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1. WO2020205477 - ANTICORPS IGA ANTI-POLYMÈRES ET MÉTHODES D'UTILISATION

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CLAIMS

What is claimed is:

1 . An isolated antibody that specifically binds polymeric immunoglobulin A (plgA), wherein the antibody comprises the following complementarity determining regions (CDRs):

(a) a CDR-H1 comprising the amino acid sequence of GFTFSNYG (SEQ ID NO: 1);

(b) a CDR-H2 comprising the amino acid sequence of INRGGDRI (SEQ ID NO: 2);

(c) a CDR-H3 comprising the amino acid sequence of RGLYYYGSDYYFDY (SEQ ID NO: 3);

(d) a CDR-L1 comprising the amino acid sequence of GNIHNY (SEQ ID NO: 4);

(e) a CDR-L2 comprising the amino acid sequence of NAK (SEQ ID NO: 5); and

(f) a CDR-L3 comprising the amino acid sequence of HHYYSTPYT (SEQ ID NO: 6).

2. The antibody of claim 1 , wherein the antibody further comprises the following heavy chain framework regions (FRs):

(a) an FR-H1 comprising the amino acid sequence of DVKLVESGEGLVKPGGSLKLSCVAS (SEQ ID NO: 7);

(b) an FR-H2 comprising the amino acid sequence of MSWVRQTPEKRLEWVAF (SEQ ID NO: 8);

(c) an FR-H3 comprising the amino acid sequence of

YYADTVKGRFTISRDNARNTLYLQMSSLKSEDTAIYYC (SEQ ID NO: 9); and

(d) an FR-H4 comprising the amino acid sequence of WGQGTTLTVSS (SEQ ID NO: 10).

3. The antibody of claim 1 , wherein the antibody further comprises the following light chain FRs:

(a) an FR-L1 comprising the amino acid sequence of DIQMTQSPASLSTSVGETVTITCRAS (SEQ ID NO: 1 1);

(b) an FR-L2 comprising the amino acid sequence of LAWSQQKQGNSPQLLVY (SEQ ID NO: 12);

(c) an FR-L3 comprising the amino acid sequence of

TLAEGVPSRFSGSGSGTQYSLKINSLQPEDFGSYYC (SEQ ID NO: 13); and

(d) an FR-L4 comprising the amino acid sequence of FGSGTKLEIK (SEQ ID NO: 14).

4. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 16.

5. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a VL domain comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence of SEQ ID NO: 16.

6. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a VL domain comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence of SEQ ID NO: 16.

7. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a VL domain comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 16.

8. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a VL domain comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 16.

9. An isolated antibody that specifically binds plgA, wherein the antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 15 and a VL domain comprising the amino acid sequence of SEQ ID NO: 16.

10. The antibody of any one of claims 1 -9, wherein the plgA is a dimeric IgA (dlgA).

11. The antibody of claim 10, wherein the dlgA is dlgA1 or dlgA2.

12. The antibody of any one of claims 1 -9, wherein the plgA is a secretory IgA (slgA).

13. The antibody of claim 12, wherein the slgA is slgA1 or slgA2.

14. The antibody of any one of claims 1 -13, wherein the antibody specifically binds to a J chain polypeptide of plgA.

15. The antibody of any one of claims 1 -14, wherein the antibody binds to intact plgA.

16. The antibody of any one of claims 1 -15, wherein the plgA is a human or a rhesus plgA.

17. The antibody of any one of claims 1 -16, wherein the antibody is a monoclonal, human, humanized, or chimeric antibody.

18. The antibody of claim 17, wherein the antibody is a monoclonal antibody.

19. The antibody of any one of claims 1 -18, wherein the antibody is a full-length antibody.

20. The antibody of any one of claims 1 -18, wherein the antibody is an antibody fragment that specifically binds plgA.

21 . The antibody of claim 20, wherein the antibody fragment is selected from the group consisting of Fab, Fab’, Fab’-SH, Fv, single chain variable fragment (scFv), and (Fab’)2 fragments.

22. The antibody of any one of claims 1 -21 , wherein the antibody is cross-reactive with human plgA and rhesus plgA.

23. The antibody of any one of claims 1 -22, wherein the antibody does not bind monomeric IgA (mlgA).

24. The antibody of any one of claims 1 -23, wherein the antibody is an IgG antibody.

25. The antibody of claim 24, wherein the antibody is an lgG1 antibody.

26. A composition comprising the antibody of any one of claims 1 -25.

27. An isolated nucleic acid encoding the antibody of any one of claims 1 -25.

28. A vector comprising the nucleic acid of claim 27.

29. A host cell comprising the vector of claim 28.

30. The host cell of claim 29, wherein the host cell is a mammalian cell.

31 . The host cell of claim 30, wherein the mammalian cell is a Chinese hamster ovary (CHO) cell.

32. The host cell of claim 29, wherein the host cell is a prokaryotic cell.

33. The host cell of claim 32, wherein the prokaryotic cell is E. coli.

34. A method of producing an antibody that specifically binds plgA, the method comprising culturing the host cell of any one of claims 29-33 in a culture medium.

35. The method of claim 34, wherein the method further comprises recovering the antibody from the host cell or the culture medium.

36. A method of purifying plgA from a sample, the method comprising contacting the sample with the antibody of any one of claims 1 -25.

37. A method of quantitating plgA in a sample, the method comprising contacting the sample with the antibody of any one of claims 1 -25.

38. The method of claim 36 or 37, wherein the sample is an antibody preparation, a plasma sample, or a mucosal secretion sample.

39. The method of any one of claims 36-38, wherein the sample is isolated from a human.

40. The method of any one of claims 36-39, wherein the plgA is dlgA.

41 . The method of claim 40, wherein the dlgA is dlgA1 or dlgA2.

42. The method of any one of claims 36-39, wherein the plgA is slgA.

43. The method of claim 42, wherein the slgA is slgA1 or slgA2.

44. A kit comprising the antibody of any one of claims 1 -25 and a package insert comprising instructions for using the antibody for purifying plgA from a sample.

45. A kit comprising the antibody of any one of claims 1 -25 and a package insert comprising instructions for using the antibody for quantitating plgA in a sample.

46. The kit of claim 44 or 45, wherein the sample is an antibody preparation, a plasma sample, or a mucosal secretion sample.

47. The kit of any one of claims 44-46, wherein the sample is isolated from a human.

48. The kit of any one of claims 44-47, wherein the plgA is dlgA.

49. The kit of claim 48, wherein the dlgA is dlgA1 or dlgA2.

50. The kit of any one of claims 44-47, wherein the plgA is slgA.

51 . The kit of claim 50, wherein the slgA is slgA1 or slgA2.