# US 2023/0265459 A1 · Compositions Useful in Treatment of Spinal Muscular Atrophy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0265459 A1 - Document ID: US20230265459A1 - Status: Published application - Kind: A1 - Application number: 18/154,096 - Filed: 2023-01-13 - Published: 2023-08-24 - Earliest claimed: 2017-02-28 - Assignees: The Trustees of the University of Pennsylvania - Applicants: The Trustees of the University of Pennsylvania - Inventors: James M. Wilson; Christian Hinderer; Nathan Katz; Qiang Wang - Web page: https://patentgrep.com/patent/US20230265459A1 ## CPC - C12N 15/86: Viral vectors - C12N 15/8645: {Adeno-associated virus} - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 25/00: Drugs for disorders of the nervous system - C07K 14/47: from mammals - C12N 15/864: Parvoviral vectors {, e.g. parvovirus, densovirus} - A01K 2227/105: Murine - A01K 2267/0318: Animal model for neurodegenerative disease, e.g. non- Alzheimer's - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - C12N 2750/14143: viral genome or elements thereof as genetic vector - C12N 2800/22: Vectors comprising a coding region that has been codon optimised for expression in a respective host - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS - 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) ## Abstract A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient. ## Claims ### Claim 1 A recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid which has packaged therein a vector genome comprising an AAV 5′ inverted terminal repeat (ITR), a CB7 promoter comprising a human cytomegalovirus immediate early enhancer and a chicken beta actin promoter, an intron, nucleic acid sequences of SEQ ID NO:1, a polyA, and an AAV 3′ ITR, wherein the AAVhu68 capsid comprises a heterogenous population of AAVhu68 vp1 proteins selected from: vp1 proteins produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of 1 to 736 of SEQ ID NO:8, vp1 proteins produced from SEQ ID NO: 7, or vp1 proteins produced from a nucleic acid sequence at least 70% identical to SEQ ID NO:7 which encodes the predicted amino acid sequence of 1 to 736 of SEQ ID NO:8, a heterogenous population of AAVhu68 vp2 proteins selected from: vp2 proteins produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of at least about amino acids 138 to 736 of SEQ ID NO:8, vp2 proteins produced from a sequence comprising at least nucleotides 412 to 2211 of SEQ ID NO:7, or vp2 proteins produced from a nucleic acid sequence at least 70% identical to at least nucleotides 412 to 2211 of SEQ ID NO:7 which encodes the predicted amino acid sequence of at least about amino acids 138 to 736 of SEQ ID NO:8, and a heterogenous population of AAVhu68 vp3 proteins selected from: vp3 produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of at least about amino acids 203 to 736 of SEQ ID NO:8, vp3 proteins produced from a sequence comprising at least nucleotides 607 to 2211 of SEQ ID NO:7, or vp3 proteins produced from a nucleic acid sequence at least 70% identical to at least nucleotides 607 to 2211 of SEQ ID NO:7 which encodes the predicted amino acid sequence of at least about amino acids 203 to 736 of SEQ ID NO:8, wherein the AAVhu68 capsid is further characterized by having a valine at position 157 and a glutamic acid at position 67. ### Claim 2 (depends on 1) A pharmaceutical composition comprising a pharmaceutically acceptable carrier, excipient and/or preservative and an AAV vector according claim 1. ### Claim 3 (depends on 1) A method for treating spinal muscular atrophy in a subject, said method comprising administering the composition of claim 1 to a subject in need thereof. ### Claim 4 (depends on 3) The method according to claim 3, wherein said composition is administered intrathecally. ### Claim 5 (depends on 3) The method according to claim 3, wherein said subject is a mammal. ### Claim 6 (depends on 3) The method according to claim 3, wherein said subject is a human. ### Claim 7 (depends on 3) The method according to claim 3, wherein said composition is administered in combination with another therapy. ### Claim 8 (depends on 3) The method according to claim 3, wherein said composition is administered at a dosage of from about 1×1010 GC/g brain mass to about 3×1014 GC/g brain mass. ### Claim 9 (depends on 8) The method according to claim 8, wherein said composition is administered at a dosage of about 5×1013 GC. ### Claim 10 (depends on 8) The method according to claim 8, wherein said composition is administered at a dosage of about 1.85×1014 GC. ### Claim 11 (depends on 8) The method according to claim 8, wherein said composition is administered more than once. ### Claim 12 A host cell comprising: (a) a nucleic acid molecule encoding a AAVhu68 VP1 protein; (b) a nucleic acid molecule encoding a vector genome comprising: an AAV 5′ inverted terminal repeat (ITR) sequence, a CB7 promoter comprising a human cytomegalovirus immediate early enhancer and a chicken beta actin promoter, an intron, nucleic acid sequences of SEQ ID NO:1, a polyA, and an AAV 3′ ITR; and (c) AAV rep functions and helper functions necessary for packaging and production of a recombinant AAV having an AAVhu68 capsid and the vector genome.