US 11,970,553 B2
Heterotandem bicyclic peptide complex
Gemma Mudd, Cambridge (GB); Punit Upadhyaya, Lexington, MA (US); Kevin McDonnell, Lexington, MA (US); and Johanna Lahdenranta, Lexington, MA (US)
Assigned to BicycleTx Limited, Cambridge (GB)
Filed by BicycleTx Limited, Cambridge (GB)
Filed on Feb. 4, 2022, as Appl. No. 17/592,966.
Application 17/592,966 is a continuation of application No. 16/941,614, filed on Jul. 29, 2020, granted, now 11,306,123.
Claims priority of provisional application 63/024,715, filed on May 14, 2020.
Claims priority of provisional application 63/022,667, filed on May 11, 2020.
Claims priority of provisional application 62/931,442, filed on Nov. 6, 2019.
Claims priority of provisional application 62/910,088, filed on Oct. 3, 2019.
Claims priority of provisional application 62/880,191, filed on Jul. 30, 2019.
Prior Publication US 2022/0242911 A1, Aug. 4, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 7/08 (2006.01); A61K 9/00 (2006.01); A61K 38/12 (2006.01); A61K 47/64 (2017.01); A61P 35/00 (2006.01); C07K 11/02 (2006.01); C07K 14/00 (2006.01); C07K 14/705 (2006.01); A61K 38/00 (2006.01)
CPC C07K 7/08 (2013.01) [A61K 9/0019 (2013.01); A61K 38/12 (2013.01); A61K 47/641 (2017.08); A61P 35/00 (2018.01); C07K 11/02 (2013.01); C07K 14/001 (2013.01); C07K 14/70578 (2013.01); A61K 38/00 (2013.01)] 21 Claims
 
1. A method of treating cancer in a patient, comprising administering to the patient a heterotandem bicyclic peptide complex comprising:
(a) a first peptide ligand, which binds to Nectin-4 and which comprises the sequence CiP[1Nal][dD]CiiM[HArg]DWSTP[HyP]WCiii (SEQ ID NO: 1); conjugated via an N-(acid-PEG3)-N-bis(PEG3-azide) linker to
(b) two second peptide ligands, each of which binds to CD137 and each of which comprises the sequence Ac-Ci[tBuAla]PE[D-Lys(PYA)]PYCiiFADPY[Nle]Ciii-A (SEQ ID NO: 2);
or a pharmaceutically acceptable salt thereof,
wherein Ci, Cii and Ciii of SEQ ID NOs: 1 and 2 each form covalent bonds with a molecular scaffold comprising 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA) thereby forming two polypeptide loops for each of SEQ ID NOs: 1 and 2; and
wherein Ac represents acetyl, HArg represents homoarginine, HyP represents trans-4-hydroxy-L-proline, 1Nal represents 1-naphthylalanine, tBuAla represents t-butyl-alanine, PYA represents 4-pentynoic acid and Nle represents norleucine.