Claims for Patent: 10,238,690

Summary for Patent: 10,238,690

Title:	Modified T lymphocytes comprising an inducible caspase and methods of apoptosis
Abstract:	Provided herein are cells, e.g., T cells expressing artificial cell death polypeptides that cause death of a cell, e.g., cells (e.g., T lymphocytes) expressing the cell death polypeptide, when the cell death polypeptide is multimerized or dimerized. Also provided herein is use of such cells, e.g., T lymphocytes, to treat diseases such as cancer.
Inventor(s):	Abbot; Stewart (San Diego, CA), Li; Tianjian (Belle Mead, NJ), Liang; Bitao (Closter, NJ)
Assignee:	CELGENE CORPORATION (Summit, NJ)
Application Number:	14/775,891
Patent Claims:	1. A T lymphocyte comprising an artificial cell death polypeptide comprising an apoptosis-inducing domain, wherein said artificial cell death polypeptide is a transmembrane protein comprising an extracellular domain that comprises a CD20 epitope, a transmembrane domain, and an intracellular domain comprising said apoptosis-inducing domain, wherein said apoptosis-inducing domain is caspase 3, caspase 8 or caspase 9, wherein said polypeptide is dimerizable using an anti-CD20 antibody that binds to said CD20 epitope, and wherein when said antibody dimerizes said polypeptide, an apoptosis-inducing signal is generated in said T lymphocyte. 2. The T lymphocyte of claim 1, wherein said antibody has been approved by the United States Food and Drug Administration for any use. 3. The T lymphocyte of claim 1, wherein said antibody is rituximab and said extracellular domain comprises a CD20 epitope to which said rituximab binds. 4. The T lymphocyte of claim 1 that additionally comprises a chimeric antigen receptor (CAR) that recognizes an antigen on a tumor cell. 5. The T lymphocyte of claim 4, wherein said tumor cell is a cell in a solid tumor. 6. The T lymphocyte of claim 4, wherein said tumor cell is a cell of a blood cancer. 7. The T lymphocyte of claim 4, wherein said antigen is Her2, prostate stem cell antigen, alpha-fetoprotein, carcinoembryonic antigen, cancer antigen-125, CA19-9, calretinin, MUC-1, epithelial membrane protein, epithelial tumor antigen, tyrosinase, melanoma-associated antigen, CD34, CD45, CD99, CD117, chromogranin, cytokeratin, desmin, glial fibrillary acidic protein, gross cystic disease fluid protein, HMB-45 antigen, protein melan-A, myo-D1, muscle-specific actin, neurofilament, neuron-specific enolase, placental alkaline phosphatase, synaptophysis, thyroglobulin, thyroid transcription factor-1, or the dimeric form of the pyruvate kinase isoenzyme type M2. 8. A method of killing a T lymphocyte, wherein said T lymphocyte comprises a plurality of artificial cell death polypeptides each comprising an apoptosis-inducing domain, wherein said artificial cell death polypeptide is a transmembrane protein comprising an extracellular domain that comprises a CD20 epitope, a transmembrane domain, and an intracellular domain comprising said apoptosis-inducing domain, wherein said apoptosis-inducing domain is caspase 3, caspase 8 or caspase 9, wherein said polypeptide is dimerizable using an anti-CD20 antibody that binds to said CD20 epitope, and wherein when said antibody dimerizes said polypeptides, an apoptosis-inducing signal is generated in said T lymphocyte, comprising contacting said T lymphocyte with an amount of said antibody sufficient for said plurality of artificial cell death polypeptides to dimerize and generate an aggregate apoptosis-inducing signal sufficient to kill said T lymphocyte. 9. The method of claim 8, wherein said antibody has been approved by the United States Food and Drug Administration for any use. 10. The method of claim 8, wherein said antibody is rituximab and said extracellular domain comprises a CD20 epitope that binds to said rituximab. 11. The method of claim 8 wherein said T lymphocyte additionally comprises a chimeric antigen receptor (CAR) that recognizes an antigen on a tumor cell. 12. The method of claim 11, wherein said antigen is Her2, prostate stem cell antigen, alpha-fetoprotein, carcinoembryonic antigen, cancer antigen-125, CA19-9, calretinin, MUC-1, epithelial membrane protein, epithelial tumor antigen, tyrosinase, melanoma-associated antigen, CD34, CD45, CD99, CD117, chromogranin, cytokeratin, desmin, glial fibrillary acidic protein, gross cystic disease fluid protein, HMB-45 antigen, protein melan-A, myo-D1, muscle-specific actin, neurofilament, neuron-specific enolase, placental alkaline phosphatase, synaptophysis, thyroglobulin, thyroid transcription factor-1, or the dimeric form of the pyruvate kinase isoenzyme type M2.

Details for Patent 10,238,690

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2033-03-15
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2033-03-15