# US 11,898,158 B2 · Methods and compositions for the treatment of lysosomal storage diseases

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- Number: US 11,898,158 B2
- Document ID: US11898158B2
- Status: Granted
- Kind: B2
- Application number: 16/842,139
- Filed: 2020-04-07
- Published: 2020-07-23
- Granted: 2024-02-13
- Earliest claimed: 2012-07-11
- Assignees: Sangamo Therapeutics, Inc.
- Applicants: Sangamo Therapeutics, Inc.
- Inventors: Edward J. Rebar
- Web page: https://patentgrep.com/patent/US11898158B2

## CPC

- C12N 15/907: {in mammalian cells}
- A61K 35/407: Liver; Hepatocytes
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 38/47: acting on glycosyl compounds (3.2), e.g. cellulases, lactases
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 9/222: {Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes}
- C12Y 301/06013: Iduronate-2-sulfatase (3.1.6.13)
- C12Y 302/0102: Alpha-glucosidase (3.2.1.20)
- C12Y 302/01021: Beta-glucosidase (3.2.1.21)
- C12Y 302/01022: Alpha-galactosidase (3.2.1.22)
- C12Y 302/01076: L-Iduronidase (3.2.1.76)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C07K 2319/81: containing a Zn-finger domain for DNA binding
- 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)
- C12Y: ENZYMES
- 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

Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of a lysosomal storage disease.

## Claims

### Claim 1

A method of treating a mouse or human with Gaucher's, Fabry's, or Pompe's disease, the method comprising
intravenously injecting first and second AAV vectors encoding first and second ZFNs of a pair of zinc finger nucleases that cleave in an endogenous albumin gene, into the mouse or human with Gaucher's, Fabry's, or Pompe's disease;
intravenously injecting a third AAV vector comprising a transgene encoding:
(a) a glucocerebrosidase (GBA) protein into the mouse or human with Gaucher's disease;
(b) an α galactosidase deficiency (GLA) protein into the mouse or human with Fabry's disease;
(c) an alpha-glucosidase (GAA) protein into the mouse or human with Pompe's disease; or
wherein the transgene is flanked by sequences having homology with the endogenous albumin gene;
wherein the first, second and third AAV vectors are delivered at a ratio of 1:1:8 and further wherein the transgene is integrated into the endogenous albumin gene in liver cells of the mouse or human and the liver cells express and secrete therapeutic amounts of the protein and a symptom of the Gaucher's, Fabry's, or Pompe's disease is treated in the mouse or human.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method treats neurological deficits associated with Gaucher's, Fabry's, or Pompe's disease.

### Claim 3 (depends on 1)

The method of claim 1, wherein expression of the transgene is driven by an endogenous albumin promoter.

### Claim 4 (depends on 1)

The method of claim 1, wherein the AAV vectors are AAV2 and/or AAV6 vectors.

### Claim 5 (depends on 1)

The method of claim 1, wherein the protein is detectable in secondary tissues in the mouse or human subject.

### Claim 6 (depends on 5)

The method of claim 5, wherein the secondary tissue is spleen.

### Claim 7 (depends on 5)

The method of claim 5, wherein the secondary tissue is blood or plasma.

### Claim 8 (depends on 5)

The method of claim 5, wherein the secondary tissue is kidney or lung.