US 12,186,278 B2
Mesothelin chimeric antigen receptor (CAR) and antibody against PD-L1 inhibitor for combined use in anticancer therapy
Jennifer Brogdon, Sudbury, MA (US); Hwai Wen Chang, San Marcos, CA (US); Boris Engels, Arlington, MA (US); Gordon James Freeman, Brookline, MA (US); Gerhard Johann Frey, San Diego, CA (US); Jennifer Marie Mataraza, Cambridge, MA (US); Reshma Singh, Cambridge, MA (US); and Arlene Helen Sharpe, Brookline, MA (US)
Assigned to Novartis AG, Basel (CH); The Trustees of the University of Pennsylvania, Philadelphia, PA (US); Dana Farber Cancer Institute, Inc., Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
Filed by Novartis AG, Basel (CH); The Trustees of the University of Pennsylvania, Philadelphia, PA (US); Dana-Farber Cancer Institute, Inc., Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
Filed on Jul. 11, 2022, as Appl. No. 17/811,606.
Application 17/811,606 is a division of application No. 16/065,387, granted, now 11,413,340, previously published as PCT/US2016/067957, filed on Dec. 21, 2016.
Claims priority of provisional application 62/270,780, filed on Dec. 22, 2015.
Prior Publication US 2023/0000964 A1, Jan. 5, 2023
Int. Cl. C07K 16/00 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)
CPC A61K 39/4636 (2023.05) [A61K 39/3955 (2013.01); A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/464468 (2023.05); A61K 45/06 (2013.01); A61P 35/00 (2018.01); A61K 2039/505 (2013.01); A61K 2039/545 (2013.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05)] 27 Claims
 
1. A composition or dosage formulation each comprising:
(a) a cell or a population of immune effector cells expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a mesothelin binding domain, a transmembrane domain, and an intracellular signaling domain; and wherein the mesothelin binding domain comprises:
(i) a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3) of an anti-mesothelin antibody selected from the group consisting of M1, M2, M3, M4, M5, M6, M7, M8, M9, M10 M11, M12, M13, M14, M15, M16, M17, M18, M19, M20, M21, M22, M23, and M24; and
(ii) a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 3 (LC CDR3) of an anti-mesothelin antibody selected from the group consisting of M1, M2, M3, M4, M5, M6, M7, M8, M9, M10, M11, M12, M13, M14, M15, M16, M17, M18, M19, M20, M21, M22, M23, and M24; and
(b) a PD-L1 inhibitor wherein the PD-L1 inhibitor is an anti-PD-L1 antibody molecule selected from the group consisting of YW243.55.S70, MPDL3280A (atezolizumab), MEDI-4736, MSB-0010718C (avelumab), MDX-1105, and an anti-PD-L1 antibody molecule comprising:
(i) a heavy chain complementarity determining region 1 (HC CDR1) amino acid sequence selected from SEQ ID NO: 287, 290, or 195, a HC CDR2 amino acid sequence of SEQ ID NO: 288, and a HC CDR3 amino acid sequence of SEQ ID NO: 289; and a light chain complementarity determining region 1 (LC CDR1) amino acid sequence of SEQ ID NO: 295, a LC CDR2 amino acid sequence of SEQ ID NO: 296, and a LC CDR3 amino acid sequence of SEQ ID NO: 297; or
(ii) a HC CDR1 amino acid sequence selected from SEQ ID NOs: 287, 290, or 195, a HC CDR2 amino acid sequence of SEQ ID NO: 291, and a HC CDR3 amino acid sequence of SEQ ID NO: 292; and a LC CDR1 amino acid sequence of SEQ ID NO: 298, a LC CDR2 amino acid sequence of SEQ ID NO: 299, and a LC CDR3 amino acid sequence of SEQ ID NO: 300;
wherein the cell or the population of immune effector cells expressing the CAR and the PD-L1 inhibitor are in different compositions or dosage formulations or compositions; and
wherein the PD-L1 inhibitor is administered to a subject having a disease associated with mesothelin expression at least 2 days prior to administration of the cell or the population of immune effector cells expressing the CAR.