DE69026306T2 - Verfahren für die Herstellung von Polyethylenglykolderivate und modifizierte Proteine. - Google Patents

Verfahren für die Herstellung von Polyethylenglykolderivate und modifizierte Proteine.

Info

Publication number
DE69026306T2
DE69026306T2 DE69026306T DE69026306T DE69026306T2 DE 69026306 T2 DE69026306 T2 DE 69026306T2 DE 69026306 T DE69026306 T DE 69026306T DE 69026306 T DE69026306 T DE 69026306T DE 69026306 T2 DE69026306 T2 DE 69026306T2
Authority
DE
Germany
Prior art keywords
polyethylene glycol
glycol derivatives
production
modified proteins
high purity
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
DE69026306T
Other languages
English (en)
Other versions
DE69026306D1 (de
Inventor
Keiichi Ono
Yoshiyuki Kai
Yoshiharu Ikeda
Hiroo Maeda
Katsukiyo Sakurai
Yoshikatsu Tanaka
Michio Kubota
Kazuhisa Kashimoto
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sumitomo Pharmaceuticals Co Ltd
Seikagaku Corp
Original Assignee
Sumitomo Pharmaceuticals Co Ltd
Seikagaku Corp
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 Sumitomo Pharmaceuticals Co Ltd, Seikagaku Corp filed Critical Sumitomo Pharmaceuticals Co Ltd
Application granted granted Critical
Publication of DE69026306D1 publication Critical patent/DE69026306D1/de
Publication of DE69026306T2 publication Critical patent/DE69026306T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/96Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D251/00Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1077General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/02Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
    • C08G65/32Polymers modified by chemical after-treatment
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/02Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
    • C08G65/32Polymers modified by chemical after-treatment
    • C08G65/329Polymers modified by chemical after-treatment with organic compounds
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/02Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
    • C08G65/32Polymers modified by chemical after-treatment
    • C08G65/329Polymers modified by chemical after-treatment with organic compounds
    • C08G65/333Polymers modified by chemical after-treatment with organic compounds containing nitrogen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
DE69026306T 1989-05-27 1990-05-23 Verfahren für die Herstellung von Polyethylenglykolderivate und modifizierte Proteine. Expired - Fee Related DE69026306T2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP13419189 1989-05-27
JP13419289 1989-05-27

Publications (2)

Publication Number Publication Date
DE69026306D1 DE69026306D1 (de) 1996-05-09
DE69026306T2 true DE69026306T2 (de) 1996-10-17

Family

ID=26468359

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69026306T Expired - Fee Related DE69026306T2 (de) 1989-05-27 1990-05-23 Verfahren für die Herstellung von Polyethylenglykolderivate und modifizierte Proteine.

Country Status (7)

Country Link
EP (1) EP0400472B1 (de)
AT (1) ATE136315T1 (de)
CA (1) CA2017543A1 (de)
DE (1) DE69026306T2 (de)
DK (1) DK0400472T3 (de)
ES (1) ES2085297T3 (de)
GR (1) GR3019991T3 (de)

Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2675807B1 (fr) * 1991-04-23 1994-07-01 Medgenix Group Sa Conjugue de calcitonine et de polyethylene glycol.
WO1993000109A1 (en) * 1991-06-28 1993-01-07 Genentech, Inc. Method of stimulating immune response using growth hormone
US5382657A (en) * 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
US5951974A (en) * 1993-11-10 1999-09-14 Enzon, Inc. Interferon polymer conjugates
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
TW517067B (en) * 1996-05-31 2003-01-11 Hoffmann La Roche Interferon conjugates
RO121474B1 (ro) 1997-06-06 2007-06-29 Kyowa Hakko Kogyo Co., Ltd. Polipeptide modificate chimic
EP0922446A1 (de) 1997-12-03 1999-06-16 Applied Research Systems Ars Holding N.V. Lösungsphase Verfahrung zur ortspezifischer Herstellung von GRF-PEG Konjugaten
ES2327606T3 (es) 2000-01-10 2009-11-02 Maxygen Holdings Ltd Conjugados de g-csf.
ES2325877T3 (es) 2000-02-11 2009-09-23 Bayer Healthcare Llc Moleculas de tipo factor vii o viia.
CA2409188A1 (en) * 2000-05-30 2001-12-06 Viridis Biotech Inc. Polyubiquitin based hydrogel and uses thereof
WO2002074806A2 (en) 2001-02-27 2002-09-26 Maxygen Aps New interferon beta-like molecules
CN1314445C (zh) 2001-05-21 2007-05-09 耐科塔医药公司 化学修饰胰岛素的肺部给药
CA2490360A1 (en) 2002-06-21 2003-12-31 Novo Nordisk Health Care Ag Pegylated factor vii glycoforms
US7553930B2 (en) 2003-01-06 2009-06-30 Xencor, Inc. BAFF variants and methods thereof
US7871607B2 (en) 2003-03-05 2011-01-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
BRPI0408116B1 (pt) 2003-03-05 2022-09-20 Halozyme, Inc Polipeptídeos de hialuronidase solúveis conjugados a polímero, composições farmacêuticas compreendendo polipeptídeos ph20 solúveis, seus usos e processo de preparação, e ácidos nucléicos que codificam polipeptídeos de hialuronidase solúveis
US20050079155A1 (en) * 2003-03-20 2005-04-14 Xencor, Inc. Generating protein pro-drugs using reversible PPG linkages
US20050107297A1 (en) * 2003-05-12 2005-05-19 Holmes Christopher P. Novel poly(ethylene glycol) modified compounds and uses thereof
EP1625156B1 (de) 2003-05-12 2012-09-19 Affymax, Inc. An den erythropoietinrezeptor bindenden peptiden
EA010095B1 (ru) 2003-05-12 2008-06-30 Афимакс, Инк. Новые пептиды, которые связываются с рецептором эритропоэтина
NZ543934A (en) 2003-05-12 2008-06-30 Affymax Inc Novel spacer moiety for poly (ethylene glycol)-modified peptide-based compounds
WO2005035565A1 (en) 2003-10-10 2005-04-21 Novo Nordisk A/S Il-21 derivatives
EP2641611A3 (de) 2003-10-17 2013-12-18 Novo Nordisk A/S Kombinationstherapie
BRPI0507169A (pt) 2004-02-02 2007-06-26 Ambrx Inc polipeptìdeos do hormÈnio de crescimento humano modificados e seu usos
MXPA06014307A (es) 2004-06-08 2007-03-12 Alza Corp Preparacion de conjugados macromoleculares por reaccion de condensacion de cuatro componentes.
JP2008503217A (ja) 2004-06-18 2008-02-07 アンブレツクス・インコーポレイテツド 新規抗原結合ポリペプチド及びそれらの使用
CA2573262C (en) * 2004-07-16 2015-02-10 Nektar Therapeutics Al, Corporation Conjugates of a gm-csf moiety and a polymer
EP1836314B1 (de) 2004-12-22 2012-01-25 Ambrx, Inc. Modifiziertes menschliches wachstumshormon
EP1674113A1 (de) 2004-12-22 2006-06-28 F. Hoffmann-La Roche Ag Konjugate von insulinähnlichem Wachstumfaktor-1 und Poly(Ethylenglykol)
US8324159B2 (en) 2005-06-03 2012-12-04 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
US7550433B2 (en) 2005-06-03 2009-06-23 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
US7919461B2 (en) 2005-06-03 2011-04-05 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
EP1893632B1 (de) 2005-06-17 2015-08-12 Novo Nordisk Health Care AG Selektive reduktion und derivatisierung manipulierter faktor vii proteine mit mindestens einem nichtnativen zystein
US20090018029A1 (en) 2005-11-16 2009-01-15 Ambrx, Inc. Methods and Compositions Comprising Non-Natural Amino Acids
RU2008145084A (ru) 2006-05-24 2010-06-27 Ново Нордиск Хелс Кеа Аг (Ch) Аналоги фактора ix, имеющие пролонгированное время полужизни in vivo
CL2007002502A1 (es) 2006-08-31 2008-05-30 Hoffmann La Roche Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer.
MX2009001691A (es) 2006-08-31 2009-02-25 Hoffmann La Roche Metodo para produccion del factor de crecimiento i tipo insulina.
JP5840345B2 (ja) 2006-09-08 2016-01-06 アンブルックス, インコーポレイテッドAmbrx, Inc. 修飾ヒト血漿ポリペプチドまたは修飾ヒトFc足場タンパク質ならびにこれらの利用
KR101476472B1 (ko) 2007-03-30 2015-01-05 암브룩스, 인코포레이티드 변형된 fgf-21 폴리펩티드 및 그 용도
DK2217265T3 (en) 2007-11-20 2017-07-03 Ambrx Inc Modified insulin polypeptides and their use
CN103694337B (zh) 2008-02-08 2016-03-02 Ambrx公司 经修饰瘦素多肽和其用途
EP3225248B1 (de) 2008-07-23 2023-06-07 Ambrx, Inc. Modifizierte bovine g-csf-polypeptide und ihre verwendung
WO2010033240A2 (en) * 2008-09-19 2010-03-25 Nektar Therapeutics Carbohydrate-based drug delivery polymers and conjugates thereof
WO2010033221A1 (en) 2008-09-19 2010-03-25 Nektar Therapeutics Polymer conjugates of protegrin peptides
WO2010033216A1 (en) 2008-09-19 2010-03-25 Nektar Therapeutics Polymer conjugates of nesiritide peptides
AU2009296397B2 (en) 2008-09-26 2012-11-08 Ambrx Inc. Modified animal erythropoietin polypeptides and their uses
KR101732054B1 (ko) 2008-09-26 2017-05-02 암브룩스, 인코포레이티드 비천연 아미노산 복제 의존성 미생물 및 백신
US8927249B2 (en) 2008-12-09 2015-01-06 Halozyme, Inc. Extended soluble PH20 polypeptides and uses thereof
EP2805964A1 (de) 2009-12-21 2014-11-26 Ambrx, Inc. Modifizierte Rinder-Somatotropinpolypeptide und deren Verwendungen
NZ600363A (en) 2009-12-21 2014-07-25 Ambrx Inc Modified porcine somatotropin polypeptides and their uses
JP6148013B2 (ja) 2010-03-05 2017-06-14 リグショスピタレト 補体活性化のキメラ抑制分子
US20120135912A1 (en) 2010-05-10 2012-05-31 Perseid Therapeutics Llc Polypeptide inhibitors of vla4
ES2661089T3 (es) 2010-07-20 2018-03-27 Halozyme Inc. Métodos de tratamiento o prevención de los efectos secundarios adversos asociados con la administración de un agente anti-hialuronano
DK2605789T3 (da) 2010-08-17 2019-09-16 Ambrx Inc Modificerede relaxinpolypeptider og anvendelser deraf
US9567386B2 (en) 2010-08-17 2017-02-14 Ambrx, Inc. Therapeutic uses of modified relaxin polypeptides
TWI480288B (zh) 2010-09-23 2015-04-11 Lilly Co Eli 牛顆粒細胞群落刺激因子及其變體之調配物
AR087020A1 (es) 2011-07-01 2014-02-05 Bayer Ip Gmbh Polipeptidos de fusion de relaxina y usos de los mismos
WO2013040501A1 (en) 2011-09-16 2013-03-21 Pharmathene, Inc. Compositions and combinations of organophosphorus bioscavengers and hyaluronan-degrading enzymes, and uses thereof
JP6162707B2 (ja) 2011-10-24 2017-07-12 ハロザイム インコーポレイテッド 抗ヒアルロナン剤治療のためのコンパニオン診断およびその使用方法
EP3130347B1 (de) 2011-12-30 2019-09-18 Halozyme, Inc. Ph20-polypeptidvarianten, formulierungen und verwendungen davon
US9913822B2 (en) 2012-04-04 2018-03-13 Halozyme, Inc. Combination therapy with an anti-hyaluronan agent and therapeutic agent
KR102172897B1 (ko) 2012-06-08 2020-11-02 서트로 바이오파마, 인크. 부위-특이적 비-천연 아미노산 잔기를 포함하는 항체, 그의 제조 방법 및 그의 사용 방법
WO2014004639A1 (en) 2012-06-26 2014-01-03 Sutro Biopharma, Inc. Modified fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use
PL3584255T3 (pl) 2012-08-31 2022-05-16 Sutro Biopharma, Inc. Modyfikowane aminokwasy zawierające grupę azydkową
US9278124B2 (en) 2012-10-16 2016-03-08 Halozyme, Inc. Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods
TW201534726A (zh) 2013-07-03 2015-09-16 Halozyme Inc 熱穩定ph20玻尿酸酶變異體及其用途
WO2015006555A2 (en) 2013-07-10 2015-01-15 Sutro Biopharma, Inc. Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use
EP3055298B1 (de) 2013-10-11 2020-04-29 Sutro Biopharma, Inc. Modifizierte aminosäuren mit funktionellen tetrazingruppen, verfahren zur herstellung und verfahren zu deren verwendung
PL3186281T3 (pl) 2014-08-28 2019-10-31 Halozyme Inc Terapia skojarzona enzymem rozkładającym hialuronian i inhibitorem punktu kontrolnego odpowiedzi immunologicznej
UY36370A (es) 2014-10-24 2016-04-29 Bristol Myers Squibb Company Una Corporación Del Estado De Delaware Polipéptidos fgf-21 modificados y sus usos
ES2963839T3 (es) 2017-02-08 2024-04-02 Bristol Myers Squibb Co Polipéptidos de relaxina modificados que comprenden un potenciador farmacocinético y usos de los mismos
US20190351031A1 (en) 2018-05-16 2019-11-21 Halozyme, Inc. Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20
JP7441826B2 (ja) 2018-09-11 2024-03-01 アンブルックス,インコーポレイテッド インターロイキン-2ポリペプチド抱合物およびその使用
AU2019361206A1 (en) 2018-10-19 2021-06-03 Ambrx, Inc. Interleukin-10 polypeptide conjugates, dimers thereof, and their uses
JP2022520792A (ja) 2019-02-12 2022-04-01 アンブルックス,インコーポレイテッド 抗体-tlrアゴニストコンジュゲートを含有する組成物、その方法、及び使用
CA3174114A1 (en) 2020-03-11 2021-09-16 Ambrx, Inc. Interleukin-2 polypeptide conjugates and methods of use thereof
JP2023538071A (ja) 2020-08-20 2023-09-06 アンブルックス,インコーポレイテッド 抗体-tlrアゴニストコンジュゲート、その方法及び使用
CA3213805A1 (en) 2021-04-03 2022-10-06 Feng Tian Anti-her2 antibody-drug conjugates and uses thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60156395A (ja) * 1984-01-17 1985-08-16 Mihama Hisaharu 修飾リパーゼ
ES8800982A1 (es) * 1985-07-05 1987-12-01 Takeda Chemical Industries Ltd Un metodo para producir la enzima superoxido-dismutasa modificada con derivados de polietilenglicol y triazina.

Also Published As

Publication number Publication date
GR3019991T3 (en) 1996-08-31
EP0400472A2 (de) 1990-12-05
ES2085297T3 (es) 1996-06-01
EP0400472A3 (de) 1991-06-26
ATE136315T1 (de) 1996-04-15
EP0400472B1 (de) 1996-04-03
CA2017543A1 (en) 1990-11-27
DK0400472T3 (da) 1996-05-13
DE69026306D1 (de) 1996-05-09

Similar Documents

Publication Publication Date Title
DE69026306D1 (de) Verfahren für die Herstellung von Polyethylenglykolderivate und modifizierte Proteine.
NO874350D0 (no) Fremgangsmaate for fremstilling av antibakterielle forbindelser.
FI906438A (fi) Menetelmä uusien, terapeuttisesti käyttökelpoisten A-nor-steroidi-3-karboksyylihappojohdannaisten valmistamiseksi
FI905956A (fi) Foerfarande foer producering av ett biologiskt aktivt protein.
ATE237613T1 (de) Verfahren für die herstellung von antiviralen substituierten 1, 3-oxathiolanen
DE3576952D1 (de) Verfahren zur herstellung von 4-phenyl-pyrrol-derivaten.
ES545195A0 (es) Un procedimiento para preparar derivados de purina
DE58908857D1 (de) Verfahren zur Herstellung von 2,6-Dichlordiphenylaminessigsäurederivaten.

Legal Events

Date Code Title Description
8364 No opposition during term of opposition
8339 Ceased/non-payment of the annual fee