Anti-CD74 antibodies, compositions comprising anti-CD74 antibodies and methods of using anti-CD74 antibodies

Patent metadata

Field	Value
Publication number	US-10975150-B2
Application number	US-201515327601-A
Country	US
Kind code	B2
Filing date	Jul 20, 2015
Priority date	Jul 22, 2014
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

Provided herein are antibodies that selectively bind to CD74 and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

First claim

What is claimed is:

1. An isolated antibody that specifically binds to CD74, wherein the antibody comprises:
a. V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 12 and 44;
a CDR-H2 comprising at least one of SEQ ID NOs: 76 and 108; and a CDR-H3 comprising SEQ ID NO: 140; and
b. a V L region comprising a CDR-L1 comprising SEQ ID NO:174; a CDR-L2 comprising SEQ ID NO:194, and a CDR-L3 comprising SEQ ID NO:214.

2. An isolated antibody that specifically binds to CD74, wherein the antibody comprises:
a. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 236, and the V L region SEQ ID NO: 267;
b. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 238, and the V L region SEQ ID NO: 256;
c. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 238, and the V L region SEQ ID NO: 265;
d. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 238, and the V L region SEQ ID NO: 267;
e. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 238, and the V L region SEQ ID NO: 269;
f. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 238, and the V L region SEQ ID NO: 271;
g. three heavy chain CDRs and three light chain CDRs of the V H region SEQ ID NO: 240, and the V L region SEQ ID NO: 267.

3. The isolated antibody of claim 2 that specifically binds to CD74, wherein the antibody comprises:
k. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 11 and 43; a CDR-H2 comprising at least one of SEQ ID NOs: 75 and 107; and a CDR-H3 comprising SEQ ID NO: 139, and a V L region comprising a CDR-L1 comprising SEQ ID NO:174; a CDR-L2 comprising SEQ ID NO:194, and a CDR-L3 comprising SEQ ID NO:214;
m. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 12 and 44; a CDR-H2 comprising at least one of SEQ ID NOs: 76 and 108; and a CDR-H3 comprising SEQ ID NO: 140, and a V L region comprising a CDR-L1 comprising SEQ ID NO:165; a CDR-L2 comprising SEQ ID NO:185, and a CDR-L3 comprising SEQ ID NO:205;
n. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 12 and 44; a CDR-H2 comprising at least one of SEQ ID NOs: 76 and 108; and a CDR-H3 comprising SEQ ID NO: 140, and a V L region comprising a CDR-L1 comprising SEQ ID NO:172; a CDR-L2 comprising SEQ ID NO:192, and a CDR-L3 comprising SEQ ID NO:212;
o. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 12 and 44; a CDR-H2 comprising at least one of SEQ ID NOs: 76 and 108; and a CDR-H3 comprising SEQ ID NO: 140, and a V L region comprising a CDR-L1 comprising SEQ ID NO:174; a CDR-L2 comprising SEQ ID NO:194, and a CDR-L3 comprising SEQ ID NO:214;
p. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 12 and 44; a CDR-H2 comprising at least one of SEQ ID NOs: 76 and 108; and a CDR-H3 comprising SEQ ID NO: 140, and a V L region comprising a CDR-L1 comprising SEQ ID NO:175; a CDR-L2 comprising SEQ ID NO:195, and a CDR-L3 comprising SEQ ID NO:215;
y. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 13 and 45; a CDR-H2 comprising at least one of SEQ ID NOs: 77 and 109; and a CDR-H3 comprising SEQ ID NO: 141, and a V L region comprising a CDR-L1 comprising SEQ ID NO:174; a CDR-L2 comprising SEQ ID NO:194, and a CDR-L3 comprising SEQ ID NO:214;
tt. a V H comprising: a CDR-H1 comprising at least one of SEQ ID NOs: 12 and 44; a CDR-H2 comprising at least one of SEQ ID NOs: 76 and 108; and a CDR-H3 comprising SEQ ID NO: 140, and a V L region comprising a CDR-L1 comprising SEQ ID NO: 180; a CDR-L2 comprising SEQ ID NO: 200, and a CDR-L3 comprising SEQ ID NO: 220.

4. The antibody of claim 3 , wherein:
e. the V H region is SEQ ID NO: 236, and the V L region is SEQ ID NO: 267;
q. the V H region is SEQ ID NO: 238, and the V L region is SEQ ID NO: 256;
s. the V H region is SEQ ID NO: 238, and the V L region is SEQ ID NO: 265;
u. the V H region is SEQ ID NO: 238, and the V L region is SEQ ID NO: 267;
w. the V H region is SEQ ID NO: 238, and the V L region is SEQ ID NO: 269;
x. the V H region is SEQ ID NO: 238, and the V L region is SEQ ID NO: 271;
hh. the V H region is SEQ ID NO: 240, and the V L region is SEQ ID NO: 267.

5. The antibody of claim 4 , further comprising at least one constant region domain comprising a sequence selected from SEQ ID NO: 304 and SEQ ID NO: 305.

6. The antibody of claim 4 , wherein the antibody is a monoclonal antibody.

7. The antibody of claim 4 , wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM.

8. The antibody of claim 4 , wherein the antibody is humanized or human.

9. The antibody of claim 4 , wherein the antibody is aglycosylated.

10. The antibody of claim 4 , wherein the antibody is an antibody fragment.

11. The antibody of claim 10 , wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′) 2 fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment.

12. The antibody of claim 11 , wherein the antibody is an scFv fragment.

13. The antibody of claim 11 , wherein the antibody is an scFv-Fc fragment.

14. The antibody of claim 13 , wherein the scFv-Fc fragment comprises SEQ ID NO: 229.

15. The antibody of claim 4 , wherein the antibody has a k a of at least about 10 5 M −1 ×sec −1 at a temperature of 25° C.

16. The antibody of claim 4 , wherein the antibody has a k d of 10 −3 sec −1 or less at a temperature of 25° C.

17. The antibody of claim 4 , wherein the antibody has a K D of 10 −9 M or less at a temperature of 25° C.

18. The antibody of claim 4 , wherein the antibody is internalized after binding to CD74 on the surface of a cell.

19. The antibody of claim 4 , wherein the Tm2 of the antibody is at least 75° C., 75.5° C., 76° C., 76.5° C., 77° C., 77.5° C., 78° C., 78.5° C., or 79° C.

20. The antibody of claim 4 , wherein the Tm1 of the antibody is less than 61° C. or less than 60° C.

21. A kit comprising an antibody of claim 4 , and instructions for use of the antibody.

22. A pharmaceutical composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier.

23. A polynucleotide encoding an antibody of claim 4 .

24. A vector comprising the polynucleotide of claim 23 .

25. A host cell comprising the vector of claim 24 .

26. The host cell of claim 25 , wherein the host cell is selected from a bacterial cell, a fungal cell, and a mammalian cell.

27. The host cell of claim 25 , wherein the host cell is selected from an E. coli cell, a Saccharomyces cerevisiae cell, and a CHO cell.

28. A method of treating a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody of claim 4 , or a pharmaceutical composition of claim 22 , wherein the disease or condition is selected from a cancer, an autoimmune disease, an inflammatory disease, and an infection.

29. The method of claim 28 , wherein the cancer is selected from multiple myeloma and pancreatic cancer.

Assignees

• Sutro Biopharma Inc

Inventors

• Penta Kalyani
• Stafford Ryan
• Gill Avinash
• Li Xiaofan
• Yam Alice
• Thanos Christopher
• Sato Aaron

Classifications

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K16/2833 Primary

  against MHC-molecules, e.g. HLA-molecules · CPC title