US 11,919,927 B2
Prefusion-stabilized hMPV F proteins
Jason McLellan, Austin, TX (US); Ching-Lin Hsieh, Austin, TX (US); Scott Rush, Austin, TX (US); and Nianshuang Wang, Austin, TX (US)
Assigned to Board of Regents, The University of Texas System, Austin, TX (US)
Filed by BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
Filed on Apr. 6, 2023, as Appl. No. 18/296,771.
Application 18/296,771 is a continuation of application No. PCT/US2021/053944, filed on Oct. 7, 2021.
Claims priority of provisional application 63/089,978, filed on Oct. 9, 2020.
Prior Publication US 2023/0357327 A1, Nov. 9, 2023
Int. Cl. C07K 14/08 (2006.01); C07K 14/115 (2006.01); C07K 14/135 (2006.01); C12N 7/00 (2006.01)
CPC C07K 14/08 (2013.01) 30 Claims
 
1. An engineered protein comprising a metapneumovirus (MPV) F protein ectodomain having at least 90% identity to amino acids 19-489 of any one of SEQ ID NOs: 4-7, said engineered protein comprising one or more of:
paired cysteine substitutions corresponding to A140C and A147C,
paired cysteine substitutions corresponding to L110C and N322C,
paired cysteine substitutions corresponding to T127C and N153C,
substitutions at positions corresponding to L219 and/or V231,
substitutions corresponding to L219K and V231I,
paired cysteine substitutions corresponding to T127C and N153C and paired cysteine substitutions corresponding to T365C and V463C,
a substitution corresponding to G366S,
substitutions corresponding to T127C, N153C, A185P, T365C, V463C, L219K, and V231I,
substitutions corresponding to T127C, N153C, A185P, T365C, V463C, L219K, V231I, and RQSR (residues corresponding to positions 99-102 of any one of SEQ ID NOs: 4-7) to RRRR (SEQ ID NO: 10),
substitutions corresponding to T127C, N153C, T365C, V463C, L219K, and V231I,
substitutions corresponding to L110C, T127C, A140C, A147C, N153C, A185P, L219K, V231I, N322C, T365C, E453Q, and V463C,
substitutions corresponding to L110C, T127C, A140C, A147C, N153C, A185P, L219K, V231I, N322C, T365C, E453Q, V463C, and RQSR (residues corresponding to positions 99-102 of any one of SEQ ID NOs: 4-7) to RRRR (SEQ ID NO: 10), and
substitutions corresponding to L110C, T127C, A140C, A147C, N153C, L219K, V231I, N322C, T365C, E453Q, and V463C,
relative to the sequence of any one of SEQ ID NOs: 4-7.