Dosing regime and formulations for type B adenovirus
Inventors
BEADLE, John William • Fisher, Kerry • WILKINSON BLANC, Christine
Assignees
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Publication Number
US-11173186-B2
Publication Date
2021-11-16
Expiration Date
Abstract
A method of treating a human patient comprising systemically administering multiple doses of a parenteral formulation of a replication capable oncolytic adenovirus of subgroup B in a single treatment cycle, wherein the total dose given in each dose is in the range of 1×1010 to 1×1014 viral particles, and wherein each dose of virus is administered over a period of 1 to 90 minutes, for example at a rate of viral particle delivery in the range of 2×1010 particles per minute to 2×1012 particles per minute. Also provided are formulations of the oncolytic adenoviruses and combination therapies of the viruses and formulations with other therapeutic agents.
Core Innovation
The invention relates to a method of treating cancer in a human patient by intravenously administering multiple doses of a formulation of a replication competent oncolytic adenovirus of subgroup B in a single treatment cycle. Each administration provides a total dose of viral particles in a defined range and delivers the particles at a defined delivery rate. The adenovirus is characterized by having a fibre and hexon of wild-type Ad11.
The described dosing-regimen and administration window focus on delivering rapid, multi-dose viral exposure within a single cycle. The approach is described as occupying/depleting viral sinks and establishing productive tumor infection, while minimizing toxicity and immune neutralization. The rationale includes maintaining blood viral levels above an infective threshold while limiting peak exposure below a toxicity-associated level.
The document further describes treatment-cycle structuring with multiple doses within the cycle and optional subsequent booster/maintenance cycles. It also describes optional prophylactic co-medications and compatibility with combination therapy, including chemotherapies and radiotherapy, with avoidance of agents that interfere with viral replication.
Formulation examples are described for the replication-competent oncolytic adenovirus, including sterile liquid formulations and parenteral formats such as prefilled syringe/vials. The document also discusses subgroup B adenovirus definitions and examples, including Ad11 and chimeric ColoAd1, and discusses potential cancer types, including colorectal and ovarian cancer, in which the adenovirus may be used.
Claims Coverage
The patent includes one independent claim (clm-00001). Its coverage centers on an intravenous multiple-dose regimen in a single treatment cycle using a replication-competent subgroup B oncolytic adenovirus formulation with specified total viral particle dose and viral particle delivery rate, and an adenovirus having wild-type Ad11 fibre and hexon. Additional inventive features are defined in dependent claims.
Intravenous multiple-dose oncolytic adenovirus subgroup B in a single treatment cycle
Administering, in a single treatment cycle, multiple intravenous doses of a formulation of a replication competent oncolytic adenovirus of subgroup B to treat cancer in a human patient.
Defined total viral particle dose per administration
Providing, in each administration, a total dose of viral particles in the range of 1×10^12 to 1×10^13 viral particles.
Defined viral particle delivery rate per administered dose
Delivering viral particles for each administered dose at a rate in the range of 2×10^10 to 6×10^11 particles per minute.
Wild-type Ad11 fibre and hexon adenovirus
Using an adenovirus having a fibre and hexon of wild-type Ad11.
Dosing interval between administrations
Setting the time interval between each dose administration to be between 6 hours and 72 hours.
Dose amount tied to administration duration options
Administering 1×10^13 viral particles over a 60 minute period per dose, or administering 6×10^12 viral particles over a 40 minute period per dose.
Blood level threshold after dosing
After administration of a second and optionally subsequent doses, reaching a blood level of at least 2×10^6 viral particles per mL.
Combination with anti-cancer therapy modalities
Administering the adenovirus together with an anti-cancer therapy that is an immunotherapeutic agent, a small molecule inhibitor, radiotherapy, radio-isotope therapy, or a combination of these.
Viral seeding of infection in cancer cells
Using multiple doses of replication-competent oncolytic adenovirus to seed viral infection in cancer cells.
Overall, claim coverage focuses on an intravenous multiple-dose regimen in a single treatment cycle for a replication-competent subgroup B oncolytic adenovirus formulation with defined per-dose viral particle totals and delivery-rate ranges, using an adenovirus having wild-type Ad11 fibre and hexon. Dependent coverage further specifies dosing intervals, alternative per-dose viral particle amounts associated with administration durations, a post-dosing blood level threshold, combination with specified anti-cancer therapies, and a functional characterization of seeding viral infection in cancer cells.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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