US 11,912,792 B2
Bicyclic peptide ligands specific for nectin-4
Paul Beswick, Cambridge (GB); Liuhong Chen, Cambridge (GB); Gemma Mudd, Cambridge (GB); Peter Park, Lincoln, MA (US); Katerine Van Rietschoten, Cambridge (GB); and Michael Rigby, Cambridge (GB)
Assigned to BicycleTx Limited, Cambridge (GB)
Filed by BicycleTx Limited, Cambridge (GB)
Filed on Aug. 17, 2022, as Appl. No. 17/820,286.
Application 17/820,286 is a division of application No. 17/491,078, filed on Sep. 30, 2021, granted, now 11,453,702.
Application 17/491,078 is a continuation of application No. 16/446,901, filed on Jun. 20, 2019, granted, now 11,180,531, issued on Nov. 23, 2021.
Claims priority of application No. 1810250 (GB), filed on Jun. 22, 2018; application No. 1815684 (GB), filed on Sep. 26, 2018; application No. 1818499 (GB), filed on Nov. 13, 2018; and application No. 1904632 (GB), filed on Apr. 2, 2019.
Prior Publication US 2023/0287047 A1, Sep. 14, 2023
Int. Cl. A61K 38/00 (2006.01); A61K 38/10 (2006.01); A61K 47/55 (2017.01); A61K 47/64 (2017.01); A61K 47/65 (2017.01); A61P 35/00 (2006.01); C07K 7/08 (2006.01); A61K 31/40 (2006.01); A61K 31/5375 (2006.01)
CPC C07K 7/08 (2013.01) [A61K 38/10 (2013.01); A61K 47/55 (2017.08); A61K 47/64 (2017.08); A61K 47/65 (2017.08); A61P 35/00 (2018.01); A61K 31/40 (2013.01); A61K 31/5375 (2013.01); A61K 38/00 (2013.01)] 18 Claims
 
1. A method for synthesizing compound BCY8245

OG Complex Work Unit Chemistry
or a salt thereof, the method comprising:
(1) providing a compound having a formula 8

OG Complex Work Unit Chemistry
or a salt thereof; and
(2) reacting the compound of formula 8 or the salt thereof with compound BCY8234 or a salt thereof to form compound BCY8245 or the salt thereof;
wherein compound BCY8234 is a bicyclic peptide ligand specific for Nectin-4 comprising a polypeptide and a molecular scaffold, wherein the polypeptide has an amino acid sequence: [β-Ala][Sar10]-(SEQ ID NO: 1);
wherein SEQ ID NO: 1 is CiP[lNal][dD]CiiM[HArg]DWSTP[HyP]WCiii; and
wherein 1NaI represents 1-naphthylalanine, HArg represents homoarginine, HyP represents hydroxyproline, and Ci,Cii, and Ciii represent, respectively, first, second, and third cysteine residues; and
wherein the molecular scaffold is 1,1 ‘,1 “-(1,3,5-tri azinane-1,3, 5-triyl)triprop-2-en-1-one (TATA), which forms covalent bonds with the cysteine residues of the polypeptide such that two polypeptide loops are formed on the molecular scaffold.