ME01758B - Humanizirano protutijelo protiv amiloida beta - Google Patents
Humanizirano protutijelo protiv amiloida betaInfo
- Publication number
- ME01758B ME01758B MEP-2013-132A MEP13213A ME01758B ME 01758 B ME01758 B ME 01758B ME P13213 A MEP13213 A ME P13213A ME 01758 B ME01758 B ME 01758B
- Authority
- ME
- Montenegro
- Prior art keywords
- fragment
- humanized antibody
- accordance
- antibody
- amyloidosis
- Prior art date
Links
Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- 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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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]
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- 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
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- 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
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- 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
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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
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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
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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
- G01N2800/56—Staging of a disease; Further complications associated with the disease
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
Claims (23)
1. Humanizirano protutijelo, ili njegov fragment, koje prepoznaje i veže se na β-amiloidni protein, naznačeno time što navedeno humanizirano protutijelo, ili njegov fragment, sadrži: i) varijabilno područje teškog lanca (HCVR), koje ima aminokiselinski slijed SEQ ID NO: 15, i ii) varijabilno područje lakog lanca (LCVR), koje ima aminokiselinski slijed SEQ ID NO: 12.
2. Humanizirano protutijelo, ili njegov fragment, u skladu s patentnim zahtjevom 1, naznačeno time što sadrži: teški lanac, koji ima aminokiselinski slijed SEQ ID NO: 16, i laki lanac, koji ima aminokiselinski slijed SEQ ID NO: 13.
3. Humanizirano protutijelo, ili njegov fragment, u skladu s patentnim zahtjevom 2, naznačeno time što je uklonjen C-terminalni Lys u konstantnom području teškog lanca.
4. Humanizirano protutijelo, ili njegov fragment, u skladu s patentnim zahtjevom 1, naznačeno time što je navedeno humanizirano protutijelo, ili njegov fragment, od izotipa IgG1, IgG2, IgG3 ili IgG4.
5. Molekula nukleinske kiseline, naznačena time što sadrži nukleotidni slijed koji kodira humanizirano protutijelo, ili njegov fragment, u skladu s bilo kojim od patentnih zahtjeva 1-4.
6. Molekula nukleinske kiseline u skladu s patentnim zahtjevom 5, naznačena time što sadrži nukleotidni slijed SEQ ID NO: 22 ili nukleotidni slijed SEQ ID NO: 21.
7. Molekula nukleinske kiseline u skladu s patentnim zahtjevom 5, naznačena time što sadrži nukleotidni slijed SEQ ID NO: 25 ili nukleotidni slijed SEQ ID NO: 24.
8. Ekspresijski vektor, naznačen time što sadrži nukleotidni slijed u skladu s bilo kojim od patentnih zahtjeva 5-7.
9. Stanica, naznačena time što sadrži ekspresijski vektor u skladu s patentnim zahtjevom 8.
10. Farmaceutski pripravak, naznačen time što sadrži humanizirano protutijelo, ili njegov fragment, u skladu s bilo kojim od patentnih zahtjeva 1 do 4, i izborno dodatno sadrži farmaceutski prihvatljiv nosač.
11. Farmaceutski pripravak u skladu s patentnim zahtjevom 10, naznačen time što izborno dodatno sadrži jedno ili više od sljedećeg: biološki aktivnu tvar, razrjeđivač ili pomoćnu tvar.
12. Farmaceutski pripravak u skladu s patentnim zahtjevom 11, naznačen time što dodatno sadrži biološki aktivnu tvar, koja je spoj kojeg se upotrebljava u liječenju amiloidoze.
13. Farmaceutski pripravak u skladu s patentnim zahtjevom 11, naznačen time što sadrži najmanje jedan od sljedećih spojeva: spoj protiv oksidativnog stresa; ancijapoptotski spoj; kelator metala; inhibitor popravka DNA, poput pirenzepina i njegovoh metabolita; 3-amino-1-propansulfonsku kiselinu (3APS); 1,3-propandisulfonat (1,3PDS); aktivator α-sekretaze; inhibitor Aβ-sekretaze; inhibitor γ-sekretaze; tau-protein; neuroprijenosnik; prekidač β-ploče; atraktant za stanične komponente koje čiste/uklanjaju amiloid beta; inhibitor N-terminalno skraćenog amiloida beta, poput piroglutamatiranog amiloida beta 3-42; protuupalnu molekulu; ili inhibitor kolinesteraze (ChEI), poput takrina, rivastigmina, donepezila i/ili galantamina; MI agonist; ili koji drugi lijek, poput lijeka koji modificira amiloid ili tau, ili dodatak prehrani.
14. Upotreba humaniziranog protutijela, ili njegovog fragmenta, u skladu s bilo kojim od patentnih zahtjeva 1 do 4 i/ili farmaceutskog pripravka u skladu s bilo kojim od patentnih zahtjeva 10 do 13, naznačena time što su protutijelo, ili njegov fragment, ili farmaceutski pripravak namijenjeni pripravi medikamenta za liječenje ili ublažavanje posljedica amiloidoze, poput sekundarne amiloidoze, staračke amiloidoze, neuroloških poremećaja, poput Alzheimerove bolesti (AD), demencije Lewyjevih tijela, Downovog sindroma, nasljednog cerebralnog krvarenja uz amiloidozu (nizozemskog tipa); guamskog kompleksa parkinsonizma s demencijom; bolesti uzrokovanih ili povezanih s proteinima slični amiloidnima, poput progresivne supranuklearne paralize, multiple skleroze; Creutzfeld-Jacobove bolesti, Parkinsonove bolesti, demencije povezane s HIV-om, ALS (amiotropne lateralne skleroze), dijabetesa s početkom u odrasloj dobi; staračke amiloidoze srca; endokrinih tumora, te degeneracije makule.
15. Upotreba u skladu s patentnim zahtjevom 14, naznačena time što liječenje životinje, poput sisavca ili čovjeka, dovodi do jednog ili više od sljedećeg: i) povećanja sposobnosti kognitivnog pamćenja; ii) zadržavanja sposobnosti kognitivnog pamćenja; i/ili iii) potpunog obnavljanja sposobnosti kognitivnog pamćenja.
16. Farmaceutski pripravak u skladu s patentnim zahtjevom 10 ili 13, naznačen time što je namijenjen upotrebi u postupku sprječavanja, liječenja ili ublažavanja posljedica amiloidoze, poput sekundarne amiloidoze i staračke amiloidoze, poput bolesti koje uključuju, no ne ograničuju se na, neurološke poremećaje, poput Alzheimerove bolesti (AD), demencije Lewyjevih tijela, Downovog sindroma, nasljednog cerebralnog krvarenja uz amiloidozu (nizozemskog tipa), guamskog kompleksa parkinsonizma s demencijom, bolesti uzrokovanih ili povezanih s proteinima slični amiloidnima, poput progresivne supranuklearne paralize, i multiple skleroze, Creutzfeld-Jacobove bolesti, Parkinsonove bolesti, demencije povezane s HIV-om, ALS (amiotropne lateralne skleroze), dijabetesa s početkom u odrasloj dobi, staračke amiloidoze srca; endokrinih tumora, te degeneracije makule.
17. Farmaceutski pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 16, naznačen time što liječenje životinje, poput sisavca ili čovjeka, dovodi do: i) povećanja sposobnosti kognitivnog pamćenja, ii) zadržavanja sposobnosti kognitivnog pamćenja, i/ili iii) povrata sposobnosti kognitivnog pamćenja i potpunog obnavljanja sposobnosti kognitivnog pamćenja.
18. Postupak određivanja veličine opterećenja amiloidogenim plakovima u uzorku tkiva i/ili uzorku tjelesne tekućine, naznačen time što se sastoji u: a) ispitivanje uzorka tkiva ili uzorka tjelesne tekućine na prisutnost amiloidnog proteina humaniziranim protutijelom, ili fragmentom protutijela, u skladu s bilo kojim od patentnih zahtjeva 1-4; b) određivanju količine protutijela, ili fragmenta protutijela, vezanog na protein; i c) izračunavanju opterećenja plakovima u uzorku tkiva ili uzorku tjelesne tekućine.
19. Komplet namijenjen detektiranju i dijagnosticiranju bolesti i stanja povezanih s amiloidima, naznačen time što sadrži, u jednom ili više spremnika, humanizirano protutijelo, ili njegov fragment, u skladu s bilo kojim od patentnih zahtjeva 1-4, reagens za detektiranje, te upute za upotrebu protutijela.
20. Humanizirano protutijelo, ili njegov fragment, u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačeno time što je namijenjeno upotrebi u disagregiranju vlakana u topljive poli- i monomerne oblike.
21. Postupak in vitro disagregiranja prethodno nastalih vlakana beta-amiloida, naznačen time što se sastoji u stavljanju u kontakt protutijela, ili njegovog fragmenta, u skladu s bilo kojim od patentnih zahtjeva 2 i 3 s prethodno nastalim vlaknima beta-amiloida.
22. Humanizirano protutijelo, ili njegov fragment, u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačeno time što je protutijelo, ili njegov fragment, namijenjeno upotrebi u zaštiti neurona od propadanja uzrokovanog od strane Aβ.
23. Upotreba humaniziranog protutijela, ili njegovog fragmenta, u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačena time što je protutijelo, ili njegov fragment, namijenjeno pripravi medikamenta za sprječavanje degeneriranja neurona nakon izlaganja oligomeru Aβ.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06014730 | 2006-07-14 | ||
| EP06020765 | 2006-10-02 | ||
| US94328907P | 2007-06-11 | 2007-06-11 | |
| US94349907P | 2007-06-12 | 2007-06-12 | |
| EP07840408.4A EP2046833B9 (en) | 2006-07-14 | 2007-07-13 | Humanized antibody against amyloid beta |
| PCT/US2007/073504 WO2008011348A2 (en) | 2006-07-14 | 2007-07-13 | Humanized antibody against amyloid beta |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME01758B true ME01758B (me) | 2014-09-20 |
Family
ID=49474825
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2010-59A ME01075B (me) | 2006-07-14 | 2007-07-13 | Antitijela |
| MEP-2013-132A ME01758B (me) | 2006-07-14 | 2007-07-13 | Humanizirano protutijelo protiv amiloida beta |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2010-59A ME01075B (me) | 2006-07-14 | 2007-07-13 | Antitijela |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20160272699A1 (me) |
| EP (1) | EP3309172B1 (me) |
| KR (6) | KR20170098978A (me) |
| CN (3) | CN106831983B (me) |
| BR (1) | BRPI0714713B1 (me) |
| CR (1) | CR20140496A (me) |
| CY (1) | CY1114604T1 (me) |
| DK (2) | DK2046833T5 (me) |
| ES (2) | ES2436112T3 (me) |
| HU (1) | HUE038438T2 (me) |
| IL (1) | IL254065B (me) |
| LT (1) | LT2468770T (me) |
| ME (2) | ME01075B (me) |
| MY (2) | MY165105A (me) |
| NZ (1) | NZ607881A (me) |
| PH (1) | PH12012501882B1 (me) |
| PT (2) | PT2046833E (me) |
| RS (2) | RS56986B1 (me) |
| RU (1) | RU2668161C2 (me) |
| SI (2) | SI2468770T1 (me) |
| TR (1) | TR201802814T4 (me) |
| TW (2) | TWI608014B (me) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2011282536B2 (en) * | 2010-07-30 | 2015-12-24 | Ac Immune S.A. | Safe and functional humanized anti beta-amyloid antibody |
| HRP20210680T1 (hr) * | 2014-07-10 | 2021-06-11 | Bioarctic Ab | POBOLJŠANA PROTUTIJELA KOJA VEŽU Aβ PROTOFIBRIL |
| EP3464350A1 (en) * | 2016-06-07 | 2019-04-10 | Biogen International Neuroscience GmbH | Methods for treating alzheimer's disease |
| SG11201903867YA (en) * | 2016-11-01 | 2019-05-30 | Anaptysbio Inc | Antibodies directed against t cell immunoglobulin and mucin protein 3 (tim-3) |
| JP7118073B2 (ja) | 2017-01-09 | 2022-08-15 | テサロ， インコーポレイテッド | 抗ｔｉｍ－３抗体を用いてがんを処置する方法 |
| US12018069B2 (en) | 2018-06-28 | 2024-06-25 | The Trustees Of Columbia University In The City Of New York | Methods and compositions for imaging amyloid deposits |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| JPS6412935A (en) | 1987-07-02 | 1989-01-17 | Mitsubishi Electric Corp | Constant-speed travel device for vehicle |
| US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
| US5843708A (en) | 1988-01-05 | 1998-12-01 | Ciba-Geigy Corporation | Chimeric antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5112596A (en) | 1990-04-23 | 1992-05-12 | Alkermes, Inc. | Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability |
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