# US 10,308,958 B2 · Method of detecting and/or identifying adeno-associated virus (AAV) sequences and isolating novel sequences identified thereby

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,308,958 B2
- Document ID: US10308958B2
- Status: Granted
- Kind: B2
- Application number: 15/633,906
- Filed: 2017-06-27
- Published: 2017-10-19
- Granted: 2019-06-04
- Earliest claimed: 2001-11-13
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Guangping Gao; James M. Wilson; Mauricio R. Alvira
- Web page: https://patentgrep.com/patent/US10308958B2

## CPC

- C12N 15/86: Viral vectors
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/4846: {Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- 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)
- C12Q 1/701: {Specific hybridization probes}
- C12Y 304/21022: Coagulation factor IXa (3.4.21.22)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- 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 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2750/14151: Methods of production or purification of viral material
- C12N 2750/14152: relating to complementing cells and packaging systems for producing virus or viral particles
- C12N 2750/14162: by genetic engineering
- C12N 2750/14171: Demonstrated in vivo effect
- C12N 2830/008: cell type or tissue specific enhancer/promoter combination
- C12N 2830/48: regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE
- C12N 2830/85: mammalian
- C12N 2830/90: avian
- C12Q 2600/158: Expression markers
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Y: ENZYMES

## Abstract

Adeno-associated virus rh.10 sequences, vectors containing same, and methods of use are provided.

## Claims

### Claim 1

A recombinant adeno-associated virus (AAV) comprising an AAV capsid comprising vp1 proteins having the sequence of amino acids 1 to 738 of SEQ ID NO: 81 or a sequence at least 95% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 81, AAV vp2 proteins, and AAV vp3 proteins, wherein the recombinant AAV further comprises, packaged within the capsid, a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR), and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell wherein the gene product is ornithine transcarbamylase, glucose-6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein.

### Claim 2 (depends on 1)

The recombinant AAV according to claim 1, wherein the sequence of the vp1 proteins is at least 97% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 81.

### Claim 3 (depends on 1)

The recombinant AAV according to claim 1, wherein the sequence of the vp1 proteins is at least 99% identical to the full-length of amino acids 1 to 738 of SEQ ID NO: 81.

### Claim 4 (depends on 1)

The recombinant AAV according to claim 1, wherein the sequence of the vp1 proteins is the full-length of amino acids 1 to 738 of SEQ ID NO: 81.

### Claim 5

A recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vp1 proteins, AAV vp2 proteins having a sequence of amino acids 138 to 738 of SEQ ID NO:81 (rh.10) or a sequence at least 95% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 81, and AAV vp3 proteins, wherein the recombinant AAV further comprises, packaged within the capsid, a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell, wherein the gene product is ornithine transcarbamylase, glucose-6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein.

### Claim 6 (depends on 5)

The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is at least 97% identical to the full length of amino acids 138 to 738 of SEQ ID NO: 81.

### Claim 7 (depends on 5)

The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is at least 99% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 81.

### Claim 8 (depends on 5)

The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is the full-length of amino acids 138 to 738 of SEQ ID NO: 81.

### Claim 9

A recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vp1 proteins, AAV vp2 proteins, and AAV vp3 proteins having a sequence of amino acids 204 to 738 of SEQ ID NO:81 (rh.10) or a sequence at least 95% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 81, wherein the recombinant AAV further comprises, packaged within the capsid, a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell, wherein the gene product is ornithine transcarbamylase, glucose-6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein.

### Claim 10 (depends on 9)

The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is at least 97% identical to the full length of amino acids 204 to 738 of SEQ ID NO: 81.

### Claim 11 (depends on 9)

The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is at least 99% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 81.

### Claim 12 (depends on 9)

The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is the full-length of amino acids 204 to 738 of SEQ ID NO: 81.

### Claim 13 (depends on 9)

The recombinant AAV according to claim 9, wherein the AAV ITR is from AAV2.

### Claim 14 (depends on 1)

A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to claim 1.

### Claim 15 (depends on 5)

A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to claim 5.

### Claim 16 (depends on 9)

A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to claim 9.

### Claim 17 (depends on 5)

A method for delivering a transgene product to a subject, said method comprising administering the adeno-associated virus (AAV) according to claim 5.

### Claim 18 (depends on 9)

A method for delivering a transgene product to a subject, said method comprising administering the adeno-associated virus (AAV) according to claim 9.

### Claim 19 (depends on 1)

The recombinant AAV according to claim 1, wherein the gene product is ornithine transcarbamylase.

### Claim 20 (depends on 1)

The recombinant AAV according to claim 1, wherein the gene product is glucose-6-phosphatase.

### Claim 21 (depends on 1)

The recombinant AAV according to claim 1, wherein the gene product is phenylalanine hydroxylase.

### Claim 22 (depends on 1)

The recombinant AAV according to claim 1, wherein the gene product is argininosuccinate synthetase.

### Claim 23 (depends on 1)

The recombinant AAV according to claim 1, wherein the gene product is a dystrophin protein.

### Claim 24 (depends on 5)

The recombinant AAV according to claim 5, wherein the gene product is ornithine transcarbamylase.

### Claim 25 (depends on 5)

The recombinant AAV according to claim 5, wherein the gene product is glucose-6-phosphatase.

### Claim 26 (depends on 5)

The recombinant AAV according to claim 5, wherein the gene product is, phenylalanine hydroxylase.

### Claim 27 (depends on 5)

The recombinant AAV according to claim 5, wherein the gene product is argininosuccinate synthetase.

### Claim 28 (depends on 5)

The recombinant AAV according to claim 5, wherein the gene product is a dystrophin protein.

### Claim 29 (depends on 9)

The recombinant AAV according to claim 9, wherein the gene product is ornithine transcarbamylase.

### Claim 30 (depends on 9)

The recombinant AAV according to claim 9, wherein the gene product is glucose-6-phosphatase.

### Claim 31 (depends on 9)

The recombinant AAV according to claim 9, wherein the gene product is, phenylalanine hydroxylase.

### Claim 32 (depends on 9)

The recombinant AAV according to claim 9, wherein the gene product is argininosuccinate synthetase.

### Claim 33 (depends on 9)

The recombinant AAV according to claim 9, wherein the gene product is a dystrophin protein.

### Claim 34 (depends on 1)

A method for delivering a transgene product to a subject, said method comprising administering the adeno-associated virus (AAV) according to claim 1.