Claims for Patent: 9,561,291

Summary for Patent: 9,561,291

Title:	Methods of targeting T-cells to tumors
Abstract:	The invention provides a method of targeting T-cells to tumor cells using a tumor-associated antigen (TAA) specific antibody and a T-cell specific antibody, wherein the two antibodies can bind to each other through a high affinity avidin/biotin or streptavidin/biotin connection. The invention further provides methods to target activated T-cells to different tumor types by using a T-cell specific antibody that is specific to an activated T-cell surface molecule like CTLA-4.
Inventor(s):	Kovesdi; Imre (Rockville, MD), Bakacs; Tibor (Budapest, HU), Szabo; Miklos (God, HU)
Assignee:
Application Number:	13/838,667
Patent Claims:	1. A method of targeting human T-cells to human tumor cells in a human host, said method comprising: (a) administering to said host a first tumor specific antibody binding to human carcinoembryonic antigen (CEA), CD19 or CD20, wherein said first tumor specific antibody is conjugated to a first member of a pair of specific binding moieties, in an amount sufficient to bind to the tumor cells in said host; (b) administering to said host a clearing compound conjugated to the second member of said pair of specific binding moieties and allowing sufficient amount of time for the non-tumor bound fraction of said conjugated first antibody to be eliminated from said host; (c) administering to said host a second T-cell specific antibody binding to human CTLA-4, wherein said second T-cell antibody is conjugated to the second member of said pair of specific binding moieties, in an amount sufficient to bind to the T-cells of said host and not more than about 5 mg; and (d) allowing sufficient amount of time for said first and second members of said pair of specific binding moieties to bind to each other, thereby targeting said T-cells to said tumor cells, wherein said method reduces immune related adverse events (irAEs) in a patient being treated for cancer relative to administration of anti-CTLA-4 antibody alone without said targeting. 2. The method of claim 1, wherein said first and second members of said pair of specific binding moieties are selected from the group consisting of avidin, streptavidin, and biotin. 3. The method of claim 2, wherein the first antibody is specific to carcinoembryonic antigen (CEA). 4. The method of claim 2, wherein the first antibody is specific to B cell surface antigen CD19 or CD20. 5. The method of claim 1 wherein the tumor cells expressed a tumor-associated antigen selected from the group consisting of CEA, CD19 and CD20, and the first tumor specific antibody is specific to said tumor-associated antigen. 6. A method of treating a tumor or cancer in a host comprising targeting T-cells to tumor or cancer cells by the method of claim 1, wherein cells of the tumor or cancer have a tumor-associated antigen selected from the group consisting of CEA, CD19 and CD20. 7. The method of claim 1, wherein the first tumor specific antibody binds to CD20, the first member of the pair of specific binding moieties is streptavidin, the clearing compound is poly(GalNAc), the second T-cell specific antibody binds to CTLA-4, the second member of the pair of specific binding moieties is biotin. 8. A method of reducing irAEs in a patient being treated for cancer by administration of anti-CTLA-4 antibody, said method comprising first targeting T-cells to tumor or cancer cells by the method of claim 1, and subsequently administering a dose of not more than about 5 mg of the anti-CTLA-4 antibody to the patient. 9. The method of claim 6, wherein the tumor-associated antigen (TAA) is carcinoembryonic antigen (CEA). 10. The method of claim 1, wherein the second T-cell specific antibody binding to human CTLA-4 is ipilimumab. 11. The method of claim 1, wherein the first antibody is specific to B cell surface antigen CD19 or CD20. 12. The method of claim 1, wherein the clearing compound is poly(GalNAc). 13. The method of claim 1, wherein the second T-cell specific antibody binding to human CTLA-4 conjugated to the second member of said pair of specific binding moieties is combined ex vivo with T-cells prior to being administered to said host in step (c).

Details for Patent 9,561,291

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2039-02-26