Cell penetrating peptides

Patent metadata

Field	Value
Publication number	US-12583889-B2
Application number	US-202117238994-A
Country	US
Kind code	B2
Filing date	Apr 23, 2021
Priority date	Feb 17, 2017
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

The present invention relates to peptides, in particular cell penetrating peptides, of 40 amino acid residues or less comprising at least one directly glycosylated amino residue and one or more arginine rich arm domains, and to conjugates of such cell penetrating peptides with a therapeutic molecule. The present invention further relates to the use of the peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders of the central nervous system.

First claim

The invention claimed is:

1 . A peptide comprising a sequence selected from the following sequences:

 (SEQ ID NO. 8)

RXRRBRRXRQFLRXRBRXRS*,

 (SEQ ID NO. 11)

S*RXRRBRRXRQFLRXRBRXR,

 (SEQ ID NO. 14)

RXRRBRRXRS*FLRXRBRXR,

 (SEQ ID NO. 47)

RXRRBRRXRS*FLRXRBRXRS*FL,

 (SEQ ID NO. 50)

RXRRBRRXRS*FQRXRBRXR,

(SEQ ID NO. 52)

RXRRBRRXRS*WFRXRBRXR,

and

 (SEQ ID NO. 53)

RXRRBRRXRS*QFRXRBRXR,

wherein X is aminohexanoic acid, B is beta-alanine, and wherein S* represents L-serine glycosylated with D-Glucose sugar.

2 . A conjugate comprising the peptide according to claim 1 covalently linked to a therapeutic molecule.

3 . The conjugate of claim 2 , wherein the therapeutic molecule is selected from: a nucleic acid, peptide nucleic acid, antisense oligonucleotide, short interfering RNA, micro RNA, peptide, cyclic peptide, protein, pharmaceutical and drug.

4 . A peptide selected from the following sequences: RXRRBRRXRS*FLRXRBRXR (SEQ ID NO.14), RXRRBRRFS*RBRXR (SEQ ID NO.17), RXRRBRRZS*RBRXR (SEQ ID NO.73), RXRRBRRFS11*RBRXR (SEQ ID NO.74), RBRBRS*RBRBR (SEQ ID NO.70) and RXRXRS*RXRXR (SEQ ID NO.71), wherein X is aminohexanoic acid, B is beta-alanine, Z is 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, S* represents L-serine glycosylated with D-Glucose sugar, and S 1 * represents D-serine glycosylated with D-Glucose sugar.

5 . A conjugate comprising the peptide according to claim 4 covalently linked to a therapeutic molecule.

6 . The conjugate of claim 5 , wherein the therapeutic molecule is selected from: a nucleic acid, peptide nucleic acid, antisense oligonucleotide, short interfering RNA, micro RNA, peptide, cyclic peptide, protein, pharmaceutical and drug.

7 . A peptide comprising a sequence selected from the following sequences:

 (SEQ ID NO. 12)

RXRRBRRXRS*QFLS*RXRBRXR,

 (SEQ ID NO. 13)

RXRRBRRXRS*QFLRXRBRXR,

 (SEQ ID NO. 43)

RXRRBRRXRS*FRXRBRXR,

and

 (SEQ ID NO. 44)

RXRRBRRXRS*RXRBRXR,

wherein X is aminohexanoic acid, B is beta-alanine and S* represents L-serine glycosylated with D-Glucose sugar.

8 . A conjugate comprising the peptide according to claim 7 covalently linked to a therapeutic molecule.

9 . The conjugate of claim 8 , wherein the therapeutic molecule is selected from: a nucleic acid, peptide nucleic acid, antisense oligonucleotide, short interfering RNA, micro RNA, peptide, cyclic peptide, protein, pharmaceutical and drug.

10 . A peptide comprising a sequence selected from the following sequences:

(SEQ ID NO. 51)

RXRRBRRFS 1 *RXRBR,

(SEQ ID NO. 111)

RXRRBRRFS 2 *RXRBR,

(SEQ ID NO. 112)

RXRRBRRFS 3 *RXRBR,

(SEQ ID NO. 116)

RXRRBRRZS*RXRBR,

(SEQ ID NO. 157)

RXRRBRRFS 4 *RXRBR,

(SEQ ID NO. 158)

RXRRBRRFS 6 *RXRBR,

(SEQ ID NO. 160)

RXRRBRRFS 5 *RXRBR,

(SEQ ID NO. 168)

RXRRBRRS 1 *RXRBR,

(SEQ ID NO. 169)

RXRRBRRS 2 *RXRBR,

(SEQ ID NO. 170)

RXRRBRRS 3 *RXRBR,

(SEQ ID NO. 171)

RXRRBRRS 4 *RXRBR,

Assignees

• Univ Oxford Innovation Ltd
• Res & Innovation Uk

Inventors

• Wood Matthew
• Hammond Suzan
• Bowerman Melissa
• Gait Michael
• Adendroth Frank
• Mcclorey Graham

Classifications

• C07K2319/91

  containing a motif for glycosylation · CPC title

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title

• C07K9/00

  Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof · CPC title

• A61K47/645 Primary

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title

• C07K14/163 Primary

  Regulatory proteins, e.g. tat, nef, rev, vif, vpu, vpr, vpt, vpx · CPC title