Method of treating mucopolysaccharidosis type I or II

• US 10,648,001 B2
• Filed: 10/01/2015
• Issued: 05/12/2020
• Est. Priority Date: 07/11/2012
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Rebar, Edward J.
• Primary Examiner(s): Wilson, Michael C
• Application Number:
  US14/872,537
• Publication Number:
  US 20160060656A1
• Time in Patent Office: 1,685 Days
• Field of Search: 435325, 424 9321, 424 932, 514 44
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• 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: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 15/907 in mammalian cells
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113
• CPC Class Codes: C12Y 301/06013 Iduronate-2-sulfatase (3.1.6.13)
• CPC Class Codes: C12Y 302/0102 Alpha-glucosidase (3.2.1.20)
• CPC Class Codes: C12Y 302/01021 Beta-glucosidase (3.2.1.21)
• CPC Class Codes: C12Y 302/01022 Alpha-galactosidase (3.2.1.22)
• CPC Class Codes: C12Y 302/01076 L-Iduronidase (3.2.1.76)

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 of treating a mouse or human with mucopolysaccharidosis type I (MPS I) or mucopolysaccharidosis type II (MPS II) 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 MPS I or MPS II disease;

intravenously injecting a third AAV vector comprising a transgene encoding (a) an iduronidase (IDUA) protein into the mouse or human with MPS I disease or (b) a DNA sequence encoding an iduronate sulfatase (IDS) protein into the mouse or human with MPS II disease, 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 IDUA or IDS protein and a symptom of the MPS I or MPS II disease is treated in the mouse or human.

2. The method of claim 1, wherein the method treats neurological deficits associated with MPS I or MPS II disease.

3. The method of claim 1, wherein the method reduces GAG accumulation in the mouse or human.

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