# US 10,287,318 B2 · Viral vector for the targeted transfer of genes in the brain and spinal cord > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,287,318 B2 - Document ID: US10287318B2 - Status: Granted - Kind: B2 - Application number: 15/303,950 - Filed: 2015-04-15 - Published: 2017-02-02 - Granted: 2019-05-14 - Earliest claimed: 2014-04-17 - Assignees: Boehringer Ingelheim International GmbH - Applicants: Boehringer Ingelheim International GmbH - Inventors: Jakob Körbelin; Stefan Michelfelder; Martin Trepel - Web page: https://patentgrep.com/patent/US10287318B2 ## CPC - C07K 7/06: having 5 to 11 amino acids - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia - A61P 25/16: Anti-Parkinson drugs - 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 - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 14/005: from viruses - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - C12N 15/86: Viral vectors - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - C12N 2710/14144: Chimeric viral vector comprising heterologous viral elements for production of another viral vector - C12N 2750/14122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2750/14133: Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory - C12N 2750/14143: viral genome or elements thereof as genetic vector - C12N 2810/6027: ssDNA viruses - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The invention relates to novel peptides, polypeptides or proteins which bind specifically to brain cells and/or to the spinal cord. The peptides, polypeptides, or proteins can be components of a viral capsid and can be used to lead a recombinant viral vector selectively to the brain and/or spinal cord after systemic administration to a subject and to ensure tissue-specific expression of one or more transgenes there. The invention also relates to a recombinant viral vector, preferably an AAV vector, which comprises a capsid containing at least one of the claimed peptides, polypeptides, or proteins and which comprises at least one transgene packaged in the capsid. Said viral vector can be used, in particular for the therapeutic treatment of a disease or disorder of the brain and/or spinal cord. The invention further relates to cells and pharmaceutical compositions that comprise the viral vector according to the invention. ## Claims ### Claim 1 A capsid protein of a viral vector characterized in that it comprises the amino acid sequence of SEQ ID NO:1. ### Claim 2 (depends on 1) The capsid protein according to claim 1, which is a capsid protein of an adeno-associated virus (AAV). ### Claim 3 (depends on 2) The capsid protein according to claim 2, which is a capsid protein of an AAV of a serotype selected from the group consisting of serotypes 2, 4, 6, 8, and 9. ### Claim 4 (depends on 3) The capsid protein according to claim 3, which is a capsid protein of an AAV of serotype 2. ### Claim 5 (depends on 4) The capsid protein according to claim 4, which is a VP1 protein of an AAV of serotype 2. ### Claim 6 (depends on 1) The capsid protein according to claim 1, comprising the amino acid sequence of SEQ ID NO:10. ### Claim 7 (depends on 6) A cell which comprises a capsid protein according to claim 6. ### Claim 8 (depends on 6) A pharmaceutical composition which comprises a capsid protein according to claim 6. ### Claim 9 (depends on 6) A method for the targeted delivery of viral vectors to the brain and/or spinal cord in a subject, comprising administering a capsid protein according to claim 6 to the subject. ### Claim 10 (depends on 1) A viral capsid which comprises the capsid protein according to claim 1. ### Claim 11 (depends on 1) A cell which comprises a capsid protein according to claim 1. ### Claim 12 (depends on 1) A pharmaceutical composition which comprises a capsid protein according to claim 1. ### Claim 13 (depends on 1) A method for the targeted delivery of viral vectors to the brain and/or spinal cord in a subject, comprising administering a capsid protein according to claim 1 to the subject. ### Claim 14 A nucleic acid which encodes a capsid protein characterized in that the capsid protein comprises the amino acid sequence of SEQ ID NO:1. ### Claim 15 (depends on 14) A plasmid which comprises a nucleic acid according to claim 14. ### Claim 16 (depends on 14) The nucleic acid of claim 14, characterized in that the capsid protein comprises the amino acid sequence of SEQ ID NO:1. ### Claim 17 A recombinant viral vector which comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein, characterized in that the capsid protein comprises the amino acid sequence of SEQ ID NO:1. ### Claim 18 (depends on 17) The recombinant viral vector according to claim 17, which is a recombinant AAV vector. ### Claim 19 (depends on 18) The recombinant viral vector according to claim 18, which is an AAV vector of a serotype selected from the group consisting of serotypes 2, 4, 6, 8, and 9. ### Claim 20 (depends on 19) The recombinant viral vector according to claim 19, which is an AAV vector of serotype 2. ### Claim 21 (depends on 17) The recombinant viral vector according to claim 17, wherein the transgene encodes one of the following proteins: a membrane or tight junction protein, a neuraminidase, glucuronidase, a chemokine antagonist, neurotrophic factor of glia cells (GDNF), neprilysine, cholesterol 24 hydroxylase, aromatic L-amino acid decarboxylase, a tyrosine hydroxylase, GTP cyclohydrolase I, and survival of motor neuron (SMN) protein. ### Claim 22 (depends on 21) The recombinant viral vector according to claim 21, wherein the transgene encodes a neuraminidase. ### Claim 23 (depends on 21) The recombinant viral vector according to claim 21, wherein said membrane or tight junction protein is a claudin or occludin. ### Claim 24 (depends on 21) The recombinant viral vector according to claim 21, wherein said neuraminidase is neuraminidase 1. ### Claim 25 (depends on 21) The recombinant viral vector according to claim 21, wherein said chemokine antagonist is CCL2-7ND. ### Claim 26 (depends on 17) The recombinant viral vector according to claim 17, wherein the transgene is in the form of an ssDNA or a dsDNA. ### Claim 27 (depends on 17) A method for the targeted delivery of viral vectors to the brain and/or spinal cord in a subject, comprising administering a recombinant viral vector according to claim 17 to the subject. ### Claim 28 (depends on 27) The method according to claim 27, wherein the subject is a mammal. ### Claim 29 (depends on 28) The method according to claim 28, wherein the mammal is a human. ### Claim 30 (depends on 27) The method according to claim 27, wherein the vector is formulated for intravenous administration. ### Claim 31 (depends on 17) A pharmaceutical composition which comprises a viral vector according to claim 17. ### Claim 32 A recombinant viral vector which comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein, characterized in that the capsid protein comprises the amino acid sequence of SEQ ID NO:10. ### Claim 33 (depends on 32) The recombinant viral vector according to claim 32, which is an AAV vector of serotype 2. ### Claim 34 (depends on 32) The recombinant viral vector according to claim 32, wherein the transgene encodes one of the following proteins: a membrane or tight junction protein, a neuraminidase, glucuronidase, a chemokine antagonist, neurotrophic factor of glia cells (GDNF), neprilysine, cholesterol 24 hydroxylase, aromatic L-amino acid decarboxylase, a tyrosine hydroxylase, GTP cyclohydrolase I, and survival of motor neuron (SMN) protein. ### Claim 35 (depends on 34) The recombinant viral vector according to claim 34, wherein the transgene encodes a neuraminidase. ### Claim 36 (depends on 34) The recombinant viral vector according to claim 34, wherein said membrane or tight junction protein is a claudin or occludin. ### Claim 37 (depends on 34) The recombinant viral vector according to claim 34, wherein said neuraminidase is neuraminidase 1. ### Claim 38 (depends on 34) The recombinant viral vector according to claim 34, wherein said chemokine antagonist is CCL2-7ND. ### Claim 39 (depends on 32) The recombinant viral vector according to claim 32, wherein the transgene is in the form of an ssDNA or a dsDNA. ### Claim 40 (depends on 32) A method for the targeted delivery of viral vectors to the brain and/or spinal cord in a subject, comprising administering a recombinant viral vector according to claim 32 to the subject. ### Claim 41 (depends on 40) The method according to claim 40, wherein the subject is a mammal. ### Claim 42 (depends on 40) The method according to claim 40, wherein the mammal is a human. ### Claim 43 (depends on 40) The method according to claim 40, wherein the vector is formulated for intravenous administration. ### Claim 44 (depends on 32) A pharmaceutical composition which comprises a viral vector according to claim 32.