Molecules for targeting compounds to various selected organs or tissues

• US 8,268,962 B2
• Filed: 01/11/2010
• Issued: 09/18/2012
• Est. Priority Date: 07/12/2007
• Status: Active Grant

• Current Assignee: BioMarin Technologies B.V.
• Original Assignee: Prosensa Technologies B.V.
• Inventors: Van Deutekom, Judith Christina Theodora, Van Kuik-Romeijn, Petra, Platenburg, Gerard Johannes, Heemskerk, Johannes Antonius
• Primary Examiner(s): ULM, JOHN D
• Application Number:
  US12/685,369
• Publication Number:
  US 20100184948A1
• Time in Patent Office: 981 Days
• Field of Search: None
• US Class Current: 530/329
• 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 the sequence or consisting of the sequence LGAQSNF (SEQ ID NO:

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

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

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

100 and a therapeutically active protein and/or a diagnostic protein.

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

5. A pharmaceutical composition comprising a conjugate according to claim 1, in combination with a pharmaceutically acceptable carrier.

6. The pharmaceutical composition according to claim 5 wherein the pharmaceutical composition is for the treatment of a muscle-cell associated disorder including cardiac disorders.

7. The pharmaceutical composition according to claim 6 wherein the pharmaceutical composition is for the treatment of a myopathy, muscular dystrophy or muscle wasting disease.

8. The pharmaceutical composition according to claim 5 wherein the pharmaceutical composition is for the treatment of diabetes mellitus type II or obesity.

10. The conjugate according to claim 2, wherein the biologically active molecule is a DNA or RNA analogue selected from the group consisting of 2′

-O-alkyl, 2′

-O -mehoxyethyl- , 2′

-O-methyl, 2′

-O-alkenyl (allyl), 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.

9. A molecule comprising a peptide or peptidomimetic comprising the sequence or consisting of the sequence LGAQSNF (SEQ ID NO:

100) and a linking portion which is not a peptide for linking the molecule to a biologically active moiety or a diagnostic moiety.