DK2454283T3 - Midler og fremgangsmåder til fremstilling af antistoffer med høj affinitet - Google Patents

Midler og fremgangsmåder til fremstilling af antistoffer med høj affinitet Download PDF

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Publication number
DK2454283T3
DK2454283T3 DK10734366.7T DK10734366T DK2454283T3 DK 2454283 T3 DK2454283 T3 DK 2454283T3 DK 10734366 T DK10734366 T DK 10734366T DK 2454283 T3 DK2454283 T3 DK 2454283T3
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Denmark
Prior art keywords
cell
bcl
cells
aid
nucleic acid
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DK10734366.7T
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English (en)
Inventor
Tim Beaumont
Hergen Spits
Mark Jeroen Kwakkenbos
Adrianus Quirinus Bakker
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Aimm Therapeutics Bv
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Publication of DK2454283T3 publication Critical patent/DK2454283T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C07K16/11—Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Virology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pulmonology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (11)

1. Fremgangsmåde in vitro til modulering af forekomsten af somatiske hypermutationer i en antistof-producerende plasmablast-lignende B-celle, hvilken fremgangsmåde omfatter: transduktion af en B-celle med et nukleinsyremolekyle, der koder for BCL6, og transduktion af B-cellen med et anti-apoptotisk nukleinsyremolekyle fra Bcl-2-familien, hvorved der genereres en antistof-producerende plasmablast-lignende B-celle; hvor fremgangsmåden endvidere omfatter at forsyne B-cellen med IL21 og CD40L; og - opnåelse af immunoglobuliner, der rummer mutationer, som ikke er til stede i B-cellen før transduktion med BCL6 og det anti-apoptotiske nukleinsyremolekyle.
2. Fremgangsmåde ifølge krav 1, hvor B-cellen er en memory-B-celle, fortrinsvis en human memory-B-celle.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor den anti-apoptotiske nukleinsyre omfatter Bcl-xL eller Mcl-1 eller en funktionel del deraf.
4. Fremgangsmåde ifølge et hvilket som helst af kravene 1-3, der omfatter reduktion af forekomsten af somatiske hypermutationer i B-cellen ved reduktion af den aktiveringsinducerede cytidindeaminases (AID) funktionelle aktivitet i B-cellen.
5. Fremgangsmåde ifølge et hvilket som helst af kravene 1-4, hvor den aktiveringsinducerede cytidindeaminases (AID) funktionelle aktivitet reduceres ved reduktion af ekspression og/eller specifik aktivitet for aktiveringsinduceret cytidindeaminase (AID) i B-cellen.
6. Fremgangsmåde ifølge et hvilket som helst af kravene 1-5, hvor ekspression af aktiveringsinduceret cytidindeaminase (AID) moduleres ved ekspression af hæmmer af DNA-binding (ID) i B-cellen.
7. Isoleret eller rekombinant antistof-producerende B-celle, der udtrykker: - Bcl-6, og - en anti-apoptotisk nukleinsyre af Bcl-2-familien, og - hæmmer af DNA-binding (ID).
8. Isoleret eller rekombinant antistof-producerende B-celle ifølge krav 7, hvor den anti-apoptotisk nukleinsyre omfatter en nukleinsyre, der er udvalgt ffa gruppen bestående af Bcl-xL og Mcl-1 og en funktionel del af Bcl-xL og en funktionel del af Mel-1.
9. Rekombinant memory-B-celle, der omfatter: - Bcl-6, og - en anti-apoptotisk nukleinsyre af Bcl-2-familien, og - en antisense-nukleinsyre eller ribozym rettet mod basis helix-loop-helix- (bHLH) protein El2 og/eller E47, der forhindrer E12 og/eller E47 mRNA i at blive translateret til protein.
10. Rekombinant antistof-producerende plasmablast-lignende B-celle, der omfatter: - Bcl-6, og - en anti-apoptotisk nukleinsyre af Bcl-2-familien, og - en supplerende aktiveringsinduceret cytidindeaminase (AID)-kodende nukleinsyresekvens.
11. Anvendelse af en antistof-producerende plasmablast-lignende B-celle med reduceret ekspression og/eller aktivitet af aktiveringsinduceret cytidindeaminase (AID) og dermed reduceret forekomst af somatiske hypermutationer i B-cellen for fremstilling af antistoffer i stor målestok.
DK10734366.7T 2009-07-15 2010-07-15 Midler og fremgangsmåder til fremstilling af antistoffer med høj affinitet DK2454283T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US22588209P 2009-07-15 2009-07-15
EP09165603 2009-07-15
PCT/NL2010/050458 WO2011008093A1 (en) 2009-07-15 2010-07-15 Means and methods for producing high affinity antibodies

Publications (1)

Publication Number Publication Date
DK2454283T3 true DK2454283T3 (da) 2018-05-07

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DK10734366.7T DK2454283T3 (da) 2009-07-15 2010-07-15 Midler og fremgangsmåder til fremstilling af antistoffer med høj affinitet

Country Status (8)

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US (2) US9273118B2 (da)
EP (1) EP2454283B1 (da)
JP (2) JP5781508B2 (da)
AU (1) AU2010271583B2 (da)
CA (1) CA2768207C (da)
DK (1) DK2454283T3 (da)
ES (1) ES2666584T3 (da)
WO (1) WO2011008093A1 (da)

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Also Published As

Publication number Publication date
ES2666584T3 (es) 2018-05-07
WO2011008093A1 (en) 2011-01-20
EP2454283B1 (en) 2018-03-14
AU2010271583B2 (en) 2015-02-12
AU2010271583A1 (en) 2012-02-09
US9273118B2 (en) 2016-03-01
JP6076413B2 (ja) 2017-02-08
CA2768207A1 (en) 2011-01-20
US20120157662A1 (en) 2012-06-21
EP2454283A1 (en) 2012-05-23
JP2015180231A (ja) 2015-10-15
US10344076B2 (en) 2019-07-09
JP5781508B2 (ja) 2015-09-24
US20160194382A1 (en) 2016-07-07
CA2768207C (en) 2019-12-03
JP2012533294A (ja) 2012-12-27

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