ANTIBODIES DIRECTED AGAINST PROGRAMMED DEATH-1 (PD-1)

• US 20160075783A1
• Filed: 05/02/2014
• Published: 03/17/2016
• Est. Priority Date: 05/02/2013
• Status: Active Grant

• Current Assignee: Anaptysbio, Inc.
• Original Assignee: Anaptysbio, Inc.
• Inventors: King, David J., Kehry, Marilyn
• Granted Patent: US 9,815,897 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to a programmed death-1 (PD-1) protein. The invention provides a PD-1-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using the PD-1-binding agent to treat a cancer or an infectious disease.

Claims

1. An isolated immunoglobulin heavy chain or light chain polypeptide, wherein the polypeptide comprises:

(I) an immunoglobulin heavy chain polypeptide which comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO;

1, a CDR2 amino acid sequence of SEQ ID NO;

2, and a CDR3 amino acid sequence of SEQ ID NO;

3, wherein optionally

(a) residue 9 of SEQ ID NO;

1 is replaced with a different amino acid residue,

(b) one or more of residues 7, 8, and 9 of SEQ ID NO;

2 is replaced with a different amino acid residue,

(c) one or more of residues 1, 2, and 5 of SEQ ID NO;

3 is replaced with a different amino acid residue, or

(d) any combination of (a)-(c);

or

(II) an isolated immunoglobulin heavy chain polypeptide which comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO;

12, a CDR2 amino acid sequence of SEQ ID NO;

13, and a CDR3 amino acid sequence of SEQ ID NO;

14, wherein optionally

(a) residue 9 of SEQ ID NO;

12 is replaced with a different amino acid residue,

(b) residue 8 and/or residue 9 of SEQ ID NO;

13 is replaced with a different amino acid residue,

(c) residue 5 of SEQ ID NO;

14 is replaced with a different amino acid residue, or

(d) any combination of (a)-(c);

or

(III) an isolated immunoglobulin heavy chain polypeptide which comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO;

19, a CDR2 amino acid sequence of SEQ ID NO;

20, and a CDR3 amino acid sequence of SEQ ID NO;

21;

or

(IV) an isolated immunoglobulin light chain polypeptide which comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO;

26 and a CDR2 amino acid sequence of SEQ ID NO;

27;

or

(V) an isolated immunoglobulin light chain polypeptide which comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO;

30 and a CDR2 amino acid sequence of SEQ ID NO;

31, wherein optionally residue 12 of SEQ ID NO;

30 is replaced with a different amino acid residue;

or

(VI) an isolated immunoglobulin light chain polypeptide which comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO;

35, a CDR2 amino acid sequence of SEQ ID NO;

36, and a CDR3 amino acid sequence of SEQ ID NO;

37, wherein optionally

(a) residue 5 of SEQ ID NO;

36 is replaced with a different amino acid residue, and/or

(b) residue 4 of SEQ ID NO;

37 is replaced with a different amino acid residue;

or

(VII) an isolated immunoglobulin heavy chain polypeptide which comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs;

4-11, SEQ ID NOs;

15-18, SEQ ID NOs;

22-25;

SEQ ID NO;

28, SEQ ID NO;

29, SEQ ID NO;

32, SEQ ID NO;

33, SEQ ID NO;

34, SEQ ID NO;

38, SEQ ID NO;

39, SEQ ID NO;

40, or SEQ ID NO;

41.

2. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

1, a CDR2 amino acid sequence of SEQ ID NO;

2, and a CDR3 amino acid sequence of SEQ ID NO;

3, except that residue 9 of SEQ ID NO;

1 is replaced with a methionine (M) residue.

4. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

1, a CDR2 amino acid sequence of SEQ ID NO;

2, and a CDR3 amino acid sequence of SEQ ID NO;

3, except that

(a) residue 7 of SEQ ID NO;

2 is replaced with an asparagine (N) residue,

(b) residue 8 of SEQ ID NO;

2 is replaced with a serine (S) residue,

(c) residue 9 of SEQ ID NO;

2 is replaced with a threonine (T) residue, or

(d) any combination of (a)-(c).

6. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

1, a CDR2 amino acid sequence of SEQ ID NO;

2, and a CDR3 amino acid sequence of SEQ ID NO;

3, except that

(a) residue 1 of SEQ ID NO;

3 is replaced with a glutamic acid (E) residue,

(b) residue 2 of SEQ ID NO;

3 is replaced with a tyrosine (Y) residue,

(c) residue 5 of SEQ ID NO;

3 is replaced with a serine (S) residue, or

(d) any combination of (a)-(c).

10. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

12, a CDR2 amino acid sequence of SEQ ID NO;

13, and a CDR3 amino acid sequence of SEQ ID NO;

14, except that residue 9 of SEQ ID NO;

12 is replaced with a leucine (L) residue.

12. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

12, a CDR2 amino acid sequence of SEQ ID NO;

13, and a CDR3 amino acid sequence of SEQ ID NO;

14, except that

(a) residue 8 of SEQ ID NO;

13 is replaced with a tyrosine (Y) residue, and/or

(b) residue 9 of SEQ ID NO;

13 is replaced with an alanine (A) residue.

14. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

12, a CDR2 amino acid sequence of SEQ ID NO;

13, and a CDR3 amino acid sequence of SEQ ID NO;

14, except that residue 5 of SEQ ID NO;

3 is replaced with a threonine (T) different residue.

24. The isolated immunoglobulin light chain polypeptide of claim 1, wherein the polypeptide comprises a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO:

30 and a CDR2 amino acid sequence of SEQ ID NO;

31, except that residue 12 of SEQ ID NO;

30 is replaced with a threonine (T) residue.

27. The isolated immunoglobulin light chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

35, a CDR2 amino acid sequence of SEQ ID NO;

36, and a CDR3 amino acid sequence of SEQ ID NO;

37, except that residue 5 of SEQ ID NO;

36 is replaced with a leucine (L) residue.

29. The isolated immunoglobulin light chain polypeptide of claim 1, which comprises a CDR1 amino acid sequence of SEQ ID NO:

35, a CDR2 amino acid sequence of SEQ ID NO;

36, and a CDR3 amino acid sequence of SEQ ID NO;

37, except that residue 4 of SEQ ID NO;

37 is replaced with an asparagine (N) residue.

31. The isolated immunoglobulin heavy chain or light chain polypeptide of claim 1, which comprises an amino acid sequence of SEQ ID NOs:

4-11, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

22, SEQ ID NO;

23, SEQ ID NO;

24, SEQ ID NO;

25, SEQ ID NO;

28, SEQ ID NO;

29, SEQ ID NO;

32, SEQ ID NO;

33, SEQ ID NO;

34, SEQ ID NO;

38, SEQ ID NO;

39, SEQ ID NO;

40, or SEQ ID NO;

41.

33. An isolated or purified nucleic acid sequence encoding the isolated immunoglobulin heavy chain or light chain polypeptide of claim 1, optionally in a vector.

36. An isolated programmed death-1 protein (PD-1)-binding agent comprising an immunoglobulin heavy chain polypeptide and an immunoglobulin light chain polypeptide of claim 1.

37. The isolated PD-1-binding agent of claim 36, which is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.

38. The isolated PD-1-binding agent of claim 36, which is an antibody fragment selected from F(ab′

)2, Fab′

, Fab, Fv, scFv, dsFv, dAb, and a single chain binding polypeptide.

39. An isolated or purified nucleic acid sequence encoding the PD-1-binding agent of claim 36, optionally in a vector.

41. An isolated cell comprising the nucleic acid, optionally in a vector, of claim 39.

42. A composition comprising the isolated PD-1-binding agent of claim 36 and a pharmaceutically acceptable carrier.

43. A method of treating a cancer or an infectious disease in a mammal, which method comprises administering an effective amount of the composition of claim 42 to a mammal having a cancer or an infectious disease, whereupon the cancer or infectious disease is treated in the mammal.

49. The method of claim 43, wherein (a) the half-life of the PD-1-binding agent in the mammal is between 30 minutes and 45 days;

(b) the PD-1-binding agent binds to PD-1 with a KD between about 1 picomolar (pM) and about 100 micromolar (μ

M);

or both (a) and (b).

51. The method of claim 43, further comprising administering to the mammal a composition comprising (i) an antibody that binds to a TIM-3 protein and (ii) a pharmaceutically acceptable carrier;

or (i) an antibody that binds to a LAG-3 protein and (ii) a pharmaceutically acceptable carrier.

3. (canceled)

5. (canceled)

7-9. -9. (canceled)

11. (canceled)

13. (canceled)

15-23. -23. (canceled)

25. (canceled)

26. (canceled)

28. (canceled)

30. (canceled)

32. (canceled)

34. (canceled)

35. (canceled)

40. (canceled)

44-48. -48. (canceled)

50. (canceled)

52. (canceled)