ES2120959T3 - Moleculas con sitios de combinacion de anticuerpos que catalizan reacciones de hidrolisis. - Google Patents

Moleculas con sitios de combinacion de anticuerpos que catalizan reacciones de hidrolisis.

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Publication number
ES2120959T3
ES2120959T3 ES91904939T ES91904939T ES2120959T3 ES 2120959 T3 ES2120959 T3 ES 2120959T3 ES 91904939 T ES91904939 T ES 91904939T ES 91904939 T ES91904939 T ES 91904939T ES 2120959 T3 ES2120959 T3 ES 2120959T3
Authority
ES
Spain
Prior art keywords
haptenic
binder
molecula
link
molecules
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 - Lifetime
Application number
ES91904939T
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English (en)
Inventor
Kim Janda
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.)
Scripps Research Institute
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Scripps Research Institute
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Application filed by Scripps Research Institute filed Critical Scripps Research Institute
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Publication of ES2120959T3 publication Critical patent/ES2120959T3/es
Anticipated expiration legal-status Critical
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
    • C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/44—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by —CHO groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
    • C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
    • C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
    • C07C215/32—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton containing hydroxy groups and carbon atoms of two six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/34—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having amino groups and esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C223/00—Compounds containing amino and —CHO groups bound to the same carbon skeleton
    • C07C223/06—Compounds containing amino and —CHO groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • 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
    • C07C233/16—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 singly-bound oxygen atoms
    • C07C233/24—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 singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/25—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 singly-bound oxygen atoms 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 an acyclic 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
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/56—Amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/16—Radicals substituted by halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Engineering & Computer Science (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)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

SE PRESENTA UNA MOLECULA DE UN ANTICUERPO O UNA MOLECULA QUE CONTIENE ZONAS DE COMBINACION DE ANTICUERPOS (MOLECULA CATALITICA) QUE HIDROLIZA CATALITICAMENTE UN AMIDO DE ACIDO CARBOXILICO PRESELECCIONADO O UN ENLACE DE UN ESTER DE UN LIGANTE REACTANTE, ASI MISMO SE PRESENTAN METODOS PARA OBTENER Y USAR LA MOLECULA CATALITICA, Y CELULAS QUE PRODUCEN ESTAS MOLECULAS. LAS MOLECULAS CATALITICAS SE UNEN A UN LIGANTE REACTANTE QUE CONTIENE EL ENLACE A HIDROLIZAR Y TAMBIEN A UN LIGANTE HAPTENICO. EL LIGANTE HAPTENICO ES ESTRUCTURALMENTE ANALOGO AL LIGANTE REACTANTE Y CONTIENE UN ATOMO DE CARBONO TETRAEDRICO QUE ESTA UNIDO A UN GRUPO HIDROXIL Y A UN ATOMO DE CARBONO SATURADO EN UNA POSICION EN EL LIGANTE HAPTENICO QUE SE CORRESPONDE CON LA POSICION DEL GRUPO CARBONIL Y DE SU HETEROATOMO ENLAZADO DEL LIGANTE REACTANTE. EL LIGANTE HAPTENICO TAMBIEN CONTIENE UN GRUPO QUE SOPORTA UNA CARGA IONICA EN UNA SOLUCION ACUOSA EN VALORES DE PH FISIOLOGICOS QUE NO ESTA PRESENTE EN UNA POSICION CORRESPONDIENTE DEL LIGANTE REACTANTE. EL GRUPO QUE SOPORTA LA CARGA IONICA ESTA SITUADA EN EL HAPTENO DENTRO DEL ANGSTROMS 7 DEL ATOMO DE CARBONO TETRAEDRICO.
ES91904939T 1990-01-26 1991-01-24 Moleculas con sitios de combinacion de anticuerpos que catalizan reacciones de hidrolisis. Expired - Lifetime ES2120959T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US47092490A 1990-01-26 1990-01-26
US07/644,909 US5187086A (en) 1990-01-26 1991-01-23 Molecules with antibody combining sites that catalyze hydrolysis reactions through use of a charged hapten

Publications (1)

Publication Number Publication Date
ES2120959T3 true ES2120959T3 (es) 1998-11-16

Family

ID=27043278

Family Applications (1)

Application Number Title Priority Date Filing Date
ES91904939T Expired - Lifetime ES2120959T3 (es) 1990-01-26 1991-01-24 Moleculas con sitios de combinacion de anticuerpos que catalizan reacciones de hidrolisis.

Country Status (14)

Country Link
US (1) US5187086A (es)
EP (1) EP0512074B1 (es)
JP (1) JP3365769B2 (es)
AT (1) ATE168718T1 (es)
AU (1) AU655412B2 (es)
CA (1) CA2034947C (es)
DE (1) DE69129845T2 (es)
DK (1) DK0512074T3 (es)
ES (1) ES2120959T3 (es)
FI (1) FI108437B (es)
IE (1) IE910277A1 (es)
NO (1) NO311432B1 (es)
PT (1) PT96584B (es)
WO (1) WO1991011512A1 (es)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US5606512A (en) * 1994-07-27 1997-02-25 The Dow Chemical Company Determining the biodegradability of iminodiacetic acid derivatives
JP2002515965A (ja) * 1995-08-18 2002-05-28 ダブリュー． ランドリ，ドナルド 抗体触媒反応の調節による有機化合物の検出
CA2249455A1 (en) * 1996-03-26 1997-10-02 Amrad Operations Pty. Ltd. Precursors of catalytic antibodies
AUPO930697A0 (en) * 1997-09-19 1997-10-09 Walter And Eliza Hall Institute Of Medical Research, The Catalytic antibodies and a method of producing same
US7226587B2 (en) * 2001-06-01 2007-06-05 Wyeth Compositions and methods for systemic administration of sequences encoding bone morphogenetic proteins
TWI267378B (en) * 2001-06-08 2006-12-01 Wyeth Corp Calcium phosphate delivery vehicles for osteoinductive proteins
US20030185858A1 (en) * 2001-08-15 2003-10-02 Birkett Ashley J. Immunogenic HBc chimer particles stabilized with an N-terminal cysteine
DE60232184D1 (de) * 2001-12-28 2009-06-10 Prysmian Spa Wasserbeständiges telekommunikations kabel
US20040009498A1 (en) * 2002-01-14 2004-01-15 Diversa Corporation Chimeric antigen binding molecules and methods for making and using them
US7556969B2 (en) * 2002-12-19 2009-07-07 Northeastern University Intensified neutral loss tags and use thereof in mass spectrometry
JP5730908B2 (ja) * 2010-01-25 2015-06-10 ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド ビタミンｄ３、ビタミンｄ２、およびこれらの代謝体の定量分析
JP5717138B2 (ja) * 2011-05-23 2015-05-13 独立行政法人産業技術総合研究所 タンパク質固定化表面修飾材料

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU3745285A (en) * 1983-11-29 1985-06-13 Igen, Inc. Method of catalyzing chemical reactions
US4792446A (en) * 1986-06-23 1988-12-20 Igen, Inc. Production of antibody catalysts

Also Published As

Publication number Publication date
FI923367A0 (fi) 1992-07-24
FI108437B (fi) 2002-01-31
EP0512074A4 (en) 1993-07-14
NO311432B1 (no) 2001-11-26
DE69129845D1 (de) 1998-08-27
CA2034947C (en) 1998-04-14
US5187086A (en) 1993-02-16
DK0512074T3 (da) 1999-04-26
ATE168718T1 (de) 1998-08-15
FI923367L (fi) 1992-07-24
WO1991011512A1 (en) 1991-08-08
AU7339591A (en) 1991-08-21
CA2034947A1 (en) 1991-07-27
EP0512074B1 (en) 1998-07-22
NO922921L (no) 1992-09-25
IE910277A1 (en) 1991-07-31
JP3365769B2 (ja) 2003-01-14
DE69129845T2 (de) 1999-03-18
PT96584B (pt) 1998-07-31
NO922921D0 (no) 1992-07-23
EP0512074A1 (en) 1992-11-11
JPH05506571A (ja) 1993-09-30
PT96584A (pt) 1991-10-15
AU655412B2 (en) 1994-12-22

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