Compositions and methods for treating hepatitis B

Patent metadata

Field	Value
Publication number	US-10155020-B2
Application number	US-201615343473-A
Country	US
Kind code	B2
Filing date	Nov 4, 2016
Priority date	Sep 26, 2012
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The present invention provides compositions and methods for treating hepatitis B virus (HBV) infection as well as methods for identifying a compound or a composition that is suitable for treating HBV infection. In addition, the present invention provides a suitable non-mammalian animal model that can be used to screen for a compound or a composition that can inhibit HBV replication or treat HBV infection in a mammal. In particular, the present invention provides compositions and methods for treating hepatitis B infection by inhibiting interaction between HBV x protein and a Bcl-2 family protein or by reducing the expression level of a Bcl-2 family protein.

First claim

What is claimed is:

1. A method for treating hepatitis B infection in a subject, comprising administering to the subject a therapeutically effective amount of a peptaibol TK selected from peptaibol TK VI (SEQ ID NO:1), peptaibol TK VII (SEQ ID NO:2), peptaibol TK VIII (SEQ ID NO:3), or a derivative thereof, or a mixture thereof.

2. The method of claim 1 , wherein the peptaibol TK derivative is a peptaibol in which at least one amino acid of the natural peptaibol TK sequence has been substituted by other amino acids, and maintains an in vitro activity within 25% of a wild type peptaibol TK.

3. The method of claim 1 , wherein the peptaibol TK derivative is a peptaibol modified at the N- or C-terminal end of the peptide sequence of peptaibol TK and have an in vitro activity within 25% of a wild type peptaibol TK.

4. The method of claim 3 , wherein the peptaibol TK derivative is an ester of a peptaibol TK selected from peptaibol TK VI (SEQ ID NO:1), peptaibol TK VII (SEQ ID NO:2), and peptaibol TK VIII (SEQ ID NO:3).

5. The method of claim 3 , wherein the peptaibol TK derivative is an amide of a peptaibol TK selected from peptaibol TK VI (SEQ ID NO:1), peptaibol TK VII (SEQ ID NO:2), and peptaibol TK VIII (SEQ ID NO:3).

6. The method of claim 3 , wherein the peptaibol TK derivative is a pegylated peptaibol TK selected from peptaibol TK VI (SEQ ID NO:1), peptaibol TK VII (SEQ ID NO:2), and peptaibol TK VIII (SEQ ID NO:3).

7. The method of claim 1 , wherein the peptaibol TK derivative is a peptaibol comprising at least one modification that prevents the destruction of the peptaibol by proteases or peptidases.

8. The method of claim 1 , wherein the peptaibol TK derivative is a peptaibol comprising at least one conservative substitution of an amino acid compared to the wild type sequence of peptaibol TK selected from peptaibol TK VI (SEQ ID NO:1), peptaibol TK VII (SEQ ID NO:2), and peptaibol TK VIII (SEQ ID NO:3).

Assignees

• Univ Colorado Regents

Inventors

• Xue Ding
• Geng Xin

Classifications

• A61K38/04 Primary

  Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof ({enzyme inhibitors A61K38/005;} gastrins {A61K38/2207}, somatostatins A61K38/31, melanotropins A61K38/34 {; protease inhibitors A61K38/55}) · CPC title

• C12N15/1131

  against viruses · CPC title

• C12N2320/31

  Combination therapy · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2330/50

  Biochemical production, i.e. in a transformed host cell · CPC title