AR125130A1 - Conjugados de amatoxina y anticuerpo específicos de linfocitos b - Google Patents

Conjugados de amatoxina y anticuerpo específicos de linfocitos b

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Publication number
AR125130A1
AR125130A1 ARP220100614A ARP220100614A AR125130A1 AR 125130 A1 AR125130 A1 AR 125130A1 AR P220100614 A ARP220100614 A AR P220100614A AR P220100614 A ARP220100614 A AR P220100614A AR 125130 A1 AR125130 A1 AR 125130A1
Authority
AR
Argentina
Prior art keywords
binding
antigen
antibody
seq
target
Prior art date
Application number
ARP220100614A
Other languages
English (en)
Inventor
Torsten Hechler
Michael Kulke
Andreas Pahl
Original Assignee
Heidelberg Pharma Res Gmbh
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 Heidelberg Pharma Res Gmbh filed Critical Heidelberg Pharma Res Gmbh
Publication of AR125130A1 publication Critical patent/AR125130A1/es

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Classifications

    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/6831—Fungal toxins, e.g. alpha sarcine, mitogillin, zinniol or restrictocin
    • 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
    • A61K47/6875—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 being a hybrid immunoglobulin
    • A61K47/6877—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 being a hybrid immunoglobulin the antibody being an immunoglobulin containing regions, domains or residues from different species
    • 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
    • A61K47/6889—Conjugates 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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]

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Toxicology (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Transplantation (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

La presente solicitud se refiere a conjugados que comprenden una amatoxina, un resto de unión a diana en donde la diana es CD37, es decir, un resto de unión a CD37 y, opcionalmente, un enlazador que une dicha amatoxina y dicho resto de unión a CD37. La invención se refiere además a la síntesis de dichos conjugados. Además, la invención se refiere a una composición farmacéutica que comprende dicho conjugado para su uso en el tratamiento de enfermedades y/o neoplasias malignas asociadas a células inmunitarias, particularmente a células B y/o al linfoma. Reivindicación 1: Un conjugado que comprende (i) un resto de unión a diana, (ii) al menos una toxina y, (iii) opcionalmente, al menos un enlazador que conecta dicho resto de unión a diana con dicha al menos una toxina, en donde dicho resto de unión a diana se une a CD37 y en donde dicha al menos una toxina es una amatoxina. Reivindicación 2: Conjugado de acuerdo con la reivindicación 1, en donde dicho resto de unión a diana se selecciona del grupo que consiste en (i) un anticuerpo, preferentemente un anticuerpo monoclonal, (ii) un fragmento de unión a antígeno del mismo, preferentemente un dominio variable (Fv), un fragmento Fab o un fragmento F(ab)₂, (iii) un derivado de unión a antígeno del mismo, preferentemente un Fv monocatenario (scFv) y (iv) una proteína similar a anticuerpo, uniéndose cada uno a CD37, preferentemente a CD37 humano, preferentemente al dominio extracelular de CD37 humano, respectivamente. Reivindicación 3: Conjugado de acuerdo con la reivindicación 2, en donde dicho anticuerpo, o fragmento de unión a antígeno del mismo o derivado de unión a antígeno del mismo, es un anticuerpo murino, quimérico, humanizado o humano, o fragmento de unión a antígeno o derivado de unión a antígeno del mismo, respectivamente. Reivindicación 4: Conjugado de acuerdo con la reivindicación 2, en donde dicho anticuerpo se selecciona del grupo que consiste en Tetulomab (Lilotomab), Otlertuzumab (TRU-016) y Naratuximab, BI836826 o GEN3009. Reivindicación 5: Conjugado de acuerdo con la reivindicación 2, en donde dicho anticuerpo, o fragmento de unión a antígeno del mismo, o derivado de unión a antígeno del mismo, respectivamente, comprende las siguientes regiones determinantes de la complementariedad (CDR): CDRH1 de acuerdo con la SEQ ID Nº 1 (DYNMY), CDRH2 de acuerdo con la SEQ ID Nº 2 (YIDPYNGDTTYNQKFKG), CDRH3 de acuerdo con la SEQ ID Nº 3 (SPYGHYAMDY), CDRL1 de acuerdo con la SEQ ID Nº 4 (KASQDVSTAVD), CDRL2 de acuerdo con la SEQ ID Nº 5 (WASTRHT), CDRL3 de acuerdo con la SEQ ID Nº 6 (RQHYSTPFT), en donde dichas CDR están comprendidas en un armazón proteínico adecuado para que sean capaces de unirse a CD37, preferentemente a CD37 humano, preferentemente al dominio extracelular de CD37 humano.
ARP220100614A 2021-03-19 2022-03-17 Conjugados de amatoxina y anticuerpo específicos de linfocitos b AR125130A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP21163784 2021-03-19

Publications (1)

Publication Number Publication Date
AR125130A1 true AR125130A1 (es) 2023-06-14

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ID=75111534

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ARP220100614A AR125130A1 (es) 2021-03-19 2022-03-17 Conjugados de amatoxina y anticuerpo específicos de linfocitos b

Country Status (13)

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US (1) US20220370632A1 (es)
EP (1) EP4308169A2 (es)
JP (1) JP2024512478A (es)
KR (1) KR20230159480A (es)
CN (1) CN117241832A (es)
AR (1) AR125130A1 (es)
AU (1) AU2022236461A1 (es)
BR (1) BR112023018189A2 (es)
CA (1) CA3208117A1 (es)
CL (1) CL2023002775A1 (es)
CO (1) CO2023012358A2 (es)
IL (1) IL304966A (es)
WO (1) WO2022194988A2 (es)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230355792A1 (en) 2022-04-07 2023-11-09 Heidelberg Pharma Research Gmbh Methods of improving the therapeutic index

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Publication number Publication date
KR20230159480A (ko) 2023-11-21
AU2022236461A1 (en) 2023-10-05
CL2023002775A1 (es) 2024-04-01
AU2022236461A9 (en) 2024-02-22
EP4308169A2 (en) 2024-01-24
CN117241832A (zh) 2023-12-15
WO2022194988A3 (en) 2022-12-29
US20220370632A1 (en) 2022-11-24
CA3208117A1 (en) 2022-09-22
BR112023018189A2 (pt) 2023-10-24
WO2022194988A2 (en) 2022-09-22
IL304966A (en) 2023-10-01
JP2024512478A (ja) 2024-03-19
CO2023012358A2 (es) 2024-01-15

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