IP Library › Granted Patent US 12,193,994
Granted Patent B2
US 12,193,994 · App. 16/761,770 · Granted Jan 14, 2025

Combination of a cell therapy and a gamma secretase inhibitor

Inventors: Damian J. Green (Seattle, WA); Stanley R. Riddell (Seattle, WA); Melissa Works (Seattle, WA)
Assignees: Juno Therapeutics, Inc.; Fred Hutchinson Cancer Center
A61K31/55A61K38/177A61K39/4611A61K39/4631A61K39/464417A61P35/00C07K14/7051C07K14/70521C07K14/70578C07K14/7151C07K16/2878C12N5/0636A61K2239/31A61K2239/38A61K2239/48C07K2317/622C07K2319/03
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Quick Facts
Patent No.
US 12,193,994
App. No.
16/761,770
Granted
Jan 14, 2025
Kind
B2
Abstract

Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Claims (69)

1. A method of treatment, the method comprising:

(a) administering a T cell therapy to a subject having multiple myeloma, the cell therapy comprising a dose of T cells expressing a recombinant receptor, wherein the recombinant receptor specifically binds to BCMA; and

(b) administering to the subject a compound of the structure:

or a stereoisomer thereof, or a pharmaceutically acceptable salt or hydrate of either of the foregoing.

2. The method of claim 1 , wherein the initiation of administration of the compound is prior to, concurrently with or subsequently to initiation of administration of the cell therapy.

3. The method of claim 2 , wherein the compound is administered prior to initiation of administration of the cell therapy.

4. The method of claim 1 , wherein initiation of administration of the compound is within 72 hours, within 96 hours or within 1 week prior to the initiation of the administration of the cell therapy.

5. The method of claim 1 , wherein the compound is administered subsequently to initiation of administration of the cell therapy.

6. The method of claim 1 , wherein the recombinant receptor is a chimeric antigen receptor.

7. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered orally.

8. The method of claim 1 , wherein

the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered at least or is administered six times daily, five times daily, four times daily, three times daily, twice daily, once daily, every other day, three times a week, at least once a week, twice a week or only one time.

9. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered once every other day.

10. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered no more than once per day.

11. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered once three times per week.

12. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered on days 2, 4, 7, 9, 11, 14, 16, and 18 after initiation of the administration of the cell therapy.

13. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered at an amount that is or is about 25 mg.

14. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered at an amount that is or is about 50 mg.

15. The method of claim 1 , wherein the multiple myeloma is a relapsed or treatment refractory multiple myeloma.

16. The method of claim 1 , wherein the method further comprises, prior to said administration of the cell therapy, selecting a subject for the administration having a cancer that, or the cells of which, express CD138, surface CD38 or a surface plasma cell marker or are derived from plasma cells.

17. The method of claim 16 , wherein the subject further comprises low expression of surface B cell maturation antigen (BCMA) and/or a level of expression of surface BCMA below a threshold level.

18. The method of claim 1 , wherein the recombinant receptor is a chimeric antigen receptor comprising an antigen-binding domain that binds BCMA, wherein the antigen-binding domain comprises:

a V H region comprising a CDRH1, a CDRH2 and a CDRH3 comprising the amino acid sequence of SEQ ID NOS: 173, 174 and 175, respectively and a V L region comprising a CDRL1, a CDRL2 and a CDRL3 comprising the amino acid sequence of SEQ ID NOS: 183, 184 and 185, respectively;

a V H region comprising a CDRH1, a CDRH2 and a CDRH3 comprising the amino acid sequence of SEQ ID NOS: 176, 177 and 175, respectively and a V L region comprising a CDRL1, a CDRL2 and a CDRL3 comprising the amino acid sequence of SEQ ID NOS: 183, 184 and 185, respectively;

a V H region comprising a CDRH1, a CDRH2 and a CDRH3 comprising the amino acid sequence of SEQ ID NOS: 178, 179 and 175, respectively and a V L region comprising a CDRL1, a CDRL2 and a CDRL3 comprising the amino acid sequence of SEQ ID NOS: 183, 184 and 185, respectively; or

a V H region comprising a CDRH1, a CDRH2 and a CDRH3 comprising the amino acid sequence of SEQ ID NOS: 180, 181 and 182, respectively and a V L region comprising a CDRL1, a CDRL2 and a CDRL3 comprising the amino acid sequence of SEQ ID NOS: 186, 187 and 185, respectively.

19. The method of claim 1 , wherein the antigen-binding domain comprises a V H region comprising an amino acid sequence having at least at or about 90% sequence identity to SEQ ID NO:24; and a V L region comprising an amino acid sequence having at least at or about 90%, sequence identity to SEQ ID NO:25.

20. The method of claim 1 , wherein the antigen-binding domain comprises a V H region comprising the amino acid sequence set forth in SEQ ID NO:24; and a V L region comprising the amino acid sequence set forth in SEQ ID NO:25.

21. The method of claim 1 , wherein the antigen-binding domain is an scFv comprising an amino acid sequence having at least at or about 90% sequence identity to SEQ ID NO:188.

22. The method of claim 21 , wherein the antigen-binding domain is an scFv comprising the amino acid sequence set forth in SEQ ID NO:188.

23. The method of claim 1 , wherein the dose of genetically engineered T cells comprises between at 2.5×10 7 CAR-expressing T cells and 1.2×10 9 CAR-expressing T cells, inclusive.

24. The method of claim 1 , wherein the method further comprises administering a lymphodepleting chemotherapy prior to administration of the T cell therapy and/or wherein the subject has received a lymphodepleting chemotherapy prior to administration of the dose of T cells expressing a recombinant receptor.

25. The method of claim 24 , wherein the lymphodepleting chemotherapy comprises administering fludarabine and/or cyclophosphamide to the subject.

26. The method of claim 1 , wherein the recombinant receptor is a chimeric antigen receptor (CAR) comprising an antigen-binding domain that binds BCMA, the antigen-binding domain having:

(a) a VH with an amino acid sequence set forth in SEQ ID NO: 18 and a VL with an amino acid sequence set forth in SEQ ID NO: 19;

(b) a VH with an amino acid sequence set forth in SEQ ID NO: 20 and a VL with an amino acid sequence set forth in SEQ ID NO: 21;

(c) a VH with an amino acid sequence set forth in SEQ ID NO: 22 and a VL with an amino acid sequence set forth in SEQ ID NO: 23;

(d) a VH with an amino acid sequence set forth in SEQ ID NO: 24 and a VL with an amino acid sequence set forth in SEQ ID NO: 25;

(e) a VH with an amino acid sequence set forth in SEQ ID NO: 32 and a VL with an amino acid sequence set forth in SEQ ID NO: 33;

(f) a VH with an amino acid sequence set forth in SEQ ID NO: 34 and a VL with an amino acid sequence set forth in SEQ ID NO: 35;

(g) a VH with an amino acid sequence set forth in SEQ ID NO: 36 and a VL with an amino acid sequence and a VL set forth in SEQ ID NO: 37;

(h) a VH with an amino acid sequence set forth in SEQ ID NO: 41 and a VL with an amino acid sequence set forth in SEQ ID NO: 42;

(i) a VH with an amino acid sequence set forth in SEQ ID NO: 43 and a VL with an amino acid sequence set forth in SEQ ID NO: 44;

(j) a VH with an amino acid sequence set forth in SEQ ID NO: 45 and a VL with an amino acid sequence set forth in SEQ ID NO: 46;

(k) a VH with an amino acid sequence set forth in SEQ ID NO: 47 and a VL with an amino acid sequence set forth in SEQ ID NO: 48;

(l) a VH with an amino acid sequence set forth in SEQ ID NO: 49 and a VL with an amino acid sequence set forth in SEQ ID NO: 50;

(m) a VH with an amino acid sequence set forth in SEQ ID NO: 51 and a VL with an amino acid sequence VL set forth in SEQ ID NO: 52;

(n) a VH with an amino acid sequence set forth in SEQ ID NO: 53 and a VL with an amino acid sequence set forth in SEQ ID NO: 54;

(o) a VH with an amino acid sequence set forth in SEQ ID NO: 55 and a VL with an amino acid sequence set forth in SEQ ID NO: 56;

(p) a VH with an amino acid sequence set forth in SEQ ID NO: 57 and a VL with an amino acid sequence set forth in SEQ ID NO: 58;

(q) a VH with an amino acid sequence set forth in SEQ ID NO: 59 and a VL with an amino acid sequence VL set forth in SEQ ID NO: 60;

(r) a VH with an amino acid sequence set forth in SEQ ID NO: 61 and a VL with an amino acid sequence set forth in SEQ ID NO: 62;

(s) a VH with an amino acid sequence set forth in SEQ ID NO: 63 and a VL with an amino acid sequence set forth in SEQ ID NO: 64;

(t) a VH with an amino acid sequence set forth in SEQ ID NO: 65 and a VL with an amino acid sequence set forth in SEQ ID NO: 66;

(u) a VH with an amino acid sequence set forth in SEQ ID NO: 67 and a VL with an amino acid sequence set forth in SEQ ID NO: 68;

(v) a VH with an amino acid sequence set forth in SEQ ID NO: 69 and a VL with an amino acid sequence set forth in SEQ ID NO: 70;

(w) a VH with an amino acid sequence set forth in SEQ ID NO: 71 and a VL with an amino acid sequence set forth in SEQ ID NO: 72;

(x) a VH with an amino acid sequence set forth in SEQ ID NO: 73 and a VL with an amino acid sequence set forth in SEQ ID NO: 74;

(y) a VH with an amino acid sequence set forth in SEQ ID NO: 75 and a VL with an amino acid sequence set forth in SEQ ID NO: 76;

(z) a VH with an amino acid sequence set forth in SEQ ID NO: 145 and a VL with an amino acid sequence set forth in SEQ ID NO: 146;

(aa) a VH with an amino acid sequence set forth in SEQ ID NO: 147 and a VL with an amino acid sequence set forth in SEQ ID NO: 148;

(bb) a VH with an amino acid sequence set forth in SEQ ID NO: 149 and a VL with an amino acid sequence set forth in SEQ ID NO: 150; or

(cc) a VH with an amino acid sequence set forth in SEQ ID NO: 151 and a VL with an amino acid sequence in SEQ ID NO: 152.

27. The method of claim 1 , wherein the recombinant receptor is a chimeric antigen receptor (CAR) comprising an antigen-binding domain that binds BCMA, wherein the antigen-binding domain comprises the VH region set forth in SEQ ID NO: 18 and the VL region set forth in SEQ ID NO:19.

28. The method of claim 1 , wherein the CAR comprises a sequence as set forth in any one of SEQ ID NOS: 90-141 or a sequence of amino acids that exhibits at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOS: 90-141.

29. The method of claim 1 , wherein the CAR comprises a sequence as set forth in SEQ ID NO: 116 or a sequence of amino acids that exhibits at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NO: 116.

30. The method of claim 1 , wherein the CAR comprises a sequence as set forth in SEQ ID NO: 124 or a sequence of amino acids that exhibits at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NO: 124.

31. The method of claim 1 , wherein the antigen-binding domain comprises a V H region comprising an amino acid sequence having at least at or about 90% sequence identity to SEQ ID NO: 18; and a V L region comprising an amino acid sequence having at least at or about 90%, sequence identity to SEQ ID NO:19.

32. The method of claim 1 , wherein the compound, stereoisomer, pharmaceutically acceptable salt or hydrate is administered at an amount of 10 mg to 100 mg.

Assignments (3)
MERGER AND CHANGE OF NAME Recorded Feb 17, 2023
From: FRED HUTCHINSON CANCER RESEARCH CENTER; SEATTLE CANCER CARE ALLIANCE
To: FRED HUTCHINSON CANCER CENTER
Reel/Frame 062737/0368 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2020
From: GREEN, DAMIAN J.; RIDDELL, STANLEY R.
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 053413/0237 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2020
From: WORKS, MELISSA
To: JUNO THERAPEUTICS, INC.
Reel/Frame 053415/0030 →
Continuity (4)
Provisional Application 62665450 · May 1, 2018
Provisional Application 62582937 · Nov 7, 2017
Provisional Application 62582308 · Nov 6, 2017
Related Publication 20200289565A1 · Sep 17, 2020
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