# US 2022/0243291 A1 · Adeno-Associated Virus Virions with Variant Capsid and Methods of Use Thereof

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- Number: US 2022/0243291 A1
- Document ID: US20220243291A1
- Status: Published application
- Kind: A1
- Application number: 17/551,030
- Filed: 2021-12-14
- Published: 2022-08-04
- Earliest claimed: 2011-04-22
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: David V. SCHAFFER; Ryan R. KLIMCZAK; James T. KOERBER; John G. FLANNERY; Deniz DALKARA MOUROT; Meike Visel; Leah C.T. BYRNE
- Web page: https://patentgrep.com/patent/US20220243291A1

## CPC

- C12Q 1/701: {Specific hybridization probes}
- 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 9/0048: {Eye, e.g. artificial tears}
- A61K 38/1709: {from mammals}
- A61K 48/0008: {characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition}
- A61K 48/0025: {wherein the non-active part clearly interacts with the delivered nucleic acid}
- A61K 48/0041: {the non-active part being polymeric}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 27/00: Drugs for disorders of the senses
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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 15/115: Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers}
- C12N 15/86: Viral vectors
- C12Q 1/70: involving virus or bacteriophage {(immunoassay for viruses G01N33/56983)}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/5058: {Neurological cells}
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/16: Aptamers
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N 2750/14021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- 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 2750/14142: virus or viral particle as vehicle, e.g. encapsulating small organic molecule
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2750/14145: Special targeting system for viral vectors
- C12N 2750/14152: relating to complementing cells and packaging systems for producing virus or viral particles
- C12N 2810/40: Vectors comprising a peptide as targeting moiety, e.g. a synthetic peptide, from undefined source
- C12Q 2600/158: Expression markers
- C12Q 2600/16: Primer sets for multiplex assays
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

## Claims

### Claim at position 1

-23. (canceled)

### Claim 24

A variant adeno-associated virus (AAV) capsid protein, wherein the variant AAV capsid protein comprises an insertion of from about 5 amino acids to about 11 amino acids wherein the amino acid insertion is in the GH loop of a native AAV capsid, wherein the insertion is a peptide of Formula I, Formula II, Formula III, or Formula IV.

### Claim at position 3

-27. (canceled)

### Claim 28 (depends on 24)

The variant adeno-associated virus (AAV) capsid protein of claim 24, wherein the variant AAV capsid protein comprises an insertion of from about 5 amino acids to about 11 amino acids wherein the amino acid insertion is in the GH loop of a native AAV capsid, wherein the insertion is a peptide of Formula IV.

### Claim 29 (depends on 28)

The variant adeno-associated virus capsid protein of claim 28, wherein the amino acid insertion comprises the amino acid sequence Y1Y2X1X2X3X4X5X6X7Y3Y4, wherein:
each of Y1-Y4, if present, is independently selected from Ala, Leu, Gly, Ser, and Thr;
X1, if present, is an uncharged amino acid;
X2 is an uncharged amino acid;
X3 is a negatively charged amino acid; or is selected from Glu, Thr, Gly, Asp, or Pro;
X4 is selected from Thr, Ile, Gly, Lys, Asp, and Gln;
X5 is a polar amino acid, an alcohol (an amino acid having a free hydroxyl group); or is selected from Thr, Ser, Val, and Ala;
X6 is a positively charged amino acid; or is selected from Arg, Val, Lys, Pro, Thr, and Asn; and
X7, if present, is a positively charged amino acid or selected from Pro, Gly, Phe, Asn and Arg.

### Claim 30 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X3 is a negatively charged amino acid.

### Claim 31 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X3 is selected from Glu, Thr, Gly, Asp, or Pro.

### Claim 32 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X3 is Asp.

### Claim 33 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X4 is Gln.

### Claim 34 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X5 is a polar amino acid.

### Claim 35 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X5 is an alcohol (an amino acid having a free hydroxyl group).

### Claim 36 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X5 is a hydrophobic amino acid.

### Claim 37 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X5 is selected from Thr, Ser, Val, and Ala.

### Claim 38 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X5 is Thr.

### Claim 39 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X6 is a positively charged amino acid.

### Claim 40 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X6 is selected from Arg, Val, Lys, Pro, Thr, and Asn.

### Claim 41 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X6 is Lys.

### Claim 42 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X7, if present, is a positively charged amino acid.

### Claim 43 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein X7, if present, is selected from Pro, Gly, Phe, Asn and Arg.

### Claim 44 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein the amino acid insertion is AVDTTKR (SEQ ID NO: 59).

### Claim 45 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein the amino acid insertion is inserted following any of amino acids in positions 570-671 in VP1 of AAV2 or a corresponding position in another wild-type AAV serotype or AAV variant.

### Claim 46 (depends on 29)

The variant adeno-associated virus capsid protein of claim 29, wherein the amino acid insertion is inserted between amino acids 587 and 588 relative to SEQ ID NO: 1.

### Claim 47

A variant adeno-associated virus (AAV) capsid protein, wherein the variant AAV capsid protein comprises an amino acid insertion selected from NETITRP (SEQ ID NO: 14), KAGQANN (SEQ ID NO: 15), KDPKTTN (SEQ ID NO: 16), KDTDTTR (SEQ ID NO: 57), RAGGSVG (SEQ ID NO: 58), AVDTTKR (SEQ ID NO: 59), or STGKVPN (SEQ ID NO: 60), wherein the amino acid insertion is in the GH loop of a native AAV capsid.

### Claim 48 (depends on 47)

The variant adeno-associated virus capsid protein of claim 47, wherein the amino acid insertion is inserted following any of amino acids in positions 570-671 in VP1 of AAV2 or a corresponding position in another wild-type AAV serotype or AAV variant.

### Claim 49 (depends on 47)

The variant adeno-associated virus capsid protein of claim 47, wherein the amino acid insertion is inserted between amino acids 587 and 588 relative to SEQ ID NO: 1.