WO2025072425A3 - Sheddase-targeting chimeras for proteostasis modulation - Google Patents

Sheddase-targeting chimeras for proteostasis modulation Download PDF

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Publication number
WO2025072425A3
WO2025072425A3 PCT/US2024/048537 US2024048537W WO2025072425A3 WO 2025072425 A3 WO2025072425 A3 WO 2025072425A3 US 2024048537 W US2024048537 W US 2024048537W WO 2025072425 A3 WO2025072425 A3 WO 2025072425A3
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WO
WIPO (PCT)
Prior art keywords
sheddase
fusion molecules
integral membrane
targeting
sheddases
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/US2024/048537
Other languages
French (fr)
Other versions
WO2025072425A2 (en
Inventor
Brett Garabedian
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.)
Scripps Research Institute
Original Assignee
Scripps Research Institute
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 Scripps Research Institute filed Critical Scripps Research Institute
Publication of WO2025072425A2 publication Critical patent/WO2025072425A2/en
Publication of WO2025072425A3 publication Critical patent/WO2025072425A3/en
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/626—Diabody or triabody

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

The invention provides fusion molecules for inducing proximity between integral membrane proteins and integral membrane proteases (sheddases), thereby promoting targeted proteolysis (shedding) of the target membrane protein ectodomain. These fusion molecules, Sheddase-Targeting Chimera (SHEDTACs), contain a protease-targeting domain and a substrate-targeting domain that respectively bind to a sheddase and a target protein of interest (e.g., a cell surface receptor). Also provided in the invention are polynucleotides encoding the fusion molecules, related expression vectors and host cells, as well as methods using the fusion molecules to accelerate integral membrane proteolysis by local sheddases.
PCT/US2024/048537 2023-09-26 2024-09-26 Sheddase-targeting chimeras for proteostasis modulation Pending WO2025072425A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363585233P 2023-09-26 2023-09-26
US63/585,233 2023-09-26

Publications (2)

Publication Number Publication Date
WO2025072425A2 WO2025072425A2 (en) 2025-04-03
WO2025072425A3 true WO2025072425A3 (en) 2025-05-01

Family

ID=95201327

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/048537 Pending WO2025072425A2 (en) 2023-09-26 2024-09-26 Sheddase-targeting chimeras for proteostasis modulation

Country Status (1)

Country Link
WO (1) WO2025072425A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008074840A2 (en) * 2006-12-19 2008-06-26 Ablynx N.V. Amino acid sequences directed against a metalloproteinase from the adam family and polypeptides comprising the same for the treatment of adam-related diseases and disorders
WO2019179365A1 (en) * 2018-03-20 2019-09-26 WuXi Biologics Ireland Limited Novel anti-lag-3 antibody polypeptide

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008074840A2 (en) * 2006-12-19 2008-06-26 Ablynx N.V. Amino acid sequences directed against a metalloproteinase from the adam family and polypeptides comprising the same for the treatment of adam-related diseases and disorders
WO2019179365A1 (en) * 2018-03-20 2019-09-26 WuXi Biologics Ireland Limited Novel anti-lag-3 antibody polypeptide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JIA YITING, KONG WEI: "ADAM17 : A Molecular Switch to Control TNFR2 During Atherogenesis In Vivo", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, LIPPINCOTT, WILLIAMS & WILKINS, vol. 37, no. 2, 1 February 2017 (2017-02-01), pages 176 - 178, XP093312945, ISSN: 1079-5642, DOI: 10.1161/ATVBAHA.116.308840 *

Also Published As

Publication number Publication date
WO2025072425A2 (en) 2025-04-03

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