DK2934597T3 - Fremgangsmåder til fremstilling af immunkonjugater - Google Patents

Fremgangsmåder til fremstilling af immunkonjugater Download PDF

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Publication number
DK2934597T3
DK2934597T3 DK13863999.2T DK13863999T DK2934597T3 DK 2934597 T3 DK2934597 T3 DK 2934597T3 DK 13863999 T DK13863999 T DK 13863999T DK 2934597 T3 DK2934597 T3 DK 2934597T3
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Denmark
Prior art keywords
buffer
immunoconjugate
antibody
refold
column
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DK13863999.2T
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English (en)
Inventor
Alan Hunter
Thomas Linke
Tim Pabst
Michaela Wendeler
Xiangyang Wang
Guoling Xi
Andrew Fulton
Chris Thompson
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Medimmune Llc
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Publication of DK2934597T3 publication Critical patent/DK2934597T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2851—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • 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
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
    • C07K1/1136—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating or stabilising agents
    • 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
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/21—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Pseudomonadaceae (F)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • C07K2317/50—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
    • C07K2319/00—Fusion polypeptide
    • C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (17)

1. Fremgangsmåde til fremstilling af et aktivt immunkonjugat, hvor immunkonjugatet deamideres i en eller flere rester, hvor deamideringen resulteret i en inhibering af styrken af immunkonjugatet, og hvor immunkonjugatet består af to polypeptidkæder, der er forbundet via en disulfidbinding, hvilken fremgangsmåde omfatter refoldning af immunkonjugatet i en fed-batch-refoldningsproces i en refoldningsbuffer med et pH på 9,5 eller derunder og oprensning af det refoldede immunkonjugat ved anvendelse af en to-cyklus-eluering på en ionbytningssøjle, hvor søjlen renses mellem en første eluring og en anden eluring med en rensebuffer, der omfatter ethanolamin, arginin, ethylendiamintetraeddikesyre (EDTA), urinstof og dithiothreitol (DTT).
2. Fremgangsmåde ifølge krav 1, hvor mængden af immunkonjugatet, der indvindes ved fremgangsmåden til fremstilling er mindst tre hundrede % (300 %) større end mængden af immunkonjugatet, der indvindes ved anvendelse af en fremgangsmåde, der ikke omfatter en fed-batch-refoldningsproces og/eller oprensning på en ionbytningssøjle, der er blevet renset ved anvendelse af rensebufferen.
3. Fremgangsmåde ifølge krav 2, hvor polypeptidet eller immunkonjugatet omfatter et antistof eller et antigenbindende fragment deraf.
4. Fremgangsmåde ifølge krav 2, hvor antistoffet eller det antigenbindende fragment omfatter et Fab, et Fab', et F(ab')2, et Fd, et enkeltkædet Fv eller scFv, et disulfidforbundet Fv, et V-NAR-domæne, et IgNar, et intrabody, et IgGACH2, et minibody, et F(ab')3, et tetrabody, et triabody, et diabody, et enkeltdomæne-antistof, DVD-Ig, Fcab, mAb2, et (scFvb eller et scFv-Fc.
5. Fremgangsmåde ifølge krav 2, hvor polypeptidet eller immunkonjugatet omfatter et toksin.
6. Fremgangsmåde ifølge krav 5, hvor toksinet er et Pseudomonas-exotoksin eller en variant deraf.
7. Fremgangsmåde ifølge krav 6, hvor Pseudomonas-exotoksinet eller varianten deraf har en aminosyresekvens valgt fra gruppen, der består af SEQ ID NO: 16-22.
8. Fremgangsmåde ifølge krav 7, hvor Pseudomonas-exotoksinet eller varianten deraf har aminosyresekvensen ifølge SEQ ID NO: 22.
9. Fremgangsmåde ifølge krav 3 eller 4, hvor antistoffet eller det antigenbindende fragment deraf omfatter en VH- og en VL-sekvens.
10. Fremgangsmåde ifølge krav 9, hvor VH-sekvensen er valgt fra gruppen, der består af SEQ ID NO: 6-11.
11. Fremgangsmåde ifølge krav 9, hvor VL-sekvensen er valgt fra gruppen, der består af SEQ ID NO: 2 og 12-15.
12. Fremgangsmåde ifølge krav 2, hvor immunkonjugatet omfatter et anti-CD22-antistof eller et antigenbindende fragment deraf og et PE eller en variant deraf.
13. Fremgangsmåde ifølge krav 12, hvor immunkonjugatet er immuntoksinet moxetumomab asudotox, der omfatter VH-PE38-subunitten ifølge SEQ ID NO: 1 og VL-subunitten ifølge SEQ ID NO: 2 .
14. Fremgangsmåde ifølge krav 2, hvor refoldningsbufferen har et pH på 9,4.
15. Fremgangsmåde ifølge krav 2, hvor fed-batch-processen benytter en tilsætningshastighed på: a) fra ca. 52 ml opløste inklusionslegemer pr. liter refoldningsbuf fer pr. time til ca. 13 ml opløste inklusionslegemer pr. liter refoldningsbuffer pr. time; b) fra ca. 35 ml opløste inklusionslegemer pr. liter ref oldningsbuf fer pr. time til ca. 17 ml opløste inklusionslegemer pr. liter refoldningsbuffer pr. time; c) fra ca. 30 ml opløste inklusionslegemer pr. liter ref oldningsbuf fer pr. time til ca. 18 ml opløste inklusionslegemer pr. liter refoldningsbuffer pr. time; eller d) ca. 26 ml opløste inklusionslegemer pr. liter refoldningsbuffer pr. time.
16. Fremgangsmåde ifølge krav 2, hvor rensebufferen omfatter ca. 0,25 til ca. 0,75 M arginin, ca. 7-9 M urinstof og ca. 9-11 mM DTT.
17. Fremgangsmåde ifølge et hvilket som helst af kravene 15-16, hvor fed-batch-processen finder sted over et tidsrum på ca. 2 til ca. 8 timer.
DK13863999.2T 2012-12-20 2013-12-19 Fremgangsmåder til fremstilling af immunkonjugater DK2934597T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261740111P 2012-12-20 2012-12-20
PCT/US2013/076625 WO2014100443A2 (en) 2012-12-20 2013-12-19 Methods of producing immunoconjugates

Publications (1)

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DK2934597T3 true DK2934597T3 (da) 2019-02-11

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US (1) US9920124B2 (da)
EP (2) EP3494992B1 (da)
JP (1) JP6553515B2 (da)
CN (2) CN110950955A (da)
AU (2) AU2013361235B2 (da)
CA (1) CA2894908C (da)
DK (1) DK2934597T3 (da)
ES (2) ES2710314T3 (da)
WO (1) WO2014100443A2 (da)

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DK3334747T5 (da) * 2015-08-13 2024-10-07 Amgen Inc Ladet dybdefiltrering af antigenbindende proteiner
EP4223775A4 (en) * 2020-09-29 2025-07-30 Kunming Sinoway Natural Pharmaceuticals Co Ltd HUMANIZED RECOMBINANT ANTI-CD22 IMMUNOTOXIN AND ITS APPLICATION

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EP3494992A1 (en) 2019-06-12
HK1216142A1 (en) 2016-10-21
CA2894908A1 (en) 2014-06-26
CN110950955A (zh) 2020-04-03
US9920124B2 (en) 2018-03-20
EP3494992B1 (en) 2022-07-27
WO2014100443A3 (en) 2015-07-16
CA2894908C (en) 2022-07-12
AU2013361235B2 (en) 2018-07-26
AU2013361235A1 (en) 2015-07-02
ES2929876T3 (es) 2022-12-02
JP2016503062A (ja) 2016-02-01
AU2018232979A1 (en) 2018-10-11
CN105007937B (zh) 2019-11-19
WO2014100443A2 (en) 2014-06-26
HK1215547A1 (zh) 2016-09-02
ES2710314T3 (es) 2019-04-24
EP2934597A2 (en) 2015-10-28
EP2934597B1 (en) 2018-10-17
US20150337040A1 (en) 2015-11-26
EP2934597A4 (en) 2016-07-20
JP6553515B2 (ja) 2019-07-31
CN105007937A (zh) 2015-10-28

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