# US 12,215,338 B2 · Adeno-associated virus (AAV) delivery of anti-FAM19A5 antibodies

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- Number: US 12,215,338 B2
- Document ID: US12215338B2
- Status: Granted
- Kind: B2
- Application number: 17/053,733
- Filed: 2019-05-08
- Published: 2021-12-16
- Granted: 2025-02-04
- Earliest claimed: 2018-05-08
- Assignees: Neuracle Science Co., Ltd.; Neuracle Genetics Inc.
- Applicants: Neuracle Science Co., Ltd.; Neuracle Genetics
- Inventors: Jong-Mook Kim; Dong Sik Kim; Juwon Shim; Soon-gu Kwon
- Web page: https://patentgrep.com/patent/US12215338B2

## CPC

- A61P 25/02: for peripheral neuropathies
- C12N 15/86: Viral vectors
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- C07K 16/24: against cytokines, lymphokines or interferons
- A01K 2207/30: Animals modified by surgical methods
- A01K 2227/105: Murine
- A01K 2267/0356: Animal model for processes and diseases of the central nervous system, e.g. stress, learning, schizophrenia, pain, epilepsy
- A61K 2039/505: {comprising antibodies}
- A61K 2039/53: {DNA (RNA) vaccination}
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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 2800/22: Vectors comprising a coding region that has been codon optimised for expression in a respective host
- 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)
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS

## Abstract

The present disclosure provides adeno-associated vims (AAV) vectors and uses thereof. In certain embodiments, the AAV vectors comprise a nucleic acid that encodes an antagonist against a family with sequence similarity 19, member A5 (FAM19A5) protein, e.g., anti-FAM19A5 antibody, e.g., anti-FAM19A5 scFv.

## Claims

### Claim 1

An adeno-associated virus (AAV) vector comprising a nucleic acid that encodes an antibody, or an antigen-binding portion thereof, which specifically binds to a family with sequence similarity 19, member A5 (FAM19A5) protein (anti-FAM19A5 antibody), wherein the anti-FAM19A5 antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, and wherein:
(i) the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 16;
(ii) the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 212;
(iii) the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 213;
(iv) the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 222;
(v) the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 225; and
(vi) the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 224.

### Claim 2 (depends on 1)

The AAV vector of claim 1, further comprising an intron, a signal peptide, one or more adeno-associated virus inverted terminal repeats (ITRs), or any combination thereof.

### Claim 3 (depends on 1)

The AAV vector of claim 1, wherein the anti-FAM19A5 antibody comprises a Fab, a Fab′, a F (ab′)2, a Fv, a single chain Fv (scFv), or a combination thereof.

### Claim 4 (depends on 3)

The AAV vector of claim 3, wherein the anti-FAM19A5 antibody is a scFv.

### Claim 5 (depends on 1)

The AAV vector of claim 1, wherein the nucleic acid is codon optimized.

### Claim 6

An adeno-associated virus (AAV) vector comprising a nucleic acid that encodes an antibody, or an antigen-binding portion thereof, which specifically binds to a family with sequence similarity 19, member A5 (FAM19A5) protein (anti-FAM19A5 antibody), wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 204, or SEQ ID NO: 301.

### Claim 7

An adeno-associated virus (AAV) vector comprising a nucleic acid that encodes an antibody, or an antigen-binding portion thereof, which specifically binds to a family with sequence similarity 19, member A5 (FAM19A5) protein (anti-FAM19A5 antibody), wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 201 or SEQ ID NO: 256.

### Claim 8 (depends on 1)

The AAV vector of claim 1, wherein the anti-FAM19A5 antibody comprises
a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 236 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 245.

### Claim 9 (depends on 1)

The AAV vector of claim 1, wherein the anti-FAM19A5 antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence which is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 236; and/or wherein the light chain variable region comprises an amino acid sequence which is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 245.

### Claim 10 (depends on 1)

The AAV vector of claim 1, wherein: (i) the anti-FAM19A5 antibody, or antigen-binding portion thereof, is capable of inhibiting the binding of a reference antibody, or antigen-binding portion thereof, to a human FAM19A5 protein by at least about 10%, as measured by a binding inhibition assay; (ii) the anti-FAM19A5 antibody, or antigen-binding portion thereof, is capable of reducing a concentration of FAM19A5 protein in a culture medium comprising an astrocyte cell line by at least about 10%, as measured by ELISA; or (iii) both (i) and (ii).

### Claim 11 (depends on 1)

A composition comprising the AAV vector of claim 1 and a carrier.

### Claim 12 (depends on 1)

An isolated host cell comprising the AAV vector of claim 1.

### Claim 13 (depends on 6)

The AAV vector of claim 6, wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 301.

### Claim 14 (depends on 13)

A composition comprising the AAV vector of claim 13 and a carrier.

### Claim 15 (depends on 7)

A composition comprising the AAV vector of claim 7 and a carrier.

### Claim 16 (depends on 7)

An isolated host cell comprising the AAV vector of claim 7.

### Claim 17 (depends on 8)

A composition comprising the AAV vector of claim 8 and a carrier.

### Claim 18 (depends on 8)

An isolated host cell comprising the AAV vector of claim 8.

### Claim 19 (depends on 9)

A composition comprising the AAV vector of claim 9 and a carrier.

### Claim 20 (depends on 9)

An isolated host cell comprising the AAV vector of claim 9.
