Combination HIV therapeutic
Inventors
Assignees
Publication Number
US-10493030-B2
Publication Date
2019-12-03
Expiration Date
2036-05-23
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Embodiments of the present invention are directed to particles having a Bryoid and a HDAC inhibitor for the treatment of latent viral disease.
Core Innovation
Embodiments of the present invention are directed to the creation of particles, in particular liposomes, containing both a Bryoid and a Histone Deacetylase (HDAC) inhibitor for the treatment of latent viral diseases. The innovation consists of a formulation wherein the Bryoid is located within the hydrophobic lipid bilayer and the HDAC inhibitor is encapsulated in the aqueous core, allowing co-delivery to the cellular target. This configuration is designed to support methods of treatment and medicaments for addressing latent infections, specifically HIV, by purging latent viral reservoirs.
The invention addresses the significant problem of persistent latent HIV-infected cellular reservoirs, which are not eliminated by standard antiretroviral therapy (ART) and constitute a source of viral reactivation. Latently infected cells provide a permanent viral source, hindering complete eradication of the virus and causing potential viral rebound upon ART interruption. Prior treatments, including HDAC inhibitors such as Vorinostat, have successfully increased HIV transcription from latency but have not succeeded in clearing latent HIV-1 reservoirs.
The present invention combines Protein Kinase C (PKC) agonists, specifically non-tumorigenic Bryoids such as Bryostatin-1, with HDAC inhibitors. By co-encapsulating these agents in targeted, pegylated immunonanosomes coated with broadly neutralizing antibodies and anti-PD-L1 nanobodies, the invention aims to effectively induce HIV latency reversal and promote immunological clearance of reactivated cells, while significantly reducing systemic toxicity. The particle design provides a mechanism for simultaneous, site-specific delivery and intended synergistic action, as well as customizable surface ligands to target viral components and upregulate CD4 cells.
Claims Coverage
There are three core inventive features identified in the independent claims of the patent, relating to liposome structure, medicament composition, and methods of treatment of latent viral diseases.
Liposome with Bryoid in bilayer and HDAC inhibitor in core
A liposome comprising: - A Bryoid incorporated within the hydrophobic lipid bilayer. - A Histone Deacetylase (HDAC) inhibitor present in the aqueous core. This structure allows both agents to be co-encapsulated within a single liposome.
Medicament with Bryoid and HDAC inhibitor co-encapsulated in particles
A medicament for treating a latent viral disease comprising: - A Histone Deacetylase (HDAC) inhibitor and a Bryoid. - The HDAC inhibitor and Bryoid are carried by one or more particles. - The particles have: (i) a core with a mixture of a hydrophilic material and HDAC inhibitor, and (ii) a surrounding material with a mixture of a hydrophobic material and Bryoid. - The surrounding material envelopes the core, and the outer surface surrounds the surrounding material.
Method of treating latent viral disease using co-encapsulated Bryoid and HDAC inhibitor
A method of treating a latent viral disease comprising the steps of: - Administering to a patient an effective amount of a Histone Deacetylase (HDAC) inhibitor and a Bryoid. - Both agents are carried and co-encapsulated in one or more particles, each having a core with a mixture of a hydrophilic material and HDAC inhibitor, and surrounding material with a hydrophobic material and Bryoid. - The surrounding material envelopes the core and the outer surface surrounds the surrounding material.
The inventive features cover liposomes with defined compartmentalization of a Bryoid and an HDAC inhibitor, medicament formulations using such particles, and methods for treating latent viral diseases by their co-administration and targeted delivery.
Stated Advantages
Provides efficient activation of latent HIV and immunological depletion of viral reservoirs while significantly reducing systemic toxicity of both Bryostatin-1 and the HDAC inhibitor.
A combination of Bryoid and HDAC inhibitor synergistically activates latent virus at lower concentrations, reducing required therapeutic concentrations and associated toxicities.
Co-encapsulation in liposomes facilitates simultaneous targeted delivery of both agents to the desired site.
Pegylation increases residence time of the nanoparticles, thereby improving therapeutic efficacy and overall therapeutic index.
Surface modification with targeting ligands and antibodies enhances specificity for viral components and upregulation of CD4 cells.
Liposome encapsulation reduces phagocytosis by leukocytes, resulting in longer circulation time and improved bioavailability.
Documented Applications
Treatment of latent viral diseases, specifically including HIV, by targeting and purging latent HIV-1 from cellular reservoirs.
Interested in licensing this patent?