Vaults engineered for hydrophobic drug delivery

Patent metadata

Field	Value
Publication number	US-10676534-B2
Application number	US-201415027467-A
Country	US
Kind code	B2
Filing date	Oct 17, 2014
Priority date	Oct 18, 2013
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

The invention relates to compositions of vault complexes for use as delivery agents for hydrophobic and/or aqueous insoluble therapeutic compounds. In one aspect, provided herein is a vault complex comprising a modified major vault protein (MVP), wherein the modified major vault protein comprises a fusion peptide, wherein said fusion peptide is fused to the N-terminus of the major vault protein, and wherein said peptide provides enhanced sequestering of a hydrophobic and/or aqueous insoluble therapeutic compound within the vault complex.

First claim

What is claimed is:

1. A major vault protein having a non-structural protein 5A (NS5A) amphipathic a-helix structure fused to its N-terminus, wherein the sequence of the major vault protein has at least 90% sequence identity to SEQ ID NO: 5.

2. The major vault protein of claim 1 , wherein the NS5A amphipathic α-helix structure comprises SEQ ID NO: 19.

3. The major vault protein of claim 1 , wherein the NS5A amphipathic comprises SEQ ID NO: 17.

4. The major vault protein of claim 1 , further comprising a peptide fused to its C-terminus.

5. The major vault protein of claim 4 , wherein the peptide comprises the Z domain of Staphylococcal Protein A (SpA) or a sequence having SEQ ID NO:18.

6. The major vault protein of claim 1 , wherein the major vault protein has at least 95% sequence identity to SEQ ID NO: 5.

7. The major vault protein of claim 1 , wherein the major vault protein has at least 90% sequence identity to SEQ ID NO: 5 and the NSSA amphipathic α-helix structure comprises SEQ ID NO: 19.

8. A composition comprising the major vault protein according to claim 1 .

9. The composition of claim 8 , further comprising a therapeutic compound and/or a lipophilic substance.

10. The composition of claim 9 , wherein therapeutic compound is selected from the group consisting of All-trans Retinoic Acid (ATRA), amphotericin B, bryostatin 1, GSK744, MK-2048, IQP0528, 5-chloro-3-phenylsulfonylindole-2-carboxamide (CSIS), and dapivirine.

11. The composition of claim 8 , further comprising a hydrogel.

12. The composition of claim 8 , further comprising a thermally responsive polymer.

13. A method of delivering a peptide to a subject which comprises administering the major vault protein according to claim 4 to the subject.

14. A method of delivering a therapeutic compound and/or a lipophilic substance to a subject, which comprises administering the composition according to claim 9 to the subject.

Assignees

• Univ California

Inventors

• Rome Leonard H
• Buehler Daniel
• Maynard Heather D

Classifications

• A61K47/6949

  inclusion complexes, e.g. clathrates, cavitates or fullerenes · CPC title

• C07K14/4702 Primary

  Regulators; Modulating activity · CPC title

• A61K31/365

  Lactones · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title