Women's and Children's Hospital

Other

Peter Roy Clements

John Joseph Hopwood

Donald Stewart Anson

Charles Phillip Morris

Peter J Wilson

Teresa Occhiodoro

Julie Bielicki

Annette Marie Orsborn

Paul Victor Nelson

Hamish Steel Scott

Hamish Steele Scott

The present invention provides a highly glycosylated iduronate-2-sulfatase enzyme comprising an iduronate-2-sulfatase polypeptide with at least 5 kilodalton (kDa) more sugar than iduronate-2-sulfatase purified from a natural source, e.g. human liver. The present invention also provides an enzymatically active polypeptide fragment or variant of such a highly glycosylated iduronate-2-sulfatase. The present invention further provides an isolated nucleic acid encoding iduronate-2-sulfatase, as well as an expression vector, a host cell and a method for producing the present highly glycosylated iduronate-2-sulfatase enzyme. In one embodiment the present invention is directed to a method for producing a glycosylated iduronate-2-sulfatase enzyme which comprises culturing a host cell containing a nucleic acid encoding an enzymatically active iduronate-2-sulfatase polypeptide wherein the host cell glycosylates the polypeptide to a greater degree than a native iduronate-2-sulfatase polypeptide expressed by a natural human liver cell.

Glycosylation variants of iduronate 2-sulfatase

The present invention relates generally to &agr;-L-iduronidase and to genetic sequences encoding same. More particularly, the present invention provides an isolated nucleic acid molecule comprising a sequence of nucleotides which encodes or are complementary to a sequence which encodes a mammalian &agr;-L-iduronidase or fragment or derivative thereof and to the recombinant enzyme encoded thereby. These molecules are useful in the investigation, diagnosis and treatment of subjects suspected of or suffering from &agr;-L-iduronidase deficiency.

Synthetic &agr;-L-iduronidase and genetic sequences encoding same

The present invention relates generally to .alpha.-L-iduronidase and to genetic sequences encoding same. More particularly, the present invention provides an isolated nucleic acid molecule comprising a sequence of nucleotides which encodes or are complementary to a sequence which encodes a mammalian .alpha.-L-iduronidase or fragment or derivative thereof and to the recombinant enzyme encoded thereby. These molecules are useful in the investigation, diagnosis and treatment of subjects suspected of or suffering from .alpha.-L-iduronidase deficiency.

Synthetic .alpha.-L-iduronidase and genetic sequences encoding same

The present invention provides a highly glycosylated iduronate-2-sulfatase enzyme comprising an iduronate-2-sulfatase polypeptide with at least 5 kilodalton (kDa) more sugar than iduronate-2-sulfatase purified from a natural source, e.g. human liver. The present invention also provides an enzymatically active polypeptide fragment or variant of such a highly glycosylated iduronate-2-sulfatase. The present intention further provides an isolated nucleic acid encoding iduronate-2-sulfatase, as well as an expression vector, a host cell and a method for producing the present highly glycosylated iduronate-2-sulfatase enzyme. In one embodiment the present invention is directed to a method for producing a glycosylated iduronate-2-sulfatase enzyme which comprises culturing a host cell containing a nucleic acid encoding an enzymatically active iduronate-2-sulfatase polypeptide wherein the host cell glycosylates the polypeptide to a greater degree than a native iduronate-2-sulfatase polypeptide expressed by a natural human liver cell.

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West Lakes, Australia

Peter Roy Clements