Recombinant human naglu protein and uses thereof
AssigneeSynageva BioPharma Corp.
InventorsAnthony Quinn, Markley C. Leavitt, Zhinan Xia
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Abstract
The present invention provides compositions comprising an isolated mixture of recombinant human NaGlu proteins in which a substantial amount of the NaGlu proteins in the mixture has increased levels of phosphorylated mannose that confer the proteins to be efficiently internalized into human cells. The present invention also provides methods of producing such mixture of NaGlu proteins, vectors used in transgenesis and expression, host cells harboring such vectors, and methods of isolating and purifying the mixture of NaGlu proteins. The invention further provides methods of treating NaGlu associated diseases.
Claims30
A composition comprising an isolated mixture of recombinant human N-acetyl-alpha-D-glucosaminidase (rhNaGlu) comprising the amino acid sequence 24-743 of SEQ ID NO:1, wherein at least 10% of said rhNaGlu in said mixture comprises at least one glycan structure having mannose-6-phosphate (M6P).
A composition comprising an isolated recombinant human N-acetyl-alpha-D-glucosaminidase (rhNaGlu) comprising one or more glycan structures having sufficient amount of mannose-6-phosphate (M6P) that allows for internalization of said rhNaGlu into a mammalian cell having NaGlu deficiency via M6P receptor-mediated endocytosis, such that when internalized in vivo into a subject showing a deficiency in NaGlu, said rhNaGlu restores at least 50% of NaGlu activity observed in a cell of the same type in a normal subject.
A method of producing a recombinant human NaGlu (rhNaGlu) comprising:
- a) producing a transgenic avian comprising a transgene having a promoter component operably linked to a nucleic acid sequence encoding the rhNaGlu set forth in 24-743 of SEQ ID NO:1, wherein said transgene is contained in the genome of the transgenic avian and expressed in an oviduct cell, such that the rhNaGlu is glycosylated in the oviduct cell of the transgenic avian, secreted into lumen of oviduct and deposited in egg white of an egg laid of the transgenic avian;
- and
- b) isolating said rhNaGlu from said egg white.
A method of delivering recombinant human NaGlu protein to the brain of a subject suffering from NaGlu deficiency, the method comprising intravenously administering recombinant human NaGlu protein to the subject.
Dependencies are inferred from the claim text.