Loading patent…
AssigneesMelbourne Health, Austin Health, Southern Health, Bayside Health, St. Vincent's Hospital (Melbourne) Ltd. trading as St. Vincent's Hospital Melbourne
InventorsAngeline Ingrid Bartholomeusz, Stephen Alister Locarnini, Anna Ayers, Lilly Ka Wai Yuen, Joseph John Sasadeusz
Estimating the term…
The present invention relates generally to viral variants exhibiting reduced sensitivity to particular agents and/or reduced interactivity with immunological reagents. More particularly, the present invention is directed to hepatitis B virus (HBV) variants exhibiting complete or partial resistance to nucleoside or nucleotide analogs and/or reduced interactivity with antibodies to viral surface components including reduced sensitivity to these antibodies. The present invention further contemplates assays for detecting such viral variants, which assays are useful in monitoring anti-viral therapeutic regimens and in developing new or modified vaccines directed against viral agents and in particular HBV variants. The present invention also contemplates the use of the viral variants to screen for and/or develop or design agents capable of inhibiting infection, replication and/or release of the virus.
An isolated Hepatitis B virus (HBV) variant wherein said variant comprises a nucleotide mutation in a gene encoding a DNA polymerase resulting in at least one amino acid addition, substitution and/or deletion to said DNA polymerase and wherein said variant exhibits decreased sensitivity to one or more nucleoside or nucleotide analogs and/or anti-HBV agents.
An isolated HBV variant comprising a nucleotide mutation in the S gene resulting in at least one amino acid addition, substitution and/or deletion to the surface antigen and which exhibits decreased sensitivity to one or more nucleoside or nucleotide analogs and/or anti-HBV agents.
A method for determining the potential for an HBV to exhibit reduced sensitivity to a nucleoside or nucleotide analog selected from ADV, LMV, TFV and FTC or optionally other nucleoside or nucleotide analogs, said method comprising isolating DNA or corresponding mRNA from said HBV and screening for a mutation in the nucleotide sequence encoding HBV DNA polymerase resulting in at least one amino acid substitution, deletion and/or addition in any one or more of domains F and A through E or a region proximal thereto of said DNA polymerase and associated with resistance or decreases sensitivity to one or more of ADV, LMV, TFV and/or FTC wherein the presence of such a mutation is an indication of the likelihood of resistance to said one or more of ADV, LMV, TFV and/or FTC.
A method for determining whether an HBV strain exhibits reduced sensitivity to a nucleoside or nucleotide analog, said method comprising isolating DNA or corresponding mRNA from said HBV and screening for a mutation in the nucleotide sequence encoding the DNA polymerase wherein the presence of a mutation in a region selected from the F to G domain, between F and A domains, the A domain, between the A and B domains, the B domain, between the B and C domains, to C domain, between the C and D domains, the D domain, between the D and E domain and the E domain or combinations thereof or an equivalent one or more other mutation is indicative of a variant wherein said variant exhibits a decreased sensitivity to one or more of ADV, LMV, TFV and/or FTC optionally other nucleoside or nucleotide analogs.
A method for detecting an agent which exhibits inhibitory activity to an HBV which exhibits resistance or decreased sensitivity to one or more of ADV, LMV, TFV and/or FTC said method comprising:
The method of claim 51 wherein the HBV variant comprises a mutation selected from rtN238T, rt180L, rtI204M, rtN238T, rtI187V, rtN248Q and rtS256G.
The method of claim 55 wherein said variant comprises a mutation in the DNA polymerase selected from rtI122V, rtA181T, rtL180M, rtA/V200V, rtM204V, rtV214A, rtH237H/P, rtV253G and rtN238T/A.
A method for detecting a variant HBV exhibiting an altered immunological profile said method comprising isolating an HBV from a subject exposed to a nucleoside or nucleotide analog selected from the listed consisting of ADV, LMV, TFV or FTC;
A method for detecting a variant HBV exhibiting an altered immunological profile said method comprising isolating a serum sample from a subject exposed to a nucleoside or nucleotide analog selected from the listed consisting of ADV, LMV, TFV or FTC;
A kit for an assay for variant HBV resistant to ADV, LMV, TFV, or FTC;
A kit for an assay for variant HBV resistant to ADV, LMV, TFV, or FTC;
A method for determining the potential for an HBV to exhibit reduced sensitivity to ADV, LMV, TFV, or FTC;
Dependencies are inferred from the claim text.