US 11,944,688 B2
Biologically active compounds
Keith Foster, Surrey (GB); Wouter Eilers, Reading (GB); and Adam James Reginald Gadd, Reading (GB)
Assigned to SUTURA THERAPEUTICS LTD, Birkenhead (GB)
Filed by SUTURA THERAPEUTICS LTD, Providenciales (TC)
Filed on Dec. 27, 2022, as Appl. No. 18/088,933.
Application 18/088,933 is a continuation of application No. 16/061,548, granted, now 11,541,124, issued on Jan. 3, 2023, previously published as PCT/GB2016/054028, filed on Dec. 21, 2016.
Claims priority of application No. 1522548 (GB), filed on Dec. 21, 2015.
Prior Publication US 2023/0158166 A1, May 25, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/64 (2017.01); A61K 47/65 (2017.01); A61K 48/00 (2006.01); A61P 21/00 (2006.01); C07C 13/00 (2006.01); C07K 1/107 (2006.01); C07K 7/02 (2006.01); C07K 19/00 (2006.01)
CPC A61K 47/65 (2017.08) [A61K 47/64 (2017.08); A61K 48/005 (2013.01); A61K 48/0075 (2013.01); A61P 21/00 (2018.01); C07C 13/00 (2013.01); C07K 7/02 (2013.01); C07K 19/00 (2013.01)] 26 Claims
 
1. A method of delivering a biologically active siRNA or antisense oligonucleotide moiety into a cell and retaining biological activity of the siRNA or antisense oligonucleotide moiety, comprising the step of contacting the cell with a molecule, the molecule comprising:
i) a biologically active siRNA or antisense oligonucleotide moiety, comprising a phosphorodiamidate morpholino oligonucleotide (PMO) covalently linked via a bi-functional linker moiety (BFL) to,
ii) a peptide moiety comprising a stapled peptide (StaP) or a stitched peptide (StiP), wherein the StaP or StiP is a stabilized peptide which has a conformation comprising at least one alpha helix by olefin cross linking comprising in the StaP an olefin cross link between two unnatural amino acids of the peptide at positions i, i+4, and/or i, i+7 and in the StiP at least two olefin cross links between at least three unnatural amino acids of the peptide at positions i, i+4, and i+11, and the StaP or the StiP can penetrate a cell membrane,
wherein the StaP or StiP has the amino acid sequence comprising SEQ ID NO: 27, 28, 33, 41, 44, 57, 88, 89, 90, 91, 92, 93, 94, 109, 140, 141, 159, 160, 162, 163, 164, or 165,
wherein the molecule can penetrate a cell membrane, and has biological activity of the siRNA or antisense oligonucleotide moiety.