CANINIZED MURINE ANTIBODIES TO HUMAN PD-1

• US 20160319018A1
• Filed: 12/19/2014
• Published: 11/03/2016
• Est. Priority Date: 12/20/2013
• Status: Active Grant

• Current Assignee: Intervet Incorporated
• Original Assignee: Intervet Incorporated
• Inventors: Bartels-Morozov, Denise, Erskine, Jason, Tarpey, Ian, Morsey, Mohamad, Zhang, Yuanzheng, Presta, Leonard G.
• Granted Patent: US 10,023,636 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention provides caninized murine anti-human PD-1 antibodies that have specific sequences and a high binding affinity for canine PD-1. The invention also relates to use of these antibodies in the treatment of dogs.

Claims

1. An isolated caninized antibody or antigen binding fragment thereof that specifically binds Programmed Cell Death Receptor 1 (PD-1) comprising a canine IgG heavy chain and a canine kappa light chain;

wherein the canine kappa light chain comprises three light chain complementary determining regions (CDRs);

CDR light 1 (CDRL1), CDR light 2 (CDRL2), and CDR light 3 (CDRL3); and

the canine IgG heavy chain comprises three heavy chain CDRs;

CDR heavy 1 (CDRH1), CDR heavy 2 (CDRH2) and CDR heavy 3 (CDRH3);

(a) wherein CDRL1 comprises the amino acid sequence of SEQ ID NO;

20, or a conservatively modified variant of SEQ ID NO;

20;

(b) wherein CDRL2 comprises the amino acid sequence comprising SEQ ID NO;

22, or a conservatively modified variant of SEQ ID NO;

22;

(c) wherein CDRL3 comprises the amino acid sequence of SEQ ID NO;

24, or a conservatively modified variant of SEQ ID NO;

24;

(d) wherein CDRH1 comprises the amino acid sequence of SEQ ID NO;

14, or a conservatively modified variant of SEQ ID NO;

14;

(e) wherein CDRH2 comprises the amino acid sequence of SEQ ID NO;

16, or a conservatively modified variant of SEQ ID NO;

16; and

(f) wherein CDRH3 comprises the amino acid sequence of SEQ ID NO;

18, or a conservatively modified variant of SEQ ID NO;

18;

wherein the antibody and fragment bind canine PD-1 and block the binding of canine PD-1 to canine Programmed Cell Death Ligand 1 (PD-L1).

2. The isolated caninized antibody of claim 1, wherein the CDRL1 comprises the amino acid sequence of SEQ ID NO:

20.

3. The isolated caninized antibody of claim 2, wherein CDRL2 comprises the amino acid sequence comprising SEQ ID NO:

22.

4. The isolated caninized antibody of claim 3, wherein CDRL3 comprises the amino acid sequence of SEQ ID NO:

24.

5. The isolated caninized antibody of claim 4, wherein the CDRH1 comprises the amino acid sequence of SEQ ID NO:

14.

6. The isolated caninized antibody of claim 5, wherein CDRH2 comprises the amino acid sequence comprising SEQ ID NO:

16.

7. The isolated caninized antibody of claim 6, wherein CDRH3 comprises the amino acid sequence of SEQ ID NO:

18.

8. The isolated caninized antibody of claim 1, wherein the IgG heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

26, a conservatively modified variant of SEQ ID NO;

26, SEQ ID NO;

28, a conservatively modified variant of SEQ ID NO;

28, SEQ ID NO;

30, and a conservatively modified variant of SEQ ID NO;

30.

9. The isolated caninized antibody of claim 8 wherein the kappa light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

32, a conservatively modified variant of SEQ ID NO;

32, SEQ ID NO;

34, and a conservatively modified variant of SEQ ID NO;

34.

10. The isolated caninized antibody of claim 9, comprising the amino acid sequence of SEQ ID NO:

28 and of SEQ ID NO;

34, or a conservatively modified variant of SEQ ID NO;

28 and of a conservatively modified variant of SEQ ID NO;

34.

11. An isolated nucleic acid that encodes the light chain of the caninized antibody of claim 1.

12. An isolated nucleic acid that encodes the heavy chain of the caninized antibody of claim 1.

13. The isolated nucleic acid of claim 12 that comprises one or more nucleotide sequences selected from the group consisting of SEQ ID NOs:

13, 15, or 17.

14. The isolated nucleic acid of claim 13 that comprises the nucleotide sequence of SEQ ID NO:

27.

15. An expression vector comprising the isolated nucleic acid of claim 12.

16. A host cell comprising the expression vectors of claim 15.

17. A pharmaceutical composition comprising the antibody or antigen binding fragment of claim 1, and a pharmaceutically acceptable carrier or diluent.

18. A method of increasing the activity of an immune cell, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 17.

19. The method of claim 18, wherein said method is used for:

a. the treatment of cancer;

b. the treatment of an infection or infectious disease;

or

c. as a vaccine adjuvant.

21. The isolated nucleic acid of claim 11 that comprises the nucleotide sequence of SEQ ID NO:

33.

20. (canceled)