Substances for targeting various selected organs or tissues

Patent metadata

Field	Value
Publication number	US-11459358-B2
Application number	US-201716461313-A
Country	US
Kind code	B2
Filing date	Nov 15, 2017
Priority date	Nov 16, 2016
Publication date	Oct 4, 2022
Grant date	Oct 4, 2022

Abstract

The invention provides conjugates, comprising an organ or tissue targeting moiety linked to a biologically active moiety or linked to a diagnostic moiety. Such a biologically active or diagnostic moiety can be, for example, an oligonucleotide, small interfering RNA, a gene, a virus, a protein, a drug, a small organic molecule, a pharmaceutical, or a detectable agent.

First claim

The invention claimed is:

1. A conjugate comprising (i) a peptide or peptidomimetic comprising a targeting sequence of SEQ ID NO: 24 or 25, wherein the peptide or peptidomimetic is cyclic or at most 30 amino acids in length, and wherein the peptide or peptidomimetic is linked to (ii) a biologically active moiety selected from the group consisting of deoxyribonucleic acid (DNA) or analog thereof and ribonucleic acid (RNA) or analog thereof.

2. The conjugate according to claim 1 , wherein the biologically active moiety comprises 2′-O-alkyl, or bridged/bicyclic nucleic acids, or peptide nucleic acids, or phosphorothioate modified nucleotides, or chirally defined phosphorothioate modified nucleotides, or phopshorylguanidine modified oligonucleotides, or morpholino based nucleotides, or combinations thereof.

3. The conjugate according to claim 1 , wherein the conjugate further comprises a nuclear localisation signal or a cell penetrating peptide.

4. The conjugate according to claim 1 , wherein the peptide or peptidomimetic is cyclic.

5. The conjugate according to claim 4 , wherein the peptide or the peptidomimetic comprises flanking moieties, wherein said flanking moieties comprise amino acid residues or other moieties that flank the targeting sequence, and wherein said flanking moieties form a bond with each other.

6. The conjugate according to claim 5 , wherein the flanking moieties form a disulfide bridge.

7. The conjugate according to claim 6 , wherein the flanking moieties comprise cysteine residues.

8. The conjugate according to claim 5 , wherein the flanking moieties are separated from the targeting sequence by 4, 3, 2, 1, or 0 amino acid residues.

9. The conjugate according to claim 8 , wherein the flanking moieties are adjacent to the targeting sequence.

10. The conjugate according to claim 1 , wherein the targeting sequence is SEQ ID NO: 25.

11. The conjugate according to claim 1 , for targeting the biological active moiety to a muscle cell.

12. The conjugate according to claim 1 , for use as a medicament.

13. The conjugate for use according to claim 12 , wherein the medicament is for the treatment of a muscle associated disorder.

14. The conjugate for use according to claim 13 , wherein the muscle associated disorder is selected from the group consisting of autoimmune disease, metabolic disorders, obesity, and diabetes mellitus type II.

15. The conjugate for use according to claim 12 , wherein the medicament is for the treatment of a myopathy, muscular dystrophy, or muscle wasting disease.

16. The conjugate for use according to claim 12 , wherein the targeting sequence is SEQ ID NO: 25.

17. A conjugate comprising (i) a peptide or peptidomimetic comprising a targeting sequence of SEQ ID NO: 24 or 25, wherein the peptide or peptidomimetic is cyclic and at most 30 amino acids in length, and wherein the peptide or peptidomimetic is linked to (ii) a diagnostic moiety.

Assignees

• Biomarin Tech Bv
• Academisch Ziekenhuis Leiden

Inventors

• De Visser Peter Christian
• Aartsma-Rus Adriana Marie
• Jirka Silvana Maria Gerarda
• 'T Hoen Peter Abraham Christiaan
• AGUILERA DIEZ Maria Begoña

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K2121/00

  Preparations for use in therapy · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• C07K2319/10

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