Tissue specific peptide conjugates and methods
1 Assignment
0 Petitions
Accused Products
Abstract
Cell-penetrating peptides useful for targeting a therapeutic compound to a selected mammalian tissue, methods for their identification, methods of forming conjugate compounds containing such peptides, and conjugates formed thereby are disclosed. The cell-penetrating peptides are 8 to 30 amino acid residues in length and consist of subsequences selected from the group consisting of RXR, RX, RB, and RBR; where R is arginine, B is β-alanine, and each X is independently —C(O)—(CHR1)n—NH—, where n is 4-6 and each R1 is independently H or methyl, such that at most two R1'"'"'s are methyl. In one embodiment, X is a 6-aminohexanoic acid residue.
-
Citations
61 Claims
-
1-41. -41. (canceled)
-
42. A peptide-antisense conjugate for treating a disease condition in mammalian muscle tissue, comprising
a phosphorodiamidate morpholino antisense oligomer directed against a gene whose expression is associated with the disease condition in said tissue, and covalently linked thereto, via a linkage X, B, or XB, a muscle tissue-targeting cell-penetrating peptide having a sequence selected from the group consisting of SEQ ID NOs: - 6, 11, 13, 19, 20, 21, 23 and 25, where B in said linkage is β
-alanine and X is a neutral linear amino acid —
C(O)—
(CH2)n—
NH—
, where n is 4-6,wherein the cell-penetrating peptide selectively localizes the antisense oligomer in said mammalian muscle tissue. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)
- 6, 11, 13, 19, 20, 21, 23 and 25, where B in said linkage is β
-
58. A muscle tissue-targeting cell-penetrating peptide having a sequence selected from the group consisting of SEQ ID NOs:
- 19, 20, 21, 23 and 25.
- View Dependent Claims (59)
-
60. In a method for treating Duchenne muscular dystrophy or a muscle-wasting disease in a mammalian subject, by administering to the subject, an antisense oligomer effective to suppress splice-variant truncations in expressed dystrophin protein, or effective to suppress myostatin expression in muscle tissue, respectively, when administered to the subject, an improvement comprising
conjugating to the oligomer to be administered, a cell-penetrating peptide having the sequence identified as SEQ ID NO:
Specification