PT91294A - Processo para a preparacao de construtos de antigenes a partir de antigenes da classe i de "complexo de histocompatibilidade principal" com moleculas de suporte especificas e de composicoes farmaceuticas que os comtem - Google Patents

Processo para a preparacao de construtos de antigenes a partir de antigenes da classe i de "complexo de histocompatibilidade principal" com moleculas de suporte especificas e de composicoes farmaceuticas que os comtem

Info

Publication number
PT91294A
PT91294A PT91294A PT9129489A PT91294A PT 91294 A PT91294 A PT 91294A PT 91294 A PT91294 A PT 91294A PT 9129489 A PT9129489 A PT 9129489A PT 91294 A PT91294 A PT 91294A
Authority
PT
Portugal
Prior art keywords
antigens
class
major histocompatibility
histocompatibility complex
antigen constructs
Prior art date
Application number
PT91294A
Other languages
English (en)
Other versions
PT91294B (pt
Inventor
Klaus Bosslet
Gerhard Seemann
Hans Harald Sedlacek
Original Assignee
Behringwerke Ag
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 Behringwerke Ag filed Critical Behringwerke Ag
Publication of PT91294A publication Critical patent/PT91294A/pt
Publication of PT91294B publication Critical patent/PT91294B/pt

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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6897—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
    • A61K47/6898—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies using avidin- or biotin-conjugated antibodies
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
PT91294A 1988-07-28 1989-07-27 Processo para a preparacao de construtos de antigenes a partir de antigenes da classe i de "complexo de histocompatibilidade principal" com moleculas de suporte especificas e de composicoes farmaceuticas que os comtem PT91294B (pt)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE3825615A DE3825615A1 (de) 1988-07-28 1988-07-28 Antigenkonstrukte von "major histocompatibility complex" klasse i antigenen mit spezifischen traegermolekuelen, ihre herstellung und verwendung

Publications (2)

Publication Number Publication Date
PT91294A true PT91294A (pt) 1990-02-08
PT91294B PT91294B (pt) 1995-03-01

Family

ID=6359731

Family Applications (1)

Application Number Title Priority Date Filing Date
PT91294A PT91294B (pt) 1988-07-28 1989-07-27 Processo para a preparacao de construtos de antigenes a partir de antigenes da classe i de "complexo de histocompatibilidade principal" com moleculas de suporte especificas e de composicoes farmaceuticas que os comtem

Country Status (12)

Country Link
US (2) US6548067B1 (pt)
EP (1) EP0352761B1 (pt)
JP (1) JP2812726B2 (pt)
KR (1) KR970010760B1 (pt)
AT (1) ATE128732T1 (pt)
AU (1) AU625065B2 (pt)
DE (2) DE3825615A1 (pt)
DK (1) DK371089A (pt)
ES (1) ES2080055T3 (pt)
FI (1) FI100973B (pt)
GR (1) GR3017915T3 (pt)
PT (1) PT91294B (pt)

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5525338A (en) * 1992-08-21 1996-06-11 Immunomedics, Inc. Detection and therapy of lesions with biotin/avidin conjugates
DE3825615A1 (de) * 1988-07-28 1990-02-01 Behringwerke Ag Antigenkonstrukte von "major histocompatibility complex" klasse i antigenen mit spezifischen traegermolekuelen, ihre herstellung und verwendung
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
DE4106389A1 (de) * 1991-02-28 1992-09-03 Behringwerke Ag Fusionsproteine zur prodrug-aktivierung, ihre herstellung und verwendung
US7241595B2 (en) 1989-10-20 2007-07-10 Sanofi-Aventis Pharma Deutschland Gmbh Glycosyl-etoposide prodrugs, a process for preparation thereof and the use thereof in combination with functionalized tumor-specific enzyme conjugates
SE9002484L (sv) 1990-07-20 1992-01-21 Kabi Pharmacia Ab Nya substituerade polyetrar
US5885570A (en) * 1991-01-23 1999-03-23 The General Hospital Corporation Induction of tolerance with modified immunogens
JP3105629B2 (ja) † 1991-04-23 2000-11-06 サングスタット メディカル コーポレイション 特異的結合ペアのメンバーの細胞活性調節接合体
DE4133791A1 (de) * 1991-10-11 1993-04-15 Behringwerke Ag Monoklonale antikoerper gegen tumorassoziierte antigene, verfahren zu ihrer herstellung und ihre verwendung
JPH05246889A (ja) * 1992-03-05 1993-09-24 Seitai Chiyousetsu Kenkyusho:Kk 制癌方法および制癌剤
US6030797A (en) * 1992-10-08 2000-02-29 Dade Behring Marburg Gmbh Monoclonal antibodies against tumor-associated antigens, processes for the preparation thereof and the use thereof
WO1997024446A2 (en) * 1995-12-29 1997-07-10 Chiron Corporation Gene delivery vehicle-targeting ligands
CA2250166A1 (en) 1996-03-28 1997-10-02 The Johns Hopkins University Soluble divalent and multivalent heterodimeric analogs of proteins
US6458354B1 (en) 1996-03-28 2002-10-01 The Johns Hopkins University Molecular complexes which modify immune responses
US6211342B1 (en) * 1996-07-18 2001-04-03 Children's Hospital Medical Center Multivalent MHC complex peptide fusion protein complex for stimulating specific T cell function
JP2001500479A (ja) * 1996-08-23 2001-01-16 マサチューセッツ インスティチュート オブ テクノロジー 細胞破壊のメディエーターとしての同種異系組織適合性複合体
US6268411B1 (en) 1997-09-11 2001-07-31 The Johns Hopkins University Use of multivalent chimeric peptide-loaded, MHC/ig molecules to detect, activate or suppress antigen-specific T cell-dependent immune responses
US6248564B1 (en) 1997-08-29 2001-06-19 Harvard University Mutant MHC class I molecules
US20020051783A1 (en) * 1998-06-05 2002-05-02 Savage Philip Michael Method for producing or enhancing a T-cell response against a target cell using a complex comprising an HLA class I molecule and an attaching means
AU2002301994B2 (en) * 1998-06-05 2008-05-15 Alexis Biotech Limited Method for producing cytotoxic T-cells
GB2339782A (en) * 1998-06-05 2000-02-09 Philip Michael Savage Chimeric protein complexes comprising HLA class I antigens
US7521197B2 (en) 1998-06-05 2009-04-21 Alexis Biotech Limited Method for producing cytotoxic T-cells
US7264965B2 (en) 1998-06-05 2007-09-04 Alexis Biotech Limited Method for producing or enhancing a T-cell response against a target cell using a complex comprising an HLA class I molecule and an attaching means
US6197591B1 (en) * 1998-09-14 2001-03-06 Pfizer Inc. Streptomyces avermitilis regulatory genes for increased avermectin production
IL151860A0 (en) * 2000-03-27 2003-04-10 Technion Res & Dev Foundation Single chain class i major histocompatibility complexes, constructs encoding same and methods of generating same
US20040191260A1 (en) 2003-03-26 2004-09-30 Technion Research & Development Foundation Ltd. Compositions capable of specifically binding particular human antigen presenting molecule/pathogen-derived antigen complexes and uses thereof
WO2001074382A1 (en) 2000-03-31 2001-10-11 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
AU2001255326B2 (en) * 2000-04-12 2005-12-15 University Of Rochester Targeted vaccine delivery systems
DK2336167T3 (da) * 2001-03-14 2019-09-02 Dako Denmark As MHC-molekylkonstrukter og deres anvendelse til diagnose og terapi
US8022190B2 (en) 2001-06-19 2011-09-20 Technion Research & Development Foundation Ltd. Immuno-molecules containing viral proteins, compositions thereof and methods of using
US20030017134A1 (en) * 2001-06-19 2003-01-23 Technion Research And Development Foundation Ltd. Methods and pharmaceutical compositions for immune deception, particularly useful in the treatment of cancer
CA2493081C (en) * 2002-07-12 2013-04-23 The Johns Hopkins University Reagents and methods for engaging unique clonotypic lymphocyte receptors
US9809654B2 (en) 2002-09-27 2017-11-07 Vaccinex, Inc. Targeted CD1d molecules
US20040210037A1 (en) * 2003-03-28 2004-10-21 Vaccinex, Inc. Targeted MHC class I alpha3 vaccine delivery systems
US20050042218A1 (en) * 2003-07-10 2005-02-24 Vaccinex, Inc. MHC class I - peptide-antibody conjugates with modified beta2-microglobulin
GB2408507B (en) * 2003-10-06 2005-12-14 Proimmune Ltd Chimeric MHC protein and oligomer thereof for specific targeting
GB2409456B (en) * 2003-10-30 2006-01-04 Proimmune Ltd Oligomeric receptor ligand pair member complexes
US20050287611A1 (en) * 2004-05-07 2005-12-29 Nugent C T Iv MHC bridging system for detecting CTL-mediated lysis of antigen presenting cells
WO2007085266A1 (en) * 2006-01-30 2007-08-02 Dako Denmark A/S High-speed quantification of antigen specific t-cells in whole blood by flow cytometry
CN101448951B (zh) * 2006-05-19 2013-04-10 泰华制药工业有限公司 融合蛋白、其用途以及制备方法
GB2442048B (en) * 2006-07-25 2009-09-30 Proimmune Ltd Biotinylated MHC complexes and their uses
JP5357782B2 (ja) 2007-02-21 2013-12-04 バクシネックス インコーポレーティッド 抗原負荷ＣＤ１ｄ分子によるＮＫＴ細胞活性の調節
EP2361930A3 (en) 2007-03-26 2011-10-26 Dako Denmark A/S Multimers of MHC-peptide complexes and uses thereof in Borrelia infectious diseases
EP3023436A1 (en) * 2007-07-03 2016-05-25 Dako Denmark A/S Improved methods for generation, labeling and use of mhc multimers
WO2009039854A2 (en) 2007-09-27 2009-04-02 Dako Denmark A/S Mhc multimers in tuberculosis diagnostics, vaccine and therapeutics
US10968269B1 (en) 2008-02-28 2021-04-06 Agilent Technologies, Inc. MHC multimers in borrelia diagnostics and disease
US10722562B2 (en) 2008-07-23 2020-07-28 Immudex Aps Combinatorial analysis and repair
GB0817244D0 (en) 2008-09-20 2008-10-29 Univ Cardiff Use of a protein kinase inhibitor to detect immune cells, such as T cells
US10369204B2 (en) 2008-10-02 2019-08-06 Dako Denmark A/S Molecular vaccines for infectious disease
US9139809B2 (en) 2009-01-08 2015-09-22 Albert Einstein College Of Medicine Of Yeshiva University Bacterial vaccines with cell wall-associated ceramide-like glycolipids and uses thereof
SG195077A1 (en) * 2011-06-22 2013-12-30 Hoffmann La Roche Removal of target cells by circulating virus-specific cytotoxic t-cells using mhc class i comprising complexes
KR20150088881A (ko) * 2012-11-30 2015-08-03 로슈 글리카트 아게 암세포 표적화된 mhc 클래스 i 포함 다중기능 단백질을 사용하는 순환 바이러스-특이적 세포독성 t-세포에 의한 암세포의 제거
JP6475167B2 (ja) 2012-12-21 2019-02-27 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ジスルフィド結合した多価ｍｈｃクラスｉを含む多機能タンパク質
US9371352B2 (en) 2013-02-08 2016-06-21 Vaccinex, Inc. Modified glycolipids and methods of making and using the same
US10294454B2 (en) 2016-08-24 2019-05-21 General Electric Company Methods and kits for cell activation

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0006916B1 (en) * 1977-09-28 1981-07-08 National Research Development Corporation Immunological preparations incorporating mhc antigens and their production
EP0031812B1 (en) * 1979-03-27 1983-06-15 National Research Development Corporation Improvements in or relating to immunological preparations
DE3329184A1 (de) * 1983-08-12 1985-02-21 Behringwerke Ag, 3550 Marburg Monoklonale antikoerper mit spezifitaet fuer membran-assoziierte antigene
DE3531301A1 (de) * 1985-09-02 1987-03-05 Behringwerke Ag Monoklonale antikoerper gegen tumorassoziierte glykoproteine, verfahren zu ihrer herstellung sowie ihre verwendung
US4894443A (en) * 1984-02-08 1990-01-16 Cetus Corporation Toxin conjugates
DE3545576A1 (de) * 1985-11-28 1987-07-02 Behringwerke Ag Hla-b 27, dafuer codierende genomische dna und ihre verwendung
US5258498A (en) * 1987-05-21 1993-11-02 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
EP0334300A1 (en) 1988-03-21 1989-09-27 Neorx Corporation The use of monoclonal antibodies and conjugates thereof as signals to direct sensitized effector cells to tumor sites
US5130297A (en) * 1988-06-23 1992-07-14 Anergen, Inc. Conjugates useful in ameliorating autoimmunity MHC-II-peptide
US5194425A (en) * 1988-06-23 1993-03-16 Anergen, Inc. Mhc-mediated toxic conjugates useful in ameliorating autoimmunity
DE3825615A1 (de) * 1988-07-28 1990-02-01 Behringwerke Ag Antigenkonstrukte von "major histocompatibility complex" klasse i antigenen mit spezifischen traegermolekuelen, ihre herstellung und verwendung
US5225538A (en) * 1989-02-23 1993-07-06 Genentech, Inc. Lymphocyte homing receptor/immunoglobulin fusion proteins
US5734023A (en) * 1991-11-19 1998-03-31 Anergen Inc. MHC class II β chain/peptide complexes useful in ameliorating deleterious immune responses

Also Published As

Publication number Publication date
KR970010760B1 (ko) 1997-06-30
AU625065B2 (en) 1992-07-02
ES2080055T3 (es) 1996-02-01
FI100973B (fi) 1998-03-31
US6548067B1 (en) 2003-04-15
EP0352761A3 (de) 1991-09-04
US20040091488A1 (en) 2004-05-13
DE3825615A1 (de) 1990-02-01
ATE128732T1 (de) 1995-10-15
EP0352761B1 (de) 1995-10-04
DK371089A (da) 1990-01-29
JPH02104599A (ja) 1990-04-17
FI893575A0 (fi) 1989-07-26
KR910003098A (ko) 1991-02-26
DK371089D0 (da) 1989-07-27
FI893575A (fi) 1990-01-29
DE58909458D1 (de) 1995-11-09
GR3017915T3 (en) 1996-01-31
EP0352761A2 (de) 1990-01-31
PT91294B (pt) 1995-03-01
AU3900589A (en) 1990-02-01
JP2812726B2 (ja) 1998-10-22

Similar Documents

Publication Publication Date Title
PT91294A (pt) Processo para a preparacao de construtos de antigenes a partir de antigenes da classe i de "complexo de histocompatibilidade principal" com moleculas de suporte especificas e de composicoes farmaceuticas que os comtem
Lu et al. Tutorial review. Oriented immobilization of antibodies and its applications in immunoassays and immunosensors
Labeta et al. Structure of asymmetric non-precipitating antibody: presence of a carbohydrate residue in only one Fab region of the molecule.
Lowey et al. An immunochemical approach to the structure of myosin and the thick filament
BR9608481A (pt) Anticorpos quiméricos para administração de antìgenos a células selecionadas do sistema imunológico.
PT856520E (pt) Metodo de preparacao de um anticorpo monoclonal, anticorpo monoclonal, uma composicao farmaceutica e um reagente de diagnostico
Ferguson et al. Isolation and characterization of a T suppressor factor by using a monoclonal antibody.
ES2149159T3 (es) Proteinas de fusion con contenido en anticuerpos monoclonales, enlazador- y beta-glucuronidasa, destinadas a la activacion de profarmacos, su preparacion y utilizacion.
Hesketh et al. Immunohistochemical evidence for an association of ribosomes with microfilaments in 3T3 fibroblasts
Gordon et al. Antigenic modulation of lymphocytic surface immunoglobulin yielding resistance to complement-mediated lysis. I. Characterization with syngeneic and xenogeneic complements.
Parkhouse Non-covalent association of IgM subunits produced by reduction and alkylation
ATE197709T1 (de) Methadonderivate und protein- und polypeptid- methadonkonjugate und markierte verbindungen
DK0464101T3 (da) Forbedringer ved radioaktiv mærkning af proteiner
JPS61234779A (ja) 細胞毒性ｔリンパ球により溶解を受け得る標的細胞の製造法
ATE395422T1 (de) Chimäre antikörper zur abgabe von antigenen an selektierte zellen des immunsystems
Warner et al. Detection of two species of antibody molecules with the same specificity
ATE125305T1 (de) Monoklonale antikörper von ratten gegen menschliche antigene und verfahren zu deren herstellung.
Schröter-Kermani et al. An inhibition ELISA for the quantification of collagens type I and type II in cyanogen bromide-digested tissues using fragment-directed antibodies
Leu et al. Photometric assays for FcRI-dependent binding, phagocytosis, and antibody-dependent cellular cytotoxicity mediated by monomeric IgGγ2a in murine peritoneal macrophages
DE68906758T2 (de) Immunoadsorbens mit geringer Freisetzungsrate und Verfahren zu seiner Herstellung.
NO974793L (no) Fremgangsmåte til fremstilling av et monoklonalt antistoff mot Onkostatin M, eller et fragment derav
Stebbings et al. MAPs and motors in insect ovaries
FR2642072A1 (fr) Adsorbants thiophiliques
KR930701201A (ko) 면역반응성 화합물
WO1988007200A1 (en) Monoclonal antibody conjugation

Legal Events

Date Code Title Description
FG3A Patent granted, date of granting

Effective date: 19940817

MM3A Annulment or lapse

Free format text: LAPSE DUE TO NON-PAYMENT OF FEES

Effective date: 20020228