Claims for Patent: 4,211,843

Summary for Patent: 4,211,843

Title:	Strain of measles virus and process of producing the same
Abstract:	The disclosure describes a process for the production of an attenuated strain of measles virus effective for the production of an attenuated measles virus vaccine. The starting material is an Edmonston strain of measles virus which has undergone a plurality of culture passages in various culture media. A sample of the last culture passage is taken and a plurality of culture passages of the sample is effected in primary cultures of fibroblasts of chicken embryos. A sample from the last culture passage is inoculated and a culture passage is effected in a primary culture of fibroblasts of chicken embryos thereby obtaining clones of virus. Clones of measles virus obtained in the last culture passage are isolated and one selects those which are thermosensitive at a temperature between about 32.degree. C. and 37.degree. C. Among the thermosensitive clones which have been selected, another selection is made of the ones with moderate cytopathic effect, and finally one isolates from the latest selection, the one which shows highest seroconversion on monkeys, thus producing an attenuated strain of measles virus.
Inventor(s):	Dubreuil, deceased; Robert (late of Montreal, CA), Ast; Orvo (Pierrefonds, CA), Pavilanis; Vytautas (Westmount, CA)
Assignee:	L\'Institut Armand-Frappier (Laval, CA)
Application Number:	05/856,202
Patent Claims:	1. A process for the production of an attenuated strain of measles virus effective for the production of an attenuated measles virus vaccine, which comprises: selecting an Edmonston strain of measles virus which has undergone a plurality of culture passages in various culture media, and taking a sample of the last culture passage; effecting a plurality of culture passages of said sample in primary cultures of fibroblasts of chicken embryos; inoculating a sample from the last culture passage and effecting a culture passage thereof in a primary culture of fibroblasts of chicken embryos thereby obtaining clones of said virus; isolating clones of measles virus obtained in the preceding step, and selecting those which are thermosensitive at a temperature between about 32.degree. C. and 37.degree. C.; among the thermosensitive clones which have been selected, making another selection of the ones with moderate cytopathogenic effect; and finally isolating from the latest selection, the one which shows highest seroconversion on monkeys, thus producing an attenuated strain of measles virus. 2. A process according to claim 1, wherein said Edmonston strain has undergone twenty-four (24) culture passages in human kidney cells, twenty-eight (28) culture passages in human amniotic cells, six (6) culture passages in the amniotic sac of embryonated eggs and thirteen (13) culture passages in cells of chicken embryos, followed by eleven (11) culture passages in cells of chicken embryos. 3. A process according to claim 2, which comprises: effecting a first culture passage of said virus sample in a primary culture of fibroblasts of chicken embryos maintained at 33.degree. C., followed by a second culture passage in a primary culture of fibroblasts of chicken embryos at 33.degree. C. 4. A process according to claim 1, wherein clones of measles virus are isolated by inoculating the strain derived from the last culture passage in a primary culture of fibroblasts of chicken embryos, in petri dishes kept in an incubator in a 5% CO.sub.2 enriched atmosphere during about 2 hours at about 32.degree. C., after which the cultures are drained and washed with phosphate buffer saline and a culture medium is added and incubation is allowed to take place for four to six days at 32.degree. C., after which the liquid medium is replaced by a methyl cellulose medium and the cultures are again incubated at 32.degree. C. for a period of about 3 to 4 days, until plaques appear and different clones can be separated. 5. A process according to claim 4, wherein forty-seven (47) samples of virus are selected from the separated clones, and are incubated for an incubation period of about 14 days, after which seven are retained which are thermosensitive at a temperature between about 32.degree. C. and 37.degree. C., each of the seven samples selected is treated for the purpose of isolating clones by producing plaques, each plaque is again isolated in order to select three clones with moderate cytopathic effect, and finally, of the three clones selected, the one which has highest seroconversion on monkeys is separated and is frozen at a temperature of -75.degree. C. 6. A process according to claim 5 which comprises suspending the attenuated measles virus in a harvest medium and adding a stabilizer comprising dextran, monosodium glutamate, d-sorbitol and normal serum albumin (human). 7. A process according to claim 6, wherein the amount of stabilizer in the composition is the following: 8. A measles vaccine whenever produced by the process of claim 1, 5 or 6. 9. A measles vaccine whenever produced by the process of claim 7 or 8.

Details for Patent 4,211,843

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2040-01-28
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2040-01-28
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2040-01-28
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2040-01-28
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2040-01-28
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	06/11/2003		2040-01-28
Csl Behring Llc	ALBUMINAR, ALBUMINAR-20, ALBUMINAR-25, ALBUMINAR-5	albumin (human)	Injection	103955	03/17/2000		2040-01-28