Molecules for targeting compounds to various selected organs, tissues or tumor cells

• US 8,609,065 B2
• Filed: 01/08/2010
• Issued: 12/17/2013
• Est. Priority Date: 07/12/2007
• Status: Expired due to Fees

• Current Assignee: BioMarin Technologies B.V.
• Original Assignee: Prosensa Technologies B.V.
• Inventors: Kuik-Romeijn, Petra Van, Platenburg, Gerard Johannes
• Primary Examiner(s): ULM, JOHN D
• Application Number:
  US12/684,534
• Publication Number:
  US 20100184947A1
• Time in Patent Office: 1,439 Days
• Field of Search: None
• US Class Current: 424/1.69
• 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 THRPPMWSPVWP (SEQ ID NO.:

1), wherein said sequence is linked to a biologically active moiety; and

wherein said biologically active moiety is an oligonucleotide, and

wherein said oligonucleotide comprises a nucleotide modification selected from the group consisting of;

2′

-O-methoxyethyl, 2′

-O-methyl and phosphorothioate modified nucleotides.

2. The conjugate of claim 1, wherein the peptide or peptidomimetic comprises a linker which is not a peptide and which links said peptide or peptidomimetic comprising THRPPMWSPVWP (SEQ ID NO.:

1) to a biologically active moiety.

4. The conjugate according to claim 1 or 3 which further comprises a nuclear localisation signal.

5. A method of targeting a biologically active moiety across the blood brain barrier to brain cells, to neuronal cells or to tumor cells of neuronal or neuroectodermal origin of a subject using a conjugate according to claim 1 or 3 comprising the steps of:

administering the conjugate to the subject; and

determining the presence of the conjugate in brain cells, neuronal cells or tumor cells of neuronal or neuroectodermal origin.

6. A method of targeting a biologically active moiety to a muscle cell, using a conjugate according to claim 1 or 3 comprising the steps of:

administering the conjugate to the subject; and

determining the presence of the conjugate in the muscle cells.

7. A method of targeting a biologically active moiety to a muscle cell of a subject having a muscular dystrophy wherein the biologically active moiety modulates splicing of a pre-mRNA present in said cell,

wherein said method comprises administering to the subject a conjugate according to claim 1 or 3;

wherein said biologically active moiety modulates splicing of said targeted pre-mRNA; and

wherein

the conjugate that is administered to the subject is biologically active.

3. A conjugate of a peptide or peptidomimetic comprising a fusion protein of a peptide selected from the group consisting of:

SEQ ID NO.;

1, SEQ ID NO.;

3, SEQ ID NO.;

10 and SEQ ID NO.;

11, wherein said sequence is linked to a biologically active moiety; and

wherein said biologically active moiety is an oligonucleotide, and

wherein said oligonucleotide comprises a nucleotide modification selected from the group consisting of;

2′

-O-methoxyethyl, 2′

-O-methyl and phosphorothioate modified nucleotides.