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AssigneeAlpine Immune Sciences, Inc.
InventorsStacey Dillon, Mark Rixon, Lawrence Evans, Daniel William Demonte, Joseph L. Kuijper, Stanford L. Peng
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Provided herein are immunomodulatory proteins that exhibit neutralizing activity of BAFF and APRIL (or BAFF/APRIL heterotrimers). The immunomodulatory proteins provided herein include variant domains of Transmembrane Activator and CAML Interactor (TACI). Among provided immunodulatory proteins are TACI-Fc fusion proteins. Also provided are nucleic acid molecules encoding the immunomodulatory proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological diseases, disorders or conditions. Also provided are compositions and methods for making and using such proteins.
A nucleic acid molecule encoding an immunomodulatory protein comprising at least one variant transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) polypeptide, wherein the at least one variant TACI polypeptide comprises two or more amino acid substitutions relative to the extracellular domain (ECD) of a reference TACI polypeptide, wherein the two or more amino acid substitutions comprise K77E and F78Y, corresponding to numbering of positions set forth in SEQ ID NO:122.
A nucleic acid molecule encoding an immunomodulatory protein comprising at least one variant transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) polypeptide, wherein the at least one variant TACI polypeptide comprises two or more amino acid substitutions relative to the extracellular domain (ECD) of a reference TACI polypeptide, wherein the two or more amino acid substitutions comprise K77E and F78Y.
A nucleic acid molecule encoding an immunomodulatory protein comprising at least one variant transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) polypeptide, wherein:
A nucleic acid molecule encoding an immunomodulatory protein comprising a variant TACI polypeptide, wherein the variant TACI polypeptide comprises the amino acid substitutions K77E, F78Y, and Y102D relative to a truncated wild-type TACI extracellular domain that consists of amino acid residues 68-110 as set forth as the amino acid sequence in SEQ ID NO:
A nucleic acid molecule encoding a variant TACI-Fc fusion protein comprising a variant TACI polypeptide linked to an Fc region, wherein the variant TACI polypeptide comprises the amino acid substitutions K77E, F78Y, and Y102D relative to a truncated wild-type TACI extracellular domain that consists of amino acid residues 68-110 as set forth as the amino acid sequence in SEQ ID NO:
A nucleic acid molecule encoding a variant TACI-Fc fusion protein, wherein the variant TACI-Fc fusion protein is set forth as the amino acid sequence in SEQ ID NO:167.
Dependencies are inferred from the claim text.