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Title (en) HUMAN METALLOTHIONEIN-II PROMOTER IN MAMMALIAN EXPRESSION SYSTEM Publication EP 0217822 B1 19930512 (EN) Application EP 86901613 A 19860211 Priority • US 70129685 A 19850213 • US 80167485 A 19851125 Abstract (en) [origin: WO8604920A1] An expression system for recombinant production of a desired protein comprises CHO cells transformed with a DNA sequence having the desired protein coding sequence under control of the human metallothionein-II promoter. The cells can be maintained on serum-free medium and induced in the presence of an induction mediator. In addition, the system may include an enhancer element and/or a resistance-conferring gene to provide increased levels of expression. The system can process genomic as well as intronless DNA, and is capable of producing proteins which have the same characteristics as those obtained from native sources. Human growth hormone which is indistinguishable from that produced by the pituitary has been thus produced. Expression systems containing genes encoding alveolar surfactant protein (ASH), apolipoproteins AI and AII (apoAI and apoAII), atrial natriuretic factor (ANF), erythropoetin (Epo), and renin are also contemplated. Inventor • KUSHNER, PETER, J. • COFER, CLAIRE, L. • FRIEDMAN, JEFFREY, S. • TALMADGE, KAREN, D. Applicant SCIOS NOVA INC. IPC 1-7 (main, further and additional classification) C07K 13/00; C07K 15/08; C12N 5/00 IPC 8 full level (invention and additional information) C07K 14/505 (2006.01); C07K 14/58 (2006.01); C07K 14/61 (2006.01); C07K 14/775 (2006.01); C07K 14/785 (2006.01); C12N 5/00 (2006.01); C12N 9/64 (2006.01); C12N 15/85 (2006.01) CPC (invention and additional information) C12N 9/6486 (2013.01); C07K 14/505 (2013.01); C07K 14/58 (2013.01); C07K 14/61 (2013.01); C07K 14/775 (2013.01); C07K 14/785 (2013.01); C12N 15/85 (2013.01); C12Y 304/23015 (2013.01) Citation (examination) • Karin et al, Proc. Natl. Acad. Sci. USA, Vol. 80, 1983, pages 4040-4044. • U.S., A, 4,446,235, Published 1 May 1984, Seeburg et al Designated contracting state (EPC) AT BE CH DE FR GB IT LI LU NL SE EPO simple patent family WO 8604920 A1 19860828; AT 89314 T 19930515; AU 5513586 A 19860910; AU 580145 B2 19890105; CA 1338829 C 19970107; DE 3688418 D1 19930617; DE 3688418 T2 19930826; DK 488386 A 19861215; DK 488386 D0 19861013; EP 0217822 A1 19870415; EP 0217822 A4 19890511; EP 0217822 B1 19930512; ES 551913 D0 19870801; ES 8707564 A1 19871016; US 5089397 A 19920218 INPADOC legal status 2007-12-31 [BE20] BE: PATENT EXPIRED - Owner name : *SCIOS NOVA INC. - Effective date : 20060211 2006-03-08 [REG GB PE20] PATENT EXPIRED AFTER TERMINATION OF 20 YEARS 2006-02-28 [REG CH PL] PATENT CEASED 2006-02-10 [PG25 GB] LAPSED IN A CONTRACTING STATE ANNOUNCED VIA POSTGRANT INFORM. FROM NAT. OFFICE TO EPO - Ref Country Code : GB - Free text : LAPSE BECAUSE OF EXPIRATION OF PROTECTION - Effective date : 20060210 2005-04-20 [PGFP BE] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : BE - Payment date : 20050420 - Year of fee payment : 20 2005-02-25 [PGFP IT] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : IT - Payment date : 20050225 - Year of fee payment : 20 2005-02-16 [PGFP CH] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : CH - Payment date : 20050216 - Year of fee payment : 20 2005-02-16 [PGFP LU] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : LU - Payment date : 20050216 - Year of fee payment : 20 2005-02-11 [PGFP AT] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : AT - Payment date : 20050211 - Year of fee payment : 20 2005-02-09 [PGFP GB] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : GB - Payment date : 20050209 - Year of fee payment : 20 2005-02-08 [PGFP FR] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : FR - Payment date : 20050208 - Year of fee payment : 20 2005-02-03 [PGFP DE] POSTGRANT: ANNUAL FEES PAID TO NATIONAL OFFICE - Ref Country Code : DE - Payment date : 20050203 - Year of fee payment : 20 2002-01-01 [REG GB IF02] EUROPEAN PATENT IN FORCE AS OF 2002-01-01 1994-05-06 [EPTA] LU: LAST PAID ANNUAL FEE 1994-04-15 [REG CH PFA] NAME/FIRM CHANGED - Free text : SCIOS NOVA INC. 1994-04-13 [RAP2] TRANSFER OF RIGHTS OF AN EP GRANTED PATENT - Owner name : SCIOS NOVA INC. 1993-10-18 [NLV1] NL: LAPSED OR ANNULLED DUE TO FAILURE TO FULFILL THE REQUIREMENTS OF ART. 29P AND 29M OF THE PATENTS ACT 1993-06-18 [ET] FR: TRANSLATION FILED 1993-06-17 [REF] CORRESPONDS TO: - Document : DE 3688418 19930617 1993-06-11 [ITF] IT: TRANSLATION FOR A EP PATENT FILED - Owner name : ST. DR. CAVATTONI ING. A. RAIMONDI 1993-05-12 [AK] DESIGNATED CONTRACTING STATES: - Kind Code of Ref Document : B1 - Designated State(s) : AT BE CH DE FR GB IT LI LU NL SE 1993-05-12 [PG25 NL] LAPSED IN A CONTRACTING STATE ANNOUNCED VIA POSTGRANT INFORM. FROM NAT. OFFICE TO EPO - Ref Country Code : NL - Effective date : 19930512 1993-05-12 [PG25 SE] LAPSED IN A CONTRACTING STATE ANNOUNCED VIA POSTGRANT INFORM. FROM NAT. OFFICE TO EPO - Ref Country Code : SE - Effective date : 19930512 1993-05-12 [REF] CORRESPONDS TO: - Document : AT 89314 T 19930515 1993-03-03 [RAP1] TRANSFER OF RIGHTS OF AN EP PUBLISHED APPLICATION - Owner name : SCIOS NOVA INC. 1990-10-24 [17Q] FIRST EXAMINATION REPORT - Effective date : 19900907 1989-11-15 [RAP1] TRANSFER OF RIGHTS OF AN EP PUBLISHED APPLICATION - Owner name : CALIFORNIA BIOTECHNOLOGY, INC. 1989-06-28 [A4] SUPPLEMENTARY SEARCH REPORT - Effective date : 19890511 1988-11-23 [RAP1] TRANSFER OF RIGHTS OF AN EP PUBLISHED APPLICATION - Owner name : BIOTECHNOLOGY RESEARCH ASSOCIATES, J.V. 1987-04-15 [17P] REQUEST FOR EXAMINATION FILED - Effective date : 19861018 1987-04-15 [AK] DESIGNATED CONTRACTING STATES: - Kind Code of Ref Document : A1 - Designated State(s) : AT BE CH DE FR GB IT LI LU NL SE