# US 11,077,132 B2 · Tau antisense oligomers and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,132 B2 - Document ID: US11077132B2 - Status: Granted - Kind: B2 - Application number: 15/549,021 - Filed: 2016-02-04 - Published: 2018-06-14 - Granted: 2021-08-03 - Earliest claimed: 2015-02-04 - Assignees: F. Hoffmann-La Roche AG - Applicants: F. Hoffmann-La Roche AG - Inventors: Richard E. Olson; Angela M. Cacace; Peter Hagedorn; Anja Mølhart Høg; Marianne Lerbech Jensen; Niels Fisker Nielsen; Dong Li; Jeffrey M. Brown; Stephen E. Mercer - Web page: https://patentgrep.com/patent/US11077132B2 ## CPC - A61K 31/712: Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose - 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 - 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)} - A61K 2121/00: Preparations for use in therapy - C12N 2310/11: Antisense - C12N 2310/315: Phosphorothioates - C12N 2310/3231: having an additional ring, e.g. LNA, ENA - C12N 2310/341: Gapmers, i.e. of the type ===---=== - C12N 2310/343: having patterns, e.g. ==--==--==-- - C12N 2310/346: having a combination of backbone and sugar modifications - 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 - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder. ## Claims ### Claim 1 An oligomer consisting of the nucleic acid sequence ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is a beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside. ### Claim 2 (depends on 1) A conjugate comprising the oligomer of claim 1, wherein the oligomer is covalently attached to at least one non-nucleotide or non-polynucleotide moiety. ### Claim 3 (depends on 1) A pharmaceutical composition comprising the oligomer of claim 1 and a pharmaceutically acceptable diluent, carrier, salt, or adjuvant. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, which is capable of down-regulating expression of the MAPT mRNA in a human cell. ### Claim 5 (depends on 4) The pharmaceutical composition of claim 4, wherein the human cell is a neuronal cell. ### Claim 6 (depends on 2) A pharmaceutical composition comprising the conjugate of claim 2 and a pharmaceutically acceptable diluent, carrier, salt, or adjuvant. ### Claim 7 A method of inhibiting or reducing Tau protein expression in a cell, the method comprising: administering a pharmaceutical composition comprising at least one of: an oligomer consisting of the nucleic acid sequence ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is a beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside; or a conjugate comprising an oligomer having a nucleic acid sequence comprising ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside, wherein the oligomer is covalently attached to at least one non-nucleotide or non-polynucleotide moiety; to the cell expressing Tau protein, wherein the Tau protein expression in the cell is inhibited or reduced after the administration. ### Claim 8 (depends on 7) The method of claim 7, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable diluent, carrier, salt, or adjuvant. ### Claim 9 A method for treating a tauopathy, the method comprising: administering an effective amount of a pharmaceutical composition comprising at least one of: an oligomer consisting of the nucleic acid sequence ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is a beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside; or a conjugate comprising an oligomer consisting of the nucleic acid sequence ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is a beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside, wherein the oligomer is covalently attached to at least one non-nucleotide or non-polynucleotide moiety. ### Claim 10 (depends on 9) The method of claim 9, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable diluent, carrier, salt, or adjuvant. ### Claim 11 A method for treating a disorder associated with over expression or expression of a mutated version of Tau protein, the method comprising: administering an effective amount of a pharmaceutical composition comprising at least one of: an oligomer consisting of the nucleic acid sequence ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is a beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside; or a conjugate comprising an oligomer consisting of the nucleic acid sequence ATTtCcaaattcacTtTtAC (SEQ ID NO:487) or ATtTCcaaattcactTTtAC (SEQ ID NO:472), wherein each upper case letter is a beta-D-oxy-LNA nucleoside, and wherein each lower case letter is a DNA nucleoside, wherein the oligomer is covalently attached to at least one non-nucleotide or non-polynucleotide moiety. ### Claim 12 (depends on 11) The method of claim 11, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable diluent, carrier, salt, or adjuvant. ### Claim 13 (depends on 11) The method of claim 11, wherein the disorder associated with over expression or expression of a mutated version of Tau protein is a tauopathy.