Nucleoside to Treat Multi-Drug Resistant Hepatitis B Infection
- *Abstract
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Background
Hepatitis B is a viral disease that affects the liver, causing a range in severity of symptoms, from mild, transitory illness to a serious, lifelong illness. Hepatitis B is spread when bodily fluids (such as blood or semen) from a person infected with the virus enters the body of someone who is not infected. This can happen through sexual contact or sharing needles or syringes, or other related equipment. Hepatitis B can also be passed frommother to child at birth.Hepatitis B can either be acute or chronic. Acute hepatitis B infection is a short-term illness that occurs within the first 6 months after someone is exposed to the hepatitis B virus.Acute infection can lead to chronic infection. Chronic hepatitis B infection is a long term illness that occurs when hepatitis B virus remains in a person's body. Chronic hepatitis B is a serious illness that can result in long term health problems, and even death.
Technology Summary
The present invention relates to the use of new carbocyclic nucleosides to treat or prevent infection with hepatitis B virus. This small molecule may be used for treatment of hepatitisB infection and secondary disease states such as cirrhosis and liver cancer, as well as a variety of other viral diseases.
The compound exhibits potent in vitro activity against wild type virus and against triple mutant lamivudine-entecavir resistant strains, with a favorable Ec50 resistance profile. The prodrug was evaluated in chimeric mice infected with wild type and entecavir/lamivudine triple mutant viruses and reduced the serum HBV DNA level by 2.2 log copies in mice infected with the wild type clone, while mice infected with entecavir/lamivudine-resistant clone, a reduction of 1.2 log copies was observed.
ProblemsAddressed (benefits/advantages)
- Nucleoside reverse transcriptase inhibitor(NRTI) agent with potential effectiveness is drug-resistant HBV; in vivoevidence suggests efficacy in viral breakthrough of laminvudine-entecavir triplemutant
- Product family includes a new nucleoside(FMCA) and a more potent nucleoside pohsphoramidate prodrug (FMCAP) as well asmethods of synthesis
- No significant mitochondrial toxicity seen indosing (FMCA) up to 100uM (hepG2 cells)
- Shown to reduce serum HBV DNA level by 2.2log copies in mice infected with the wild type clone
- Potent against lamivudine-entecavir triplemutants – reduced serum HBV DNA by 1.2 log copies in mice infected withentecavir/lamivudine-resistant clone
- Prodrug form was unexpectedly found to be exceptionally active against drug resistantforms of hepatitis B virus
Applications
- Treatment of acute and chronic hepatitis B infection Prophylaxis for hepatitis B infection
- Treatment of patents with multi-drug resistant hepatitis B infection
- Treatment of hepatitis B and C co-infection
- *IP Issue Date
- None
- *IP Type
- Utility
- 國家
- United States
- 申請號碼
- 8,816,074
- 國家/地區
- 美國
