Compositions and methods for transport across the blood brain barrier

• US 9,913,915 B2
• Filed: 11/14/2016
• Issued: 03/13/2018
• Est. Priority Date: 06/03/2011
• Status: Active Grant

• Current Assignee: Ophidion, Inc.
• Original Assignee: Ophidion, Inc.
• Inventors: Walz, Andreas
• Primary Examiner(s): Ahmed, Hasan S
• Assistant Examiner(s): Dabkowski, Erinne R
• Application Number:
  US15/351,024
• Publication Number:
  US 20170056515A1
• Time in Patent Office: 484 Days
• 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 heterologous transporter peptide consisting of SEQ ID NO:

4, 6, or 7.

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

3. The composition of claim 2, wherein the effector agent is selected from the group consisting of siRNA, shRNA, microRNA, double stranded RNA, strand template RNA, oligonucleotides, modified oligonucleotides, aptamers, 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.

4. The composition of claim 2, wherein the effector agent is siRNA.

5. A composition comprising a transporter peptide conjugate comprising:

an effector agent; and

a transporter peptide consisting of SEQ ID NO;

4, 6, or 7,

the effector agent being conjugated to the transporter peptide.

8. A method of transporting the composition of claim 5 to a target found across the blood brain barrier, comprising:

transporting the composition to the target, wherein the target is in vivo or in vitro.

9. A method of transporting the composition of claim 5 to a target found across the blood brain barrier, the method comprising:

transporting the transporter peptide conjugate to a receptor of the blood brain barrier.

10. The method of claim 9, wherein the transporting the transporter peptide conjugate to the target occurs in an in vitro cell culture.

11. The method of claim 9, wherein the transporting the transporter peptide conjugate to the target occurs in a mouse or human subject.

12. The method of claim 9, wherein the receptor of the blood brain barrier is on a cell or an extracellular molecule.

13. The method of claim 12, 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.

14. The method of claim 9, wherein the receptor of the blood brain barrier is a nicotinic receptor.

15. The method of claim 12, wherein the extracellular molecule comprises a protein.

16. The method 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, 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.

17. The method of claim 5, wherein the effector agent is siRNA.

18. The method of claim 5, wherein the composition is a pharmaceutical composition.

6. A composition comprising a heterologous transporter peptide comprising SEQ ID NO:

4.

7. The composition of claim 6, further comprising an effector agent conjugated to the heterologous transporter peptide.