US 12,435,107 B2
Heterotandem bicyclic peptide complex
Gemma Mudd, Lexington, MA (US); Punit Upadhyaya, Lexington, MA (US); Kevin McDonnell, Cambridge (GB); and Johanna Lahdenranta, Lexington, MA (US)
Assigned to BicycleTx Limited, Cambridge (GB)
Filed by BicycleTx Limited, Cambridge (GB)
Filed on Jan. 26, 2024, as Appl. No. 18/424,386.
Application 18/424,386 is a continuation of application No. 17/592,966, filed on Feb. 4, 2022, granted, now 11,970,553.
Application 17/592,966 is a continuation of application No. 16/941,614, filed on Jul. 29, 2020, granted, now 11,306,123, issued on Apr. 19, 2022.
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 2024/0336656 A1, Oct. 10, 2024
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 synthesizing compound BCY11863:

OG Complex Work Unit Chemistry
or a salt thereof, comprising:
a step of reacting compound BCY12476 or a salt thereof with BCY8928 or a salt thereof;
wherein BCY12476 is a compound of formula:

OG Complex Work Unit Chemistry
wherein BCY8116 is a peptide ligand which comprises a polypeptide having amino acid sequence:
 
 (SEQ ID NO: 1)
 
 CiP[1Nal][dD]CiiM[HArg]DWSTP[HyP]WCiii,
wherein the three reactive cysteine groups (Ci, Cii and Ciii) are separated by two loop sequences, and wherein the peptide ligand further comprises a molecular scaffold which is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl) triprop-2-en-1-one (TATA) and which forms covalent bonds with the reactive cysteine groups of the polypeptide such that two polypeptide loops are formed on the molecular scaffold; or a salt thereof;
wherein BCY8928 is a peptide ligand which comprises a polypeptide having amino acid sequence:
(SEQ ID NO: 2)
Ac-Ci[tBuAla]PE[D-Lys(PYA)]PYCiiFADPY[Nle]Ciii-A,
wherein the three reactive cysteine groups (Ci, Cii and Ciii) are separated by two loop sequences, and wherein the peptide ligand further comprises a molecular scaffold which is 1,1′,1″-(1,3,5-triazinane-1,3,5-triyl) triprop-2-en-1-one (TATA) and which forms covalent bonds with the reactive cysteine groups of the polypeptide such that two polypeptide loops are formed on the molecular scaffold, or a salt thereof,
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.