AR110955A1 - COMPOSICIÓN FARMACÉUTICA DE BAJO pH QUE COMPRENDE CONSTRUCTOS DE ANTICUERPO QUE ACOPLAN CÉLULAS T - Google Patents

COMPOSICIÓN FARMACÉUTICA DE BAJO pH QUE COMPRENDE CONSTRUCTOS DE ANTICUERPO QUE ACOPLAN CÉLULAS T

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Publication number
AR110955A1
AR110955A1 ARP180100246A ARP180100246A AR110955A1 AR 110955 A1 AR110955 A1 AR 110955A1 AR P180100246 A ARP180100246 A AR P180100246A AR P180100246 A ARP180100246 A AR P180100246A AR 110955 A1 AR110955 A1 AR 110955A1
Authority
AR
Argentina
Prior art keywords
domain
pharmaceutical composition
composition according
liquid pharmaceutical
antibody
Prior art date
Application number
ARP180100246A
Other languages
English (en)
Inventor
Bharadwaj Jagannathan
Michael Treuheit
Jeff Abel
Joon Huh
Sekhar Kanapuram
Arnold Mauley
Pavan Ghattyvenkatakrishna
Original Assignee
Amgen Res Munich Gmbh
Amgen Inc
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Publication date
Application filed by Amgen Res Munich Gmbh, Amgen Inc filed Critical Amgen Res Munich Gmbh
Publication of AR110955A1 publication Critical patent/AR110955A1/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591Stabilisation, fragmentation
    • 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
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], 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
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], 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
    • C07K16/2809Immunoglobulins [IGs], 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 the T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863Immunoglobulins [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
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/524CH2 domain
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/526CH3 domain
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/53Hinge
    • 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)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
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  • Virology (AREA)
  • Epidemiology (AREA)
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  • Microbiology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Una composición farmacéutica con pH bajo que comprende (a) una construcción de anticuerpos que comprende un primer dominio que se une a un antígeno de superficie celular diana, un segundo dominio que se une a un segundo antígeno y preferentemente un tercer dominio, que es una modalidad de FC específica, (b) al menos un agente amortiguador, (c) al menos un sacárido y (d) al menos un tensioactivo; y en donde el pH de la composición farmacéutica se encuentra en el intervalo de entre 3, 5 y 6. Reivindicación 1: Una composición farmacéutica líquida, caracterizada porque comprende (a) un constructo de anticuerpo que comprende al menos tres dominios, en donde: un primer dominio se une a un antígeno de superficie celular objetivo y tiene un punto isoeléctrico (pI) en el rango de 4 a 9,5; un segundo dominio se une a un segundo antígeno; y tiene un pI en el rango de 8 a 10, preferiblemente 8,5 a 9,5; y un tercer dominio comprende dos monómeros de polipéptidos, cada uno comprende una bisagra, un dominio de CH2 y un dominio de CH3, en donde los dos monómeros de polipéptidos están fusionados entre sí a través de un enlazante de péptido; (b) al menos un agente amortiguador; (c) al menos un sacárido; y (d) al menos un tensioactivo; y en donde el pH de la composición farmacéutica esta en el rango de 3,5 a 6. Reivindicación 3: La composición farmacéutica líquida de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque el tercer dominio comprende en orden de amino a carboxilo: bisagra-dominio de CH2-dominio de CH3-enlazante-bisagra-dominio de CH2-dominio de CH3. Reivindicación 5: La composición farmacéutica líquida de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque el antígeno de superficie celular objetivo es un antígeno de tumor, un antígeno específico para un trastorno inmunológico o un antígeno viral. Reivindicación 6: La composición farmacéutica líquida de conformidad con la reivindicación 5, caracterizada porque el antígeno de tumor se selecciona del grupo que consiste de CDH19, MSLN, DLL3, FLT3, EGFR, EGFRvIII, BCMA, PSMA, CD33, CD19, CD20 y CD70. Reivindicación 7: La composición farmacéutica de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque el segundo dominio es un epítope extracelular de CD3 en la cadena CD3e humana y/o de Macaca. Reivindicación 9: La composición farmacéutica de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque cada uno de los monómeros de polipéptidos del tercer dominio tiene una secuencia de aminoácidos que es idéntica al menos 90% a una secuencia seleccionada del grupo que consiste de SEQ ID Nº 17 - 24, o tiene una secuencia de aminoácidos seleccionada del grupo que consiste de SEQ ID Nº 17 - 24. Reivindicación 12: La composición farmacéutica de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque (i) el primer dominio comprende dos dominios variables de anticuerpo y el segundo dominio comprende dos dominios variables de anticuerpo; (ii) el primer dominio comprende un dominio variable de anticuerpo y el segundo dominio comprende dos dominios variables de anticuerpo; (iii) el primer dominio comprende dos dominios variables de anticuerpo y el segundo dominio comprende un dominio variable de anticuerpo; o (iv) el primer dominio comprende un dominio variable de anticuerpo y el segundo dominio comprende un dominio variable de anticuerpo. Reivindicación 13: La composición farmacéutica líquida de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque el constructo de anticuerpo comprende preferiblemente en un orden de amino a carboxilo: (a) el primer dominio; (b) un enlazante de péptido que tiene una secuencia de aminoácidos seleccionada del grupo que consiste de SEQ ID Nº 1 - 3; (c) el segundo dominio; (d) un enlazante de péptido que tiene una secuencia de aminoácidos seleccionada del grupo que consiste de SEQ ID Nº 1, 2, 3, 9, 10, 11 y 12; (e) el primer monómero de polipéptido del tercer dominio; (f) un enlazante de péptido que tiene una secuencia de aminoácidos seleccionada del grupo que consiste de SEQ ID Nº 5, 6, 7 y 8; y (g) el segundo monómero de polipéptido del tercer dominio. Reivindicación 18: La composición farmacéutica líquida de conformidad con la reivindicación 16, caracterizada porque el alcohol de azúcar es sorbitol. Reivindicación 26: La composición farmacéutica líquida de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque la composición está libre de aniones inorgánicos. Reivindicación 27: La composición farmacéutica liquida de conformidad con cualquiera de las reivindicaciones precedentes, caracterizada porque la composición comprende (a) el constructo de anticuerpo de conformidad con cualquiera de las reivindicaciones precedentes, (b) glutamato o acetato 10 mM, (c) 9% (m/v) de sacarosa o 6% (m/v) de sacarosa y 6% (m/v) de hidroxipropil-b-ciclodextrina, (d) 0,01% (m/v) de polisorbato 80 y en donde el pH de la composición farmacéutica líquida es 4,2.
ARP180100246A 2017-02-02 2018-02-02 COMPOSICIÓN FARMACÉUTICA DE BAJO pH QUE COMPRENDE CONSTRUCTOS DE ANTICUERPO QUE ACOPLAN CÉLULAS T AR110955A1 (es)

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US201762453952P 2017-02-02 2017-02-02

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AR110955A1 true AR110955A1 (es) 2019-05-22

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US (1) US20200332000A1 (es)
EP (1) EP3576788A1 (es)
JP (2) JP7189141B2 (es)
KR (2) KR102658637B1 (es)
CN (1) CN110582297A (es)
AR (1) AR110955A1 (es)
AU (1) AU2018214223A1 (es)
BR (1) BR112019016104A2 (es)
CA (1) CA3052098A1 (es)
CL (1) CL2019002178A1 (es)
CO (1) CO2019009480A2 (es)
CR (1) CR20190408A (es)
EA (1) EA201991769A1 (es)
IL (1) IL268351A (es)
JO (1) JOP20190189A1 (es)
MA (1) MA47425A (es)
MX (1) MX2019009133A (es)
NZ (1) NZ756016A (es)
PE (1) PE20200153A1 (es)
PH (1) PH12019501796A1 (es)
SG (1) SG11201907048UA (es)
TN (1) TN2019000225A1 (es)
WO (1) WO2018141910A1 (es)
ZA (1) ZA201905674B (es)

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