US 12,115,225 B2
GLP-1 receptor ligand moiety conjugated oligonucleotides and uses thereof
Brett P. Monia, Encinitas, CA (US); Thazha P. Prakash, Carlsbad, CA (US); Garth A. Kinberger, San Diego, CA (US); Richard Lee, Oceanside, CA (US); Punit P. Seth, Carlsbad, CA (US); Shalini Andersson, Södertälje (SE); Eva Carina Ämmälä, Mölndal (SE); Daniel Laurent Knerr, Mölndal (SE); Maria Astrid Ölwegård-Halvarsson, Mölndal (SE); Eric Valeur, Mölndal (SE); and William John Drury, III, Mölndal (SE)
Assigned to ASTRAZENECA AB, Södertälje (SE); and IONIS PHARMACEUTICALS, INC., Carlsbad, CA (US)
Filed by AstraZeneca AB, Södertälje (SE); and Ionis Pharmaceuticals, Inc., Carlsbad, CA (US)
Filed on Apr. 15, 2021, as Appl. No. 17/231,409.
Application 17/231,409 is a continuation of application No. 16/098,971, abandoned, previously published as PCT/US2017/031010, filed on May 4, 2017.
Claims priority of provisional application 62/333,080, filed on May 6, 2016.
Prior Publication US 2021/0346509 A1, Nov. 11, 2021
Int. Cl. C07H 21/04 (2006.01); A61K 31/7125 (2006.01); A61K 31/713 (2006.01); A61K 38/17 (2006.01); A61K 47/54 (2017.01); A61K 47/64 (2017.01); A61K 47/65 (2017.01); C12N 15/11 (2006.01); A61P 35/00 (2006.01)
CPC A61K 47/6425 (2017.08) [A61K 31/7125 (2013.01); A61K 31/713 (2013.01); A61K 38/1796 (2013.01); A61K 47/549 (2017.08); A61K 47/65 (2017.08); C12N 15/111 (2013.01); A61P 35/00 (2018.01); C12N 2310/11 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/3341 (2013.01); C12N 2310/3513 (2013.01); C12N 2310/3521 (2013.01); C12N 2310/3525 (2013.01); C12N 2310/3533 (2013.01); C12N 2320/32 (2013.01)] 12 Claims
 
1. A method of modulating the expression of a nucleic acid target in a pancreatic beta-islet cell, wherein the cell expresses GLP-1 receptor on the surface, the method comprising contacting the cell with a compound comprising a modified oligonucleotide, a GLP-1 peptide conjugate moiety capable of binding to the GLP-1 receptor and a conjugate linker linking the modified oligonucleotide to the GLP-1 peptide conjugate moiety, wherein the oligonucleotide has a nucleobase sequence complementary to that of the nucleic acid target, thereby modulating expression of the nucleic acid target in the cell.