# US 12,178,845 B2 · Methods and compositions relating to the treatment of tumors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,178,845 B2 - Document ID: US12178845B2 - Status: Granted - Kind: B2 - Application number: 16/466,336 - Filed: 2017-12-06 - Published: 2019-11-07 - Granted: 2024-12-31 - Earliest claimed: 2016-12-07 - Assignees: The General Hospital Corporation - Applicants: The General Hospital Corporation - Inventors: Gary J. Brenner; Giulia Fulci; Sherif Ahmed - Web page: https://patentgrep.com/patent/US12178845B2 ## CPC - A61K 38/1761: {Apoptosis related proteins, e.g. Apoptotic protease-activating factor-1 (APAF-1), Bax, Bax-inhibitory protein(s)(BI; bax-I), Myeloid cell leukemia associated protein (MCL-1), Inhibitor of apoptosis [IAP] or Bcl-2} - A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct} - A61P 35/00: Antineoplastic agents - C07K 14/4747: {Apoptosis related proteins} - 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 - A01K 2207/12: Animals modified by administration of exogenous cells - A01K 2227/105: Murine - A01K 2267/0331: Animal model for proliferative diseases - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered} - 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 2750/14171: Demonstrated in vivo effect - C12N 2840/007: cell or tissue specific - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS ## Abstract Described herein are methods and compositions relating to the treatment of a tumor (e.g., schwannoma) by increasing expression of Apoptosis-associated Speck-like protein containing a CARD (ASC) and/or gasdermin D. In some embodiment, the increased expression is provided by means of a vector or construct comprising a nucleic acid encoding Apoptosis-associated Speck-like protein containing a CARD (ASC) and/or gasdermin D operably linked to a Schwann-lineage cell-specific promoter. In some embodiments, the vector is a viral vector. ## Claims ### Claim 1 A method of treating a schwannoma in a subject in need thereof, the method comprising: administering a viral vector comprising a nucleic acid encoding Apoptosis-associated Speck-like protein containing a CARD (ASC) operably linked to a Schwann cell-specific promoter; and wherein the subject is not administered a viral vector comprising a caspase gene. ### Claim 2 (depends on 1) The method of claim 1, wherein the ASC is a human, mouse, or rat ASC. ### Claim 3 (depends on 1) The method of claim 1, wherein the Schwann cell-specific promoter is a myelin basic protein (P0), a peripheral myelin protein 22 (PMP22), or a myelin basic protein (MBP) promoter. ### Claim 4 (depends on 1) The method of claim 1, wherein the promoter is a human or murine promoter. ### Claim 5 (depends on 1) The method of claim 1, wherein the subject in need of treatment for a schwannoma is a subject having or diagnosed as having a condition selected from the group consisting of: neurofibromatosis 1 (NF1); neurofibromatosis 2 (NF2); schwannomatosis; meningioma; nerve sheath tumor; schwannoma; vestibular schwannoma; sporadic schwannoma; neurofibrosarcoma; neurofibroma; neurofibromatosis (NF); malignant peripheral nerve sheath tumor; and a combination thereof. ### Claim 6 (depends on 1) The method of claim 1, wherein the viral vector is a recombinant adeno-associated virus (rAAV). ### Claim 7 (depends on 6) The method of claim 6, wherein the rAAV is of serotype AAV1 or AAV9. ### Claim 8 (depends on 1) The method of claim 1, wherein the vector further comprises a polyadenylation signal. ### Claim 9 (depends on 8) The method of claim 8, wherein the polyadenylation signal comprises a bovine growth hormone polyadenylation signal (BGHpA), a SV40 polyadenylation signal or a rabbit beta-globin polyadenylation signal. ### Claim 10 (depends on 8) The method of claim 8, wherein the vector further comprises a first AAV inverted terminal repeat (ITR) located upstream of the Schwann cell specific promoter and a second AAV ITR located downstream of the polyadenylation signal. ### Claim 11 (depends on 10) The method of claim 10, wherein the first or second AAV inverted terminal repeat comprises a deletion of a terminal resolution site. ### Claim 12 (depends on 1) The method of claim 1, wherein the vector is a polynucleotide. ### Claim 13 (depends on 1) The method of claim 1, wherein the vector is a single-stranded or double-stranded AAV. ### Claim 14 (depends on 1) The method of claim 1, wherein the vector is a self-complementary AAV (scAAV). ### Claim 15 (depends on 1) The method of claim 1, wherein the vector is a virus particle. ### Claim 16 (depends on 1) The method of claim 1, wherein the vector is administered directly to a nerve affected by the schwannoma. ### Claim 17 (depends on 1) The method of claim 1, wherein administering is intranervously, intracranially, intratumorally, intramuscularly, intravenously, intradermally, or subcutaneously, or a combination thereof. ### Claim 18 (depends on 1) The method of claim 1, wherein the subject is also treated by surgical removal or reduction of the schwannoma. ### Claim 19 (depends on 1) The method of claim 1, wherein the subject in need of treatment for a schwannoma is a subject having or diagnosed as having a condition selected from the group consisting of: neurofibromatosis 1 (NF1); neurofibromatosis 2 (NF2); schwannomatosis; meningioma; nerve sheath tumor; schwannoma; vestibular schwannoma; sporadic schwannoma; neurofibrosarcoma; neurofibroma; neurofibromatosis (NF); and a combination thereof. ### Claim 20 (depends on 1) The method of claim 1, wherein the subject is also treated by surgical removal of the schwannoma. ### Claim 21 (depends on 1) The method of claim 1, wherein the schwannoma is benign.