Systems and methods for nucleic acid expression in vivo

Inventors

Debs, Robert James • Heath, Timothy D. • Handumrongkul, Chakkrapong

Assignees

DNARx

Abstract

The present invention provides compositions, systems, kits, and methods for expression of one or more biomolecules in a subject, human or non-human mammal, (e.g., at therapeutic levels for the extended periods of time required to produce therapeutic effects). In certain embodiments, compositions, systems, kits, and methods are provided that comprise a first composition comprising polycationic structures (e.g., empty cationic liposomes, cationic micelles, cationic emulsions, or cationic polymers) and a second composition comprising expression vectors (e.g., non-viral expression vectors not associated with liposomes or other carriers) encoding one or more biomolecules of interest.

Core Innovation

The patent describes methods and compositions for expressing a monoclonal antibody (mAb) or an antigen binding portion thereof in a subject. The method includes administering dexamethasone to a subject infected with a virus, followed by administering a first composition and then a second composition within a defined time window.

The first composition comprises cationic liposomes that include cationic lipids and dexamethasone palmitate, where the cationic liposomes are small uni-lamellar vesicles (SUVs). The first composition further comprises neutral liposomes that include neutral lipids and dexamethasone palmitate, where the neutral liposomes are multi-lamellar vesicles (MLV); the first composition is free, or essentially free, of nucleic acid molecules.

Within about 300 minutes of administering the first composition, the method administers a second composition comprising non-viral expression vectors encoding an mAb or an antigen binding portion thereof that specifically binds to the virus. The result is expression of the mAb or antigen binding portion in the subject as a consequence of administering dexamethasone, the liposome first composition, and the non-viral expression vectors.

Claims Coverage

The independent claim identifies 4 inventive features centered on sequential, dexamethasone-associated delivery for in-subject expression of a virus-binding mAb or antigen binding portion. Dependent claims further refine antibody format, virus specificity, timing, and vector constraints.

Overall claim coverage centers on expressing a virus-specific mAb (or antigen binding portion) by combining dexamethasone with a first liposome composition comprising dexamethasone palmitate in cationic SUVs and neutral MLVs that are free, or essentially free, of nucleic acids, followed shortly thereafter by non-viral expression vectors encoding the virus-binding antibody for expression in the subject. Dependent claims further refine antibody format, influenza A virus, a tighter administration window, CpG-reduced vectors, and plasmid constructs encoding both antibody heavy and light chains.

Stated Advantages

Documented Applications