Treatment of lysosomal disorders (il-1 antagonists)

Patent metadata

Field	Value
Publication number	US-2017190772-A1
Application number	US-201515325368-A
Country	US
Kind code	A1
Filing date	Jul 8, 2015
Priority date	Jul 11, 2014
Publication date	Jul 6, 2017
Grant date	—

Abstract

The invention relates to methods for treating a Lysosomal storage disease (LSD) in a patient. Kits for use in such methods are also provided.

First claim

1 . A method for preventing or treating a lysosomal storage disorder (LSD) in a patient, wherein the method comprises administering to the patient an Interleukin 1β (IL-1β) antagonist and thereby treating the LSD.

2 . The method according to claim 1 , wherein the IL-1β antagonist comprises a small molecule, a polypeptide, a peptide or peptidomimetic, a polynucleotide, an oligonucleotide, an antisense RNA, small interfering RNA (siRNA) or small hairpin RNA (shRNA), an aptamer, or an antibody or antibody fragment.

3 . The method according to claim 1 , wherein the IL-1β antagonist reduces the activity of IL-1β and/or Interleukin 1β Receptor (IL-1βR) and/or Interleukin 1β Receptor Accessory Protein (IL-1βRA), or any allelic variant thereof.

4 . The method according to claim 1 , wherein the IL-1β antagonist comprises an antibody or antibody fragment which specifically binds to IL-1β, IL-1βR, IL-1βRAP or any allelic variant thereof.

5 . The method according to claim 4 , wherein IL-1β comprises the sequence as shown in SEQ ID NO: 3, wherein IL-1βR comprises the sequence as shown in SEQ ID NOs: 6 or 9 or wherein IL-1βRA comprises the sequence as shown in SEQ ID NOs: 14 or 17.

6 . The method according to claim 4 , wherein the antibody is a monoclonal antibody.

7 . The method according to claim 6 , wherein the monoclonal antibody is Canakinumab.

8 . The method according to claim 1 , wherein the IL-1β antagonist comprises a fragment of IL-1β, IL-1βR, IL-1βR type II, IL-1βRA and/or IL-1βRAP.

9 . The method according to claim 8 , wherein the IL-1β antagonist is Anakinra.

10 . The method according to claim 8 , wherein the IL-1β antagonist is Rilonacept.

11 . The method according to claim 1 , wherein the IL-1β antagonist decreases the expression of IL-1β and/or IL-1βR and/or IL-1βRA.

12 . The method according to claim 11 , wherein the IL-1β antagonist comprises:
(a) an oligonucleotide or polynucleotide which specifically hybridises to a part of SEQ ID NO: 2, SEQ ID NOs: 5 or 8, or SEQ ID NOs: 13 or 16 or any allelic variant thereof or (b) an oligonucleotide which comprises about 50 or fewer consecutive nucleotides from SEQ ID NO: 1, SEQ ID NOs: 4 or 7 or SEQ ID NOs: 12 or 15, or a variant thereof which has at least about 90% identity to SEQ ID NO: 1 or SEQ ID NOs: 4, 7, 12 or 15 over its entire sequence.

13 . The method according to claim 1 , wherein the LSD is any of Niemann-Pick type C (NPC1), NPC2, Smith-Lemli-Opitz Syndrome (SLOS), an inborn error of cholesterol synthesis, Tangier disease, Pelizaeus-Merzbacher disease, the Neuronal Ceroid Lipofuscinoses, primary glycosphingolipidoses (i.e. Gaucher, Fabry, GM1, GM2 gangliosidoses, Krabbe and MLD), Farber disease and Multiple Sulphatase Deficiency.

14 . The method according to claim 1 , wherein the method further comprises administering another therapy or agent intended to prevent or treat the LSD.

15 . (canceled)

16 . An agent for the prevention or treatment of a LSD, comprising an IL-1β antagonist as an active ingredient.

17 . A kit for preventing or treating a LSD, comprising a means for diagnosing or prognosing a LSD and an IL-1β antagonist.

18 . A kit according to claim 16 , wherein the means is LysoTracker®.

Assignees

• Univ Oxford Innovation Ltd

Inventors

• Platt Frances
• Platt Nick
• Luqmani Raashid

Classifications

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• G01N33/6869

  Interleukin · CPC title

• A61K38/2006 Primary

  IL-1 · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• C12N2310/11

  Antisense · CPC title