Aqueous pharmaceutical compositions containing a fusion protein of an antibody and a lysosomal enzyme as an active ingredient, which are stable enough to be marketed, are disclosed. The aqueous pharmaceutical composition, for example, comprises the fusion protein of the antibody and the lysosomal enzyme at a concentration of 0.5 to 20 mg/mL, sodium chloride at a concentration of 0.3 to 1.2 mg/mL, sucrose at a concentration of 50 to 100 mg/mL, a nonionic surfactant at a concentration of 0.15 to 3 mg/mL, a buffer at a concentration of 3 to 30 mM, and is adjusted to pH 5.0 to 7.5.

The invention provides a nucleic acid molecule comprising a gene encoding a fusion protein of a ligand and a protein having physiological activity, to be used for expressing the fusion protein in cells, tissue or the body. The invention further provides a nucleic acid molecule comprising the fusion protein-encoding gene, which is in the form of a plasmid, in a form encapsulated in a recombinant virus virion, or a form encapsulated in liposomes or lipid nanoparticles. The invention further relates to the use of a medicine which is a nucleic acid molecule comprising the fusion protein-encoding gene.

Compositions and methods are described for the delivery of recombinant human iduronate-2-sulfatase (IDS) produced by human neuronal or glial cells to the cerebrospinal fluid of the central nervous system (CNS) of a human subject diagnosed with mucopolysaccharidosis II (MPS II).

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.

The present invention provides, among other things, improved methods for purifying I2S protein produced recombinantly for enzyme replacement therapy. The present invention is, in part, based on the surprising discovery that recombinant I2S protein can be purified from unprocessed biological materials, such as, I2S-containing cell culture medium, using a process involving as few as four chromatography columns.

The present invention provides, among other things, improved methods for purifying 12S protein produced recombinantly for enzyme replacement therapy. The present invention is, in part, based on the surprising discovery that recombinant 12S protein can be purified from unprocessed biological materials, such as, 12S-containing cell culture medium, using a process involving as few as four chromatography columns.

[Problem] To provide a pharmaceutical composition containing a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, which is stable enough to permit its distribution to the market.

[Solution] A lyophilized formulation containing; a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, and further containing a neutral salt, a disaccharide, a nonionic surfactant, and a buffer. Such a lyophilized formulation includes, for example, as an active ingredient, a fusion protein comprising an anti-transferrin receptor antibody and human iduronate-2-sulfatase, and further containing sodium chloride as the neutral salt, sucrose as the disaccharide, poloxamer as the nonionic surfactant, and phosphate buffer as the buffer.

Compositions and methods are described for the delivery of recombinant human iduronate-2-sulfatase (IDS) produced by human neuronal or glial cells to the cerebrospinal fluid of the central nervous system (CNS) of a human subject diagnosed with mucopolysaccharidosis II (MPS II).

A method to prevent, inhibit or treat one or more neurological symptoms associated with a central nervous system disorder, e.g. MPSI or MPSII by, for example, intrathecally, intracerebroventricularly or intravenously administering a rAAV encoding gene product associated with the disease, e.g., administering to an adult mammal in which the gene product is absent, defective or present at a reduced level relative to a mammal without the disease.

Provided are fusion proteins between p97 (melanotransferrin) and iduronate-2-sulfatase (IDS), and related compositions and methods of use thereof, for instance, to facilitate delivery of IDS across the blood-brain barrier (BBB) and/or improve its tissue penetration in CNS and/or peripheral tissues, and thereby treat and/or diagnose Hunter Syndrome (Mucopolysaccharidosis type II; MPS II) and related lysosomal storage disorders, including those having a central nervous system (CNS) component.