Granted Patent B2

US 10,675,358 · App. 16/140,309 · Granted Jun 9, 2020

Inventors: Michael Nathaniel Alonso (Santa Clara, CA); Edgar George Engleman (Atherton, CA); Shelley Erin Ackerman (Mountain View, CA); Justin Kenkel (Mountain View, CA); Arthur Lee (San Jose, CA); David Y. Jackson (Belmont, CA)

Assignees: The Board of Trustees of the Leland Stanford Junior University; Bolt Biotherapeutics, Inc.

A61K47/6801A61K47/6849A61K47/6851A61K47/6855A61P35/00C07K16/2818C07K16/28C07K16/30

Abstract

Claims (34)

1. An immunoconjugate according to Formula IVb:

or a pharmaceutically acceptable salt thereof, wherein Ab is an antibody comprising (i) an antigen binding domain and (ii) an Fc domain, Adj is an adjuvant moiety of formula:

wherein R 4 is an alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl group comprising from 1 to 8 carbons, each J is hydrogen, each U is N, each t is 2, Q is not present, the dashed line (“ ”) represents a point of attachment of the adjuvant to G 1 , and G 1 is a bond; subscript a is an integer from 1 to 40; and subscript r is an integer from 1 to 10.

2. The immunoconjugate of claim 1 , wherein the antibody comprises a modified Fc region.

3. The immunoconjugate of claim 2 , wherein the modified Fc region contains at least one amino acid insertion, deletion, or substitution.

4. The immunoconjugate of claim 2 , wherein the modified Fc region is deglycosylated or afucosylated.

5. The immunoconjugate of claim 1 , wherein a is an integer from 1 to 20.

6. The immunoconjugate of claim 1 , wherein a is an integer from 1 to 10.

7. The immunoconjugate of claim 1 , wherein R 4 is a heteroalkyl group comprising from 1 to 8 carbons.

8. The immunoconjugate of claim 1 , wherein R 4 is an alkyl group comprising from 1 to 8 carbons.

9. The immunoconjugate of claim 1 , wherein R 4 is butyl.

10. The immunoconjugate of claim 1 , wherein r is an integer from 1 to 4.

11. The immunoconjugate of claim 1 , wherein the antigen binding domain binds to an antigen selected from the group consisting of CDH1, CD19, CD20, CD29, CD30, CD38, CD40, CD47, EpCAM, MUC1, MUC16, EGFR, VEGF, HER2, SLAMF7, PDGFRa, gp75, CTLA4, PD-1, PD-L1, PD-L2, LAG-3, B7-H4, KIR, TNFRSF4, OX40L, IDO-1, IDO-2, CEACAM1, BTLA, TIM3, A2Ar, VISTA, CLEC4C (BDCA-2, DLEC, CD303, CLECSF7), CLEC4D (MCL, CLECSF8), CLEC4E (Mincle), CLEC6A (Dectin-2), CLEC5A (MDL-1, CLECSF5), CLEC1B (CLEC-2), CLEC9A (DNGR-1), and CLEC7A (Dectin-1).

12. The immunoconjugate of claim 1 , wherein the antigen binding domain binds to HER2.

13. The immunoconjugate of claim 8 , wherein the antigen binding domain binds to HER2.

14. The immunoconjugate of claim 1 , wherein the antigen binding domain binds to PD-L1.

15. The immunoconjugate of claim 5 , wherein the antigen binding domain binds to PD-L1.

16. The immunoconjugate of claim 1 , wherein the antibody is selected from the group consisting of pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, obinutuzumab, trastuzumab, cetuximab, rituximab, pertuzumab, bevacizumab, daratumumab, etanercept, olaratumab, elotuzumab, margetuximab, and a biosimilar thereof.

17. The immunoconjugate of claim 8 , wherein the antibody is selected from the group consisting of pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, obinutuzumab, trastuzumab, cetuximab, rituximab, pertuzumab, bevacizumab, daratumumab, etanercept, olaratumab, elotuzumab, margetuximab, and a biosimilar thereof.

18. The immunoconjugate of claim 1 , wherein the antibody is trastuzumab.

19. The immunoconjugate of claim 8 , wherein the antibody is trastuzumab.

20. The immunoconjugate of claim 1 , wherein the antibody is a biosimilar of trastuzumab.

21. The immunoconjugate of claim 8 , wherein the antibody is a biosimilar of trastuzumab.

22. A composition comprising a plurality of immunoconjugates according to claim 1 .

23. The composition of claim 22 , wherein the composition further comprises one or more pharmaceutically acceptable excipients.

24. An immunoconjugate according to Formula IVb:

or a pharmaceutically acceptable salt thereof, wherein Ab is trastuzumab, Adj is an adjuvant moiety of formula:

wherein R 4 is butyl, each J is hydrogen, each U is N, each t is 2, Q is not present, the dashed line (“ ”) represents a point of attachment of the adjuvant to G 1 , and G 1 is a bond; subscript a is an integer from 1 to 40; and subscript r is an integer from 1 to 4.

25. The immunoconjugate of claim 24 , wherein the antibody comprises a modified Fc region.

26. The immunoconjugate of claim 25 , wherein the modified Fc region (1) contains at least one amino acid insertion, deletion, or substitution or (2) is deglycosylated or afucosylated.

27. The immunoconjugate of claim 24 , wherein a is an integer from 1 to 20.

28. The immunoconjugate of claim 24 , wherein a is an integer from 1 to 10.

29. A composition comprising a plurality of immunoconjugates according to claim 24 .

30. The composition of claim 29 , wherein the composition further comprises one or more pharmaceutically acceptable excipients.

Assignments (4)

Continuity (8)