KR930701601A - O-글리코실화 ifn-알파 - Google Patents

O-글리코실화 ifn-알파

Info

Publication number
KR930701601A
KR930701601A KR1019930700049A KR930700049A KR930701601A KR 930701601 A KR930701601 A KR 930701601A KR 1019930700049 A KR1019930700049 A KR 1019930700049A KR 930700049 A KR930700049 A KR 930700049A KR 930701601 A KR930701601 A KR 930701601A
Authority
KR
South Korea
Prior art keywords
ifn
interferon alpha
glycosylated
pad
protein
Prior art date
Application number
KR1019930700049A
Other languages
English (en)
Inventor
귄터 아돌프
히믈러 아돌프
요안 아호른 호르스트
칼스너 인게
마우러-포기 인그리드
Original Assignee
디이터 라우디엔, 루돌프 호프만
베링거 인겔하임 인터내셔날 게엠베하
루돌프 호프만
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
Priority claimed from DE19904021917 external-priority patent/DE4021917A1/de
Priority claimed from DE19904035877 external-priority patent/DE4035877A1/de
Application filed by 디이터 라우디엔, 루돌프 호프만, 베링거 인겔하임 인터내셔날 게엠베하, 루돌프 호프만 filed Critical 디이터 라우디엔, 루돌프 호프만
Publication of KR930701601A publication Critical patent/KR930701601A/ko

Links

Classifications

    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/56—IFN-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Plant Pathology (AREA)
  • Communicable Diseases (AREA)
  • Toxicology (AREA)
  • Virology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Saccharide Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

본 발명은 0-글리코실화 IFN-α, 그의 제조방법 및 약제학적 조성물로서 0-글리코실화 단백질의 용도에 관한 것이다.

Description

O-글리코실화 IFN-알파
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 플라스미드 pCMV+SV40의 작제, 제2도는 플라스미드 pAD-CMV10A의 작제, 제3도는 플라스미드pAD-CMV15의 작제.

Claims (16)

  1. O-글리코실화되고, 필수적으로 IFN-α2의 생물학적 및/또는 면역학적 특성을 가지며, 바람직하게는 O-글리코실화 인체 IFN-α2a, IFN-α2b 또는 IFN-α2c임을 특징으로 하는 인터페론 알파.
  2. 제1항에 있어서, 트레오닌-106(THR-106)이 O-글리코실화됨을 특징으로 하는 인터페론 알파.
  3. 제1항 또는 제2항에 있어서, 올리고당이 바람직하게는 중성 이당류 Gal-GalNAc, 그의 모노-또는 디시알릴화 변이체, 또는 중성 사당류 Gal-(Gal-GlcNAc)-GalNAc임을 특징으로 하는 인터페론 알파.
  4. a) 백혈구, 바람직하게는 인체 백혈구를 바이러스로 유도하고, b) 유도된 인터페론 알파를, pH가 8.0을 넘지않도록 하면서 온화한 단백질-침전/단백질 용해 단계를 수행해서 정재하고 ["칸텔(Cantell)" 방법], c)a) 또는 a) 및 b)에 따라 수득된 인터페론 혼합물을 안티-IFN-α2 모노클로날 항체를 갖는 면역친화성 칼럼에 결합시키고, d) 결합된 단백질을 적당한 방법으로 용출시키고, e) 용출된 단백질을 수거하여 임의로 면역친화성 칼럼을 거쳐 수회 정제함을 특징으로 하여, 제1항에 따르는 인터페론 알파를 제조하는 방법.
  5. 제4항에 있어서, 안티-IFN-α2 모노클로날 항체로서 EBI-10 또는 그의 동족체를 사용함을 특징으로 하는 방법.
  6. 제4항에 있어서, 단계(e)다음에 추가의 크로마토그래피 정제를 더 수행함을 특징으로 하는 인터페론 알파의 제조방법.
  7. a) IFN-α2를 코드화하는 DNA를 다세포 유기체 세포의 형질 감염에 적합한 발현 플라스미드에 도입시키고, b) 이렇게 하여 수득된 발현 플라스미드로 다세포 유기체 세포, 바람직하게는 척추동물 세포를 형질감염시키고, c) 형질감염된 유기체를 적당한 배지에서 배양하여, d) 세포 상등액을 수거하고, e) O-글리코실화 IFN-α를 분리하여 그 자체가 공지된 방법으로 정제함을 특징으로 하여, 제1항에 따르는 인터페론 알파를 제조하는 방법.
  8. 제7항에 있어서, 단계 a)에서 사용된 발현 플라스미드가 pAD-CMV13, 15 또는 19, 바람직하게는 pAD-CMV19이며, 단계 a)에서 삽입되는 DNA가 필수적으로 IFN-α2의 생물학적 및/또는 면역학적 특성을 갖는 단백질, 바람직하게는 인체 IFN-α2a, IFN-α2b 또는 IFN-α2c, 더욱 특히는 인체 IFN-α2c를 코드화함을 특징으로 하는 방법.
  9. 제7항 또는 8항에 있어서, 사용된 발현 플라스미드가 pAD19B-IFN임을 특징으로 하는 방법.
  10. 제7항, 8항 또는 9항에 있어서, 다세포 유기체 세포로서 CHO세포가 사용됨을 특징으로 하는 방법.
  11. pAD-CMV13, pAD-CMV 15 또는 pAD-CMV 19임을 특징으로 하는 다세포 유기체의 형질감염을 위한 발현 플라스미드.
  12. 제4항 내지 10항중의 어느 하나에 제조될 수 있는 O-글리코실화 인터페론 알파.
  13. 약제학적 조성물로서 사용하기 위한, 제1항 내지 3항중의 어느 하나 또는 제12항에 따르는 인터페론 알파.
  14. 제1항 내지 3항중의 어느 하나 또는 제12항에 따르는 인터페론 알파를 함유하는 바이러스성 또는 종양성 질환 치료제.
  15. 제14항에 있어서, 적어도 2가지의 O-글리코실화 단백질 IFN-α2a, IFN-α2b 또는 IFN-α2c의 혼합물로 구성됨을 특징으로 하는 제제.
  16. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019930700049A 1990-07-10 1991-07-06 O-글리코실화 ifn-알파 KR930701601A (ko)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE19904021917 DE4021917A1 (de) 1990-07-10 1990-07-10 Glykosyliertes ifnalpha
DEP4021917.8 1990-07-10
DEP4035877.1 1990-11-12
DE19904035877 DE4035877A1 (de) 1990-11-12 1990-11-12 O-glycosyliertes ifn-alfa2
PCT/EP1991/001266 WO1992001055A1 (de) 1990-07-10 1991-07-06 O-glycosyliertes ifn-alpha

Publications (1)

Publication Number Publication Date
KR930701601A true KR930701601A (ko) 1993-06-12

Family

ID=25894855

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019930700049A KR930701601A (ko) 1990-07-10 1991-07-06 O-글리코실화 ifn-알파

Country Status (16)

Country Link
EP (1) EP0538300B1 (ko)
JP (1) JPH06502987A (ko)
KR (1) KR930701601A (ko)
AT (1) ATE104348T1 (ko)
AU (1) AU650893B2 (ko)
CA (1) CA2084514A1 (ko)
CZ (1) CZ386392A3 (ko)
DE (1) DE59101397D1 (ko)
DK (1) DK0538300T3 (ko)
ES (1) ES2063515T3 (ko)
FI (1) FI930058A0 (ko)
HU (1) HUT65846A (ko)
NO (1) NO930059D0 (ko)
PL (1) PL297610A1 (ko)
SK (1) SK386392A3 (ko)
WO (1) WO1992001055A1 (ko)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ245771A (en) * 1992-02-07 1994-08-26 New England Medical Center Inc Mammalian gastrin/cholecystokinin b (cck-b) receptor and antagonists
US5541071A (en) * 1992-02-07 1996-07-30 New England Medical Center Hospitals, Inc. Assay for identifying antagonists of gastrin and CCK-B receptors
EP0626448A3 (de) * 1993-05-26 1998-01-14 BOEHRINGER INGELHEIM INTERNATIONAL GmbH Verfahren zur Herstellung und Reinigung von alpha-Interferon
WO1996013608A2 (en) * 1994-10-28 1996-05-09 Innogenetics N.V. Polynucleic acid sequences for use in the detection and differentiation of prokaryotic organisms
ATE253122T1 (de) * 1996-08-14 2003-11-15 Us Gov Health & Human Serv Vektor für polynukleotidimpfstoffe
GB9904695D0 (en) * 1999-03-01 1999-04-21 Imp Cancer Res Tech Peptide
CA2405709A1 (en) 2000-04-12 2001-10-25 Human Genome Sciences, Inc. Albumin fusion proteins
US7214660B2 (en) 2001-10-10 2007-05-08 Neose Technologies, Inc. Erythropoietin: remodeling and glycoconjugation of erythropoietin
US7173003B2 (en) 2001-10-10 2007-02-06 Neose Technologies, Inc. Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
EP2298354B1 (en) * 2001-10-10 2014-03-19 ratiopharm GmbH Remodelling and glycoconjugation of interferon-beta
CA2471363C (en) 2001-12-21 2014-02-11 Human Genome Sciences, Inc. Albumin fusion proteins
CA2519092C (en) 2003-03-14 2014-08-05 Neose Technologies, Inc. Branched water-soluble polymers and their conjugates
PL1615945T3 (pl) 2003-04-09 2012-03-30 Ratiopharm Gmbh Sposoby glikopegylacji i białka/peptydy wytwarzane tymi sposobami
US8791070B2 (en) 2003-04-09 2014-07-29 Novo Nordisk A/S Glycopegylated factor IX
US9005625B2 (en) 2003-07-25 2015-04-14 Novo Nordisk A/S Antibody toxin conjugates
US8633157B2 (en) 2003-11-24 2014-01-21 Novo Nordisk A/S Glycopegylated erythropoietin
US20080305992A1 (en) 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
US20060040856A1 (en) 2003-12-03 2006-02-23 Neose Technologies, Inc. Glycopegylated factor IX
KR101439880B1 (ko) 2004-01-08 2014-09-12 라티오팜 게엠베하 펩티드의 오-결합형 글리코실화
EP1771066A2 (en) 2004-07-13 2007-04-11 Neose Technologies, Inc. Branched peg remodeling and glycosylation of glucagon-like peptide-1 glp-1
EP1799249A2 (en) 2004-09-10 2007-06-27 Neose Technologies, Inc. Glycopegylated interferon alpha
WO2006050247A2 (en) 2004-10-29 2006-05-11 Neose Technologies, Inc. Remodeling and glycopegylation of fibroblast growth factor (fgf)
NZ556436A (en) 2005-01-10 2010-11-26 Biogenerix Ag Glycopegylated granulocyte colony stimulating factor
EP2386571B1 (en) 2005-04-08 2016-06-01 ratiopharm GmbH Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants
JP5216580B2 (ja) 2005-05-25 2013-06-19 ノヴォ ノルディスク アー／エス グリコペグ化第ｉｘ因子
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
US20090048440A1 (en) 2005-11-03 2009-02-19 Neose Technologies, Inc. Nucleotide Sugar Purification Using Membranes
AR078117A1 (es) 2006-06-20 2011-10-19 Protech Pharma S A Una muteina recombinante del interferon alfa humano glicosilado, un gen que codifica para dicha muteina, un metodo de produccion de dicho gen, un metodo para obtener una celula eucariota productora de dicha muteina, un metodo para producir dicha muteina, un procedimiento para purificar dicha muteina
ES2516694T3 (es) 2006-07-21 2014-10-31 Ratiopharm Gmbh Glicosilación de péptidos a través de secuencias de glicosilación con unión en O
WO2008057683A2 (en) 2006-10-03 2008-05-15 Novo Nordisk A/S Methods for the purification of polypeptide conjugates
BRPI0809670A8 (pt) 2007-04-03 2018-12-18 Biogenerix Ag métodos para aumentar a produção de célula tronco, para aumentar o número de granulócitos em um indivíduo, para prevenir, tratar e aliviar a mielossupressão que resulta de uma terapia contra o câncer, para tratar uma condição em um indivíduo, para tratar neutropenia e trombocitopenia em um mamífero, para expandir células tronco hematopoiéticas em cultura, para aumentar a hematopoiese em um indivíduo, para aumentar o número de célulars progenitoras hematopoiéticas em um indivíduo, e para fornecer enxerto estável da medula óssea, e, forma de dosagem oral.
CN101778859B (zh) 2007-06-12 2014-03-26 诺和诺德公司 改良的用于生产核苷酸糖的方法
US8207112B2 (en) 2007-08-29 2012-06-26 Biogenerix Ag Liquid formulation of G-CSF conjugate
CN103497246B (zh) 2008-02-27 2016-08-10 诺沃—诺迪斯克有限公司 缀合的因子viii分子
WO2014102103A2 (en) 2012-12-31 2014-07-03 Boehringer Ingelheim International Gmbh Heterologous intron within a signal peptide
WO2014102101A1 (en) 2012-12-31 2014-07-03 Boehringer Ingelheim International Gmbh Novel intron sequences
RU2610173C1 (ru) * 2016-03-30 2017-02-08 Илья Александрович Марков Рекомбинантная плазмида pFM-IFN-17, обеспечивающая экспрессию интерферона альфа-2b человека, рекомбинантная плазмида pFM-АР, обеспечивающая экспрессию фермента метионинаминопептидазы E. coli, биплазмидный штамм Escherichia coli FM-IFN-АР (pFM-IFN-17, pFM-АР) - продуцент (Met-) рекомбинантного интерферона альфа-2b человека

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN150740B (ko) * 1978-11-24 1982-12-04 Hoffmann La Roche
WO1983000693A1 (en) * 1981-08-14 1983-03-03 Berg, Kurt, Frimann SUBJECTS RELATING TO HUMAN INTEFERON-'alpha' SUBTYPE PROTEINS AND CORRESPONDING ANTIBODIES
DE3306060A1 (de) * 1983-02-22 1984-08-23 Boehringer Ingelheim International GmbH, 6507 Ingelheim Neue immunglobulin-produzierende hybridzellinien, deren verwendung und verfahren zu deren herstellung
FR2560212B1 (fr) * 1984-02-24 1989-12-29 Unicet Anticorps monoclonaux contre l'interferon a2 et hybridomes produisant de tels anticorps

Also Published As

Publication number Publication date
AU650893B2 (en) 1994-07-07
CA2084514A1 (en) 1992-01-11
DE59101397D1 (de) 1994-05-19
DK0538300T3 (da) 1994-10-10
HUT65846A (en) 1994-07-28
ES2063515T3 (es) 1995-01-01
WO1992001055A1 (de) 1992-01-23
FI930058A (fi) 1993-01-08
EP0538300B1 (de) 1994-04-13
AU8208291A (en) 1992-02-04
NO930059L (no) 1993-01-08
ATE104348T1 (de) 1994-04-15
SK386392A3 (en) 1994-08-10
JPH06502987A (ja) 1994-04-07
NO930059D0 (no) 1993-01-08
HU9300036D0 (en) 1993-04-28
EP0538300A1 (de) 1993-04-28
CZ386392A3 (en) 1993-08-11
PL297610A1 (ko) 1992-07-13
FI930058A0 (fi) 1993-01-08

Similar Documents

Publication Publication Date Title
KR930701601A (ko) O-글리코실화 ifn-알파
Pestka The human interferon α species and receptors
Pestka The interferons: 50 years after their discovery, there is much more to learn
Stern et al. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells.
Conrad et al. Effect of B cell stimulatory factor-1 (interleukin 4) on Fc epsilon and Fc gamma receptor expression on murine B lymphocytes and B cell lines.
Robb et al. T cell growth factor receptors. Quantitation, specificity, and biological relevance
KR100223255B1 (ko) 개량된 알파 인터페론 조성물 및 인간 말초혈 백혈구로 부터의 제조 방법
US5723121A (en) Sugar modified interferon
DE69520088T3 (de) Interferon-gamma-induzierendes Polypeptid monoklonal Antikörper, und Zusammensetzung für Interferon-gamma gebunden Krankheiten
ES2353006T3 (es) Fármaco de il-7, composición que comprende il-7, preparación y usos de los mismos.
EP0240975B1 (en) Human gamma interferon-specific receptor protein, antibody against said protein, methods for obtaining said protein and said antibody and compositions containing said protein and antibody
Ziegler-Heitbrock et al. Tumor necrosis factor as effector molecule in monocyte mediated cytotoxicity
IL87621A0 (en) Conjugates of cytokines with immunoglobulins,their preparation and pharmaceutical compositions containing them
Schreiber Identification of gamma-interferon as a murine macrophage-activating factor for tumor cytotoxicity
EP1066050B2 (de) Verwendung von hsp70 protein
DK0537166T3 (da) Vandopløselige polypeptider med stor affinitet for alfa og beta-interferon
US6319691B1 (en) Fusion proteins comprising IFN-alpha2b and TM-alpha1
KR920012440A (ko) 인간 인터류킨-5 수용체
BR9707142A (pt) Polinucleotìdeo purificado, dna, vetor, célula hospedeira, linhagem celular de hibridoma, anticorpo monoclonal, processos para produzir exodus, para aumentar a resistência à infecção por vìrus de imonudeficiência humana (hiv), para tratamento de infecção por vìrus de imonodeficiência humana (hiv), para proteção de células progenitoras de medula óssea contra os efeitos citotóxicos e para tratamento de doenças mieloproliferativas, e, uso de produto de proteina de exodus.
Havell Isolation of a subspecies of murine interferon antigenically related to human leukocyte interferon
DE3515336C2 (de) Verfahren zur Herstellung und Reinigung von â-Interferon
EP0553667B1 (en) Soluble LDL receptor, its production and use
Yodoi et al. Formation of IgE-binding factors by rat T lymphocytes. I. Induction of IgE-binding factors by poly I: C and interferon.
US5427781A (en) Method of activating T cells with lymphokine SAF
WO2000006596A2 (en) INTERFERON HYBRIDS- alpha

Legal Events

Date Code Title Description
WITN Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid