IP Library › Granted Patent US 11,059,884
Granted Patent B2
US 11,059,884 · App. 16/596,445 · Granted Jul 13, 2021

Antibodies directed against

Inventors: Christine Tkaczyk (Gaithersburg, MD); Bret Sellman (Gaithersburg, MD); Qun Du (Gaithersburg, MD); Melissa Damschroder (Gaithersburg, MD); Davide Corti (Bellinzona, CH); Andrea Minola (Bellinzona, CH)
Assignees: MedImmune, LLC; Humabs BioMed SA
C07K16/1271A61P31/04G01N33/56938C07K2317/41C07K2317/51C07K2317/515C07K2317/565C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 11,059,884
App. No.
16/596,445
Granted
Jul 13, 2021
Kind
B2
Abstract

The present disclosure is directed to leukotoxin-binding antibodies and antigen-binding fragments thereof. The antibodies and fragments can be used, for example, to detect leukotoxin and/or in methods of treating and preventing Staphylococcus aureus infections.

Claims (28)

1. An antibody or antigen-binding fragment thereof that specifically binds to at least one S. aureus leukotoxin wherein the antibody or antigen-binding fragment comprises a variable heavy chain (VH) complementarity determining region (CDR) 1, a VH CDR2, a VH CDR3, a variable light chain (VL) CDR1, a VL CDR2, and a VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprise sequences selected from the group consisting of: (a) SEQ ID NOs:1, 2, 3, 12, 5, and 6, respectively; (b) SEQ ID NOs:1-6, respectively; (c) SEQ ID NOs:1, 2, 17, 4, 5, and 6, respectively; (d) SEQ ID NOs: 1, 2, 17, 12, 5, and 6, respectively; and (e) SEQ ID NOs: 1, 20, 3, 4, 5, and 6, respectively.

2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH comprises the amino acid sequence of SEQ ID NO:7, 15, 18, 21, or 23 and/or the VL comprises the amino acid sequence of SEQ ID NO:8 or 13.

3. The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise sequences selected from the group consisting of: (a) SEQ ID NOs:15 and 13, respectively; (b) SEQ ID NOs:7 and 8, respectively; (c) SEQ ID NOs:7 and 13, respectively; (d) SEQ ID NOs:15 and 8, respectively; (e) SEQ ID NOs:18 and 8, respectively; (f) SEQ ID NOs:18 and 13, respectively; (g) SEQ ID NOs:21 and 8, respectively; and (h) SEQ ID NOs:23 and 13, respectively.

4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain comprising the sequence of SEQ ID NO:16, 9, 11, 22, 24 or 28 and/or a light chain comprising the sequence of SEQ ID NO:14 or 10.

5. The antibody or antigen-binding fragment thereof of claim 4 , wherein the antibody comprises a heavy chain and a light chain, wherein the heavy and light chains comprise sequences selected from the group consisting of: (a) SEQ ID NOs: 16 and 14, respectively; (b) SEQ ID NOs:9 and 10, respectively; (c) SEQ ID NOs:11 and 10, respectively; (d) SEQ ID NOs:11 and 14, respectively; (e) SEQ ID NOs:16 and 10, respectively; (f) SEQ ID NOs:19 and 10, respectively; (g) SEQ ID NOs:19 and 14, respectively; (h) SEQ ID NOs:22 and 10, respectively; (i) SEQ ID NOs:24 and 14, respectively; and (j) SEQ ID NOs: 28 and 14, respectively.

6. The antibody or antigen-binding fragment thereof of claim 1 , wherein (a) the antibody or antigen-binding fragment binds to LukF, LukD, and/or HlgB and/or (b) the antibody or antigen-binding fragment neutralizes LukF, LukD, and/or HlgB.

7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment further comprises a heavy chain constant region and/or comprises a light chain constant region.

8. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is an IgG antibody or antigen-binding fragment thereof.

9. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an Fc region that has been engineered to improve half-life.

10. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an Fc region with a YTE mutation.

11. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is a full-length antibody.

12. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is an antigen-binding fragment.

13. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof has an affinity of less than 75 pM for S. aureus LukF, LukD, and HlgB.

14. The antibody or antigen-binding fragment thereof of claim 1 , further comprising a detectable label.

15. A composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically-acceptable carrier.

16. The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise the sequences of SEQ ID NOs:15 and 13, respectively.

17. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or antigen-binding fragment thereof is an IgG antibody or antigen-binding fragment thereof.

18. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or antigen-binding fragment thereof comprises an Fc region that has been engineered to improve half-life.

19. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or antigen-binding fragment thereof comprises an Fc region with a YTE mutation.

20. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or antigen-binding fragment is a full-length antibody.

21. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or antigen-binding fragment is an antigen-binding fragment.

22. A composition comprising the antibody or antigen-binding fragment thereof of claim 16 and a pharmaceutically-acceptable carrier.

23. The antibody or antigen-binding fragment thereof of claim 4 , wherein the antibody comprises a heavy chain and a light chain, wherein the heavy and light chains comprise the sequences of SEQ ID NOs:28 and 14, respectively.

24. A composition comprising the antibody or antigen-binding fragment thereof of claim 23 and a pharmaceutically-acceptable carrier.

25. The antibody or antigen-binding fragment thereof of claim 4 , wherein the antibody comprises a heavy chain and a light chain, wherein the heavy and light chains comprise the sequences of SEQ ID NOs:16 and 14, respectively.

26. A composition comprising the antibody or antigen-binding fragment thereof of claim 25 and a pharmaceutically-acceptable carrier.

27. The antibody of claim 1 , wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprise the sequences of SEQ ID NOs:1, 2, 3, 12, 5, and 6, respectively.

28. A composition comprising the antibody or antigen-binding fragment thereof of claim 27 and a pharmaceutically-acceptable carrier.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2020
From: TKACZYK, CHRISTINE; SELLMAN, BRET; DU, QUN; DAMSCHRODER, MELISSA
To: MEDIMMUNE LLC
Reel/Frame 051580/0893 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2020
From: CORTI, DAVIDE; MINOLA, ANDREA
To: HUMABS BIOMED SA
Reel/Frame 051583/0452 →
Continuity (2)
Provisional Application 62743501 · Oct 9, 2018
Related Publication 20200109190A1 · Apr 9, 2020
Cited By (1)
US 12,264,194