RU2016108598A - Функционализированные полипептиды - Google Patents

Функционализированные полипептиды Download PDF

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RU2016108598A
RU2016108598A RU2016108598A RU2016108598A RU2016108598A RU 2016108598 A RU2016108598 A RU 2016108598A RU 2016108598 A RU2016108598 A RU 2016108598A RU 2016108598 A RU2016108598 A RU 2016108598A RU 2016108598 A RU2016108598 A RU 2016108598A
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linker
amino acid
seq
scfv
sequence shown
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RU2016108598A
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Дэвид УРЕХ
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ИЭсБиЭйТЕК, ЭН АЛЬКОН БАЙОМЕДИКАЛ РИСЕРЧ ЮНИТ ЭлЭлСи
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Publication of RU2016108598A publication Critical patent/RU2016108598A/ru

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1037Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/56Medicinal 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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59Medicinal 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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal 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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/65Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241Tumor Necrosis Factors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1062Isolating an individual clone by screening libraries mRNA-Display, e.g. polypeptide and encoding template are connected covalently
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/40Immunoglobulins specific features characterized by post-translational modification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/40Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41Glycosylation, sialylation, or fucosylation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/31Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin

Claims (10)

1. Способ модификации фармакокинетических (PK) свойств scFv, включающий применение аминокислотного линкера, содержащего последовательность аминокислот, представленную в SEQ ID No.2, который соединяет домены VH и VL scFv, при этом модификатор PK способен связываться с линкером.
2. Способ по п.1, где линкер включает последовательность аминокислот, представленную в SEQ ID No.3.
3. Способ по п.1, где модификатор РК представляет собой сывороточный альбумин, гиалуроновую кислоту, коллаген типа II, Fc-области антител, рецепторы антител Fc, муцины, интегрины, белки плотного контакта, трансферрин или факторы комплемента.
4. Способ по п.1, где линкер включает последовательность аминокислот, представленную в SEQ ID No.4.
5. Способ по п.1, где scFv включает последовательность аминокислот, представленную в SEQ ID No.6 или 8.
6. Способ по любому из пп.1-5, где
по меньшей мере один цистеиновый остаток в линкере является ковалентно связанным с функциональным фрагментом; или
два цистеиновых остатка в линкере являются ковалентно связанными с функциональным фрагментом.
7. Способ по п.6, где функциональный фрагмент представляет собой ПЭГ, молекулы углеводов или HES.
8. Фармацевтическая композиция, содержащая терапевтически эффективное количество scFv, полученного в соответствии со способом по п.1, и фармацевтически приемлемый носитель.
RU2016108598A 2008-06-30 2009-06-30 Функционализированные полипептиды RU2016108598A (ru)

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US7677508P 2008-06-30 2008-06-30
US61/076,775 2008-06-30

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US (3) US8637022B2 (ru)
EP (2) EP2304033B1 (ru)
JP (3) JP5988580B2 (ru)
KR (2) KR101678925B1 (ru)
CN (2) CN105153300A (ru)
AU (1) AU2009270405B2 (ru)
BR (1) BRPI0915343A2 (ru)
CA (1) CA2729185A1 (ru)
MX (2) MX2011000006A (ru)
RU (2) RU2016108598A (ru)
WO (1) WO2010006454A2 (ru)
ZA (1) ZA201008596B (ru)

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CN102089431A (zh) 2011-06-08
KR20160046927A (ko) 2016-04-29
EP3130603A1 (en) 2017-02-15
US20160354479A1 (en) 2016-12-08
JP2016147909A (ja) 2016-08-18
EP2304033B1 (en) 2016-09-07
RU2011103168A (ru) 2012-08-10
US20110200594A1 (en) 2011-08-18
EP2304033A2 (en) 2011-04-06
US8637022B2 (en) 2014-01-28
JP2014111670A (ja) 2014-06-19
JP2011526145A (ja) 2011-10-06
KR20110039274A (ko) 2011-04-15
AU2009270405A1 (en) 2010-01-21
MX2011000006A (es) 2011-08-03
US9371525B2 (en) 2016-06-21
RU2582244C2 (ru) 2016-04-20
ZA201008596B (en) 2012-02-29
BRPI0915343A2 (pt) 2015-10-27
CN105153300A (zh) 2015-12-16
JP5988580B2 (ja) 2016-09-07
WO2010006454A3 (en) 2010-03-25
KR101678925B1 (ko) 2016-11-24
MX344076B (es) 2016-12-05
AU2009270405B2 (en) 2014-06-05
US20140178386A1 (en) 2014-06-26
CA2729185A1 (en) 2010-01-21
KR101711472B1 (ko) 2017-03-02
WO2010006454A2 (en) 2010-01-21

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