HRP20140760T1 - Citotoksiäśni imunoglobulin - Google Patents

Citotoksiäśni imunoglobulin Download PDF

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Publication number
HRP20140760T1
HRP20140760T1 HRP20140760AT HRP20140760T HRP20140760T1 HR P20140760 T1 HRP20140760 T1 HR P20140760T1 HR P20140760A T HRP20140760A T HR P20140760AT HR P20140760 T HRP20140760 T HR P20140760T HR P20140760 T1 HRP20140760 T1 HR P20140760T1
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Croatia
Prior art keywords
antibody according
modular
modular antibody
amino acids
library
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HRP20140760AT
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English (en)
Inventor
Gottfried Himmler
Geert Mudde
Anton Bauer
Gerda Redl
Florian Rueker
Gordana Wozniak-Knopp
Maximillian Woisetschlaeger
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F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H
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Publication of HRP20140760T1 publication Critical patent/HRP20140760T1/hr

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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
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • C07K16/30—Immunoglobulins [IGs], 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
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • 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
    • C07K2317/565—Complementarity determining region [CDR]
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]
    • 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)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Claims (16)

1. Citotoksično modularno protutijelo, naznačeno time, da se specifično veže za cilj na površini stanice s afinitetom vezanja od Kd<10-8 M, pri čemu je to Fc (Fcab) koji veže antigen molekule protutijela s funkcijom efektora, koje ima barem jednu od ADCC, ADCP i CD aktivnosti, s mjestom vezanja antigena uređenim na području čvorova od domene CH3 za vezanje na spomenuti cilj na površini stanice, pri čemu cilj na površini stanice je receptor iz razreda erbB.
2. Modularno protutijelo prema zahtjevu 1, naznačeno time, da ima aktivnost ADCC.
3. Modularno protutijelo prema zahtjevu 1 ili 2, naznačeno time, da spomenuto mjesto vezanja antigena sadrži nasumce odabranu sekvencu protutijela.
4. Modularno protutijelo prema bilo kojem zahtjevu od 1 do 3, naznačeno time, da je spomenuto mjesto vezanja antigena postavljeno u rasponu aminokiselina od 7 do 21, aminokiselina od 25 do 39, aminokiselina od 41 do 81, aminokiselina od 83 do 85, aminokiselina od 89 do 103 i aminokiselina od 106 do 117, pri čemu numeriranje odgovara brojčanoj shemi IMTG.
5. Modularno protutijelo prema bilo kojem zahtjevu od 1 do 4, naznačeno time, da je to IgG1 Fc.
6. Modularno protutijelo prema bilo kojem zahtjevu od 1 do 5, naznačeno time, da je spomenuti cilj odabran iz skupine koju čine: EGFR, Her2, Her2neu, HER3 i HER4.
7. Modularno protutijelo prema zahtjevu 6, naznačeno time, da se spomenuto mjesto vezanja antigena specifično veže na Her2 i sadrži aminokiselinsku sekvencu odabranu iz skupine koja se sastoji od SEQ ID brojeva popisanih u Tablici 4 i Tablici 5, te koja je u sastavu čvora EF i/ili čvora AB i/ili čvora CD.
8. Modularno protutijelo prema bilo kojem zahtjevu od 1 do 7, naznačeno time, da se može dobiti iz biblioteke oligomera od domena modularnih protutijela, koje se vežu za ligand-efektor.
9. Kombinirana molekula, naznačena time, da obuhvaća modularno protutijelo prema bilo kojem zahtjevu od 1 do 8, zajedno s ostalim peptidima ili polipeptidima.
10. Kombinirano modularno protutijelo, naznačeno time, da obuhvaća modularno protutijelo prema bilo kojem zahtjevu od 1 do 8, dodatno u kombinaciji s jednim ili više modificiranih modularnih protutijela ili s nemodificiranim protutijelima ili njihovim dijelovima.
11. Kombinirano modularno protutijelo prema zahtjevu 10, naznačeno time, da je to kompletna molekula protutijela.
12. Farmaceutski sastav, naznačen time, da obuhvaća modularno protutijelo prema bilo kojem zahtjevu od 1 do 11.
13. Postupak proizvodnje modularnog protutijela prema bilo kojem zahtjevu od 1 do 8, naznačen time, da obuhvaća sljedeće korake: a. pribavljanje Fcab-biblioteke, b. kontaktiranje spomenute biblioteke sa spomenutim ciljem u prisutnosti liganda-efektora, c. odabir člana biblioteke, koji ima oba sljedeća svojstva: (i) afinitet vezanja za cilj od Kd<10-8 M ili IC50<10-8 M, i (ii) aktivnost ADCC, ADCP ili CDC, i d. proizvodnja preparata modularnog protutijela.
14. Postupak prema zahtjevu 13, naznačen time, da članovi koji sastavljaju biblioteku, imaju nasumce izabranu sekvencu protutijela.
15. Postupak prema zahtjevu 13 ili 14, naznačen time, da nadalje obuhvaća korak dozrijevanja afiniteta od spomenutog člana biblioteke.
16. Modularno protutijelo prema bilo kojem zahtjevu od 1 do 11, naznačeno time, da se upotrebljava za liječenje pacijenta koji boluje od čvrstog tumora, kada tumor izražava receptor iz razreda erbB.
HRP20140760AT 2008-05-02 2014-08-11 Citotoksiäśni imunoglobulin HRP20140760T1 (hr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08450068A EP2113255A1 (en) 2008-05-02 2008-05-02 Cytotoxic immunoglobulin
PCT/EP2009/052509 WO2009132876A1 (en) 2008-05-02 2009-03-03 Cytotoxic immunoglobulin

Publications (1)

Publication Number Publication Date
HRP20140760T1 true HRP20140760T1 (hr) 2014-11-07

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ID=39745473

Family Applications (3)

Application Number Title Priority Date Filing Date
HRP20140760AT HRP20140760T1 (hr) 2008-05-02 2014-08-11 Citotoksiäśni imunoglobulin
HRP20161630TT HRP20161630T1 (hr) 2008-05-02 2016-12-05 Citotoksični imunoglobulin
HRP20181267TT HRP20181267T1 (hr) 2008-05-02 2018-08-03 Citotoksični imunoglobulin

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Application Number Title Priority Date Filing Date
HRP20161630TT HRP20161630T1 (hr) 2008-05-02 2016-12-05 Citotoksični imunoglobulin
HRP20181267TT HRP20181267T1 (hr) 2008-05-02 2018-08-03 Citotoksični imunoglobulin

Country Status (15)

Country Link
US (4) US8859738B2 (hr)
EP (4) EP2113255A1 (hr)
JP (2) JP5693447B2 (hr)
CN (2) CN102083464B (hr)
CA (1) CA2721614C (hr)
CY (1) CY1119508T1 (hr)
DK (3) DK2630970T3 (hr)
ES (3) ES2609359T3 (hr)
HR (3) HRP20140760T1 (hr)
HU (2) HUE039975T2 (hr)
LT (2) LT2698165T (hr)
PL (3) PL2274012T3 (hr)
PT (1) PT2630970T (hr)
SI (2) SI2274012T1 (hr)
WO (1) WO2009132876A1 (hr)

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