Granted Patent
B2
US 12,404,330 · App. 16/955,197 · Granted Sep 2, 2025
Antibodies to ICOS
Inventors:
Aksana Labokha (Cambridge, GB); Nahida Parveen (Cambridge, GB); Jacob Galson (Cambridge, GB); Richard Charles Alfred Sainson (Cambridge, GB); Stephen John Arkinstall (Cambridge, MA)
Assignee:
KYMAB LIMITED
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Abstract
Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Combinations of anti-ICOS antibodies and other drugs for immunooncology.
Claims (36)
1. An isolated antibody that binds the extracellular domain of human and mouse ICOS, wherein the antibody comprises a VH domain comprising a set of heavy chain complementarity determining regions (HCDRs) HCDR1, HCDR2 and HCDR3, and a VL domain comprising a set of light chain complementarity determining regions (LCDRs) LCDR1, LCDR2 and LCDR3, wherein the HCDRs and LCDRs have amino acid sequences as follows:
HCDR1 comprises an amino acid sequence identical to SEQ ID NO: 992 or SEQ ID NO: 995;
HCDR2 comprises an amino acid sequence identical to SEQ ID NO: 993 or SEQ ID NO: 996;
HCDR3 comprises an amino acid sequence identical to SEQ ID NO: 994 or SEQ ID NO: 997;
LCDR1 comprises an amino acid sequence identical to SEQ ID NO: 1000 or SEQ ID NO: 1003;
LCDR2 comprises an amino acid sequence identical to SEQ ID NO: 1001 or SEQ ID NO: 1004; and
LCDR3 comprises an amino acid sequence identical to SEQ ID NO: 1002.
2. The antibody according to claim 1 , wherein
the antibody comprises a VH domain which comprises the amino acid sequence of the STIM021 VH domain or which comprises that amino acid sequence with 1, 2, 3, 4 or 5 conservative amino acid substitutions, and/or wherein
the antibody comprises a VL domain which comprises the amino acid sequence of the STIM021 VL domain or which comprises that amino acid sequence with 1, 2, 3, 4 or 5 conservative amino acid substitutions.
3. The antibody according to claim 1 , wherein
the antibody comprises a VH domain having at least 95% sequence identity to the amino acid sequence of the STIM021 VH domain, and wherein
the antibody comprises a VL domain having at least 95% sequence identity to the amino acid sequence of the STIM021 V L domain.
4. The antibody according to claim 1 , comprising the STIM021 VH domain and the STIM021 VL domain.
5. The antibody according to claim 1 , wherein the VH domain comprises an amino acid sequence of SEQ ID NO: 998 and the VL domain comprises an amino acid sequence of SEQ ID NO: 1005.
6. A method of modulating the balance of regulatory T cells (Tregs) to effector T cells (Teffs) to increase Teff response in a patient, comprising administering an antibody according to claim 1 to the patient.
7. A method of treating a disease or condition amenable to therapy by depleting regulatory T cells (Tregs) and/or increasing effector T cell (Teff) response in a patient, the method comprising administering an antibody according to claim 1 to the patient.
8. A method of treating cancer in a human patient, comprising administering an antibody according to claim 1 to the patient.
9. The method according to claim 6 , wherein the method comprises administering the antibody and another therapeutic agent and/or radiation therapy to the patient.
10. The method according to claim 6 , wherein
the anti-ICOS antibody is conjugated to a pro-drug, and wherein the method comprises
administering the anti-ICOS antibody to a patient; and
selectively activating the pro-drug at a target tissue site.
11. A method of treating a patient, the method comprising administering an anti-ICOS antibody according to claim 1 to a patient who has an increased level of ICOS-positive regulatory T cells following treatment with another therapeutic agent.
12. A method of treating cancer in a patient by in vivo vaccination of the patient against their cancer cells, the method comprising
treating the patient with a therapy that causes immunological cell death of the cancer cells, resulting in presentation of antigen to antigen-specific effector T cells, and
administering an anti-ICOS antibody according to claim 1 to the patient, wherein the anti-ICOS antibody enhances the antigen-specific effector T cell response.
13. A method of treating cancer in a patient by in vivo vaccination of the patient against their cancer cells, the method comprising administering an anti-ICOS antibody according to claim 1 , wherein
the patient is one who has been previously treated with a therapy that causes immunological cell death of the cancer cells, resulting in presentation of antigen to antigen-specific effector T cells, and wherein the anti-ICOS antibody enhances the antigen-specific effector T cell response.
14. A method of treating a cancer in a patient, wherein the cancer is or has been characterised as being positive for expression of ICOS ligand and/or FOXP3, the method comprising administering an anti-ICOS antibody according to claim 1 to the patient.
15. A method of treating a cancer in a patient, wherein the cancer is or has been characterised as being refractory to treatment with an immunooncology drug, the method comprising administering an anti-ICOS antibody according to claim 1 to the patient.
16. The method according to claim 15 , wherein the method comprises treating the patient with an anti-CD20 antibody;
determining that the cancer is not responsive to the anti-CD20 antibody;
testing a sample from a patient to determine that the cancer expresses ICOS ligand;
selecting the patient for treatment with the anti-ICOS antibody; and
administering the anti-ICOS antibody to the patient.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 18, 2020
From: LABOKHA, AKSANA; PARVEEN, NAHIDA; GALSON, JACOB; SAINSON, RICHARD CHARLES ALFRED; ARKINSTALL, STEPHEN JOHN
To: KYMAB LIMITED
Reel/Frame 052974/0773 →
Priority Claims (1)
GB 1721338
· Dec 19, 2017
· national
Continuity (1)
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