Claims for Patent: 10,533,174

Summary for Patent: 10,533,174

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:	15/723,966
Patent Claims:	1. A pharmaceutical composition comprising 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## or a pharmaceutically acceptable salt thereof, wherein each R.sup.1 is independently a C.sub.1-C.sub.6 alkyl, and a pharmaceutically acceptable carrier. 2. The pharmaceutical composition of claim 1, wherein the 5' terminal morpholino subunit of the oligomer is of a formula: ##STR00002## wherein each P.sub.i is independently a purine or pyrimidine base-pairing moiety. 3. The pharmaceutical composition 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.sub.i is independently a purine or pyrimidine base-pairing moiety; X is an integer from 3 to 19; and R.sup.3 is H. 4. The pharmaceutical composition of claim 3, wherein each R.sup.1 is independently selected from methyl, ethyl, isopropyl, n-butyl, isobutyl, and t-butyl. 5. The pharmaceutical composition of claim 3, wherein each R.sup.1 is methyl. 6. The pharmaceutical composition of claim 3, wherein each P.sub.i is independently selected from adenine, cytosine, guanine, uracil, and thymine. 7. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for intravenous administration. 8. The pharmaceutical composition of claim 1, wherein the oligomer is of a formula: ##STR00004## or a pharmaceutically acceptable salt thereof, wherein: each R.sup.1 is independently a C1-C6 alkyl; each P.sub.i is independently a purine or pyrimidine base-pairing moiety; X is an integer from 6 to 38; and R.sup.3 is H. 9. The pharmaceutical composition of claim 8, wherein each R.sup.1 is independently selected from methyl, ethyl, isopropyl, n-butyl, isobutyl, and t-butyl. 10. The pharmaceutical composition of claim 8, wherein each R.sup.1 is methyl. 11. The pharmaceutical composition of claim 8, wherein each P.sub.i is independently selected from adenine, cytosine, guanine, uracil, and thymine. 12. A pharmaceutical composition comprising a compound of formula: ##STR00005## or a pharmaceutically acceptable salt thereof, wherein X is an integer from 3 to 19, and each P.sub.i is independently a purine or pyrimidine base-pairing moiety selected from adenine, cytosine, guanine, uracil, and thymine, and a pharmaceutically acceptable carrier. 13. A pharmaceutical composition comprising a compound of formula: ##STR00006## or a pharmaceutically acceptable salt thereof, wherein X is an integer from 6 to 38, and each P.sub.i is independently a purine or pyrimidine base-pairing moiety selected from adenine, cytosine, guanine, uracil, and thymine, and a pharmaceutically acceptable carrier.