DK2421898T3 - Cadherin-17-specifikke antistoffer - Google Patents

Cadherin-17-specifikke antistoffer Download PDF

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DK2421898T3
DK2421898T3 DK10714548.4T DK10714548T DK2421898T3 DK 2421898 T3 DK2421898 T3 DK 2421898T3 DK 10714548 T DK10714548 T DK 10714548T DK 2421898 T3 DK2421898 T3 DK 2421898T3
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antibody
seq
pta001
cadherin
antibodies
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Christian Rohlff
Jonathan Alexander Terrett
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Oxford Biotherapeutics Ltd
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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
    • 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
    • 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
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
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    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
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    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • 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
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/54—F(ab')2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • 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
    • C07K2317/50—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
    • C07K2317/50—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
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • 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
    • C07K2317/77—Internalization into the cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies

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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Claims (16)

1. Isoleret anti-Cadherin-17-antistof, der omfatter: en variabel tungkæderegion-CDRl, der omfatter SEQ ID NO: 4; en variabel tungkæderegion-CDR2, der omfatter SEQ ID NO: 8; en variabel tungkæderegion-CDR3, der omfatter SEQ ID NO: 17; en variabel letkæderegion-CDRl, der omfatter SEQ ID NO: 24; en variabel letkæderegion-CDR2, der omfatter SEQ ID NO: 30 og en variabel letkæderegion-CDR3, der omfatter SEQ ID NO: 34, eventuelt, hvor en hvilken som helst af SEQ ID NO: 4, 8, 17, 24, 30 eller 34 uafhængigt omfatter én, to, tre, fire eller fem konservative aminosyresubstitutioner, hvor antistoffet kan internaliseres i en celle, der udtrykker Cadherin-17.
2. Isoleret anti-Cadherin-17-antistof ifølge krav 1, hvor en hvilken som helst af SEQ ID NO: 4, 8, 17, 24, 30 eller 34 uafhængigt omfatter én, to, tre, fire eller fem konservative substitutioner af aminosyrer med basiske sidekæder.
3. Isoleret anti-Cadherin-17-antistof ifølge krav 1, hvor en hvilken som helst af SEQ ID NO: 4, 8, 17, 24, 30 eller 34 uafhængigt omfatter én eller to konservative aminosyresubstitutioner.
4. Antistof ifølge et hvilket som helst af kravene 1 til 3, hvor antistoffet er et fuldlængde antistof af en IgGl-, IgG2-, IgG3- eller IgG4-isotype.
5. Antistof ifølge et hvilket som helst af de foregående krav, hvor antistoffet er udvalgt fra gruppen bestående af: et helt antistof, et monoklonalt antistof, et antistoffragment, et humaniseret antistof, et enkeltkædeantistof, et defucosyleret antistof, et antistofmimetikum og et bispecifikt antistof, fortrinsvis hvor fragmentet er et domæneantistof.
6. Immunkonjugat, der omfatter et antistof ifølge et hvilket som helst af de foregående krav konjugeret til et terapeutisk middel.
7. Immunkonjugat ifølge krav 6, hvor det teerapeutiske middel er et cytotoxin eller en radioaktiv isotop.
8. Sammensætning, der omfatter det isolerede antistof eller den antigenbindende del deraf ifølge et hvilket som helst af kravene 1 til 5, eller et immunkonjugat ifølge krav 6 eller krav 7, og en farmaceutisk acceptabel bærer.
9. Isoleret nukleinsyremolekyle, der koder for de tunge og lette kæder af antistoffet eller den antigenbindende del deraf ifølge et hvilket som helst af kravene 1 til 5.
10. Ekspressionsvektor, der omfatter nukleinsyremolekylet ifølge krav 9.
11. Værtscelle, der omfatter: (i) ekspressionsvektoren ifølge krav 10 eller (ii) en første ekspressionsvektor, der koder for den tunge kæde af antistoffet eller den antigenbindende del deraf ifølge et hvilket som helst af kravene 1 til 5 og en anden ekspressionsvektor, der koder for den lette kæde af antistoffet eller den antigenbindende del deraf ifølge et hvilket som helst af kravene 1 til 5.
12. Fremgangsmåde til fremstilling af et anti-Cadherin-17-antistof, hvilken fremgangsmåde omfatter følgende trin: opnåelse af en værtscelle, der indeholder ét eller flere nukleinsyremolekyler, der koder for antistoffet ifølge et hvilket som helst af kravene 1 til 5; dyrkning af værtscellen i en værtscellekultur; tilvejebringelse af værtscelledyrkningsforhold, hvor det ene eller flere nukleinsyremolekyler udtrykkes; og genvinding af antistoffet fra værtscellen eller fra værtscellekulturen.
13. Fremgangsmåde til fremstilling af anti-Cadherin-17-antistoffer, hvilken fremgangsmåde omfatter følgende trin: genvinding af mRNA fra B-celleme af et dyr, der er immuniseret med et Cadherin-17-peptid; omdannelse af mRNA’et til cDNA; ekspression af cDNA’et i phager, således at anti-Cadherin-17-antistoffer, der er kodet for af cDNA’et, præsenteres på overfladen af phageme; udvælgelse af phager, der præsenterer anti-Cadherin-17-antistoffer; genvinding af nukleinsyremolekyler fra de udvalgte phager, der koder for anti-Cadherin-17-immunoglobulineme; ekspression af de genvundne nukleinsyremolekyler i en værtscelle; og genvinding af antistoffer som defineret i et hvilket som helst af kravene 1 til 3 fra den værtscelle, der binder Cadherin-17.
14. Anti-Cadherin-17-antistof, eller antigenbindende del deraf ifølge et hvilket som helst af kravene 1 til 5, eller immunkonjugat ifølge krav 6 eller krav 7, til anvendelse i behandling eller forebyggelse af en cancer forbundet med målceller, der udtrykker Cadherin-17.
15. Antistof, eller antigenbindende del deraf til anvendelse ifølge krav 14, hvor sygdommen er en human cancer.
16. Antistof, eller antigenbindende del deraf til anvendelse ifølge krav 15, hvor den humane cancer er colorectalcancer.
DK10714548.4T 2009-04-20 2010-04-20 Cadherin-17-specifikke antistoffer DK2421898T3 (da)

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Application Number Priority Date Filing Date Title
US17098009P 2009-04-20 2009-04-20
PCT/US2010/031719 WO2010123874A1 (en) 2009-04-20 2010-04-20 Antibodies specific to cadherin-17

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US (2) US9181339B2 (da)
EP (2) EP3009454A3 (da)
JP (2) JP6141638B2 (da)
KR (1) KR101736076B1 (da)
CN (2) CN106188295A (da)
AP (1) AP2011005984A0 (da)
AU (3) AU2010239351C1 (da)
BR (1) BRPI1014262A2 (da)
CA (1) CA2759538C (da)
CL (1) CL2011002611A1 (da)
CO (1) CO6450618A2 (da)
CR (1) CR20110559A (da)
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EA (1) EA030182B1 (da)
EC (1) ECSP11011466A (da)
ES (1) ES2574236T3 (da)
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