     
     
         54 . A method for treating neoplasm which express ErbB-3 in a mammal using the antibody of  claim 29 . 
     
     
         55 . A method for preparing the antibody of  claim 29 , wherein the method comprises:
 a. providing an antigen comprising the amino acid sequence set forth in SEQ ID NO:3, amino acid residues 24-81 of the amino acid sequence set forth in SEQ ID NO: 14, or amino acid residues 2-139 of the amino acid sequence set forth in SEQ ID NO:16;   b. exposing an antibody repertoire or potential antibody repertoire to one of the above amino acid sequences; and   c. selecting from the repertoire an antibody which specifically binds to one of the above amino acid sequences.