IP Library › Granted Patent US 12,491,161
Granted Patent B2
US 12,491,161 · App. 18/180,801 · Granted Dec 9, 2025

Single vial vaccine formulations

Inventors: Christopher B. Fox (Sumner, WA); Thomas Vedvick (Federal Way, WA); Lucien Barnes, V (Seattle, WA); Ryan M. Kramer (Seattle, WA); Steven G. Reed (Bellevue, WA)
Assignee: ACCESS TO ADVANCED HEALTH INSTITUTE
A61K9/19A61K39/00A61K39/04A61K39/39A61K47/10A61K47/22A61K47/26A61K2039/552A61K2039/55511A61K2039/55572
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Quick Facts
Patent No.
US 12,491,161
App. No.
18/180,801
Granted
Dec 9, 2025
Kind
B2
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.

Claims (24)

1 . A thermostable lyophilized vaccine composition comprising:

a metabolizable oil;

a cake-forming excipient, wherein the cake-forming excipient is (1) a combination of mannitol and trehalose or (2) trehalose; and

an adjuvant,

wherein the composition is formed by lyophilization of an oil-in-water emulsion formulation that does not comprise glycerol, is in the form of a cake, does not contain liposomes, forms an oil-in-water emulsion upon reconstitution, and is thermostable a temperature between about 8° C. to about 60° C. for at least 10 months.

2 . The composition of claim 1 , wherein the oil-in-water emulsion formulation does not contain alum.

3 . The composition of claim 1 , wherein thermostability of the composition is determined prior to reconstitution of the composition, following reconstitution of the composition, by inspection of the oil-in-water emulsion formed upon reconstitution for creaming, or by assay of components of the oil-in-water emulsion formed upon reconstitution.

4 . The composition of claim 1 , wherein the adjuvant is a TLR4 agonist.

5 . The composition of claim 4 , wherein the TLR4 agonist is MPL, 3d-MPL, or synthetic GLA.

6 . The composition of claim 5 , wherein the synthetic GLA has the following structure:

wherein, R 1 , R 3 , R 5 , and R 6 are C 11 -C 20 alkyl; and R 2 and R 4 are C 9 -C 20 alkyl.

7 . The composition of claim 1 , further comprising an antigen that is a polypeptide, a nucleic acid encoding a polypeptide, or a pathogen.

8 . The composition of claim 1 , wherein the metabolizable oil is squalene, synthetic squalene, grape seed oil, olive oil, or a synthetic isoprenoid.

9 . The composition of claim 1 , further comprising 1,2-dimyristoy 1-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), egg phosphatidylcholine (PC), lecithin, a polysorbate surfactant, or a combination thereof.

10 . The composition of claim 1 , further comprising a surfactant.

11 . The composition of claim 1 , further comprising an antioxidant.

12 . A single vial comprising the thermostable lyophilized vaccine composition of claim 1 , wherein the composition is contained in the single vial.

13 . A method for generating the thermostable lyophilized vaccine composition of claim 1 , comprising the step of lyophilizing an oil-in-water emulsion to form the thermostable lyophilized vaccine composition, wherein the oil-in-water emulsion prior to lyophilization comprises the metabolizable oil and the cake-forming excipient.

14 . A method of stimulating an immune response in a subject comprising:

(a) reconstituting the thermostable lyophilized vaccine composition of claim 1 into an oil-in-water emulsion; and

(b) administering the oil-in-water emulsion to the subject, thereby stimulating the immune response in the subject.

15 . The composition of claim 10 , wherein the surfactant is poloxomer 188.

16 . The composition of claim 11 , wherein the antioxidant is vitamin E.

17 . The composition of claim 1 , wherein the adjuvant is present at about 50 μg/mL or less.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2023
From: FOX, CHRISTOPHER B.; VEDVICK, THOMAS S.; BARNES V., LUCIEN; KRAMER, RYAN M.; REED, STEVEN G.
To: INFECTIOUS DISEASE RESEARCH INSTITUTE
Reel/Frame 062925/0663 →
CHANGE OF NAME Recorded Mar 8, 2023
From: INFECTIOUS DISEASE RESEARCH INSTITUTE
To: ACCESS TO ADVANCED HEALTH INSTITUTE
Reel/Frame 063024/0829 →
Continuity (3)
Continuation 15108773
Provisional Application 61922761 · Dec 31, 2013
Related Publication 20230293440A1 · Sep 21, 2023
References Cited (38)
US 5576016A · Amselem et al. · 1996 [cited by applicant]
US 5709879A · Barchfeld et al. · 1998 [cited by applicant]
US 20070191314A1 · Klucker et al. · 2007 [cited by applicant]
US 20080131466A1 · Reed et al. · 2008 [cited by applicant]
US 20090060906A1 · Barry et al. · 2009 [cited by applicant]
US 20150335752A1 · Look et al. · 2015 [cited by applicant]
US 20170191314A1 · Faircloth et al. · 2017 [cited by applicant]
EP 2148697B1 · 2012 [cited by applicant]
EP 3089754B1 · 2021 [cited by applicant]
EP 3915579A1 · 2021 [cited by applicant]
WO 2011129120A1 · 2011 [cited by applicant]
WO 2012085872A2 · 2012 [cited by applicant]
WO 2013006837A1 · 2013 [cited by applicant]
Landrau: Pluronic F68, 4 pgs. [cited by examiner]
Draber et al., J Immunological Methods, 181, 1995, 37-43. [cited by examiner]
Office Action for related patent application from Brazil Patent Office, application No. BR 11 2016 015422-3, mailed Dec. 26, 2023, 15 pages (with translation). [cited by applicant]
Office Action for related patent application from Brazil Patent Office, application No. BR 11 2016 015422-3, mailed Sep. 5, 2023, 12 pages (with translation). [cited by applicant]
Office Action for related patent application from Korea KIPO, application No. 10-2022-7020632, mailed Oct. 13, 2023, 8 pages (with translation). [cited by applicant]
Notice Prior to Acceptance for related application from Israel PTO, application No. 246456, mailed Nov. 23, 2023, 1 page. [cited by applicant]
CA2935620—Office Action, mailed on Nov. 17, 2021, 3 pages. [cited by applicant]
IL246456—Office Action, mailed on Oct. 27, 2021, 6 pages. (with English translation). [cited by applicant]
EP21160158.8—Extended European Search Report, mailed on Nov. 2, 2021, 13 pages. [cited by applicant]
MX MX/a/2016/008640—Office Action, mailed on Oct. 6, 2021, 9 pages. (with English translation). [cited by applicant]
KR20167020820—Office Action, mailed on Dec. 22, 2021, 4 pages. (with English translation). [cited by applicant]
KR20227020632—Office Action, mailed on Feb. 17, 2023, 20 pages. (with English translation). [cited by applicant]
Fox et al., “Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy”, Influenza and Other Respiratory Viruses, vol. 7, No. 5, Nov. 5, 2012, pp.… [cited by applicant]
Orr et al., “Elimination of the cold-chain dependence of a nanoemulsion adjuvanted vaccine against tuberculosis by yophilization”, Journal of Controlled Release, vol. 177, Mar. 10, 2014, pp. 20-26. [cited by applicant]
U.S. Appl. No. 15/108,773—Non-Final Office Action, mailed on May 11, 2022, 14 pages. [cited by applicant]
U.S. Appl. No. 15/108,773—Final Office Action, mailed on Nov. 23, 2022, 16 pages. [cited by applicant]
U.S. Appl. No. 15/108,773—Notice of Allowance, mailed on Jul. 3, 2023, 9 pages. [cited by applicant]
EA-201691348—Office Action, mailed Oct. 27, 2021, 4 pages, (with English translation). [cited by applicant]
Orr MT et al. Adjuvant formulation structure and composition are critical for the development of an effective vaccine against tuberculosis. J Control Release. Nov. 28, 2013;172(1):190-200. doi: 10.1016/j.jconrel.2013.07… [cited by applicant]
Baldwin SL et al. “The importance of adjuvant formulation in the development of a tuberculosis vaccine”, The Journal of Immunology, 188(5):2189-97; Mar. 1, 2012 (Mar. 1, 2012). [cited by applicant]
Fox CB. “Squalene emulsions for parenteral vaccine and drug delivery”, Molecules, 14(9):3286-312; Sep. 1, 2009 (Sep. 1, 2009). [cited by applicant]
Office Action for related Canadian Patent Application No. 2,935,620, mailed Apr. 16, 2024, 8 pages. [cited by applicant]
Related foreign patent Office Action Chinese Patent Application No. 2014800766201, mailed Jul. 3, 2024, 14 pages. [cited by applicant]
Office Action for Mexican Patent Application No. MX/a2022/002106, dated Aug. 23, 2024, 20 pages (with machine translation). [cited by applicant]
Notification of Reexamination for related Chinese Application No. 201480076620.1 issued Nov. 19, 2024, 16 pages (with translation). [cited by applicant]