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Oligonucleotide targeting strategy for hbv cccdna

An oligonucleotide and nucleotide technology, applied in the field of oligonucleotide targeting strategy for HBV CCcDNA, can solve problems such as inability to cure

Inactive Publication Date: 2019-09-13
JANSSSEN BIOPHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Accumulating evidence shows that due to the persistence of cccDNA, current antiviral treatments such as nucleoside (acid) analogs (NA) or interferon (IFN) alone are not yet curative for most chronic hepatitis B (CHB )patient

Method used

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  • Oligonucleotide targeting strategy for hbv cccdna
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  • Oligonucleotide targeting strategy for hbv cccdna

Examples

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Embodiment 1

[0245] Example 1: Oligonucleotides of the Disclosure Reduce Viral Antigens in Infected Primary Human Hepatocytes

[0246] All oligonucleotides were prepared by solid phase synthesis. About 200 different oligonucleotides spanning (+) or (-) DNA strands were synthesized. The biological effects of different oligonucleotides on HBV gene expression (eg HBsAg, HBeAg, tox) were screened in HBV(+) primary human hepatocytes (PHH) at 3 different doses (0.3, 3 or 30 μM).

[0247] Culture and infection: Primary human hepatocytes (PHH) (BioreclamationIVT, Baltimore, MD) were thawed and inoculated into Biocoat according to the manufacturer's instructions. TMCollagen I Cellware 96-well, 24-well or 6-well plate (Corning Inc., Corning, New York). Cells were thawed in a water bath at 37°C and centrifuged at 100 xg for 10 minutes in primary hepatocyte thawing and seeding medium (ThermoFisher Scientific, Inc., Waltham, MA). Cells were resuspended and 8 × 10 5 / ml was plated in Hepatocyte Ma...

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Abstract

The present disclosure provides oligonucleotide compositions that target the covalently closed circular (ccc) DNA of hepatitis B virus (HBV). Also disclosed herein are methods for treating a subject diagnosed with, or suspected of having an HBV infection and / or an HBV-associated disorder, e.g., chronic hepatitis B infection, liver failure or cirrhosis and hepatocellular carcinoma.

Description

[0001] Cross References to Related Applications [0002] This patent application claims the benefit and priority of U.S. Patent Application 62 / 420,801, filed November 11, 2016, and U.S. Patent Application 62 / 558,770, filed September 14, 2017, the contents of which are hereby incorporated by reference in their entirety way incorporated into this article. technical field [0003] The present disclosure relates to oligonucleotide compositions targeting covalently closed circular (ccc) DNA of hepatitis B virus (HBV), and the use of said compositions for the treatment of diagnosed or suspected HBV infection and / or HBV Approaches to subjects with related disorders, such as chronic hepatitis B infection. Background technique [0004] The following description of the background of the present disclosure is provided only as an aid in understanding the present disclosure, and is not intended to admit that such disclosure is prior art to the present disclosure. [0005] HBV is one o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113
CPCC12N2310/11C12N15/1131A61P31/20A61K31/7125C12N15/113A61K45/06C12N2310/314C12N2310/315C12N2310/321C12N2310/3341C12N2310/34
Inventor S.格利亚兹诺夫M.菲茨杰拉德A.D.斯托里舍娃J.洪
Owner JANSSSEN BIOPHARMA INC
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