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RU-2023118672-A - Antibodies against TNF alpha and NGF for veterinary use

RU2023118672ARU 2023118672 ARU2023118672 ARU 2023118672ARU-2023118672-A

Inventors

  • ПИРС, Стефани, А.
  • Преста, Леонард
  • ЛИ, Шир, Цзяннь
  • НГУЙЕН, Лам
  • ЧИНЬ, Ричард
  • ЧЖАНЬ, Ханцзюнь

Assignees

  • ЭЛАНКО ЮС ИНК.

Dates

Publication Date
20260508
Application Date
20211217
Priority Date
20201218

Claims (20)

  1. 1. An isolated antibody that binds to canine TNFα, wherein the antibody is a caninized antibody comprising a variable light chain comprising (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 2; (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 3; and (iv) an LC-FR2 comprising glutamine at position 3 and lysine at position 8.
  2. 2. An isolated antibody according to claim 1, comprising a variable heavy chain comprising (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5; and (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 6.
  3. 3. An isolated antibody according to any one of the preceding claims, wherein LC-FR2 comprises the amino acid sequence of SEQ ID NO: 45.
  4. 4. An isolated antibody according to any one of the preceding claims, comprising (i) a variable light chain comprising the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 46, or a variant thereof, wherein 1, 2, 3, 4, 5, or 6 amino acids of the variable light chain are replaced with a different amino acid, (ii) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 22, or a variant thereof, wherein 1, 2, 3, 4, 5, or 6 amino acids of the variable heavy chain are replaced with a different amino acid, or (iii) a variable light chain as in (i) and a variable heavy chain as in (ii).
  5. 5. An isolated antibody according to any one of the preceding claims, comprising (i) a variable light chain comprising the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 46, or a variant thereof having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 46, (ii) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 22, or a variant thereof having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 22, or (iii) a variable light chain as in (i) and a variable heavy chain as in (ii).
  6. 6. An isolated antibody that binds to canine TNFα, comprising: (i) a variable light chain comprising the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 25, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 43, or SEQ ID NO: 46; (ii) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 22; or (iii) a variable light chain as in (i) and a variable heavy chain as in (ii).
  7. 7. An isolated antibody that binds to canine TNFα, comprising a variable light chain comprising the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 25, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 43, or SEQ ID NO: 46, and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 22.
  8. 8. An isolated antibody that binds to canine TNFα, comprising a variable light chain comprising the amino acid sequence of SEQ ID NO: 43 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 22.
  9. 9. An isolated antibody that binds to canine TNFα, comprising a variable light chain comprising the amino acid sequence of SEQ ID NO: 46 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 22.
  10. 10. An isolated antibody that binds to canine TNFα, wherein the antibody is a caninized antibody comprising:
  11. (a) a light chain comprising (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 49; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 50; (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 51; and (iv) a variable light chain comprising the amino acid sequence of SEQ ID NO: 55 or SEQ ID NO: 56, or a variant thereof, wherein 1, 2, 3, 4, 5, or 6 amino acids of the variable light chain are replaced with a different amino acid;
  12. (b) a heavy chain comprising (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 52; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 53; (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 54; and (iv) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 57 or SEQ ID NO: 58, or a variant thereof, wherein 1, 2, 3, 4, 5, or 6 amino acids of the variable heavy chain are replaced with a different amino acid; or
  13. (c) a light chain as in (a) and a heavy chain as in (b).
  14. 11. An isolated antibody that binds to canine TNFα, wherein the antibody is a caninized antibody comprising:
  15. (a) a light chain comprising (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 49; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 50; (iii) a CDR L3 comprising the amino acid sequence of SEQ ID NO: 51; and (iv) a variable light chain comprising the amino acid sequence of SEQ ID NO: 55 or SEQ ID NO: 56, or a variant thereof having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 55 or SEQ ID NO: 56;
  16. (b) a heavy chain comprising (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 52; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 53; (iii) a CDR H3 comprising the amino acid sequence of SEQ ID NO: 54; and (iv) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 57 or SEQ ID NO: 58, or a variant thereof having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 57 or SEQ ID NO: 58; or
  17. (c) a light chain as in (a) and a heavy chain as in (b).
  18. 12. An isolated antibody that binds to canine TNFα, comprising: (i) a variable light chain comprising the amino acid sequence of SEQ ID NO: 55 or SEQ ID NO: 56; (ii) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 57 or SEQ ID NO: 58; or (iii) a variable light chain as in (i) and a variable heavy chain as in (ii).
  19. 13. An antibody according to any of the preceding claims, comprising a canine heavy chain constant region and/or a canine light chain constant region.
  20. 14. An antibody according to any one of the preceding claims, comprising a canine heavy chain constant region selected from the constant region of IgG-A, IgG-B, IgG-C and IgG-D.