# US 11,299,751 B2 · Compositions for the treatment of disease

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- Number: US 11,299,751 B2
- Document ID: US11299751B2
- Status: Granted
- Kind: B2
- Application number: 16/097,446
- Filed: 2017-04-28
- Published: 2020-05-28
- Granted: 2022-04-12
- Earliest claimed: 2016-04-29
- Assignees: Voyager Therapeutics, Inc.
- Applicants: Voyager Therapeutics, Inc.
- Inventors: Steven Paul; Donna T. Ward
- Web page: https://patentgrep.com/patent/US11299751B2

## CPC

- C12N 15/86: Viral vectors
- A61K 35/76: Viruses; Subviral particles; Bacteriophages
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/1282: Clostridium (G)
- 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)}
- 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 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2310/141: MicroRNAs, miRNAs
- 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)
- 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 invention provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody-like polypeptides, for the prevention and/or treatment of diseases and/or disorders.

## Claims

### Claim 1

An adeno associated virus (AAV) particle comprising a capsid and a viral genome, said viral genome comprising at least one inverted terminal repeat (ITR) region and a payload region, said payload region comprising a first nucleic acid segment encoding one or more payload antibody polypeptides which targets a Clostridium difficile toxin, wherein said one or more payload antibody polypeptides comprise an antibody heavy chain, an antibody light chain, and a linker; wherein said antibody heavy chain comprises the polypeptide of SEQ ID NO: 3072; and wherein said antibody light chain comprises the polypeptide of SEQ ID NO: 3073.

### Claim 2 (depends on 1)

The AAV particle of claim 1, wherein the viral genome is single stranded.

### Claim 3 (depends on 1)

The AAV particle of claim 1, wherein the viral genome is self-complementary.

### Claim 4 (depends on 1)

The AAV particle of claim 1, wherein the first nucleic acid segment is codon-optimized.

### Claim 5 (depends on 1)

The AAV particle of claim 1, wherein the linker is selected from the group consisting of: SEQ ID NOs: 899-2947, CHP, FKK, HAA, ERK, ARL, DWY, GGS, IDQ, NKV, SEA, DWK, SAV, LSD, DAG, NSG, TSA, VPR, ONK, LGI, IDY, PGS, ATK, ASK, ANR, YDP, DEG, ECF, AIS, QRE, EHV, LME, TVQ, KQI, YKR, HRG, SNP, DIT, NSD, TDT, KLR, QAA, RHP, KNL, EIY, KRP, DIR, HKN, QAV, GGK, QGM, SGC, DTF, LCA, ALS, MDA, SII, FSP, RQF, ALS, AGV, ELE, DHK, AGY, EES, IPI, KEL, PDL, ITP, EVV, SAP, RQP, SDP, G, S, GG, GS, GGS, GGG, YDK, GSV, GWK, IAE, KRQ, QDT, TPN, DSS, YEQ, KNA, VGF, NKP, KFA, AEP, PTL, ASE, QDP, VKL, ASN, AIF, FFI, VTQ, SLV, KST, GAE, ISE, DKC, SAS, ATE, HNA, RET, VRP, EGK, PAT, THW, EIP, CAY, ISP, ADT, AVG, TLI, ILM, EGV, LEL, DGV, DLT, LGL, YGT, DGL, IDL, RLK, LNF, QSN, LKS, SGE, LFR, YGM, IAI, ITF, LID, ING, LLA, VPL, WGI, SKE, TLQ, PEI, NAR, RNP, FTK, VNK, DRN, AIQ, PLP, TNG, DKA, KFR, CAA, YVP, FNP, SAL, VRL, ERV, QYP, ITD, LTE, RHA, QFD, ETG, NIT, SLT, VRE, SRR, NDE, SSF, AKP, EYF, RFE, LMQ, ADG, RQP, IDP, VPV, VSN, RRI, LEA, QMH, TLR, VHP, TAK, KSY, LDG, LLE, and TYS.

### Claim 6 (depends on 1)

The AAV particle of claim 1, wherein the first nucleic acid segment encodes from 5′ to 3′, the antibody heavy chain, the linker, and the antibody light chain.

### Claim 7 (depends on 1)

The AAV particle of claim 1, wherein the first nucleic acid segment encodes from 5′ to 3′, the antibody light chain, the linker, and the antibody heavy chain.

### Claim 8 (depends on 1)

A method of producing a functional antibody in a subject, comprising administering to said subject the AAV particle of claim 1.

### Claim 9 (depends on 8)

A pharmaceutical composition comprising an AAV particle of claim 8 and a pharmaceutically acceptable excipient.

### Claim 10 (depends on 9)

A method of treating Clostridium difficile infection in a subject, the method comprising administering to said subject the pharmaceutical composition of claim 9.

### Claim 11 (depends on 6)

The AAV particle of claim 6, wherein the first nucleic acid segment encoding the linker (a) comprises an internal ribosome entry site (IRES), (b) encodes a T2A peptide, an F2A peptide, a furin cleavage site, or a glycine serine linker, or (c) is a combination of (a) and (b).

### Claim 12 (depends on 7)

The AAV particle of claim 7, wherein the first nucleic acid segment encoding the linker (a) comprises an internal ribosome entry site (IRES), (b) encodes a T2A peptide, an F2A peptide, a furin cleavage site, or a glycine serine linker, or (c) is a combination of (a) and (b).

### Claim 13 (depends on 1)

The AAV particle of claim 1, wherein the capsid comprises an AAV9 capsid protein, an AAV2 capsid protein, or a functional variant thereof.

### Claim 14 (depends on 1)

The AAV particle of claim 1, wherein the viral genome further comprises a promoter operably linked to the payload region.

### Claim 15 (depends on 14)

The AAV particle of claim 14, wherein the promoter comprises a tissue-specific promoter or a ubiquitous promoter.

### Claim 16 (depends on 14)

The AAV particle of claim 14, wherein the promoter comprises an EF-1α promoter, a chicken β-actin (CBA) promoter and/or its derivative CAG, a cytomegalovirus (CMV) immediate-early enhancer and/or promoter, a β glucuronidase (GUSB) promoter, a ubiquitin C (UBC) promoter, a neuron-specific enolase (NSE), a platelet-derived growth factor (PDGF) promoter, a platelet-derived growth factor B-chain (PDGF-β) promoter, a synapsin (Syn) promoter, a methyl-CpG binding protein 2 (MeCP2) promoter, a Ca2+/calmodulin-dependent protein kinase II (CaMKII) promoter, a metabotropic glutamate receptor 2 (mGluR2) promoter, a neurofilament light (NFL) or heavy (NFH) promoter, a β-globin minigene nβ2 promoter, a preproenkephalin (PPE) promoter, an enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), a glial fibrillary acidic protein (GFAP) promoter, a myelin basic protein (MBP) promoter or a functional variant thereof.

### Claim 17 (depends on 1)

The AAV particle of claim 1, wherein the viral genome further comprises:
(i) an enhancer;
(ii) an intron;
(iii) a Kozak sequence; and/or
(iv) a polyadenylation sequence.

### Claim 18 (depends on 17)

The AAV particle of claim 17, wherein the enhancer comprises a Cytomegalovirus Major Immediate-Early (CMVie) enhancer.

### Claim 19 (depends on 17)

The AAV particle of claim 17, wherein the intron comprises a β-globin SD/immunoglobulin heavy chain splice acceptor (β-globin intron), or an SV40 late splice donor/splice acceptor (SV40 intron).

### Claim 20 (depends on 1)

The AAV particle of claim 1, wherein the viral genome comprises a first ITR region positioned 5′ relative to the payload region, and a second ITR region positioned 3′ relative to the payload region.