Caninized and felinized antibodies to human NGF

Claims

1. A felinized antibody or antigen-binding fragment thereof that binds to feline nerve growth factor (NGF), wherein said antibody or antigen-binding fragment comprises a heavy chain and a light chain; wherein the light chain comprises three light chain complementarity determining regions (CDRs), each of which comprises the amino acid sequence of light chain CDR 1 (CDRL1), light chain CDR 2 (CDRL2), and light chain CDR 3 (CDRL3); and wherein the heavy chain comprises three heavy chain CDRs, each of which comprises the amino acid sequence of heavy chain CDR 1 (CDRH1), heavy chain CDR 2 (CDRH2), and heavy chain CDR 3 (CDRH3), wherein: a) CDRH1 comprises the amino acid sequence of SEQ ID NO: 1; b) CDRH2 comprises the amino acid sequence of SEQ ID NO: 2; c) CDRH3 comprises the amino acid sequence of SEQ ID NO: 3; d) CDRL1 comprises the amino acid sequence of SEQ ID NO: 4; e) CDRL2 comprises the amino acid sequence of SEQ ID NO: 5; and f) CDRL3 comprises the amino acid sequence of SEQ ID NO:

6.

2. The felinized antibody or antigen-binding fragment thereof according to claim 1, which comprises a feline heavy chain constant region; wherein the feline heavy chain constant region comprises an amino acid sequence that is at least 90%, 95%, 98%, 99% or 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 54, wherein the aspartic acid residue (D) at position 151 and the asparagine residue (N) at position 183 of the amino acid sequence are replaced by an alanine residue (A), and SEQ ID NO: 55, wherein the aspartic acid residue (D) at position 151 and the asparagine residue (N) at position 183 of the amino acid sequence are replaced by an alanine residue (A).

3. A felinized antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the variable region of the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO:

60.

4. A felinized antibody or antigen-binding fragment thereof according to any one of claims 1-3, wherein the variable region of the light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 61 and SEQ ID NO:

62.

5. A felinized antibody or antigen-binding fragment thereof according to any one of claims 1-4, wherein the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 57 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 61; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 57 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 62; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 58 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 61; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 58 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 62; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 59 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 61; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 59 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 62; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 60 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO: 61; or the variable region of the heavy chain comprises the amino acid sequence of SEQ ID NO: 60 and the variable region of the light chain comprises the amino acid sequence of SEQ ID NO:

62.

6. A felinized antibody or antigen-binding fragment thereof according to any one of claims 1-5, wherein the light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 68 and SEQ ID NO:

69.

7. A felinized antibody or antigen-binding fragment thereof according to any one of claims 1-6, wherein the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66 and SEQ ID NO:

67.

8. A felinized antibody or antigen-binding fragment thereof according to any one of claims 1-7, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 64 and the light chain comprises the amino acid sequence of SEQ ID NO: 68; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 64 and the light chain comprises the amino acid sequence of SEQ ID NO: 69; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 65 and the light chain comprises the amino acid sequence of SEQ ID NO: 68; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 65 and the light chain comprises the amino acid sequence of SEQ ID NO: 69; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 66 and the light chain comprises the amino acid sequence of SEQ ID NO: 68; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 66 and the light chain comprises the amino acid sequence of SEQ ID NO: 69; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 67 and the light chain comprises the amino acid sequence of SEQ ID NO: 68; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 67 and the light chain comprises the amino acid sequence of SEQ ID NO:

69.

9. A felinized antibody or antigen-binding fragment thereof according to claim 8, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 65 and the light chain comprises the amino acid sequence of SEQ ID NO: 68; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 65 and the light chain comprises the amino acid sequence of SEQ ID NO: 69; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 67 and the light chain comprises the amino acid sequence of SEQ ID NO: 68; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 67 and the light chain comprises the amino acid sequence of SEQ ID NO:

69.

10. A nucleic acid encoding a light chain according to any one of claims 1 to 9.

11. A nucleic acid encoding the heavy chain of any one of claims 1 to 9.

12. A pair of nucleic acids, wherein one of the pair of nucleic acids contains a nucleotide sequence that encodes the heavy chain of a specific felinized antibody of any of the antibodies according to claims 1-9, and the other of the pair of nucleic acids contains a nucleotide sequence that encodes the light chain of said specific felinized antibody.

13. An expression vector comprising a pair of nucleic acids according to claim 12 or a nucleic acid according to claim 10 or 11.

14. A pair of expression vectors, one of which comprises one of the pair of nucleic acids according to claim 12, which comprises a nucleotide sequence encoding the heavy chain of a specific felinized antibody, and the other comprises the other of the pair of nucleic acids, which comprises a nucleotide sequence encoding the light chain of a specific felinized antibody.

15. A host cell containing the expression vector of claim 13 or a pair of expression vectors of claim 14.

16. A pair of host cells, wherein one of the pair of host cells contains an expression vector that contains one of the pair of nucleic acids according to claim 12, which contains a nucleotide sequence encoding the heavy chain of a specific felinized antibody, while the other of the pair of host cells contains an expression vector that contains the other of the pair of nucleic acids that contains a nucleotide sequence encoding the light chain of a specific felinized antibody.

17. A pharmaceutical composition comprising a felinized antibody according to any one of claims 1-9, or an expression vector according to claim 13, or a pair of expression vectors according to claim 14, or any combination thereof and a pharmaceutically acceptable carrier or diluent.

18. A method for treating a condition associated with pain in a feline, comprising administering to the feline a therapeutically effective amount of the pharmaceutical composition of claim 17.

19. The method of claim 18, wherein said method is used to treat osteoarthritis, hyperalgesia, allodynia, pain, or any combination thereof.

20. A method for producing a feline NGF-binding feline antibody, comprising: a) culturing each of the pair of host cells of claim 16 in a culture medium, alone or in combination, under conditions that express nucleic acids, thereby producing a polypeptide comprising a felinized antibody light chain, a felinized antibody heavy chain, or both; and b) isolating the felinized antibody light chain, the felinized antibody heavy chain, or both from the pair of host cells or the culture medium.

21. A pharmaceutical composition for treating a condition associated with pain in a feline, comprising a felinized antibody according to any one of claims 1-9, or an expression vector according to claim 13, or a pair of expression vectors according to claim 14, or any combination thereof, and a pharmaceutically acceptable carrier or diluent.