ES2722924T3 - Conjugados de proteínas y péptidos multivalentes de penetración celular y sus usos - Google Patents

Conjugados de proteínas y péptidos multivalentes de penetración celular y sus usos Download PDF

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Publication number
ES2722924T3
ES2722924T3 ES13802328T ES13802328T ES2722924T3 ES 2722924 T3 ES2722924 T3 ES 2722924T3 ES 13802328 T ES13802328 T ES 13802328T ES 13802328 T ES13802328 T ES 13802328T ES 2722924 T3 ES2722924 T3 ES 2722924T3
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seq
cpp
cell penetration
dendrimer
multivalent
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ES13802328T
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Matthias Strieker
Walter Mier
Uwe Haberkorn
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Universitaet Heidelberg
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Universitaet Heidelberg
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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
    • C07K16/28—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
    • 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
    • A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/641—Branched, dendritic or hypercomb peptides
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • 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
    • A61K51/1027—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 receptors, cell-surface antigens or cell-surface determinants
    • A61K51/103—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 receptors, cell-surface antigens or cell-surface determinants against receptors for growth factors or receptors for growth regulators
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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

Abstract

Un conjugado que comprende una proteína, y uno o varios péptidos multivalentes de penetración celular (CPP multivalentes) comprendiendo cada CPP multivalente al menos dos péptidos de penetración celular (CPP), en el que el o los CPP multivalentes están unidos covalentemente a la proteína, en el que cada uno de el o los CPP multivalentes es un dendrímero de péptidos de penetración celular (dendrímero peptídico de penetración celular, dCPP) que comprende un núcleo del dendrímero y al menos dos péptidos de penetración celular (CPP), que están acoplados al núcleo del dendrímero, dicho núcleo del dendrímero es un núcleo del dendrímero peptídico que comprende lisinas como puntos de ramificación y una o más cisteínas como uno o más grupos de anclaje, y comprende o consiste en **(Ver fórmula)** o **(Ver fórmula)** en las que K es Lys, A es Ala y C es Cys, en el que el uno o más péptidos de penetración celular comprenden la secuencia de aminoácidos de penetratina (SEQ ID NO. 1), TAT (47-60) (transactivador de la transcripción derivado del virus de la inmunodeficiencia humana, SEQ ID NO. 2), PreS2-TLM (motivo de translocación derivado del dominio preS2 del virus de la hepatitis B, SEQ ID NO. 3), R9 (SEQ ID NO. 4), MTS (señal de translocación de membrana, SEQ ID NO. 5), SynB1 (CPP derivado de protegrina 1 porcina sintética, SEQ ID NO. 6), pVEC (CPP derivado de cadherina endotelial vascular, SEQ ID NO. 7), NLS (señal de localización nuclear, SEQ ID NO. 8), o combinaciones de los mismos.
ES13802328T 2012-12-05 2013-12-04 Conjugados de proteínas y péptidos multivalentes de penetración celular y sus usos Active ES2722924T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261733619P 2012-12-05 2012-12-05
PCT/EP2013/075494 WO2014086835A1 (en) 2012-12-05 2013-12-04 Conjugates of proteins and multivalent cell-penetrating peptides and their uses

Publications (1)

Publication Number Publication Date
ES2722924T3 true ES2722924T3 (es) 2019-08-20

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US (1) US10253099B2 (es)
EP (1) EP2928502B1 (es)
ES (1) ES2722924T3 (es)
TR (1) TR201905612T4 (es)
WO (1) WO2014086835A1 (es)

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AU2006283726C1 (en) 2005-08-24 2015-05-07 Immunogen, Inc. Process for preparing maytansinoid antibody conjugates
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ME03353B (me) 2011-03-29 2019-10-20 Immunogen Inc Priprema konjugata antitela i majtanzinoida jednostepenim postupkom
NZ707091A (en) 2012-10-04 2018-12-21 Immunogen Inc Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates
US9745421B2 (en) * 2013-03-20 2017-08-29 The Regents Of The University Of California Dendronized polymers for nucleic acid delivery
US9492544B2 (en) 2013-04-11 2016-11-15 Vanderbilt University Compositions and methods for targeting nuclear import shuttles and treating inflammatory disorders
US11571455B2 (en) 2013-04-11 2023-02-07 Vanderbilt University Methods and compositions for treating alcoholic liver disease
US10287331B2 (en) 2013-04-15 2019-05-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Mitochondrial proteins constructs and uses thereof
WO2015162287A1 (en) * 2014-04-25 2015-10-29 Phi Pharma Sa Keratan sulfate specific transporter molecules
US20220241426A1 (en) * 2014-08-14 2022-08-04 Friedrich-Schiller-Universitaet Jena Peptide for use in the reduction of side effects in the form of immunostimulatory reactions/effects
EP3031820A1 (en) 2014-12-08 2016-06-15 Life Science Inkubator JC Polyomavirus VLP (virus-like particle) with a targeting peptide
SG10202011833TA (en) 2015-05-29 2021-01-28 Univ Pennsylvania Compositions and methods for degradation of misfolded proteins
AU2016305703B2 (en) 2015-08-11 2019-07-25 Coherent Biopharma I, Limited Multi-ligand drug conjugates and uses thereof
JP2019501964A (ja) * 2015-12-14 2019-01-24 ハン， スーＨＡＮ， Ｓｕ ポリペプチド化合物、並びにその調製方法及び適用
WO2017160662A1 (en) 2016-03-12 2017-09-21 The Regents Of The University Of California Biodegradable vectors for efficient rna delivery
EP3440096A4 (en) * 2016-04-06 2019-11-13 Ewha University-Industry Collaboration Foundation PEPTIDE WITH ABILITY TO CELL MEMBRANE PENETRATION
WO2017176076A1 (en) 2016-04-06 2017-10-12 Ewha University - Industry Collaboration Foundation A peptide with ability to penetrate cell membrane
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CN112020555A (zh) * 2018-05-02 2020-12-01 国立大学法人新潟大学 肽及其应用
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CN112512546A (zh) * 2018-05-23 2021-03-16 匹兹堡大学联邦系统高等教育 心脏特异性靶向肽(ctp)、其组合物和用途
CN110655585A (zh) * 2018-06-28 2020-01-07 中央研究院 合成多肽及其用途
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US10253099B2 (en) 2019-04-09
WO2014086835A1 (en) 2014-06-12
EP2928502A1 (en) 2015-10-14
TR201905612T4 (tr) 2019-05-21
EP2928502B1 (en) 2019-01-23
US20150297742A1 (en) 2015-10-22

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