JP-2022515140-A5 -

Dates

Publication Date

20221214

Application Date

20191220

Description

In some embodiments, the present invention may be described as follows. [Aspect 1] An oligomer compound comprising a modified oligonucleotide consisting of 12 to 50 linked nucleosides, wherein the nucleic acid base sequence of the modified oligonucleotide is at least 90% complementary to the isolength portion of PMP22 RNA, and the modified oligonucleotide comprises at least one modification selected from modified sugars, sugar substitutes, and modified nucleoside-to-nucleoside bonds. [Aspect 2] An oligomeric compound comprising a modified oligonucleotide consisting of 12 to 50 linked nucleosides, and having a nucleic acid base sequence containing at least 12, 13, 14, 15, or 16 nucleic acid bases from any of SEQ ID NOs. 37 to 5373. [Aspect 3] comprising a modified oligonucleotide consisting of 12 to 50 linked nucleosides, The isoformed portion of nucleic acid bases 4,169 to 4,198 in Sequence ID No. 2, The isoformed portion of nucleic acid bases 8,812 to 8,907 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 10,019 to 10,050 in sequence number 2, The equal-length portion of nucleic acid bases 11,247 to 11,276 in Sequence ID No. 2, The isoformed portion of nucleic acid bases 12,058 to 12,096 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 12,357 to 13,387 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 15,721 to 15,769 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 15,914 to 15,971 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 17,354 to 17,403 in sequence number 2, The isoformed portion of nucleic acid bases 19,959 to 19,997 in Sequence ID No. 2, The isoformed portion of nucleic acid bases 27,054 to 27,086 in sequence number 2, The equal-length portion of nucleic acid bases 29,734 to 29,761 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 30,528 to 30,558 in sequence number 2, The equal-length portion of nucleic acid bases 30,678 to 30,717 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 31,450 to 31,479 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 37,363 to 37,401 in Sequence ID No. 2, The equal-length portion of nucleic acid bases 37,651 to 37,856 in Sequence ID No. 2, or An oligomeric compound having a nucleic acid base sequence complementary to at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleic acid bases in the equilength portion of nucleic acid bases 38,107 to 38,223 of Sequence ID No. 2. [Aspect 4] The oligomer compound according to any one of aspects 1 to 3, wherein the modified oligonucleotide has a nucleic acid base sequence that is at least 80%, 85%, 90%, 95%, or 100% complementary to any of the nucleic acid base sequences of SEQ ID NOs: 1 to 8 when measured over the entire nucleic acid base sequence of the modified oligonucleotide. [Aspect 5] The oligomer compound according to any one of aspects 1 to 4, wherein the modified oligonucleotide comprises at least one modified nucleoside. [Aspect 6] The oligomer compound according to aspect 5, wherein the modified oligonucleotide comprises at least one modified nucleoside including a modified sugar moiety. [Aspect 7] The oligomer compound according to aspect 6, wherein the modified oligonucleotide comprises at least one modified nucleoside including a bicyclic sugar moiety. [Aspect 8] The oligomer compound according to aspect 7, wherein the modified oligonucleotide comprises at least one modified nucleoside having a bicyclic sugar moiety having a 2'-4' bridge, and the 2'-4' bridge is selected from -O- CH2- and -O-CH( CH3 )-. [Aspect 9] The oligomer compound according to any one of aspects 5 to 8, wherein the modified oligonucleotide comprises at least one modified nucleoside including a non-bicyclic modified sugar moiety. [Aspect 10] The oligomer compound according to aspect 9, wherein the modified oligonucleotide comprises at least one modified nucleoside containing a non-bicyclic modified sugar moiety including a 2'-MOE modified sugar or a 2'-OMe modified sugar. [Aspect 11] The oligomer compound according to any one of aspects 5 to 10, wherein the modified oligonucleotide comprises at least one modified nucleoside containing a sugar substitute. [Aspect 12] The oligomer compound according to aspect 11, wherein the modified oligonucleotide comprises at least one modified nucleoside containing a sugar substitute selected from morpholino and PNA. [Aspect 13] The modified oligonucleotide is A 5' region consisting of 1 to 5 linked 5' region nucleosides, It has a sugar motif comprising a central region consisting of 6 to 10 linked central region nucleosides, and a 3' region consisting of 1 to 5 linked 3' region nucleosides, The oligomer compound according to any one of embodiments 1 to 12, wherein each of the 5'-region nucleosides and each of the 3'-region