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US 2025/0025549 A1Published application
Coronavirus vaccine formulations
AssigneeNovavax, Inc.
InventorsGale SMITH, Michael J. MASSARE, Jing-Hui TIAN
Life of this patent
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Abstract
Disclosed herein are coronavirus Spike (S) proteins and nanoparticles comprising the same, which are suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.
Claims75
A coronavirus (CoV) Spike (S) glycoprotein comprising
- (i) an S1 subunit with an inactivated furin cleavage site, wherein the S1 subunit comprises an N-terminal domain (NTD), a receptor binding domain (RBD), subdomains 1 and 2 (SD1/2), wherein the inactivated furin cleavage site has an amino acid sequence of QQAQ (SEQ ID NO:
- 7);
- wherein the NTD optionally comprises one or more modifications selected from the group consisting of:
- (a) deletion of one or more amino acids selected from the group consisting of amino acid 11-14, 56, 57, 130, 131, 132, 144, 145, 198, 199, 228, 229, 230, 231, 234, 235, 236, 237, 238, 239, 240 and combinations thereof, and
- (b) mutation of one or more amino acids selected from the group consisting of amino acid 5, 6, 7, 11, 12, 13, 14, 51, 53, 54, 56, 57, 62, 63, 67, 70, 82, 125, 129, 131, 132, 133, 134, 139, 143, 144, 145, 170, 177, 197, 198, 199, 200, 201, 202, 209, 229, 233, 239, 240, 244, 245, and combinations thereof, and
- (c) insertion of a tripeptide having the amino acid sequence of EPE between amino acids 214 and 215;
- wherein the RBD optionally comprises mutation of one or more amino acids selected from the group consisting of amino acid 326, 333, 355, 358, 360, 362, 363, 392, 395, 404, 419, 426, 427, 431, 432, 433, 439, 440, 447, 464, 465, 471, 473, 477, 480, 481, 483, 485, 488, 492, and combinations thereof, and
- wherein the SD1/2 domain optionally comprises mutation of one or more amino acids selected from the group consisting of 534, 557, 591, 600, 601, 626, 642, 645, 664, 666, 668, and combinations thereof, and
- (ii) an S2 subunit, wherein amino acids 973 and 974 are proline,
- wherein the S2 subunit optionally comprises one or more modifications selected from the group consisting of:
- (a) deletion of one or more amino acids from 676-685, 676-702, 702-711, 775-793, 806-815 and combinations thereof, and
- (b) mutation of one or more amino acids selected from the group consisting of 688, 691, 703, 751, 783, 843, 846, 875, 937, 941, 956, 968, 969, 1014, 1058, 1105, 1163, 1186 and combinations thereof, and
- (c) deletion of one or more amino acids from the TMCT;
- and combinations of any one of the modifications in (i)(a)-(c) and (ii)(a)-(c);
- wherein the amino acids of the CoV S glycoprotein are numbered with respect to a polypeptide having the sequence of SEQ ID NO:
- 2.
13 more elements
Dependencies are inferred from the claim text.