HRP20210124T1 - Humanizirana tau antitijela u alzheimerovoj bolesti - Google Patents
Humanizirana tau antitijela u alzheimerovoj bolesti Download PDFInfo
- Publication number
- HRP20210124T1 HRP20210124T1 HRP20210124TT HRP20210124T HRP20210124T1 HR P20210124 T1 HRP20210124 T1 HR P20210124T1 HR P20210124T T HRP20210124T T HR P20210124TT HR P20210124 T HRP20210124 T HR P20210124T HR P20210124 T1 HRP20210124 T1 HR P20210124T1
- Authority
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- Croatia
- Prior art keywords
- inhibitor
- beta
- inhibitors
- amyloid
- secretase
- Prior art date
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- 208000024827 Alzheimer disease Diseases 0.000 title claims 4
- 239000003112 inhibitor Substances 0.000 claims 14
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims 8
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims 8
- 239000003814 drug Substances 0.000 claims 8
- SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Aminopropanesulfonate Chemical compound NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 claims 6
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims 6
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims 6
- 239000003540 gamma secretase inhibitor Substances 0.000 claims 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 6
- 229940044551 receptor antagonist Drugs 0.000 claims 6
- 239000002464 receptor antagonist Substances 0.000 claims 6
- 229940124597 therapeutic agent Drugs 0.000 claims 6
- LZXHHNKULPHARO-UHFFFAOYSA-M (3,4-dichlorophenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].C1=C(Cl)C(Cl)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LZXHHNKULPHARO-UHFFFAOYSA-M 0.000 claims 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 4
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 claims 4
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 claims 4
- 230000033616 DNA repair Effects 0.000 claims 4
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 4
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims 4
- 239000002738 chelating agent Substances 0.000 claims 4
- 239000000544 cholinesterase inhibitor Substances 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims 4
- 238000002649 immunization Methods 0.000 claims 4
- 230000003053 immunization Effects 0.000 claims 4
- 238000002560 therapeutic procedure Methods 0.000 claims 4
- 229940124648 γ-Secretase Modulator Drugs 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 3
- VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 claims 2
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 claims 2
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims 2
- 229940126077 BACE inhibitor Drugs 0.000 claims 2
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims 2
- 229940122041 Cholinesterase inhibitor Drugs 0.000 claims 2
- 102000016607 Diphtheria Toxin Human genes 0.000 claims 2
- 108010053187 Diphtheria Toxin Proteins 0.000 claims 2
- 101000854943 Enterobacteria phage T4 Valyl-tRNA ligase modifier Proteins 0.000 claims 2
- 108010001483 Glycogen Synthase Proteins 0.000 claims 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 claims 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 102000004895 Lipoproteins Human genes 0.000 claims 2
- 108090001030 Lipoproteins Proteins 0.000 claims 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims 2
- 108010025020 Nerve Growth Factor Proteins 0.000 claims 2
- 102000007072 Nerve Growth Factors Human genes 0.000 claims 2
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims 2
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims 2
- 229940124154 Phospholipase inhibitor Drugs 0.000 claims 2
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims 2
- 229940122777 Tau aggregation inhibitor Drugs 0.000 claims 2
- 208000034799 Tauopathies Diseases 0.000 claims 2
- 229930003427 Vitamin E Natural products 0.000 claims 2
- 239000012190 activator Substances 0.000 claims 2
- 230000002776 aggregation Effects 0.000 claims 2
- 238000004220 aggregation Methods 0.000 claims 2
- 239000000556 agonist Substances 0.000 claims 2
- 150000001413 amino acids Chemical group 0.000 claims 2
- 230000006933 amyloid-beta aggregation Effects 0.000 claims 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims 2
- 239000003242 anti bacterial agent Substances 0.000 claims 2
- 230000002424 anti-apoptotic effect Effects 0.000 claims 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims 2
- 230000002529 anti-mitochondrial effect Effects 0.000 claims 2
- 229940088710 antibiotic agent Drugs 0.000 claims 2
- 239000000739 antihistaminic agent Substances 0.000 claims 2
- 239000003524 antilipemic agent Substances 0.000 claims 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 claims 2
- 239000003963 antioxidant agent Substances 0.000 claims 2
- 235000006708 antioxidants Nutrition 0.000 claims 2
- 229950001863 bapineuzumab Drugs 0.000 claims 2
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 claims 2
- 229950001954 crenezumab Drugs 0.000 claims 2
- 235000015872 dietary supplement Nutrition 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 229960003530 donepezil Drugs 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 230000004064 dysfunction Effects 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 229960003980 galantamine Drugs 0.000 claims 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims 2
- 229950002508 gantenerumab Drugs 0.000 claims 2
- 239000003102 growth factor Substances 0.000 claims 2
- 239000003324 growth hormone secretagogue Substances 0.000 claims 2
- 239000005556 hormone Substances 0.000 claims 2
- 229940088597 hormone Drugs 0.000 claims 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 2
- 230000006951 hyperphosphorylation Effects 0.000 claims 2
- 102000018358 immunoglobulin Human genes 0.000 claims 2
- 229940125425 inverse agonist Drugs 0.000 claims 2
- 229940043355 kinase inhibitor Drugs 0.000 claims 2
- 229960004640 memantine Drugs 0.000 claims 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 claims 2
- 239000002207 metabolite Substances 0.000 claims 2
- 229910052751 metal Inorganic materials 0.000 claims 2
- 239000002184 metal Substances 0.000 claims 2
- 239000003149 muscarinic antagonist Substances 0.000 claims 2
- 239000002858 neurotransmitter agent Substances 0.000 claims 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims 2
- 239000003428 phospholipase inhibitor Substances 0.000 claims 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 2
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 claims 2
- 229960004633 pirenzepine Drugs 0.000 claims 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims 2
- MGNVWUDMMXZUDI-UHFFFAOYSA-N propane-1,3-disulfonic acid Chemical compound OS(=O)(=O)CCCS(O)(=O)=O MGNVWUDMMXZUDI-UHFFFAOYSA-N 0.000 claims 2
- 239000003909 protein kinase inhibitor Substances 0.000 claims 2
- 239000000018 receptor agonist Substances 0.000 claims 2
- 229940044601 receptor agonist Drugs 0.000 claims 2
- 239000002469 receptor inverse agonist Substances 0.000 claims 2
- 229960004136 rivastigmine Drugs 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000003381 stabilizer Substances 0.000 claims 2
- 229960001685 tacrine Drugs 0.000 claims 2
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 claims 2
- 229950005628 tarenflurbil Drugs 0.000 claims 2
- 229960003570 tramiprosate Drugs 0.000 claims 2
- 229910052723 transition metal Inorganic materials 0.000 claims 2
- 150000003624 transition metals Chemical class 0.000 claims 2
- 235000019165 vitamin E Nutrition 0.000 claims 2
- 229940046009 vitamin E Drugs 0.000 claims 2
- 239000011709 vitamin E Substances 0.000 claims 2
- 241000699802 Cricetulus griseus Species 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940127121 immunoconjugate Drugs 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
Classifications
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- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- 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
-
- 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
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- 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
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- 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
- C07K2317/565—Complementarity determining region [CDR]
-
- 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
- C07K2317/567—Framework region [FR]
-
- 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
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- 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
- G01N2800/50—Determining the risk of developing a disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/70—Mechanisms involved in disease identification
- G01N2800/7047—Fibrils-Filaments-Plaque formation
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Toxicology (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
Claims (15)
1. Humanizirano anti-tau antitijelo naznačeno time da sekvencija varijabilne regije teškog lanca sadrži SEQ ID NO. 16, sekvencija varijabilne regije lakog lanca sadrži SEQ ID NO. 26, te da antitijelo jest izotip IgG1 ili IgG4.
2. Anti-tau antitijelo iz patentnog zahtjeva 1, naznačeno time da rečeno antitijelo sadrži:
a. teški lanac koji ima aminokiselinsku sekvenciju SEQ ID NO. 31 ili 46; te
b. laki lanac koji ima aminokiselinsku sekvenciju SEQ ID NO. 57 ili 58.
3. Antitijelo iz bilo kojeg od patentnih zahtjeva 1 ili 2, naznačeno time da je rečeno antitijelo proizvedeno rekombinantno u staničnoj liniji ovarija kineskog hrčka (CHO).
4. Farmaceutski pripravak koji sadrži antitijelo prema bilo kojem od patentnih zahtjeva 1-3 te farmaceutski prihvatljiv nosač, razrjeđivač, ekscipijens, ili stabilizator.
5. Pripravak iz patentnog zahtjeva 4 koji dalje sadrži drugo terapeutsko sredstvo.
6. Pripravak iz patentnog zahtjeva 5 naznačeno time da su drugo terapeutsko sredstvo i antitijelo kemijski konjugirani.
7. Pripravak iz patentnog zahtjeva 5 ili 6, naznačeno time da je drugo terapeutsko sredstvo korisno u liječenju Alzheimerove bolesti, te da je drugo terapeutsko sredstvo odabrano od jednog ili više tau-peptida, beta-amiloidnih peptida, N-terminalnih amiloidnih beta-peptida, mutiranog toksina difterije; ostalih anti-tau antitijela, antitijela na beta-amiloid, bapineuzumab, solaneuzumab, gantenerumab, crenezumab, IVIG imunoglobulina, ostalih imunizacijskih terapija koje ciljaju Abeta-oligomere, spojeva koji sprječavaju hiperfosforilaciju tau, aktivnih i pasivnih imunizacijskih terapija koje ciljaju tau agregate, inhibitora agregacije beta-amiloida, Tramiprosata, inhibitora gama-sekretaze, semagakestata, modulatora gama-sekretaze, tarenflurbila, inhibitora acetilkolinesteraze, donepezila,rivastigmina, galantamina, takrina, suplemenata prehrani, antagonista receptora N-metil-D-aspartata (NMDA), memantina, inhibitora reparacije DNA, pirenzepina ili njegovog metabolita, kelatora prijelaznog metala, faktora rasta, hormona, nesteroidnih protuupalnih lijekova (NSAID), antioksidansa, sredstava za smanjivanje lipida, inhibitora selektivne fosfodiesteraze, inhibitora tau-agregacije, inhibitora protein kinaza, lijekova koji su inhibitori anti-mitohondrijalne disfunkcije, neurotrofina, inhibitora proteina toplotnog udara, inhibitora fosfolipaze povezane s lipoproteinom A2, anti-apoptičkog spoja, metalnog kelatora, inhibitora reparacije DNA, 3-amino-1-propansulfonske kiseline (3APS), 1,3-propandisulfonat (1,3PDS), aktivatora sekretaze, inhibitora beta-sekretaze, inhibitora gama-sekretaze, beta-amiloidnog peptida, anti-beta-amiloidnog antitijela, neurotransmitera, beta-nabranog umetka, protuupalne molekule, inhibitora BACE, muskarinskih antagonista, inhibitora kolinesteraze, inhibitora gama-sekretaze, modulatora gama-sekretaze, inhibitora HMG-CoA reduktaze, nesteroidnih protuupalnih sredstava, antagonista receptora N-metil-D-aspartata, anti-amiloidnih antitijela, vitamina E, agonista receptora nikotinskog acetilkolina, inverznih agonista CB1 receptora, antagonista CB1 receptora, antibiotika, sekretagogi hormona rasta, antagonista histamina H3, agonista AMPA, inhibitora PDE4, inverznih agonista GABAA, inhibitora amiloidne agregacije, inhibitora glikogen sintaza beta-kinaze, promotora aktivnosti alfa-sekretaze, inhibitora PDE-10, inhibitora apsorpcije kolesterola, te bilo koje njihove farmaceutski prihvatljive soli.
8. Dijagnostički reagens koji sadrži antitijelo prema bilo kojem od patentnih zahtjeva 1-3 te nosač, razrjeđivač, ekscipijens, ili stabilizator.
9. Imunokonjugat koji ima formulu (A)-(L)-(C), naznačeno time da: (A) jest antitijelo iz bilo kojeg od patentnih zahtjeva 1-3; (L) je poveznica; te (C) jest sredstvo; te da rečena poveznica (L) povezuje (A) na (C).
10. Molekula nukleinske kiseline koja kodira bilo koje od antitijela iz bilo kojeg od patentnih zahtjeva 1-3.
11. Vektor koji sadrži nukleinsku kiselinu prema patentnom zahtjevu 10.
12. Stanica domaćina koja sadrži vektor prema patentnom zahtjevu 11.
13. Antitijelo prema bilo kojem od patentnih zahtjeva 1-3, ili pripravak prema bilo kojem od patentnih zahtjeva 4-7 za upotrebu u liječenju Alzheimerove bolesti ili druge taupatije kod subjekta koji ima Alzheimerovu bolest ili drugu taupatiju.
14. Antitijelo za upotrebu prema patentnom zahtjevu 13, naznačeno time da se efektivna količina najmanje jednog dodatnog terapeutskog sredstva daje istovremeno ili sekvencijalno rečenom subjektu.
15. Antitijelo za upotrebu prema patentnom zahtjevu 14, naznačeno time da je dodatno terapeutsko sredstvo odabrano od jednog ili više tau-peptida, beta-amiloidnih peptida, N-terminalnih amiloidnih beta-peptida, mutiranog toksina difterije; ostalih anti-tau antitijela, antitijela na beta-amiloid, bapineuzumab, solaneuzumab, gantenerumab, crenezumab, IVIG imunoglobulina, ostalih imunizacijskih terapija koje ciljaju Abeta-oligomere, spojeva koji sprječavaju hiperfosforilaciju tau, aktivnih i pasivnih imunizacijskih terapija koje ciljaju tau agregate, inhibitora agregacije beta-amiloida, Tramiprosata, inhibitora gama-sekretaze, semagakestata, modulatora gama-sekretaze, tarenflurbila, inhibitora acetilkolinesteraze, donepezila,rivastigmina, galantamina, takrina, suplemenata prehrani, antagonista receptora N-metil-D-aspartata (NMDA), memantina, inhibitora reparacije DNA, pirenzepina ili njegovog metabolita, kelatora prijelaznog metala, faktora rasta, hormona, nesteroidnih protuupalnih lijekova (NSAID), antioksidansa, sredstava za smanjivanje lipida, inhibitora selektivne fosfodiesteraze, inhibitora tau-agregacije, inhibitora protein kinaza, lijekova koji su inhibitori anti-mitohondrijalne disfunkcije, neurotrofina, inhibitora proteina toplotnog udara, inhibitora fosfolipaze povezane s lipoproteinom A2, anti-apoptičkog spoja, metalnog kelatora, inhibitora reparacije DNA, 3-amino-1-propansulfonske kiseline (3APS), 1,3-propandisulfonat (1,3PDS), aktivatora sekretaze, inhibitora beta-sekretaze, inhibitora gama-sekretaze, beta-amiloidnog peptida, anti-beta-amiloidnog antitijela, neurotransmitera, beta-nabranog umetka, protuupalne molekule, inhibitora BACE, muskarinskih antagonista, inhibitora kolinesteraze, inhibitora gama-sekretaze, modulatora gama-sekretaze, inhibitora HMG-CoA reduktaze, nesteroidnih protuupalnih sredstava, antagonista receptora N-metil-D-aspartata, anti-amiloidnih antitijela, vitamina E, agonista receptora nikotinskog acetilkolina, inverznih agonista CB1 receptora, antagonista CB1 receptora, antibiotika, sekretagogi hormona rasta, antagonista histamina H3, agonista AMPA, inhibitora PDE4, inverznih agonista GABAA, inhibitora amiloidne agregacije, inhibitora glikogen sintaza beta-kinaze, promotora aktivnosti alfa-sekretaze, inhibitora PDE-10, inhibitora apsorpcije kolesterola, te bilo koje njihove farmaceutski prihvatljive soli.
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