HRP20220871T1 - Biciklički peptidni ligandi specifični za epha2 - Google Patents

Biciklički peptidni ligandi specifični za epha2 Download PDF

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Publication number
HRP20220871T1
HRP20220871T1 HRP20220871TT HRP20220871T HRP20220871T1 HR P20220871 T1 HRP20220871 T1 HR P20220871T1 HR P20220871T T HRP20220871T T HR P20220871TT HR P20220871 T HRP20220871 T HR P20220871T HR P20220871 T1 HRP20220871 T1 HR P20220871T1
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HR
Croatia
Prior art keywords
drug conjugate
peptide ligand
cancer
epha2
harg
Prior art date
Application number
HRP20220871TT
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English (en)
Inventor
Liuhong CHEN
Philip Huxley
Silvia PAVAN
Katerine VAN RIETSCHOTEN
Original Assignee
Bicycletx Limited
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 GBGB1721259.8A external-priority patent/GB201721259D0/en
Priority claimed from GBGB1804102.0A external-priority patent/GB201804102D0/en
Priority claimed from GBGB1818603.1A external-priority patent/GB201818603D0/en
Application filed by Bicycletx Limited filed Critical Bicycletx Limited
Publication of HRP20220871T1 publication Critical patent/HRP20220871T1/hr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05Dipeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10Peptides having 12 to 20 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/65Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids

Claims (15)

1. Peptidni ligand specifičan za EphA2 koji sadrži polipeptid koji sadrži najmanje tri cisteinska ostatka, odvojena s najmanje dvije sekvence petlje, i nearomatsku molekularnu skelu koji tvori kovalentne veze s cisteinskim ostacima polipeptida tako da su najmanje dvije polipeptidne petlje formirane na molekularnoj skeli, pri čemu peptidni ligand sadrži aminokiselinsku sekvencu: Ci(HyP)LVNPLCiiLHP(D-Asp)W(HArg)Ciii (SEQ ID NO: 1); pri čemu je HyP hidroksiprolin, HArg je homoarginin i Ci, Cii i Ciii predstavljaju prve, druge i treće cisteinske ostatke, odnosno njegovu farmaceutski prihvatljivu sol.
2. Peptidni ligand kako je definiran u zahtjevu 1, naznačen time što je molekularna skela 1,1’,1"-(1,3,5-triazinan-1,3,5-triil)triprop-2-en-1-one (TATA).
3. Peptidni ligand kako je definiran u zahtjevu 1 ili zahtjevu 2, naznačen time što peptidni ligand sadrži aminokiselinsku sekvencu: (β-Ala)-Sar10-A(HArg)D-Ci(HyP)LVNPLCiiLHP(D-Asp)W(HArg)Cii (SEQ ID NO: 2) (BCY6099); pri čemu je Sar sarkozin, HArg je homoarginin i HyP je hidroksiprolin.
4. Peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 3, naznačen time što je farmaceutski prihvatljiva sol odabrana između slobodne kiseline ili natrijeve, kalijeve, kalcijeve, amonijeve soli.
5. Peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 4, naznačen time što je EphA2 ljudski EphA2.
6. Konjugat lijeka koji sadrži peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 5, konjugiran s jednom ili više efektorskih i/ili funkcionalnih skupina, kao što je citotoksično sredstvo, posebno DM1 ili MMAE, posebno MMAE.
7. Konjugat lijeka kako je definiran u zahtjevu 6, koji dodatno sadrži poveznicu između navedenog peptidnog liganda i navedenih citotoksičnih sredstava.
8. Konjugat lijeka kako je definiran u zahtjevu 7, naznačen time što navedeno citotoksično sredstvo je MMAE i poveznica je odabrana između: -Val-Cit-, -Trp-Cit-, -Val-Lys-, -D-Trp-Cit-, -Ala-Ala-Asn-, D-Ala-Phe-Lys- ili -Glu-Pro-Cit-Gly-hPhe-Tyr-Leu- (SEQ ID NO: 3), kao što je -Val-Cit-.
9. Konjugat lijeka kako je definiran u zahtjevu 7, naznačen time što navedeno citotoksično sredstvo je DM1 i poveznica je odabrana između: -S-S-, -SS(SO3H)-, -SS-(Me)-, -(Me)-SS-(Me)-, -SS-(Me2)- ili -SS-(Me)-SO3H-, kao što su -S-S- i -SS(SO3H)-.
10. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 6 do 9, koji je odabran između bilo kojeg od BCY6027, BCY6028, BCY6135, BCY6136, BCY6173, BCY6174 i BCY6175, kao što je BCY6136.
11. Konjugat lijeka prema bilo kojem od zahtjeva 6 do 9, koji je odabran između bilo kojeg od: BCY6031, BCY6033, BCY6082, BCY6135, BCY6136, BCY6173, BCY6174 i BCY6175, kao što je BCY6136.
12. Farmaceutski pripravak koji sadrži peptidni ligand prema bilo kojem od zahtjeva 1 do 5 ili konjugat lijeka prema bilo kojem od zahtjeva 6 do 11, u kombinaciji s jednim ili više farmaceutski prihvatljivih ekscipijenata.
13. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 6 do 11, za uporabu u prevenciji, suzbijanju ili liječenju bolesti ili poremećaja naznačenog po prekomjernoj ekspresiji EphA2 u oboljelom tkivu.
14. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 6 do 11, za uporabu u prevenciji, suzbijanju ili liječenju raka, kao što je rak prostate, rak pluća (kao što su karcinomi pluća nemalih stanica (NSCLC)), rak dojke (kao što je trostruko negativni rak dojke), rak želuca, rak jajnika, rak jednjaka, multipli mijelom i fibrosarkom.
15. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 6 do 11, za uporabu u metodi prevencije, supresije ili liječenja raka kod pacijenta, pri čemu je navedeni pacijent identificiran da ima povećanu varijaciju broja kopija (CNV) EphA2.
HRP20220871TT 2017-12-19 2018-12-19 Biciklički peptidni ligandi specifični za epha2 HRP20220871T1 (hr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GBGB1721259.8A GB201721259D0 (en) 2017-12-19 2017-12-19 Bicyclic peptide ligands specific for EphA2
GBGB1804102.0A GB201804102D0 (en) 2018-03-14 2018-03-14 Bicycle peptide ligands specific for EphA2
GBGB1818603.1A GB201818603D0 (en) 2018-11-14 2018-11-14 Bicyclic peptide ligands specific for epha2
EP18829437.5A EP3727460B1 (en) 2017-12-19 2018-12-19 Bicyclic peptide ligands specific for epha2
PCT/GB2018/053675 WO2019122860A1 (en) 2017-12-19 2018-12-19 Bicyclic peptide ligands specific for epha2

Publications (1)

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HRP20220871T1 true HRP20220871T1 (hr) 2022-12-23

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HRP20220871TT HRP20220871T1 (hr) 2017-12-19 2018-12-19 Biciklički peptidni ligandi specifični za epha2

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US (4) US11484602B2 (hr)
EP (3) EP3727460B1 (hr)
JP (3) JP7404241B2 (hr)
KR (2) KR20200105839A (hr)
CN (2) CN111787955A (hr)
AU (2) AU2018387417B2 (hr)
BR (2) BR112020012246A2 (hr)
CA (2) CA3085253A1 (hr)
DK (1) DK3727460T3 (hr)
ES (1) ES2922632T3 (hr)
HR (1) HRP20220871T1 (hr)
HU (1) HUE059126T2 (hr)
IL (2) IL275440B2 (hr)
LT (1) LT3727460T (hr)
MX (2) MX2020006474A (hr)
PH (1) PH12020550929A1 (hr)
PL (1) PL3727460T3 (hr)
PT (1) PT3727460T (hr)
SG (2) SG11202005494QA (hr)
SI (1) SI3727460T1 (hr)
TW (1) TWI825046B (hr)
WO (2) WO2019122860A1 (hr)

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