WO1992013951A1 - Production de serumalbumine humaine dans des cellules de levure methylotrophique - Google Patents

Production de serumalbumine humaine dans des cellules de levure methylotrophique Download PDF

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Publication number
WO1992013951A1
WO1992013951A1 PCT/US1992/001015 US9201015W WO9213951A1 WO 1992013951 A1 WO1992013951 A1 WO 1992013951A1 US 9201015 W US9201015 W US 9201015W WO 9213951 A1 WO9213951 A1 WO 9213951A1
Authority
WO
WIPO (PCT)
Prior art keywords
hsa
dna fragment
dna
pastoris
gene
Prior art date
Application number
PCT/US1992/001015
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English (en)
Inventor
Geneva Ruth Davis
Sally Ann Provow
Original Assignee
The Salk Institute Biotechnology/Industrial Associates, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Salk Institute Biotechnology/Industrial Associates, Inc. filed Critical The Salk Institute Biotechnology/Industrial Associates, Inc.
Publication of WO1992013951A1 publication Critical patent/WO1992013951A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76—Albumins
    • C07K14/765—Serum albumin, e.g. HSA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • C12N15/815—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts for yeasts other than Saccharomyces
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Definitions

  • HSA peptides can very efficiently be produced in, and secreted from, methylotrophic yeast such as P. pastoris, by transforming a methylotrophic yeast with, and preferably integrating into the yeast genome, at least one copy of a first DNA sequence operably encoding an HSA peptide, wherein said first DNA sequence is operably associated with a second DNA sequence encoding a secretion signal sequence selected from the S.
  • methylotrophic yeast such as P. pastoris
  • S. cerevisiae AMF pre-pro sequence including the proteolytic processing site: lys-arg, or
  • HSA peptides are produced by methylotrophic yeast cells containing in their genome at least one copy of a DNA sequence operably encoding HSA peptides operably associated with DNA encoding a secretion signal sequence selected from (1) the S. cerevisiae AMF pre-pro sequence (including the proteolytic processing site: lys-arg), or (2) the native HSA secretion signal sequence, both under the regulation of a promoter region of a methanol responsive gene of a methylotrophic yeast.
  • a DNA sequence operably encoding HSA peptides includes DNA sequences encoding the 585 amino acid form of HSA or any other "HSA peptide" as defined hereinabove.
  • the expression cassette is integrated into the host genome by any of the gene addition or replacement techniques known in the art. such as by one-step gene replacement [see e.g., Rothstein, Methods Enzvmol. 101- 202 (1983); Cregg et al., Bio/Technology 5 , 479 (1987)] or by two-step gene replacement methods [see e.g., Scherer and Davis, Proc. Natl. Acad. Sci. USA. 76, 4951 (1979)].
  • Single-stranded vector was prepared from positive plaques and used to transform JM103 cells. The resultant plaques were screened again and single positives were sequenced. One mutagenized clone, pHSA102, was selected and sequenced to verify the addition of EcoRI and BamHI restriction sites.
  • the mutagenized clone, pHSA105 was sequenced to verify the addition of the signal sequence and t._.a
  • Plasmid pBR322 ⁇ RIBGL was digested with a Sail and Bglll and the large fragment (approximately 2.97 kbp) was isolated.
  • Plasmid pBSAGISI which is described in European Patent Application Publication No. 0 226 752, was" digested completely with Bglll and Xho and an approximately 850 bp fragment from a region of the P. pastoris AOXl locus downstream from the AOXl gene transcription terminator (relative to the direction of transcription from the AOXl promoter) was isolated.
  • Plasmid pA0 ⁇ 04 has one Sall-Clal fragment of about 1.5 kbp and another of abut 5.0 kbp and a Clal-Clal fragment of 1.3 kbp; this indicates that the direction of transcription of the HIS4 gene in the plasmid is the same as the direction of transcription of the ampicillin resistance gene and opposite the direction of transcription from the AOXl promoter.
  • the orientation of the HIS4 gene in pA0804 is not critical to the function of the plasmid or of its derivatives with cDNA coding segments inserted at the EcoRI site between the AOXl promoter and terminator segments. Thus, a plasmid with the HIS4 gene in the orientation opposite that of the HIS4 gene in pA0804 would also be effective for use in accordance with the present invention. h. Construction of plasmid pA0815
  • Goat anti-HSA antibody was obtained from Atlantic Antibodies (Scarborough, ME) .
  • the horseradish peroxidase substrate, o-phenylenediamine (OPD) was purchased from Sigma Chemicals (St. Louis, MO) . All other chemicals were reagent grade and obtained from general suppliers. b. Method
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)

Abstract

On prépare de la sérumalbumine humaine, polypeptide naturelle à chaîne unique, en cultivant des transformants de levure méthylotrophique dont le génome renferme au moins une copie d'une séquence d'ADN qui code, de manière efficace, pour la sérumalbumine humaine (HSA) en association fonctionnelle avec une séquence d'ADN qui code pour une séquence de signaux de sécrétion choisie entre: (1) la séquence pré-pro du facteur de croisement alpha de S. cerevisiae (y compris le site de traitement protéolytique: lys-arg), ou (2) la séquence de signaux de sécrétion de la sérumalbumine humaine native, dans laquelle le fragment qui code pour celle-ci et la séquence de signaux de sécrétion sont régulés par une région de promotion d'un gène d'une levure méthylotrophique dans des conditions permettant l'expression desdites séquences d'ADN, ainsi que la sécrétion de l'HSA dans le milieu de culture. On décrit également de nouveaux fragments d'ADN et de nouvelles souches recombinantes de levure utiles à la mise en ÷uvre de cette invention.
PCT/US1992/001015 1991-02-04 1992-02-04 Production de serumalbumine humaine dans des cellules de levure methylotrophique WO1992013951A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65004091A 1991-02-04 1991-02-04
US650,040 1991-02-04

Publications (1)

Publication Number Publication Date
WO1992013951A1 true WO1992013951A1 (fr) 1992-08-20

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1992/001015 WO1992013951A1 (fr) 1991-02-04 1992-02-04 Production de serumalbumine humaine dans des cellules de levure methylotrophique

Country Status (1)

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WO (1) WO1992013951A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007356A1 (fr) * 1993-09-04 1995-03-16 Basf Aktiengesellschaft Procede de preparation de proteines par recombinaison dans la levure d'hansenula
WO1995035384A1 (fr) * 1994-06-17 1995-12-28 Novo Nordisk A/S Proteines comportant une extension a l'extremite n-terminale, exprimees par une levure
US5541112A (en) * 1991-04-01 1996-07-30 Salk Institute Biotechnology/Industrial Associates Genes which influence pichia proteolytic activity, and uses therefor
EP0736605A1 (fr) * 1994-10-25 1996-10-09 The Green Cross Corporation Procede de production de proteines
US5612198A (en) * 1990-09-04 1997-03-18 The Salk Institute Production of insulin-like growth factor-1 in methylotrophic yeast cells
EP0794256A2 (fr) * 1996-03-04 1997-09-10 Suntory Limited Procédé de culture de micro-organismes capable de métaboliser le méthanol
WO1999000518A1 (fr) * 1997-06-26 1999-01-07 Abbott Laboratories Membre de la famille du facteur de necrose tumorale (tnf) utile pour le traitement et le diagnostic de maladies
EP0947581A1 (fr) * 1996-08-08 1999-10-06 Yoshitomi Pharmaceutical Industries, Ltd. Milieu de culture et ses applications
EP1008651A2 (fr) * 1998-12-09 2000-06-14 Bioteknologisk Institut Séquences d'ADN modifiées, codantes pour l'hexose oxidase, et leur usage
US6500645B1 (en) 1994-06-17 2002-12-31 Novo Nordisk A/S N-terminally extended proteins expressed in yeast
US6867037B1 (en) * 1998-08-10 2005-03-15 Meiji Dairies Corp. High level secretory expression system of intact MK family protein
WO2015041718A1 (fr) * 2013-09-20 2015-03-26 The General Hospital Corporation Utilisations de protéines de type hormone anti-müllérienne (ham) modifiée pour le traitement de maladies neurodégénératives
US11084860B2 (en) 2013-03-12 2021-08-10 The General Hospital Corporation Modified Mullerian inhibiting substance (MIS) proteins and uses thereof for the treatment of diseases
US11130979B2 (en) 2017-06-20 2021-09-28 Albumedix Ltd Protein expression strains
US11135269B2 (en) 2013-12-11 2021-10-05 The General Hospital Corporation Use of mullerian inhibiting substance (MIS) proteins for contraception and ovarian reserve preservation
US11518793B2 (en) 2016-12-14 2022-12-06 The General Hospital Corporation Mullerian inhibiting substance (MIS) proteins for ovarian and uterine oncoprotection, and ovarian reserve and uterine preservation
EP4202035A1 (fr) 2021-12-22 2023-06-28 Gelita AG Expression améliorée de peptides

Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0263311A2 (fr) * 1986-09-22 1988-04-13 Phillips Petroleum Company Production du facteur de nécrose de tumeurs par des levures
AU1469988A (en) * 1985-10-25 1988-07-21 Research Corporation Technologies, Inc. Dna fragment
US4808537A (en) * 1984-10-30 1989-02-28 Phillips Petroleum Company Methanol inducible genes obtained from pichia and methods of use
US4812405A (en) * 1986-02-18 1989-03-14 Phillips Petroleum Company Double auxotrophic mutants of Pichia pastoris and methods for preparation
US4816564A (en) * 1986-01-31 1989-03-28 Merck & Co., Inc. Method for producing hepatitis B virus proteins in yeast
US4818700A (en) * 1985-10-25 1989-04-04 Phillips Petroleum Company Pichia pastoris argininosuccinate lyase gene and uses thereof
US4837148A (en) * 1984-10-30 1989-06-06 Phillips Petroleum Company Autonomous replication sequences for yeast strains of the genus pichia
US4855231A (en) * 1984-10-30 1989-08-08 Phillips Petroleum Company Regulatory region for heterologous gene expression in yeast
US4857467A (en) * 1986-07-23 1989-08-15 Phillips Petroleum Company Carbon and energy source markers for transformation of strains of the genes Pichia
EP0337492A1 (fr) * 1988-04-15 1989-10-18 Research Corporation Technologies, Inc. Purification de protéines de l'hépatite
GB2217332A (en) * 1988-04-11 1989-10-25 Phillips Petroleum Co Expression of salmon growth hormone in methylotrophic yeast of genus pichia
EP0339567A1 (fr) * 1988-04-25 1989-11-02 Phillips Petroleum Company Expression de protéine de PreS 2 de l'hépatite B en levures méthylotrophiques
US4879231A (en) * 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4885242A (en) * 1984-10-30 1989-12-05 Phillips Petroleum Company Genes from pichia histidine pathway and uses thereof
EP0344459A2 (fr) * 1988-04-25 1989-12-06 Research Corporation Technologies, Inc. Expression de l'albumine du sérum humain dans des levures méthylotrophigues
US4895800A (en) * 1985-11-26 1990-01-23 Phillips Petroleum Company Yeast production of hepatitis B surface antigen
WO1990002810A1 (fr) * 1988-09-09 1990-03-22 The Salk Institute Biotechnology/Industrial Associates, Inc. Production de polypeptides d'interleukine-2 dans des cellules de levure de pichia pastoris
WO1990003431A1 (fr) * 1988-09-26 1990-04-05 The Salk Institute Biotechnology/Industrial Associates, Inc. Fermentation de levure de recombinaison a alimentation melangee
US4929555A (en) * 1987-10-19 1990-05-29 Phillips Petroleum Company Pichia transformation
WO1990009434A1 (fr) * 1989-02-13 1990-08-23 The Salk Institute Biotechnology/Industrial Associates, Inc. Production de peroxyde dismutase dans des cellules de levure de pichia pastoris
WO1990010697A1 (fr) * 1989-03-15 1990-09-20 The Salk Institute Biotechnology/Industrial Associates, Inc. Production du facteur de croissance epidermique dans des cellules methylotrophiques de levure
US4963483A (en) * 1987-10-13 1990-10-16 Merck & Co., Inc. Method for producing hepatitis B virus proteins in yeast
US5011915A (en) * 1987-10-26 1991-04-30 Merck & Co., Inc. Process for purifying recombinant hepatitis antigens
US5026828A (en) * 1987-02-27 1991-06-25 Merck & Co., Inc. Method of purifying recombinant pres-1/S-2/S/S hepatitis B antigen from yeast
US5032516A (en) * 1985-10-25 1991-07-16 Phillips Petroleum Company Pichia pastoris alcohol oxidase II regulatory region
US5041236A (en) * 1989-10-27 1991-08-20 The Procter & Gamble Company Antimicrobial methods and compositions employing certain lysozymes and endoglycosidases
US5082778A (en) * 1986-06-03 1992-01-21 Unilever Patent Holdings B.V. Production of guar alpha-galactosidase by hosts transformed with recombinant dna. methods
US5102989A (en) * 1991-03-15 1992-04-07 Merck & Co., Inc. Method of stabilizing recombinant hepatitis B virus surface proteins from recombinant host cells

Patent Citations (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4837148A (en) * 1984-10-30 1989-06-06 Phillips Petroleum Company Autonomous replication sequences for yeast strains of the genus pichia
US4879231A (en) * 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4808537A (en) * 1984-10-30 1989-02-28 Phillips Petroleum Company Methanol inducible genes obtained from pichia and methods of use
US4885242A (en) * 1984-10-30 1989-12-05 Phillips Petroleum Company Genes from pichia histidine pathway and uses thereof
US4855231A (en) * 1984-10-30 1989-08-08 Phillips Petroleum Company Regulatory region for heterologous gene expression in yeast
US5032516A (en) * 1985-10-25 1991-07-16 Phillips Petroleum Company Pichia pastoris alcohol oxidase II regulatory region
US4818700A (en) * 1985-10-25 1989-04-04 Phillips Petroleum Company Pichia pastoris argininosuccinate lyase gene and uses thereof
US4882279A (en) * 1985-10-25 1989-11-21 Phillips Petroleum Company Site selective genomic modification of yeast of the genus pichia
AU1469988A (en) * 1985-10-25 1988-07-21 Research Corporation Technologies, Inc. Dna fragment
US4895800A (en) * 1985-11-26 1990-01-23 Phillips Petroleum Company Yeast production of hepatitis B surface antigen
US4816564A (en) * 1986-01-31 1989-03-28 Merck & Co., Inc. Method for producing hepatitis B virus proteins in yeast
US4812405A (en) * 1986-02-18 1989-03-14 Phillips Petroleum Company Double auxotrophic mutants of Pichia pastoris and methods for preparation
US5082778A (en) * 1986-06-03 1992-01-21 Unilever Patent Holdings B.V. Production of guar alpha-galactosidase by hosts transformed with recombinant dna. methods
US4857467A (en) * 1986-07-23 1989-08-15 Phillips Petroleum Company Carbon and energy source markers for transformation of strains of the genes Pichia
US5002876A (en) * 1986-09-22 1991-03-26 Phillips Petroleum Company Yeast production of human tumor necrosis factor
EP0263311A2 (fr) * 1986-09-22 1988-04-13 Phillips Petroleum Company Production du facteur de nécrose de tumeurs par des levures
US5026828A (en) * 1987-02-27 1991-06-25 Merck & Co., Inc. Method of purifying recombinant pres-1/S-2/S/S hepatitis B antigen from yeast
US4963483A (en) * 1987-10-13 1990-10-16 Merck & Co., Inc. Method for producing hepatitis B virus proteins in yeast
US4929555A (en) * 1987-10-19 1990-05-29 Phillips Petroleum Company Pichia transformation
US5011915A (en) * 1987-10-26 1991-04-30 Merck & Co., Inc. Process for purifying recombinant hepatitis antigens
GB2217332A (en) * 1988-04-11 1989-10-25 Phillips Petroleum Co Expression of salmon growth hormone in methylotrophic yeast of genus pichia
EP0337492A1 (fr) * 1988-04-15 1989-10-18 Research Corporation Technologies, Inc. Purification de protéines de l'hépatite
US5004688A (en) * 1988-04-15 1991-04-02 Phillips Petroleum Company Purification of hepatitis proteins
EP0339567A1 (fr) * 1988-04-25 1989-11-02 Phillips Petroleum Company Expression de protéine de PreS 2 de l'hépatite B en levures méthylotrophiques
EP0344459A2 (fr) * 1988-04-25 1989-12-06 Research Corporation Technologies, Inc. Expression de l'albumine du sérum humain dans des levures méthylotrophigues
WO1990002810A1 (fr) * 1988-09-09 1990-03-22 The Salk Institute Biotechnology/Industrial Associates, Inc. Production de polypeptides d'interleukine-2 dans des cellules de levure de pichia pastoris
WO1990003431A1 (fr) * 1988-09-26 1990-04-05 The Salk Institute Biotechnology/Industrial Associates, Inc. Fermentation de levure de recombinaison a alimentation melangee
WO1990009434A1 (fr) * 1989-02-13 1990-08-23 The Salk Institute Biotechnology/Industrial Associates, Inc. Production de peroxyde dismutase dans des cellules de levure de pichia pastoris
WO1990010697A1 (fr) * 1989-03-15 1990-09-20 The Salk Institute Biotechnology/Industrial Associates, Inc. Production du facteur de croissance epidermique dans des cellules methylotrophiques de levure
US5102789A (en) * 1989-03-15 1992-04-07 The Salk Institute Biotechnology/Industrial Associates, Inc. Production of epideramal growth factor in pichia pastoris yeast cells
US5041236A (en) * 1989-10-27 1991-08-20 The Procter & Gamble Company Antimicrobial methods and compositions employing certain lysozymes and endoglycosidases
US5102989A (en) * 1991-03-15 1992-04-07 Merck & Co., Inc. Method of stabilizing recombinant hepatitis B virus surface proteins from recombinant host cells

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BIO/TECHNOLOGY, Vol. 5, issued December 1987, TSCHOPP et al., "High-Level Secretion of Glycosylated Invertase in the Methylotrophic Yeast, Pichia Pastoris", pages 1305-1308. *
DEV. IND. MICROBIOL., Vol. 29, issued 1988, CREGG et al., "Development of the Methylotrophic Yeast, Pichia Pastoris, as a Host System for the Production of Foreign Proteins", Abstract No. 89-00614. *
GIM 90, Part I, issued 1990, THILL et al., "Positive and Negative Effects of Multiple Copy Intergrated Expression Vectors on Protein Expression in Pichia Pastoris", pages 477-490. *
ICSU SHORT REPORT, Vol. 8, issued 1988, CREGG et al., "High-Level Expression and Secretion of Heterologous Proteins From the Methylotrophic Yeast Pichia Pastoris", Abstract No. 89-11304. *
YEAST, Vol. 6, Special issue, s427, issued 1990, ROMANOS et al., "Expression of the Tetanus Toxin Fragment C in Saccharomyces", Abstract No. 90-13480. *
YEAST, Vol. 6, Special issue, s435, Issued 1990, HODGKINS et al., "Secretion of HSA From Hansenula Polymorpha". *
YEAST, Vol. 6, Special issue, s447, Issued 1990, STREEKRISHNA et al., "Expression of HSA in Pichia Pastoris". *

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5612198A (en) * 1990-09-04 1997-03-18 The Salk Institute Production of insulin-like growth factor-1 in methylotrophic yeast cells
US5831053A (en) * 1991-04-01 1998-11-03 Sibia Neurosciences, Inc. Genes which influence pichia proteolytic activity, and uses therefor
US5541112A (en) * 1991-04-01 1996-07-30 Salk Institute Biotechnology/Industrial Associates Genes which influence pichia proteolytic activity, and uses therefor
US5691166A (en) * 1991-04-01 1997-11-25 Sibia Neurosciences, Inc. Genes which influence pichia proteolytic activity, and uses therefor
US6051419A (en) * 1991-04-01 2000-04-18 Sibia Neurosciences, Inc. Genes which influence pichia proteolytic activity, and uses therefor
WO1995007356A1 (fr) * 1993-09-04 1995-03-16 Basf Aktiengesellschaft Procede de preparation de proteines par recombinaison dans la levure d'hansenula
US5741674A (en) * 1993-09-04 1998-04-21 Rhein Biotech Gesellschaft Fur Neue Biotechnologische Prozesse Und Produkte, Mbh Recombinant production of proteins in yeast
WO1995035384A1 (fr) * 1994-06-17 1995-12-28 Novo Nordisk A/S Proteines comportant une extension a l'extremite n-terminale, exprimees par une levure
US6500645B1 (en) 1994-06-17 2002-12-31 Novo Nordisk A/S N-terminally extended proteins expressed in yeast
US6068995A (en) * 1994-10-25 2000-05-30 Yoshitomi Pharmaceutical Industries, Ltd. Method for producing protein
EP0736605A4 (fr) * 1994-10-25 1998-04-01 Green Cross Corp Procede de production de proteines
EP0736605A1 (fr) * 1994-10-25 1996-10-09 The Green Cross Corporation Procede de production de proteines
EP0794256A2 (fr) * 1996-03-04 1997-09-10 Suntory Limited Procédé de culture de micro-organismes capable de métaboliser le méthanol
EP0794256A3 (fr) * 1996-03-04 1998-06-17 Suntory Limited Procédé de culture de micro-organismes capable de métaboliser le méthanol
US6171828B1 (en) * 1996-03-04 2001-01-09 Suntory Limited Method for culturing microorganisms having a methanol metabolic pathway
EP0947581A4 (fr) * 1996-08-08 2004-07-28 Mitsubishi Pharma Corp Milieu de culture et ses applications
EP0947581A1 (fr) * 1996-08-08 1999-10-06 Yoshitomi Pharmaceutical Industries, Ltd. Milieu de culture et ses applications
WO1999000518A1 (fr) * 1997-06-26 1999-01-07 Abbott Laboratories Membre de la famille du facteur de necrose tumorale (tnf) utile pour le traitement et le diagnostic de maladies
US6171787B1 (en) 1997-06-26 2001-01-09 Abbott Laboratories Member of the TNF family useful for treatment and diagnosis of disease
US6867037B1 (en) * 1998-08-10 2005-03-15 Meiji Dairies Corp. High level secretory expression system of intact MK family protein
EP1008651A2 (fr) * 1998-12-09 2000-06-14 Bioteknologisk Institut Séquences d'ADN modifiées, codantes pour l'hexose oxidase, et leur usage
EP1008651A3 (fr) * 1998-12-09 2000-06-21 Bioteknologisk Institut Séquences d'ADN modifiées, codantes pour l'hexose oxidase, et leur usage
US11084860B2 (en) 2013-03-12 2021-08-10 The General Hospital Corporation Modified Mullerian inhibiting substance (MIS) proteins and uses thereof for the treatment of diseases
WO2015041718A1 (fr) * 2013-09-20 2015-03-26 The General Hospital Corporation Utilisations de protéines de type hormone anti-müllérienne (ham) modifiée pour le traitement de maladies neurodégénératives
US10258668B2 (en) 2013-09-20 2019-04-16 The General Hospital Corporation Viral vectors for expressing a modified mullerian inhibiting substance (MIS) protein
US11135269B2 (en) 2013-12-11 2021-10-05 The General Hospital Corporation Use of mullerian inhibiting substance (MIS) proteins for contraception and ovarian reserve preservation
US11518793B2 (en) 2016-12-14 2022-12-06 The General Hospital Corporation Mullerian inhibiting substance (MIS) proteins for ovarian and uterine oncoprotection, and ovarian reserve and uterine preservation
US11130979B2 (en) 2017-06-20 2021-09-28 Albumedix Ltd Protein expression strains
US11396670B2 (en) 2017-06-20 2022-07-26 Albumedix Limited Protein expression strains
EP4202035A1 (fr) 2021-12-22 2023-06-28 Gelita AG Expression améliorée de peptides
WO2023118318A1 (fr) 2021-12-22 2023-06-29 Gelita Ag Expression améliorée de peptides

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Designated state(s): JP