Antibodies specific to FCRN
The disclosure relates to antibodies specific to FcRn, formulations comprising the same, use of each in therapy, processes for expressing and optionally formulating said antibody, DNA encoding the antibodies and hosts comprising said DNA.
1. An isolated DNA molecule or a pair of isolated DNA molecules encoding the heavy and light chains of an anti-FcRn antibody or FcRn-binding fragment thereof, wherein
the heavy chain comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and
the light chain comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6.
2. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the anti-FcRn antibody or FcRn-binding fragment thereof has a heavy chain comprising the sequence given in SEQ ID NO:12 and a light chain comprising the sequence given in SEQ ID NO: 8.
3. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the antibody is humanized.
4. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16.
5. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 59 and the light chain comprises the sequence given in SEQ ID NO: 51.
6. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the heavy chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 25 and wherein the light chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 16.
7. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the FcRn-binding fragment is a scFv, Fv, Fab or Fab′ fragment.
8. The isolated DNA molecule or pair of isolated DNA molecules according to claim 7 , wherein the FcRn-binding fragment is a Fab′ fragment having a heavy chain comprising the sequence given in SEQ ID NO: 33 and a light chain comprising the sequence given in SEQ ID NO: 20.
9. The isolated DNA molecule or pair of isolated DNA molecules according to claim 7 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20.
10. The isolated DNA molecule or pair of isolated DNA molecules according to claim 7 , wherein the FcRn-binding fragment is a Fab′ fragment having a heavy chain comprising the sequence given in SEQ ID NO: 63 and a light chain comprising the sequence given in SEQ ID NO: 55.
11. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , encoding a Fab-dsFv having a heavy chain comprising the sequence given in SEQ ID NO: 42 and a light chain comprising the sequence given in SEQ ID NO: 40.
12. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the anti-FcRn antibody is a full length antibody.
13. The isolated DNA molecule or pair of isolated DNA molecules according to claim 12 , wherein the full length antibody is selected from the group consisting of an IgG1, IgG4 and IgG4P.
14. The isolated DNA molecule or pair of isolated DNA molecules according to claim 13 , wherein the antibody has a heavy chain comprising the sequence given in SEQ ID NO: 37, SEQ ID NO:39 or SEQ ID NO:73 and a light chain comprising the sequence given in SEQ ID NO: 20.
15. A cloning or expression vector or a pair of cloning or expression vectors encoding the heavy and light chains of an anti-FcRn antibody or FcRn-binding fragment thereof, wherein
the heavy chain comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and
the light chain comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6.
16. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , wherein the antibody is humanized.
17. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16.
18. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , wherein the heavy chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 25 and wherein the light chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 16.
19. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , wherein the FcRn-binding fragment is a scFv, Fv, Fab or Fab′ fragment.
20. The cloning or expression vector or pair of cloning or expression vectors according to claim 19 , wherein the FcRn-binding fragment is a Fab′ fragment having a heavy chain comprising the sequence given in SEQ ID NO: 33 and a light chain comprising the sequence given in SEQ ID NO: 20.
21. The cloning or expression vector or pair of cloning or expression vectors according to claim 19 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20.
22. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , encoding a Fab-dsFv having a heavy chain comprising the sequence given in SEQ ID NO: 42 and a light chain comprising the sequence given in SEQ ID NO: 40.
23. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , wherein the anti-FcRn antibody is a full length antibody.
24. The cloning or expression vector or pair of cloning or expression vectors according to claim 23 , wherein the full length antibody is selected from the group consisting of an IgG1, IgG4 and IgG4P.
25. The cloning or expression vector or pair of cloning or expression vectors according to claim 24 , wherein the antibody has a heavy chain comprising the sequence given in SEQ ID NO: 37, SEQ ID NO:39 or SEQ ID NO:73 and a light chain comprising the sequence given in SEQ ID NO: 20.
26. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , which comprises (i) the sequence given in SEQ ID NO: 30, 32, 34 or 36 and the sequence given in SEQ ID NO: 21 or 24 or (ii) the sequence given in SEQ ID NO: 38 and the sequence given in SEQ ID NO: 22, or (iii) the sequence given in SEQ ID NO: 74 and the sequence given in SEQ ID NO: 22 or (iv) the sequence given in SEQ ID NO: 41 and the sequence given in SEQ ID NO: 43.
27. A host cell comprising a cloning or expression vector or a pair of cloning or expression vectors encoding the heavy and light chains of an anti-FcRn antibody or FcRn-binding fragment thereof, wherein
the heavy chain comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and
the light chain comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6.
28. The host cell according to claim 27 , wherein the antibody is humanized.
29. The host cell according to claim 27 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16.
30. The host cell according to claim 27 , wherein the heavy chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 25 and wherein the light chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 16.
31. The host cell according to claim 27 , wherein the FcRn-binding fragment is a scFv, Fv, Fab or Fab′ fragment.
32. The host cell according to claim 31 , wherein the FcRn-binding fragment is a Fab′ fragment having a heavy chain comprising the sequence given in SEQ ID NO: 33 and a light chain comprising the sequence given in SEQ ID NO: 20.
33. The host cell according to claim 31 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20.
34. The host cell according to claim 27 , wherein the vector or pair of vectors encode a Fab-dsFv having a heavy chain comprising the sequence given in SEQ ID NO: 42 and a light chain comprising the sequence given in SEQ ID NO: 40.
35. The host cell according to claim 27 , wherein the anti-FcRn antibody is a full length antibody.
36. The host cell according to claim 35 , wherein the full length antibody is selected from the group consisting of an IgG1, IgG4 and IgG4P.
37. The host cell according to claim 36 , wherein the anti-FcRn antibody has a heavy chain comprising the sequence given in SEQ ID NO: 37, SEQ ID NO:39 or SEQ ID NO:73 and a light chain comprising the sequence given in SEQ ID NO: 20.
38. A process for the production of an anti-FcRn antibody or FcRn-binding fragment thereof, the process comprising culturing a host cell that comprises a cloning or expression vector or a pair of cloning or expression vectors encoding the heavy and light chains of an anti-FcRn antibody or FcRn-binding fragment thereof and isolating said antibody or fragment, wherein
the heavy chain comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and
the light chain comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6.
39. The process of claim 38 , wherein the antibody is humanized.
40. The process of claim 38 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16.
41. The process of claim 38 , wherein the heavy chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 25 and wherein the light chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 16.
42. The process of claim 38 , wherein the FcRn-binding fragment is a scFv, Fv, Fab or Fab′ fragment.
43. The process of claim 42 , wherein the FcRn-binding fragment is a Fab′ fragment having a heavy chain comprising the sequence given in SEQ ID NO: 33 and a light chain comprising the sequence given in SEQ ID NO: 20.
44. The process of claim 42 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20.
45. The process of claim 38 , wherein vector or pair of vectors encode a Fab-dsFv having a heavy chain comprising the sequence given in SEQ ID NO: 42 and a light chain comprising the sequence given in SEQ ID NO: 40.
46. The process of claim 38 , wherein the anti-FcRn antibody is a full length antibody.
47. The process of claim 46 , wherein the full length antibody is selected from the group consisting of an IgG1, IgG4 and IgG4P.
48. The process of claim 47 , wherein the anti-FcRn antibody has a heavy chain comprising the sequence given in SEQ ID NO: 37, SEQ ID NO:39 or SEQ ID NO:73 and a light chain comprising the sequence given in SEQ ID NO: 20.
49. The isolated DNA molecule or pair of isolated DNA molecules according to claim 1 , wherein the sequence encoding the heavy chain comprises the sequence given in SEQ ID NO: 26 and the sequence encoding the light chain comprises the sequence given in SEQ ID NO: 17.
50. The cloning or expression vector or pair of cloning or expression vectors according to claim 15 , wherein the sequence encoding the heavy chain comprises the sequence given in SEQ ID NO: 26 and the sequence encoding the light chain comprises the sequence given in SEQ ID NO: 17.
51. The host cell according to claim 27 , wherein the sequence encoding the heavy chain comprises the sequence given in SEQ ID NO: 26 and the sequence encoding the light chain comprises the sequence given in SEQ ID NO: 17.
52. The process of claim 38 , wherein the sequence encoding the heavy chain comprises the sequence given in SEQ ID NO: 26 and the sequence encoding the light chain comprises the sequence given in SEQ ID NO: 17.