HRP20210809T1 - Biciklični peptidni ligandi specifični za mt1-mmp - Google Patents

Biciklični peptidni ligandi specifični za mt1-mmp Download PDF

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HRP20210809T1
HRP20210809T1 HRP20210809TT HRP20210809T HRP20210809T1 HR P20210809 T1 HRP20210809 T1 HR P20210809T1 HR P20210809T T HRP20210809T T HR P20210809TT HR P20210809 T HRP20210809 T HR P20210809T HR P20210809 T1 HRP20210809 T1 HR P20210809T1
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amino acid
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Daniel Paul Teufel
Catherine Lucy STACE
Silvia PAVAN
Edward Walker
Leonardo Baldassarre
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Bicyclerd Limited
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Priority claimed from GBGB1515245.7A external-priority patent/GB201515245D0/en
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Publication of HRP20210809T1 publication Critical patent/HRP20210809T1/hr
Publication of HRP20210809T8 publication Critical patent/HRP20210809T8/hr

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    • 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
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    • A61K47/547—Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-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
    • A—HUMAN NECESSITIES
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    • 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
    • A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
    • A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
    • A—HUMAN NECESSITIES
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    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/02—Linear peptides containing at least one abnormal peptide link
    • 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

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Claims (22)

1. Peptidni ligand specifičan za MT1-MMP, koji sadrži polipeptid koji sadrži najmanje tri ostatka cisteina, odvojena s najmanje dvije sekvence petlje, i molekularni skelet koji tvori kovalentne veze s ostacima cisteina polipeptida tako da nastaju najmanje dvije polipeptidne petlje na molekularnom skeletu, gdje peptidni ligand sadrži aminokiselinski slijed formule (I): -Ci-X1-U/O2-X3-X4-G5-Cii-E6-D7-F8-Y9-X10-X11-Ciii- (SEQ ID NO: 1) (I) ili njegova farmaceutski prihvatljiva sol; pri čemu: Ci, Cii i Ciii predstavljaju prvi, drugi i treći ostatak cisteina; odnosno; X predstavlja bilo koji aminokiselinski ostatak; U predstavlja polarni, nenabijeni aminokiselinski ostatak odabran između N, C, Q, M, S i T; i O predstavlja nepolarni alifatski aminokiselinski ostatak odabran između G, A, I, L, P i V.
2. Peptidni ligand kako je definiran u zahtjevu 1, naznačen time, da: (i) X1 je odabran iz bilo koje od sljedećih aminokiselina: Y, M, F ili V, poput Y, M ili F, posebno Y ili M, točnije Y; i/ili (ii) U/O2 je odabran od U, poput N, ili O, kao G; i/ili (iii) X3 je odabran između U ili Z, pri čemu U predstavlja polarni, nenabijeni aminokiselinski ostatak odabran od N, C, Q, M, S i T, a Z predstavlja polarni, negativno nabijeni aminokiselinski ostatak odabran od D ili E, posebno U na položaju 3 odabire se iz Q ili Z na položaju 3 odabire se iz E; i/ili (iv) X4 je odabran između J, gdje J predstavlja nepolarni aromatski aminokiselinski ostatak odabran između F, W i Y; i/ili (v) X10 je odabran između Z, gdje Z predstavlja polarni, negativno nabijeni aminokiselinski ostatak odabran između D ili E, kao što je D; i/ili (vi) X11 je odabran između O, gdje O predstavlja nepolarni ostatak alifatske aminokiseline odabran između G, A, I, L, P i V, kao što je I.
3. Peptidni ligand kako je definiran u patentnom zahtjevu 1 ili zahtjevu 2, naznačen time što je spoj formule (I) spoj formule (Ia): -Ci-Y/M/F/V-U/O-U/Z-J-G-Cii-E-D-F-Y-Z-O-Ciii- (SEQ ID NO: 6) (Ia) pri čemu su U, O, J i Z kako su gore definirani; ili spoj formule (Ib): -Ci-Y/M/F/V-N/G-E/Q-F-G-Cii-E-D-F-Y-D-I-Ciii- (SEQ ID NO: 7) (Ib);ili spoj formule (Ic): -Ci-Y/M/F-N/G-E/Q-F-G-Cii-E-D-F-Y-D-I-Ciii- (SEQ ID NO: 8) (Ic); ili spoj formule (Id): -Ci-Y/M-N-E/Q-F-G-Cii-E-D-F-Y-D-I-Ciii- (SEQ ID NO: 9) (Id); ili spoj formule (Ie): -Ci-Y-N-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-07) (SEQ ID NO: 2) (Ie).
4. Peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 3, naznačen time što peptid formule (I) sadrži sekvencu odabranu od: -Ci-Y-N-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-07) (SEQ ID NO: 2); -Ci-M-N-Q-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-12) (SEQ ID NO: 10); -Ci-F-G-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-02) (SEQ ID NO: 11); -Ci-V-N-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-03) (SEQ ID NO: 12); -Ci-F-N-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-04) (SEQ ID NO: 13); -Ci-Y-N-E-Y-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-07-N057) (SEQ ID NO: 14); i -Ci-Y-N-E-W-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-44-N002) (SEQ ID NO: 15), kao: -Ci-Y-N-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-07) (SEQ ID NO: 2); i -Ci-M-N-Q-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-12) (SEQ ID NO: 10), posebice: -Ci-Y-N-E-F-G-Cii-E-D-F-Y-D-I-Ciii- (17-69-07) (SEQ ID NO: 2).
5. Peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 4, koji uključuje jednu ili više modifikacija odabranih između: (i) modifikacija N-kraja korištenjem prikladne amino-reaktivne kemije i / ili modifikacija C-kraja uporabom prikladne karboksi-reaktivne kemije; (ii) N-terminalna modifikacija koja obuhvaća dodavanje molekularne razmakne skupine koja olakšava konjugaciju efektorskih skupina i zadržavanje potencijala bicikličkog peptida na njegovom cilju, kao što su Ala, G-Sar10-A skupina ili bAla- Grupa Sar10-A; (iii) N-terminalna i / ili C-terminalna modifikacija koja obuhvaća dodavanje citotoksičnog sredstva; (iv) zamjena aminokiselinskog ostatka na položaju 4 ne-prirodnim aminokiselinskim ostatkom odabranim od: 1-naftilalanina; 2-naftilalanina; 3,4-diklorofenilalanina; i homofenilalanina, kao što je 1-naftilalanin; 2-naftilalanin; i 3,4-diklorofenilalanin, posebice 1-naftilalanin; (v) zamjena aminokiselinskog ostatka na položaju 9 i / ili 11 s neprirodnim aminokiselinskim ostatkom odabranim između: 4-bromfenilalanina ili pentafluoro-fenilalanina za položaj 9 i / ili tert-butilglicina za položaj 11; (vi) zamjena aminokiselinskog ostatka na položaju 9 s neprirodnim aminokiselinskim ostatkom, koji je 4-bromfenilalanin; (vii) zamjena aminokiselinskog ostatka na položaju 11 s neprirodnim aminokiselinskim ostatkom koji je terc-butilglicin; (viii) 2, 3, 4 ili 5 sljedećih modifikacija, posebno svih sljedećih 5 modifikacija: D-alanin na položaju 1 i / ili 5, 1-naftilalanin na položaju 4, 4-bromfenilalanin na položaju 9 i terc-butilglicin na položaju 11; (ix) gdje je aminokiselinski ostatak na položaju 1 supstituiran za D-alanin; ili (x) pri čemu je aminokiselinski ostatak na položaju 5 supstituiran za D-alanin ili D-arginin.
6. Peptidni ligand kako je definiran u zahtjevu 5, koji je: (β-Ala)-Sar10-AC(D-Ala)NE(1Nal)(D-Ala)CEDFYD(tBuGly)C (SEQ ID NO: 5), ili njegova farmaceutski prihvatljiva sol.
7. Peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 6, naznačen time što je molekularni skelet TBMB, koji je 1,3,5-tris(bromometil)benzen.
8. Konjugat lijeka koji sadrži peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 7, konjugiran s jednom ili više efektorskih i/ili funkcionalnih skupina, kao što je citotoksično sredstvo ili metalni kelator.
9. Konjugat lijeka prema zahtjevu 8, naznačen time, što je citotoksično sredstvo povezano s bicikličkim peptidom cijepljivom vezom, poput disulfidne veze ili veze osjetljive na proteazu.
10. Konjugat lijeka prema zahtjevu 8 ili zahtjevu 9, naznačen time što je citotoksično sredstvo odabrano od DM1 koji ima sljedeću strukturu: [image] ili MMAE koja ima sljedeću strukturu: [image]
11. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 8 do 10, koji je spoj koji ima sljedeću strukturu: [image] ili [image]
12. Konjugat lijeka kako je definiran u patentnom zahtjevu 8 ili zahtjevu 9, naznačen time što je citotoksično sredstvo maytansinoid i odabrano iz spoja formule (II): [image] gdje n predstavlja cijeli broj odabran od 1 do 10; i R1 i R2 neovisno predstavljaju vodik, C1-6 alkil ili karbociklil ili heterociklil skupina, poput vodika ili metila.
13. Konjugat lijeka prema zahtjevu 12, naznačen time, što: n predstavlja 1 i R1 i R2 oba predstavljaju vodik (npr. derivat majtanzina DM1); ili n predstavlja 2, R1 predstavlja vodik i R2 predstavlja metilnu skupinu (npr. derivat majtanzina DM3); ili n predstavlja 2 i R1 i R2 oba predstavljaju metilnu skupinu (npr. derivat majtanzina DM4).
14. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 8 do 13, naznačen time, da biciklična peptidna komponenta konjugata ima strukturu prikazanu u formuli (III): [image] pri čemu m predstavlja cijeli broj odabran od 0 do 10, i R3 i R4 neovisno predstavlja vodik, C1-6 alkil ili karbociklil ili heterociklil skupina, poput vodika ili metila.
15. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 8 do 14, naznačen time da je citotoksično sredstvo povezano s bicikličkim peptidom veznikom definiranim u formuli (IV): [image] pri čemu R1, R2, R3 i R4 predstavljaju vodik, C1-6 alkil ili karbociklil ili heterociklil skupinu, poput vodika ili metila; Toksin se odnosi na bilo koje prikladno citotoksično sredstvo; Bicikl predstavlja peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 7; n predstavlja cijeli broj odabran od 1 do 10; i m predstavlja cijeli broj odabran od 0 do 10.
16. Konjugat lijeka kako je definiran u patentnom zahtjevu 15, naznačen time što je toksin spoja (IV) majtanzin i konjugat sadrži spoj formule (V): [image] pri čemu R1, R2, R3 i R4 predstavljaju vodik, C1-6 alkil ili karbociklil ili heterociklil skupinu; Bicikl predstavlja peptidni ligand kako je definiran u bilo kojem od zahtjeva 1 do 7; n predstavlja cijeli broj odabran od 1 do 10; i m predstavlja cijeli broj odabran od 0 do 10.
17. Konjugat lijeka prema zahtjevu 16, naznačen time, da: n predstavlja 1 i R1, R2, R3 i R4 svaki predstavlja vodik, npr. Spoj formule (V)a: [image] ili n predstavlja 1, R1 predstavlja metil i R2, R3 i R4 svaki predstavlja vodik, npr. Spoj formule (V)b: [image] ili n predstavlja 2, R1 i R2 oba predstavljaju vodik i R3 i R4 oba predstavljaju metil, npr. spoj formule (V)c: [image] ili n predstavlja 2, R1 i R3 oba predstavljaju metil i R2 i R4 oba predstavljaju vodik, npr. spoj formule (V)d: [image]
18. Konjugat lijeka kako je definiran u zahtjevu 8, naznačen time što je odabran između: BT17BDC-9: [image] BT17BDC-17: [image] BT17BDC-18: [image] BT17BDC-19: [image] i BT17BDC-20: [image]
19. Konjugat lijeka kako je definiran u patentnom zahtjevu 18, koji je BT17BDC-18: [image]
20. Postupak za pripremu konjugata lijeka kako je definiran u patentnom zahtjevu 19, koji obuhvaća sintetski put opisan u Prikazu III: [image]
21. Farmaceutski pripravak, naznačen time što sadrži peptidni ligand prema bilo kojem od zahtjeva 1 do 7 ili konjugat lijeka prema bilo kojem zahtjevu 8 do 19, u kombinaciji s jednom ili više farmaceutski prihvatljivih pomoćnih tvari.
22. Konjugat lijeka kako je definiran u bilo kojem od zahtjeva 8 do 19, za uporabu u prevenciji, suzbijanju ili liječenju karcinoma, posebno solidnih tumora kao što su karcinomi pluća nemalih stanica.
HRP20210809TT 2014-10-29 2021-05-19 Biciklični peptidni ligandi specifični za mt1-mmp HRP20210809T8 (hr)

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Application Number Priority Date Filing Date Title
GBGB1419237.1A GB201419237D0 (en) 2014-10-29 2014-10-29 Novel polypeptides
GBGB1515245.7A GB201515245D0 (en) 2015-08-27 2015-08-27 Novel polypeptides
PCT/GB2015/053247 WO2016067035A1 (en) 2014-10-29 2015-10-29 Bicyclic peptide ligands specific for mt1-mmp
EP15790220.6A EP3215518B1 (en) 2014-10-29 2015-10-29 Bicyclic peptide ligands specific for mt1-mmp

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KR20230133938A (ko) 2014-10-29 2023-09-19 바이시클러드 리미티드 Mt1-mmp에 특이적인 바이사이클릭 펩타이드 리간드
GB201600911D0 (en) * 2016-01-18 2016-03-02 Bicycle Therapeutics Ltd Stabilized peptide derivatives
GB201607827D0 (en) * 2016-05-04 2016-06-15 Bicycle Therapeutics Ltd Bicyclic peptide-toxin conjugates specific for MT1-MMP
EP3544621A1 (en) 2016-11-27 2019-10-02 BicycleRD Limited Methods for treating cancer
CN110603261A (zh) * 2016-12-23 2019-12-20 拜斯科阿迪有限公司 具有新型键结构的肽衍生物
KR20190126294A (ko) * 2016-12-23 2019-11-11 바이사이클티엑스 리미티드 Ｍｔ１－ｍｍｐ에 대한 결합용 펩티드 리간드
US10624968B2 (en) 2017-01-06 2020-04-21 Bicyclerd Limited Compounds for treating cancer
GB201706477D0 (en) * 2017-04-24 2017-06-07 Bicycle Therapeutics Ltd Modification of polypeptides
EP3615550A1 (en) 2017-04-27 2020-03-04 BicycleTx Limited Bicyclic peptide ligands and uses thereof
EP3645549A1 (en) 2017-06-26 2020-05-06 BicycleRD Limited Bicyclic peptide ligands with detectable moieties and uses thereof
ES2926195T3 (es) 2017-08-04 2022-10-24 Bicycletx Ltd Ligandos peptídicos bicíclicos específicos de CD137
WO2019034866A1 (en) 2017-08-14 2019-02-21 Bicyclerd Limited BICYCLIC PEPTIDE LIGANDS CONJUGATES AND USES THEREOF
EP3668550A1 (en) 2017-08-14 2020-06-24 Bicyclerd Limited Bicyclic peptide ligand prr-a conjugates and uses thereof
GB201721265D0 (en) 2017-12-19 2018-01-31 Bicyclerd Ltd Bicyclic peptide ligands specific for EphA2
TWI825046B (zh) 2017-12-19 2023-12-11 英商拜西可泰克斯有限公司 Epha2特用之雙環胜肽配位基
BR112020020349A2 (pt) * 2018-04-04 2021-01-05 Bicycletx Limited Complexos de peptídeos bicíclicos em heterotandem
GB201810327D0 (en) * 2018-06-22 2018-08-08 Bicycletx Ltd Peptide ligands for binding to IL-17
GB201810316D0 (en) 2018-06-22 2018-08-08 Bicyclerd Ltd Peptide ligands for binding to EphA2
GB201810329D0 (en) * 2018-06-22 2018-08-08 Bicycletx Ltd Peptide ligands for binding to integrin avB3
US11180531B2 (en) * 2018-06-22 2021-11-23 Bicycletx Limited Bicyclic peptide ligands specific for Nectin-4
GB201810325D0 (en) * 2018-06-22 2018-08-08 Bicycletx Ltd Peptide ligands for binding to PSMA
GB201810320D0 (en) * 2018-06-22 2018-08-08 Bicycletx Ltd Peptide ligands for binding to CD38
CN112955459A (zh) * 2018-10-23 2021-06-11 拜斯科技术开发有限公司 双环肽配体和其用途
SG11202104356VA (en) * 2018-10-30 2021-05-28 Bicyclerd Ltd Bt1718 for use in treating cancer
GB201820320D0 (en) * 2018-12-13 2019-01-30 Bicyclerd Ltd Bicyclic peptide ligands specific for FAPalpha
GB201820325D0 (en) 2018-12-13 2019-01-30 Bicyclerd Ltd Bicyclic peptide ligands specific for psma
GB201820295D0 (en) * 2018-12-13 2019-01-30 Bicyclerd Ltd Bicyclic peptide ligands specific for MT1-MMP
GB201820316D0 (en) * 2018-12-13 2019-01-30 Bicyclerd Ltd Bicyclic peptide ligands specific for IL-17
BR112021011340A2 (pt) * 2018-12-13 2021-09-08 Bicycletx Limited Ligantes de peptídeo bicíclico específicos para mt1-mmp
GB201820288D0 (en) * 2018-12-13 2019-01-30 Bicycle Tx Ltd Bicycle peptide ligaands specific for MT1-MMP
JP2022514618A (ja) 2018-12-21 2022-02-14 バイスクルテクス・リミテッド Ｐｄ－ｌ１に特異的な二環式ペプチドリガンド
CN113260420A (zh) * 2018-12-21 2021-08-13 拜斯科阿迪有限公司 Pd-l1特异性的双环肽配体
GB201900526D0 (en) 2019-01-15 2019-03-06 Bicyclerd Ltd Bicyclic peptide ligands specific for caix
GB201900528D0 (en) 2019-01-15 2019-03-06 Bicyclerd Ltd Bicyclic peptide ligands specific for integrin AVB3
GB201900527D0 (en) 2019-01-15 2019-03-06 Bicycletx Ltd Bicyclic peptide ligands specific for integrin avb3
GB201900530D0 (en) 2019-01-15 2019-03-06 Bicyclerd Ltd Bicyclic peptide ligands specific for CD38
GB201900525D0 (en) 2019-01-15 2019-03-06 Bicycletx Ltd Bicyclic peptide ligands specific for caix
GB201900529D0 (en) 2019-01-15 2019-03-06 Bicycletx Ltd Bicyclic peptide ligands specific for CD38
WO2020165600A1 (en) 2019-02-14 2020-08-20 Bicycletx Limited Bicyclic peptide ligand sting conjugates and uses thereof
WO2020178574A1 (en) 2019-03-04 2020-09-10 Bicyclerd Limited Synthesis of bicycle toxin conjugates, and intermediates thereof
CA3137095A1 (en) 2019-05-09 2020-11-12 Bicycletx Limited Bicyclic peptide ligands specific for ox40
TW202108165A (zh) 2019-05-10 2021-03-01 英商拜西克爾德有限公司 治療癌症之方法
TW202110485A (zh) * 2019-07-30 2021-03-16 英商拜西可泰克斯有限公司 異質雙環肽複合物
GB201912320D0 (en) * 2019-08-28 2019-10-09 Bicycletx Ltd PBP Binding Bicyclic Peptide Ligands
WO2021064428A1 (en) * 2019-10-03 2021-04-08 Bicycletx Limited Heterotandem bicyclic peptide complexes
GB201914872D0 (en) 2019-10-15 2019-11-27 Bicycletx Ltd Bicyclic peptide ligand drug conjugates
WO2021074647A1 (en) 2019-10-16 2021-04-22 Bicyclerd Limited Methods for treating cancer
GB201918558D0 (en) 2019-12-16 2020-01-29 Bicycle Tx Ltd Bicyclic peptide ligands specific for IL-17
EP4077349A1 (en) 2019-12-16 2022-10-26 BicycleTX Limited Bicyclic peptide ligands specific for il-17
GB201918559D0 (en) 2019-12-16 2020-01-29 Bicycle Tx Ltd Bicyclic peptide ligands specific for IL-17
GB201918557D0 (en) 2019-12-16 2020-01-29 Bicycle Tx Ltd Bicyclic peptide ligands specific for IL-17
GB202002705D0 (en) * 2020-02-26 2020-04-08 Bicycletx Ltd Anti-infective bicyclic peptide conjugates
BR112023001428A2 (pt) 2020-08-03 2023-02-23 Bicycletx Ltd Ligantes à base de peptídios
GB202016331D0 (en) 2020-10-15 2020-12-02 Bicyclerd Ltd Bicyclic peptide ligand drug conjugates
CA3206529A1 (en) 2021-01-08 2022-07-14 Bicycletx Limited Heterotandem bicyclic peptide complexes
KR20230146528A (ko) 2021-01-11 2023-10-19 바이사이클티엑스 리미티드 암을 치료하기 위한 방법
CN112852378B (zh) * 2021-01-13 2022-11-18 广东省京极盛新材料科技有限公司 一种反应型聚氨酯热熔胶
BR112023012422A2 (pt) 2021-01-24 2023-12-12 Michael David Forrest Inibidores da atp sintase - usos cosmético e terapêutico
AU2022356942A1 (en) * 2021-09-29 2024-05-09 Conjustar (Zhuhai) Biologics Co., Ltd. Tricyclic polypeptide conjugated drug and use thereof
GB202114282D0 (en) 2021-10-06 2021-11-17 Bicyclerd Ltd Bicyclic peptide ligand drug conjugates
GB202114279D0 (en) 2021-10-06 2021-11-17 Bicycletx Ltd Bicyclic peptide ligand drug conjugates
CN118251405A (zh) * 2021-11-16 2024-06-25 西藏海思科制药有限公司 Mt1-mmp的双环肽配体及其缀合物
CN114656525B (zh) * 2022-04-25 2024-02-02 合肥师范学院 用于癌细胞整合素的rgd环肽及其在制备肿瘤药物中的应用
CN115028685B (zh) * 2022-06-24 2023-10-20 张金强 一种阳离子双环抗菌肽及其应用

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1452868A2 (en) 2003-02-27 2004-09-01 Pepscan Systems B.V. Method for selecting a candidate drug compound
EP1844337B1 (en) 2005-01-24 2013-07-03 Pepscan Systems B.V. Binding compounds, immunogenic compounds and peptidomimetics
CN101232326B (zh) 2007-01-22 2012-01-11 中兴通讯股份有限公司 用于无源光网络系统的动态带宽分配装置及其实现方法
CN101497878B (zh) * 2008-01-30 2012-11-07 房学迅 特异性高效亲和膜ⅰ型基质金属蛋白酶(mt1-mmp)的多肽、蛋白及其应用
PL2257624T3 (pl) 2008-02-05 2012-09-28 Medical Res Council Sposoby i kompozycje
FR2932189A1 (fr) 2008-06-10 2009-12-11 Commissariat Energie Atomique Biopuces pour la detection de l'activite enzymatique d'une enzyme protease
GB0913775D0 (en) 2009-08-06 2009-09-16 Medical Res Council Multispecific peptides
GB0914110D0 (en) * 2009-08-12 2009-09-16 Medical Res Council Peptide libraries
JP2013518558A (ja) * 2010-02-04 2013-05-23 メディカル リサーチ カウンシル 構造化されたペプチドプロセシング
JP2013518807A (ja) * 2010-02-04 2013-05-23 メディカル リサーチ カウンシル 多重特異性ペプチド
AU2012320407B2 (en) * 2011-10-07 2017-04-20 Bicyclerd Limited Modulation of structured polypeptide specificity
US9556229B2 (en) * 2012-05-18 2017-01-31 The Regents Of The University Of California Modification of peptides using a bis(thioether)arylbridge approach
US20140274759A1 (en) 2013-03-15 2014-09-18 Bicycle Therapeutics Limited Modification of polypeptides
GB201306623D0 (en) * 2013-04-11 2013-05-29 Bicycle Therapeutics Ltd Modulation of structured polypeptide specificity
KR20230133938A (ko) 2014-10-29 2023-09-19 바이시클러드 리미티드 Mt1-mmp에 특이적인 바이사이클릭 펩타이드 리간드
GB201607827D0 (en) 2016-05-04 2016-06-15 Bicycle Therapeutics Ltd Bicyclic peptide-toxin conjugates specific for MT1-MMP
EP3544621A1 (en) 2016-11-27 2019-10-02 BicycleRD Limited Methods for treating cancer
KR20190126294A (ko) 2016-12-23 2019-11-11 바이사이클티엑스 리미티드 Ｍｔ１－ｍｍｐ에 대한 결합용 펩티드 리간드
EP3615550A1 (en) 2017-04-27 2020-03-04 BicycleTx Limited Bicyclic peptide ligands and uses thereof
SG11202104356VA (en) 2018-10-30 2021-05-28 Bicyclerd Ltd Bt1718 for use in treating cancer

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