Claims for Patent: 10,149,901

Summary for Patent: 10,149,901

Title:	Influenza vaccines with reduced amounts of squalene
Abstract:	Influenza vaccines include hemagglutinin from at least one influenza A virus strain and at least one influenza B virus strain. They also include an oil-in-water emulsion adjuvant with submicron oil droplets, comprising squalene. In some embodiments the hemagglutinin concentration is >12 .mu.g/ml per strain. In some embodiments the squalene concentration is <19 mg/ml. In some embodiments the vaccine is mercury-free. In some embodiments the vaccine has a unit dose volume between 0.2-0.3 mL. In some embodiments the squalene concentration is 9.75 mg/mL or 4.88 mg/mL. In some embodiments the vaccine includes antigens from two influenza A virus strains and two influenza B virus strains.
Inventor(s):	Contorni; Mario (Siena, IT), O\'Hagan; Derek (Cambridge, MA), Groth; Nicola (Buonconvento, IT)
Assignee:	Seqirus UK Limited (Berkshire, GB)
Application Number:	15/007,719
Patent Claims:	1. An influenza virus vaccine composition in unit dosage form wherein the unit dose volume is between 0.2-0.3mL, wherein the vaccine composition comprises: (i) at least one influenza A virus strain hemagglutinin and at least one influenza B virus strain hemagglutinin; and (ii) an oil-in-water emulsion adjuvant with submicron oil droplets, comprising squalene, where the concentration of squalene in the vaccine is .ltoreq.19 mg/ml. 2. The vaccine composition of claim 1 which includes at least two influenza A virus strain hemagglutinins. 3. The vaccine composition of claim 2, wherein the influenza A virus strain hemagglutinins are an H1 subtype and an H3 subtype. 4. The vaccine composition of claim 1 which includes a single influenza B virus strain hemagglutinin, which B virus strain is a B/Victoria/2/87-like strain or a B/Yamagata/16/88-like strain. 5. The vaccine composition of claim 1 which includes two influenza A virus strain hemagglutinins and two influenza B virus strain hemagglutinins. 6. The vaccine composition of claim 5 comprising: (i) a H1N1 influenza A virus strain hemagglutinin; (ii) a H3N2 influenza A virus strain hemagglutinin; (iii) a B/Victoria/2/87-like influenza B virus strain hemagglutinin; and (iv) B/Yamagata/16/88-like influenza B virus strain hemagglutinin. 7. The vaccine composition of claim 1, wherein the unit dose volume is about 0.25ml. 8. The vaccine composition of claim 1, wherein the concentration of squalene is .ltoreq.10mg/ml. 9. The vaccine composition of claim 1, wherein the concentration of squalene is in the range of 2.5mg/ml to 19mg/ml. 10. The vaccine composition of claim 9, wherein the concentration of squalene is in the range of 2.5 to 10mg/ml. 11. The vaccine composition of claim 10, wherein the concentration of squalene is 9.75mg/mL or 4.88mg/mL. 12. The vaccine composition of claim 1, wherein the amount of squalene per dose is 2.7mg, 2.4mg, or 1.2mg. 13. The vaccine composition of claim 1, wherein the concentration of hemagglutinin per strain is .gtoreq.12.mu.g/ml, .gtoreq.25.mu.g/ml or .gtoreq.30.mu.g/ml. 14. The vaccine composition of claim 13, wherein the concentration of hemagglutinin per strain is about 30.mu.g/ml. 15. The vaccine composition of claim 1, wherein the amount of hemagglutinin per strain is about 7.5.mu.g. 16. The vaccine composition of claim 1, wherein: (a) the concentration of hemagglutinin is the same for each strain in the composition; and/or (b) the weight ratio of squalene to hemagglutinin in the vaccine is in the range from 20 to 180; (c) the vaccine is an inactivated influenza virus vaccine; and/or (d) the hemagglutinin is in the form of split virions, or purified surface antigens, or virosomes. 17. The vaccine composition of claim 1, wherein: (a) the influenza virus strains have not been passaged through eggs; and/or (b) the vaccine is substantially free from mercurial material; and/or (c) the vaccine is free of preservatives. 18. The vaccine composition of claim 17, wherein the mercurial material is thiomersal and the vaccine is substantially free from the thiomersal. 19. The vaccine composition of claim 1, wherein the submicron oil-in-water emulsion adjuvant includes polysorbate 80 and/or .alpha.-tocopherol. 20. The vaccine composition of claim 1, wherein the vaccine is: (a) a trivalent influenza vaccine with a A/H1N1 strain hemagglutinin, a A/H3N2strain hemagglutinin and a B strain hemagglutinin, having a hemagglutinin concentration of about 30.mu.g/ml per strain, a squalene concentration of about 9.75mg/ml, and a unit dosage volume of about 0.25ml; or (b) a trivalent influenza vaccine with a A/H1N1 strain hemagglutinin, a A/H3N2strain hemagglutinin and a B strain hemagglutinin, having a hemagglutinin concentration of about 30.mu.g/ml per strain, a squalene concentration of about 4.88mg/ml, and a unit dosage volume of about 0.25ml. 21. The vaccine composition of claim 5, wherein the vaccine is: (a) a tetravalent influenza vaccine with a A/H1N1 strain hemagglutinin, a A/H3N2strain hemagglutinin, a B/Yamagata lineage hemagglutinin, and a B/Victoria lineage hemagglutinin, wherein the vaccine has a hemagglutinin concentration of about 30.mu.g/ml per strain, a squalene concentration of about 9.75mg/ml, and a unit dosage volume of about 0.25ml, or (b) a tetravalent influenza vaccine with a A/H1N1 strain hemagglutinin, a A/H3N2strain hemagglutinin, a B/Yamagata lineage hemagglutinin, and a B/Victoria lineage hemagglutinin, wherein the vaccine has a hemagglutinin concentration of about 30.mu.g/ml per strain, a squalene concentration of about 4.88mg/ml, and a unit dosage volume of about 0.25ml. 22. The vaccine composition of claim 1, wherein the vaccine is suitable for immunizing a child. 23. The vaccine composition of claim 22, wherein the child is .ltoreq.5 years old. 24. The vaccine composition of claim 1, characterized in that when the vaccine is administered to a population of at least 50 patients, the vaccine elicits efficacy that satisfies at least two of the following criteria: (i) .gtoreq.70% seroprotection; (ii) .gtoreq.40% seroconversion or significant increase; and/or (iii) a geometric mean titer increase of .gtoreq.2.5-fold.

Details for Patent 10,149,901

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Seqirus Vaccines Limited	FLUVIRIN	influenza virus vaccine	Injection	103837	11/03/1998		2029-02-10
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	12/09/1999		2029-02-10
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	12/23/1909		2029-02-10
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	05/09/2011		2029-02-10