Antibodies against Campylobacter species

Patent metadata

Field	Value
Publication number	US-12297258-B2
Application number	US-201917260966-A
Country	US
Kind code	B2
Filing date	Jul 16, 2019
Priority date	Jul 17, 2018
Publication date	May 13, 2025
Grant date	May 13, 2025

Abstract

The instant disclosure provides antibodies and antigen-binding fragments thereof that are specific for Campylobacter and, in certain embodiments, are capable of neutralizing a Campylobacter infection in a subject. In certain embodiments, the antibody or antigen binding fragment comprises an IgA antibody, such as, for example, a secretory IgA antibody. Also provided are pharmaceutical compositions comprising a disclosed antibody or antigen-binding fragment. Methods of using the antibodies, antigen-binding fragments, and compositions to treat or prevent a Campylobacter infection in a subject are also provided. In certain embodiments, recombinant secretory IgA antibodies of the instant disclosure are administered orally to a subject having or at risk of developing a Campylobacter infection.

First claim

What is claimed is:

1. An isolated antibody, or an antigen-binding fragment thereof, that is specific for a Campylobacter flagellum capping protein (FliD) epitope, wherein:
(i) the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 9-14, respectively, and is an IgA2, IgG, IgD, IgE, or IgM isotype; or
(ii) the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30, respectively, and is an IgA, IgD, IgE, IgG1, or IgM isotype.

2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment is capable of binding to the FliD epitope with an EC50 of less than about 0.1 μg/mL, or less than about 0.05 μg/mL, or less than about 0.03 μg/mL, as measured by ELISA.

3. The antibody or antigen-binding fragment of claim 1 , wherein the Campylobacter comprises Campylobacter jejuni, Campylobacter coli , or both.

4. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises:
(i) VH having at least 85% amino acid identity to SEQ ID NO:2, and a VL having at least 85% amino acid identity to SEQ ID NO:4; or
(ii) VH having at least 85% amino acid identity to SEQ ID NO:22, and a VL having at least 85% amino acid identity to SEQ ID NO:24.

5. The antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment comprises:
(i) a VH according to SEQ ID NO:2, and a VL according to SEQ ID NO:4; or
(ii) a VH according to SEQ ID NO:22, and a VL according to SEQ ID NO:24.

6. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 9-14, respectively and is an IgA2 isotype.

7. The antibody or antigen-binding fragment of claim 6 , comprising a heavy chain constant region having at least 90% identity to SEQ ID NO:41 or SEQ ID NO:42.

8. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30, respectively, is an IgA2 isotype.

9. The antibody or antigen-binding fragment of claim 8 , comprising a heavy chain constant region having at least 90% to SEQ ID NO:41 or SEQ ID NO:42.

10. The antibody or antigen-binding fragment of claim 8 , comprising a heavy chain constant region according to SEQ ID NO:41 or SEQ ID NO:42.

11. The antibody or antigen-binding fragment claim 1 , wherein the antibody or antigen-binding fragment comprises a Fc polypeptide or a fragment thereof.

12. The antibody or antigen-binding fragment of claim 11 , comprising a VH according to SEQ ID NO:2, a VL according to SEQ ID NO:4, and a heavy chain constant region according to SEQ ID NO:41 or SEQ ID NO:42.

13. The antibody or antigen-binding fragment of claim 11 , comprising a VH according to SEQ ID NO:22, a VL according to SEQ ID NO:24, and a heavy chain constant region according to SEQ ID NO:41 or SEQ ID NO:42.

14. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises an IgA2 dimer molecule and/or a secretory IgA2 molecule.

15. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen binding fragment is (i) monoclonal and/or (ii) chimeric, humanized, or human.

16. A composition, comprising the antibody or antigen-binding fragment of claim 1 , and a pharmaceutically acceptable carrier, excipient, or diluent.

17. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 9-14, respectively and is an IgG1 isotype.

18. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30, respectively, is an IgG1 isotype.

19. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30, respectively, and is an IgA1 isotype.

20. The antibody or antigen-binding fragment of claim 19 , comprising a heavy chain constant region having at least 90% identity to SEQ ID NO:40.

21. The antibody or antigen-binding fragment of claim 19 , comprising a heavy chain constant region according to SEQ ID NO:40.

22. The antibody or antigen-binding fragment of claim 19 , wherein the antibody or antigen-binding fragment comprises an IgA1 dimer molecule and/or a secretory IgA1 molecule.

23. A kit, comprising:
(i) a first antibody or an antigen-binding fragment thereof comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 9-14, respectively, and is an IgA2, IgG, IgD, IgE, or IgM isotype, and
(ii) a second antibody or an antigen-binding fragment thereof comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30, respectively, and is an IgA, IgD, IgE, IgG1, or IgM isotype.

24. The kit of claim 23 , wherein:
(i) the first antibody or antigen-binding fragment comprises a VH having at least 85% amino acid identity to SEQ ID NO:2, and a VL having at least 85% amino acid identity to SEQ ID NO:4; and
(ii) the second antibody or antigen-binding fragment comprises a VH having at least 85% amino acid identity to SEQ ID NO:22, and a VL having at least 85% amino acid identity to SEQ ID NO:24.

25. The kit of claim 24 , wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment are each a secretory IgA2 molecule.

26. The kit of claim 24 , wherein:
(i) the first antibody or antigen-binding fragment comprises a VH according to SEQ ID NO: 2, and a VL according to SEQ ID NO:4; and
(ii) the second antibody or antigen-binding fragment comprises a VH according to SEQ ID NO:22, and a VL according to SEQ ID NO:24.

27. An isolated polynucleotide encoding the antibody or antigen-binding fragment of claim 1 .

28. A vector comprising the polynucleotide of claim 27 .

29. The isolated polynucleotide of claim 27 , wherein the polynucleotide is codon-optimized for expression in a host cell.

30. A recombinant host cell comprising the isolated polynucleotide claim 27 , or the vector of claim 28 .

31. A method for treating a Campylobacter infection in a subject, the method comprising administering to the subject an effective amount of the antibody or antigen-binding fragment of claim 1 .

32. The method of claim 31 , further comprising reducing intestinal inflammation and/or increasing intestinal shedding in a subject having a Campylobacter infection.

33. The method of claim 31 , wherein the administering comprises oral administration of the antibody or antigen-binding fragment.

34. The method of claim 31 , wherein following the administering:
(i) a stool sample from the subject comprises an increased number of Campylobacter colony-forming units (CFUs) as compared to a stool

Assignees

• Humabs Biomed Sa
• Inst Res Biomedicine

Inventors

• Pizzuto Matteo Samuele
• Benigni Fabio
• Corti Davide
• Grassi Fabio
• Perruzza Lisa

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• A61K2039/542

  oral/gastrointestinal · CPC title