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AssigneeDenali Therapeutics Inc.
InventorsAnnie ARGUELLO, Akhil BHALLA, Jeffrey Mark HARRIS, Matthew D. TROYER
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Certain embodiments provide a method of providing added peripheral IDS activity to a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein comprising an IDS amino acid sequence and a TfR binding domain. The added peripheral IDS activity can be measured by comparing levels of keratan sulfate (KS) in the subject after administration of the pharmaceutical composition relative to a baseline level. Certain embodiments also provide methods of providing a clinical benefit to a subject with Hunter syndrome and improving treatment in a patient having non-neuronopathic Hunter syndrome, as well as methods and treatment regimens for resolving infusion related reactions (IRRs).
A method of providing added peripheral iduronate 2-sulfatase (IDS) activity relative to a standard-of-care treatment to a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein, wherein the administration of the pharmaceutical composition reduces serum levels of keratan sulfate (KS) in the subject relative to a baseline level measured in the subject prior to the administration, and wherein the protein comprises an IDS amino acid sequence and a transferrin receptor (TfR) binding domain.
A method of providing added peripheral iduronate 2-sulfatase (IDS) activity relative to a standard-of-care treatment to a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein, wherein the administration of the pharmaceutical composition reduces serum levels of keratan sulfate (KS) in the subject to a baseline level measured in a healthy subject or in a subject that does not have Hunter syndrome, and wherein the protein comprises an IDS amino acid sequence and a transferrin receptor (TfR) binding domain.
A method of reducing and/or normalizing serum keratan sulfate (KS) levels in a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein, wherein the protein comprises an iduronate 2-sulfatase (IDS) amino acid sequence and a transferrin receptor (TfR) binding domain.
A method for evaluating peripheral iduronate 2-sulfatase (IDS) activity in a subject having Hunter syndrome, comprising:
A method of providing added peripheral iduronate 2-sulfatase (IDS) activity relative to a standard-of-care treatment to a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein, wherein the administration of the pharmaceutical composition normalizes levels of urine heparan sulfate (HS) and/or dermatan sulfate (DS) in the subject by at least 12 weekly doses, and wherein normalization is sustained after at least 23 weekly doses, and wherein the protein comprises an IDS amino acid sequence and a transferrin receptor (TfR) binding domain.
A method of providing added peripheral iduronate 2-sulfatase (IDS) activity relative to a standard-of-care treatment to a subject with Hunter syndrome, comprising administering to the subject at least 23 weekly therapeutically effective doses of a pharmaceutical composition comprising a protein, wherein the administration of the pharmaceutical composition normalizes levels of urine heparan sulfate (HS) and/or dermatan sulfate (DS) in the subject by at least 12 weekly doses, and wherein normalization is sustained after at least 23 weekly doses, and wherein the protein comprises an IDS amino acid sequence linked to an Fc polypeptide;
A method of normalizing urine heparan sulfate (HS) and/or dermatan sulfate (DS) levels in a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein, wherein the HS and/or DS levels in the subject are normalized by at least 12 weekly doses, wherein normalization is sustained after at least 23 weekly doses, and wherein the protein comprises an IDS amino acid sequence and a transferrin receptor (TfR) binding domain.
A method of normalizing urine heparan sulfate (HS) and/or dermatan sulfate (DS) levels in a subject with Hunter syndrome, comprising administering to the subject at least 23 weekly therapeutically effective doses of a pharmaceutical composition comprising a protein, wherein the HS and/or DS levels in the subject are normalized by at least 12 weekly doses, wherein normalization is sustained after at least 23 weekly doses, and wherein the protein comprises an IDS amino acid sequence and a transferrin receptor (TfR) binding domain.
A method of providing a clinical benefit to a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein, wherein the administration of the pharmaceutical composition produces an improvement in a clinical outcome as measured by one or more clinical Global Impression of Change instruments relative to baseline levels measured in the subject prior to the administration, and wherein the protein comprises:
A method of improving treatment in a patient having non-neuronopathic Hunter syndrome, comprising switching the patient from idursulfase enzyme replacement therapy to treatment with a pharmaceutical composition comprising a protein, wherein the protein comprises:
A method of resolving an infusion-related reaction (IRR) in a subject receiving treatment for Hunter syndrome, wherein the subject is being intravenously administered or was intravenously administered an initial dose of a pharmaceutical composition comprising a protein, the method comprising reducing the amount and/or the infusion rate of administration of a subsequent dose of the pharmaceutical composition, wherein the protein comprises:
A method of resolving an IRR in a subject receiving treatment for Hunter syndrome, comprising modifying the subject's treatment regimen, wherein the treatment regimen comprises intravenous administration of an initial dose of a pharmaceutical composition comprising a protein, and the modified regimen comprises administering a subsequent dose of the pharmaceutical composition to the subject, wherein the subsequent dose is a reduced dose and/or is administered at a reduced rate of infusion, and wherein the protein comprises:
Dependencies are inferred from the claim text.