# US 10,480,011 B2 · Recombinant AAV variants and uses thereof

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- Number: US 10,480,011 B2
- Document ID: US10480011B2
- Status: Granted
- Kind: B2
- Application number: 15/520,977
- Filed: 2015-10-21
- Published: 2018-01-25
- Granted: 2019-11-19
- Earliest claimed: 2014-10-21
- Assignees: University of Massachusetts
- Applicants: University of Massachusetts
- Inventors: Guangping Gao; Jun Xie; Terence Flotte
- Web page: https://patentgrep.com/patent/US10480011B2

## CPC

- C12N 15/86: Viral vectors
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid}
- C07K 14/005: from viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- 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 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic)
- A01K 2217/206: Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
- A01K 2267/03: Animal model, e.g. for test or diseases
- A61K 35/00: Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2750/14121: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2750/14122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2750/14141: Use of virus, viral particle or viral elements as a vector
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2750/14145: Special targeting system for viral vectors
- C12N 2810/6027: ssDNA viruses
- C12N 2830/008: cell type or tissue specific enhancer/promoter combination
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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)

## Abstract

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

## Claims

### Claim 1

A recombinant adeno-associated viral particle comprising an adeno-associated virus capsid and at least one heterologous transgene, wherein the adeno-associated virus capsid comprises a protein comprising an amino acid sequence selected from any one of SEQ ID NOs: 54 to 61.

### Claim 2 (depends on 1)

A composition comprising the rAAV of claim 1 and a pharmaceutically acceptable carrier.

### Claim 3 (depends on 1)

A method for delivering a transgene to a subject comprising administering the recombinant adeno-associated viral particle of claim 1 to a subject, wherein the recombinant adeno-associated viral particle comprises the at least one heterologous transgene, and wherein the recombinant adeno-associated viral particle infects cells of a target tissue of the subject.

### Claim 4 (depends on 1)

A method for generating a somatic transgenic non-human animal model comprising administering the recombinant adeno-associated viral particle of claim 1 to a non-human animal, wherein the recombinant adeno-associated viral particle comprises the at least one heterologous transgene, and wherein the recombinant adeno-associated viral particle infects cells of a target tissue of the non-human animal.

### Claim 5 (depends on 3)

The method of claim 3, wherein the at least one heterologous transgene is a protein coding gene or encodes a small interfering nucleic acid.

### Claim 6 (depends on 5)

The method of claim 5, wherein the small interfering nucleic acid is a miRNA or a shRNA.

### Claim 7 (depends on 3)

The method of claim of claim 3, wherein the target tissue is skeletal muscle, heart, liver, pancreas, brain or lung.

### Claim 8 (depends on 3)

The method of claim 3, wherein the recombinant adeno-associated viral particle is administered intravenously, transdermally, intraocularly, intrathecally, orally, intramuscularly, subcutaneously, intranasally, or by inhalation.

### Claim 9 (depends on 3)

The method of claim 3, wherein the subject is selected from a mouse, a rat, a rabbit, a dog, a cat, a sheep, a pig, a non-human primate, or a human.

### Claim 10 (depends on 4)

A somatic transgenic non-human animal model produced by the method of claim 4.

### Claim 11 (depends on 1)

A kit comprising a container housing the recombinant adeno-associated viral particle of claim 1, wherein the container is a syringe.