DK2758532T3 - Screening-fremgangsmåder og anvendelser deraf - Google Patents

Screening-fremgangsmåder og anvendelser deraf Download PDF

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DK2758532T3
DK2758532T3 DK12766050.4T DK12766050T DK2758532T3 DK 2758532 T3 DK2758532 T3 DK 2758532T3 DK 12766050 T DK12766050 T DK 12766050T DK 2758532 T3 DK2758532 T3 DK 2758532T3
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ligand
ligands
target
construct
antibody
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DK12766050.4T
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Jenny Mattsson
Björn Frendéus
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Bioinvent Int Ab
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1037—Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • G01N33/6857—Antibody fragments
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Virology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Plant Pathology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Oncology (AREA)

Claims (14)

1. Fremgangsmåde til isolering af mindst én anti-ligand, hvor anti-liganden er et polypeptid, til mindst én differentielt-udtrykt målligand, hvor målliganden er et celleoverfladeantigen, hvor den differentielt-udtrykte målligand er en lavt udtrykt ligand, hvor den lavt udtrykte ligand udtrykkes ved mellem 5000 og 20.000 kopier pr. celle, hvor fremgangsmåden omfatter trinnene at: (a) udføre differential biopanning på et bibliotek af anti-ligander for at isolere mindst én anti-ligand, hvor differential-biopanningstrinnet yderligere omfatter undertrinnene af at: (i) tilvejebringe et bibliotek af anti-ligander; (ii) tilvejebringe en første population af ligander omfattende en ligand fastgjort til eller inkorporeret i et subtractor ligandkonstrukt; (iii) tilvejebringe en anden population af ligander omfattende den samme ligand som trin (ii), fastgjort til eller inkorporeret i et subtractor ligandkonstrukt; (iv) bestemme en mængde af subtractor-ligandkonstruktet og målligandkonstruktet i populationerne under anvendelse af én eller flere ligninger afledt fra den universelle lov af massevirkning [C]c[D]rf =K [OW hvor: A, B, C & D = er deltagerne i omsætningen (reaktanter og produkter) a, b, c, & d = koefficienterne der er nødvendige for en balanceret kemisk ligning for at tillade isolation af anti-ligand til differentielt udtrykt målligand, hvor ligningen enten er:
hvor
bA = bundet anti-ligand A = totalt antal anti-ligand T = totalt antal ligander C = Avogadro's konstant (6,022 x 1023 partikler/mol) V = omsætningsvolumen (liter) Kd = ligevægts-dissociationskonstant eller
hvor bAP = bundet anti-ligand TP = antallet af ligander på CP Ts = antallet af ligander på Cs CP = antallet af målligandkonstrukter Cs = antallet af subtractor-ligandkonstrukter A = totalt antal af anti-ligand T = totalt antal af ligander C = Avogadro's konstant (6.022 x 1023 partikler/mol) V = omsætningsvolumen (liter) Kd = ligevægts-dissociationskonstant; (v) tilvejebringe mængde af subtractor-ligandkonstrukt som bestemt i trin (iv); (vi) tilvejebringe mængden af målligandkonstrukt som bestemt i trin (iv); (vii) tilvejebringe separationsorgan til isolering af anti-ligand bundet til målligandkonstruktet fra anti-ligand bundet til et subtractor-ligandkonstrukt; (viii) eksponere biblioteket af (i) til ligandkonstrukterne tilvejebragt ved (v) og (vi) til at tillade binding af anti-ligander til ligander; og
(ix) anvende separationsorganet til at isolere anti-ligand bundet til liganden fastgjort til eller inkorporeret i målligandkonstruktet; (b) derefter udføre højt gennemløbs-sekvensering på anti-ligander isoleret under trin (a); og, (c) derefter udføre ko nform ato risk screening for specifik binding af anti-liganden til den differentielt udtrykte ligand.
2. Fremgangsmåden ifølge krav 1, hvor celleoverfladeantigenet er i sin native form, eventuelt hvor celleoverfladeantigenet er en celleoverfladereceptor.
3. Fremgangsmåden ifølge kravene 1 eller 2, hvor det høje gennemløbssekvenseringstrin udføres ved 454 sekvensering, Illumina, SOLiD-fremgangsmåder eller Helicos-systemer, og/eller; hvor det konformatoriske screeningstrin udføresved Flow-cytometry, FMAT, ELISA, MSD eller CBA.
4. Fremgangsmåden ifølge krav 1, hvor liganden ikke udtrykkes på en af enten targetkonstruktet eller subtractorkonstruktet, og/eller; omfatter et yderligere trin at frigive anti-liganden fra liganden.
5. Fremgangsmåden ifølge kravene 1 eller 4, hvor trinnene (ii) til (ix) udføresparallelt for at isolere en flerhed af anti-ligander til en flerhed af forskellige ligander, og/eller; hvor trinnene (ii) til (ix) gentages én eller flere gange.
6. Fremgangsmåden ifølge kravene 1, 4 eller 5, hvor mængden af ét af subtractorkonstruktet eller målkonstruktet tilvejebringes i overskud af mængden af den anden af subtractorkonstruktet eller targetkonstruktet, hvor overskudsliganden er mellem 10 og 1000 gange, eller 2 og 10 gange, eller 1000 og 1.000.000 gange.
7. Fremgangsmåden ifølge krav 1 eller 4 til 6, hvor separationsorganet er valgt fra mindst én af en fast bærer, cellemembran og/eller dele deraf, syntetisk membran, kugler, kemiske mærker og fri ligand.
8. Fremgangsmåden ifølge krav 1 eller 4 til 7, hvor separationsorganet af subtractoren og målkonstrukter har en forskellig densitet.
9. Fremgangsmåden ifølge krav 1 eller 4 til 8, hvor separationsorganet af subtractorkonstruktet er et membranvesikel eller en hel cellemembran.
10. Fremgangsmåden ifølge krav 1 eller 4 til 9 hvor trin (ix) udføres ved mindst én af densitetscentrifugering, fastbærersekvestrering, magnetisk kuglesekvestrering, kemisk mærkebinding og vandig faseseparation.
11. Fremgangsmåden ifølge et hvilket som helst af de foregående krav, hvor biblioteket af trin (a) er et display-bibliotek omfattende en flerhed af bibliotekselementer der fremviser anti-ligander, hvor eventuelt biblioteket er et phage-displaybibliotek.
12. Fremgangsmåden ifølge et hvilket som helst af de foregående krav, hvor liganden er mindst én valgt fra antigener; receptorligander; og enzymmål der omfatter mindst én fra carbohydrat; protein; peptid; lipid; polynukleotid; uorganiske molekyler og konjugerede molekyler.
13. Fremgangsmåden ifølge et hvilket som helst af de foregående krav, hvor anti-ligandbiblioteket er konstrueret fra mindst én fra antistoffer, og antigensbindingsvarianter, derivativer eller fragmenter deraf; scaffold-molekyler med bearbejdede variable overflader; receptorer; og enzymer.
14. Fremgangsmåden ifølge krav 1 eller 4 til 13 omfattende et yderligere trin af eksponere liganden og dets separationsorgan til en stimulus der indfluerer på ekspressionen af målligander på ligandkonstruktene.
DK12766050.4T 2011-09-22 2012-09-20 Screening-fremgangsmåder og anvendelser deraf DK2758532T3 (da)

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GBGB1116364.9A GB201116364D0 (en) 2011-09-22 2011-09-22 Screening methods and uses thereof
PCT/EP2012/068576 WO2013041643A1 (en) 2011-09-22 2012-09-20 Screening methods and uses thereof

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US (1) US10191049B2 (da)
EP (1) EP2758532B1 (da)
JP (2) JP6370220B2 (da)
KR (1) KR102024125B1 (da)
CN (2) CN103827302A (da)
AU (1) AU2012311542B2 (da)
CA (1) CA2848932C (da)
DK (1) DK2758532T3 (da)
ES (1) ES2690783T3 (da)
GB (1) GB201116364D0 (da)
HK (1) HK1200486A1 (da)
HU (1) HUE040567T2 (da)
IN (1) IN2014DN01795A (da)
PL (1) PL2758532T3 (da)
PT (1) PT2758532T (da)
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GB2392723B (en) 2002-09-04 2005-01-12 Bioinvent Int Ab Screening methods
GB201116364D0 (en) 2011-09-22 2011-11-02 Bioinvent Int Ab Screening methods and uses thereof
EP3730624A1 (en) * 2013-11-22 2020-10-28 Molcure, Inc. Method for determining and system for determining polypeptide bonding to target molecule
CA2957535C (en) 2014-08-07 2023-10-03 The General Hospital Corporation Stabilization of whole blood samples
CN109651506B (zh) * 2017-10-11 2021-12-07 上海交通大学 一种快速获得抗原特异性抗体的方法
WO2023242125A1 (en) 2022-06-13 2023-12-21 Bioinvent International Ab Methods of isolating anti-ligands

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US5366862A (en) 1990-02-14 1994-11-22 Receptor Laboratories, Inc. Method for generating and screening useful peptides
DE69128362T2 (de) 1990-06-01 1998-05-20 Chiron Corp Zusammensetzungen und verfahren zur identifizierung von molekülen mit biologischer wirksamkeit
CA2180140A1 (en) 1993-12-27 1995-07-06 Jeffrey I. Weitz Methods and compositions for inhibiting thrombogenesis
US6794128B2 (en) 1998-04-24 2004-09-21 The Regents Of The University Of California Methods of selecting internalizing antibodies
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GB2392723B (en) 2002-09-04 2005-01-12 Bioinvent Int Ab Screening methods
CN100575489C (zh) 2003-05-14 2009-12-30 多曼蒂斯有限公司 从多肽全能文库恢复可逆可解折叠多肽的方法
EP1627062A1 (en) * 2003-05-14 2006-02-22 Domantis Limited A process for recovering polypeptides that unfold reversibly from a polypeptide repertoire
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GB201116364D0 (en) 2011-09-22 2011-11-02 Bioinvent Int Ab Screening methods and uses thereof

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AU2012311542B2 (en) 2017-09-21
IN2014DN01795A (da) 2015-05-15
CN107663238A (zh) 2018-02-06
SI2758532T1 (sl) 2018-12-31
RU2622089C2 (ru) 2017-06-09
ES2690783T3 (es) 2018-11-22
GB201116364D0 (en) 2011-11-02
RU2014115956A (ru) 2015-10-27
US10191049B2 (en) 2019-01-29
HUE040567T2 (hu) 2019-03-28
HK1200486A1 (en) 2015-08-07
JP2018154627A (ja) 2018-10-04
CN103827302A (zh) 2014-05-28
KR102024125B1 (ko) 2019-09-23
CA2848932A1 (en) 2013-03-28
PL2758532T3 (pl) 2018-12-31
AU2012311542A1 (en) 2014-03-20
KR20140080504A (ko) 2014-06-30
WO2013041643A1 (en) 2013-03-28
US20140227249A1 (en) 2014-08-14
JP6370220B2 (ja) 2018-08-08
EP2758532A1 (en) 2014-07-30
EP2758532B1 (en) 2018-07-11
CA2848932C (en) 2020-12-29
PT2758532T (pt) 2018-11-07
JP2015501289A (ja) 2015-01-15

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