Nucleic acid molecules encoding B7-DC variants
AssigneeMayo Foundation for Medical Education and Research
InventorLieping Chen
Life of this patent
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Abstract
Variant costimulatory polypeptides, nucleic acids encoding such polypeptides, and methods for using the polypeptides and nucleic acids to enhance a T cell response are provided herein.
Claims61
An isolated nucleic acid molecule encoding a variant B7-DC polypeptide comprising an IgV domain, wherein the variant polypeptide is a variant of wild-type B7-DC polypeptide, has altered binding affinity for PD-1 compared to the wild-type B7-DC polypeptide, and comprises a substitution of an amino acid in the A′, B, C, C′, C″, D, E, F, or G β strand of wild-type B7-DC polypeptide according to SEQ ID NO:5 or 6.
An isolated nucleic acid molecule encoding a polypeptide fragment of murine B7-DC (SEQ ID NO:6) or human B7-DC (SEQ ID NO:5), the polypeptide fragment comprising amino acids 67-71, amino acids 101-105, or amino acids 111-113 of SEQ ID NO:6, wherein the polypeptide inhibits binding of endogenous B7-DC to PD-1.
An isolated nucleic acid molecule encoding a fusion polypeptide comprising a first fusion partner comprising a variant B7-DC polypeptide comprising an IgV domain, wherein the variant polypeptide is a variant of wild-type B7-DC polypeptide, has altered binding affinity for PD-1 compared to the wild-type B7-DC polypeptide, and comprises a substitution of an amino acid in the A′, B, C, C′, C″, D, E, F, or G β strand of wild-type B7-DC polypeptide according to SEQ ID NO:5 or 6, and a second fusion partner.
An isolated nucleic acid molecule encoding a fusion polypeptide comprising the IgV domain of B7-DC fused to a second polypeptide, wherein the IgV domain of B7-DC is from human (SEQ ID NO:5) or murine B7-DC (SEQ ID NO:6) and comprises an amino acid substitution relative to wildtype human (SEQ ID NO:5) or murine (SEQ ID NO:6) B7-DC IgV domain, wherein the substitution alters binding affinity for PD-1 compared to the wild-type B7-DC polypeptide.
Dependencies are inferred from the claim text.