Claims for Patent: 9,416,361

Summary for Patent: 9,416,361

Title:	Splice-region antisense composition and method
Abstract:	Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5' end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.
Inventor(s):	Iversen; Patrick L. (Corvallis, OR), Hudziak; Robert (Blodgett, OR)
Assignee:	Sarepta Therapeutics, Inc. (Cambridge, MA)
Application Number:	14/535,098
Patent Claims:	1. An oligomer of 8 to 40 morpholino subunits connected by phosphorous-containing intersubunit linkages, wherein the 5' terminal morpholino subunit comprises a group of the formula: ##STR00001## wherein each R.sup.1 is independently a C.sub.1-C.sub.6 alkyl. 2. The oligomer of claim 1, wherein the 5' terminal morpholino subunit is of a formula: ##STR00002## wherein each P is independently a purine or pyrimidine base-pairing moiety. 3. The oligomer of claim 1, wherein the oligomer is of a formula: ##STR00003## or a pharmaceutically acceptable salt thereof, wherein: each R.sup.1 is independently a C.sub.1-C.sub.6 alkyl; each P is independently a purine or pyrimidine base-pairing moiety; X is an integer from 3 to 19; and R.sup.3 is selected from H and trityl. 4. The oligomer of claim 1, wherein each R.sup.1 is independently selected from methyl, ethyl, isopropyl, n-butyl, isobutyl, and t-butyl. 5. The oligomer of claim 3, wherein each R.sup.1 is methyl. 6. The oligomer of claim 3, wherein R.sup.3 is H. 7. The oligomer of claim 3, wherein each R.sup.1 is methyl, and R.sup.3 is H. 8. The oligomer of claim 3, wherein each P is independently selected from adenine, cytosine, guanine, uracil, and thymine. 9. A compound of formula: ##STR00004## or a pharmaceutically acceptable salt thereof, wherein X is an integer from 3 to 19, and each P is independently a purine or pyrimidine base-pairing moiety selected from adenine, cytosine, guanine, uracil, and thymine. 10. The oligomer of claim 1, wherein the oligomer is of a formula: ##STR00005## or a pharmaceutically acceptable salt thereof, wherein: each R.sup.1 is independently a C.sub.1-C.sub.6 alkyl; each P is independently a purine or pyrimidine base-pairing moiety; X is an integer from 6 to 38; and R.sup.3 is selected from H and trityl. 11. The oligomer of claim 10, wherein each R.sup.1 is independently selected from methyl, ethyl, isopropyl, n-butyl, isobutyl, and t-butyl. 12. The oligomer of claim 10, wherein each R.sup.1 is methyl. 13. The oligomer of claim 10, wherein R.sup.3 is H. 14. The oligomer of claim 10, wherein each R.sup.1 is methyl, and R.sup.3 is H. 15. The oligomer of claim 10, wherein each P is independently selected from adenine, cytosine, guanine, uracil, and thymine. 16. A compound of formula: ##STR00006## or a pharmaceutically acceptable salt thereof, wherein X is an integer from 6 to 38, and each P is independently a purine or pyrimidine base-pairing moiety selected from adenine, cytosine, guanine, uracil, and thymine.