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 cell division of an endothelial cell, comprising contacting the endothelial cell with an effective amount of an antibody that: (a) specifically binds to the cysteine loop domain at amino acids 177 to 184 of a human β3 integrin, wherein said amino acids consist of SEQ ID NO: 82; (b) does not specifically bind to the RGD binding site of a human β3 integrin; and (c) specifically binds to the cysteine loop domain at amino acids 177 to 184 of a pig β3 integrin, wherein said amino acids consist of SEQ ID NO: 82, thereby inhibiting cell division of the endothelial cell.
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 β3 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 β3 integrin.
7. A method of inhibiting vitronectin occupancy of a human β3 integrin, comprising contacting an endothelial cell comprising a human β3 integrin in the presence of vitronectin with an effective amount of an antibody that: (a) specifically binds to the cysteine loop domain at amino acids 177 to 184 of a human β3 integrin, wherein said amino acids consist of SEQ ID NO: 82; (b) does not specifically bind to the RGD binding site of a human β3 integrin; and (c) specifically binds to the cysteine loop domain at amino acids 177 to 184 of a pig β3 integrin, wherein said amino acids consist of SEQ ID NO: 82, thereby inhibiting vitronectin occupancy of the human β3 integrin.
8. The method of claim 7 , wherein the antibody is coupled to a detectable group.
9. The method of claim 7 , wherein the antibody is coupled to a therapeutic group.
10. The method of claim 7 , wherein the antibody is a monoclonal antibody.
11. The method of claim 7 , wherein the antibody does not specifically inhibit ligand occupancy of the RGD binding site of the β3 integrin.
12. The method of claim 7 , 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 β3 integrin.