# US 11,110,154 B2 · Methods and compositions for treating Huntington's Disease

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- Number: US 11,110,154 B2
- Document ID: US11110154B2
- Status: Granted
- Kind: B2
- Application number: 14/706,747
- Filed: 2015-05-07
- Published: 2015-11-26
- Granted: 2021-09-07
- Earliest claimed: 2014-05-08
- Assignees: Sangamo Therapeutics, Inc.; CHDI Foundation, Inc.
- Applicants: Sangamo BioSciences, Inc.; CHDI Foundation, Inc.
- Inventors: Steven Froelich; Seung Kwak; Ignacio Munoz-Sanjuan; H. Steve Zhang
- Web page: https://patentgrep.com/patent/US11110154B2

## CPC

- A61K 38/54: Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
- 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)
- A61K 38/1709: {from mammals}
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- C12N 15/62: DNA sequences coding for fusion proteins
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N 15/86: Viral vectors
- C12N 15/8645: {Adeno-associated virus}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/001152: {Transcription factors, e.g. SOX or c-MYC}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/71: containing domain for transcriptional activaation, e.g. VP16
- C07K 2319/80: containing a DNA binding domain, e.g. Lacl or Tet-repressor
- C07K 2319/81: containing a Zn-finger domain for DNA binding
- C12N 2750/14121: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2750/14171: Demonstrated in vivo effect
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

Disclosed herein are methods and compositions for treating or preventing Huntington's Disease.

## Claims

### Claim 1

A method of reducing expression of a mutant Huntingtin (mHtt) gene to reduce or prevent the formation of Htt aggregates in a medium spiny neuron in a subject with Huntington's Disease (HD), the method comprising
administering to the striatum of the subject a polynucleotide encoding a repressor of a mutant Htt (mHtt) allele, the repressor comprising a zinc finger protein designated 30640, 30645 or 33074, wherein the polynucleotide comprises an adeno-associated virus (AAV) vector administered at 2×1010 vector genomes, wherein the transcription factor repressor reduces mHtt expression by at least 85% in HD neurons in the striatum of the subject and reduces the formation of Htt aggregates in the medium spiny neuron by 20 to 50% as compared to an untreated subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein cellular activity in HD neuron is increased.

### Claim 3 (depends on 1)

The method of claim 1, wherein apoptosis in the HD neuron is reduced.

### Claim 4 (depends on 1)

The method of claim 1, wherein motor deficits in the subject are reduced.

### Claim 5 (depends on 4)

The method of claim 4, wherein the motor deficit comprises clasping.

### Claim 6

A method of increasing DARPP32 expression in a medium spiny neuron in a subject with Huntington's Disease (HD), the method comprising
administering to the striatum of the subject a polynucleotide encoding a repressor of a mutant Htt (mHtt) allele to the subject, the repressor comprising a zinc finger protein designated 30640, 30645 or 33074, wherein the polynucleotide comprises an adeno-associated virus (AAV) vector administered at 2×1010 vector genomes, thereby increasing DARPP32 expression in the medium spiny neuron of the subject.