DE09001901T1 - Verfahren zur Herstellung von spezifischen Bindungspaargliedern - Google Patents

Verfahren zur Herstellung von spezifischen Bindungspaargliedern Download PDF

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DE09001901T1
DE09001901T1 DE09001901T DE09001901T DE09001901T1 DE 09001901 T1 DE09001901 T1 DE 09001901T1 DE 09001901 T DE09001901 T DE 09001901T DE 09001901 T DE09001901 T DE 09001901T DE 09001901 T1 DE09001901 T1 DE 09001901T1
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binding
filamentous bacteriophage
bacteriophage particles
molecule
nucleic acid
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John Mccafferty
Anthony Richard Pope
Kevin Stuart Johnson
Hendricus Renerus Jacobus Mattheus Hoogenboom
Andrew David Griffiths
Ronald Henry Jackson
Kaspar Philipp Holliger
James David Marks
Timothy Piers Clackson
David John Chiswell
Gregory Paul Winter
Timothy Peter Bonnert
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Medical Research Council
MedImmune Ltd
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Medical Research Council
MedImmune Ltd
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Priority claimed from GB909024503A external-priority patent/GB9024503D0/en
Priority claimed from GB919104744A external-priority patent/GB9104744D0/en
Priority claimed from GB919110549A external-priority patent/GB9110549D0/en
Application filed by Medical Research Council, MedImmune Ltd filed Critical Medical Research Council
Publication of DE09001901T1 publication Critical patent/DE09001901T1/de
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/005—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies constructed by phage libraries
    • 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
    • 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
    • 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
    • C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
    • 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
    • C07K16/34—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood group antigens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • 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
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
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    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
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    • 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
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    • 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
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    • C12N15/62—DNA sequences coding for fusion proteins
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    • 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
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • C12N15/73—Expression systems using phage (lambda) regulatory sequences
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    • C40—COMBINATORIAL TECHNOLOGY
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    • C40B40/02—Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
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    • C07K2317/55—Fab or Fab'
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C—CHEMISTRY; METALLURGY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • C07K2319/41—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a Myc-tag
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    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/735—Fusion polypeptide containing domain for protein-protein interaction containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/867—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof involving immunoglobulin or antibody produced via recombinant dna technology

Abstract

Verfahren zur Herstellung eines Moleküls, das in Bezug auf ein spezielles Target Bindungsspezifität aufweist, wobei das Verfahren Folgendes umfasst:
das Herstellen einer Population filamentöser Bakteriophagenpartikel, die an ihrer Oberfläche eine Population von Bindungsmolekülen mit einer Reihe von Bindungsspezifitäten präsentieren, worin die Bindungsmoleküle Antigenbindungsdomänen für spezifische komplementäre Bindungspaarelemente aufweisen, worin die Bindungsmoleküle auf der Oberfläche der filamentösen Bakteriophagenpartikel durch die Fusion mit einem Gen-III-Protein der filamentösen Bakteriophagenpartikel präsentiert werden und worin jeder filamentöse Bakteriophagenpartikel Nucleinsäure enthält, die für das aus der Nucleinsäure exprimierte und von dem Partikel auf seiner Oberfläche präsentierte Bindungsmolekül kodiert;
das Selektieren eines filamentösen Bakteriophagenpartikels, das ein Bindungsmolekül mit einer gewünschten Spezifität präsentiert, durch Kontaktieren der Population filamentöser Bakteriophagenpartikel mit einem bestimmten Target, so dass einzelne Bindungsmoleküle mit der gewünschten Bindungseigenschaft, die auf filamentösen Bakteriophagenpartikeln präsentiert werden, an das Target binden;
das Trennen von gebundenen filamentösen Bakteriophagenpartikeln von dem Target;
das Gewinnen abgetrennter...

Claims (5)

  1. Verfahren zur Herstellung eines Moleküls, das in Bezug auf ein spezielles Target Bindungsspezifität aufweist, wobei das Verfahren Folgendes umfasst: das Herstellen einer Population filamentöser Bakteriophagenpartikel, die an ihrer Oberfläche eine Population von Bindungsmolekülen mit einer Reihe von Bindungsspezifitäten präsentieren, worin die Bindungsmoleküle Antigenbindungsdomänen für spezifische komplementäre Bindungspaarelemente aufweisen, worin die Bindungsmoleküle auf der Oberfläche der filamentösen Bakteriophagenpartikel durch die Fusion mit einem Gen-III-Protein der filamentösen Bakteriophagenpartikel präsentiert werden und worin jeder filamentöse Bakteriophagenpartikel Nucleinsäure enthält, die für das aus der Nucleinsäure exprimierte und von dem Partikel auf seiner Oberfläche präsentierte Bindungsmolekül kodiert; das Selektieren eines filamentösen Bakteriophagenpartikels, das ein Bindungsmolekül mit einer gewünschten Spezifität präsentiert, durch Kontaktieren der Population filamentöser Bakteriophagenpartikel mit einem bestimmten Target, so dass einzelne Bindungsmoleküle mit der gewünschten Bindungseigenschaft, die auf filamentösen Bakteriophagenpartikeln präsentiert werden, an das Target binden; das Trennen von gebundenen filamentösen Bakteriophagenpartikeln von dem Target; das Gewinnen abgetrennter filamentöser Bakteriophagenpartikel, die ein Bindungsmolekül mit der gewünschten Bindungseigenschaft präsentieren; das Isolieren von Nucleinsäure, die für das Bindungsmolekül kodiert, aus den abgetrennten filamentösen Bakteriophagenpartikeln; das Insertieren von für das Bindungsmolekül kodierender Nucleinsäure oder einem Fragment oder Derivat davon mit Bindungsspezifität in Bezug auf das Target in ein Rekombinationssystem; und das Produzieren eines von den filamentösen Bakteriophagenpartikeln getrennten Moleküls mit Bindungsspezifität für das Target in dem Rekombinationssystem, worin das Molekül das Bindungsmolekül oder ein Fragment oder Derivat davon mit Bindungsspezifität für das Target ist.
  2. Verfahren nach Anspruch 1, worin die für die Bindungsmoleküle in der Population kodierende Nucleinsäure durch In-vitro-Kombination von nicht neugeordneten V-Segmenten mit D- und J-Segmenten bereitgestellt wird.
  3. Verfahren nach Anspruch 1, worin die für die Bindungsmoleküle in der Population kodierende Nucleinsäure durch In-vitro-Mutagenese einer bestehenden, für einen Antikörper kodierenden Sequenz abgeleitet wird.
  4. Filamentöses Bakteriophagenpartikel, das auf seiner Oberfläche ein Bindungsmolekül präsentiert, das eine Bindungsdomäne umfasst, die in der Lage ist, an ein spezifisches komplementäres Bindungspaarelement zu binden, worin das Bindungsmolekül auf der Oberfläche des filamentösen Bakteriophagenpartikels durch Fusion mit einem Gen-III-Protein des filamentösen Bakteriophagenpartikels präsentiert wird, worin die Bindungsdomäne eine Antikörper-Antigen-Bindungsdomäne ist, wobei das Partikel Nucleinsäure enthält, die für das aus der Nucleinsäure exprimierte und von dem Partikel auf seiner Oberfläche präsentierte Bindungsmolekül kodiert.
  5. Population filamentöser Bakteriophagenpartikel nach Anspruch 4, die eine Population der Bindungsmoleküle mit einer Reihe von Bindungsspezifitäten präsentiert.
DE09001901T 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern Pending DE09001901T1 (de)

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
GB9015198 1990-07-10
GB909015198A GB9015198D0 (en) 1990-07-10 1990-07-10 Binding substance
GB9022845 1990-10-19
GB909022845A GB9022845D0 (en) 1990-07-10 1990-10-19 Antibodies
GB909024503A GB9024503D0 (en) 1990-11-12 1990-11-12 Binding substances
GB9024503 1990-11-12
GB9104744 1991-03-06
GB919104744A GB9104744D0 (en) 1991-03-06 1991-03-06 Binding substances
GB9110549 1991-05-15
GB919110549A GB9110549D0 (en) 1991-05-15 1991-05-15 Binding substances

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DE09001901T1 true DE09001901T1 (de) 2009-09-03

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DE09001901T Pending DE09001901T1 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern
DE69133625T Expired - Lifetime DE69133625D1 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern
DE69132920T Expired - Lifetime DE69132920C5 (de) 1990-07-10 1991-07-10 Methode zur Herstellung von filamentösen, antikörper-präsentierenden Bakteriophagenpartikeln durch Verwendung von Phagemiden und die daduch hergestellten Bakteriophagenpartikel
DE69123156T Expired - Lifetime DE69123156T3 (de) 1990-07-10 1991-07-10 VERFAHREN ZUR ERZEUGUNG FUNKTIONELLER, EINKETTIGER Fv ANTIKOERPER-FRAGMENTE AUF BAKTERIOPHAGEN-OBERFLÄCHEN
DE69133568T Expired - Lifetime DE69133568T2 (de) 1990-07-10 1991-07-10 Bakteriophagenpartikeln,die dAbs präsentieren
DE69133545T Expired - Lifetime DE69133545T2 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern
DE122010000026C Active DE122010000026I2 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern

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DE69133625T Expired - Lifetime DE69133625D1 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern
DE69132920T Expired - Lifetime DE69132920C5 (de) 1990-07-10 1991-07-10 Methode zur Herstellung von filamentösen, antikörper-präsentierenden Bakteriophagenpartikeln durch Verwendung von Phagemiden und die daduch hergestellten Bakteriophagenpartikel
DE69123156T Expired - Lifetime DE69123156T3 (de) 1990-07-10 1991-07-10 VERFAHREN ZUR ERZEUGUNG FUNKTIONELLER, EINKETTIGER Fv ANTIKOERPER-FRAGMENTE AUF BAKTERIOPHAGEN-OBERFLÄCHEN
DE69133568T Expired - Lifetime DE69133568T2 (de) 1990-07-10 1991-07-10 Bakteriophagenpartikeln,die dAbs präsentieren
DE69133545T Expired - Lifetime DE69133545T2 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern
DE122010000026C Active DE122010000026I2 (de) 1990-07-10 1991-07-10 Verfahren zur Herstellung von spezifischen Bindungspaargliedern

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US (7) US5969108A (de)
EP (7) EP0774511B1 (de)
JP (1) JP3176917B2 (de)
KR (1) KR100222326B1 (de)
AT (6) ATE542898T1 (de)
AU (1) AU664155B2 (de)
CA (1) CA2086936C (de)
DE (7) DE09001901T1 (de)
DK (5) DK0774511T3 (de)
ES (5) ES2171581T3 (de)
GB (2) GB9015198D0 (de)
GR (1) GR3022126T3 (de)
HK (1) HK1131637A1 (de)
LU (1) LU91623I2 (de)
NL (1) NL300423I1 (de)
WO (1) WO1992001047A1 (de)

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EP0368684B2 (de) * 1988-11-11 2004-09-29 Medical Research Council Klonierung von Immunglobulin sequenzen aus den variabelen Domänen.
US7413537B2 (en) 1989-09-01 2008-08-19 Dyax Corp. Directed evolution of disulfide-bonded micro-proteins
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US5723286A (en) 1990-06-20 1998-03-03 Affymax Technologies N.V. Peptide library and screening systems
GB9015198D0 (en) * 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US6916605B1 (en) * 1990-07-10 2005-07-12 Medical Research Council Methods for producing members of specific binding pairs
US7063943B1 (en) 1990-07-10 2006-06-20 Cambridge Antibody Technology Methods for producing members of specific binding pairs
GB9206318D0 (en) * 1992-03-24 1992-05-06 Cambridge Antibody Tech Binding substances
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