DrugPatentWatch Database Preview➤ Get the DrugPatentWatch Daily Briefing
« Back to Dashboard
Summary for Patent: 4,889,803
|Title:||Production of interferon gamma|
|Abstract:||Interferon .gamma. is produced in highly purified form (activity exceeding 10.sup.8 units/ml-day) by CHO cells cotransformed by a first plasmid bearing the genomic human interferon gene under the control of the SV40 early promoter, and a second plasmid bearing a DHFR gene under similar control. Methotrexate selection yielded a clone which was a particularly efficient producer. Production of interferon .gamma. may also be facilitated by a Harvey sarcoma virus enhancer sequence.|
|Inventor(s):||Revel; Michel (Rehovot, IL), Rubinstein; Menachem (Givat-Shmuel, IL), Mory; Yvez (Rehovot, IL)|
|Assignee:||Yeda Research & Development Co., Ltd. (Rehovot, IL)|
|Patent Claims:||1. A method of producing human gamma interferon which comprises (a) providing Chinese hamster ovary cells bearing a first DNA sequence which codes on expression for human gamma
interferon and includes at least one intron of the genomic human gamma interferon gene, said first DNA sequence being operably linked to a constitutive promoter functional in such cells, said promoter being a non-interferon promoter, said cells also
bearing a gene coding on expression for dihydrofolate reductase, said gene likewise being operably linked to a constitutive promoter functional in such cells; (b) cultivating the cells in a medium containing methotrexate at a level toxic to cells which
do not constitutively express dihydrofolate reductase, whereby the DHFR gene and the gamma interferon gene are co-amplified, and (c) cultivating such cells under conditions in which the cells constitutively express human gamma interferon in recoverable
2. The method of claim 1 wherein the first DNA sequence comprises the entire sequence of the genomic human gamma interferon gene.
3. The method of claim 2 wherein such cells produce human gamma interferon at a rate of at least about 190,000 units/ml-day.
4. The method of claim 2 wherein such cells produce human gamma interferon at a rate of at least about 260,000 units/ml-day.
5. The method of claim 2 wherein such cells produce human gamma interferon at a rate of at least about 800,000 units/ml-day.
6. The method of claim 2 wherein the cells are resistant to at least about 20 nM methotrexate and the DHFR and gamma interferon genes are co-amplified with at least about 20 nM methoxtrexate.
7. The method of claim 2 wherein the cells are resistant to at least about 50 nM methotrexate and the DHFR and gamma interferon genes are co-amplified with at least about 50 nM methotrexate.
8. The method of claim 2 wherein the cells are resistant to at least about 300 mM methotrexate and the DHFR and gamma interferon genes are co-amplified with at least about 300 nM methotrexate.
9. The method of claim 2 wherein after amplification with methotrexate, such cells contain at least about 50 times more human gamma interferon-specific mRNA than such cells contained prior to amplification.
10. The method of claim 2 wherein the constitutive promoter operably linked to the first DNA sequence is the SV40 early promoter or a derivative thereof which includes the 72 base pair repeat of the SV40 early promoter.
11. The method of claim 10, wherein the Harvey murine sarcoma virus enhancer sequence is operably associated with said first DNA sequence and enhances expression of the human gamma interferon encoded by that sequence.
12. Recombinant DNA molecules having the identifying characteristics of the vector pSVEgamma121.
13. Chinese hamster ovary cells cotransformed with pSVEgamma121 and a plasmid conferring a DHFR.sup.+ phenotype.
14. The method of claim 1 wherein the cells bear the plasmid pSVEgamma121.
15. The method of claim 2 wherein cells bearing the plasmid pSVEgamma121 are cultivated in step (b) in a medium containing at least 300 nM methotrexate, and the cells produce interferon gamma at a rate of at least about 400,000 units/ml-day.
Summary for Patent: ⤷ Free Forever Trial
|Foriegn Application Priority Data|
|Foreign Country||Foreign Patent Number||Foreign Patent Date|
|Israel||71691||Apr 27, 1984|
|Applicant||Tradename||Biologic Ingredient||Dosage Form||BLA||Number||Approval Date||Patent No.||Assignee||Estimated Patent Expiration||Status||Orphan||Source|
|Schering||INTRON A||interferon alfa-2b||VIAL||103132||001||1986-06-04||⤷ Free Forever Trial||Yeda Research & Development Co., Ltd. (Rehovot, IL)||2006-12-26||RX||search|
|Schering||INTRON A||interferon alfa-2b||VIAL||103132||002||1986-06-04||⤷ Free Forever Trial||Yeda Research & Development Co., Ltd. (Rehovot, IL)||2006-12-26||RX||search|
|Schering||INTRON A||interferon alfa-2b||VIAL||103132||003||1986-06-04||⤷ Free Forever Trial||Yeda Research & Development Co., Ltd. (Rehovot, IL)||2006-12-26||RX||search|
|>Applicant||>Tradename||>Biologic Ingredient||>Dosage Form||>BLA||>Number||>Approval Date||>Patent No.||>Assignee||>Estimated Patent Expiration||>Status||>Orphan||>Source|
|Country||Patent Number||Estimated Expiration|
|Australia||4175385||⤷ Free Forever Trial|
|Australia||587576||⤷ Free Forever Trial|
|Canada||1304704||⤷ Free Forever Trial|
|Germany||159714||⤷ Free Forever Trial|
|Germany||3586335||⤷ Free Forever Trial|
|European Patent Office||0159714||⤷ Free Forever Trial|
|>Country||>Patent Number||>Estimated Expiration|
Make Better Decisions: Try a trial or see plans & pricing
Serving leading biopharmaceutical companies globally:
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.