FC ANTIBODY VARIANTS

RU2024102534A3Pending Publication Date: 2026-07-07ПЭТМЕДИКС ЛТД

View PDF 0 Cites 0 Cited by

Patent Information

Authority / Receiving Office: RU · RU
Patent Type: Applications
Current Assignee / Owner: ПЭТМЕДИКС ЛТД
Filing Date: 2022-08-05
Publication Date: 2026-07-07

Patent Text Reader

Need to check novelty before this filing date? Find Prior Art

No text content released.

Claims

1. A canine or caninized IgG-B polypeptide or Fc region thereof, comprising a modified Fc region, wherein said Fc region comprises the following elements: a) an amino acid substitution selected from a modification at position 119 of SEQ ID NO: 11-G, an amino acid substitution at position 120 of SEQ ID NO: 11-S or -A, and / or an amino acid substitution at position 121 of SEQ ID NO: 11-A; and / or b) an amino acid substitution at position 156 of SEQ ID NO: 11-N and / or c) the amino acid substitution is selected from one of the following modifications: c1) a modification at position 211 of SEQ ID NO: 11-H, in combination with an amino acid substitution at position 212 of SEQ ID NO: 11-1 and an amino acid substitution at position 213 of SEQ ID NO: 11-G; c2) an amino acid substitution at position 215 of SEQ ID NO: 11-G; c3) an amino acid substitution at position 217 of SEQ ID NO: 11-S or c4) combination of c1-c3, wherein the Fc region is not an Fc region having only two substitutions, namely at position 120 of SEQ ID NO: 11-A and an amino acid substitution at position 121 of SEQ ID NO: 11-A, and wherein said Fc region is an Fc region of a canine antibody that binds canine CD20.

2. A canine or caninized IgG-B polypeptide or Fc region thereof according to claim 1, wherein said Fc region comprises an amino acid substitution as set forth in paragraph a) below, and, optionally, an amino acid substitution as set forth in paragraph b) below and / or c) below, wherein a) the amino acid substitution is selected from a modification at position 119 of SEQ ID NO: 11-G, an amino acid substitution at position 120 of SEQ ID NO: 11-S or -A and / or an amino acid substitution at position 121 of SEQ ID NO: 11-A; b) the amino acid substitution is selected from a modification at position 153 of SEQ ID NO: 11-G, an amino acid substitution at position 154 of SEQ ID NO: 11-R and / or an amino acid substitution at position 156 of SEQ ID NO: 11-N and / or c) the amino acid substitution is selected from a modification at position 211 of SEQ ID NO: 11-H, an amino acid substitution at position 212 of SEQ ID NO: 11-1, an amino acid substitution at position 213 of SEQ ID NO: 11-G, an amino acid substitution at position 215 of SEQ ID NO: 11-G and / or an amino acid substitution at position 217 of SEQ ID NO: 11-S.

3. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-S; b) an amino acid substitution at position 153 of SEQ ID NO: 11-G and an amino acid substitution at position 154 of SEQ ID NO: 11-R and c) an amino acid substitution at position 211 of SEQ ID NO: 11-H, an amino acid substitution at position 212 of SEQ ID NO: 11-1, and an amino acid substitution at position 213 of SEQ ID NO: 11-G.

4. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-S; b) an amino acid substitution at position 153 of SEQ ID NO: 11-G and an amino acid substitution at position 154 of SEQ ID NO: 11-R and c) an amino acid substitution at position 211 of SEQ ID NO: 11-H, an amino acid substitution at position 212 of SEQ ID NO: 11-1 and an amino acid substitution at position 213 of SEQ ID NO: 11-G and an amino acid substitution at position 217 of SEQ ID NO: 11-S.

5. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-S; b) an amino acid substitution at position 153 of SEQ ID NO: 11-G and an amino acid substitution at position 154 of SEQ ID NO: 11-R and c) an amino acid substitution at position 211 of SEQ ID NO: 11-H, an amino acid substitution at position 212 of SEQ ID NO: 11-1 and an amino acid substitution at position 213 of SEQ ID NO: 11-G and an amino acid substitution at position 215 of SEQ ID NO: 11-G.

6. A canine or caninized IgG-B polypeptide or Fc region thereof according to claim 1 or 2, characterized in that said Fc region comprises an amino acid substitution at position 120 of SEQ ID NO: 11-A and at position 121-A.

7. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-A and at position 121-A and b) an amino acid substitution at position 217 of SEQ ID NO: 11-S.

8. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-A and at position 121-A and b) an amino acid substitution at position 215 of SEQ ID NO: 11-G.

9. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 119 of SEQ ID NO: 11-G and b) an amino acid substitution at position 156 of SEQ ID NO: 11-N.

10. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-A and at position 121-A; b) an amino acid substitution at position 156 of SEQ ID NO: 11-N and c) an amino acid substitution at position 217 of SEQ ID NO: 11-S.

11. A canine or caninized IgG-B polypeptide or its Fc region according to claim 1 or 2, characterized in that said Fc region contains the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 11-S and b) an amino acid substitution at position 211 of SEQ ID NO: 11-H, an amino acid substitution at position 212 of SEQ ID NO: 11-1, and an amino acid substitution at position 213 of SEQ ID NO: 11-G.

12. A canine or caninized IgG-B polypeptide or Fc region thereof according to claim 1, characterized in that said polypeptide comprises SEQ ID No. 12, 13, 14, 15, 16, 17, 18, 19 or 20 or a sequence containing at least 90% or 95% sequence identity thereto.

13. A canine or caninized IgG-B polypeptide or Fc region thereof according to the preceding paragraph, characterized in that the polypeptide has reduced Fc-mediated effector function compared to the same polypeptide containing the Fc domain of wild-type IgG-B.

14. A canine or caninized IgG-B polypeptide or Fc region thereof according to claim 13, wherein the effector function is antibody-dependent cell-mediated cytotoxicity (ADCC).

15. A canine or caninized IgG-B polypeptide or Fc region thereof according to claim 13, wherein the effector function is complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated phagocytosis (ADCP).

16. A canine or caninized IgG-B polypeptide or Fc region thereof according to the preceding claim, characterized in that the polypeptide has a lower affinity for the Fc gamma receptor (FcγR) compared to the same polypeptide containing the Fc domain of wild-type IgG1.

17. A canine or caninized IgG-B polypeptide or Fc region thereof according to the preceding claim, characterized in that the polypeptide or Fc region retains binding to FcRn.

18. A pharmaceutical composition comprising a polypeptide or its Fc region according to any one of claims 1-17.

19. A method for suppressing effector function in vitro, ex vivo or in vivo, comprising contacting a cell or tissue with a polypeptide or its Fc region according to any one of claims 1-17.

20. The method according to claim 19, characterized in that the effector function is antibody-dependent cell-mediated cytotoxicity (ADCC).

21. The method according to claim 19, characterized in that the effector function is complement-dependent cytotoxicity (CDC).

22. A nucleic acid encoding a polypeptide or its Fc region according to any one of claims 1-17.

23. A vector containing a nucleic acid or its Fc region according to claim 22.

24. A host cell containing the nucleic acid of claim 22 or the vector of claim 23.

25. A kit containing a polypeptide or its Fc region according to any one of claims 1-17 or a pharmaceutical composition according to claim 18.

26. A feline or feline IgG-1 polypeptide or Fc region thereof comprising a modified Fc region, wherein said Fc region comprises the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 31-A and an amino acid substitution at position 121 of SEQ ID NO: 31-A or an amino acid substitution at position 120 of SEQ ID NO: 31-1 and an amino acid substitution at position 121 of SEQ ID NO: 31-P and / or b) one or more of the following modifications: an amino acid substitution at position 217 of SEQ ID NO: 31-S or -A, an amino acid substitution at position 215 of SEQ ID NO: 31-G, and / or an amino acid substitution at position 123 of SEQ ID NO: 31-A.

27. A feline or feline IgG-1 polypeptide or Fc region thereof according to claim 26, comprising a modified Fc region, wherein said Fc region comprises the following elements: a) an amino acid substitution at position 120 of SEQ ID NO: 31-A, an amino acid substitution at position 121 of SEQ ID NO: 31-A and further comprises either an amino acid substitution at position 217 of SEQ ID NO: 31-S or an amino acid substitution at position 215 of SEQ ID NO: 31-G or b) an amino acid substitution at position 120 of SEQ ID NO: 31-1, an amino acid substitution at position 121 of SEQ ID NO: 31-P, and further comprises either an amino acid substitution at position 217 of SEQ ID NO: 31-A or an amino acid substitution at position 123 of SEQ ID NO: 31-A.

28. A feline or felinized IgG-1 polypeptide or Fc region thereof according to claim 26 or 27, comprising a modified Fc region, wherein said Fc region comprises an amino acid substitution at position 120 of SEQ ID NO: 31-A, an amino acid substitution at position 121 of SEQ ID NO: 31-A, and an amino acid substitution at position 217 of SEQ ID NO: 31-S.

29. A feline or felinized IgG-1 polypeptide or Fc region thereof according to claim 26 or 27, wherein said Fc region comprises an amino acid substitution at position 120 of SEQ ID NO: 31-A, an amino acid substitution at position 121 of SEQ ID NO: 31-A, and an amino acid substitution at position 215 of SEQ ID NO: 31-G.

30. A feline or felinized IgG-1 polypeptide or Fc region thereof according to claim 26 or 27, wherein said Fc region comprises an amino acid substitution at position 120 of SEQ ID NO: 31-1, an amino acid substitution at position 121 of SEQ ID NO: 31-P and an amino acid substitution at position 123 of SEQ ID NO: 31-A and optionally an amino acid substitution at position 217 of SEQ ID NO: 31-A.

31. A feline or felinized IgG-1 polypeptide or Fc region thereof according to claim 26 or 27, wherein said Fc region comprises an amino acid substitution at position 120 of SEQ ID NO: 31-1, an amino acid substitution at position 121 of SEQ ID NO: 31-P, and an amino acid substitution at position 217 of SEQ ID NO: 31-A.

32. A feline or feline IgG-1 polypeptide or Fc region thereof according to any one of claims 26-31, wherein the polypeptide has reduced Fc-mediated effector function compared to the same polypeptide containing the Fc domain of wild-type IgG-1.

33. A feline or feline IgG-1 polypeptide or Fc region thereof according to any one of claims 26-31, wherein the effector function is antibody-dependent cell-mediated cytotoxicity (ADCC).

34. A feline or feline IgG-1 polypeptide or Fc region thereof according to claim 33, wherein the effector function is complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated phagocytosis (ADCP).

35. A feline or feline IgG-1 polypeptide or Fc region thereof according to any one of claims 26-34, characterized in that the polypeptide has a lower affinity for the Fc gamma receptor (FcγR) compared to the same polypeptide containing the Fc domain of wild-type IgG1.

36. A feline or feline IgG-1 polypeptide or Fc region thereof according to any one of claims 26-35, characterized in that the polypeptide or Fc region retains binding to FcRn.

37. A pharmaceutical composition comprising a polypeptide or its Fc region according to any one of claims 26-36.

38. A method for suppressing effector function in vitro, ex vivo or in vivo, comprising contacting a cell or tissue with a polypeptide or its Fc region according to any one of claims 26-36 or a pharmaceutical composition according to claim 37.

39. The method according to claim 38, wherein the effector function is antibody-dependent cell-mediated cytotoxicity (ADCC).

40. The method according to claim 39, characterized in that the effector function is complement-dependent cytotoxicity (CDC).

41. A nucleic acid encoding a polypeptide or its Fc region according to any one of claims 26-36.

42. A vector containing a nucleic acid according to claim 41.

43. A host cell containing the nucleic acid of claim 41 or the vector of claim 42.

44. A kit containing a polypeptide or its Fc region according to any one of claims 26-36 or a pharmaceutical composition according to claim 37.

45. A feline or feline polypeptide or Fc region thereof according to any one of claims 26-36 or a pharmaceutical composition according to claim 37 for the treatment of a disease, such as an inflammatory or autoimmune disease.

46. A method of treating a disease in a subject, comprising administering an effective amount of a feline or feline polypeptide or its Fc region according to any one of claims 26-36 or a pharmaceutical composition according to claim 37, wherein the disease is inflammatory or autoimmune.

47. An isolated feline IgG-3 polypeptide comprising SEQ ID 33 or the Fc region thereof.

48. An isolated feline IgG-3 polynucleotide encoding the polypeptide of claim 47.

49. An isolated recombinant antibody comprising the polypeptide or its Fc region according to claim 47.