ICOS ligand variant immunomodulatory proteins and uses thereof
AssigneeAlpine Immune Sciences, Inc.
InventorsRyan Swanson, Michael Kornacker
Life of this patent
Estimating the term…
Abstract
Provided herein are immunomodulatory proteins comprising ICOSL variants and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.
Claims45
A variant ICOS Ligand (ICOSL) polypeptide, comprising one or more amino acid substitutions in the amino acid sequence of an unmodified ICOSL at one or more amino acid positions corresponding to amino acid position(s) selected from the group consisting of 52, 57, 100, 110, 115, 172, and 198 with reference to amino acid positions set forth in SEQ ID NO:32, wherein corresponding amino acid positions are identified by alignment of the unmodified ICOSL polypeptide with the polypeptide set forth in SEQ ID NO:32, wherein:
- the one or more amino acid substitutions are selected from the group consisting of N52H, N52D, N52S, N52Y, N52K, N57D, N57Y, Q100R, Q100K, Q100P, V110D, V110N, V110A, H115R, H115Q, F172S, and C198R;
- and
- the unmodified ICOSL comprises (i) the sequence of amino acids set forth in SEQ ID NO:32, or (ii) a portion of the sequence of (i) comprising an immunoglobulin superfamily (IgSF) domain which is one or both of an IgV domain or IgC domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5 and the IgC domain is amino acids 141-227 of SEQ ID NO:5.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked to an Fc domain, wherein the variant ICOSL polypeptide comprises the amino acid substitutions N52H/N57Y/Q100P in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked to an Fc domain, wherein the variant ICOSL polypeptide comprises the amino acid substitutions N52H/N57Y/Q100R in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked to an Fc domain, wherein the variant ICOSL polypeptide comprises the amino acid substitutions N52H/Q100R in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked to an Fc domain, wherein the variant ICOSL polypeptide comprises the amino acid substitution N52D in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked, via a linker, to an Fc domain, wherein:
- (i) the variant ICOSL polypeptide comprises the amino acid substitutions N52H/N57Y/Q100P in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5;
- and
- (ii) the Fc domain is a variant human IgG1 Fc with reduced effector function.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked, via a linker, to an Fc domain, wherein:
- (i) the variant ICOSL polypeptide comprises the amino acid substitutions N52H/N57Y/Q100R in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5;
- and
- (ii) the Fc domain is a variant human IgG1 Fc with reduced effector function.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked, via a linker, to an Fc domain, wherein:
- (i) the variant ICOSL polypeptide comprises the amino acid substitutions N52H/Q100R in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5;
- and
- (ii) the Fc domain is a variant human IgG1 Fc with reduced effector function.
A variant ICOSL-Fc fusion, comprising a variant ICOSL polypeptide linked, via a linker, to an Fc domain, wherein:
- (i) the variant ICOSL polypeptide comprises the amino acid substitution N52D in the amino acid sequence set forth in SEQ ID NO:32 or a portion thereof comprising an IgV domain, wherein the IgV domain is amino acids 19-129 of SEQ ID NO:5;
- and
- (ii) the Fc domain is a variant human IgG1 Fc with reduced effector function.
Dependencies are inferred from the claim text.