Antibody therapeutics that bind TIM3

• US 9,873,741 B2
• Filed: 03/04/2016
• Issued: 01/23/2018
• Est. Priority Date: 03/06/2015
• Status: Active Grant

• Current Assignee: Sorrento Therapeutics Inc.
• Original Assignee: Sorrento Therapeutics Inc.
• Inventors: Gray, John Dixon, Zhou, Heyue, Krapf, Irina
• Primary Examiner(s): ROARK, JESSICA HOPE
• Application Number:
  US15/061,832
• Publication Number:
  US 20160257758A1
• Time in Patent Office: 690 Days
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

There is disclosed compositions and methods relating to or derived from anti-TIM3 antibodies. More specifically, there is disclosed fully human antibodies that bind TIM3, TIM3-antibody binding fragments and derivatives of such antibodies, and TIM3-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease.

Claims

1. A recombinant anti-TIM3 antibody, or an antigen-binding fragment thereof, that binds human TIM3 and that comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of:

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

1 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

2;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

25 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

26;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

53 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

54;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

57 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

58; and

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

67 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

68.

3. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 1 or claim 2, wherein the antibody or antigen-binding fragment binds human TIM3 with a K_D of at least 1×

10<sup>−

6</sup> M.

4. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 1 or claim 2, wherein the antibody or antigen-binding fragment induces or increases the activity of human TIM3.

5. The recombinant anti-TIM3 antibody of claim 1 or claim 2, wherein the antibody is an IgG, IgM, IgD, IgA, or IgE isotype antibody.

6. The recombinant anti-TIM3 antibody of claim 1 or claim 2, wherein the antibody is an IgG1 or an IgG4 isotype.

7. The recombinant anti-TIM3 antigen-binding fragment of claim 1 or claim 2, wherein the antigen-binding fragment is a Fab, a Fab′

, a F(ab′

)2, an Fv, a single-chain antibody, a single-chain Fv, a diabody, a triabody, or a tetrabody.

8. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 1 or claim 2, wherein the antibody or antigen-binding fragment is fully human.

9. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 1 or claim 2, wherein the antibody or antigen-binding fragment further comprises a detectable or therapeutic moiety.

10. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 1, wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:

1 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

2.

12. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 1, wherein the antibody or antigen-binding fragment comprises a single chain Fv (scFv) that comprises a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:

1 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

2.

14. A pharmaceutical composition comprising the recombinant anti-TIM3 antibody or the antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.

16. A bispecific antibody comprising the recombinant anti-TIM3 antibody or the antigen-binding fragment of claim 1.

2. A recombinant anti-TIM3 antibody, or an antigen-binding fragment thereof, that binds human TIM3 and that comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of:

a heavy chain variable domain comprising complementarity determining regions (CDRs) 1, 2, and 3 as set forth in SEQ ID NO;

1 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

2;

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

25 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

26;

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

53 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

54;

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

57 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

58; and

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

67 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

68.

11. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 2, wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO:

1 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

2.

13. The recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, of claim 2, wherein the antibody or antigen-binding fragment comprises a single chain Fv (scFv) that comprises a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO:

1 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

2.

15. A pharmaceutical composition comprising the recombinant anti-TIM3 antibody or the antigen-binding fragment of claim 2 and a pharmaceutically acceptable carrier.

17. A bispecific antibody comprising the recombinant anti-TIM3 antibody or the antigen-binding fragment of claim 2.

18. An antigen binding protein that binds human TIM3 and that comprises a recombinant anti-TIM3 antibody, or the antigen-binding fragment thereof, that comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of:

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

1 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

2;

a heavy chain variable domain comprising complementarity determining regions (CDRs) 1, 2, and 3 as set forth in SEQ ID NO;

1 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

2;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

25 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

26;

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

25 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

26;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

53 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

54;

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

53 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

54;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

57 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

58;

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

57 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

58;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

67 and a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO;

68; and

a heavy chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

67 and a light chain variable domain comprising CDRs 1, 2, and 3 as set forth in SEQ ID NO;

68.

19. A pharmaceutical composition comprising the antigen binding protein of claim 18 and a pharmaceutically acceptable carrier.