IP Library › Granted Patent US 12,234,265
Granted Patent B2
US 12,234,265 · App. 18/068,867 · Granted Feb 25, 2025

Stabilized RSV F proteins and uses thereof

Inventors: Lan Zhang (Chalfont, PA); Arthur Fridman (Lake Ariel, PA); Eberhard Durr (Quakertown, PA); Andrew Bett (Lansdale, PA)
Assignee: Merck Sharp & Dohme LLC
C07K14/135A61K39/155C12N7/00A61K2039/54A61K2039/55505A61K2039/55555C12N2760/18534
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Quick Facts
Patent No.
US 12,234,265
App. No.
18/068,867
Granted
Feb 25, 2025
Kind
B2
Abstract

The disclosure relates to stable RSV F proteins and immunogenic compositions containing the same, as well as methods of using the immunogenic compositions and compositions comprising the RSV F proteins.

Claims (14)

1. A recombinant respiratory syncytial virus (RSV) F protein trimer, comprising:

an amino acid sequence set forth in SEQ ID NOs: 26 or 27 and a pharmaceutically acceptable excipient.

2. An RSV immunogenic composition comprising the recombinant RSV F trimer of claim 1 , wherein the immunogenic composition formulated in an effective amount to produce an antigen-specific immune response directed against the recombinant RSV F trimer.

3. The immunogenic composition of claim 2 , wherein the immunogenic composition is formulated with an adjuvant.

4. The immunogenic composition of claim 3 , wherein the adjuvant is an aluminum adjuvant selected from amorphous aluminum hydroxyphosphate sulfate or an aqueous suspension of aluminum hydroxyphosphate.

5. The immunogenic composition of claim 3 formulated with a lipid nanoparticle comprising one or more cationic lipids and a poly(ethyleneglycol)-lipid (PEG lipid).

6. The immunogenic composition of claim 5 , wherein the cationic lipids are selected from the group consisting of (2S)-1-({6-[(3))-cholest-5-en-3-yloxy]hexyl}oxy)-N,N-dimethyl-3-[(9 Z)-octadec-9-en-1-yloxy]propan-2-amine; (13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine; and N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine; or a pharmaceutically acceptable salt thereof, or a stereoisomer of any of the foregoing.

7. The immunogenic composition of claim 5 , which comprises 30-75 mole % ionizable cationic lipid and 0.1-20 mole % PEG-lipid.

8. The immunogenic composition of claim 3 , wherein the adjuvant comprises one or more non-cationic lipids selected from a phospholipid, a phospholipid derivative, a fatty acid, a sterol, or a combination thereof, wherein the sterol is cholesterol, stigmasterol or stigmastanol;

wherein the phospholipid is selected from phosphatidylserine, 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), dilauroylphosphatidylcholine (DLPC), 1,2-dieicosenoyl-sn-glycero-3-phosphocholine, and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC);

wherein the PEG-lipid is 1,2-Dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG), PEG-disteryl glycerol (PEG-DSG), PEG-dipalmetoleyl, PEG-dioleyl, PEG-distearyl, PEG-diacylglycamide (PEG-DAG), PEG-dipalmitoyl phosphatidylethanolamine (PEG-DPPE), or PEG-1,2-dimyristyloxlpropyl-3-amine (PEG-c-DMA).

9. A method of producing an immune response to RSV F in a subject, the method comprising administering to the subject an effective amount of the RSV F trimer of claim 1 .

10. The RSV immunogenic composition of claim 2 , wherein the amino acid sequence is set forth in SEQ ID NO: 26.

11. The RSV immunogenic composition of claim 2 , wherein the amino acid sequence is set forth in SEQ ID NO: 27.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 21, 2022
From: ZHANG, LAN; FRIDMAN, ARTHUR; DURR, EBERHARD; BETT, ANDREW
To: MERCK SHARP & DOHME CORP.
Reel/Frame 062167/0734 →
MERGER Recorded Dec 21, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 062167/0792 →
Continuity (3)
Continuation 16964118
Provisional Application 62623184 · Jan 29, 2018
Related Publication 20230141153A1 · May 11, 2023
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