Methods for the treatment of hepatitis B and hepatitis D infections
Inventors
Bazinet, Michel • Vaillant, Andrew
Assignees
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Publication Number
US-9284556-B2
Publication Date
2016-03-15
Expiration Date
Abstract
It is disclosed a method for the treatment of hepatitis B (HBV) infection or HBV/hepatitis D (HDV) co-infection, the method comprising administering to a subject in need of treatment a first pharmaceutically acceptable agent that removes the hepatitis B surface antigen from the blood and a second pharmaceutically acceptable agent which stimulates immune function.
Core Innovation
The document describes combination therapy for hepatitis B infection or hepatitis B/hepatitis D co-infection in which an HBsAg-targeting agent is used together with an immunotherapeutic agent. It states that circulating hepatitis B surface antigen (HBsAg) suppresses immunotherapy and that clearance of circulating HBsAg enables immune recovery and enhanced immunotherapy efficacy.
The described approach administers a first agent that removes circulating HBsAg, including through inhibition of subviral particle (SVP) formation/release or suppression of HBsAg release, together with a second immunotherapeutic agent that stimulates immune function. The disclosure indicates that rapid and/or stronger anti-HBsAg immune recovery is observed when HBsAg clearance is achieved, producing synergistic enhancement of immunotherapy compared with monotherapies.
The document includes antisense-based implementations for reducing HBsAg by catalyzing degradation of mRNA encoding HBsAg, and it also discusses nucleic acid polymer (NAP) and chelate complexes as mechanisms for HBsAg clearance. It lists example second agents for immune stimulation, including thymosin b11 and pegylated interferon b1-2a, and it describes enumerated classes of first agents and second agents within the combination therapy framework.
Claims Coverage
The partial content provides three independent claims (clm-00001, clm-00002, and clm-00004). Each claim centers on an HBsAg mRNA-targeting antisense component that catalyzes degradation of HBV genome mRNA encoding hepatitis B surface antigen, combined with at least one named pharmaceutically acceptable agent, and one claim further requires an additional group of anti-HBV agents.
Antisense oligonucleotide targeting HBsAg mRNA with immune-modulating agent combination
Administering to a patient an antisense oligonucleotide that targets mRNA of the HBV genome encoding the hepatitis B surface antigen (HBsAg) and catalyzes degradation of that mRNA, together with at least one pharmaceutically acceptable agent selected from thymosin b11; interferon b2-1a; interferon b2-1b; interferon b3-1b; interferon bb1; interferon bb2; interferon b33; pegylated interferon b11; pegylated interferon b12; GS-9620; dehydroepiandrosterone; androstenediol; and androstenetriol.
Antisense chelate complex formulation targeting HBsAg mRNA with immune-modulating agent combination
Administering to a patient an antisense chelate complex formulation comprising an antisense oligonucleotide catalyzing the degradation of a mRNA used to produce the hepatitis B surface antigen (HBsAg) protein, together with at least one pharmaceutically acceptable agent selected from thymosin b11; interferon b12-2a; interferon b12-2b; interferon b12-N3; interferon b2-1a; interferon b2-1b; interferon b3-1b; interferon bb1; interferon bb2; interferon b33; pegylated interferon b12-2a; pegylated interferon b12-2b; pegylated interferon b11; pegylated interferon b12; GS-9620; dehydroepiandrosterone; androstenediol; and androstenetriol.
Antisense HBsAg mRNA degradation with immune agent plus second anti-HBV agent combination
Administering to a patient an antisense oligonucleotide that targets mRNA of the HBV genome encoding the hepatitis B surface antigen (HBsAg) and catalyzes degradation of that mRNA, together with at least one pharmaceutically acceptable agent selected from thymosin b11; interferon b12-2a; interferon b12-2b; interferon b12-N3; interferon b2-1a; interferon b2-1b; interferon b3-1b; interferon bb1; interferon bb2; interferon b33; pegylated interferon b12-2a; pegylated interferon b12-2b; pegylated interferon b11; pegylated interferon b12; GS-9620; dehydroepiandrosterone; androstenediol; and androstenetriol, and at least one second pharmaceutically acceptable agent selected from tenofovir disoproxil fumarate; entecavir; telbuvidine; adefovir dipivoxil; and lamivudine.
Across the independent claims, the core inventive structure is a hepatitis B surface antigen (HBsAg)-mRNA-directed antisense mechanism that catalyzes degradation of HBV mRNA encoding HBsAg. The claims require combination with named immune-modulating agents, and one claim additionally requires at least one named second anti-HBV agent selected from a specified antiviral group.
Stated Advantages
Enables strong anti-HBsAg immune recovery after HBsAg clearance.
Provides synergistic enhancement of immunotherapy efficacy compared with monotherapies.
Produces substantially faster/higher anti-HBsAg antibody responses.
Improves off-treatment control versus monotherapies.
Documented Applications
Treatment of hepatitis B infection and hepatitis B/hepatitis D co-infection using combination therapy that includes an HBsAg-removing component and an immunotherapeutic immune-stimulating component.
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