PT85750B - Processo de preparacao de molecula receptora e de hidrolise catalitica - Google Patents

Processo de preparacao de molecula receptora e de hidrolise catalitica Download PDF

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Publication number
PT85750B
PT85750B PT85750A PT8575087A PT85750B PT 85750 B PT85750 B PT 85750B PT 85750 A PT85750 A PT 85750A PT 8575087 A PT8575087 A PT 8575087A PT 85750 B PT85750 B PT 85750B
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PT
Portugal
Prior art keywords
ligand
antibodies
reagent
compound
ester
Prior art date
Application number
PT85750A
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English (en)
Portuguese (pt)
Other versions
PT85750A (en
Inventor
Kim D Janda
Richard A Lerner
Alfonso Tramontano
Original Assignee
Scripps Clinic Res
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 Scripps Clinic Res filed Critical Scripps Clinic Res
Publication of PT85750A publication Critical patent/PT85750A/pt
Publication of PT85750B publication Critical patent/PT85750B/pt

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    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0002—Antibodies with enzymatic activity, e.g. abzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/54—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/24—Oxygen atoms attached in position 8
    • C07D215/26—Alcohols; Ethers thereof
    • C07D215/32—Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/40—Nitrogen atoms attached in position 8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4056—Esters of arylalkanephosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/42—Halides thereof
    • C07F9/425—Acid or estermonohalides thereof, e.g. RP(=X)(YR)(Hal) (X, Y = O, S; R = H, or hydrocarbon group)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/5537—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom the heteroring containing the structure -C(=O)-N-C(=O)- (both carbon atoms belong to the heteroring)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/60—Quinoline or hydrogenated quinoline ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Wood Science & Technology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pyridine Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Catalysts (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PT85750A 1986-09-17 1987-09-17 Processo de preparacao de molecula receptora e de hidrolise catalitica PT85750B (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US90831386A 1986-09-17 1986-09-17
US07/086,896 US5030717A (en) 1986-09-17 1987-08-18 Antibodies which catalyze hydrolysis of ester bonds

Publications (2)

Publication Number Publication Date
PT85750A PT85750A (en) 1987-10-01
PT85750B true PT85750B (pt) 1990-08-31

Family

ID=26775276

Family Applications (1)

Application Number Title Priority Date Filing Date
PT85750A PT85750B (pt) 1986-09-17 1987-09-17 Processo de preparacao de molecula receptora e de hidrolise catalitica

Country Status (13)

Country Link
US (1) US5030717A (US06566495-20030520-M00011.png)
EP (1) EP0260939B1 (US06566495-20030520-M00011.png)
JP (1) JP2556869B2 (US06566495-20030520-M00011.png)
AU (1) AU620019B2 (US06566495-20030520-M00011.png)
CA (1) CA1312835C (US06566495-20030520-M00011.png)
DE (1) DE3785633T2 (US06566495-20030520-M00011.png)
DK (1) DK175518B1 (US06566495-20030520-M00011.png)
ES (1) ES2053552T3 (US06566495-20030520-M00011.png)
FI (1) FI94026C (US06566495-20030520-M00011.png)
GR (1) GR3007997T3 (US06566495-20030520-M00011.png)
IE (1) IE61322B1 (US06566495-20030520-M00011.png)
NO (1) NO171223C (US06566495-20030520-M00011.png)
PT (1) PT85750B (US06566495-20030520-M00011.png)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5229272A (en) * 1989-04-25 1993-07-20 Igen, Inc. Catalytic antibody components
US4963355A (en) * 1986-06-23 1990-10-16 Igen, Inc. Production of antibody catalysts
AU2425788A (en) * 1987-09-02 1989-03-31 Neville R. Kallenbach Production of immunoproximity catalysts
ZA893284B (en) * 1988-05-04 1990-03-28 Igen Inc Peptide analogs and their use as haptens to elicit catalytic antibodies
US6702705B1 (en) * 1988-05-04 2004-03-09 Igen International, Inc. Prodrugs activated by targeted catalytic proteins
US5215889A (en) * 1988-11-18 1993-06-01 The Regents Of The University Of California Catalytic and reactive polypeptides and methods for their preparation and use
US5236825A (en) * 1989-01-17 1993-08-17 Scripps Clinic And Research Foundation Polyvalent metal ion-containing antibody combining site catalysts
US5429936A (en) * 1989-04-21 1995-07-04 The Regents Of The University Of California Antibody-mediated juxtaposition of reactive moieties
US5599538A (en) * 1989-04-25 1997-02-04 Igen, Inc. Autoantibodies which enhance the rate of a chemical reaction
US5194585A (en) * 1989-04-25 1993-03-16 Igen, Inc. Inhibitors of catalytic antibodies
US5658753A (en) * 1989-04-25 1997-08-19 Paul; Sudhir Catalytic antibody components
US5236836A (en) * 1989-04-25 1993-08-17 Igen, Inc. Autoantibodies which enhance the rate of a chemical reaction
US6048717A (en) * 1989-04-25 2000-04-11 Igen International, Inc. Inhibitors of catalytic antibodies
DK547589D0 (da) * 1989-11-02 1989-11-02 Novo Nordisk As Fremgangsmaade til fremstilling af organiske forbindelser
US5444155A (en) * 1991-09-10 1995-08-22 The Scripps Research Institute Molecules with antibody combining sites that induce asymmetry
US5250426A (en) * 1991-10-22 1993-10-05 The Scripps Research Institute Molecules with antibody combining sites that induce asymmetry
US5463028A (en) * 1992-04-03 1995-10-31 The Trustees Of Columbia University In The City Of New York Reagents for generating a polyclonal hydrolytic antibody response against cocaine and the monoclonal hydrolytic antibodies against cocaine derived through these reagents
JP2721296B2 (ja) * 1993-09-08 1998-03-04 株式会社蛋白工学研究所 糖エステル誘導体を位置選択的に加水分解する触媒抗体
US5571681A (en) * 1994-03-10 1996-11-05 The Scripps Research Institute Chemical event selection by suicide substrate conjugates
GB9510830D0 (en) * 1995-05-27 1995-07-19 Zeneca Ltd Proteins
AU727445B2 (en) * 1995-08-18 2000-12-14 Donald W Landry Detection of organic compounds through regulation of antibody-catalyzed reactions
US5948658A (en) 1996-06-25 1999-09-07 The Trustees Of Columbia University In The City Of New York Anti-cocaine catalytic antibody
BR0015145A (pt) * 1999-10-29 2002-07-16 Wakamoto Pharma Co Ltd Anticorpo monoclonal, hibridoma, método de imunoensaio e kit para diagnose
SG11201405468QA (en) 2012-03-14 2014-10-30 Regeneron Pharma Multispecific antigen-binding molecules and uses thereof
SG10202112460VA (en) 2015-07-06 2021-12-30 Regeneron Pharma Multispecific antigen-binding molecules and uses thereof
EP3448891A1 (en) 2016-04-28 2019-03-06 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
WO2018226861A1 (en) 2017-06-07 2018-12-13 Regeneron Pharmaceuticals, Inc. Compositions and methods for internalizing enzymes

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2540508B2 (ja) * 1983-11-29 1996-10-02 イージエン・インコーポレイテッド 化学反応を触媒する方法
US4659567A (en) * 1984-09-07 1987-04-21 Scripps Clinic & Research Foundation Molecules with antibody combining sites that bind to hydrolytic transition states
US4963355A (en) * 1986-06-23 1990-10-16 Igen, Inc. Production of antibody catalysts
US4792446A (en) * 1986-06-23 1988-12-20 Igen, Inc. Production of antibody catalysts

Also Published As

Publication number Publication date
FI874047A0 (fi) 1987-09-16
NO171223B (no) 1992-11-02
NO171223C (no) 1993-02-10
JPS63159325A (ja) 1988-07-02
EP0260939A3 (en) 1990-04-18
GR3007997T3 (US06566495-20030520-M00011.png) 1993-08-31
US5030717A (en) 1991-07-09
AU620019B2 (en) 1992-02-13
DK486087D0 (da) 1987-09-16
EP0260939B1 (en) 1993-04-28
NO873884L (no) 1988-03-18
NO873884D0 (no) 1987-09-16
JP2556869B2 (ja) 1996-11-27
EP0260939A2 (en) 1988-03-23
DK175518B1 (da) 2004-11-22
CA1312835C (en) 1993-01-19
IE61322B1 (en) 1994-11-02
FI94026B (fi) 1995-03-31
DE3785633T2 (de) 1993-08-12
PT85750A (en) 1987-10-01
ES2053552T3 (es) 1994-08-01
DK486087A (da) 1988-03-18
FI94026C (fi) 1995-07-10
DE3785633D1 (de) 1993-06-03
IE872512L (en) 1988-03-17
FI874047A (fi) 1988-03-18
AU7843487A (en) 1988-03-24

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