Detection of oligosaccharides
AssigneeBiomarin Pharmaceutical Inc.
InventorsBrett E. CRAWFORD, Jillian R. BROWN, Charles A. GLASS
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Abstract
Provided herein are processes for detecting oligosaccharides in a biological sample. In specific instances, the biological sample is provided from an individual suffering from a disorder associated with abnormal glycosaminoglycan accumulation.
Claims46
1-30. (canceled)
A method of determining in an individual the presence, identity, and/or severity of an MPS III disorder, the method comprising:
- (a) generating a biomarker comprising one or more saturated non-reducing end oligosaccharides, wherein the biomarker is generated by treating a population of heparan sulfate oligosaccharides, in or isolated from a biological sample from the individual, with at least one digesting glycosaminoglycan lyase, wherein prior to lyase treatment, the biomarker is not present in abundance in samples from individuals with the MPS III disorder relative to individuals without the MPS III disorder;
- and
- (b) using an analytical instrument to detect the presence of and/or measure the amount of the biomarker produced and displaying or recording the presence of or the measure of the biomarker produced;
- wherein the presence of and/or measure of the amounts of the biomarker are utilized to determine the presence, identity, and/or severity of the MPS III disorder;
- and
- wherein the biomarker is of Formula II:
- [GlcN(Ac)m-(IdoA/GlcA)-GlcN(Ac)n](SO3R)p, wherein (IdoA/GlcA) is IdoA or GlcA;
- m and n are each independently 0 or 1;
- p is 0, 1, 2, 3, 4, or 5;
- and R is hydrogen or a negative charge.
A method for determining response to a therapy in an individual having an MPS III disorder, the method comprising:
- (a) generating a biomarker comprising one or more saturated non-reducing end oligosaccharides, wherein the biomarker is generated by treating a population of heparan sulfate oligosaccharides, in or isolated from a biological sample from the individual, with at least one digesting glycosaminoglycan lyase, wherein prior to lyase treatment, the biomarker is not present in abundance in samples from individuals with the MPS III disorder relative to individuals without the MPS III disorder;
- and
- (b) using an analytical instrument to detect the presence of and/or measure the amount of the biomarker produced and displaying or recording the presence of or the measure of the biomarker produced;
- wherein the presence of and/or measure of the amounts of the biomarker are utilized to monitor the treatment of the MPS III disorder;
- and
- wherein the biomarker is of Formula II:
- [GlcN(Ac)m-(IdoA/GlcA)-GlcN(Ac)n](SO3R)p, wherein (IdoA/GlcA) is IdoA or GlcA;
- m and n are each independently 0 or 1;
- p is 0, 1, 2, 3, 4, or 5;
- and R is hydrogen or a negative charge.
The method of claim 47, wherein the detectable label is a mass label, a radio label, a fluorescent label, a chromophore label, or affinity label.
An oligosaccharide of Formula II:
- [GlcN(Ac)m-(IdoA/GlcA)-GlcN(Ac)n](SO3R)p, wherein (IdoA/GlcA) is IdoA or GlcA;
- m and n are each independently 0 or 1;
- p is 0, 1, 2, 3, 4, or 5;
- and R is hydrogen or a negative charge.
Dependencies are inferred from the claim text.