Emulsion adjuvant for intramuscular, intradermal and subcutaneous administration

Inventors

Baker, Jr., James R. • Smith, Douglas M. • Ciotti, Susan

Assignees

University of Michigan System • Bluewillow Biologics Inc

Abstract

The present invention provides compositions comprising emulsion adjuvant and one or more active agents or substances formulated for infusion or injection into a subject (e.g., using a syringe and needle), as well as methods of formulating and using the same (e.g., as an injectable medicinal composition (e.g., a vaccine)). The emulsion adjuvant of an immunogenic composition of the invention in its preferred form comprises a cationic lipid containing a polar head group and a hydrophobic component (e.g., a dual chain hydrophobic group (e.g., the cationic surfactant dioctadecyl dimethyl ammonium chloride (DODAC) and dioctadecyl dimethyl ammonium bromine (DODAB))). Compositions of the invention comprising emulsion adjuvant and one or more active agents or substances formulated for administration via injection to a subject find use in treatment and/or prevention of infectious disease, cancer and/or allergy.

Core Innovation

The immunogenic composition is formulated for administration via injection and includes an oil in water emulsion comprising dioctadecyldimethylammonium chloride (DODAC), a non-ionic surfactant, an organic solvent, oil, and water. The surfactant blend ratio of DODAC to non-ionic surfactant is 1:6, and the composition further includes an antigen selected from an inactivated microbial pathogen, an isolated protein from a microbial pathogen, and/or a recombinant protein from a microbial pathogen.

The composition produces a cell mediated immune response comprising elevated levels of IFN-gamma and detectable, antigen-specific neutralizing antibody titers when administered via injection. The composition is also defined by failure to produce the same response when administered intranasally via the nasal mucosa, and this injection-versus-intranasal distinction is presented as a key functional characteristic.

Additional disclosed concepts include injectable compositions for intramuscular, intradermal, and subcutaneous routes, compared with intranasal administration via the nasal mucosa. Additional formulation options include sterilization and stability concepts for the nanoemulsion and component selection covering cationic dual-chain lipid, including DODAC and DODAB, with non-ionic surfactant families.

Claims Coverage

The independent claim covers an injection-formulated oil-in-water emulsion immunogenic composition containing DODAC and a non-ionic surfactant at a defined blend ratio of 1:6, together with an antigen, and defines a specific differential immune response outcome versus intranasal administration. Dependent claims further refine non-ionic surfactant selection, add a quantified autoclave stability constraint, and recast the composition as a pharmaceutical composition, vaccine, and syringe product.

Across the independent claim and refinements, the key inventive structure is an injection-formulated oil in water emulsion using DODAC and a non-ionic surfactant at a 1:6 blend ratio, combined with an antigen from an inactivated microbial pathogen, isolated protein, and/or recombinant protein. The claim defines a specific differential outcome: elevated IFN-gamma and antigen-specific neutralizing antibody titers after injection, while failing to produce the same response after intranasal administration via the nasal mucosa. Dependent claims further restrict the non-ionic surfactant options, require physical stability after autoclaving at 121°C for 15 minutes, and recast the composition as a pharmaceutical composition, vaccine, and syringe.

Stated Advantages

Documented Applications