WO2022218970A3 - Pyrrolobenzodiazepine conjugates - Google Patents

Pyrrolobenzodiazepine conjugates Download PDF

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Publication number
WO2022218970A3
WO2022218970A3 PCT/EP2022/059730 EP2022059730W WO2022218970A3 WO 2022218970 A3 WO2022218970 A3 WO 2022218970A3 EP 2022059730 W EP2022059730 W EP 2022059730W WO 2022218970 A3 WO2022218970 A3 WO 2022218970A3
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WO
WIPO (PCT)
Prior art keywords
pyrrolobenzodiazepine conjugates
pyrrolobenzodiazepine
conjugates
formula
unit
Prior art date
Application number
PCT/EP2022/059730
Other languages
French (fr)
Other versions
WO2022218970A2 (en
Inventor
Philip Wilson Howard
Luke Masterton
Arnaud Charles Tiberghien
Ian Hutchinson
Stephen John Gregson
Thais CAILLEAU
Original Assignee
Medimmune Limited
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 Medimmune Limited filed Critical Medimmune Limited
Publication of WO2022218970A2 publication Critical patent/WO2022218970A2/en
Publication of WO2022218970A3 publication Critical patent/WO2022218970A3/en

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    • 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
    • A61K47/6851—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 determinant of a tumour cell
    • A61K47/6855—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 determinant of a tumour cell the tumour determinant being from breast cancer cell
    • 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
    • A61K47/68035—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
    • 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
    • A61K47/6851—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 determinant of a tumour cell
    • A61K47/6863—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 determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A conjugate of formula (I): L - (DL)p, wherein L is a Ligand unit (i.e., a targeting agent), p is from 1 to 20, DL is a Drug Linker unit of formula (I'); RLL is a linker for connection to the Ligand Unit, D represents D1; D' represents D'1.
PCT/EP2022/059730 2021-04-12 2022-04-12 Pyrrolobenzodiazepine conjugates WO2022218970A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB2105187.5A GB202105187D0 (en) 2021-04-12 2021-04-12 Pyrrolobenzodiazepine conjugates
GB2105187.5 2021-04-12

Publications (2)

Publication Number Publication Date
WO2022218970A2 WO2022218970A2 (en) 2022-10-20
WO2022218970A3 true WO2022218970A3 (en) 2022-12-29

Family

ID=75949628

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2022/059730 WO2022218970A2 (en) 2021-04-12 2022-04-12 Pyrrolobenzodiazepine conjugates

Country Status (2)

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GB (1) GB202105187D0 (en)
WO (1) WO2022218970A2 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013177481A1 (en) * 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazepines and conjugates thereof
WO2014057074A1 (en) * 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2020079229A1 (en) * 2018-10-19 2020-04-23 Medimmune Limited Pyrrolobenzodiazepine conjugates
WO2020205564A1 (en) * 2019-03-29 2020-10-08 Immunogen, Inc. Cytotoxic bis-benzodiazepine derivatives and conjugates thereof with cell-binding agents for inhibiting abnormal cell growth or for treating proliferative diseases

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JPS58180487A (en) 1982-04-16 1983-10-21 Kyowa Hakko Kogyo Co Ltd Antibiotic dc-81 and its preparation
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PL2270010T3 (en) 2004-03-01 2012-07-31 Medimmune Ltd 11-hydroxy-5h-pyrrolo[2,1-c][1,4]benzodiazepin-5-one derivatives as key intermediates for the preparation of c2 substituted pyrrolobenzodiazepins
BRPI0516284A (en) 2004-09-23 2008-09-02 Genentech Inc cysteine-constructed antibody, method of selecting antibodies, drug-antibody conjugated compounds, pharmaceutical composition, method for killing or inhibiting tumor cell proliferation, methods of inhibiting cell proliferation and tumor cell growth, manufactured article and method to produce a compound
NZ563136A (en) 2005-04-21 2009-11-27 Spirogen Ltd Pyrrolobenzodiazepines
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Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013177481A1 (en) * 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazepines and conjugates thereof
WO2014057074A1 (en) * 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2020079229A1 (en) * 2018-10-19 2020-04-23 Medimmune Limited Pyrrolobenzodiazepine conjugates
WO2020205564A1 (en) * 2019-03-29 2020-10-08 Immunogen, Inc. Cytotoxic bis-benzodiazepine derivatives and conjugates thereof with cell-binding agents for inhibiting abnormal cell growth or for treating proliferative diseases

Non-Patent Citations (4)

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Title
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GREGSON STEPHEN J ET AL: "Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual [beta]-glucuronide and dipeptide triggers", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 179, 18 June 2019 (2019-06-18), pages 591 - 607, XP085772542, ISSN: 0223-5234, [retrieved on 20190618], DOI: 10.1016/J.EJMECH.2019.06.044 *
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WO2022218970A2 (en) 2022-10-20
GB202105187D0 (en) 2021-05-26

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