# US 2019/0167815 A1 · Methods and compositions for the treatment of rare diseases

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- Number: US 2019/0167815 A1
- Document ID: US20190167815A1
- Status: Published application
- Kind: A1
- Application number: 16/169,420
- Filed: 2018-10-24
- Published: 2019-06-06
- Earliest claimed: 2017-10-24
- Applicants: Sangamo Therapeutics, Inc.
- Inventors: Michael C. Holmes; Brigit E. Riley; Thomas Wechsler; Bryan Zeitler; Lei Zhang
- Web page: https://patentgrep.com/patent/US20190167815A1

## CPC

- 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}
- 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 9/0043: {Nose}
- A61K 9/0085: {Brain, e.g. brain implants; Spinal cord}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- 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 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- A61K 48/0091: {Purification or manufacturing processes for gene therapy compositions}
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07K 14/4702: {Regulators; Modulating activity}
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- 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 2319/00: Fusion polypeptide
- C07K 2319/50: containing protease site
- C07K 2319/71: containing domain for transcriptional activaation, e.g. VP16
- C07K 2319/81: containing a Zn-finger domain for DNA binding
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- 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)

## Abstract

The present disclosure is in the field of modulation of genes involved in rare diseases including for diagnostics and therapeutics for rare diseases such as Angelman's Syndrome, Facioscapulohumeral Muscular Dystrophy (FHMD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal dementia (FTD) and Spinal Muscular Atrophy (SMA).

## Claims

### Claim 1

A genetic modulator of a C9orf72 gene, the modulator comprising
a DNA-binding domain that binds to a target site of at least 12 nucleotides in the C9orf72 gene; and
a transcriptional regulatory domain or nuclease domain.

### Claim 2 (depends on 1)

The genetic modulator of claim 1, wherein the DNA-binding domain comprises a zinc finger protein (ZFP), a TAL-effector domain protein (TALE) or single guide RNA.

### Claim 3 (depends on 1)

The genetic modulator of claim 1, wherein the transcriptional regulatory domain comprises a repression domain or activation domain.

### Claim 4 (depends on 1)

A polynucleotide encoding the genetic modulator according to claim 1.

### Claim 5 (depends on 4)

A gene delivery vehicle comprising the polynucleotide according to claim 4.

### Claim 6 (depends on 5)

The gene delivery vehicle of claim 5, wherein the gene delivery vehicle comprises
an AAV vector.

### Claim 7 (depends on 4)

A pharmaceutical composition comprising one or more polynucleotides according to claim 4.

### Claim 8 (depends on 7)

The pharmaceutical composition of claim 7, wherein the genetic modulator comprises a nuclease domain and the genetic modulator cleaves the C9orf72 gene.

### Claim 9 (depends on 8)

The pharmaceutical composition of claim 8, further comprising a donor molecule that is integrated into the cleaved C9orf72 gene.

### Claim 10 (depends on 1)

An isolated cell comprising one or more genetic modulators according to claim 1.

### Claim 11 (depends on 4)

An isolated cell comprising one or more polynucleotides according to claim 4.

### Claim 12 (depends on 1)

A method of modulating C9orf72 gene expression in a cell, the method comprising administering one or more genetic modulators according to claim 1 to a cell.

### Claim 13 (depends on 12)

The method of claim 12, wherein C9orf72 gene expression is repressed.

### Claim 14 (depends on 13)

The method of claim 13, wherein both sense and antisense C9orf72 gene expression is repressed.

### Claim 15 (depends on 14)

The method of claim 14, wherein the administration is intracerebroventricular, intrathecal, intracranial, retro-orbital (RO), intravenous, intranasal or intracisternal.

### Claim 16 (depends on 15)

A method of treating and/or preventing Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal dementia (FTD) in a subject, the method comprising repressing C9orf72 expression according to the method of claim 15.

### Claim 17 (depends on 6)

A kit comprising one or more of gene delivery vehicles according to claim 6 and/or instructions for use.