MOLECULES FOR TARGETING COMPOUNDS TO VARIOUS SELECTED ORGANS, TISSUES OR TUMOR CELLS

• US 20100184947A1
• Filed: 01/08/2010
• 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: Kuik-Romeijn, Petra Van, Platenburg, Gerard Johannes
• Granted Patent: US 8,609,065 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: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents

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 neuronal or neuromuscular disease, or a pathology of the brain, or a tumor of neuronal or neuroectodermal origin, 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 brain cells or neuronal cells, or by the tumor cells of neuronal or neuroectodermal origin. The invention also provides a method of identifying and measuring neurite growth in neuronal cells.

Claims

1. A conjugate of a peptide or peptidomimetic comprising a sequence or consisting of a sequence selected form the group consisting of LPWKPLG (SEQ ID NO:

2) and THRPPMWSPVWP (SEQ ID NO;

     1) linked to a moiety selected from a biologically active moiety and diagnostic moiety.

2. The conjugate according to claim 1, wherein the biologically active moiety is selected form 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.

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

2 or SEQ ID NO;

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

4. The conjugate according to claim 3 which further comprises a nuclear localisation signal.

5. Use of a conjugate according to claim 1—

for the preparation of a medicament for targeting a biological active moiety or a diagnostic moiety across the blood brain barrier to brain cells, to neuronal cells or to tumor cells of neuronal or neuroectodermal origin.

6. The use according to claim 5 wherein the medicament is for the treatment of a brain disorder.

7. The use according to claim 5 wherein the medicament is for the treatment of a neuronal or neuromuscular disease.

8. The use according to claim 5 wherein the medicament is for the treatment of a tumor of neuronal or neuroectodermal origin.

9. A molecule comprising a peptide or peptidomimetic comprising a sequence or consisting of a sequence selected from the group consisting of LPWKPLG and THRPPMWSPVWP and a linking part which is not a peptide for linking the molecule to a biologically active moiety or a diagnostic moiety.

10. Use of a conjugate comprising a peptide or peptidomimetic comprising or consisting of the sequence THRPPMWSPVWP for the preparation of a composition for monitoring neurite growth in neuronal cells.