# US 9,518,090 B2 · Compositions and methods for treating hepatitis B

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- Number: US 9,518,090 B2
- Document ID: US9518090B2
- Status: Granted
- Kind: B2
- Application number: 14/431,622
- Filed: 2013-09-26
- Published: 2015-08-20
- Granted: 2016-12-13
- Earliest claimed: 2012-09-26
- Assignees: The Regents of the University of Colorado, a body corporate
- Applicants: The Regents of the University of Colorado, A Body Corporate
- Inventors: Ding Xue; Xin Geng
- Web page: https://patentgrep.com/patent/US9518090B2

## CPC

- A61K 38/04: 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})
- A61P 31/20: for DNA viruses
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C12N 15/1131: {against viruses}
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/5085: {of invertebrates}
- A61K 38/00: 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)
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2320/31: Combination therapy
- C12N 2330/50: Biochemical production, i.e. in a transformed host cell
- G01N 2333/02: Hepadnaviridae, e.g. hepatitis B virus
- G01N 2500/02: Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
- G01N 2500/10: involving cells
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## 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.

## Claims

### Claim 1

A method for treating hepatitis B infection in a subject, said method comprising administering to a subject in need of such a treatment a composition (i) that is capable of inhibiting binding of hepatitis B virus X protein to a Bcl-2 family member protein in said subject; (ii) that is capable of reducing the expression of Bcl-2family member protein in said subject; or (iii) a combination thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein said Blc-2 family member protein comprises Bcl-2, Bcl-xL, or a combination thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein said composition comprises a binding inhibitor that is capable of inhibiting binding of hepatitis B virus X protein to said Bcl-2 family member protein.

### Claim 4 (depends on 3)

The method of claim 3, wherein said binding inhibitor is capable of interacting with Bcl-2 homology 3 (BH3)-like motif of hepatitis B virus X protein or a Bcl-2 family member.

### Claim 5 (depends on 1)

The method of claim 1, wherein said composition comprises an expression inhibitor that is capable of reducing the expression of Bcl-2 family member protein.

### Claim 6 (depends on 5)

The method of claim 5, wherein said expression inhibitor is a siRNA or a small RNA that is capable of reducing the expression of Bcl-2, Bcl-xL, or a combination thereof.

### Claim 7

A method for identifying a composition that is capable of treating hepatitis B virus (HBV) infection in a mammal, said method comprising determining the effect of said composition in an interaction between HBV X protein and CED-9 protein of C. elegans, wherein modulation of the interaction between HBV X protein and CED-9 protein in the presence of said composition is an indication that said composition is capable of treating HBV infection in a mammal.

### Claim 8

A method for treating hepatitis B infection in a subject, said method comprising administering to a subject in need of such a treatment a therapeutically effective amount of a composition comprising peptaibol TK.

### Claim 9 (depends on 8)

The method of claim 8, wherein said peptaibol TK comprises peptaibol TK VI (SEQ ID NO: 1), peptaibol TK VII (SEQ ID NO: 2), peptaibol TK VIII (SEQ ID NO: 3) or a mixture thereof.