Lysosomal storage disease enzymes
AssigneeAlexion Pharmaceuticals, Inc.
InventorsAnthony Quinn, Alex J. Harvey
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Abstract
The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.
Claims20
An isolated recombinant human lysosomal acid lipase glycoprotein (rhLAL), wherein the rhLAL consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:19, with N-glycans bonded to the asparagine residues (Asn) that correspond to Asn36, Asn101, Asn161, Asn273 and Asn321 of SEQ ID NO:1, with the proviso that the N-glycans do not comprise fucose, and the proviso that the rhLAL does not contain O-glycans.
An isolated recombinant human lysosomal acid lipase glycoprotein (rhLAL), wherein the rhLAL consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:19, with N-glycans bonded to the asparagine residues (Asn) that correspond to Asn36, Asn101, Asn161, Asn273 and Asn321 of SEQ ID NO:1, with the proviso that the N-glycans do not comprise fucose, and the proviso that the rhLAL does not contain O-glycans, and wherein the N-glycans bonded to the Asn residues that correspond to Asn36, Asn101, Asn161, Asn273 and Asn321 of SEQ ID NO:1 are:
- a) at Asn36, GlcNAc4Man3GlcNAc2, or
- Gal1GlcNAc4Man3GlcNAc2;
- b) at Asn101, Phos2Man7GlcNAc2;
- c) at Asn161, Phos1Man6GlcNAc2,
- GlcNAc1Phos1Man6GlcNAc2;
- Man3GlcNAc2;
- GlcNAc2Man3GlcNAc2;
- GlcNAc3Man3GlcNAc2;
- GlcNAc4Man3GlcNAc2, or
- Gal1GlcNAc4Man3GlcNAc2;
- d) at Asn273, Man7GlcNAc2,
- Man8GlcNAc2,
- Man9GlcNAc2,
- Phos1Man8GlcNAc2, or
- Phos1Man9GlcNAc2;
- and
- e) at Asn321, GlcNAc2Man3GlcNAc2,
- GlcNAc3Man3GlcNAc2,
- GlcNAc4Man3GlcNAc2,
- Gal1GlcNAc4Man3GlcNAc2,
- GlcNAc5Man3GlcNAc2,
- Gal1GlcNAc5Man3GlcNAc2,
- GlcNAc6Man3GlcNAc2, or
- Gal1GlcNAc6Man3GlcNAc2;
- wherein
- Man=mannose,
- GlcNAc=N-Acetyl Glucosamine,
- Phos=phosphate, and
- Gal=galactose.
Dependencies are inferred from the claim text.