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.
Claims29
1-18. (canceled)
An HBc polypeptide comprising the amino acid sequence of any one of SEQ ID NO:3-31, 34-52.
20-23. (canceled)
25-26. (canceled)
A stabilized, chimeric virus like particle (VLP) having an artificial disulfide bond network comprising multiple HBc polypeptides wherein:
- a. 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 transplanted spike polypeptide sequence of an HBc polypeptide which is different from the spike polypeptides sequence of the wildtype HBc polypeptide of (a);
- and
- c. wherein two HBc polypeptides of (b) dimerized to form a spike.
28-29. (canceled)
38-39. (canceled)
The stabilized VLP of claim 29, wherein the 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.
The HBc polypeptide of claim 1 further comprising an internal sequence from a second different HBc polypeptide, wherein the internal sequence of the second, different HBc polypeptide comprises a spike tip with a lower number of net negative charges at neutral pH and is used to substitute a corresponding portion of the HBc polypeptide thereby resulting in a chimeric HBc polypeptide having lower net negative charges at the spike tip than two net negative charges at neutral pH at the spike tip of an unsubstituted HBc polypeptide or amino acid residues 74-81 of SEQ ID NO:1.
(canceled)
46-47. (canceled)
The HBc polypeptide of claim 18, wherein the additional moiety so conjugated is any one or more of an antibody or a fragment or derivative thereof, a cytokine, a bacterial protein and a tumor antigen.
(canceled)
52-56. (canceled)
A kit for the display of an antigen on the surface of VLP comprising a chimeric VLP with a transplanted spike or portion thereof stabilized by artificial disulfide bond network and comprised of an non-natural amino acid, and an informational insert.
Dependencies are inferred from the claim text.