Peptide for use in the reduction of side effects in the form of immunostimulatory reactions/effects

Patent metadata

Field	Value
Publication number	US-12472262-B2
Application number	US-202217650216-A
Country	US
Kind code	B2
Filing date	Feb 7, 2022
Priority date	Aug 14, 2014
Publication date	Nov 18, 2025
Grant date	Nov 18, 2025

Abstract

What is described is a peptide for use in the reduction of side-effects in form of immunostimulatory reactions/effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy. Furthermore, such a peptide is described for use in the reduction of side-effects in form of immunostimulatory reactions/effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy, wherein the immunostimulatory reactions/effects are induced by activation of IFIT1/2, IRF9, TLR3, TLR7, TLR8 or PKR.

First claim

What is claimed is:

1 . A coupled peptide, the coupled peptide comprising a peptide covalently coupled to a nucleic acid molecule, wherein
a cleavage sequence of the peptide consists of Ala-Ala-Asn, or Ala-Ala-Asn-Gly (SEQ ID NO:28), or Gly-Gly-Ala-Phe-Leu-Val-Leu-Pro (SEQ ID NO: 4), or Glu-Gly-Arg; the nucleic acid molecule is covalently coupled to the peptide by a linker, the linker consisting of an amino Cn linker, with n being an integer of 1-6; the nucleic acid is an siRNA, the siRNA comprising a nucleotide sequence selected from

(SEQ ID NO: 8)

(5-3) UCA UAU UCG ACU UUG GUU GCC,

(SEQ ID NO: 9)

(5-3) UCA AAC UCC AUC AUG AUC U,

(SEQ ID NO: 10)

(5-3) UCC AUC AUG AUC UUC UGG A,

(SEQ ID NO: 11)

(5-3) UUC AUA AAC ACA GUU CUC C,

(SEQ ID NO: 12)

(5-3) UCA AAU UGA GGC ACU GUG C,

(SEQ ID NO: 13)

(5-3) UUU CUU CAG AGC AGG AGC A,

(SEQ ID NO: 14)

(5-3) AUA CAC ACC CUU UGC CUC A,

(SEQ ID NO: 15)

(5-3) AUU UCA GGC UCA UAU UCC U,

(SEQ ID NO: 16)

(5-3) CAC AAU UCC CAC UUU GAG C,

(SEQ ID NO: 17)

(5-3) GUU ACC CAC AAU UCC CAC U,

(SEQ ID NO: 18)

(5-3) UUU CUU CUC UUU GUC UGG G,

(SEQ ID NO: 19)

(5-3) UAU UCU CCA AAC AAU GUG C;

and wherein the peptide may further comprise up to 100 additional amino acids, and the additional amino acids are placed at a N-terminal end of the cleavage sequence.

2 . The coupled peptide according to claim 1 , wherein the siRNA comprises the nucleotide sequence

(SEQ ID NO: 9)

(5-3) UCA AAC UCC AUC AUG AUC U;

or

(SEQ ID NO: 18)

(5-3) UUU CUU CUC UUU GUC UGG G.

3 . The coupled peptide according to claim 1 , wherein the coupled peptide is covalently or non-covalently linked to at least one molecule selected from the group of a cell-penetrating peptide, an enzyme substrate, a polyethyleneimine, a nanocontainer, a nanoparticle, a lipid, or a receptor-ligand complex for introduction into cells or for targeted introduction into specific cells.

4 . A gene therapy method, comprising administering to a subject in need thereof the coupled peptide according to claim 1 .

5 . The gene therapy method according to claim 4 , wherein the immunostimulatory reactions/effects are induced by activation of the IFIT1/2 (interferon-induced protein tetratricopeptide with repeats 1/interferon-induced protein tetratricopeptide with repeats 2), IRF9 (interferon regulatory factor 9), TLR3 (toll-like receptor 3), TLR7 (toll-like receptor 7), TLR8 (toll-like receptor 8) or PKR (protein kinase R).

6 . The coupled peptide of claim 1 , wherein the cleavage sequence consists of Ala-Ala-Asn.

7 . The coupled peptide of claim 1 , wherein the cleavage sequence consists of Ala-Ala-Asn-Gly (SEQ ID NO:28).

8 . The coupled peptide of claim 1 , wherein the cleavage sequence consists of Gly-Gly-Ala-Phe-Leu-Val-Leu-Pro (SEQ ID NO:4).

9 . The coupled peptide of claim 1 , wherein the cleavage sequence consists of Glu-Gly-Arg.

Assignees

• Univ Jena Friedrich Schiller

Inventors

• Poehlmann Tobias
• Guenther Rolf
• Reuter Michael
• Ludwig Mirko

Classifications

• A61K48/0033 Primary

  the non-active part being non-polymeric · CPC title

• A61K47/64 Primary

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title