Patent EA-004401-B1 (EA)
Title: Therapeutic applications of t-bam (cd40l) technology to treat diseases involving smooth muscle cells
Inventor: YELLIN MICHAEL J
IPC: C12R1/91
Filed: 1997-07-03
Abstract: 1. A method of inhibiting activation by CD40 ligand of smooth muscle cells bearing CD40 on the surface of the cells, wherein said CD40 bearing cells are the smooth muscle cells of the bladder, vascular smooth muscle cells, aortic smooth muscle cells, coronary smooth muscle cells, pulmonary smooth muscle cells, or gastrointestinal smooth muscle cells, said method comprising administering to the subject a therapeutically effective amount of an antibody, a Fab-fragment or a single chain antibody, if said an antibody, the Fab-fragment or the single chain antibody is capable to inhibit activation of the CD40-bearing smooth muscle cells by administering to the subject CD40-ligand capable of inhibiting interaction between CD40 ligand and CD40 on the smooth muscle cells. 2. The method of claim 1, wherein said gastrointestinal smooth muscle cells are selected from esophageal smooth muscle cells, stomachic smooth muscle cells, smooth muscle cells of the small intestine, or smooth muscle cells of the large intestine. 3. The method of claim 1, wherein said antibody, Fab or single chain antibody specifically inhibits the binding of CD40 ligand to CD40 on said smooth muscle cells. 4. The method according to claim 1, wherein said antibody, Fab or single chain antibody specifically binds the epitope to which monoclonal antibody 5c8, produced by the hybridoma having ATCC Accession No. HB 10916, specifically binds. 5. The method according to claim 1, wherein said antibody, Fab or single chain antibody specifically recognizes the protein to which monoclonal antibody 5c8, produced by the hybridoma having ATCC Accession No. HB 10916, binds. 6. The method according to claim 1, wherein said antibody, Fab or single chain antibody specifically binds to CD40 ligand. 7. The method according to claim 1, wherein said antibody is selected from the group consisting of: monoclonal antibodies, polyclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, primatized antibodies and antibodies which include a CDR region from a first human and an antibody scaffold from a second human. 8. The method according to claim 6 wherein said monoclonal antibody is monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. 9. The method according to claim 1, wherein said antibody, Fab or single chain antibody is selected or designed by structure optimization of a lead inhibitory antibody, Fab or single chain antibody based on a three-dimensional structure of a complex of soluble extracellular region CD40 ligand or a portion thereof with the lead inhibitory antibody, Fab or single chain antibody. 10. The method according to claim 1, wherein said antibody, Fab or single chain antibody specifically inhibits cell activation by CD40 ligand of CD40-bearing smooth muscle cells which are involved in a smooth muscle cell-dependent disease. 11. The method according to claim 10, wherein said smooth muscle cell-dependent disease is selected from the group consisting of: vascular disease, bladder disease and gastrointestinal disease. 12. The method according to claim 11, wherein said gastrointestinal disease is selected from the group consisting of: esophageal dysmotility, inflammatory bowel disease and scleroderma. 13. The method according to claim 11, wherein said vascular disease is atherosclerosis. 14. A method of inhibiting activation, by CD40 ligand, of smooth muscle cells bearing CD40 on the surface of the cells, comprising the step of contacting said smooth muscle cells in vitro with an antibody, a Fab or a single chain antibody capable of inhibiting the interaction between CD40 ligand and CD40, wherein said smooth muscle cells are smooth muscle cells of the bladder, vascular smooth muscle cells, aortic smooth muscle cells, coronary smooth muscle cells, pulmonary smooth muscle cells or gastrointestinal smooth muscle cells. 15. The method according to claim 14, wherein said gastrointestinal smooth muscle cells are selected from the group consisting of: esophageal smooth muscle cells, stomachic smooth muscle cells, smooth muscle cells of the intestine and smooth muscle cells of the small intestine. 16. The method according to claim 14, wherein said antibody, Fab or single chain antibody specifically inhibits the binding of CD40 ligand to CD40 on said smooth muscle cells. 17. The method according to claim 14, wherein said antibody, Fab or single chain antibody specifically binds the epitope to which monoclonal antibody 5c8, produced by the hybridoma having ATCC Accession No. HB 10916, specifically binds. 18. The method according to claim 14, wherein said antibody, Fab or single chain antibody specifically recognizes the protein to which monoclonal antibody 5c8, produced by the hybridoma having ATCC Accession No. HB 10916, binds. 19. The method according to claim 14, wherein said antibody, Fab or single chain antibody specifically binds to CD40 ligand. 20. The method according to any one of claims 16-19, wherein said antibody is selected from the group consisting of: monoclonal antibodies, polyclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, primatized antibodies and antibodies which include a CDR region from a first human and an antibody scaffold from a second human. 21. The method according to claim 20 wherein said monoclonal antibody is monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. 22. The method according to claim 14, wherein said antibody, Fab or single chain antibody is selected or designed by structure optimization of a lead inhibitory antibody, Fab or single chain antibody based on a three-dimensional structure of a complex of soluble extracellular region CD40 ligand or a portion thereof with the lead inhibitory antibody, Fab or single chain antibody. 23. The method according to claim 14, wherein said antibody, Fab or single chain antibody specifically inhibits cell activation by CD40 ligand of CD40-bearing smooth muscle cells which are involved in a smooth muscle cell-dependent disease. 24. The method according to claim 23, wherein said smooth muscle cell-dependent disease is selected from the group consisting of: vascular disease, bladder disease and gastrointestinal disease. 25. The method according to claim 24, wherein said gastrointestinal disease is selected from the group consisting of: esophageal dysmotility, inflammatory bowel disease and scleroderma. 26. The method according to claim 24, wherein said vascular disease is atherosclerosis.