Single vial vaccine formulations
Inventors
FOX, Christopher B. • Vedvick, Thomas • BARNES V., Lucien • KRAMER, Ryan M. • Reed, Steven G.
Assignees
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Publication Number
US-11801223-B2
Publication Date
2023-10-31
Expiration Date
Abstract
The invention provides for thermostable lyophilized formulations, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response, and methods of use thereof. The lyophilized formulations generally comprise an antigen and/or an adjuvant, a metabolizable oil, and a cake-forming excipient.
Core Innovation
A thermostable lyophilized vaccine composition is provided as a cake made by lyophilization of an oil-in-water emulsion formulation. The composition comprises a metabolizable oil and a cake-forming excipient selected as either a combination of mannitol and trehalose or trehalose alone, and further comprises an adjuvant that is a TLR4 agonist. The composition excludes glycerol and liposomes, and forms an oil-in-water emulsion upon reconstitution.
The composition is thermostable at a temperature between about 8 C. to about 60 C. for at least 10 months, with embodiments at about 50 C. for at least 10 months. The document describes characterization of the reconstituted emulsion quality, including particle size and physicochemical attributes such as pH, together with visual inspection and instrumental measurements for particle size and stability.
The formulations additionally specify embodiments in which the TLR4 agonist is MPL, 3d-MPL, synthetic GLA, GLA, monophosphoryl lipid A, or 3-deacylated monophosphoryl lipid A. In further embodiments, the composition includes squalene and DMPC, and the cake shows no browning by visual inspection after storage.
Claims Coverage
The relevant independent claims are clm-00001, clm-00036, and clm-00042. Across these independent claims, the coverage centers on three inventive feature groups.
Thermostable lyophilized cake from oil-in-water emulsion for TLR4 agonist
A thermostable lyophilized vaccine composition formed by lyophilization of an oil-in-water emulsion formulation into a cake; the composition forms an oil-in-water emulsion upon reconstitution, comprises an adjuvant that is a TLR4 agonist, does not comprise glycerol, does not contain liposomes, and is thermostable at a temperature between about 8 C. to about 60 C. for at least 10 months.
Thermostable lyophilized cake with trehalose excipient and defined thermostability
A thermostable lyophilized vaccine composition comprising a metabolizable oil, a cake-forming excipient wherein the cake-forming excipient is either a combination of mannitol and trehalose or trehalose alone, and an adjuvant wherein the adjuvant is a TLR4 agonist; wherein the composition is formed by lyophilization of an oil-in-water emulsion formulation, does not comprise glycerol, does not contain liposomes, is in the form of a cake, forms an oil-in-water emulsion upon reconstitution, and is thermostable at a temperature of about 50 C. for at least 10 months.
Squalene/DMPC lyophilized cake with GLA adjuvant and thermostability
A thermostable lyophilized vaccine composition comprising a metabolizable oil wherein the metabolizable oil is squalene, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), a cake-forming excipient wherein the cake-forming excipient is either a combination of mannitol and trehalose or trehalose alone, and an adjuvant wherein the adjuvant is glucopyranosyl lipid adjuvant (GLA); wherein the composition is in the form of a cake, is formed by lyophilization of an oil-in-water emulsion formulation, the oil-in-water emulsion formulation does not comprise glycerol, and the composition is thermostable at a temperature between 8 C. to 60 C. for at least 10 months.
The independent claims collectively cover thermostable lyophilized vaccine cakes made by lyophilizing oil-in-water emulsion formulations, using cake-forming excipients of mannitol and trehalose or trehalose alone and a TLR4 agonist adjuvant, while excluding glycerol and liposomes and maintaining thermostability for at least 10 months. Additional claim-specific scope includes embodiments at about 50 C. thermostability and embodiments specifying squalene with DMPC and a GLA adjuvant.
Stated Advantages
Thermostability at about 8 C. to about 60 C. for at least 10 months.
Thermostability at about 50 C. for at least 10 months.
Forms an oil-in-water emulsion upon reconstitution.
Cake-form does not comprise glycerol and does not contain liposomes.
In an embodiment, the cake shows no browning by visual inspection after storage.
Documented Applications
Not explicitly described in patent.
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