SG11201705986QA - Antibody molecules and peptide delivery systems for use in alzheimer's disease and related disorders - Google Patents
Antibody molecules and peptide delivery systems for use in alzheimer's disease and related disordersInfo
- Publication number
- SG11201705986QA SG11201705986QA SG11201705986QA SG11201705986QA SG11201705986QA SG 11201705986Q A SG11201705986Q A SG 11201705986QA SG 11201705986Q A SG11201705986Q A SG 11201705986QA SG 11201705986Q A SG11201705986Q A SG 11201705986QA SG 11201705986Q A SG11201705986Q A SG 11201705986QA
- Authority
- SG
- Singapore
- Prior art keywords
- alzheimer
- disease
- delivery systems
- antibody molecules
- related disorders
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1018—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
- C07K14/08—RNA viruses
- C07K14/18—Togaviridae; Flaviviridae
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4709—Amyloid plaque core protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/56—Staging of a disease; Further complications associated with the disease
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Optics & Photonics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Psychology (AREA)
- Mycology (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PT10818115 | 2015-01-29 | ||
PT10818215 | 2015-01-29 | ||
PCT/IB2016/050467 WO2016120843A1 (en) | 2015-01-29 | 2016-01-29 | Antibody molecules and peptide delivery systems for use in alzheimer's disease and related disorders |
Publications (1)
Publication Number | Publication Date |
---|---|
SG11201705986QA true SG11201705986QA (en) | 2017-08-30 |
Family
ID=55409873
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG11201705986QA SG11201705986QA (en) | 2015-01-29 | 2016-01-29 | Antibody molecules and peptide delivery systems for use in alzheimer's disease and related disorders |
Country Status (8)
Country | Link |
---|---|
US (2) | US10654917B2 (en) |
EP (2) | EP4183795A1 (en) |
JP (1) | JP6986967B2 (en) |
CN (1) | CN107531781B (en) |
AU (1) | AU2016210835B2 (en) |
CA (1) | CA2975059C (en) |
SG (1) | SG11201705986QA (en) |
WO (1) | WO2016120843A1 (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2017354743A1 (en) | 2016-11-07 | 2019-06-06 | DegenRx B.V | Novel amyloid beta oligomer specific binding molecule |
EP3873934A2 (en) * | 2018-10-29 | 2021-09-08 | Biogen MA Inc. | Humanized and stabilized fc5 variants for enhancement of blood brain barrier transport |
US20200230218A1 (en) * | 2019-01-18 | 2020-07-23 | L & J Bio Co., Ltd. | Method of treating central nervous system disease |
TW202300517A (en) | 2021-03-12 | 2023-01-01 | 美商美國禮來大藥廠 | Anti-amyloid beta antibodies and uses thereof |
WO2022251048A1 (en) | 2021-05-24 | 2022-12-01 | Eli Lilly And Company | Anti-amyloid beta antibodies and uses thereof |
WO2022270396A1 (en) * | 2021-06-21 | 2022-12-29 | 株式会社Epsilon Molecular Engineering | Double-screening method |
AU2022307967A1 (en) * | 2021-07-07 | 2024-01-25 | Faculdade De Medicina Veterinária Da Universidade De Lisboa | Highly specific rabbit single -domain antibodies for drug delivery in immunotherapy applications |
CN116212049B (en) * | 2022-12-19 | 2023-11-24 | 江南大学 | Application of chiral nanomaterial based on microglial inflammatory aging regulation in preparation of medicine for treating Alzheimer disease |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
DE69435112D1 (en) | 1993-09-10 | 2008-08-21 | Univ Columbia | USE OF GREEN FLUORESCENCE PROTEIN |
US6311415B1 (en) | 1998-09-14 | 2001-11-06 | Lind Shoe Company | Bowling shoe with replaceable tip |
US6962793B2 (en) * | 2000-10-27 | 2005-11-08 | Mount Sinai Hospital | Methods for detecting Alzheimers disease |
EP1543331B1 (en) * | 2002-07-30 | 2009-02-11 | The J. David Gladstone Institutes | Method of diagnosing alzheimer's disease |
WO2004031400A2 (en) * | 2002-10-01 | 2004-04-15 | Northwestern University | Amyloid beta-derived diffusible ligands (addls), addl-surrogates, addl-binding molecules, and uses thereof |
JPWO2005105998A1 (en) * | 2004-04-27 | 2008-07-31 | 財団法人化学及血清療法研究所 | Human anti-amyloid β peptide antibody and antibody fragment thereof |
WO2006040153A2 (en) * | 2004-10-13 | 2006-04-20 | Ablynx N.V. | Single domain camelide anti -amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenarative neural diseases such as alzheimer's disease |
CN101076543A (en) * | 2004-10-13 | 2007-11-21 | 阿布林克斯公司 | Single domain camelide anti-amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenerative neural diseases such as alzheimer's disease |
EP1963363A2 (en) * | 2005-11-30 | 2008-09-03 | Abbott Laboratories | Methods of preparation of recombinant forms of human beta-amyloid protein and uses of these proteins |
US10280211B2 (en) | 2007-05-04 | 2019-05-07 | Technophage, Investigação E Desenvolvimento Em Biotecnologia, Sa | Engineered rabbit antibody variable domains and uses thereof |
JP5570998B2 (en) * | 2007-12-31 | 2014-08-13 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Antibody to TNFα |
DK2419447T3 (en) * | 2009-04-17 | 2017-09-25 | Immunas Pharma Inc | ANTIBODIES THAT SPECIFICALLY BIND TO A BETA OLIGOMER AND USE THEREOF |
DK2462161T3 (en) * | 2009-08-06 | 2017-06-06 | Immunas Pharma Inc | Antibodies specifically binding to A-beta oligomers and their use |
EP2497782A1 (en) * | 2011-03-08 | 2012-09-12 | Alzinova AB | Anti oligomer antibodies and uses thereof |
PL2723771T3 (en) | 2011-06-23 | 2020-04-30 | Ablynx Nv | Serum albumin binding proteins |
WO2013043071A1 (en) | 2011-09-23 | 2013-03-28 | Technophage, Investigação E Desenvolvimento Em Biotecnologia, Sa | Modified albumin-binding domains and uses thereof to improve pharmacokinetics |
MX350378B (en) | 2012-01-10 | 2017-09-05 | Biogen Ma Inc | Enhancement of transport of therapeutic molecules across the blood brain barrier. |
WO2013167681A1 (en) * | 2012-05-10 | 2013-11-14 | Georg-August-Universität Göttingen | CONFORMATIONAL-SPECIFIC ANTIBODIES AGAINST Αβ OLIGOMERS |
EP3721942A1 (en) * | 2012-10-15 | 2020-10-14 | Medimmune Limited | Antibodies to amyloid beta |
-
2016
- 2016-01-29 AU AU2016210835A patent/AU2016210835B2/en active Active
- 2016-01-29 CA CA2975059A patent/CA2975059C/en active Active
- 2016-01-29 CN CN201680014071.4A patent/CN107531781B/en active Active
- 2016-01-29 EP EP22198181.4A patent/EP4183795A1/en active Pending
- 2016-01-29 EP EP16705995.5A patent/EP3250595B1/en active Active
- 2016-01-29 JP JP2017538943A patent/JP6986967B2/en active Active
- 2016-01-29 US US15/545,399 patent/US10654917B2/en active Active
- 2016-01-29 SG SG11201705986QA patent/SG11201705986QA/en unknown
- 2016-01-29 WO PCT/IB2016/050467 patent/WO2016120843A1/en active Application Filing
-
2020
- 2020-04-30 US US16/863,184 patent/US20210355200A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
AU2016210835B2 (en) | 2021-01-21 |
US20180009883A1 (en) | 2018-01-11 |
CN107531781B (en) | 2021-12-07 |
EP3250595A1 (en) | 2017-12-06 |
US20210355200A1 (en) | 2021-11-18 |
US10654917B2 (en) | 2020-05-19 |
AU2016210835A8 (en) | 2017-08-17 |
JP2018513670A (en) | 2018-05-31 |
EP4183795A1 (en) | 2023-05-24 |
CN107531781A (en) | 2018-01-02 |
WO2016120843A1 (en) | 2016-08-04 |
JP6986967B2 (en) | 2021-12-22 |
AU2016210835A1 (en) | 2017-08-10 |
CA2975059C (en) | 2023-02-21 |
CA2975059A1 (en) | 2016-08-04 |
EP3250595B1 (en) | 2024-04-24 |
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