IP Library › Granted Patent US 12,187,792
Granted Patent B2
US 12,187,792 · App. 16/805,481 · Granted Jan 7, 2025

IL-4/IL-13 pathway inhibitors for enhanced efficacy in treating cancer

Inventors: Caroline Liot (New York, NY); Frank Kuhnert (Cortlandt Manor, NY)
Assignee: Regeneron Pharmaceuticals, Inc.
C07K16/247A61K39/3955A61K39/4636A61K45/06A61P35/00C07K16/244C07K16/28C07K16/2818C07K16/2866
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Quick Facts
Patent No.
US 12,187,792
App. No.
16/805,481
Granted
Jan 7, 2025
Kind
B2
Abstract

The disclosure relates to methods for treating or inhibiting the growth of a tumor, wherein the methods include selecting and administering to a subject in need thereof a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor and a therapeutically effective amount of a programmed death 1 (PD-1) inhibitor. In certain embodiments, the IL-4/IL-13 pathway inhibitor enhances the anti-tumor efficacy of PD-1 blockade.

Claims (45)

1. A method of treating or inhibiting the growth of a tumor, comprising:

(a) selecting a subject with a Type 2 immunity-dependent cancer; and

(b) administering to the subject a therapeutically effective amount of an anti-interleukin-4 receptor (IL-4R) antibody and a therapeutically effective amount of an anti-programmed death 1 (PD-1) antibody;

wherein:

the anti-IL-4R antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2; and

the anti-PD-1 antibody comprises a HCVR comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) and a LCVR comprising three light chain CDRs (LCDR1, LCDR2 and LCDR3), wherein: HCDR1 has the amino acid sequence of SEQ ID NO: 13; HCDR2 has the amino acid sequence of SEQ ID NO: 14; HCDR3 has the amino acid sequence of SEQ ID NO: 15; LCDR1 has the amino acid sequence of SEQ ID NO: 16; LCDR2 has the amino acid sequence of SEQ ID NO: 17; and LCDR3 has the amino acid sequence of SEQ ID NO: 18.

2. The method according to claim 1 , wherein the Type 2 immunity-dependent cancer is pancreatic cancer, breast cancer, colorectal cancer, ovarian cancer, brain cancer, skin cancer, prostate cancer, kidney cancer, lung cancer, Hodgkin's lymphoma, or bladder cancer.

3. The method according to claim 1 , wherein the Type 2 immunity-dependent cancer is pancreatic cancer.

4. The method according to claim 1 , wherein the Type 2 immunity-dependent cancer is non-small cell lung cancer.

5. The method according to claim 1 , wherein the Type 2 immunity-dependent cancer is lung squamous cell carcinoma.

6. The method according to claim 1 , wherein the cancer is primary, metastatic, or recurrent.

7. The method according to claim 1 , wherein the subject has been treated with a prior anti-tumor therapeutic agent or therapy.

8. The method according to claim 1 , wherein the subject has been treated with a PD-1 inhibitor.

9. The method according to claim 1 , wherein the cancer is resistant or non-responsive to prior treatment with a therapeutic agent or therapy.

10. The method according to claim 1 , wherein the subject exhibits upregulation of at least one cytokine.

11. The method according to claim 10 , wherein the at least one cytokine comprises at least one of IL-4 and IL-13.

12. The method according to claim 1 , wherein the subject exhibits increased production of at least one cytokine.

13. The method according to claim 12 , wherein the at least one cytokine comprises IL-4.

14. The method according to claim 1 , wherein the subject exhibits increased hyaluronic acid (HA) content in the tumor.

15. The method according to claim 1 , wherein the HCVR of the anti-IL-4R antibody comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) and the LCVR of the anti-IL-4R antibody comprises three light chain CDRs (LCDR1, LCDR2 and LCDR3), wherein: HCDR1 has the amino acid sequence of SEQ ID NO: 3; HCDR2 has the amino acid sequence of SEQ ID NO: 4; HCDR3 has the amino acid sequence of SEQ ID NO: 5; LCDR1 has the amino acid sequence of SEQ ID NO: 6; LCDR2 has the -amino acid sequence of SEQ ID NO: 7; and LCDR3 has the amino acid sequence of SEQ ID NO: 8.

16. The method according to claim 1 , wherein the anti-IL-4R antibody comprises a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence of SEQ ID NO: 9.

17. The method according to claim 1 , wherein the anti-IL-4R antibody comprises a heavy chain and a light chain, wherein the light chain has the amino acid sequence of SEQ ID NO: 10.

18. The method according to claim 1 , wherein the anti-IL-4R antibody comprises a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence of SEQ ID NO: 9 and the light chain has the amino acid sequence of SEQ ID NO: 10.

19. The method according to claim 1 , wherein the anti-IL-4R antibody is dupilumab or a bioequivalent thereof.

20. The method according to claim 1 , wherein the HCVR of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 11 and the LCVR of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 12.

21. The method according to claim 1 , wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence of SEQ ID NO: 19.

22. The method according to claim 1 , wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the light chain has the amino acid sequence of SEQ ID NO: 20.

23. The method according to claim 1 , wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence of SEQ ID NO: 19 and the light chain has the amino acid sequence of SEQ ID NO: 20.

24. The method according to claim 1 , wherein the anti-PD-1 antibody is cemiplimab or a bioequivalent thereof.

25. The method according to claim 1 , wherein the anti-PD-1 antibody is cemiplimab.

26. The method according to claim 1 , wherein one or more doses of the anti-IL-4R antibody is administered in combination with one or more doses of the anti-PD-1 antibody.

27. The method according to claim 26 , wherein at least one dose of the anti-IL-4R antibody comprises about 0.1 mg/kg to about 50 mg/kg of the subject's body weight.

28. The method according to claim 26 , wherein at least one dose of the anti-IL-4R antibody comprises about 0.05 to about 1000 mg.

29. The method according to claim 26 , wherein each dose of the anti-IL-4R antibody is administered 0.5 to 12 weeks after the immediately preceding dose.

30. The method according to claim 26 , wherein at least one dose of the anti-PD-1 antibody comprises about 0.1 mg/kg to about 20 mg/kg of the subject's body weight.

31. The method according to claim 26 , wherein at least one dose of the anti-PD-1 antibody comprises about 0.05 to about 500 mg.

32. The method according to claim 26 , wherein each dose of the anti-PD-1 antibody is administered 0.5 to 12 weeks after the immediately preceding dose.

33. The method according to claim 1 , wherein the anti-IL-4R antibody is administered concurrently with the anti-PD-1 antibody.

34. The method according to claim 1 , wherein the anti-IL-4R antibody is administered prior to the anti-PD-1 antibody.

35. The method according to claim 1 , wherein the anti-IL-4R antibody is administered after the anti-PD-1 antibody.

36. The method according to claim 1 , wherein the method promotes tumor regression, delays tumor growth, reduces tumor cell load, reduces tumor burden, and/or prevents tumor recurrence in the subject.

37. The method according to claim 1 , wherein the method promotes at least about 10% more tumor regression in the treated subject as compared to an untreated subject or a subject treated with either antibody as monotherapy.

38. The method according to claim 1 , wherein the method leads to at least 30% or more decrease in tumor cells or tumor size as compared to an untreated subject or a subject treated with either antibody as monotherapy.

39. The method according to claim 1 , further comprising administering at least one additional therapeutic agent or therapy.

40. The method according to claim 39 , wherein the additional therapeutic agent or therapy comprises chemotherapy, cyclophosphamide, surgery, radiation, a cancer vaccine, a Lymphocyte Activation Gene 3 (LAG3) inhibitor, a Glucocorticoid-Induced TNFR-Related (GITR) agonist, a T-cell immunoglobulin and mucin domain 3 (TIM3) inhibitor, a B- and T-lymphocyte attenuator (BTLA) inhibitor, a T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) inhibitor, a Cluster of Differentiation 38 (CD 38) inhibitor, a Cluster of Differentiation 47 (CD47) inhibitor, an Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor, an Indoleamine 2, 3-dioxygenase 2 (IDO2) inhibitor, a Vascular Endothelial Growth Factor (VEGF) antagonist, an Angiopoietin 2 (Ang2) inhibitor, a Transforming Growth Factor Beta (TGFB) inhibitor, an Epidermal Growth Factor Receptor (EGFR) inhibitor, a V-domain Ig suppressor of T cell activation (VISTA) inhibitor, a Cluster of Differentiation 40 (CD40) agonist, a Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor, C-C Motif Chemokine Receptor 2 (CCR2) inhibitor, C-X-C Motif Chemokine Receptor 4 (CXCR4) inhibitor, C-X-C Motif Chemokine Receptor 2 (CXCR2) inhibitor, C-C Motif Chemokine Receptor 4 (CCR4) inhibitor, C-X-C Motif Chemokine Ligand 12 (CXCL12) inhibitor, a Cluster of Differentiation 28 (CD28) activator, an agonist to a co-stimulatory receptor, an antibody to a tumor-specific antigen, an anti-Cluster of Differentiation 3 (CD3)/anti-Cluster of Differentiation 20 (CD20) bispecific antibody, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), a cytotoxin, an oncolytic virus, an Interleukin 6 Receptor (IL-6R) inhibitor, an Interleukin 10 Receptor (IL-10) inhibitor, a cytokine, an antibody-drug conjugate (ADC), chimeric antigen receptor T cells, an anti-inflammatory drug, a non-steroidal anti-inflammatory drug (NSAID), and/or a dietary supplement.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 11, 2020
From: LIOT, CAROLINE; KUHNERT, FRANK
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 053751/0688 →
Continuity (3)
Provisional Application 62966760 · Jan 28, 2020
Provisional Application 62814648 · Mar 6, 2019
Related Publication 20200283518A1 · Sep 10, 2020
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