EP4788690A1 - Peptide conjugates derived from natural toxin and machine learning, binding to the claudin-4 (cldn4) for the radionuclide imaging and therapy of pancreatic cancer - Google Patents

Peptide conjugates derived from natural toxin and machine learning, binding to the claudin-4 (cldn4) for the radionuclide imaging and therapy of pancreatic cancer

Info

Publication number
EP4788690A1
EP4788690A1 EP24875533.2A EP24875533A EP4788690A1 EP 4788690 A1 EP4788690 A1 EP 4788690A1 EP 24875533 A EP24875533 A EP 24875533A EP 4788690 A1 EP4788690 A1 EP 4788690A1
Authority
EP
European Patent Office
Prior art keywords
cldn4
claudin
therapy
pancreatic cancer
binding
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
EP24875533.2A
Other languages
German (de)
French (fr)
Inventor
Katherine W Ferrara
Jai Woong Seo
James Wang
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.)
Leland Stanford Junior University
Original Assignee
Leland Stanford Junior 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
Application filed by Leland Stanford Junior University filed Critical Leland Stanford Junior University
Publication of EP4788690A1 publication Critical patent/EP4788690A1/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Chemical compounds have been designed specifically from Claudin-4 binder peptides (C4BP) for radiopharmaceuticals. Specifically, compounds and compositions integrating C4BP have been designed with the distinct application in pancreatic cancer detection and therapy. Embodiments are compounds having a peptide, spacer (or without spacer), and chelator where this compound binds to CLDN4. The compound can incorporate the metallic radioisotopes to produce radiopharmaceuticals. Applications for these compounds include diagnostic procedures, therapeutic interventions, and targeted delivery of radionuclides to tissues that express CLDN4. Methods detailed herein delineate the use of radiopharmaceutical with CPB for diagnosis, treatment, and targeted delivery within CLDN4 expressing tissues.

Description

. , , - . . , , , , . , . . , , . - , . . , . . -, - 2 - - 2 , -, -2- - - , -, -2- -- , - , - 2 , 4, 44,1,2 4 7 m 111, 1. ,,,,,, , - , ,,, , , 47,7.,,, 1, 14 , 11 177 1 1 212 21 22 22 22 227 , , , , -. . , .' , . , .- ... ’ . . ... . . ., - .- -2- --2 4- .. , .- 4- 2- -2-2- - 2 4.-.-.2- -.2 -. .- - .. , , , - , . , . - - , . - . , . - .- . 4- -2-re -2. -.- 2-. ER -2 - .4- . . .. , . ,, ~ ,- , - ..4- -2- .2 , . , . .. . - LL-tTomatoLL- tTomato reE,R , . ..4- - n+ . .-,. .., - , . ..- . – - . . , -,. , , . - , . -, ., , , , . - ., , .. . . . 177-- . - .. , , , - . .- , .. , .. .’, , ,, ,. . . . , , ’ , . , , , . - D, . . - ....D. – , . , - .-. ’ , -2- . -2. 4 4 2.. - -2- - - , 4- -2- -2 ... .,. ... - ~ .. ~ . LSL-G12D/.+ LSL-tTom-ato/LSL-tTomato CreER / . , .-.4- -2- -2=, - ~. , .-. - .-. - ~ ~ .. ~ , . .. , , . . , - -,, , - - ., , .. -, = . ., , ., . , . . - - ..,, ., . . . . - ,. , . . , . , , , , .. , - Chelator—spacer—claudin-4 binding = - 2 , , - - , . , - -2, - . - , Chelator—spacer— cla cudin-4 binding X yclic peptide . , - - , , .- - . , . , - - -2, -- . - , chelator l spacer H l R1 N claudin-4 . , - - , . - . .- - -2 -- . - . , , 4- 44 1 4 ,,,1,2,4,7,,,,m, -- ,, 47 7 1 14 , 11 177 1 1 212 21 22 , 22, 22, 227,,,,,7,,, 177, 21,2,, 22,., . - . - - , - . =,,,,,,,, ,, H N O n On =,,,,,,,,,, N O H n O ,,,,,,,,, H N n O - . HO O O N N N ,,- O HO O OH N O N HO N ,,,,,,-- - O N O HO O OH N O HO N N OH O N --- -,,,- HO O -,,,- O OH N O HO N N O N ,,,,,,-- - HO O O OH N O HO N N OH O N --- -,,,- HO O -,,,-- N O HO N N O N ,-- -,,,- NH H2N NH HN HN NH NH HN -,,-,- ..- ,,-- ..- -,- - O H2N NH - - HN O O O O HN HO N HO N ---- O N HN - OH - - -'--'-- HO O O OH N N N O O O -,,”,”-- O -’-- H OH HO O O OH N N N ---- - O O O OH --- OH OH HO O O OH N N N - O O O OH OH OH --,-----,- ---,- N O O N N OH O HN N ,','','''--- -. HO HN O O N HN O OH HO ,- N O O N ,- - -- . ---,- --- .. .. - – - - - - -2 . . , , - . . . . , .., , - . -2- −. . . ., ... +,-1221 -- -2- -.- +. ., ... , 12412 - -2- - -- -- . - -.. -2- . −- . ., ... +, 1421 2 -- -2- -. ., .. -. +,.41212 - -2- - - -- . -. - . -2- . −- . ., ... +, 12 2 - -- - . . - -. . +,122 ., .. -, -2 . - . - - ... +,741112 ., -, -2 . - ., . . ,- . + 121227 - -, - 4- -2- 4 2 - . . - . +,1-247 ., ..- --, -- -2 . . ... ,- -. + 1127 ., 4 1/2=.,4 2 ,. . -2- . ,. , .,.. , - , ° - . . . . . ~.-. . , . - . , , , ,, - ., - , , = - , ~ . - 4- ,.. . . , =,= , 4 4 - - ~- .. , , . . . - .. , , . . .... – -

Claims

. , , -, -2- -2 -, -2- - - , -, -2- -- - , -2 . , , , , ,, , 4 m, 111, 1. , 44,1 2 4 7 , -. , , , ,, , ,,, 47 1 14 , 11177 1 1 212 21 22, 22, 22,7 2,27., . -. , -
EP24875533.2A 2023-10-05 2024-10-04 Peptide conjugates derived from natural toxin and machine learning, binding to the claudin-4 (cldn4) for the radionuclide imaging and therapy of pancreatic cancer Pending EP4788690A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363542580P 2023-10-05 2023-10-05
PCT/US2024/050092 WO2025076450A1 (en) 2023-10-05 2024-10-04 Peptide conjugates derived from natural toxin and machine learning, binding to the claudin-4 (cldn4) for the radionuclide imaging and therapy of pancreatic cancer

Publications (1)

Publication Number Publication Date
EP4788690A1 true EP4788690A1 (en) 2026-08-12

Family

ID=95283990

Family Applications (1)

Application Number Title Priority Date Filing Date
EP24875533.2A Pending EP4788690A1 (en) 2023-10-05 2024-10-04 Peptide conjugates derived from natural toxin and machine learning, binding to the claudin-4 (cldn4) for the radionuclide imaging and therapy of pancreatic cancer

Country Status (5)

Country Link
EP (1) EP4788690A1 (en)
KR (1) KR20260085153A (en)
CN (1) CN121969639A (en)
AU (1) AU2024356403A1 (en)
WO (1) WO2025076450A1 (en)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060280687A1 (en) * 2005-03-18 2006-12-14 Zhen Cheng Compounds for tissue imaging and methods of use thereof
US8343458B2 (en) * 2008-04-03 2013-01-01 The Board Of Trustees Of The Leland Stanford Junior University Probes for in vivo targeting of active cysteine proteases
WO2009134962A2 (en) * 2008-04-30 2009-11-05 The Regents Of The University Of California Claudin-4 binding peptides, compositions and methods of use
US10517964B2 (en) * 2011-02-28 2019-12-31 The Board Of Trustees Of The Leland Stanford Junior University Optical imaging probes, optical imaging systems, methods of optical imaging, and methods of using optical imaging probes
US20230381349A1 (en) * 2020-10-06 2023-11-30 Washington University Methods and compositions for imaging and treating cancer

Also Published As

Publication number Publication date
CN121969639A (en) 2026-05-01
AU2024356403A1 (en) 2026-04-16
WO2025076450A1 (en) 2025-04-10
KR20260085153A (en) 2026-06-08

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