BH-S100/BH-S200 United States Patent 5,078,998

Product Design:The BH-S100 suppressing hybrid antibody, built on an antibody backbone, is composed of Fab fragments of an antibody-binding site specific for a group of surface proteins called HLA molecules expressed on the cells of the graft. Isogenis' suppressing hybrid antibody is specific for HLA-A2 as the anchoring structure, which is the most widely represented Class I HLA in humans.The other arm of BH-S100 is engineered to present a CD8 protein to a corresponding CD8 protein on the T cell activation molecule, inducing the veto effect, and allowing the “labeled” cell to survive.Another suppressing hybrid antibody, BH-S200, will use the HLA-A3 as the anchoring structure.With these two suppressing hybrid antibodies, we estimate that considering the distribution of HLA-A2 and HLA-A3 in the population it will be possible to provide more than 90% of all patients with transplants.

Due to the special features of the suppressing hybrid antibody therapy, more patients will have access to transplants, and more disease processes will become treatable by transplantation.

Product Advantage:Suppressing hybrid antibodies are superior to other transplant therapies presently in use and under development in seven key respects:

1. The cost of existing transplant rejection therapies is approximately $5,000 per year for the remaining life of the patient. At present, a transplanted organ survives on average for ten years.The total cost of the immunosuppressive therapy amounts to $50,000.We believe its therapeutic can be profitably delivered at a total cost of $20,000 per patient, or less than one-half the cost of the present immunosuppressive therapy.
2. Patients have greater access to transplants.The chances of finding a “matching” organ will improve from 1 in 100,000 to 1 in 4.
3. Just with the two suppressing hybrid antibodies Bh-S100 and BH-S200, it will be possible to provide more than 90% of patients with a suitable organ.With the production of three additional suppressing hybrid antibodies that anchor to other MHC molecules, it will be possible to treat close to 100% of transplant recipients.
4. Suppressing hybrid antibodies are cell selective.They protect the transplanted tissue by inhibiting transplant-reactive killer T cells that are prone to destroying it.T cells with other reactivities are not inhibited. Patients undergoing treatment with BH-S100/BH-S200 can still defend themselves against infectious diseases. Patients receiving current anti-rejection drugs are less able to do so.
5. Suppressing hybrid antibodies are non-toxic because they are composed of naturally occurring human proteins.They do not contain any toxic substances, which affect healthy tissues.Therefore, the many systemic side effects are avoided.
6. Suppressing hybrid antibodies are administered as a short course of therapy. Antigen presenting cells disappear from the transplant within several weeks.Based on product design and current scientific knowledge, Isogenis Inc. expects that the suppressing hybrid antibody will only be given during this time frame. Life long therapy regimens presently required will no longer be necessary.
7. Suppressing hybrid antibodies can be used in different transplant situations.They will be used in the transplantation of solid organs including, kidney, heart, liver, and lung, as well as bone marrow
8. Another problem faced by many transplant recipients is graft-versus-host disease, which is caused by donor immune cells carried within the transplanted tissue.These donor-derived cells attack the recipient’s own organs.  The same suppressing hybrid antibodies will be able to inhibit this disease process.