# US 2014/0155813 A1 · Therapeutic muscular dystrophy drug having bubble liposome loaded with morpholino as active ingredient > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155813 A1 - Document ID: US20140155813A1 - Status: Published application - Kind: A1 - Application number: 14/116,316 - Filed: 2012-04-25 - Published: 2014-06-05 - Earliest claimed: 2011-05-09 - Assignees: Nepa Gene Co., Ltd. - Inventors: Yoichi Negishi; Yoko Takahashi; Kazuo Maruyama; Yukihiko Aramaki - Web page: https://patentgrep.com/patent/US20140155813A1 ## CPC - A61K 47/6911: {the form being a liposome} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 41/0028: {Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds} - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61P 21/04: for myasthenia gravis - C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} - C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle - C12N 2310/11: Antisense - C12N 2310/3233: Morpholino-type ring - C12N 2310/3515: Lipophilic moiety, e.g. cholesterol - C12N 2320/32: Special delivery means, e.g. tissue-specific - C12N 2320/33: Alteration of splicing - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract To provide a technology for introducing a PMO with remarkably enhanced cell permeability, leading to significantly enhanced introduction efficiency to thereby provide a therapeutic drug that dramatically ameliorates a medical condition of DMD. Also provided is a therapeutic drug for Duchenne muscular dystrophy, including as an active ingredient a Bubble liposome having a specific morpholino oligomer (PMO) bound to a surface thereof, in which the PMO is introduced into a muscle fiber (muscle cell) of a muscle tissue with high efficiency by administration of the therapeutic drug into the muscle tissue or into a blood vessel followed by ultrasound irradiation to the muscle tissue transcutaneously. ## Claims ### Claim 1 A therapeutic drug comprising as an active ingredient: a Bubble liposome; and a morpholino oligomer bound to a surface of the Bubble liposome wherein the morpholino oligomer in a splicing process for a pre-mRNA of a dystrophin gene having a stop codon resulting from a mutation, produces a mature mRNA skipping an exon having the mutation therein; the morpholino oligomer comprises a base sequence complementary to a region comprising a splicing enhancer sequence for the exon; and the morpholino oligomer has a polymerization degree of from 15 to 50 mer. ### Claim 2 (depends on 1) The therapeutic drug according to claim 1, wherein the exon comprises any one of exons 2, 8, 23, 43 to 46, and 50 to 53. ### Claim 3 (depends on 1) The therapeutic drug according to claim 1, wherein the Bubble liposome comprises a PEG-liposome encapsulating a perfluorohydrocarbon, and the Bubble liposome has an average particle diameter of from 50 to 500 nm. ### Claim at position 4 4-5. (canceled) ### Claim 6 A method for treating Duchenne muscular dystrophy in a subject in need there of, the method comprising: administrating a Bubble liposome and a morpholino oligomer bound to a surface of the Bubble liposome into a muscle tissue or a blood vessel of the subject, and transcutaneously irradiating the muscle tissue with ultrasound, wherein the morpholino oligomer in a splicing process for a pre-mRNA of a dystrophin gene having a stop codon resulting from a mutation, produces a mature mRNA skipping an exon having the mutation therein; the morpholino oligomer comprises a base sequence complementary to a region comprising a splicing enhancer sequence for the exon; and the morpholino oligomer has a polymerization degree of from 15 to 50 mer. ### Claim 7 (depends on 6) The method according to claim 6, wherein the exon comprises any one of exons 2, 8, 23, 43 to 46, and 50 to 53. ### Claim 8 (depends on 6) The method according to claim 6, wherein the Bubble liposome comprises a PEG-liposome encapsulating a perfluorohydrocarbon, and the Bubble liposome has an average particle diameter of from 50 to 500 nm. ### Claim 9 (depends on 6) The method according to claim 6, wherein the administrating comprises systemic administration via the blood vessel. ### Claim 10 (depends on 9) The method according to claim 9, wherein the muscle tissue comprises a heart muscle tissue, a diaphragm muscle tissue, or both.