Cancer therapy compositions and uses thereof

Inventors

Reed, Steven Gregory • Carter, Darrick Albert • Duthie, Malcolm Scott • Berglund, Lars Peter Aksel • Erasmus, Jesse Hong-Sae • Kim, Jiho

Abstract

The disclosure provides compositions, methods of treatment, and methods of making and using compositions to deliver a nucleic acid to a subject. Compositions described herein include lipid carriers, optionally including an inorganic particle, capable of admixing with nucleic acids. Nucleic acids provided herein include those encoding for cancer antigens (full length proteins or fragments) as well as antibodies. Methods of using the compositions as a therapeutic vaccine for the treatment of a cancer are also provided.

Core Innovation

The invention provides cancer vaccine compositions comprising lipid nanoparticles characterized by a z-average diameter particle size measurement of about 20 nm to about 60 nm when measured using dynamic light scattering. The lipid nanoparticles comprise a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant, and the compositions further include at least one nucleic acid.

The nucleic acid comprises a sequence encoding for an RNA-dependent polymerase and a sequence encoding for a transmembrane-binding domain, an outer cell membrane-contacting domain, and an inner cell membrane-contacting domain of a prostein protein. In described embodiments, the RNA-dependent polymerase is a Venezuelan equine encephalitis virus RNA polymerase, and the polymerase sequence is referenced by SEQ ID NO:71.

The disclosure also includes nanoparticle formulation features and optional components, including hydrophobic oil cores and inorganic or metal particles. It further describes dried or lyophilized and spray-dried formulations using cryoprotectants such as sucrose and trehalose, including stabilization and formulation-related measurements supporting the use of the lipid nanoparticle compositions.

Claims Coverage

The independent claim covers a composition with three main inventive features: lipid nanoparticles with a specified z-average diameter range by dynamic light scattering, a defined lipid nanoparticle component set, and nucleic acid including an RNA-dependent polymerase encoding sequence and a prostein protein domain architecture.

Overall, the claim coverage focuses on a z-average 20–60 nm lipid nanoparticle system composed of cationic lipid plus hydrophilic and hydrophobic surfactants, combined with nucleic acids encoding an RNA-dependent polymerase and prostein protein membrane-contacting domain architecture. Dependent claims further narrow the prostein protein by sequence identity, specify the RNA polymerase as VEEV with SEQ ID NO:71, and optionally add inorganic particles with specified metal-oxide species.

Stated Advantages

Documented Applications