WO2023178202A3 - Bifunctional small molecules to target the selective degradation of circulating proteins - Google Patents

Bifunctional small molecules to target the selective degradation of circulating proteins Download PDF

Info

Publication number
WO2023178202A3
WO2023178202A3 PCT/US2023/064470 US2023064470W WO2023178202A3 WO 2023178202 A3 WO2023178202 A3 WO 2023178202A3 US 2023064470 W US2023064470 W US 2023064470W WO 2023178202 A3 WO2023178202 A3 WO 2023178202A3
Authority
WO
WIPO (PCT)
Prior art keywords
receptor
small molecules
crbm
moiety
target
Prior art date
Application number
PCT/US2023/064470
Other languages
French (fr)
Other versions
WO2023178202A2 (en
Inventor
David Spiegel
David CAIANIELLO
Mengwen ZHANG
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 US17/695,645 external-priority patent/US20230083388A1/en
Application filed by Yale University filed Critical Yale University
Publication of WO2023178202A2 publication Critical patent/WO2023178202A2/en
Publication of WO2023178202A3 publication Critical patent/WO2023178202A3/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
    • A61K47/54—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
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol

Abstract

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.
PCT/US2023/064470 2022-03-15 2023-03-15 Bifunctional small molecules to target the selective degradation of circulating proteins WO2023178202A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US17/695,645 2022-03-15
US17/695,645 US20230083388A1 (en) 2018-04-09 2022-03-15 Bifunctional Small Molecules to Target the Selective Degradation of Circulating Proteins

Publications (2)

Publication Number Publication Date
WO2023178202A2 WO2023178202A2 (en) 2023-09-21
WO2023178202A3 true WO2023178202A3 (en) 2023-10-26

Family

ID=88024440

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/064470 WO2023178202A2 (en) 2022-03-15 2023-03-15 Bifunctional small molecules to target the selective degradation of circulating proteins

Country Status (1)

Country Link
WO (1) WO2023178202A2 (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
WO2023178202A2 (en) 2023-09-21

Similar Documents

Publication Publication Date Title
DK1166382T3 (en) Manufacture of tubular fuel cells, fuel cell modules, basic elements and ion exchange membranes
GB9822576D0 (en) Membrane
WO2010102085A4 (en) Stabilized reverse transcriptase fusion proteins
DK1654776T3 (en) MEMBRANE ELECTRODE UNIT FOR ELECTROCHEMICAL DEVICES
TW200623499A (en) Polymer electrolyte material, polymer electrolyte component, membrane electrolyte complex, and polymer electrolyte fuel cell
TW200735447A (en) Laminated electrolyte membrane for solid polymer fuel cells, membrane-electrode combine and fuel cells
WO2007142884A3 (en) Membranes electrode assemblies prepared from fluoropolymer dispersions
WO2006098484A3 (en) Graft polymer
WO2006028704A3 (en) Compositions containing functionalized carbon materials
DK1846974T3 (en) Membrane electrode assemblies for fuel cells, their manufacture and use and fuel cells containing them
NO20060701L (en) Membrane electrode unit for electrolysis of water
ATE257848T1 (en) ACID-BASE POLYMER BLENDS AND THEIR USE IN MEMBRANE PROCESSES
Krause et al. The mitochondrial message-specific mRNA protectors Cbp1 and Pet309 are associated in a high-molecular weight complex
WO2006076031A3 (en) Solid polymer electrolyte membranes
Zimmerman et al. Synthesis of a small, cysteine-rich, 29 amino acids long peptide in Mycoplasma pneumoniae
US10745692B2 (en) Production method for charged non-protein amino acid-containing peptide
WO2023178202A3 (en) Bifunctional small molecules to target the selective degradation of circulating proteins
WO2002024912A3 (en) Isolated nucleic acid molecules which encode a soluble il-tif/il-22 receptor or binding protein which binds to il-tif/il-22, and uses thereof
JP2021525528A (en) ADH protein family mutants and their use
EP3087088B1 (en) Methods and compositions for ribosomal synthesis of macrocyclic peptides
Aronsson et al. POR hits the road: import and assembly of a plastid protein
EP2344524B1 (en) Kit for the optimisation of protein synthesis/secretion
Anderson et al. Cleavage of the precursor of pea chloroplast cytochrome ƒ by leader peptidase from Escherichia coli
Lopitz-Otsoa et al. Properties of natural and artificial proteins displaying multiple ubiquitin-binding domains
US20170029461A1 (en) Heparin affinity tag and applications thereof

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: 23771648

Country of ref document: EP

Kind code of ref document: A2