MX2022007202A - Fármacos bioactivables a base de citocinas y metodos de uso de los mismos. - Google Patents

Fármacos bioactivables a base de citocinas y metodos de uso de los mismos.

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Publication number
MX2022007202A
MX2022007202A MX2022007202A MX2022007202A MX2022007202A MX 2022007202 A MX2022007202 A MX 2022007202A MX 2022007202 A MX2022007202 A MX 2022007202A MX 2022007202 A MX2022007202 A MX 2022007202A MX 2022007202 A MX2022007202 A MX 2022007202A
Authority
MX
Mexico
Prior art keywords
vitokine
moiety
tissue
domain
bioactivatable
Prior art date
Application number
MX2022007202A
Other languages
English (en)
Inventor
Yue-Sheng Li
Jing Xu
Lingyun Rui
Original Assignee
Cugene Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cugene Inc filed Critical Cugene Inc
Publication of MX2022007202A publication Critical patent/MX2022007202A/es

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    • 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6813Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C07K14/52Cytokines; Lymphokines; Interferons
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    • A61K47/6425Drug-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 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
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    • A61K47/68Medicinal 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
    • A61K47/6889Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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    • C07K16/2818Immunoglobulins [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 against CD28 or CD152
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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La presente exposición proporciona una plataforma de constructo de fármaco bioactivable basada en citocinas ("VitoKine") que tiene como objetivo reducir las toxicidades sistémicas basadas en mecanismos y conducir a una utilidad terapéutica más amplia para proteínas y citocinas tal como IL-15 e IL-2 para el tratamiento de cáncer, enfermedades autoinmunes, enfermedades inflamatorias, infección viral, trasplante y varios otros trastornos. Los nuevos constructos de VitoKine de la presente invención comprenden: 1) un dominio D1 de la fracción dirigida al tejido o sitio de la enfermedad ("Dl"), 2) un dominio D2 de la fracción bioactivable ("D2") y un dominio D3 de la fracción de ocultamiento ("D3"). Es importante destacar que, debido a que la "fracción activa" del constructo de VitoKine permanecerá inerte hasta que se active localmente por proteasas que se regulan al alza en los tejidos enfermos, esto limitará la unión de la fracción activa a los receptores o a los objetivos en la periferia o en la superficie celular de células y tejidos no enfermos para evitar la sobre-activación de la vía y reducir las toxicidades indeseables "en el objetivo" "fuera del tejido". Además, la inertidad de la fracción activa de VitoKine antes de la activación con la proteasa disminuirá significativamente el antígeno potencial o la extinción objetivo y, por lo tanto, prolongará la vida media in vivo y dará como resultado una biodistribución, biodisponibilidad y eficacia terapéutica mejoradas.
MX2022007202A 2019-12-13 2020-12-11 Fármacos bioactivables a base de citocinas y metodos de uso de los mismos. MX2022007202A (es)

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