Methods of treating cancer by administering IGF-IR binding molecules
The present invention provides innovative proteins that bind to insulin-like growth factor-I receptor (IGF-IR), as well as other important proteins. The invention also provides innovative proteins in pharmaceutical preparations and derivatives of such proteins and the uses of same in diagnostic, research and therapeutic applications. The invention further provides cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and vectors comprising the polynucleotides encoding the innovative proteins.
1. A method of treating a subject that has a cancer associated with increased insulin-like growth factor activity, the method comprising administering to a subject in need thereof a pharmaceutically effective amount of a polypeptide comprising an altered tenth fibronectin type III ( 10 Fn3) domain comprising an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 184-203, and wherein the 10 Fn3 domain binds human insulin-like growth factor-I receptor (IGF-IR) with a dissociation constant of about 1 μM or less.
2. The method of claim 1 , wherein the altered 10 Fn3 domain binds human IGF-IR with a disassociation constant of about 10 nM or less.
3. The method of claim 1 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 184-203.
4. The method of claim 1 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 184-203.
5. The method of claim 1 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 184-203.
6. The method of claim 1 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is identical to any one of SEQ ID NOs: 184-203.
7. The method of claim 1 , wherein the altered 10 Fn3 domain comprises an amino acid sequence of SEQ ID NO: 184.
8. The method of claim 1 , wherein the polypeptide further comprises one or more pharmacokinetic (PK) moieties selected from: a polyoxyalkylene moiety, a human serum albumin binding protein, sialic acid, human serum albumin, transferrin, and an Fc fragment.
9. The method of claim 8 , wherein the PK moiety is the polyoxyalkylene moiety and said polyoxyalkylene moiety is polyethylene glycol.
10. The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, colon cancer, ovarian carcinoma, osteosarcoma, cervical cancer, prostate cancer lung cancer, synovial carcinoma, pancreatic cancer, plasmacytoma, rhabdomyosarcoma and multiple myeloma.