Claims for Patent: 4,664,912

Summary for Patent: 4,664,912

Title:	Process for the large scale production of rabies vaccine
Abstract:	In the large-scale production of rabies vaccine a cell stock comprising a VERO cell strain and a liquid nutritive medium containing serum and microcarriers suspended therein is successively passed into biogenerators of increasing volume. The last of the passages is carried out in a biogenerator having a volume of at least 150 liters. The liquid nutritive medium is drawn off at the end of the final passage and replaced with a serum-free liquid nutritive medium. The cell stock is inoculated in the last passage biogenerator with virus which is allowed to develop. The virus is then cultured, withdrawn and filtered. The filtered liquid suspension is then ultrafiltered, with inactivated beta-propiolactone and purified by zonal centrifugation or chromatography.
Inventor(s):	Wiktor; Tadeusz J. (Wynnewood, PA), Fanget; Bernard J. (Fleurieux sur l\'Arbresle 69 210, FR), Fournier; Pierre (69 005 Lyon, FR), Montagnon; Bernard J. (69 210 L\'Arbresle, FR)
Assignee:
Application Number:	06/656,762
Patent Claims:	1. A process for the large-scale production of rabies vaccine comprising (a) successively passing into biogenerators of increasing volume a cell stock comprising a VERO cell strain and a liquid nutritive medium containing serum, said liquid nutritive medium having suspended therein microcarriers present in an amount ranging from 1 to 10 grams per liter of said liquid nutritive medium, each such passage being carried out with stirring at a rate not greater than 40 rpm and for a period of time ranging from 5 to 8 days, the last of said passages being carried out in a biogenerator having a volume of at least 150 liters, (b) drawing off said liquid nutritive medium at the end of the final passage and replacing said liquid nutritive medium with a serum-free liquid nutritive medium, (c) inoculating said cell stock in the last passage biogenerator with virus and allowing the virus to develop at a temperature between 35.degree.-37.degree. C. at a pH of about 7.4 to 7.8 and at a partial oxygen pressure of about 10-50 percent while stirring at a rate not greater than 40 rpm, (d) culturing the said virus for a period of at least 5 days, (e) withdrawing the liquid suspension of cultured virus, (f) filtering the withdrawn liquid suspension, (g) ultrafiltering the filtered liquid suspension so as to concentrate the same at least 100 times, (h) inactivating the concentrated suspension with beta-propiolactone and (i) purifying the inactivated suspension by zonal centrifugation or chromatography. 2. The process of claim 1 wherein the liquid nutritive medium withdrawn in step (b) is contacted with a dilute solution of purified protease so as to separate the cells from the microcarriers. 3. The process of claim 1 wherein said cell stock is inoculated in step (c) with a Pitman-Moore PM 1.503-3 M rabies virus strain. 4. The process of claim 1 wherein the molecular separating power of the ultrafiltration in step (g) is at a molecular point of 10,000 to one million.

Details for Patent 4,664,912

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bavarian Nordic A/s	RABAVERT	rabies vaccine	For Injection	103334	10/20/1997		2040-01-28
Sanofi Pasteur Sa	IMOVAX RABIES	rabies vaccine	For Injection	103931	02/04/2000		2040-01-28