IP Library › Granted Patent US 9,540,445
Granted Patent B2
US 9,540,445 · App. 14/997,136 · Granted Jan 10, 2017

Compositions and methods for treatment of cancer

Inventors: Carl H. June (Merion Station, PA); Bruce L. Levine (Cherry Hill, NJ); David L. Porter (Springfield, PA); Michael D. Kalos (Philadelphia, PA); Michael C. Milone (Cherry Hill, NJ)
Assignee: The Trustees of the University of Pennsylvania
C07K16/2896A61K35/17A61K38/177A61K38/1774A61K39/0011A61K39/39558A61K45/06A61K48/005C07K14/525C07K14/7051C07K14/70517C07K14/70521C07K14/70578C07K14/70596C07K16/2803C07K16/30C07K16/3061C12N5/0636C12N7/00C12N15/85A61K2039/505A61K2039/5156A61K2039/5158A61K2039/5256A61K2039/585C07K2317/53C07K2317/622C07K2317/76C07K2317/80C07K2319/00C07K2319/02C07K2319/03C07K2319/30C07K2319/33C07K2319/74C12N2501/515C12N2510/00C12N2740/15034C12N2740/15043C12N2740/15071
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Quick Facts
Patent No.
US 9,540,445
App. No.
14/997,136
Granted
Jan 10, 2017
Kind
B2
Abstract

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Claims (30)

1. A pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the T cells comprise a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising, from the amino to the carboxy terminus, a light chain variable region and a heavy chain variable region of SEQ ID NO:20, wherein the CAR further comprises a transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cells are from a human having cancer.

2. The composition of claim 1 , wherein the anti-tumor effective amount of T cells is 10 4 to 10 9 cells per kg body weight of a human in need of such cells.

3. The composition of claim 1 , wherein the anti-tumor effective amount of T cells is 10 5 to 10 6 cells per kg body weight of a human in need of such cells.

4. The composition of claim 1 , wherein said antigen binding fragment is a scFv.

5. The composition of claim 4 , wherein the scFv comprises the amino acid sequence of SEQ ID NO:20.

6. The composition of claim 1 , wherein the transmembrane domain is CD8α transmembrane domain.

7. The composition of claim 6 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.

8. The composition of claim 1 , wherein the CAR further comprises a hinge domain.

9. The composition of claim 8 , wherein the hinge domain is a CD8α hinge domain.

10. The composition of claim 9 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO:21.

11. The composition of claim 1 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:23.

12. The composition of claim 1 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 24.

13. The composition of claim 1 , wherein the CD19 antigen binding domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 14.

14. The composition of claim 6 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.

15. The composition of claim 10 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.

16. The composition of claim 11 , wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO: 17.

17. The composition of claim 12 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 18.

18. The composition of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO:12.

19. The composition of claim 18 , wherein the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:8.

20. The composition of claim 1 , wherein the CAR further comprises a CD28 costimulatory signaling region.

21. The composition of claim 1 , wherein the T cells are T cells of a human having a cancer.

22. The composition of claim 21 , wherein the cancer is a hematological cancer.

23. The composition of claim 1 , wherein the T cells comprise a vector that comprises the nucleic acid sequence.

24. The composition of claim 23 , wherein the vector is a lentiviral vector.

25. The composition of claim 23 , wherein the vector further comprises a promoter.

26. The composition of claim 25 , wherein the promoter is an EF-1α promoter.

27. The composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent or excipient.

28. The composition of claim 1 , wherein the pharmaceutical composition comprises a buffer.

29. The composition of claim 28 , wherein the buffer is neutral buffer saline or phosphate buffered saline.

30. The composition of claim 1 , wherein the pharmaceutical composition further comprises a carbohydrate.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2024
From: JUNE, CARL H.; LEVINE, BRUCE L.; PORTER, DAVID L.; KALOS, MICHAEL D.; MILONE, MICHAEL C.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 067599/0455 →
CONFIRMATORY LICENSE Recorded Jan 28, 2019
From: UNIVERSITY OF PENNSYLVANIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 049650/0306 →
Continuity (4)
Continuation 13992622
Provisional Application 61421470 · Dec 9, 2010
Provisional Application 61502649 · Jun 29, 2011
Related Publication 20160208012A1 · Jul 21, 2016