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WO2023178179A3 - Bi-functional molecules to degrade circulating proteins - Google Patents

Bi-functional molecules to degrade circulating proteins Download PDF

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Publication number
WO2023178179A3
WO2023178179A3 PCT/US2023/064436 US2023064436W WO2023178179A3 WO 2023178179 A3 WO2023178179 A3 WO 2023178179A3 US 2023064436 W US2023064436 W US 2023064436W WO 2023178179 A3 WO2023178179 A3 WO 2023178179A3
Authority
WO
WIPO (PCT)
Prior art keywords
degrade
mif
igg
conditions
functional molecules
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.)
Ceased
Application number
PCT/US2023/064436
Other languages
French (fr)
Other versions
WO2023178179A2 (en
Inventor
David Spiegel
David CAIANIELLO
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.)
Yale University
Original Assignee
Yale University
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
Priority claimed from US17/695,259 external-priority patent/US20230097887A1/en
Priority to AU2023234543A priority Critical patent/AU2023234543A1/en
Priority to CN202380040375.8A priority patent/CN119212726A/en
Priority to IL315581A priority patent/IL315581A/en
Priority to JP2024555118A priority patent/JP2025509736A/en
Priority to KR1020247033971A priority patent/KR20250004953A/en
Application filed by Yale University filed Critical Yale University
Priority to EP23771634.5A priority patent/EP4493220A2/en
Publication of WO2023178179A2 publication Critical patent/WO2023178179A2/en
Publication of WO2023178179A3 publication Critical patent/WO2023178179A3/en
Priority to MX2024011358A priority patent/MX2024011358A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K47/54—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 organic compound
    • A61K47/55—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C07H15/08—Polyoxyalkylene derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C07H15/10—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical containing unsaturated carbon-to-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/056—Triazole or tetrazole radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Described herein is a bi-functional compound for removing macrophage migration inhibitory factor (MIF) or immunoglubin G (IgG). Further described herein is a pharmaceutical composition which comprise these bi-functional compounds. Further described herein is a method for treating disease states and/or conditions with the compounds or the composition. The disease states and/or conditions are mediated through MIF/IgG or where MIF/IgG is a contributing factor to the development and perpetuation of diseases and/or conditions, such as autoimmune diseases and cancer, among others.
PCT/US2023/064436 2022-03-15 2023-03-15 Bi-functional molecules to degrade circulating proteins Ceased WO2023178179A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP23771634.5A EP4493220A2 (en) 2022-03-15 2023-03-15 Bi-functional molecules to degrade circulating proteins
CN202380040375.8A CN119212726A (en) 2022-03-15 2023-03-15 Bifunctional molecules for degradation of circulating proteins
IL315581A IL315581A (en) 2022-03-15 2023-03-15 Bi-functional molecules to degrade circulating proteins
JP2024555118A JP2025509736A (en) 2022-03-15 2023-03-15 Bifunctional molecules for degrading circulating proteins
KR1020247033971A KR20250004953A (en) 2022-03-15 2023-03-15 Bifunctional molecules for degrading circulating proteins
AU2023234543A AU2023234543A1 (en) 2022-03-15 2023-03-15 Bi-functional molecules to degrade circulating proteins
MX2024011358A MX2024011358A (en) 2022-03-15 2024-09-13 BIFUNCTIONAL MOLECULES FOR DEGRADING CIRCULATING PROTEINS

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US17/695,259 US20230097887A1 (en) 2018-04-09 2022-03-15 Bi-functional Molecules to Degrade Circulating Proteins
US17/695,259 2022-03-15

Publications (2)

Publication Number Publication Date
WO2023178179A2 WO2023178179A2 (en) 2023-09-21
WO2023178179A3 true WO2023178179A3 (en) 2023-10-26

Family

ID=88024435

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/064436 Ceased WO2023178179A2 (en) 2022-03-15 2023-03-15 Bi-functional molecules to degrade circulating proteins

Country Status (8)

Country Link
EP (1) EP4493220A2 (en)
JP (1) JP2025509736A (en)
KR (1) KR20250004953A (en)
CN (1) CN119212726A (en)
AU (1) AU2023234543A1 (en)
IL (1) IL315581A (en)
MX (1) MX2024011358A (en)
WO (1) WO2023178179A2 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017058944A1 (en) * 2015-09-29 2017-04-06 Amgen Inc. Asgr inhibitors
WO2019199621A1 (en) * 2018-04-09 2019-10-17 Yale University Bi-functional molecules to degrade circulating proteins
WO2019199634A1 (en) * 2018-04-09 2019-10-17 Yale University Bifunctional small molecules to target the selective degradation of circulating proteins
WO2021155317A1 (en) * 2020-01-31 2021-08-05 Avilar Therapeutics, Inc. Asgpr-binding compounds for the degradation of extracellular proteins
US20220023434A1 (en) * 2018-12-19 2022-01-27 The Board Of Trustees Of The Leland Stanford Junior University Bifunctional Molecules for Lysosomal Targeting and Related Compositions and Methods

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017058944A1 (en) * 2015-09-29 2017-04-06 Amgen Inc. Asgr inhibitors
WO2019199621A1 (en) * 2018-04-09 2019-10-17 Yale University Bi-functional molecules to degrade circulating proteins
WO2019199634A1 (en) * 2018-04-09 2019-10-17 Yale University Bifunctional small molecules to target the selective degradation of circulating proteins
US20220023434A1 (en) * 2018-12-19 2022-01-27 The Board Of Trustees Of The Leland Stanford Junior University Bifunctional Molecules for Lysosomal Targeting and Related Compositions and Methods
WO2021155317A1 (en) * 2020-01-31 2021-08-05 Avilar Therapeutics, Inc. Asgpr-binding compounds for the degradation of extracellular proteins

Also Published As

Publication number Publication date
MX2024011358A (en) 2025-01-09
IL315581A (en) 2024-11-01
AU2023234543A1 (en) 2024-10-03
EP4493220A2 (en) 2025-01-22
WO2023178179A2 (en) 2023-09-21
JP2025509736A (en) 2025-04-11
CN119212726A (en) 2024-12-27
KR20250004953A (en) 2025-01-08

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