Monoclonal antibodies for enhancing or inhibiting insulin-like growth factor-I
View Patent ↗The present invention provides αVβ3 integrin cysteine loop domain agonists and antagonists (including peptide agonists and antagonists and analogs thereof), along with methods of using the same.
1. A method of inhibiting IGF-1 actions in a subject in need of treatment for nephropathy, comprising administering to the subject an effective amount of an antibody that: (a) specifically binds to the cysteine loop domain at amino acids 177 to 184 of a human β 3 integrin, wherein said amino acids consist of SEQ ID NO:82; (b) does not specifically bind to the RGD binding site of a human β 3 integrin or utilize the RGD binding site of human β 3 integrin; and (c) specifically binds to the cysteine loop domain at amino acids 177 to 184 of a pig β 3 integrin, wherein said amino acids consist of SEQ ID NO:82, thereby inhibiting IGF-1 actions in the subject and treating the nephropathy in the subject.
2. The method of claim 1 , wherein the antibody is coupled to a detectable group.
3. The method of claim 1 , wherein the antibody is coupled to a therapeutic group.
4. The method of claim 1 , wherein the antibody is a monoclonal antibody.
5. The method of claim 1 , wherein the antibody does not specifically inhibit ligand occupancy of the RGD binding site of the β 3 integrin.
6. The method of claim 1 , wherein the antibody does not stimulate the specific biochemical events that are stimulated by peptides that bind to the RGD domain binding site of human β 3 integrin.
7. The method of claim 1 , wherein the subject is in need of treatment for diabetic nephropathy.