Process for producing influenza vaccine

Patent metadata

Field	Value
Publication number	US-9636394-B2
Application number	US-201013503859-A
Country	US
Kind code	B2
Filing date	Oct 25, 2010
Priority date	Oct 27, 2009
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

A process for producing a split influenza virus preparation or subunit influenza preparation comprising the steps of: (i) providing a whole virus preparation; (ii) splitting the whole virus preparation in the presence of a first detergent; (iii) adding t-octylphenoxypolyethoxyethanol (TRITON X-100™) to the resulting split virus preparation; and (iv) filtering the split virus preparation.

First claim

We claim:

1. A process for producing a split monovalent influenza virus preparation or subunit influenza preparation comprising the steps of: (i) providing a whole virus preparation; (ii) splitting the whole virus preparation in the presence of a first detergent, wherein the first detergent is not t-octylphenoxypolyethoxyethanol, thereby producing a split virus preparation; (iii) adding t-octylphenoxypolyethoxyethanol to the split virus preparation, wherein t-octylphenoxypolyethoxyethanol is present in an amount of 0.1-0.4% (w/v); and (iv) filtering the split virus preparation in the presence of t-octylphenoxypolyethoxyethanol.

2. The process of claim 1 wherein the filtering step is performed using one or more filter membranes, wherein at least one filter membrane is sterile grade.

3. The process of claim 1 wherein t-octylphenoxypolyethoxyethanol is present in an amount sufficient to increase HA yield in the filtered split virus preparation as compared to HA yield from a process in which t-octylphenoxypolyethoxyethanol is not added to the split virus preparation.

4. The process of claim 1 wherein t-octylphenoxypolyethoxyethanol is present in an amount of 0.25% w/v.

5. The process of claim 1 further comprising the step of inactivating the split influenza virus preparation.

6. The process of claim 5 wherein the inactivation step is performed after step (iii) and before step (iv).

7. The process of claim 5 wherein the inactivation step is performed after step (iv).

8. The process of claim 1 comprising a second step of filtering the split influenza virus preparation in addition to the filtration step of step (iv).

9. The process of claim 1 wherein the first detergent is selected from the group consisting of: cetyl trimethyl ammonium bromide (CTAB), laurylsulfate, taurodeoxycholate, polyoxyethylene sorbitan monooleate and sodium deoxycholate.

10. The process of claim 1 further comprising the step of ultracentrifuging the split influenza virus preparation.

11. The process of claim 1 further comprising the step of clarifying the whole virus preparation.

12. The process of claim 1 further comprising the step of ultrafiltering the whole virus preparation.

13. The process of claim 1 wherein the split influenza virus preparation is derived from a pandemic strain.

14. The process of claim 1 wherein the split influenza virus preparation is derived from an interpandemic strain.

15. The process of claim 1 wherein the first detergent is sodium deoxycholate.

16. The process of claim 1 wherein steps (iii) and (iv) are performed simultaneously.

17. The process of claim 1 wherein the HA concentration in the filtered split influenza virus preparation or subunit preparation is more than 50% greater than the HA concentration from a process in which t-octylphenoxypolyethoxyethanol is not added to the split virus preparation prior to filtration.

18. The process of claim 1 wherein the HA concentration in the filtered split influenza virus preparation or subunit preparation is more than 50% greater than the HA concentration from a process in which polyoxyethylene sorbitan monooleate is added to step (ii) and wherein t-octylphenoxypolyethoxyethanol is not added to the split virus preparation prior to filtration.

Assignees

• D'Hondt Erik Jozef
• Engelmann Hans Bernd
• Glaxosmithkline Biologicals Sa
• Glaxosmithkline Biologicals Niederlassung Der Smithkline Beecham Pharma Gmbh & Co Kg

Inventors

• D'Hondt Erik Jozef
• Engelmann Hans Bernd

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C12N2760/16134

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

• C12N2760/16151

  Methods of production or purification of viral material · CPC title