MOLECULES FOR TARGETING COMPOUNDS TO VARIOUS SELECTED ORGANS OR TISSUES

• US 20100184948A1
• Filed: 01/11/2010
• Published: 07/22/2010
• Est. Priority Date: 07/12/2007
• Status: Active Grant

• Current Assignee: BioMarin Technologies B.V.
• Original Assignee: Prosensa Technologies B.V.
• Inventors: HEEMSKERK, JOHANNES ANTONIUS, PLATENBURG, GERARD JOHANNES, VAN DEUTEKOM, JUDITH CHRISTINA THEODORA, VAN KUIK-ROMEIJN, PETRA
• Granted Patent: US 8,268,962 B2
• Time in Patent Office: Days
• US Class Current: 530/322
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: A61K 49/0047 Green fluorescent protein [GFP]
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The invention provides conjugates, comprising an organ, tissue or tumor cell homing molecule linked to a moiety. Such a moiety can be, for example, an oligonucleotide, small interfering RNA, gene, virus, protein, pharmaceutical or detectable agent. In addition the invention provides methods to diagnose or treat a pathology of the muscle or heart, by administrating to a subject having or suspected of having a pathology a molecule or conjugate that homes to, binds to and is taken up by the muscle cells or heart cells.

Claims

1. A conjugate of a peptide or peptidomimetic comprising a sequence or consisting of a sequence selected from the group consisting of

2. The conjugate according to claim 1, wherein the peptide or peptidomimetic according to the invention is selected from the group consisting of YQDSAKT, VTYKTAS, EPLQLKM, WSLQASH, TLWVPSR, QGMHRGT, LYQDYSL, SESMSIK, LPWKPLG, QSPHTAP, TPAHPNY, SLLGSTP, TALPPSY, VNSATHS, LPLTPLP, NQLPLHA, GNTPSRA, TQTPLKQ, AMISAIH, NLTRLHT, HVIANAG, HAIYPRH and LGAQSNF.

3. The conjugate according to claim 1, wherein the peptide or peptidomimetic according to the invention is selected from the group consisting of SPNSIGT, STFTHPR, QLFTSAS, STIHGST, SAPRPLY, AAQTSTP, YQDSAKT, EPLQLKM, TLWVPSR, LYQDYSL, LPWKPLG, TPAHPNY, TALPPSY, LPLTPLP, HAIYPRH and GNTPSRA.

4. The conjugate according to claim 1, wherein the peptide or peptidomimetic according to the invention is selected from the group consisting of YQDSAKT, EPLQLKM, TLWVPSR, LYQDYSL, LPWKPLG, TPAHPNY, TALPPSY, LPLTPLP, HAIYPRH and GNTPSRA.

5. The conjugate according to claim 1, wherein the peptide or peptidomimetic according to the invention is selected from the group consisting of YQDSAKT and GNTPSRA.

6. The conjugate according to claim 1, wherein the peptide or peptidomimetic according to the invention is selected from the group consisting of LGAQSNF (SEQ ID NO:

85), QLFTSAS (SEQ ID NO;

     3) and LYQDYSL (SEQ ID NO;

     85).

7. The conjugate according to claim 1, wherein the biologically active moiety is selected from the group consisting of DNA, RNA or analogues thereof, such as compounds comprising 2′

-O-alkyl, in particular 2′

-O-mehoxyethyl- and 2′

-O-methyl, or 2′

-O-alkenyl (allyl) or 2′

-O-alkynyl nucleotides, locked nucleic acids (LNAs), peptide nucleic acids (PNAs), ethylene bridged nucleic acids (ENAs), phosphorothioate modified nucleotides, morpholino based nucleotides and combinations thereof

8. The conjugate according to claim 1 which is a fusion protein of a peptide of SEQ ID NO:

1-100 with a therapeutically active protein and/or a diagnostic protein.

9. The conjugate according to claim 8 which further comprises a nuclear localisation signal.

10. Use of a conjugate according claim 1 for the preparation of a medicament for targeting a biological active moiety or a diagnostic moiety to a muscle cell.

11. The use according to claim 10 wherein the medicament is for the treatment of a muscle-cell associated disorder including cardiac disorders.

12. The use according to claim 11 wherein the medicament is for the treatment of a myopathy, muscular dystrophy or muscle wasting disease

13. The use according to claim 10 wherein the medicament is for the treatment of diabetes mellitus type II or obesity.

14. A molecule comprising a peptide or peptidomimetic comprising a sequence or consisting of a sequence selected from the group consisting of