Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Abstract: The present invention provides, among oilier things, compositions and methods for CNS delivery of lysosomal enzymes (e.g., recombinant human arylsulfatase A (rhASA)) for effective treatment of lysosomal storage diseases (e.g. Metachromatic Leukodystrophy Disease), In some embodiments, the present invention includes a stable formulation for intrathecal administration comprising an ASA protein and a poloxamer, wherein less than 3% of the ASA protein exists in aggregated form.

Abstract: The present invention provides, among other things, stable formulations comprising an anti-oncostatin M receptor (OSMR) antibody and having a pH ranging from approximately 6.0-7.6, wherein less than approximately 5% of the anti-OSMR antibody exists as high molecular weight (HMW) species in the formulation.

Abstract: The present invention provides, among other things, stable formulations comprising an anti-oncostatin M receptor (OSMR) antibody and having a pH ranging from approximately 6.0-7.6, wherein less than approximately 5% of the anti-OSMR antibody exists as high molecular weight (HMW) species in the formulation.

Abstract: The present invention relates to the methods of developing recombinant proteins with a fingerprint like similarity to the reference product or the originator. The method is particularly useful in the development of biosimilar products. This method can also be used to establish comparability during the manufacturing process change for the originator products. Hie methods described herein are used to obtain a recipe for the production of a biosimilar product or a recombinant protein using a process that may be different from the original but that yields a recombinant protein that has fingerprint level of similarity to the reference product. The methods described herein can also used to obtain a fingerprinting analysis package for a biosimilar that can be submitted to regulatory agency for abbreviated biosimilar approval.

Abstract: Compositions of proteins having free thiols, and methods of making and using such compositions, are described.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

Abstract: Compositions of proteins having free thiols, and methods of making and using such compositions, are described.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Abstract: The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Abstract: The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

Abstract: The present invention describes methods for the characterization of mRNA molecules during mRNA production. Characterizing mRNA includes processes such as oligonucleotide mapping, reverse transcriptase sequencing, charge distribution analysis, and detection of RNA impurities. Oligonucleotide mapping includes using an RNase to digest antisense duplexes from an RNA transcript, and then subjecting the digested RNA to reverse phase HPLC, anion exchange HPLC, and/or mass spectrometry analysis. Reverse transcriptase sequencing involves reverse transcription of an RNA transcript followed by DNA sequencing. Charge distribution analysis can comprise procedures such as anion exchange HPLC, or capillary electrophoresis. Detection of impurities includes detecting short mRNA transcripts, RNA-RNA hybrids, and RNA-DNA hybrids.

Abstract: Reversed phase-High Performance (High Pressure) Liquid Chromatography (RP-HPLC) and Size Exclusion Chromatography (SEC) methods have been developed for monitoring structural and size heterogeneity as well as stability of large RNA transcripts, including lengths of up to at least 10,000 nucleotides. The methods are designed for significantly larger mRNAs that could be monitored in the past, including lengths of up to at least 10,000 nucleotides, and including chemically modified RNA transcripts. SEC techniques are also used in the preparative purification of large RNA transcripts to remove impurities, including hybridized nucleic acid impurities and multimeric RNA species. All of these techniques are also beneficial in that they can be used for large scale manufacturing of therapeutics.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

Abstract: The invention relates, in part, to improved methods of administering ?-galactosidase A for the treatment of ?-galactosidase A deficiencies including Fabry disease.

Abstract: Compositions of proteins having free thiols, and methods of making and using such compositions, are described.

Abstract: Compositions of proteins having free thiols, and methods of making and using such compositions, are described.