US 12,473,345 B2
Methods for treatment using chimeric antigen receptors specific for B-cell maturation antigen
Blythe D. Sather, Seattle, WA (US); Eric L. Smith, New York, NY (US); Semih Tareen, Seattle, WA (US); Aye Chen, Seattle, WA (US); Cyr De Imus, Seattle, WA (US); Erik Hess, Seattle, WA (US); Audrey Olshefsky, Seattle, WA (US); Stefan Ponko, Seattle, WA (US); and Mariana Cota Stirner, Seattle, WA (US)
Assigned to Juno Therapeutics, Inc., Seattle, WA (US); and Memorial Sloan Kettering Cancer Center, New York, NY (US)
Appl. No. 17/290,065
Filed by Juno Therapeutics, Inc., Seattle, WA (US); and Memorial Sloan Kettering Cancer Center, New York, NY (US)
PCT Filed Oct. 31, 2019, PCT No. PCT/US2019/059271
§ 371(c)(1), (2) Date Apr. 29, 2021,
PCT Pub. No. WO2020/092848, PCT Pub. Date May 7, 2020.
Claims priority of provisional application 62/845,817, filed on May 9, 2019.
Claims priority of provisional application 62/777,066, filed on Dec. 7, 2018.
Claims priority of provisional application 62/774,856, filed on Dec. 3, 2018.
Claims priority of provisional application 62/774,167, filed on Nov. 30, 2018.
Claims priority of provisional application 62/754,577, filed on Nov. 1, 2018.
Prior Publication US 2021/0393690 A1, Dec. 23, 2021
Int. Cl. C07K 14/725 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/42 (2025.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C07K 16/28 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/4215 (2025.01); A61P 35/00 (2018.01); C07K 14/70521 (2013.01); C07K 14/70578 (2013.01); C07K 16/2878 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/545 (2013.01); A61K 2239/17 (2023.05); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/46 (2023.05); A61K 2239/48 (2023.05); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/53 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01)] 37 Claims
 
1. A method of treating a subject having or suspected of having relapsed or refractory multiple myeloma (R/R MM), the method comprising administering to the subject a dose of engineered T cells comprising a chimeric antigen receptor (CAR), the CAR comprising:
(a) an extracellular antigen-binding domain that binds to a B cell maturation antigen (BCMA), comprising:
a variable heavy chain (VH) comprising a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2) and a heavy chain complementarity determining region 3 (CDR-H3) contained within the sequence set forth in SEQ ID NO: 116 and a variable light chain (VL) comprising a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the sequence set forth in SEQ ID NO: 119;
(b) a spacer set forth by the sequence in SEQ ID NO: 174 or a sequence with at least 95% sequence identity to the sequence of SEQ ID NO:174;
(c) a transmembrane domain; and
(d) an intracellular signaling region comprising a cytoplasmic signaling domain of a CD3-zeta (CD3ζ) chain and a costimulatory signaling region comprising an intracellular signaling domain of a T cell costimulatory molecule or a signaling portion thereof;
wherein,
(i) prior to the administration, the subject has received a lymphodepleting therapy comprising the administration of fludarabine at or about 20-40 mg/m2 body surface area of the subject, daily, for 2-4 days, and cyclophosphamide at or about 200-400 mg/m2 body surface area of the subject, daily, for 2-4 days; and
(ii) the subject has relapsed or been refractory to one or more prior therapies for treating the multiple myeloma selected from among:
autologous stem cell transplant (ASCT);
an immunomodulatory agent;
a proteasome inhibitor; and
an anti-CD38 antibody.