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US 9,896,483 B2Granted
Stabilized hepatitis B core polypeptides
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsYuan Lu, James Robert Swartz
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Abstract
Genetically modified HBc polypeptides are provided.
Claims10
A stabilized, chimeric virus like particle (VLP) having an artificial disulfide bond network comprising multiple HBc polypeptides:
- a. wherein at least two amino acids of each of the HBc polypeptides are substituted with cysteine residues that can form interdimer disulfide bonds after the HBc is assembled into the VLP thereby forming the artificial disulfide bond network that stabilizes the VLP;
- b. wherein each of the HBc polypeptides comprises a spike sequence—which has been modified to have a lower negative charge or neutral charge compared to the spike sequence of the wild-type HBc polypeptide at neutral pH;
- and
- c. wherein two HBc polypeptides of (b) are dimerized to form a spike, and wherein the at least two amino acids are selected from the group consisting of P134-P135, P134-N136, P134-A137, and P135-N136 as provided in SEQ ID NO:1 or SEQ ID NO:2 or amino acid pairs at corresponding positions in aligned sequences of HBC polypeptides.
1 more element
A stabilized, chimeric virus like particle (VLP) having an artificial disulfide bond network comprising multiple HBc polypeptides wherein:
- a. wherein at least two amino acids of each of the HBc polypeptides are substituted with cysteine residues that can form interdimer disulfide bonds after the HBc is assembled into the VLP thereby forming the artificial disulfide bond network that stabilizes the VLP;
- b. wherein each of the HBc polypeptides comprises a spike sequence of an HBc polypeptide which has been modified to have a lower negative charge or neutral charge compared to the spike sequence of the wild-type HBc polypeptide at neutral pH;
- and
- c. wherein two HBc polypeptides of (b) are dimerized to form a spike and wherein the at least two amino acids of the HBC polypeptide so substituted are any of P134-P135, P134-N136, P134-A137, or P135-N136 as shown in SEQ ID NO:1 or SEQ ID NO:2.
1 more element
Dependencies are inferred from the claim text.