WO2022218970A3 - Pyrrolobenzodiazepine conjugates - Google Patents

Pyrrolobenzodiazepine conjugates Download PDF

Info

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
Authority
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

Links

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
    • A61K47/6851—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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (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
GB2105187.5 2021-04-12
GBGB2105187.5A GB202105187D0 (en) 2021-04-12 2021-04-12 Pyrrolobenzodiazepine conjugates

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)

Country Link
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

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58180487A (en) 1982-04-16 1983-10-21 Kyowa Hakko Kogyo Co Ltd Antibiotic dc-81 and its preparation
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
PL1720881T3 (en) 2004-03-01 2013-05-31 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
SI1791565T1 (en) 2004-09-23 2016-08-31 Genentech, Inc. Cysteine engineered antibodies and conjugates
PT1879901E (en) 2005-04-21 2010-03-29 Spirogen Ltd Pyrrolobenzodiazepines
PL1813614T3 (en) 2006-01-25 2012-03-30 Sanofi Sa Cytotoxic agents comprising new tomaymycin derivatives
CA2683568A1 (en) 2007-05-08 2008-11-20 Genentech, Inc. Cysteine engineered anti-muc16 antibodies and antibody drug conjugates
US8937161B2 (en) 2007-10-19 2015-01-20 Genentech, Inc. Cysteine engineered anti-TENB2 antibodies and antibody drug conjugates
JP5972864B2 (en) 2010-04-15 2016-08-17 メディミューン リミテッド Pyrrolobenzodiazepines and their conjugates
FR2967466B1 (en) 2010-11-16 2014-10-24 Renault Sa METHOD FOR DETECTING COMBUSTION FAULTS OF AN INTERNAL COMBUSTION ENGINE
GB201106173D0 (en) 2011-04-12 2011-05-25 Adc Biotechnology Ltd System for purifyng, producing and storing biomolecules
EP2935268B2 (en) 2012-12-21 2021-02-17 MedImmune Limited Pyrrolobenzodiazepines and conjugates thereof
RU2711485C2 (en) 2014-04-11 2020-01-17 МЕДИММЬЮН, ЭлЭлСи Conjugated compounds containing cysteine-constructed antibodies
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
KR20190083654A (en) 2016-11-10 2019-07-12 메디뮨 엘엘씨 Binding molecules specific for ASCT2 and uses thereof
CN112203696A (en) 2018-05-25 2021-01-08 免疫医疗有限公司 Pyrrolobenzodiazepine conjugates

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)

* Cited by examiner, † Cited by third party
Title
BREANNA S. VOLLMAR ET AL: "Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual [beta]-glucuronide and dipeptide triggers", BIOCONJUGATE CHEMISTRY, vol. 28, no. 10, 22 September 2017 (2017-09-22), pages 2538 - 2548, XP055551756, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.7b00365 *
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 *
KATIE E. ARCHER ET AL: "Synthesis of Highly Potent N-10 Amino-Linked DNA-Alkylating Indolinobenzodiazepine Antibody-Drug Conjugates (ADCs)", ACS MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 8, 22 July 2019 (2019-07-22), pages 1211 - 1215, XP055705444, ISSN: 1948-5875, DOI: 10.1021/acsmedchemlett.9b00254 *
NAZZARENO DIMASI ET AL: "Efficient Preparation of Site-Specific Antibody-Drug Conjugates Using Cysteine Insertion", MOLECULAR PHARMACEUTICS, vol. 14, no. 5, 16 March 2017 (2017-03-16), pages 1501 - 1516, XP055417109, ISSN: 1543-8384, DOI: 10.1021/acs.molpharmaceut.6b00995 *

Also Published As

Publication number Publication date
WO2022218970A2 (en) 2022-10-20
GB202105187D0 (en) 2021-05-26

Similar Documents

Publication Publication Date Title
WO2006060533A3 (en) Conjugates of 1, 8-bis-naphthalimides with an antibody
WO2007064345A3 (en) Heterocyclic-substituted bis-1,8 naphthalimide compounds, antibody drug conjugates, and methods of use
MY197127A (en) Pyrrolobenzodiazepine conjugates
AU3000800A (en) Phosphocholine linked prodrug derivatives
MX2013014583A (en) Protein-polymer-drug conjugates.
NZ588851A (en) Potent conjugates and hydrophilic linkers
TW200500069A (en) Vitamin-receptor binding drug delivery conjugates
JO2744B1 (en) Cytotoxic agents comprising new tomaymycin derivatives and their therapeutic use
NZ597964A (en) Long acting insulin composition
MX2018009585A (en) Pyrrolobenzodiazepine conjugates.
MA28653B1 (en) NEW FLUOROGLYCOSIDE DERIVATIVES OF PYRAZOLES, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND THEIR USE
TW200637869A (en) The spiroketal derivatives and the use as therapeutical agent for diabetes of the same
GB0220198D0 (en) Modified saccharides,conjugates thereof and their manufacture
MA34469B1 (en) ANTICANCER DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
WO2008076333A3 (en) Polymer-drug conjugates with tether groups for controlled drug delivery
WO2011010084A8 (en) Cyclosporin conjugates
Ghosh et al. Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products
AU2003250391A1 (en) Conjugates of biocompatible polymers with nuclide activation therapy reagents
MX2022008997A (en) Compounds and conjugates thereof.
AU2002215904A1 (en) Compounds with a branched linker
MX2023001648A (en) Antibody drug conjugate.
JOP20210083A1 (en) Antibody drug conjugates comprising ecteinascidin derivatives
BR0112807A (en) Indole derivatives and their application as a medicine
WO2006105201A3 (en) Conjugates comprised of fatty acid and hiv gp41-derived peptide
WO2022218970A3 (en) Pyrrolobenzodiazepine conjugates

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22722261

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22722261

Country of ref document: EP

Kind code of ref document: A2