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WO2024238872A3 - Isoindolinone-glutarimide antibody conjugates, and uses thereof - Google Patents

Isoindolinone-glutarimide antibody conjugates, and uses thereof Download PDF

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Publication number
WO2024238872A3
WO2024238872A3 PCT/US2024/029822 US2024029822W WO2024238872A3 WO 2024238872 A3 WO2024238872 A3 WO 2024238872A3 US 2024029822 W US2024029822 W US 2024029822W WO 2024238872 A3 WO2024238872 A3 WO 2024238872A3
Authority
WO
WIPO (PCT)
Prior art keywords
antibody conjugates
isoindolinone
glutarimide
antibody
provides
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
PCT/US2024/029822
Other languages
French (fr)
Other versions
WO2024238872A2 (en
Inventor
Luca Arista
John A. Flygare
Freya M. HARVEY
Thomas Ryckmans
Sean Wesley Smith
Christoph C. GROHMANN
Bernhard Geierstanger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Firefly Bio Inc
Original Assignee
Firefly Bio 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 Firefly Bio Inc filed Critical Firefly Bio Inc
Publication of WO2024238872A2 publication Critical patent/WO2024238872A2/en
Publication of WO2024238872A3 publication Critical patent/WO2024238872A3/en
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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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
    • A61K47/6851—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
    • 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
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

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

Abstract

The invention provides antibody conjugates of Formula I comprising an antibody linked by conjugation to one or more isoindolinone-glutarimide moieties. The invention also provides isoindolinone-glutarimide derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the antibody conjugates through a linker or linking moiety. The invention further provides methods of treating diseases and disorders such as cancer with the antibody conjugates.
PCT/US2024/029822 2023-05-18 2024-05-17 Isoindolinone-glutarimide antibody conjugates, and uses thereof Pending WO2024238872A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202363467543P 2023-05-18 2023-05-18
US63/467,543 2023-05-18
US202463557080P 2024-02-23 2024-02-23
US63/557,080 2024-02-23

Publications (2)

Publication Number Publication Date
WO2024238872A2 WO2024238872A2 (en) 2024-11-21
WO2024238872A3 true WO2024238872A3 (en) 2024-12-19

Family

ID=91829919

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/029822 Pending WO2024238872A2 (en) 2023-05-18 2024-05-17 Isoindolinone-glutarimide antibody conjugates, and uses thereof

Country Status (2)

Country Link
TW (1) TW202500195A (en)
WO (1) WO2024238872A2 (en)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018227018A1 (en) * 2017-06-07 2018-12-13 Silverback Therapeutics, Inc. Antibody conjugates of immune-modulatory compounds and uses thereof
WO2019140003A1 (en) * 2018-01-10 2019-07-18 Development Center For Biotechnology Antibody protac conjugates
WO2020006264A1 (en) * 2018-06-29 2020-01-02 Dana-Farber Cancer Institute, Inc. Ligands to cereblon (crbn)
EP3865152A1 (en) * 2018-10-09 2021-08-18 Eubulus Biotherapeutics Inc. Targeted protease degradation platform
WO2021198965A1 (en) * 2020-03-31 2021-10-07 Orum Therapeutics, Inc. Neodegrader conjugates
WO2021198966A1 (en) * 2020-03-31 2021-10-07 Orum Therapeutics, Inc. Conjugates
WO2023037268A1 (en) * 2021-09-08 2023-03-16 Orum Therapeutics, Inc. Linkers for use in antibody drug conjugates
WO2024138128A2 (en) * 2022-12-23 2024-06-27 Genentech, Inc. Cereblon degrader conjugates, and uses thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018227018A1 (en) * 2017-06-07 2018-12-13 Silverback Therapeutics, Inc. Antibody conjugates of immune-modulatory compounds and uses thereof
WO2019140003A1 (en) * 2018-01-10 2019-07-18 Development Center For Biotechnology Antibody protac conjugates
WO2020006264A1 (en) * 2018-06-29 2020-01-02 Dana-Farber Cancer Institute, Inc. Ligands to cereblon (crbn)
EP3865152A1 (en) * 2018-10-09 2021-08-18 Eubulus Biotherapeutics Inc. Targeted protease degradation platform
WO2021198965A1 (en) * 2020-03-31 2021-10-07 Orum Therapeutics, Inc. Neodegrader conjugates
WO2021198966A1 (en) * 2020-03-31 2021-10-07 Orum Therapeutics, Inc. Conjugates
WO2023037268A1 (en) * 2021-09-08 2023-03-16 Orum Therapeutics, Inc. Linkers for use in antibody drug conjugates
WO2024138128A2 (en) * 2022-12-23 2024-06-27 Genentech, Inc. Cereblon degrader conjugates, and uses thereof

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
JIANG YIXIANG ET AL: "Single-Domain Antibody-Based Protein Degrader for Synucleinopathies", BIORXIV, 13 March 2024 (2024-03-13), XP093199568, Retrieved from the Internet <URL:https://www.biorxiv.org/content/10.1101/2024.03.11.584473v1.full.pdf> DOI: 10.1101/2024.03.11.584473 *
JOSHUA D. HANSEN ET AL: "Protein Degradation via CRL4 CRBN Ubiquitin Ligase: Discovery and Structure-Activity Relationships of Novel Glutarimide Analogs That Promote Degradation of Aiolos and/or GSPT1", JOURNAL OF MEDICINAL CHEMISTRY, vol. 61, no. 2, 13 April 2017 (2017-04-13), US, pages 492 - 503, XP055757970, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01911 *
KOTLA VENUMADHAV ET AL: "Mechanism of action of lenalidomide in hematological malignancies", JOURNAL OF HEMATOLOGY & ONCOLOGY, BIOMED CENTRAL LTD, LONDON UK, vol. 2, no. 1, 12 August 2009 (2009-08-12), pages 36, XP021060855, ISSN: 1756-8722, DOI: 10.1186/1756-8722-2-36 *
YU Y-H: "Abstract LB209: An ADC composed of daratumumab and lenalidomide is extremely powerful in killing multiple myeloma cells", 14 April 2023 (2023-04-14), XP093199572, Retrieved from the Internet <URL:https://aacrjournals.org/cancerres/article/83/8_Supplement/LB209/725230/Abstract-LB209-An-ADC-composed-of-daratumumab-and> *
YU YUEH-HSIANG ET AL: "An Antibody-Drug Conjugate for Multiple Myeloma Prepared by Multi-Arm Linkers", ADVANCED SCIENCE, vol. 11, no. 20, 1 May 2024 (2024-05-01), Germany, XP093199571, ISSN: 2198-3844, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132082/pdf/ADVS-11-2307852.pdf> DOI: 10.1002/advs.202307852 *

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Publication number Publication date
WO2024238872A2 (en) 2024-11-21
TW202500195A (en) 2025-01-01

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