METHODS AND COMPOSITIONS FOR THE TREATMENT OF LYSOSOMAL STORAGE DISEASES

• US 20180110808A1
• Filed: 12/13/2017
• Published: 04/26/2018
• Est. Priority Date: 07/11/2012
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Rebar, Edward J.
• Granted Patent: US 10,293,000 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/46 Hydrolases (3)
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 15/8645 Adeno-associated virus
• CPC Class Codes: C12N 15/907 in mammalian cells
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113

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

1. A method for providing a protein to a human subject with a lysosomal storage disease and lacking or deficient in the protein, the method comprising:

administering an artificial nuclease and a donor sequence comprising a transgene encoding the protein to the human subject, wherein the artificial nuclease cleaves an endogenous albumin gene in a liver cell of the human subject and the transgene is integrated into the endogenous albumin gene following cleavage and the liver cell expresses and secretes the protein such that the protein is provided to the subject.

2. The method of claim 1, wherein the protein is selected from the group consisting of glucocerbrosidase (GBA), α

-galactosidase A (GLA), iduronate sulfatase, (IDS), iduronidase (IDUA), α

-Glucosidase (GAA) or a sphingomyelin protein.

2-1. The method of claim 1, wherein expression of the transgene is driven by an endogenous albumin promoter.

3. The method of claim 1, wherein the artificial nuclease and donor sequence are co-administered.

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

5. The method of claim 1, wherein the protein is secreted from the liver into the blood, spleen, kidney, lymph nodes and/or brain of the human subject.

6. A method of treating a human subject with a lysosomal storage disease in a human subject, the method comprising

providing a protein to the human subject according to the method of claim 1, such that the lysosomal storage disease is treated.