IP Library Granted Patent US 8,168,183
Granted Patent B2
US 8,168,183 · App. 12/431,661 · Granted May 1, 2012

Antibodies to granulocyte-macrophage colony-stimulating factor

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Quick Facts
Patent No.
US 8,168,183
App. No.
12/431,661
Granted
May 1, 2012
Kind
B2
Abstract

The current invention relates to high-affinity antibodies to Granulocyte-Macrophage Colony-Stimulating Factor that have reduced immunogenicity when administered to a human to treat diseases and method of using such antibodies.

Claims (47)

1. An isolated anti-GM-CSF antibody, comprising:

a V H that has a CDR1 having a sequence NYYIH (SEQ ID NO:25), a CDR2 having a sequence WINAGNGNTKYSQKFQG (SEQ ID NO:27), and a CDR3 having a sequence RQRFPYYFDY (SEQ ID NO:16); and

a V L that has a CDR1 having a sequence RASQSVGTNVA (SEQ ID NO:31) or RASQSIGSNLA (SEQ ID NO:32), a CDR2 having a sequence STSSRAT (SEQ ID NO:33), and a CDR3 having a sequence QQFNKSPLT (SEQ ID NO:18) or QQFNRSPLT (SEQ ID NO:28).

2. The antibody of claim 1 , wherein the J segment comprises YFDYWGQGTLVTVSS (SEQ ID NO:14).

3. The antibody of claim 1 , wherein the V H region comprises a V-segment sequence from a V H region VH#3 (SEQ ID NO:3), VH#4 (SEQ ID NO:4), or VH#5 (SEQ ID NO:5).

4. The antibody of claim 1 , wherein the V H has the sequence of VH#3 (SEQ ID NO:3), VH#4 (SEQ ID NO:4), or VH#5 (SEQ ID NO:5).

5. The antibody of claim 1 , wherein the antibody comprises a human germline JK4 region.

6. The antibody of claim 1 , wherein the V L region CDR3 comprises QQFNKSPLT (SEQ ID NO:18).

7. The antibody of claim 6 , wherein the V L region CDR1 has the sequence RASQSIGSNLA (SEQ ID NO:32).

8. The antibody of claim 1 , wherein the V L region CDR3 comprises QQFNRSPLT (SEQ ID NO:28).

9. The antibody of claim 8 , wherein the V L region CDR1 has the sequence RASQSVGTNVA (SEQ ID NO:31).

10. The antibody of claim 1 , wherein the V L region comprises a V segment sequence from a V L region VK#1 (SEQ ID NO:6), VK#2 (SEQ ID NO:7), VK#3 (SEQ ID NO:8), or VK#4 (SEQ ID NO:9).

11. The antibody of claim 1 , wherein the V L region has the sequence of VK#1 (SEQ ID NO:6), VK#2 (SEQ ID NO:7), VK#3 (SEQ ID NO:8), or VK#4 (SEQ ID NO:9).

12. The antibody of claim 1 , wherein the antibody is an IgG.

13. The antibody of claim 12 , wherein the antibody comprises a heavy chain constant region having the amino acid sequence set forth in SEQ ID NO:11.

14. The antibody of claim 1 , wherein the antibody comprises a kappa light chain constant region having the amino acid sequence set forth in SEQ ID NO:10.

15. The antibody of claim 1 , wherein the V H region or the V L region, or both the V H and V L region amino acid sequences comprise a methionine at the N-terminus.

16. The antibody of claim 1 , wherein the antibody comprises a V H region having a sequence of VH#3 (SEQ ID NO:3), VH#4 (SEQ ID NO:4), or VH#5 (SEQ ID NO:5) and a V L region having a sequence of VK#1 (SEQ ID NO:6), VK#2 (SEQ ID NO:7), VK#3 (SEQ ID NO:8), or VK#4 (SEQ ID NO:9).

17. The antibody of claim 16 , wherein the antibody is an IgG.

18. The antibody of claim 17 , wherein the antibody comprises a heavy chain constant region having the amino acid sequence set forth in SEQ ID NO:11.

19. The antibody of claim 16 , wherein the antibody comprises a kappa light chain constant region having the amino acid sequence set forth in SEQ ID NO:10.

20. The antibody of claim 1 , wherein the antibody has:

a heavy chain and a light chain variable region combination selected from the group consisting of:

a) VH#4 (SEQ ID NO:4), VK#1 (SEQ ID NO:6);

b) VH#4 (SEQ ID NO:4), VK#2 (SEQ ID NO:7;

c) VH#4 (SEQ ID NO:4), VK#3 (SEQ ID NO:8)

d) VH#4 (SEQ ID NO:4), VK#4 (SEQ ID NO:9);

e) VH#5 (SEQ ID NO:5), VK#1 (SEQ ID NO:6);

f) VH#5 (SEQ ID NO:5), VK#2 (SEQ ID NO:7;

g) VH#5 (SEQ ID NO:5), VK#3 (SEQ ID NO:8); and

d) VH#5 (SEQ ID NO:5), VK#4 (SEQ ID NO:9).

21. The antibody of claim 20 , wherein the heavy chain variable region is VH#4 (SEQ ID NO:4) and the light chain variable region is VK#1 (SEQ ID NO:6).

22. The antibody of claim 20 , wherein the heavy chain variable region is VH#4 (SEQ ID NO:4) and the light chain variable region is VK#2 (SEQ ID NO:7).

23. The antibody of claim 20 , wherein the heavy chain variable region is VH#4 (SEQ ID NO:4) and the light chain variable region is VK#3 (SEQ ID NO:8).

24. The antibody of claim 20 , wherein the heavy chain variable region is VH#4 (SEQ ID NO:4) and the light chain variable region is VK#4 (SEQ ID NO:9).

25. The antibody of claim 20 , wherein the heavy chain variable region is VH#5 (SEQ ID NO:5) and the light chain variable region is VK#1 (SEQ ID NO:6).

26. The antibody of claim 20 , wherein the heavy chain variable region is VH#5 (SEQ ID NO:5) and the light chain variable region is VK#2 (SEQ ID NO:7).

27. The antibody of claim 20 , wherein the heavy chain variable region is VH#5 (SEQ ID NO:5) and the light chain variable region is VK#3 (SEQ ID NO:8).

28. The antibody of claim 20 , wherein the heavy chain variable region is VH#5 (SEQ ID NO:5) and the light chain variable region is VK#4 (SEQ ID NO:9).

29. The antibody of claim 20 , wherein the antibody comprises a heavy chain constant region having the amino acid sequence set forth in SEQ ID NO:11.

30. The antibody of claim 29 , wherein the antibody comprises a kappa light chain constant region having the amino acid sequence set forth in SEQ ID NO:10.

31. An isolated anti-GM-CSF antibody comprising a V H region and a V L region, wherein the V H region has the amino acid sequence set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5.

32. The isolated antibody of claim 31 wherein the antibody comprises the V H region set forth in SEQ ID NO:5.

33. The isolated antibody of claim 31 wherein the antibody comprises the V H region set forth in SEQ ID NO:4.

34. The isolated antibody of claim 31 wherein the antibody comprises the V H region set forth in SEQ ID NO:3.

35. The isolated antibody of claim 31 wherein the antibody comprises the V H region set forth in SEQ ID NO:2.

36. The isolated antibody of claim 31 wherein the antibody comprises the V H region set forth in SEQ ID NO:1.

Assignments (8)
RELEASE OF SECURITY INTEREST Recorded Jun 12, 2020
From: BLACK HORSE CAPITAL MASTER FUND LTD.
To: HUMANIGEN, INC.
Reel/Frame 052920/0631 →
CHANGE OF NAME Recorded May 15, 2020
From: KALOBIOS PHARMACEUTICALS, INC.
To: HUMANIGEN, INC.
Reel/Frame 052679/0552 →
SECURITY INTEREST Recorded Jul 16, 2019
From: HUMANIGEN, INC.
To: BLACK HORSE CAPITAL MASTER FUND LTD.
Reel/Frame 049769/0067 →
RELEASE OF SECURITY INTEREST Recorded Mar 30, 2018
From: BLACK HORSE CAPITAL MASTER FUND LTD.
To: KALOBIOS PHARAMECUTICALS, INC.
Reel/Frame 045855/0533 →
RELEASE OF SECURITY INTEREST Recorded Mar 30, 2018
From: BLACK HORSE CAPITAL MASTER FUND LTD.
To: KALOBIOS PHARAMECUTICALS, INC.
Reel/Frame 045788/0148 →
SECURITY INTEREST Recorded Dec 22, 2016
From: KALOBIOS PHARAMECUTICALS, INC.
To: BLACK HORSE CAPITAL MASTER FUND LTD.
Reel/Frame 041181/0605 →
SECURITY INTEREST Recorded May 23, 2016
From: KALOBIOS PHARMACEUTICALS, INC.
To: BLACK HORSE CAPITAL, LP
Reel/Frame 038788/0266 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2009
From: BEBBINGTON, CHRISTOPHER R.; LUEHRSEN, KENNETH; YARRANTON, GEOFFREY T.
To: KALOBIOS PHARMACEUTICALS, INC.
Reel/Frame 022949/0967 →