BioMarin Pharmaceutical Inc.

The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), and novel pharmaceutical compositions and formulations comprising CNP variant peptides for the treatment of skeletal dysplasias, one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and other disorders having a skeletal dysplasia and/or CNP-associated symptom or component.

The present invention relates in general to therapeutic fusion proteins useful to treat lysosomal storage diseases and methods for treating such diseases. Exemplary therapeutic fusion proteins comprise a lysosomal enzyme, a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide. Also provided are compositions and methods for treating Mucopolysaccharidosis Type IIIB (Sanfilippo B Syndrome), comprising a targeted therapeutic fusion protein comprising alpha-N-acetylglucosaminidase (Naglu), a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide.

The invention provides completely packaged adeno-associated virus (AAV) Factor VIII (FVIII) vectors. This invention also provides completely packaged AAV FVIII vectors with high expression activity.

The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), for the treatment of skeletal dysplasias in children, and improvement in one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and use in other disorders having a skeletal dysplasia and/or CNP-associated symptom or component.

The present disclosure provides conjugates of phenylalanine ammonia-lyase and poly(oligo(ethylene glycol)methacrylate (POEGMA) and methods for their use. In particular, the POEGMA-PAL conjugates disclosed herein are immune-masked for a reduced immune response upon administration to a subject.

The disclosure provides various compositions comprising novel adeno-associated virus (AAV) capsid sequences and functional fragments thereof. Also provided, are methods of delivery, treatment and manufacture using the compositions provided by the disclosure.

The present invention provides processes for producing and characterizing adenoassociated virus particles and baculovirus particles. The present invention is directed to methods of improving adeno associated virus (AAV) production. The present invention addresses the problems associated with the production of rAAV using baculovirus infected Sf9 cells and achieves an improved method for producing rAAV. The present invention developed different methods for producing recombinant baculovirus (rBV) and recombinant adeno-associated virus (rAA V). These methods address issues such as genome instability and also result in improved production of rAA V, as well as produce rAA V with improved properties.

The invention provides improved adeno-associated virus (AAV) Factor VIII (FVIII) vectors, including AAV FVIII vectors that produce a functional Factor VIII polypeptide and AAV FVIII vectors with high expression activity.

treatment of skeletal dysplasias in children, and improvement in one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, by administering variants of C-type natriuretic peptide (CNP) is described.

The disclosure relates to the use of variants of C-type natriuretic peptide (CNP) to treat osteoarthritis, to ameliorate one or more symptoms of osteoarthritis, and to treat disorders having an osteoarthritis component.