LT2285408T - Aminorūgščių sekos, nukreiptos prieš viruso apvalkalo baltymus, ir tokias sekas turintys polipeptidai, skirti virusinių ligų gydymui - Google Patents
Aminorūgščių sekos, nukreiptos prieš viruso apvalkalo baltymus, ir tokias sekas turintys polipeptidai, skirti virusinių ligų gydymuiInfo
- Publication number
- LT2285408T LT2285408T LTEP09757629.2T LT09757629T LT2285408T LT 2285408 T LT2285408 T LT 2285408T LT 09757629 T LT09757629 T LT 09757629T LT 2285408 T LT2285408 T LT 2285408T
- Authority
- LT
- Lithuania
- Prior art keywords
- polypeptides
- virus
- treatment
- amino acid
- acid sequences
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—RNA viruses
- C07K16/108—Orthomyxoviridae (F), e.g. influenza virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—RNA viruses
- C07K16/106—Picornaviridae (F), e.g. hepatitis A virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—RNA viruses
- C07K16/11—Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
-
- 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
-
- 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
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
-
- 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
- C07K2317/35—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
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/50—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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pulmonology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5905508P | 2008-06-05 | 2008-06-05 | |
| US9299108P | 2008-08-29 | 2008-08-29 | |
| US13913008P | 2008-12-19 | 2008-12-19 | |
| US14465309P | 2009-01-14 | 2009-01-14 | |
| US17291409P | 2009-04-27 | 2009-04-27 | |
| US17410809P | 2009-04-30 | 2009-04-30 | |
| PCT/EP2009/056975 WO2009147248A2 (en) | 2008-06-05 | 2009-06-05 | Amino acid sequences directed against envelope proteins of a virus and polypeptides comprising the same for the treatment of viral diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LT2285408T true LT2285408T (lt) | 2019-01-25 |
Family
ID=41055279
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LTEP09757629.2T LT2285408T (lt) | 2008-06-05 | 2009-06-05 | Aminorūgščių sekos, nukreiptos prieš viruso apvalkalo baltymus, ir tokias sekas turintys polipeptidai, skirti virusinių ligų gydymui |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US9193780B2 (lt) |
| EP (2) | EP3424526A1 (lt) |
| JP (2) | JP5809557B2 (lt) |
| CN (1) | CN102112155B (lt) |
| AU (1) | AU2009254501B2 (lt) |
| CA (1) | CA2726652A1 (lt) |
| CY (1) | CY1121687T1 (lt) |
| DK (1) | DK2285408T3 (lt) |
| ES (1) | ES2713864T3 (lt) |
| HR (1) | HRP20182195T1 (lt) |
| HU (1) | HUE042053T2 (lt) |
| LT (1) | LT2285408T (lt) |
| PL (1) | PL2285408T3 (lt) |
| PT (1) | PT2285408T (lt) |
| SI (1) | SI2285408T1 (lt) |
| WO (1) | WO2009147248A2 (lt) |
| ZA (1) | ZA201009135B (lt) |
Families Citing this family (106)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9023352B2 (en) | 2007-02-20 | 2015-05-05 | Tufts University | Methods, compositions and kits for treating a subject using a recombinant heteromultimeric neutralizing binding protein |
| LT2285408T (lt) * | 2008-06-05 | 2019-01-25 | Ablynx N.V. | Aminorūgščių sekos, nukreiptos prieš viruso apvalkalo baltymus, ir tokias sekas turintys polipeptidai, skirti virusinių ligų gydymui |
| CA2746395C (en) | 2008-12-10 | 2019-07-09 | Ablynx N.V. | Polypeptides comprising amino acid sequences directed against tie 2 for the treatment of diseases and disorders related to angiogenesis |
| AU2015200057B9 (en) * | 2009-06-05 | 2017-03-09 | Ablynx Nv | Monovalent, bivalent and trivalent anti human respiratory syncytial virus (hRSV) Nanobody constructs for the prevention and/or treatment of respiratory tract infections |
| CN102459332B (zh) * | 2009-06-05 | 2015-08-19 | 埃博灵克斯股份有限公司 | 用于预防和/或治疗呼吸道感染的单价、二价和三价抗人呼吸道合胞病毒(hrsv)纳米抗体构建体 |
| WO2011064382A1 (en) | 2009-11-30 | 2011-06-03 | Ablynx N.V. | Improved amino acid sequences directed against human respiratory syncytial virus (hrsv) and polypeptides comprising the same for the prevention and/or treatment of respiratory tract infections |
| SI2533761T1 (sl) | 2010-02-11 | 2019-08-30 | Ablynx N.V. | Postopki in sestavki za pripravo aerosolov |
| GB201014715D0 (en) | 2010-09-06 | 2010-10-20 | Vib Vzw | Nanobodies stabilizing functional conformational states of GPCRS |
| WO2012042026A1 (en) | 2010-09-30 | 2012-04-05 | Ablynx Nv | Biological materials related to c-met |
| US11644471B2 (en) | 2010-09-30 | 2023-05-09 | Ablynx N.V. | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
| US20120195900A1 (en) * | 2010-12-22 | 2012-08-02 | Abbott Laboratories | Tri-variable domain binding proteins and uses thereof |
| US9527925B2 (en) | 2011-04-01 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules binding to VEGF and ANG2 |
| AU2012273928A1 (en) | 2011-06-23 | 2014-02-06 | Ablynx Nv | Immunoglobulin single variable domains directed against IgE |
| LT3466972T (lt) | 2011-06-23 | 2026-06-25 | Ablynx Nv | Serumo albuminą surišantys baltymai |
| CA3141978A1 (en) | 2011-06-23 | 2012-12-27 | Ablynx Nv | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
| CA2880791A1 (en) * | 2011-08-03 | 2013-02-07 | Children's Medical Center Corporation | A broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza hemagglutinin |
| US9346884B2 (en) | 2011-09-30 | 2016-05-24 | Ablynx N.V. | Biological materials related to c-Met |
| CN108610421B (zh) | 2012-02-27 | 2022-08-19 | 阿布林克斯有限公司 | Cx3cr1结合多肽 |
| PL2831111T3 (pl) * | 2012-03-30 | 2019-09-30 | Boehringer Ingelheim International Gmbh | Cząsteczki wiążące Ang2 |
| US9969794B2 (en) | 2012-05-10 | 2018-05-15 | Visterra, Inc. | HA binding agents |
| US11339208B1 (en) | 2012-05-31 | 2022-05-24 | United States Of America As Represented By The Secretary Of The Air Force | Camelidae single-domain antibodies against Yersinia pestis and methods of use |
| WO2014087010A1 (en) | 2012-12-07 | 2014-06-12 | Ablynx N.V. | IMPROVED POLYPEPTIDES DIRECTED AGAINST IgE |
| EP2970397A2 (en) | 2013-03-14 | 2016-01-20 | University Of Washington Through Its Center For Commercialization | Polypeptides for treating and/or limiting influenza infection |
| UY35484A (es) * | 2013-03-15 | 2014-10-31 | Amgen Res Munich Gmbh | Molécula de unión de cadena simple que comprenden ABP de extremo N |
| EP2981286A4 (en) * | 2013-04-05 | 2016-08-24 | Hoffmann La Roche | ANTI-IL-4 ANTIBODIES AND BISPECIFIC ANTIBODIES AND USES THEREOF |
| US9637542B2 (en) * | 2013-08-21 | 2017-05-02 | Boehringer Ingelheim International Gmbh | CX3CR1-targeting imaging agents and their use in the diagnosis and treatment of disease |
| MX2016006486A (es) * | 2013-11-25 | 2016-08-05 | Oxford Biotherapeutics Ltd | Anticuerpos. |
| SG11201702688UA (en) * | 2014-10-10 | 2017-04-27 | Ablynx Nv | Methods of treating rsv infections |
| US11001625B2 (en) | 2014-12-10 | 2021-05-11 | Tufts University | VHH based binding antibodies for anthrax and botulinum toxins and methods of making and using therefor |
| EP3247407A4 (en) | 2015-01-21 | 2018-08-22 | Inhibrx LP | Non-immunogenic single domain antibodies |
| CA2975655C (en) * | 2015-02-05 | 2023-09-19 | Janssen Vaccines & Prevention B.V. | Binding molecules directed against influenza hemagglutinin and uses thereof |
| US11306139B2 (en) * | 2015-03-20 | 2022-04-19 | Ablynx N.V. | Glycosylated immunoglobulin single variable domains |
| WO2016156468A1 (en) | 2015-03-31 | 2016-10-06 | Vhsquared Limited | Polypeptides |
| AU2016239949A1 (en) | 2015-03-31 | 2017-09-07 | Sorriso Pharmaceuticals, Inc. | Peptide construct having a protease-cleavable linker |
| EP3277706A1 (en) * | 2015-03-31 | 2018-02-07 | VHsquared Limited | Polypeptide comprising an immunoglobulin chain variable domain which binds to clostridium difficile toxin b |
| EP3277719B1 (en) | 2015-03-31 | 2022-03-16 | Sorriso Pharmaceuticals, Inc. | Polypeptides |
| EP3297672B1 (en) | 2015-05-21 | 2021-09-01 | Harpoon Therapeutics, Inc. | Trispecific binding proteins and methods of use |
| EP3124042A1 (en) | 2015-07-28 | 2017-02-01 | VIB, vzw | Immunoglobulin single variable domain antibody against rsv prefusion f protein |
| RU2730671C2 (ru) | 2015-06-18 | 2020-08-24 | Виб Взв | Иммуноглобулин с одним вариабельным доменом против f-белка pcb |
| JP6807606B2 (ja) | 2015-07-16 | 2021-01-06 | インヒブルクス インコーポレイテッド | 多価及び多重特異性dr5結合融合タンパク質 |
| JP2017036258A (ja) * | 2015-08-07 | 2017-02-16 | パナソニックIpマネジメント株式会社 | インフルエンザウィルスに結合する抗体 |
| JP6975709B2 (ja) * | 2015-09-02 | 2021-12-01 | ヤンセン ファッシンズ アンド プリベンション ベーフェーJanssen Vaccines & Prevention B.V. | 安定化したウイルスクラスi融合タンパク質 |
| WO2017083627A1 (en) | 2015-11-13 | 2017-05-18 | Visterra, Inc. | Compositions and methods for treating and preventing influenza |
| CA3015347A1 (en) | 2016-02-24 | 2017-08-31 | Visterra, Inc. | Formulations of antibody molecules to influenza virus |
| KR102530742B1 (ko) | 2016-05-20 | 2023-05-09 | 하푼 테라퓨틱스, 인크. | 단일 도메인 혈청 알부민 결합 단백질 |
| HRP20251020T1 (hr) | 2016-05-20 | 2025-10-24 | Harpoon Therapeutics, Inc. | Proteini s jednolančanim varijabilnim fragmentom koji vežu cd3 |
| US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
| US11840569B2 (en) * | 2016-11-16 | 2023-12-12 | Ablynx N.V. | T cell recruiting polypeptides capable of binding CD123 and TCR alpha/beta |
| JP7215997B2 (ja) | 2016-11-23 | 2023-01-31 | ハープーン セラピューティクス,インク. | 前立腺特異的膜抗原(psma)を標的とする三重特異性タンパク質と使用方法 |
| KR102275008B1 (ko) | 2016-11-23 | 2021-07-13 | 하푼 테라퓨틱스, 인크. | 전립선 특이 막 항원 결합 단백질 |
| WO2018160754A2 (en) | 2017-02-28 | 2018-09-07 | Harpoon Therapeutics, Inc. | Inducible monovalent antigen binding protein |
| US10730954B2 (en) | 2017-05-12 | 2020-08-04 | Harpoon Therapeutics, Inc. | MSLN targeting trispecific proteins and methods of use |
| SG10202107880XA (en) | 2017-05-12 | 2021-09-29 | Harpoon Therapeutics Inc | Mesothelin binding proteins |
| AU2017435322A1 (en) * | 2017-10-11 | 2020-04-30 | Nanjing Legend Biotech Co., Ltd. | Compositions and methods for increasing protein half-life in a serum |
| CA3078969A1 (en) | 2017-10-13 | 2019-04-18 | Harpoon Therapeutics, Inc. | Trispecific proteins and methods of use |
| IL315737A (en) | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| KR20210005090A (ko) * | 2018-04-23 | 2021-01-13 | 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 | 키메라 벡터 |
| MX2020012217A (es) | 2018-05-14 | 2021-03-02 | Harpoon Therapeutics Inc | Porción de unión para activación condicional de moléculas de inmunoglobulina. |
| CN108794626B (zh) * | 2018-06-18 | 2021-10-12 | 上海大学 | 一种多肽以及能靶向HIV包膜蛋白gp120的金纳米抗体 |
| CN108640978A (zh) * | 2018-06-20 | 2018-10-12 | 上海大学 | 特异性结合HIV病毒上蛋白gp120的多肽及其应用 |
| RU2764740C1 (ru) * | 2018-08-09 | 2022-01-20 | Бейцзин Уиздомаб Байотекнолоджи Ко., Лтд | Биспецифическое антитело против вируса бешенства и его применение |
| JP7190675B2 (ja) | 2018-08-23 | 2022-12-16 | パナソニックIpマネジメント株式会社 | ノロウイルスに結合する抗体、複合体、それを用いた検出装置及び検出方法 |
| JP7190674B2 (ja) | 2018-08-23 | 2022-12-16 | パナソニックIpマネジメント株式会社 | ノロウイルスに結合する抗体、複合体、それを用いた検出装置及び検出方法 |
| CN109097341B (zh) * | 2018-08-28 | 2021-09-24 | 青岛农业大学 | 一种同时表达ha和hef的复制缺陷型重组流感病毒 |
| US12195544B2 (en) | 2018-09-21 | 2025-01-14 | Harpoon Therapeutics, Inc. | EGFR binding proteins and methods of use |
| CN119306844A (zh) | 2018-09-25 | 2025-01-14 | 哈普恩治疗公司 | Dll3结合蛋白及使用方法 |
| AU2019364823B2 (en) | 2018-10-25 | 2025-10-30 | Km Biologics Co., Ltd. | Modified CMV gB protein and CMV vaccine including same |
| WO2020144164A1 (en) | 2019-01-07 | 2020-07-16 | Bactolife Aps | Pathogen binding proteins |
| EP3946613A1 (en) | 2019-03-25 | 2022-02-09 | Visterra, Inc. | Compositions and methods for treating and preventing influenza |
| WO2020232303A1 (en) | 2019-05-14 | 2020-11-19 | Harpoon Therapeutics, Inc. | EpCAM BINDING PROTEINS AND METHODS OF USE |
| US12570736B2 (en) | 2019-06-21 | 2026-03-10 | Sorriso Pharmaceuticals, Inc. | Compositions |
| CA3144566A1 (en) | 2019-06-21 | 2020-12-24 | Sorriso Pharmaceuticals, Inc. | Polypeptides |
| JP7692844B2 (ja) | 2019-06-21 | 2025-06-16 | ソリッソ ファーマシューティカルズ,インク. | ポリペプチド |
| KR20220166787A (ko) * | 2020-02-06 | 2022-12-19 | 브이아이비 브이지더블유 | 코로나 바이러스 결합제 |
| BR112022016550A2 (pt) | 2020-02-21 | 2022-11-16 | Harpoon Therapeutics Inc | Proteínas de ligação a flt3 e métodos de uso |
| CN111393512B (zh) * | 2020-03-24 | 2021-03-02 | 北京中科微盾生物科技有限责任公司 | 一种抑制流感病毒的多肽及其在制备预防和治疗流感病毒感染药物中的应用 |
| JP7512413B2 (ja) * | 2020-03-31 | 2024-07-08 | ビオテウス・インコーポレイテッド | 抗pd-l1およびpd-l2抗体ならびにその誘導体および用途 |
| CN116194083B (zh) * | 2020-04-20 | 2025-01-24 | 华润生物医药有限公司 | 抗冠状病毒抗体和其用途 |
| US20210330700A1 (en) * | 2020-04-23 | 2021-10-28 | Johnson & Johnson Consumer Inc. | Methods and compositions for inhibiting influenza viruses using low molecular weight hydrophobically modified polymers and polyalkylene glycols |
| JP2023526274A (ja) * | 2020-05-12 | 2023-06-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Sars-cov2中和単一ドメイン抗体構築物 |
| WO2022006219A2 (en) | 2020-07-02 | 2022-01-06 | Trustees Of Tufts College | Vhh polypeptides that bind to clostridium difficile toxin b and methods of use thereof |
| CA3189896A1 (en) * | 2020-08-19 | 2022-02-24 | Yi Shi | Coronavirus nanobodies and methods for their use and identification |
| EP4221747A4 (en) * | 2020-09-29 | 2024-11-27 | Academia Sinica | Clec2 fusion protein and uses thereof |
| US20240109963A1 (en) * | 2020-11-16 | 2024-04-04 | Ab Therapeutics, Inc. | Multispecific antibodies and uses thereof |
| CN112851811B (zh) * | 2021-01-28 | 2022-08-09 | 姜国胜 | 一种cd44v6纳米抗体及其作为白血病研究试剂的应用 |
| JP2022165899A (ja) * | 2021-04-20 | 2022-11-01 | 株式会社デンソー | 融合体 |
| CN113234151B (zh) * | 2021-06-08 | 2022-02-15 | 皖南医学院第一附属医院(皖南医学院弋矶山医院) | 一种基于靶向SARS-CoV2病毒S蛋白的三聚体纳米抗体的CAR-NK的研制 |
| US11970548B2 (en) * | 2021-08-27 | 2024-04-30 | Innovative Cellular Therapeutics Holdings, Ltd. | Nanobody target GCC and uses in chimeric antigen receptor cell therapy |
| WO2023039528A1 (en) * | 2021-09-10 | 2023-03-16 | The Board Of Trustees Of The Leland Stanford Junior University | Nanobody-mediated control of gene expression and epigenetic memory |
| WO2023177821A2 (en) * | 2022-03-16 | 2023-09-21 | Myeloid Therapeutics, Inc. | Binding domains and methods of use thereof |
| US20260159606A1 (en) * | 2022-09-27 | 2026-06-11 | Vib Vzw | Antivirals Against Human Parainfluenza Virus |
| US20240415974A1 (en) | 2022-12-23 | 2024-12-19 | Ablynx N.V. | Protein-based conjugation carriers |
| IL322519A (en) | 2023-02-17 | 2025-10-01 | Ablynx Nv | Polypeptides that bind to the neonatal fc receptor |
| CN116375852B (zh) * | 2023-03-10 | 2024-02-02 | 华南农业大学 | 重组荧光纳米抗体及其在制备狂犬病病毒检测试剂中的应用 |
| CN117777279B (zh) * | 2023-06-13 | 2025-02-14 | 康元医疗科技(大连)有限公司 | 一种纳米抗体、包含该纳米抗体的多肽及其应用 |
| WO2024259305A1 (en) | 2023-06-14 | 2024-12-19 | The Broad Institute, Inc. | Vhh polypeptides that bind to mesothelin, compositions and methods of use thereof |
| CN116987194B (zh) * | 2023-09-26 | 2023-12-26 | 江西乐成欣生生物技术研究有限责任公司 | 人st2抗原的模拟表位肽的抗独特型纳米抗体及应用 |
| CN117683137B (zh) * | 2023-12-04 | 2024-09-17 | 江苏省农业科学院 | 靶向新城疫病毒和h9亚型禽流感病毒的重组双特异性纳米抗体及其制备方法和应用 |
| CN122438859A (zh) | 2023-12-22 | 2026-07-21 | 阿布林克斯有限公司 | 用于核内递送的基于蛋白质的缀合载体 |
| CN117843801B (zh) * | 2023-12-29 | 2024-08-02 | 北京贝来药业有限公司 | 以白介素家族成员为靶点的新型抗体以及下游产品 |
| CN117986360B (zh) * | 2024-02-01 | 2024-08-27 | 生物岛实验室 | Il18蛋白的特异性抗体及其制备方法与应用 |
| WO2025262150A2 (en) | 2024-06-18 | 2025-12-26 | Ablynx Nv | Antibody-recruiting molecules |
| WO2026060159A1 (en) * | 2024-09-13 | 2026-03-19 | Gilead Sciences, Inc. | Vhhs against hsv and uses of the same |
| WO2026076388A1 (en) | 2024-10-03 | 2026-04-09 | The Broad Institute, Inc. | Vhh polypeptides that bind to claudin-18, compositions and methods of use thereof |
| CN119978135B (zh) * | 2025-01-02 | 2025-11-21 | 生物岛实验室 | Sumo标签蛋白的特异性抗体及其制备方法与应用 |
| CN120623329B (zh) * | 2025-01-15 | 2026-04-10 | 中国人民解放军军事科学院军事医学研究院 | 抗埃博拉病毒vp40蛋白的纳米抗体3e07及在病毒检测中的应用 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1120945A (en) | 1964-08-11 | 1968-07-24 | Fisons Pharmaceuticals Ltd | Applicator in combination with a pressurised aerosol dispensing container |
| FI903489A7 (fi) | 1988-11-11 | 1990-07-10 | Medical Res Council | Yhden osan sisältävät ligandit, näitä ligandeja sisältävät reseptorit, menetelmiä niiden valmistamiseksi sekä ligandien ja reseptorien käytt ö |
| SE509359C2 (sv) | 1989-08-01 | 1999-01-18 | Cemu Bioteknik Ab | Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel |
| CA2090126C (en) | 1990-08-02 | 2002-10-22 | John W. Schrader | Methods for the production of proteins with a desired function |
| US5824307A (en) * | 1991-12-23 | 1998-10-20 | Medimmune, Inc. | Human-murine chimeric antibodies against respiratory syncytial virus |
| CA2135408A1 (en) | 1992-05-08 | 1993-11-25 | Peter C. Keck | Chimeric multivalent protein analogues and methods of use thereof |
| US5811524A (en) | 1995-06-07 | 1998-09-22 | Idec Pharmaceuticals Corporation | Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof |
| US6020182A (en) | 1996-07-12 | 2000-02-01 | Connaught Laboratories Limited | Subunit respiratory syncytial virus vaccine preparation |
| JP2001510329A (ja) | 1996-11-01 | 2001-07-31 | スミスクライン・ビーチャム・コーポレイション | ヒトモノクローナル抗体 |
| US7122636B1 (en) * | 1997-02-21 | 2006-10-17 | Genentech, Inc. | Antibody fragment-polymer conjugates and uses of same |
| AU3596599A (en) | 1998-01-26 | 1999-08-09 | Unilever Plc | Method for producing antibody fragments |
| ATE276359T1 (de) | 1999-01-19 | 2004-10-15 | Unilever Nv | Verfahren zur herstellung von antikörperfragmenten |
| CN1252264C (zh) * | 1999-04-22 | 2006-04-19 | 荷兰联合利华有限公司 | 利用单价抗原-结合蛋白抑制病毒感染 |
| US6133571A (en) * | 1999-04-26 | 2000-10-17 | Lockheed Martin Corporation | Resonant cavity field enhancing boundary |
| US7550143B2 (en) * | 2005-04-06 | 2009-06-23 | Ibc Pharmaceuticals, Inc. | Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses |
| CO5280147A1 (es) | 1999-05-18 | 2003-05-30 | Smithkline Beecham Corp | Anticuerpo humano monoclonal |
| US7608681B2 (en) | 1999-12-24 | 2009-10-27 | Genentech, Inc. | Methods and compositions for prolonging elimination half-times of bioactive compounds |
| US20030190598A1 (en) | 2000-05-26 | 2003-10-09 | Jasmid Tanha | Single-domain antigen-binding antibody fragments derived from llama antibodies |
| CA2441903C (en) | 2000-05-26 | 2012-07-31 | National Research Council Of Canada | Single-domain brain-targeting antibody fragments derived from llama antibodies |
| US6818216B2 (en) * | 2000-11-28 | 2004-11-16 | Medimmune, Inc. | Anti-RSV antibodies |
| US7211395B2 (en) | 2001-03-09 | 2007-05-01 | Dyax Corp. | Serum albumin binding moieties |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| US20060073141A1 (en) | 2001-06-28 | 2006-04-06 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| JP4213586B2 (ja) | 2001-09-13 | 2009-01-21 | 株式会社抗体研究所 | ラクダ抗体ライブラリーの作製方法 |
| JP2005289809A (ja) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 突然変異重鎖抗体 |
| EP1456410A2 (en) | 2001-12-11 | 2004-09-15 | AlgoNomics N.V. | Method for displaying loops from immunoglobulin domains in different contexts |
| CN1622828A (zh) * | 2001-12-18 | 2005-06-01 | 基因创新有限公司 | 用于诊断和治疗用途的纯化的丙型肝炎病毒外被蛋白 |
| JP4323317B2 (ja) | 2001-12-21 | 2009-09-02 | フラームス・インテルウニフェルシタイル・インステイチュート・フォール・ビオテヒノロヒー・ヴェーゼットウェー(ヴェーイーベー・ヴェーゼットウェー) | 可変領域配列のクローニング方法 |
| AU2003210060B2 (en) | 2002-03-22 | 2010-02-25 | Aprogen, Inc. | Humanized antibody and process for preparing same |
| US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
| CN1678634A (zh) | 2002-06-28 | 2005-10-05 | 多曼蒂斯有限公司 | 免疫球蛋白单个变体抗原结合区及其特异性构建体 |
| WO2004051268A1 (en) | 2002-12-03 | 2004-06-17 | Celltech R & D Limited | Assay for identifying antibody producing cells |
| GB0228210D0 (en) | 2002-12-03 | 2003-01-08 | Babraham Inst | Single chain antibodies |
| GB0312481D0 (en) | 2003-05-30 | 2003-07-09 | Celltech R&D Ltd | Antibodies |
| WO2004106375A1 (en) * | 2003-05-30 | 2004-12-09 | Merus Biopharmaceuticals B.V. I.O. | Fab library for the preparation of anti vegf and anti rabies virus fabs |
| US7070786B2 (en) | 2003-06-06 | 2006-07-04 | Centocor, Inc. | RSV proteins, antibodies, compositions, methods and uses |
| JP2007521234A (ja) | 2003-08-12 | 2007-08-02 | ウィリアム エム ヤーブロー | 尋常性ざ瘡の治療薬及び使用方法 |
| ES2385829T3 (es) | 2003-08-20 | 2012-08-01 | Ucb Pharma, S.A. | Métodos para obtener anticuerpos |
| EP1737971B1 (en) * | 2004-01-20 | 2017-08-16 | Merus N.V. | Mixtures of binding proteins |
| AU2005214988A1 (en) | 2004-02-17 | 2005-09-01 | Absalus, Inc. | Super-humanized antibodies against respiratory syncytial virus |
| EP1771205B1 (en) | 2004-06-18 | 2016-10-26 | Ambrx, Inc. | Novel antigen-binding polypeptides and their uses |
| US20050279676A1 (en) | 2004-06-21 | 2005-12-22 | Izzy Zuhair A | Fluid filter assembly for a dispensing faucet |
| EP1776383B1 (en) | 2004-07-22 | 2014-08-20 | Erasmus University Medical Center Rotterdam | Binding molecules |
| US7563443B2 (en) | 2004-09-17 | 2009-07-21 | Domantis Limited | Monovalent anti-CD40L antibody polypeptides and compositions thereof |
| JP2008513540A (ja) * | 2004-09-21 | 2008-05-01 | メディミューン,インコーポレーテッド | 呼吸器合胞体ウイルスに対する抗体及び該ウイルス用のワクチンを製造する方法 |
| 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 |
| WO2006040154A2 (en) | 2004-10-14 | 2006-04-20 | Dublin City University | Prokaryotic two hybrid system |
| TW200636064A (en) | 2004-10-28 | 2006-10-16 | Centocor Inc | Anti-respiratory syncytial virus antibodies, antigens and uses thereof |
| CA2585891A1 (en) | 2004-10-29 | 2006-05-11 | Medimmune, Inc. | Methods of preventing and treating rsv infections and related conditions |
| JP2008528010A (ja) | 2005-01-31 | 2008-07-31 | アブリンクス ナームローゼ フェンノートシャップ | 重鎖抗体の可変ドメイン配列を作出する方法 |
| CA2604032C (en) | 2005-04-06 | 2017-08-22 | Ibc Pharmaceuticals, Inc. | Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses |
| JP4976376B2 (ja) * | 2005-04-08 | 2012-07-18 | メディミューン,エルエルシー | 哺乳動物メタニューモウイルスに対する抗体 |
| AU2007237501A1 (en) | 2006-04-14 | 2007-10-25 | Ablynx N.V. | DP-78-like nanobodies |
| WO2008000279A1 (en) | 2006-06-26 | 2008-01-03 | Aida Centre, S.L. | Blister package integrating rfid based tags |
| JP2010500876A (ja) | 2006-08-18 | 2010-01-14 | アブリンクス エン.ヴェー. | Il−6媒介性シグナル伝達に関連する疾患及び障害の治療のための、il−6rに指向性を有するアミノ酸配列及びこれを含むポリペプチド |
| WO2008049897A1 (en) | 2006-10-27 | 2008-05-02 | Ablynx N.V. | Intranasal delivery of polypeptides and proteins |
| JP2010511397A (ja) | 2006-12-05 | 2010-04-15 | アブリンクス エン.ヴェー. | 血清タンパク質と結合可能なペプチド |
| AU2007337983A1 (en) | 2006-12-22 | 2008-07-03 | Ablynx N.V. | Anti-chemokine (CCL2, CCL3, CCL5, CXCL11, CXCL12) single-domain antibodies |
| EP2096121A1 (en) | 2008-02-29 | 2009-09-02 | Institut Pasteur Of Shanghai | Antiviral peptides comprising lipid attachment signals and methods of use |
| LT2285408T (lt) * | 2008-06-05 | 2019-01-25 | Ablynx N.V. | Aminorūgščių sekos, nukreiptos prieš viruso apvalkalo baltymus, ir tokias sekas turintys polipeptidai, skirti virusinių ligų gydymui |
| ES2701649T3 (es) | 2009-01-14 | 2019-02-25 | Ablynx Nv | Administración pulmonar de dominios variables individuales de inmunoglobulina y constructos de los mismos |
| CA2759370C (en) | 2009-04-30 | 2020-02-11 | Peter Schotte | Method for the production of domain antibodies |
| CN102459332B (zh) | 2009-06-05 | 2015-08-19 | 埃博灵克斯股份有限公司 | 用于预防和/或治疗呼吸道感染的单价、二价和三价抗人呼吸道合胞病毒(hrsv)纳米抗体构建体 |
| WO2011064382A1 (en) | 2009-11-30 | 2011-06-03 | Ablynx N.V. | Improved amino acid sequences directed against human respiratory syncytial virus (hrsv) and polypeptides comprising the same for the prevention and/or treatment of respiratory tract infections |
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| US20110182897A1 (en) | 2011-07-28 |
| US20190077847A1 (en) | 2019-03-14 |
| JP2011521662A (ja) | 2011-07-28 |
| DK2285408T3 (en) | 2019-02-04 |
| WO2009147248A3 (en) | 2010-07-15 |
| ES2713864T3 (es) | 2019-05-24 |
| CN102112155B (zh) | 2016-08-10 |
| US20200123233A1 (en) | 2020-04-23 |
| US10550174B2 (en) | 2020-02-04 |
| CY1121687T1 (el) | 2020-07-31 |
| ZA201009135B (en) | 2012-06-27 |
| CA2726652A1 (en) | 2009-12-10 |
| AU2009254501B2 (en) | 2014-07-31 |
| PL2285408T3 (pl) | 2019-05-31 |
| HUE042053T2 (hu) | 2019-06-28 |
| US11518799B2 (en) | 2022-12-06 |
| JP5809557B2 (ja) | 2015-11-11 |
| EP2285408B1 (en) | 2018-10-24 |
| US9834595B2 (en) | 2017-12-05 |
| SI2285408T1 (sl) | 2019-02-28 |
| US20160152693A1 (en) | 2016-06-02 |
| PT2285408T (pt) | 2019-02-01 |
| JP2015156867A (ja) | 2015-09-03 |
| US9193780B2 (en) | 2015-11-24 |
| EP3424526A1 (en) | 2019-01-09 |
| HRP20182195T1 (hr) | 2019-02-22 |
| EP2285408A2 (en) | 2011-02-23 |
| AU2009254501A1 (en) | 2009-12-10 |
| CN102112155A (zh) | 2011-06-29 |
| WO2009147248A2 (en) | 2009-12-10 |
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