Cell-penetrating peptides

Patent metadata

Field	Value
Publication number	US-12268749-B2
Application number	US-201917266939-A
Country	US
Kind code	B2
Filing date	Aug 9, 2019
Priority date	Aug 9, 2018
Publication date	Apr 8, 2025
Grant date	Apr 8, 2025

Abstract

The present invention relates to peptides, in particular cell-penetrating peptides, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

First claim

The invention claimed is:

1. A cell-penetrating peptide consisting of the amino acid sequence

(SEQ ID NO: 27)

RBRRBRRFQILYRBRBR,

(SEQ ID NO: 31)

RBRRBRRYQFLIRBRBR,

(SEQ ID NO: 32)

RBRRBRRILFQYRBRBR,

(SEQ ID NO: 35)

RBRRBRFQILYBRBR,

(SEQ ID NO: 37)

RBRRBRRFQILYRBHBH,

(SEQ ID NO: 38)

RBRRBRRFQILYHBHBR,

(SEQ ID NO: 44)

RBRRBRFQILYRBHBH,

(SEQ ID NO: 29)

RBRRBRFQILYRRBRBR,

(SEQ ID NO: 30)

RBRBRFQILYRBRRBRR,

(SEQ ID NO: 33)

RBRRBRFQILYRBRBR,

(SEQ ID NO: 36)

RBRRBFQILYRBRBR,

(SEQ ID NO: 39)

RBRRBRRFQILYHBRBH,

(SEQ ID NO: 40)

RBRRBRRYQFLIRBHBH,

(SEQ ID NO: 41)

RBRRBRRILFQYRBHBH,

(SEQ ID NO: 42)

RBRHBHRFQILYRBRBR,

(SEQ ID NO: 52)

RBRRBRRFQILYHBHBH,

(SEQ ID NO: 104)

RBRRBRWWWBRBR,or

(SEQ ID NO: 105)

RBRRBRWWPWWBRBR,

wherein B in the amino acid sequences is beta-alanine, and wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsullfonylated, or methylsulfonylated.

2. The cell-penetrating peptide of claim 1 , wherein the N-terminus of the cell-penetrating peptide is acetylated.

3. The cell-penetrating peptide of claim 1 , wherein cell-penetrating peptide consists of the amino acid sequence RBRRBRRFQILYRBRBR (SEQ ID NO: 27), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

4. The cell-penetrating peptide of claim 1 , wherein cell-penetrating peptide consists of the amino acid sequence RBRRBRRYQFLIRBRBR (SEQ ID NO: 31), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

5. The cell-penetrating peptide of claim 1 , wherein the cell-penetrating peptide consists of the amino acid sequence RBRRBRRILFQYRBRBR (SEQ ID NO: 32), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

6. The cell-penetrating peptide of claim 1 , wherein the cell-penetrating peptide consists of the amino acid sequence RBRRBRFQILYBRBR (SEQ ID NO:35), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

7. The cell-penetrating peptide of claim 6 , wherein the N-terminus of the cell-penetrating peptide is acetylated.

8. The cell-penetrating peptide of claim 1 , wherein the cell-penetrating peptide consists of the amino acid sequence RBRRBRRFQILYRBHBH (SEQ ID NO: 37), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

9. The cell-penetrating peptide of claim 1 , wherein the cell-penetrating peptide consists of the amino acid sequence RBRRBRRFQILYHBHBR (SEQ ID NO: 38), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

10. The cell-penetrating peptide of claim 1 , wherein of the cell-penetrating peptide consists of the amino acid sequence RBRRBRFQILYRBHBH (SEQ ID NO: 44), wherein the N-terminus of the cell-penetrating peptide is optionally acetylated, methylated, trifluoroacetylated, trifluoromethylsulfonylated, or methylsulfonylated.

11. The cell-penetrating peptide of claim 10 , wherein the N-terminus of the cell-penetrating peptide

Assignees

• Univ Oxford Innovation Ltd
• Res & Innovation Uk

Inventors

• Wood Matthew
• Manzano Raquel
• Godfrey Caroline
• Mcclorey Graham
• Raz Richard
• Gait Michael
• Arzumanov Andrey
• O'Donovan Liz
• Hazell Gareth
• Holland Ashling
• Varela Miguel

Classifications

• A61K38/00 Primary

  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

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C12N2310/3513

  Protein; Peptide · CPC title

• C12N2310/11

  Antisense · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title