Back to results
US 10,538,589 B2Granted
Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU
AssigneeArmagen, Inc.
InventorsWilliam M. Pardridge, Ruben J. Boado
Life of this patent
Estimating the term…
Abstract
Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibody provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in mucopolysaccharidosis IIIB (MPS-IIIB). The fusion antibodies provided herein comprise alpha-N-acetylgulcosaminidase (NAGLU). The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein.
Claims10
A fusion antibody comprising:
- (a) a fusion protein comprising the amino acid sequences of an immunoglobulin heavy chain (Ig-HC) of an anti-human insulin receptor antibody (HIR Ab), a linker and an alpha-N-acetylglucosaminidase (NAGLU);
- wherein the carboxyl terminus of the Ig-HC is linked to the amino terminus of the NAGLU through the linker;
- and wherein the amino acid sequence of the Ig-HC is the amino acid sequence of SEQ ID NO:
- 7;
- the amino acid sequence of the NAGLU is the amino acid sequence of SEQ ID NO:9;
- and the amino acid sequence of the linker comprises amino acids 462-484 of SEQ ID NO:10 or amino acids 462-492 of SEQ ID NO:18;
- and (b) an immunoglobulin light chain (Ig-LC) of the HIR Ab comprising the amino acid sequence of SEQ ID NO:8;
- wherein the fusion antibody crosses the blood brain barrier (BBB) and wherein the NAGLU retains at least 20% of its activity compared to its activity as a separate entity.
5 more elements
A fusion antibody comprising:
- (a) a fusion protein comprising the amino acid sequences of an Ig-HC of an anti-human insulin receptor antibody (HIR Ab) and an alpha-N-acetylglucosaminidase (NAGLU);
- wherein the fusion protein comprises the amino acid sequence of SEQ ID NO:
- 10, 18 or 20;
- and (b) an Ig-LC of the HIR Ab comprising the amino acid sequence of SEQ ID NO:8;
- wherein the fusion antibody crosses the blood brain barrier (BBB);
- and wherein the NAGLU retains at least 20% of its activity compared to its activity as a separate entity.
3 more elements
Dependencies are inferred from the claim text.