IP Library › Granted Patent US 12,234,285
Granted Patent B2
US 12,234,285 · App. 17/112,664 · Granted Feb 25, 2025

Antibodies that bind interleukin-2 and uses thereof

Inventors: Marina Roell (Berkeley, CA); Mark Rubinstein (Charleston, SC); Hassan Issafras (Emeryville, CA); Llewelyn Lao (San Francisco, CA); Ou Li (Dublin, CA); Daniel H. Bedinger (Pleasant Hill, CA); Kristin Camfield Lind (Oakland, CA); Agnes Choppin Holmes (Mountain View, CA); Toshihiko Takeuchi (Oakland, CA); Lauren Schwimmer (Alameda, CA); Hoa Giang (Alameda, CA); Amer M. Mirza (San Francisco, CA); Kirk W. Johnson (Moraga, CA)
Assignees: XOMA (US) LLC; MUSC FOUNDATION FOR RESEARCH DEVELOPMENT
C07K16/246A61K38/2013A61K39/395A61K39/3955A61P11/06A61P31/04A61P35/00A61P37/06C07K16/18C07K16/28A61K2039/505A61K2039/507C07K2317/24C07K2317/32C07K2317/33C07K2317/565C07K2317/73C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,234,285
App. No.
17/112,664
Granted
Feb 25, 2025
Kind
B2
Abstract

The present disclosure relates, in general, to human antibodies against human interleukin 2 (IL-2) and methods of use of such antibodies for modulating IL-2 activity and use in the treatment of conditions such as cancer, autoimmune disease, or infection.

Claims (32)

1. A method for treating a disease, condition or disorder associated with increased interleukin-2 (IL-2) or interleukin-2 receptor (IL-2 R) levels or activity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a human or humanized antibody that binds human interleukin-2 (IL-2) with an affinity K D of 1×10 −10 M or less and inhibits binding of IL-2 with an IL-2 receptor alpha (IL-2 Rα) subunit,

wherein the antibody inhibits IL-2 signaling through IL-2 Rαβγ and through IL-2 Rβγ, and

wherein the antibody inhibits IL-2 signaling through IL-2 Rαβγ to a greater extent than through IL-2 Rβγ,

wherein the disease, condition or disorder is cancer, and

wherein the antibody is administered in combination with IL-2 or an IL-2 variant.

2. The method of claim 1 , wherein the cancer is selected from the group consisting of melanoma, renal cell carcinoma, lymphoma, sarcoma, breast cancer, lung cancer, bladder cancer, colon cancer, gastric cancer, non small cell lung carcinoma (NSCLC), head and neck cancer, skin cancer, and squamous cell carcinoma (SCC).

3. The method of claim 2 , wherein the administration reduces tumor volume in the subject.

4. The method of claim 1 wherein the administration increases the ratio of CD8+T cells to CD4+T cells in the subject.

5. The method of claim 1 wherein the antibody is administered intravenously, intratumorally, intraarterially, intraperitoneally, intramuscularly, intradermally or subcutaneously.

6. The method of claim 1 , wherein the antibody is administered in combination with an additional therapeutic agent, optionally wherein the therapeutic agent is a checkpoint inhibitor, a chimeric antigen receptor T-cells/tumor-infiltrating lymphocytes (CART/TIL) agent, an antibody to a tumor antigen or a vaccine.

7. The method of claim 1 , wherein the antibody is administered once per week, once every 2 weeks, twice per month, once monthly, once every two months, or once every three months.

8. The method of claim 1 wherein the antibody comprises

i)

(a) a heavy chain CDR1 amino acid sequence set forth in SEQ ID NOs: 17, 20, 23, or 26;

(b) a heavy chain CDR2 amino acid sequence set forth in SEQ ID NOs: 18, 21, 24, or 27 that is from the same heavy chain variable region as (a); and

(c) a heavy chain CDR3 amino acid sequence set forth SEQ ID NOs: 19, 22, 25, or 28 that is from the same heavy chain variable region as (a); and,

ii)

(a) a light chain CDR1 amino acid sequence set forth in SEQ ID NOs: 29, 32, 35, or 38;

(b) a light chain CDR2 amino acid sequence set forth in SEQ ID NOs: 30, 33, 36, or 39 that is from the same light chain variable region as (a); and

(c) a light chain CDR3 amino acid sequence set forth in SEQ ID NOs: 31, 34, 37, or 40 that is from the same light chain variable region as (a).

9. The method of claim 8 , wherein the antibody comprises

an amino acid sequence at least 90% identical to a heavy chain variable region amino acid sequence set forth in SEQ ID NOs: 1, 3, 5, or 7, and/or

an amino acid sequence at least 90% identical to a light chain variable region amino acid sequence set forth in any one of SEQ ID NOs: 9, 11, 13, or 15.

10. The method of claim 1 , further comprising a heavy chain constant region, wherein the heavy chain constant region is a modified or unmodified IgG, IgM, IgA, IgD, IgE, a fragment thereof, or combinations thereof.

11. The method of claim 1 , in which one or more light chain framework amino acids have been replaced with corresponding amino acid(s) from another human antibody amino acid sequence.

12. The method of claim 1 , wherein the antibody comprises

(a) heavy chain HCDR1-HCDR3 amino acid sequences set forth in SEQ ID NOs: 17-19; and

(b) light chain LCDR1-LCDR3 amino acid sequences set forth in SEQ ID NOs: 29-31.

13. The method of claim 1 , wherein the antibody comprises a heavy chain variable region amino acid sequence set forth in SEQ ID NO: 1 and a light chain variable region amino acid sequence set forth in SEQ ID NO: 9.

14. A method for suppressing IL-2 activity in a cell in vitro comprising the step of contacting the cell with an amount of an antibody that binds human interleukin-2 (IL-2) effective to suppress IL-2 activity in the cell, wherein the antibody is a human or humanized antibody that binds human interleukin-2 (IL-2) with an affinity K D of 1×10 −10 M or less and inhibits binding of IL-2 with an IL-2 receptor alpha (IL-2 Rα) subunit,

wherein the antibody inhibits IL-2 signaling through IL-2 Rαβγ and through IL-2 Rβγ, and

wherein the antibody inhibits IL-2 signaling through IL-2 Rαβγ to a greater extent than through IL-2 Rβγ.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2021
From: ROELL, MARINA; RUBINSTEIN, MARK; ISSAFRAS, HASSAN; LAO, LLEWELYN; LI, OU; BEDINGER, DANIEL H.; LIND, KRISTIN CAMFIELD; HOLMES, AGNES CHOPPIN; TAKEUCHI, TOSHIHIKO; SCHWIMMER, LAUREN; GIANG, HOA; MIRZA, AMER M.; JOHNSON, KIRK W.
To: XOMA (US) LLC
Reel/Frame 055500/0073 →
Continuity (4)
Division 15718152 · Sep 28, 2017
Provisional Application 62421038 · Nov 11, 2016
Provisional Application 62401158 · Sep 28, 2016
Related Publication 20210188969A1 · Jun 24, 2021
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