# US 10,369,213 B2 · Thermostable respiratory synctial virus (RSV) vaccine compositions

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- Number: US 10,369,213 B2
- Document ID: US10369213B2
- Status: Granted
- Kind: B2
- Application number: 15/029,064
- Filed: 2014-10-13
- Published: 2016-09-01
- Granted: 2019-08-06
- Earliest claimed: 2013-10-16
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme Corp.
- Inventors: Akhilesh Bhambhani; Robert K. Evans; Lynne A. Isopi
- Web page: https://patentgrep.com/patent/US10369213B2

## CPC

- A61K 39/155: Paramyxoviridae, e.g. parainfluenza virus
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 39/12: Viral antigens
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61P 31/14: for RNA viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 2039/5254: {avirulent or attenuated}
- C12N 2760/18521: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/18534: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18551: Methods of production or purification of viral material
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Methods for improving the drying yield and stability of RSV vaccines comprising a highly thermolabile enveloped live virus and/or one or more RSV protein subunits, are described. Methods for rapid drying of RSV formulations containing between 17.5% and 60% w/w of a non-polymeric sugar and using either conduction or radiation dominant drying mechanisms, are disclosed. The disclosed methods provide for; 1) a dried RSV formulation with improved stability profile; 2) faster drying; and 3) integration of dried RSV into a primary device (such as dual chamber cartridges, foil-pouch devices etc.), pre- as well as post-drying.

## Claims

### Claim 1

A method for drying a vaccine composition comprising a live attenuated respiratory syncytial virus (RSV) comprising the steps of:
a) providing an aqueous composition in a primary container comprising the live attenuated RSV, a buffer, and from 17.5% w/w to 60% w/w of one or more non-polymeric sugars, wherein the pH of the buffer is between 6 and 8;
b) freezing the aqueous composition by aliquoting the aqueous composition on a chilled mold or surface having a temperature less than −100° C., thereby forming at least one frozen pellet comprising the buffer in frozen form; and
c) drying the aqueous composition by microwave vacuum drying.

### Claim 2 (depends on 1)

The method according to claim 1, characterized in that the sugar is selected from monomeric and/or dimeric sugar molecules.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the sugar is glucose, galactose, maltose, sucrose, trehalose, fructose, lactose, saccharose, mannitol, sorbitol, xylitol or a combination thereof.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the sugar is sucrose, trehalose or a combination thereof.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the amount of the sugar in the aqueous composition is chosen from the group that consists of the ranges 20-55% w/w, 20-50% w/w, 20-45% w/w, 25-45% w/w, 25-47.5% w/w, 25-40% w/w, 30-47.5% w/w, 30-40% w/w, 25-35% w/w or 27-30% w/w.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the buffer is selected from Tris, histidine, phosphate and combinations thereof.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the microwave vacuum drying comprises applying microwave radiation in a traveling wave format at a power in a range of between 0.5 and 8 KW/hr/Kg to the frozen pellet under a pressure below atmospheric pressure.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the pressure is a pressure in the range of 20 to 500 mTorr.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the pressure is a pressure in the range of 20 to 200 mTorr.