Mecp2 based therapy

Patent metadata

Field	Value
Publication number	US-2025387519-A1
Application number	US-202519051709-A
Country	US
Kind code	A1
Filing date	Feb 12, 2025
Priority date	Mar 24, 2017
Publication date	Dec 25, 2025
Grant date	—

Abstract

MeCP2 based therapy. The present invention relates to synthetic polypeptides that are useful in the treatment of disorders associated with reduced MeCP2 activity, including Rett syndrome. The present invention provides synthetic polypeptides comprising: i) an MBD amino acid sequence showing at least 70% similarity with the amino acid sequence as depicted in SEQ ID NO: 1; and ii) an NID amino acid sequence showing at least 70% similarity with the amino acid sequence as depicted in SEQ ID NO: 2, wherein the polypeptide has a deletion of at least 50 amino acids, when compared to the full length MeCP2 e1 and e2 sequences. The invention further provides nucleic acid constructs, expression vectors, virions, pharmaceutical compositions, and cells providing polynucleotides of the invention. The invention further provides methods of treating or preventing disease in an animal comprising administering to said animal a synthetic polypeptide according to the invention.

First claim

1 .- 28 . (canceled)

29 . A pharmaceutical composition comprising:
an expression vector comprising a MECP2 expression cassette comprising a MecP2 gene, wherein the MecP2 gene comprises a deletion of at least 50 amino acids compared to the full length human MeCP2 e1 and e2 sequences (SEQ ID NOs 3 and 4) and a pharmaceutically acceptable carrier.

30 . The pharmaceutical composition of claim 1 , wherein the expression cassette further comprises two ITR sequences.

31 . The pharmaceutical composition of claim 2 , wherein the two ITR sequences are AAV2 ITR sequences.

32 . The pharmaceutical composition of claim 1 , wherein the vector is an AAV9 vector.

33 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier is a diluent, solubilizing or emulsifying agent, or a salt.

34 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier is a buffered saline solution.

35 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier is phosphate buffered saline solution.

36 . The pharmaceutical composition of claim 1 , wherein the formulation has pH of 7.0-8.0.

37 . A method of treating a neurological disorder associated with inactivating mutation of MeCP2 in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an expression vector comprising a MECP2 expression cassette comprising a MecP2 gene, wherein the MecP2 gene comprises a deletion of at least 50 amino acids compared to the full length human MeCP2 e1 and e2 sequences (SEQ ID NOs 3 and 4) and a pharmaceutically acceptable carrier.

38 . The method of claim 37 , wherein the pharmaceutical composition is administered to the central nervous system (“CNS”).

39 . The method of claim 37 , wherein the neurological disorder is Rett Syndrome.

Assignees

• Univ Court Univ Of Edinburgh
• Univ Glasgow Court

Inventors

• Bird Adrian
• Tillotson Rebekah
• Cobb Stuart Robert
• Hector Ralph David

Classifications

• C07K14/001

  by chemical synthesis · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C12N15/86

  Viral vectors · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title