US 12,239,710 B2
FN3 domain-siRNA conjugates and uses thereof
Swapnil Kulkarni, Philadelphia, PA (US); Russell C. Addis, Philadelphia, PA (US); Steven G. Nadler, Philadelphia, PA (US); Yao Xin, Philadelphia, PA (US); Zhanna Druzina, Philadelphia, PA (US); Karyn T. O'Neil, Philadelphia, PA (US); Robert V. Kolakowski, Philadelphia, PA (US); and Stephen J. Anderson, Philadelphia, PA (US)
Assigned to ARO BIOTHERAPEUTICS COMPANY, Philadelphia, PA (US)
Filed by ARO BIOTHERAPEUTICS COMPANY, Philadelphia, PA (US)
Filed on Apr. 14, 2022, as Appl. No. 17/720,996.
Claims priority of provisional application 63/324,437, filed on Mar. 28, 2022.
Claims priority of provisional application 63/203,776, filed on Jul. 30, 2021.
Claims priority of provisional application 63/174,776, filed on Apr. 14, 2021.
Prior Publication US 2022/0370626 A1, Nov. 24, 2022
Int. Cl. A61K 47/54 (2017.01); A61P 21/00 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/549 (2017.08) [A61P 21/00 (2018.01); C12N 15/1137 (2013.01); C12N 2310/11 (2013.01); C12N 2310/14 (2013.01); C12N 2310/3125 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/346 (2013.01); C12N 2310/3513 (2013.01)] 57 Claims
OG exemplary drawing
 
1. A composition comprising an siRNA molecule comprising a sense strand and an antisense strand, wherein the sense strand is a modified oligonucleotide 19-23 nucleotides in length that comprises the nucleobase sequence of SEQ ID NO: 1071 and the antisense strand is a modified oligonucleotide 21-23 nucleotides in length that comprises the nucleobase sequence of SEQ ID NO: 1072.
 
11. A conjugate molecule comprising an siRNA molecule linked to a FN3 polypeptide domain, wherein the siRNA comprises a sense strand and an antisense strand; wherein the sense strand is a modified oligonucleotide 19-23 nucleotides in length that comprises the nucleobase sequence of SEQ ID NO: 1071 and the antisense strand is a modified oligonucleotide 21-23 nucleotides in length that comprises the nucleobase sequence of SEQ ID NO: 1072; wherein the FN3 polypeptide domain comprises a cysteine residue substitution at a position that corresponds to position 6, 8, 10, 11, 14, 15, 16, 20, 30, 34, 38, 40, 41, 45, 47, 48, 53, 54, 59, 60, 62, 64, 70, 88, 89, or 90 of SEQ ID NO: 445; and wherein the sense strand of the siRNA molecule is linked to the FN3 polypeptide domain at the cysteine residue.