# US 2014/0154269 A1 · Targeted nanovectors and their use for treatment of brain tumors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154269 A1 - Document ID: US20140154269A1 - Status: Published application - Kind: A1 - Application number: 14/114,051 - Filed: 2012-04-26 - Published: 2014-06-05 - Earliest claimed: 2011-04-26 - Assignees: The Methodist Hospital Research Institute; William Marsh Rice University - Inventors: James M. Tour; Jacob Berlin; Daniela Marcano; David S. Baskin; Martyn A. Sharpe - Web page: https://patentgrep.com/patent/US20140154269A1 ## CPC - A61K 9/0085: {Brain, e.g. brain implants; Spinal cord} - A61K 9/5123: {Organic compounds, e.g. fats, sugars} - A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol - A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble} - C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation - C12N 2810/859: from immunoglobulins - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract In some embodiments, the invention pertains to therapeutic compositions for treating a brain tumor. Such therapeutic compositions generally comprise: (1) a nanovector; (2) an active agent associated with the nanovector with activity against brain tumor cells; and (3) a targeting agent associated with the nanovector with recognition activity for a marker of the brain tumor cells. In some embodiments, the active agent and the targeting agent are non-covalently associated with the nanovector. Additional embodiments of the present invention pertain to methods of treating a brain tumor in a subject (e.g., a human being) by administering the aforementioned therapeutic compositions to the subject. Further embodiments of the present disclosure pertain to methods of formulating therapeutic compositions for treating a brain tumor in a subject in a personalized manner. ## Claims ### Claim 1 A therapeutic composition for treating a brain tumor, wherein the therapeutic composition comprises: a nanovector; an active agent associated with the nanovector, wherein the active agent has activity against brain tumor cells; and a targeting agent associated with the nanovector, wherein the targeting agent has recognition activity for a marker of the brain tumor cells. ### Claim 2 (depends on 1) The therapeutic composition of claim 1, wherein the active agent is non-covalently associated with the nanovector. ### Claim 3 (depends on 1) The therapeutic composition of claim 1, wherein the active agent is covalently associated with the nanovector. ### Claim 4 (depends on 1) The therapeutic composition of claim 1, wherein the targeting agent is non-covalently associated with the nanovector. ### Claim 5 (depends on 1) The therapeutic composition of claim 1, wherein the targeting agent is covalently associated with the nanovector. ### Claim 6 (depends on 1) The therapeutic composition of claim 1, wherein the nanovector comprises hydrophobic domains and hydrophilic domains, and wherein the active agent is associated with the hydrophobic domains. ### Claim 7 (depends on 1) The therapeutic composition of claim 1, wherein the nanovector is selected from the group consisting of single-walled nanotubes, double-walled nanotubes, triple-walled nanotubes, multi-walled nanotubes, ultra-short nanotubes, graphene, graphene nanoribbons, graphite, graphite oxide nanoribbons, carbon black, oxidized carbon black, hydrophilic carbon clusters and combinations thereof. ### Claim 8 (depends on 1) The therapeutic composition of claim 1, wherein the nanovector is functionalized with a plurality of solubilizing groups. ### Claim 9 (depends on 8) The therapeutic composition of claim 8, wherein the solubilizing groups are selected from the group consisting of polyethylene glycols, polypropylene glycols, poly(p-phenylene oxide), polyethylene imines, poly(vinyl alcohol), poly(acrylic acid), poly(vinyl amines) and combinations thereof. ### Claim 10 (depends on 1) The therapeutic composition of claim 1, wherein the nanovector is an ultra-short single-walled nanotube, and wherein the nanotube is functionalized with a plurality of solubilizing groups. ### Claim 11 (depends on 1) The therapeutic composition of claim 1, wherein the nanovector is a polyethylene glycol functionalized hydrophilic carbon cluster (PEG-HCC). ### Claim 12 (depends on 1) The therapeutic composition of claim 1, wherein the active agent is selected from the group consisting of small molecules, proteins, DNA, antisense oligonucleotides, miRNA, siRNA, aptamers, and combinations thereof. ### Claim 13 (depends on 1) The therapeutic composition of claim 1, wherein the active agent is hydrophobic. ### Claim 14 (depends on 1) The therapeutic composition of claim 1, wherein the active agent is selected from the group consisting of Cis-platin, SN-38, Vinblastine, Daunorubicin, Paclitaxel, Docetaxel, Iadarubicin, Oxaliplatin, 1,2,3,4-tetrahydronaphthalene-2,3-diamine, 2,2-dichloro-octahydrocyclohexa 1,3-diaza-2-platinacyclopentane, 2,2-dichloro-hexahydro-naphtho-1,3-diaza-2-platinacyclopentane, 4,4-dichloro-3,5-diaza-4-platinatetracycloheptadecahexaene, nitrogen mustards, spermine mustards, estrogen mustards, cholesterol mustards, and combinations thereof. ### Claim 15 (depends on 1) The therapeutic composition of claim 1, wherein the marker of the brain tumor cells comprises an epitope on a surface of the brain tumor cells. ### Claim 16 (depends on 1) The therapeutic composition of claim 1, wherein the marker of the brain tumor cells is glial fibrillary acidic protein (GFAP). ### Claim 17 (depends on 1) The therapeutic composition of claim 1, wherein the marker of the brain tumor cells is a receptor on a surface of the brain tumor cells, wherein the receptor is selected from the group consisting of epidermal growth factor receptors, cytokine receptors, interleukin receptors, and combinations thereof. ### Claim 18 (depends on 1) The therapeutic composition of claim 1, wherein the targeting agent is selected from the group consisting of antibodies, proteins, RNA, DNA, aptamers, small molecules, dendrimers, and combinations thereof. ### Claim 19 (depends on 1) The therapeutic composition of claim 1, wherein the targeting agent is an antibody directed against a marker of the brain tumor cells. ### Claim 20 (depends on 1) The therapeutic composition of claim 1, wherein the brain tumor to be treated is selected from the group consisting of gliomas, glioblastomas, astrocytomas, neuroblastomas, retinoblastomas, meduloblastomas, oligodendrogliomas, ependymomas, choroid plexus papillomas, meningiomas, pituitary adenomas, and combinations thereof. ### Claim 21 (depends on 1) The therapeutic composition of claim 1, wherein the brain tumor to be treated is a primary glioblastoma multiforme (GBM). ### Claim 22 A method of treating a brain tumor in a subject, wherein the method comprises: administering a therapeutic composition to the subject, wherein the therapeutic composition comprises: a nanovector; an active agent associated with the nanovector, wherein the active agent has activity against brain tumor cells, and a targeting agent associated with the nanovector, wherein the targeting agent has recognition activity for a marker of the brain tumor cells. ### Claim 23 (depends on 22) The method of claim 22, wherein the subject is a human being. ### Claim 24 (depends on 22) The method of claim 22, wherein the administering of the therapeutic composition comprises intravenous administration. ### Claim 25 (depends on 22) The method of claim 22, wherein the nanovector is selected from the group consisting of single-walled nanotubes, double-walled nanotubes, triple-walled nanotubes, multi-walled nanotubes, ultra-short nanotubes, graphene, graphene nanoribbons, graphite, graphite oxide nanoribbons, carbon black, oxidized carbon black, hydrophilic carbon clusters and combinations thereof. ### Claim 26 (depends on 22) The method of claim 22, wherein the nanovector is an ultra-short single-walled nanotube, wherein the nanotube is functionalized with a plurality of solubilizing groups. ### Claim 27 (depends on 22) The method of claim 22, wherein the nanovector is a polyethylene glycol functionalized hydrophilic carbon cluster (PEG-HCC). ### Claim 28 (depends on 22) The method of claim 22, wherein the active agent is selected from the group consisting of small molecules, proteins, DNA, antisense oligonucleotides, miRNA, siRNA, aptamers, and combinations thereof. ### Claim 29 (depends on 22) The method of claim 22, wherein the active agent is selected from the group consisting of Cis-platin, SN-38, Vinblastine, Daunorubicin, Docetaxel, Paclitaxel, Iadarubicin, Oxaliplatin, 1,2,3,4-tetrahydronaphthalene-2,3-diamine, 2,2-dichloro-octahydrocyclohexa 1,3-diaza-2-platinacyclopentane, 2,2-dichloro-hexahydro-naphtho-1,3-diaza-2-platinacyclopentane, 4,4-dichloro-3,5-diaza-4-platinatetracycloheptadecahexaene, nitrogen mustards, spermine mustards, estrogen mustards, cholesterol mustards, and combinations thereof. ### Claim 30 (depends on 22) The method of claim 22, wherein the marker of the brain tumor cells is a receptor on a surface of the brain tumor cells. ### Claim 31 (depends on 22) The method of claim 22, wherein the targeting agent is selected from the group consisting of antibodies, proteins, RNA, DNA, aptamers, small molecules, dendrimers, and combinations thereof. ### Claim 32 (depends on 22) The method of claim 22, wherein the targeting agent is an antibody directed against a marker of the brain tumor cells. ### Claim 33 (depends on 22) The method of claim 22, wherein the brain tumor to be treated is selected from the group consisting of gliomas, glioblastomas, astrocytomas, neuroblastomas, retinoblastomas, meduloblastomas, oligodendrogliomas, ependymomas, choroid plexus papillomas, meningiomas, pituitary adenomas, and combinations thereof. ### Claim 34 (depends on 22) The method of claim 22, wherein the brain tumor to be treated is a primary glioblastoma multiforme (GBM). ### Claim 35 A method of formulating a therapeutic composition for treating a brain tumor in a subject, wherein the method comprises: isolating brain tumor cells from the subject; determining expression levels of one or more markers of the brain tumor cells; and formulating the therapeutic composition, wherein the formulated therapeutic composition comprises: a nanovector; an active agent associated with the nanovector; and a targeting agent associated with the nanovector, wherein the targeting agent has recognition activity for a marker of the brain tumor cells, and wherein the targeting agent is selected based on the determined expression levels of the one or more markers of the brain tumor cells. ### Claim 36 (depends on 35) The method of claim 35, further comprising a step of determining susceptibility of the brain tumor cells to one or more active agents, and selecting the active agent based on the determined susceptibility of the brain tumor cells to the one or more active agents ### Claim 37 (depends on 36) The method of claim 36, wherein the susceptibility of the brain tumor cells to one or more active agents is determined by growing different batches of the brain tumor cells in the presence of different active agents and comparing growth rates of the different batches with the growth rate of untreated brain tumor cells. ### Claim 38 (depends on 35) The method of claim 35, wherein the isolating of the brain tumor cells comprises an excision of a portion of a brain tumor from the subject. ### Claim 39 (depends on 35) The method of claim 35, wherein the expression levels of one or more markers of the brain tumor cells are determined by treating the brain tumor cells with targeting agents that are specific for the markers. ### Claim 40 (depends on 35) The method of claim 35, wherein the subject is a human.