Patent EA-004270-B1 (EA)
Title: Method of treating multiple myeloma and myeloma-induced bone resorption using integrin antagonists
Inventor: MUNDY GREGORY R
IPC: A61K45/00
Filed: 1999-09-13
Abstract: 1. A method for the treating multiple myeloma comprising administering to an individual a therapeutically effective amount of an alpha4 integrin binding agent. 2. A method for the treating multiple myeloma comprising administering to an individual a therapeutically effective amount of an alpha4 integrin ligand binding agent. 3. The method of claim 1, wherein the alpha4 integrin binding agent is selected from the group consisting of: a) an antibody homolog that antagonizes the interaction of both VLA-4 and alpha4beta7 with their respective alpha4 ligands; b) an antibody homolog that antagonizes the interaction of VLA-4 with its alpha4 ligand; and c) an antibody homolog that antagonizes the interaction of alpha4beta7 with its alpha4 ligand. 4. The method of claim 3, wherein the antibody homolog is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof. 5. The method of claim 2, wherein the alpha4 integrin ligand binding agent is an anti VCAM-1 antibody homolog. 6. The method of claim 5, wherein the antibody homolog is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof. 7. The method of claim 1 or 2, wherein the agent is a small molecule with a molecular weight less than 2000. 8. A method of claim 1, wherein the composition is administered at a dosage so as to provide from about 0.1 to about 20 mg/kg body weight. 9. A method for inhibiting bone resorption associated with tumors of bone marrow, the method comprising administering to a mammal with said tumors a composition comprising a therapeutically effective amount of an alpha4 integrin binding agent. 10. The method of claim 9, wherein the alpha4 integrin binding agent is an anti-VLA-4 antibody homolog or anti-alpha4beta7 antibody homolog. 11. The method of claim 10, wherein the antibody homolog is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof. 12. The method for inhibiting bone resorption associated with tumors of bone marrow, the method comprising administering to a mammal with said tumors a composition comprising a therapeutically effective amount of the alpha4 integrin ligand binding agent. 13. The method of claim 12, wherein the alpha4 integrin ligand binding agent is an anti VCAM-1 antibody homolog. 14. The method of claim 13, wherein the antibody homolog is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof. 15. The method of claim 9 or 12, wherein the antagonist is a small molecule with a molecular weight less than 2000. 16. A method of claim 9 or 12, wherein the composition is administered at a dosage so as to provide from about 0.1 to about 20 mg/kg, based on the weight of the individual. 17. The method of claim 15, wherein the antagonist is administered in an amount effective to provide a dosage of small molecule of about 0.1-30 mg/kg body weight. 18. A method of treating a subject having a disorder characterized by the presence of osteoclastogenesis, the method comprising administering to the subject a composition comprising an alpha4 integrin binding agent in an amount sufficient to suppress the osteoclastogenesis. 19. The method of claim 18, wherein the alpha4 integrin binding agent is an anti-VLA-4 antibody homolog or an anti-alpha4beta7 binding agent. 20. The method of claim 19, wherein the antibody homolog is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof. 21. The method of claim 1, 9 or 18, wherein the alpha4 integrin ligand binding agent is an anti VLA-4 antibody homolog or a fragment thereof. 22. The method of claim 21, wherein the anti VLA-4 antibody is HP1/2 antibody. 23. The method of claim 21, wherein the anti VLA-4 antibody is HP2/1 antibody. 24. The method of claim 21, wherein the anti VLA-4 antibody is HP2/4 antibody. 25. The method of claim 21, wherein the anti VLA-4 antibody is L25 antibody. 26. The method of claim 21, wherein the anti VLA-4 antibody is P4C2 antibody. 27. The method of claim 21, wherein the anti VLA-4 antibody is P4G9 antibody. 28. The method of claim 21, wherein the anti VLA-4 antibody is a humanized light chain and a humanized heavy chain, both light and heavy chains comprise hupervariable regions (CDR1, CDR2 and CDR3) from mouse 21-6 anti VLA-4 antibody. 29. The method of claim 21, wherein (a) the humanized light chain comprises a variable region framework from variable region frame sequence from the kappa human light chain, wherein at least one amino acid position is occupied by the same amino acid present in the equivalent position of the mouse 21-6 immunoglobulin light chain variable region framework and (b) the humanized heavy chain comprises a variable region framework from variable region frame sequence from the kappa human heavy chain, wherein at least one amino acid position is occupied by the same amino acid present in the equivalent position of the mouse 21-6 immunoglobulin heavy chain variable region framework. 30. A method of treating a subject having a disorder characterized by the presence of osteoclastogenesis, the method comprising administering to the subject a composition comprising an alpha4 integrin ligand binding agent in an amount sufficient to suppress the osteoclastogenesis. 31. The method of claim 30, wherein the alpha4 integrin ligand binding agent is an anti-VLA-4 antibody homolog or an anti-alpha4beta7 binding agent. 32. The method of claim 31, wherein the antibody homolog is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof. 33. The method of claim 18 or 30, wherein the antagonist is a small molecule with a molecular weight less than 2000. 34. A method of claim 18 or 30, wherein the composition is administered at a dosage so as to provide from about 0.1 to about 20 mg/kg, based on the weight of the individual. 35. The method of claim 33, wherein the antagonist is administered in an amount effective to provide a dosage of small molecule of about 0.1-20 mg/kg body weight.