ES2985805T3 - Ligandos de formación de imágenes de TAU y sus usos en el diagnóstico y el tratamiento de tauopatías - Google Patents
Ligandos de formación de imágenes de TAU y sus usos en el diagnóstico y el tratamiento de tauopatías Download PDFInfo
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- ES2985805T3 ES2985805T3 ES15818480T ES15818480T ES2985805T3 ES 2985805 T3 ES2985805 T3 ES 2985805T3 ES 15818480 T ES15818480 T ES 15818480T ES 15818480 T ES15818480 T ES 15818480T ES 2985805 T3 ES2985805 T3 ES 2985805T3
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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| US10358503B2 (en) | 2015-08-13 | 2019-07-23 | New York University | Antibody-based molecules selective for the {P}Ser404 epitope of Tau and their uses in the diagnosis and treatment of tauopathy |
| EP3334453A4 (en) | 2015-08-13 | 2019-02-06 | New York University | ANTIBODY-BASED SPECIFIC MOLECULES AND THEIR USES IN THE DIAGNOSIS AND TREATMENT OF TAUOPATHY, FOR TAU'S SPECIFIC ASP421 EPITOP |
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| BR112018067721A2 (pt) * | 2017-01-04 | 2019-01-08 | H. Lundbeck A/S | anticorpos específicos para tau hiperfosforilada para o tratamento de doenças oculares |
| CN110520440A (zh) | 2017-02-17 | 2019-11-29 | 戴纳立制药公司 | 抗τ抗体及其使用方法 |
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| CN109406469B (zh) * | 2018-10-24 | 2021-04-09 | 中国医科大学 | 基于蛋白结合诱导dna双链变构的检测色氨酸的方法 |
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Family Cites Families (66)
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|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS5896026A (ja) | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| DE3380726D1 (en) | 1982-06-24 | 1989-11-23 | Japan Chem Res | Long-acting composition |
| US4681581A (en) | 1983-12-05 | 1987-07-21 | Coates Fredrica V | Adjustable size diaper and folding method therefor |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US5101827A (en) | 1985-07-05 | 1992-04-07 | Immunomedics, Inc. | Lymphographic and organ imaging method and kit |
| US4735210A (en) | 1985-07-05 | 1988-04-05 | Immunomedics, Inc. | Lymphographic and organ imaging method and kit |
| US5776093A (en) | 1985-07-05 | 1998-07-07 | Immunomedics, Inc. | Method for imaging and treating organs and tissues |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4861581A (en) | 1986-12-05 | 1989-08-29 | Cancer Biologics, Inc. | Detection of necrotic malignant tissue and associated therapy |
| US5750172A (en) | 1987-06-23 | 1998-05-12 | Pharming B.V. | Transgenic non human mammal milk |
| US5648471A (en) | 1987-12-03 | 1997-07-15 | Centocor, Inc. | One vial method for labeling antibodies with Technetium-99m |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| EP0486622B1 (en) | 1989-08-09 | 1998-11-04 | Rhomed, Incorporated | Direct radiolabeling of antibodies and other proteins with technetium or rhenium |
| US5633076A (en) | 1989-12-01 | 1997-05-27 | Pharming Bv | Method of producing a transgenic bovine or transgenic bovine embryo |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1992003918A1 (en) | 1990-08-29 | 1992-03-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| WO1992022645A1 (en) | 1991-06-14 | 1992-12-23 | Genpharm International, Inc. | Transgenic immunodeficient non-human animals |
| CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
| EP0593592B1 (en) | 1991-07-08 | 1998-03-25 | The University Of Massachusetts At Amherst | Thermotropic liquid crystal segmented block copolymer |
| US5434050A (en) | 1991-08-13 | 1995-07-18 | Regents Of The University Of Minnesota | Labelled β-amyloid peptide and methods of screening for Alzheimer's disease |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| DK0618968T3 (da) | 1991-12-06 | 2000-04-10 | Max Planck Gesellschaft | Midler til diagnostisering og behandling af Alzheimer's sygdom |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| ES2146648T3 (es) | 1993-03-09 | 2000-08-16 | Genzyme Corp | Procedimiento de aislamiento de proteinas de la leche. |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US6077835A (en) | 1994-03-23 | 2000-06-20 | Case Western Reserve University | Delivery of compacted nucleic acid to cells |
| US6136548A (en) | 1994-11-22 | 2000-10-24 | Rutgers, The State University Of New Jersey | Methods for identifying useful T-PA mutant derivatives for treatment of vascular hemorrhaging |
| US5670477A (en) | 1995-04-20 | 1997-09-23 | Joseph F. Poduslo | Method to enhance permeability of the blood/brain blood/nerve bariers to therapeutic agents |
| US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
| KR970029803A (ko) | 1995-11-03 | 1997-06-26 | 김광호 | 반도체 메모리장치의 프리차지 회로 |
| KR20000015893A (ko) | 1996-05-22 | 2000-03-15 | 댄 마이클 | 특이적으로 암세포를 검출하는 항원 결합 단편, 상기 단편을 코딩하는 뉴클레오티드 및 암의 예방 및 검출에 사용되는 이들의 용도 |
| AU5508798A (en) | 1996-11-19 | 1998-06-10 | Trustees Of The University Of Pennsylvania, The | Diagnostic and therapeutic reagents for alzheimer's disease |
| IL144084A0 (en) | 1999-02-03 | 2002-05-23 | Biosante Pharmaceuticals Inc | Therapeutic calcium phosphate particles and methods of manufacture and use |
| US6281005B1 (en) | 1999-05-14 | 2001-08-28 | Copernicus Therapeutics, Inc. | Automated nucleic acid compaction device |
| CA2380813A1 (en) | 1999-07-29 | 2001-02-08 | Medarex, Inc. | Human monoclonal antibodies to her2/neu |
| WO2001014424A2 (en) | 1999-08-24 | 2001-03-01 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| EP1347731B1 (en) | 2000-11-02 | 2007-04-25 | Cornell Research Foundation, Inc. | In vivo multiphoton diagnostic detection and imaging of a neurodegenerative disease |
| DE60131456T2 (de) | 2000-11-30 | 2008-07-10 | Medarex, Inc., Milpitas | Transchromosomale transgen-nagetiere zur herstellung von humanen antikörpern |
| AT500379B8 (de) | 2001-02-02 | 2009-08-15 | Axon Neuroscience | Tau-proteine |
| AU2002314794A1 (en) | 2001-05-23 | 2002-12-03 | New York University | Detection of alzheimer's amyloid by magnetic resonance imaging |
| IL166244A0 (en) | 2001-07-12 | 2006-01-15 | Jefferson Foote | Super humanized antibodies |
| BRPI0610093A2 (pt) | 2005-05-05 | 2008-12-09 | Merck & Co Inc | composiÇço farmacÊutica, e, mÉtodo para prevenir ou tratar uma doenÇa associada com os depàsitos de amilàides de alfa-beta no cÉrebro de um paciente |
| EA016609B1 (ru) | 2005-11-28 | 2012-06-29 | Генмаб А/С | Рекомбинантные моновалентные антитела и способы их получения |
| US8012936B2 (en) | 2006-03-29 | 2011-09-06 | New York University | Tau fragments for immunotherapy |
| US20080220449A1 (en) | 2007-02-08 | 2008-09-11 | Oligomerix, Inc. | Biomarkers and assays for Alzheimer's disease |
| DK2408807T3 (da) | 2009-03-18 | 2021-08-09 | Ac Immune Sa | Fremgangsmåde til terapeutisk anvendelse |
| UA107571C2 (xx) * | 2009-04-03 | 2015-01-26 | Фармацевтична композиція | |
| JP5917394B2 (ja) | 2009-06-10 | 2016-05-11 | ニューヨーク・ユニバーシティ | 病理学的タウタンパク質の免疫学的標的化方法 |
| AU2010277254B2 (en) | 2009-07-30 | 2015-05-07 | Pfizer Vaccines Llc | Antigenic tau peptides and uses thereof |
| EP3135689B1 (en) * | 2011-10-07 | 2018-12-19 | AC Immune S.A. | Phosphospecific antibodies recognising tau |
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2015
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- 2015-07-06 CN CN201580047108.9A patent/CN107073297B/zh active Active
- 2015-07-06 JP JP2017500891A patent/JP6913018B2/ja active Active
- 2015-07-06 US US15/324,141 patent/US10132818B2/en active Active
- 2015-07-06 WO PCT/US2015/039205 patent/WO2016007414A1/en not_active Ceased
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2018
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| Publication number | Publication date |
|---|---|
| CN107073297A (zh) | 2017-08-18 |
| WO2016007414A1 (en) | 2016-01-14 |
| EP3166688A4 (en) | 2017-12-20 |
| US10859582B2 (en) | 2020-12-08 |
| EP3166688B1 (en) | 2024-08-21 |
| CN107073297B (zh) | 2021-09-14 |
| JP6913018B2 (ja) | 2021-08-04 |
| US11519920B2 (en) | 2022-12-06 |
| US20210055309A1 (en) | 2021-02-25 |
| EP3166688A1 (en) | 2017-05-17 |
| EP3166688C0 (en) | 2024-08-21 |
| US20190025331A1 (en) | 2019-01-24 |
| JP2017532288A (ja) | 2017-11-02 |
| US20170212131A1 (en) | 2017-07-27 |
| US10132818B2 (en) | 2018-11-20 |
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