US 12,233,124 B2
Recombinant metapneumovirus f proteins and their use
Peter Kwong, Washington, DC (US); Michael Gordon Joyce, Washington, DC (US); Baoshan Zhang, Bethesda, MD (US); Yongping Yang, Potomac, MD (US); Peter Collins, Kensington, MD (US); Ursula Buchholz, Silver Spring, MD (US); Davide Corti, Bellinzona (CH); Antonio Lanzavecchia, Bellinzona (CH); and Guillaume Stewart-Jones, Cambridge, MA (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Institute for Research in Biomedicine, Bellinzona (CH)
Filed by The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Institute For Research in Biomedicine, Bellinzona (CH)
Filed on Sep. 6, 2023, as Appl. No. 18/462,340.
Application 18/462,340 is a division of application No. 17/334,505, filed on May 28, 2021, granted, now 11,786,591.
Application 17/334,505 is a division of application No. 16/578,748, filed on Sep. 23, 2019, granted, now 11,027,007, issued on Jun. 8, 2021.
Application 16/578,748 is a division of application No. 15/539,640, granted, now 10,420,834, issued on Sep. 24, 2019, previously published as PCT/IB2015/059991, filed on Dec. 24, 2015.
Claims priority of provisional application 62/096,744, filed on Dec. 24, 2014.
Prior Publication US 2024/0024458 A1, Jan. 25, 2024
Int. Cl. C07K 14/115 (2006.01); A61K 39/155 (2006.01); A61K 39/39 (2006.01); A61K 48/00 (2006.01); C07K 14/005 (2006.01); C07K 14/135 (2006.01)
CPC A61K 39/155 (2013.01) [A61K 39/39 (2013.01); A61K 48/00 (2013.01); C07K 14/005 (2013.01); C07K 14/135 (2013.01); C07K 2319/70 (2013.01); C07K 2319/73 (2013.01); C12N 2760/18322 (2013.01); C12N 2760/18334 (2013.01); C12N 2760/18522 (2013.01); C12N 2760/18534 (2013.01)] 35 Claims
 
1. A method for generating an immune response to metapneumovirus (MPV) F protein in a subject, comprising:
administering to the subject an effective amount of a nucleic acid molecule encoding a recombinant MPV F protein or immunogenic fragment thereof stabilized in a prefusion conformation by one or more amino acid substitutions compared to a native MPV F protein sequence, wherein the recombinant MPV F protein comprises a F2 polypeptide and a F1 ectodomain, wherein the one or more amino acid substitutions introduce one or more non-native intra- or inter-protomer disulfide bonds that, alone or in combination with other modifications, stabilize the MPV F protein in the prefusion conformation.