Anti-IGF-I receptor antibody

Abstract

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to, and inhibit, insulin-like growth factor-I receptor, antagonize the effects of IGF-I, IGF-II and serum on the growth and survival of tumor cells, and which are substantially devoid of agonist activity. Said antibodies and fragments thereof may be used, optionally in conjunction with other therapeutic agents, in the treatment of tumors that express elevated levels of IGF-I receptor, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma, prostate cancer and pancreatic cancer, and said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of IGF-I receptor.

1 .- 31 . (canceled)  
     
     
         32 . An IGF-IR antagonist comprising a recombinant single-chain antibody capable of effectively inhibiting IGF-IR-agonist interaction.  
     
     
         33 . An IGF-IR antagonist according to  claim 32 , wherein, the antibody is a chimeric single-chain recombinant antibody.  
     
     
         34 . An IGF-IR antagonist according to  claim 33 , wherein the antibody is a humanized single-chain recombinant antibody.  
     
     
         35 . An IGF-IR single-chain recombinant antibody capable of effectively inhibiting IGF-IR-agonist interaction wherein the recombinant antibody consists essentially of a V L  domain antigen binding portion linked to a V H  domain antigen binding portion through a peptide linker.  
     
     
         36 . A recombinant antibody according to  claim 35 , wherein said antigen binding portions of said V L  and V H  domains are murine antibody domains.  
     
     
         37 . A recombinant antibody according to  claim 35 , wherein the antibody consists essentially of a V L  domain antigen binding portion linked through a peptide linker to a V H  domain antigen binding portion linked to an immunoglobulin constant domain.  
     
     
         38 . A recombinant antibody according to  claim 37 , wherein said V L  and V H  domains are murine antibody domains.  
     
     
         39 . A recombinant antibody according to  claim 37 , wherein said immunoglobulin constant domain comprises C H2  and C H3  regions of a constant domain.  
     
     
         40 . A recombinant antibody according to  claim 39 , wherein said C H2  and C H3  regions are from a non-murine mammalian immunoglobulin domain.  
     
     
         41 . A recombinant antibody according to  claim 40 , wherein said C H2  and C H3  regions are human immunoglobulin regions.