US 12,281,145 B2
Truncated dysferlin for treatment of dysferlinopathy
Matthew Louis Hirsch, Chapel Hill, NC (US); and R. Bryan Sutton, Lubbock, TX (US)
Assigned to The University of North Carolina at Chapel Hill, Chapel Hill, NC (US); and Texas Tech University System, Lubbock, TX (US)
Appl. No. 16/310,207
Filed by The University of North Carolina at Chapel Hill, Chapel Hill, NC (US); and Texas Tech University System, Lubbock, TX (US)
PCT Filed Jun. 16, 2017, PCT No. PCT/US2017/037822
§ 371(c)(1), (2) Date Dec. 14, 2018,
PCT Pub. No. WO2017/218866, PCT Pub. Date Dec. 21, 2017.
Claims priority of provisional application 62/351,701, filed on Jun. 17, 2016.
Prior Publication US 2020/0010521 A1, Jan. 9, 2020
Int. Cl. C07K 14/47 (2006.01); A61K 38/00 (2006.01); A61K 48/00 (2006.01); A61P 21/00 (2006.01); C12N 15/86 (2006.01)
CPC C07K 14/4707 (2013.01) [A61P 21/00 (2018.01); C12N 15/86 (2013.01); A61K 38/00 (2013.01); A61K 48/00 (2013.01); C12N 2750/14143 (2013.01)] 15 Claims
 
1. A polynucleotide encoding a truncated variant of a wild-type mammalian dysferlin polypeptide, the wild-type mammalian dysferlin polypeptide comprising an amino acid sequence for each of domains C2A, C2B, C2C, FerA, DysF, C2D, C2E, C2F, C2G, and TM, wherein the truncated variant of the wild-type mammalian dysferlin polypeptide comprises, in order, at least 95% of the amino acid sequence of each of domains C2A, C2B, C2C, FerA, DysF, C2G, and TM of the wild-type mammalian dysferlin polypeptide, wherein at least 95% of the amino acid sequence of each of domains C2D, C2E, and C2F of the wild-type mammalian dysferlin polypeptide is deleted, wherein the truncated variant of the wild-type mammalian dysferlin polypeptide exhibits sarcolemma localization and/or maintains muscle membrane integrity, and wherein the polynucleotide is: (a) a polynucleotide comprising a sequence at least 95% identical to any one of SEQ ID NOS: 2 or 5 or (b) a polynucleotide comprising a sequence encoding a polypeptide identical to any one of SEQ ID NOS: 7 or 10.