Methods and uses of variant cd80 fusion proteins and related constructs
AssigneeAlpine Immune Sciences, Inc.
InventorsRyan SWANSON, Mark F. MAURER, Stanford L. PENG, Jing YANG, Kristine M. SWIDEREK
Life of this patent
Estimating the term…
Abstract
Provided herein are variant CD80 polypeptides, immunomodulatory proteins comprising variant CD80 polypeptides, and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of oncological conditions. Compositions and methods for making and using such proteins are provided.
Claims50
A method of treating a cancer in a subject, the method comprising:
- (a) administering to a subject having a cancer a variant CD80-Fc fusion protein, wherein the variant CD80 fusion protein comprises (1) a variant CD80 extracellular domain or a portion thereof comprising an IgV domain and (2) an Fc domain, wherein the variant CD80 extracellular domain or the portion thereof comprises one or more amino acid substitutions at one or more positions in the sequence of amino acids of the extracellular domain or a portion thereof of an unmodified CD80 polypeptide,
- wherein the variant CD80 fusion protein exhibits increased binding to PD-L1 compared to a fusion protein comprising the extracellular domain or portion thereof of the unmodified CD80 for PD-L1;
- and
- (b) administering to the subject a therapeutically effective amount of an anti-cancer agent.
3-6. (canceled)
A method of treating a cancer in a subject, the method comprising:
- (a) administering to a subject having a cancer a variant CD80-Fc fusion protein, wherein the variant CD80-Fc fusion protein comprises (1) a variant CD80 extracellular domain or a portion thereof comprising an IgV domain and (2) an Fc domain, wherein the variant CD80 extracellular domain or the portion thereof comprises one or more amino acid substitutions at one or more positions in the sequence of amino acids of the extracellular domain or a portion thereof of an unmodified CD80 polypeptide,
- wherein the variant CD80 fusion protein exhibits increased binding to PD-L1 compared to a fusion protein comprising the extracellular domain or portion thereof of the unmodified CD80 for PD-L1;
- and
- (b) administering to the subject a therapeutically effective amount of a PD-1 inhibitor, wherein the PD-1 inhibitor disrupts the interaction between Programmed Death-1 (PD-1) and a ligand thereof.
9-12. (canceled)
16-22. (canceled)
25-31. (canceled)
A method of treating a cancer in a subject, the method comprising intratumorally administering to a subject having a cancer a therapeutically effective amount of a variant CD80-Fc fusion protein, wherein the variant CD80-Fc fusion protein comprises (1) a variant CD80 extracellular domain or a portion thereof comprising an IgV domain and (2) an Fc domain, wherein the variant CD80 extracellular domain or the portion thereof comprises one or more amino acid substitutions at one or more positions in the sequence of amino acids of the extracellular domain or a portion thereof of an unmodified CD80 polypeptide wherein the variant CD80 fusion protein exhibits increased binding to PD-L1 compared to a fusion protein comprising the extracellular domain or portion thereof of the unmodified CD80 for PD-L1.
33-42. (canceled)
A method of treating a cancer in a subject, the method comprising administering to a subject having a cancer a variant CD80-Fc fusion protein in an amount of between about 1.0 mg/kg to 10 mg/kg, inclusive, once every week (Q1W), wherein the variant CD80-Fc fusion protein comprises (1) a variant CD80 extracellular domain or a portion thereof comprising an IgV domain and (2) a an Fc domain, wherein the variant CD80 extracellular domain or the portion thereof comprises one or more amino acid substitutions at one or more positions in the sequence of amino acids of the extracellular domain or a portion thereof of an unmodified CD80 polypeptide, wherein the variant CD80 fusion protein exhibits increased binding to PD-L1 compared to a fusion protein comprising the extracellular domain or portion thereof of the unmodified CD80 for PD-L1.
(canceled)
A method of treating a cancer in a subject, the method comprising administering to a subject having a cancer a variant CD80-Fc fusion protein in an amount of between about 1.0 mg/kg to 40 mg/kg, inclusive, once every three weeks (Q3W), wherein the variant CD80-Fc fusion protein comprises (1) a variant CD80 extracellular domain or a portion thereof comprising an IgV domain and (2) an Fc domain, wherein the variant CD80 extracellular domain or the portion thereof comprises one or more amino acid substitutions at one or more positions in the sequence of amino acids of the extracellular domain or a portion thereof of an unmodified CD80 polypeptide, wherein the variant CD80 fusion protein exhibits increased binding to PD-L1 compared to a fusion protein comprising the extracellular domain or portion thereof of the unmodified CD80 for PD-L1.
50-54. (canceled)
A method of treating a cancer in a subject, the method comprising administering a variant CD80-Fc fusion protein to a subject selected as having a tumor comprising cells surface negative for a cell surface ligand selected from CD80 or CD86, and/or surface positive for CD28, wherein the variant CD80-Fc fusion protein comprises (1) a variant CD80 extracellular domain or a portion thereof comprising an IgV domain and (1) an Fc domain, said variant CD80 extracellular domain or the portion thereof comprising one or more amino acid substitutions at one or more positions in the sequence of amino acids of the extracellular domain or a portion thereof of an unmodified CD80 polypeptide.
57-58. (canceled)
60-67. (canceled)
(canceled)
73-76. (canceled)
78-81. (canceled)
84-85. (canceled)
87-89. (canceled)
98-223. (canceled)
Dependencies are inferred from the claim text.