WO2022169913A3 - Synthetic degrader system for targeted protein degradation - Google Patents

Synthetic degrader system for targeted protein degradation Download PDF

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Publication number
WO2022169913A3
WO2022169913A3 PCT/US2022/014998 US2022014998W WO2022169913A3 WO 2022169913 A3 WO2022169913 A3 WO 2022169913A3 US 2022014998 W US2022014998 W US 2022014998W WO 2022169913 A3 WO2022169913 A3 WO 2022169913A3
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WO
WIPO (PCT)
Prior art keywords
fusion protein
degradation
binding element
synthetic
protein degradation
Prior art date
Application number
PCT/US2022/014998
Other languages
French (fr)
Other versions
WO2022169913A2 (en
Inventor
Howell MOFFETT
Duy Nguyen
Robert LANGAN
Scott BOYKEN
Marc Lajoie
Glenna FOIGHT
Original Assignee
Outpace 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 Outpace Bio, Inc. filed Critical Outpace Bio, Inc.
Priority to EP22710773.7A priority Critical patent/EP4288529A2/en
Priority to TW111104424A priority patent/TW202246309A/en
Publication of WO2022169913A2 publication Critical patent/WO2022169913A2/en
Publication of WO2022169913A3 publication Critical patent/WO2022169913A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1025—Acyltransferases (2.3)
    • C12N9/104—Aminoacyltransferases (2.3.2)
    • 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
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y203/00—Acyltransferases (2.3)
    • C12Y203/02—Aminoacyltransferases (2.3.2)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
    • C07K2319/81—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor containing a Zn-finger domain for DNA binding

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

A fusion protein is provided having a binding element and a degradation initiator, where the binding element selectively binds a target molecule, and the degradation initiator has a sequence isolated or derived from an E3 ligase. A composition is provided comprising: (a) a first fusion protein comprising a first binding element; and (b) a second fusion protein comprising a second binding element; wherein: (1) the first fusion protein further comprises a degradation initiator or a functional variant thereof and the second fusion protein further comprises a target molecule; or (2) the first fusion protein further comprises a target molecule and the second fusion protein further comprises a degradation initiator or a functional variant thereof. The fusion proteins and compositions may be used for the targeted degradation of endogenous and exogenous proteins, optionally, in a cell or in vivo, for the treatment or prevention of a disease or disorder.
PCT/US2022/014998 2021-02-02 2022-02-02 Synthetic degrader system for targeted protein degradation WO2022169913A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP22710773.7A EP4288529A2 (en) 2021-02-02 2022-02-02 Synthetic degrader system for targeted protein degradation
TW111104424A TW202246309A (en) 2021-02-02 2022-02-07 Synthetic degrader system for targeted protein degradation

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202163144895P 2021-02-02 2021-02-02
US63/144,895 2021-02-02
US202163248516P 2021-09-26 2021-09-26
US63/248,516 2021-09-26

Publications (2)

Publication Number Publication Date
WO2022169913A2 WO2022169913A2 (en) 2022-08-11
WO2022169913A3 true WO2022169913A3 (en) 2022-09-29

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2022/014998 WO2022169913A2 (en) 2021-02-02 2022-02-02 Synthetic degrader system for targeted protein degradation

Country Status (3)

Country Link
EP (1) EP4288529A2 (en)
TW (1) TW202246309A (en)
WO (1) WO2022169913A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023150649A2 (en) * 2022-02-02 2023-08-10 Outpace Bio, Inc. Synthetic degrader system for targeted protein degradation
WO2024124311A1 (en) * 2022-12-16 2024-06-20 Recepta Biopharma S.A. Plp2-derived peptides, pharmaceutical compositions, methods and uses of thereof
WO2024153211A1 (en) * 2023-01-19 2024-07-25 Nanjing Legend Biotech Co., Ltd. Fusion polypeptides for targeted protein degradation and mehtods of use thereof
CN118252913B (en) * 2024-02-07 2024-09-17 中国医学科学院阜外医院 Polypeptide conjugate and application thereof in heart failure with ejection fraction reserved

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020093043A1 (en) * 2018-11-02 2020-05-07 Chen Zibo Orthogonal protein heterodimers

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104126009B (en) 2011-10-07 2019-05-10 国立大学法人三重大学 Chimeric antigen receptor
CN113330520A (en) 2018-12-04 2021-08-31 华盛顿大学 Reagents and methods for controlling protein function and interaction

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020093043A1 (en) * 2018-11-02 2020-05-07 Chen Zibo Orthogonal protein heterodimers

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
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BALTZ MORGAN R ET AL: "Design and functional characterization of synthetic E3 ubiquitin ligases for targeted protein depletion: Selective protein knockout using engineered ubiquibodies", CURRENT PROTOCOLS IN CHEMICAL BIOLOGY, 1 March 2018 (2018-03-01), pages 72 - 90, XP055920080, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062852/pdf/nihms920139.pdf> [retrieved on 20220511], DOI: 10.1002/cpch.37 *
BUCKLEY DENNIS L ET AL: "HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins", ACS CHEMICAL BIOLOGY, ACS PUBLICATIONS, USA, vol. 10, no. 8, 21 August 2015 (2015-08-21), pages 1831 - 1837, XP002762672, ISSN: 1554-8937 *
CHEN ZIBO ET AL: "Programmable design of orthogonal protein heterodimers", NATURE, NATURE PUBLISHING GROUP UK, LONDON, vol. 565, no. 7737, 19 December 2018 (2018-12-19), pages 106 - 111, XP036664328, ISSN: 0028-0836, [retrieved on 20181219], DOI: 10.1038/S41586-018-0802-Y *
DENG WEN ET AL: "Supplementary information Tunable light and drug induced depletion of target proteins", NATURE COMMUNICATIONS, 16 January 2020 (2020-01-16), pages 1 - 24, XP055933148, Retrieved from the Internet <URL:https://static-content.springer.com/esm/art:10.1038/s41467-019-14160-8/MediaObjects/41467_2019_14160_MOESM1_ESM.pdf> [retrieved on 20220620] *
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SCHNEEKLOTH A R ET AL: "Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 18, no. 22, 15 November 2008 (2008-11-15), pages 5904 - 5908, XP025627166, ISSN: 0960-894X, [retrieved on 20080731], DOI: 10.1016/J.BMCL.2008.07.114 *

Also Published As

Publication number Publication date
TW202246309A (en) 2022-12-01
WO2022169913A2 (en) 2022-08-11
EP4288529A2 (en) 2023-12-13

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