COMPOSITIONS AND METHODS FOR TRANSPORT ACROSS THE BLOOD BRAIN BARRIER

• US 20140162961A1
• Filed: 12/09/2013
• Published: 06/12/2014
• Est. Priority Date: 06/03/2011
• Status: Active Grant

• Current Assignee: Ophidion, Inc.
• Original Assignee: Ophidion, Inc.
• Inventors: Walz, Andreas
• Granted Patent: US 9,522,193 B2
• Time in Patent Office: Days
• US Class Current: 514/20.9
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/56 the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 14/00 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific

Abstract

Compositions and methods are provided including a transporter peptide derived from the loop2 domain of the neuronally-derived lynx1 protein which can be conjugated to an effector agent to form a transporter-effector complex for transport of the therapeutic effector agent to a target that is found across the blood brain barrier.

Claims

1. A composition, comprising a peptide comprising a sequence of SEQ ID NO:

1.

2. The composition of claim 1, wherein the SEQ ID NO:

1 sequence is selected from SEQ ID NOs;

2, 3, 4, and 5.

3. The composition of claim 1, wherein the SEQ ID NO:

1 sequence is SEQ ID NO;

2 further comprising a peptide of SEQ ID NO;

8 inserted between residues X₃ and X₄.

4. The composition of claim 1, wherein the SEQ ID NO:

1 sequence further comprises a peptide having a sequence of SEQ ID NO;

8 inserted between residues X₃ and X₄.

5. The composition of claim 1, further comprising an effector agent.

6. The composition of claim 5, wherein the effector agent is selected from the group consisting of siRNA, shRNA, microRNA, double stranded RNA, strand template RNA, oligonucleotides, modified oligonucleotides, aptamers, analogs and combinations of oligonucleotides, genes, peptides, proteins, small chemical molecules, large chemical molecules, viral particles, liposomes, endosomes, exosomes, nanoparticles, dendrimers, positron emission tomography (PET) ligands, eukaryotic cells, prokaryotic cells, microspheres, nanogels, and bionanocapsules.

7. The composition of claim 5, wherein the effector agent is siRNA.

8. The composition of claim 5, wherein the effector agent is siRNA conjugated to the peptide.

9. A composition comprising:

a peptide comprising a sequence of SEQ ID NO;

13.

10. The composition of claim 9, wherein the SEQ ID NO:

13 sequence is selected from SEQ ID NO;

14 or SEQ ID NO;

15.

11. The composition of claim 9, further comprising an effector agent.

12. A method of transporting a peptide composition to a target found within the blood brain barrier, comprising:

providing the peptide composition comprising the sequence of SEQ ID NO;

1 to the target, wherein the target may be in vivo or in vitro.

13. A method of transporting an effector agent to a target found within the blood brain barrier, comprising:

conjugating a peptide comprising the sequence of SEQ ID NO;

1 to an effector agent to form a complex; and

providing the complex to the target, wherein the target may be in vivo or in vitro.

14. The method of claim 13, wherein the SEQ ID NO:

1 sequence is selected from SEQ ID NOs;

2, 3, 4, 5, or 10.

15. The method of claim 13, wherein providing the complex to the target occurs in an in vitro cell culture.

16. The method of claim 13, wherein providing the complex to the target occurs in a mouse or human subject.

17. The method of claim 13, wherein the target is a cell or an extracellular molecule.

18. The method of claim 17, wherein the cell is selected from the group consisting of neurons, neuronal cells, brain cells, glial cells, astrocytes, neuronal supporting cells, and cells of the central nervous system.

19. The method of claim 17, wherein the target is a cell comprising a nicotinic receptor.

20. The method of claim 17, wherein the extracellular molecule comprises a protein.

21. The method of claim 13, wherein the effector agent is selected from the group consisting of siRNA, shRNA, microRNA, double stranded RNA, strand template RNA, oligonucleotides, modified oligonucleotides, aptamers, analogs and combinations of oligonucleotides, genes, peptides, proteins, small chemical molecules, large chemical molecules, viral particles, liposomes, endosomes, exosomes, nanoparticles, dendrimers, positron emission tomography (PET) ligands, eukaryotic cells, prokaryotic cells, microspheres, nanogels, and bionanocapsules.

22. The method of claim 13, wherein the effector agent is siRNA.

23. The method of claim 13, wherein the composition is a pharmaceutical composition.

24. A method of transporting a peptide composition to a target found within the blood brain barrier, comprising:

providing the peptide composition comprising the sequence of SEQ ID NO;

13 to the target, wherein the target may be in vivo or in vitro.

25. A method of transporting an effector agent to a target found within the blood brain barrier, comprising:

conjugating a peptide comprising a sequence of SEQ ID NO;

13 to an effector agent to form a complex; and

providing the complex to the target, wherein the target may be in vivo or in vitro.

26. The method of claim 25, wherein the peptide of SEQ ID NO:

13 has a sequence of SEQ ID NO;

14 or SEQ ID NO;

15.