RSV F protein mutants

Patent metadata

Field	Value
Publication number	US-12364749-B2
Application number	US-202318192352-A
Country	US
Kind code	B2
Filing date	Mar 29, 2023
Priority date	Dec 23, 2015
Publication date	Jul 22, 2025
Grant date	Jul 22, 2025

Abstract

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

First claim

The invention claimed is:

1. A method of preventing Respiratory Syncytial Virus (RSV) infection in a human infant comprising administering to a pregnant woman an effective amount of a pharmaceutical composition comprising (1) a mutant of a wild-type RSV F protein and (2) a pharmaceutically acceptable carrier, wherein the mutant comprises (a) a F1 polypeptide and a F2 polypeptide and (b) at least one introduced amino acid mutation relative to the amino acid sequence of the wild-type RSV F protein, wherein the introduced amino acid mutation is a pair of cysteine mutations selected from the group consisting of: (i) 55C and 188C; (ii) 103C and 148C; and (iii) 142C and 371C, and wherein amino acid positions are numbered according to SEQ ID NO:1.

2. The method of claim 1 , wherein the pharmaceutical composition comprises: (1) a mutant of the F protein of a subtype-A wild-type RSV; (2) a mutant of the F protein of a subtype-B wild-type RSV; and (3) a pharmaceutically acceptable carrier, wherein each of the mutants comprises a F2 polypeptide and F1 polypeptide, wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-A wild-type RSV comprise the amino acid sequence of SEQ ID NO:45 and the amino acid sequence of SEQ ID NO:46, respectively, and wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-B wild-type RSV comprise the amino acid sequence of SEQ ID NO: 49 and the amino acid sequence of SEQ ID NO:50, respectively.

3. A method of eliciting an immune response against Respiratory Syncytial Virus (RSV) in a human infant comprising administering to a pregnant woman an effective amount of a pharmaceutical composition comprising a mutant of a wild-type RSV F protein and a pharmaceutically acceptable carrier, wherein the mutant comprises (a) a F1 polypeptide and a F2 polypeptide and (b) at least one introduced amino acid mutation relative to the amino acid sequence of the wild-type RSV F protein, wherein the introduced amino acid mutation is a pair of cysteine mutations selected from the group consisting of: (i) 55C and 188C; (ii) 103C and 148C; and (iii) 142C and 371C, and wherein amino acid positions are numbered according to SEQ ID NO:1.

4. The method of claim 3 , wherein the pharmaceutical composition comprises: (1) a mutant of the F protein of a subtype-A wild-type RSV; (2) a mutant of the F protein of a subtype-B wild-type RSV; and (3) a pharmaceutically acceptable carrier, wherein each of the mutants comprises a F2 polypeptide and F1 polypeptide, wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-A wild-type RSV comprise the amino acid sequence of SEQ ID NO:45 and the amino acid sequence of SEQ ID NO:46, respectively, and wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-B wild-type RSV comprise the amino acid sequence of SEQ ID NO:49 and the amino acid sequence of SEQ ID NO:50, respectively.

5. The method according to claim 4 , wherein the C-terminus of the F1 polypeptide of the mutant is linked to a phage T4 fibritin foldon domain.

6. The method according to claim 5 , wherein the pharmaceutical composition further comprises an adjuvant.

7. The method according to claim 6 , wherein the adjuvant is aluminum hydroxide.

8. The method according to claim 4 , wherein the human infant is a newborn.

9. The method according to claim 4 , wherein the human infant is an infant in utero.

10. The method according to claim 5 , wherein the human infant is a newborn.

11. The method according to claim 5 , wherein the human infant is an infant in utero.

12. The method according to claim 2 , wherein the C-terminus of the F1 polypeptide of the mutant is linked to a phage T4 fibritin foldon domain.

13. The method according to claim 12 , wherein the pharmaceutical composition further comprises an adjuvant.

14. The method according to claim 13 , wherein the adjuvant is aluminum hydroxide.

15. The method according to claim 2 , wherein the human infant is a newborn.

16. The method according to claim 2 , wherein the human infant is an infant in utero.

17. The method according to claim 12 , wherein the human infant is a newborn.

18. The method according to claim 12 , wherein the human infant is an infant in utero.

Assignees

• Pfizer

Inventors

• Che Ye
• Dormitzer Philip Ralph
• Gribenko Alexey Vyacheslavovich
• Handke Luke David
• Prasad Avvari Krishna
• Qiu Xiayang
• Ruppen Mark Edward
• Song Xi
• Swanson Kena Anne
• Kodali Srinivas
• Xu Xin
• Efferen KariAnn Sweeney
• Cai Ping
• Tompkins Kristin Rachael
• Nunez Lorna del Pilar

Classifications

• C12N2760/18571

  Demonstrated in vivo effect · CPC title

• C12N2760/18534

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2760/18522

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C07K2319/735

  containing a domain for self-assembly, e.g. a viral coat protein (includes phage display) · CPC title