Claims for Patent: 8,377,435

Summary for Patent: 8,377,435

Title:	Antibody induced cell membrane wounding
Abstract:	Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.
Inventor(s):	Bhat; Neelima M. (Los Altos, CA), Bieber; Marcia M. (Los Altos, CA), Teng; Nelson N. H. (Hillsborough, CA), Sanders; Martin E. (Hillsborough, CA)
Assignee:	The Board of Trustees of the Leland Stanford Junior University (Palo Alto, CA)
Application Number:	11/267,935
Patent Claims:	1. A method of treating a mammal suffering from a condition characterized by hyperproliferation of B cells, wherein said hyperproliferating B-cells are cancer cells, comprising administering a cell membrane-wounding VH4-34 antibody that binds to the CDIM epitope on the surface of B cells, in combination with a second cytotoxic agent, wherein said cell membrane wounding VH4-34 antibody is administered at a dosage that was determined to cause membrane pores that allow the second cytotoxic agent to enter said hyperproliferating B-cells to synergistically reduce viability of said hyperproliferating B cells. 2. The method of claim 1, wherein the mammal is a human. 3. The method of claim 1, wherein the mammal is a nonhuman mammal. 4. The method of claim 1, wherein the hyperproliferating B cells are stimulated into a hyperproliferating condition by growth factors, cytokines, or Epstein Barr Virus infection. 5. The method of claim 1, wherein the second cytotoxic agent is a chemotherapeutic agent, a radioactive isotope, a cytotoxic antibody, an immunoconjugate, a ligand conjugate, an immunosuppressant, a cell growth regulator or inhibitor, a toxin, or mixtures thereof. 6. The method of claim 5, wherein the chemotherapeutic agent is vincristine, daunorubicin, L-asparaginase, or colchicine. 7. The method of claim 1, wherein the condition characterized by a hyperproliferation of B cells is lymphoid cancer. 8. The method of claim 1, wherein the viability of hyperproliferating B cells is reduced to 42 percent. 9. The method of claim 1, wherein the viability of hyperproliferating B cells is reduced to 30 percent. 10. The method of claim 1, wherein said cell membrane wounding VH4-34 antibody is administered at a dosage of 1.25 mg/kg bodyweight. 11. A method of killing neoplastic B cells in a mammal, comprising administering to neoplastic B cells a cytotoxic amount of a cell membrane wounding VH4-34 antibody that binds to the CDIM epitope on the surface of the neoplastic B cells in combination with a second cytotoxic agent, wherein said cell membrane wounding VH4-34 antibody is administered at a dosage that was determined to cause membrane pores that allow the second cytotoxic agent to enter said neoplastic B cells to synergistically reduce the viability of the neoplastic B cells. 12. The method of claim 11, wherein the mammal is a human. 13. The method of claim 11, wherein the mammal is a nonhuman mammal. 14. The method of claim 11, wherein the neoplastic B cells are stimulated into a hyperproliferating condition by growth factors, cytokines, or Epstein Barr Virus infection. 15. The method of claim 11 wherein the second cytotoxic agent is a chemotherapeutic agent, a radioactive isotope, a cytotoxic antibody, an immunoconjugate, a ligand conjugate, an immunosuppressant, a cell growth regulator or inhibitor, a toxin, or mixtures thereof. 16. The method of claim 11, wherein the second cytotoxic agent is vincristine, daunorubicin, L-asparaginase, or colchicine. 17. The method of claim 11, wherein the mammal has lymphoid cancer. 18. The method of claim 11, wherein the viability of neoplastic B cells is reduced to 42 percent. 19. The method of claim 11, wherein the viability of neoplastic B cells is reduced to 30 percent. 20. The method of claim 11, wherein said cell membrane wounding VH4-34 antibody is administered at a dosage of 1.25 mg/kg bodyweight.

Details for Patent 8,377,435

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2024-11-05