EP0904540A1 - Techniques de synthese d'une bibliotheque combinatoire a distribution controlee dispersee dans l'espace - Google Patents

Techniques de synthese d'une bibliotheque combinatoire a distribution controlee dispersee dans l'espace

Info

Publication number
EP0904540A1
EP0904540A1 EP97916869A EP97916869A EP0904540A1 EP 0904540 A1 EP0904540 A1 EP 0904540A1 EP 97916869 A EP97916869 A EP 97916869A EP 97916869 A EP97916869 A EP 97916869A EP 0904540 A1 EP0904540 A1 EP 0904540A1
Authority
EP
European Patent Office
Prior art keywords
series
arrays
solid supports
array
supports
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.)
Withdrawn
Application number
EP97916869A
Other languages
German (de)
English (en)
Inventor
Edmund J. Moran
John F. Cargill
Romaine R. Maiefski
Thomas J. Baiga
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.)
Ontogen Corp
Original Assignee
Ontogen 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 Ontogen Corp filed Critical Ontogen Corp
Publication of EP0904540A1 publication Critical patent/EP0904540A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/047—Simultaneous synthesis of different peptide species; Peptide libraries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00452—Means for the recovery of reactants or products
    • B01J2219/00454—Means for the recovery of reactants or products by chemical cleavage from the solid support
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00457—Dispensing or evacuation of the solid phase support
    • B01J2219/0047—Pins
    • B01J2219/00472—Replaceable crowns
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/0059—Sequential processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00592—Split-and-pool, mix-and-divide processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
    • C40B50/14—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Definitions

  • solid support-based chemistry it is common in the practice to employ solid support-based chemistry for these methods.
  • a collection of solid supports are split into individual pools. These pools are then exposed to a series of reactive monomers, followed by a recombination step, in which the position of all solid supports is randomized.
  • the solid supports are then split into a new set of individual pools, exposed to a new series of reactive monomers, followed by a second recombination step. By repeating this split, react and recombine process all possible combinations of oligomers or compounds from the series of monomers employed are obtained, providing a large excess of solid supports are utilized.
  • the first, second and third rows of supports from the second and third arrays in the second series are redistributed to the third series of arrays for chemical transformation step #3 in a similar fashion.
  • the redistribution of supports between the chemical transformation steps # 1 and #2 and between steps #2 and #3 is functionally identical if one simply reorients the arrays such that rows become columns and columns become rows (such as accomplished by a 90 degree rotation). If such a reorientation of the second series of arrays occurs then the columns from the second series of arrays are redistributed to columns in the third series of arrays. Following this second redistribution, chemical transformation step #3 is carried out on the supports.
  • Step 10 The crown holders are positioned such that the crowns fit mto the wells of eight 96 2 mL-well polypropylene microtiter plates (available from Beckman Corp , Brea, CA), marked Plate 1, 2, 3, through 8 such that holder S3.1 is positioned with Plate 1, holder S3 2 is positioned with Plate 2, etc
  • the onentation is such that the columns (and therefore the rows) of the holders are aligned with the columns (and therefore the rows) of the plates
  • the dimensions of an array coverage in a plate would be from Rows A through H and from Columns 1 through 8 using the nomenclature common to the microtiter plate format
  • the crowns are treated with 5% tnfluoroacetic acid in dichloromethane for 30 m.
  • the crown holders are removed and the volatile contents of the microtiter plates evaporated under reduced pressure (20 mmHg)
  • the methods described in the body of the invention may be used to produce non-peptide, low molecular weight organic compound libraries.
  • the synthetic chemistry protocols are more complex in the syntheses of many of these compounds than those utilized to construct peptide libraries. Additionally, there are no general methods available to directly sequence the structure of most of these compounds. Thus, the ease by which a library is de-coded using the method described herein renders it suitable for the svnthesis of low molecular weight compounds.
  • the synthesis of a heterocyclic library is demonstrated. The synthesis of 1,4- benzodiazapin-2-ones follows the procedure of Ellman et. al. 17 and is shown in the accompanying schematic.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention porte sur une technique utile en chimie combinatoire. Elle porte plus particulièrement sur des techniques de synthèse de bibliothèques d'oligomères dispersés dans l'espace, dont la position est codée et qui relèvent de la chimie combinatoire, synthèse effectuée sur divers supports solides eux-mêmes distribués sous forme d'une série de matrices. La position de chaque support solide dans chaque matrice détermine l'identité exacte de l'oligomère.
EP97916869A 1996-03-22 1997-03-21 Techniques de synthese d'une bibliotheque combinatoire a distribution controlee dispersee dans l'espace Withdrawn EP0904540A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US1389796P 1996-03-22 1996-03-22
US13897P 1996-03-22
PCT/US1997/004500 WO1997035198A1 (fr) 1996-03-22 1997-03-21 Techniques de synthese d'une bibliotheque combinatoire a distribution controlee dispersee dans l'espace

Publications (1)

Publication Number Publication Date
EP0904540A1 true EP0904540A1 (fr) 1999-03-31

Family

ID=21762395

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97916869A Withdrawn EP0904540A1 (fr) 1996-03-22 1997-03-21 Techniques de synthese d'une bibliotheque combinatoire a distribution controlee dispersee dans l'espace

Country Status (5)

Country Link
EP (1) EP0904540A1 (fr)
JP (1) JP2001519763A (fr)
AU (1) AU2537397A (fr)
CA (1) CA2249419A1 (fr)
WO (1) WO1997035198A1 (fr)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6284459B1 (en) 1995-04-25 2001-09-04 Discovery Partners International Solid support matrices with memories and combinatorial libraries therefrom
US5961923A (en) * 1995-04-25 1999-10-05 Irori Matrices with memories and uses thereof
US6100026A (en) * 1995-04-25 2000-08-08 Irori Matrices with memories and uses thereof
CA2216645A1 (fr) 1995-04-25 1996-11-21 Irori Matrices programmables a distance et dotees de memoires, et leur utilisation
US5925562A (en) * 1995-04-25 1999-07-20 Irori Remotely programmable matrices with memories
US6362009B1 (en) 1997-11-21 2002-03-26 Merck & Co., Inc. Solid phase synthesis of heterocycles
HUP0103260A3 (en) * 1998-03-23 2002-03-28 Harvard College Peptidomimetic compounds and process for their synthesis
US6541211B1 (en) * 1998-05-20 2003-04-01 Selectide Corporation Apparatus and method for synthesizing combinational libraries
US6284197B1 (en) 1998-06-05 2001-09-04 The Regents Of The University Of California Optical amplification of molecular interactions using liquid crystals
US6858423B1 (en) 1998-06-05 2005-02-22 The Regents Of The University Of California Optical Amplification of molecular interactions using liquid crystals
CA2346989A1 (fr) 1998-10-19 2000-04-27 The Board Of Trustees Of The Leland Stanford Junior University Bibliotheque de chimie combinatoire a matrice d'adn
SE9902479D0 (sv) * 1999-06-30 1999-06-30 Amersham Pharm Biotech Ab Particle classification as marker
EP1235932A2 (fr) 1999-10-08 2002-09-04 Protogene Laboratories, Inc. Procede et appareil destines a produire un grand nombre de reactions au moyen d'une plaque matrice
US6625546B2 (en) * 2000-02-03 2003-09-23 Nanoscale Combinatorial Synthesis, Inc. Structure identification methods using mass measurements
US7129326B2 (en) 2000-04-14 2006-10-31 Genencor International, Inc. Methods for selective targeting
US20020098524A1 (en) 2000-04-14 2002-07-25 Murray Christopher J. Methods for selective targeting
EP1401850A1 (fr) 2001-06-20 2004-03-31 Nuevolution A/S Derives nucleosidiques pour elaboration de bibliotheque combinatoire
US7842498B2 (en) 2001-11-08 2010-11-30 Bio-Rad Laboratories, Inc. Hydrophobic surface chip
US10731151B2 (en) 2002-03-15 2020-08-04 Nuevolution A/S Method for synthesising templated molecules
AU2003214031A1 (en) 2002-03-15 2003-09-29 Nuevolution A/S An improved method for synthesising templated molecules
EP1539980B1 (fr) 2002-08-01 2016-02-17 Nuevolution A/S Synthese en plusieurs etapes de molecules synthetisees
WO2004038415A1 (fr) * 2002-10-24 2004-05-06 Biacore Ab Test avec des ligands co-immobilises
EP2348124B1 (fr) 2002-10-30 2013-12-11 Nuevolution A/S Synthése de complexes bifonctionnels
WO2004056994A2 (fr) 2002-12-19 2004-07-08 Nuevolution A/S Procedes de synthese guidee a fonction et structure quasi-selectives
US20070026397A1 (en) 2003-02-21 2007-02-01 Nuevolution A/S Method for producing second-generation library
US20040235056A1 (en) * 2003-05-07 2004-11-25 Mallouk Thomas E. Method of assembling particle libraries
US11118215B2 (en) 2003-09-18 2021-09-14 Nuevolution A/S Method for obtaining structural information concerning an encoded molecule and method for selecting compounds
US7795007B2 (en) 2003-09-23 2010-09-14 Wisconsin Alumni Research Foundation Detection of post-translationally modified peptides with liquid crystals
JP4668911B2 (ja) 2003-09-23 2011-04-13 ウィスコンシン アルムニ リサーチ ファンデイション アフィニティー・マイクロコンタクトプリントされた生体分子を検出するための液晶の使用
US7341872B1 (en) 2004-04-29 2008-03-11 Uop Llc Multiautoclave with set of vessels for combinatorial synthesis of zeolites and other materials
PT3305900T (pt) 2005-12-01 2021-10-27 Nuevolution As Métodos de codificação enzimática para síntese eficaz de bibliotecas grandes
EP3540059A1 (fr) 2010-04-16 2019-09-18 Nuevolution A/S Complexes bifonctionnels et procédés de fabrication et d'utilisation de tels complexes

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5585275A (en) * 1992-09-02 1996-12-17 Arris Pharmaceutical Corporation Pilot apparatus for peptide synthesis and screening

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9735198A1 *

Also Published As

Publication number Publication date
WO1997035198A1 (fr) 1997-09-25
JP2001519763A (ja) 2001-10-23
CA2249419A1 (fr) 1997-09-25
AU2537397A (en) 1997-10-10

Similar Documents

Publication Publication Date Title
EP0904540A1 (fr) Techniques de synthese d'une bibliotheque combinatoire a distribution controlee dispersee dans l'espace
US5770455A (en) Methods and apparatus for synthesizing labeled combinatorial chemistrylibraries
Terrett et al. Combinatorial synthesis—the design of compound libraries and their application to drug discovery
Jacobs et al. Combinatorial chemistry—applications of light-directed chemical synthesis
Chabala Solid-phase combinatorial chemistry and novel tagging methods for identifying leads
Terrett Combinatorial chemistry
US6528324B1 (en) Apparatus for pre-determined mass sorting of positional-encoded solid phase synthesis supports
US6165717A (en) Method of synthesizing diverse collections of oligomers
US5591646A (en) Method and apparatus for peptide synthesis and screening
EP1095054A1 (fr) Procede d'utilisation d'une bibliotheque universelle amelioree d'acides nucleiques de peptides permettant d'optimiser l'hybridation des sequences d'adn
Desai et al. Recent advances in the generation of chemical diversity libraries
Frank Simultaneous and combinatorial chemical synthesis techniques for the generation and screening of molecular diversity
Williard et al. Combinatorial chemistry: a rational approach to chemical diversity
Beck-Sickinger et al. Combinatorial strategies in biology and chemistry
Hlaváč et al. PRACTICAL ASPECTS OF COMBINATORIAL SOLID-PHASE
Khanuja et al. REVIEW ON COMBINATORIAL CHEMISTRY
Figliozzi et al. 14 Automated Synthesis of Nonnatural Oligomer Libraries: The Peptoid Concept
Klebe Combinatorics: Chemistry with Big Numbers
US20020048773A1 (en) Method and apparatus for facile manipulation of spatially addressed solid supports for combinatorial chemical synthesis
Furka Combinatorial chemistry
Singh et al. Combinatorial chemistry: a review
Antonenko et al. Combinatorial chemistry
Prajapati et al. Combinatorial Chemistry: A New Approch for Drug Discovery
Ambre et al. Combinatorial Chemistry: Role in Lead Discovery
NANDAN et al. PREMLATA K. AMBRE, ANISH N. GOMATAM

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19981020

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): DE FR GB

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20021001