BR112019012691A2 - anticorpos contra a lif e seus usos - Google Patents
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- BR112019012691A2 BR112019012691A2 BR112019012691-0A BR112019012691A BR112019012691A2 BR 112019012691 A2 BR112019012691 A2 BR 112019012691A2 BR 112019012691 A BR112019012691 A BR 112019012691A BR 112019012691 A2 BR112019012691 A2 BR 112019012691A2
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- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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- 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
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
- C07K16/248—IL-6
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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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- A—HUMAN NECESSITIES
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- A61K2039/55527—Interleukins
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- C—CHEMISTRY; METALLURGY
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- 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
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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
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
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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
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- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
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- 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]
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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
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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Landscapes
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- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
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- Biophysics (AREA)
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- Epidemiology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Endocrinology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| EP17382683 | 2017-10-13 | ||
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| BR112019012691A2 true BR112019012691A2 (pt) | 2019-11-19 |
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| LT3555132T (lt) * | 2016-12-19 | 2024-02-26 | Medimmune Limited | Antikūnai prieš lif ir jų panaudojimas |
| SG11202009966SA (en) * | 2018-04-12 | 2020-11-27 | Medimmune Ltd | Combination of lif inhibitors and pd-1 axis inhibitors for use in treating cancer |
| EP4069736A1 (en) * | 2019-12-04 | 2022-10-12 | MedImmune Limited | Antibodies against lif and uses thereof |
| TWI841810B (zh) | 2020-01-24 | 2024-05-11 | 日商西斯美股份有限公司 | 提升抗體對抗原之親和性的方法及其用途 |
| CN117043189A (zh) | 2020-12-31 | 2023-11-10 | 诺纳生物(苏州)有限公司 | 人lifr抗原结合蛋白及其制备方法和应用 |
| TW202306993A (zh) * | 2021-05-14 | 2023-02-16 | 美商建南德克公司 | Trem2之促效劑 |
Family Cites Families (40)
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| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
| AU4231393A (en) | 1992-05-08 | 1993-12-13 | Genentech Inc. | Antibodies to leukemia inhibitory factor |
| AU4241693A (en) | 1992-05-15 | 1993-12-13 | Re/Map Incorporated | Electromagnetic shielding for a liquid conditioning device |
| WO1994029351A2 (en) | 1993-06-16 | 1994-12-22 | Celltech Limited | Antibodies |
| EP1287832B1 (en) | 1995-04-24 | 2005-12-21 | Genentech, Inc. | Use of leukemia inhibitory factor antagonist |
| ES2694002T3 (es) | 1999-01-15 | 2018-12-17 | Genentech, Inc. | Polipéptido que comprende una región Fc de IgG1 humana variante |
| US6399857B1 (en) * | 1999-09-22 | 2002-06-04 | Paradigm Genetics, Inc. | Modified nucleotide sequence encoding a LexA DNA binding domain optimized for arabidopsis species |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| WO2003085093A2 (en) | 2002-04-01 | 2003-10-16 | Human Genome Sciences, Inc. | Antibodies that specifically bind to gmad |
| US7361740B2 (en) | 2002-10-15 | 2008-04-22 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
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| AP2007004243A0 (en) | 2005-04-25 | 2007-12-31 | Pfizer | Antibodies to myostatin |
| US8768629B2 (en) | 2009-02-11 | 2014-07-01 | Caris Mpi, Inc. | Molecular profiling of tumors |
| EP2084185A4 (en) | 2006-10-04 | 2010-11-17 | Scripps Research Inst | HUMAN ANTIBODIES THAT NEUTRALIZE HUMAN METAPNEUMOVIRUS |
| CN101440128A (zh) | 2007-11-21 | 2009-05-27 | 中国人民解放军第二军医大学 | 人脑胶质瘤中差异表达的蛋白及其用途 |
| CA2742969A1 (en) * | 2008-11-07 | 2010-05-14 | Fabrus Llc | Anti-dll4 antibodies and uses thereof |
| ES2363358B1 (es) | 2009-04-03 | 2012-06-21 | FUNDACIÓ INSTITUT DE RECERCA HOSPITAL UNIVERSITARI VALL D'HEBRON (Titular al | Agentes terapéuticos para el tratamiento de enfermedades asociadas con una proliferación celular indeseable. |
| US8221753B2 (en) * | 2009-09-30 | 2012-07-17 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
| EP2483406A2 (en) | 2009-09-30 | 2012-08-08 | President and Fellows of Harvard College | Methods for modulation of autophagy through the modulation of autophagy-inhibiting gene products |
| WO2011057144A2 (en) | 2009-11-06 | 2011-05-12 | La Jolla Institute For Allergy And Immunology | Methods for modulating lif activity, treating immune disorders and diseases, and stimulatings immune responses |
| CN102167742B (zh) | 2010-02-25 | 2014-05-14 | 上海百迈博制药有限公司 | 一种全人源抗her2单克隆抗体、其制备方法及用途 |
| EP2371860A1 (en) * | 2010-04-05 | 2011-10-05 | Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron | Antibody recognising human leukemia inhibitory factor (LIF) and use of anti-LIF antibodies in the treatment of diseases associated with unwanted cell proliferation |
| US9790268B2 (en) | 2012-09-12 | 2017-10-17 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
| IL275376B2 (en) | 2013-03-11 | 2024-01-01 | Genzyme Corp | Hyperglycosylated binding polypeptides |
| US20140314741A1 (en) | 2013-04-18 | 2014-10-23 | Developmen Center For Biotechnology | Human Antibody against Interleukin-20 and Treatment for Inflammatory Diseases |
| US10633429B2 (en) | 2013-08-20 | 2020-04-28 | Japan Science And Technology Agency | Human antibody κ type light chain complex-containing composition and method for producing same |
| US20150056195A1 (en) | 2013-08-23 | 2015-02-26 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Compositions and methods for inihibiting tumorigenicity of senescent cancer cells induced by chemotherapy |
| US20160237158A1 (en) | 2013-09-23 | 2016-08-18 | Institut National De La Santé Et Da La Recherche Médicale (Inserm) | Methods and Compositions for Targeting Tumor Microenvironment and for preventing Metastasis |
| JP6496719B2 (ja) | 2013-10-09 | 2019-04-03 | リサーチ ディベロップメント ファウンデーション | モノクローナルolfml−3抗体及びその使用 |
| TWI486172B (zh) | 2013-11-08 | 2015-06-01 | Univ Chang Gung | 鼻咽癌治療的醫藥 |
| WO2015106080A2 (en) | 2014-01-10 | 2015-07-16 | Anaptysbio, Inc. | Antibodies directed against interleukin-33 (il-33) |
| EP4640239A2 (en) | 2014-03-19 | 2025-10-29 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
| WO2016040657A1 (en) | 2014-09-10 | 2016-03-17 | The Regents Of The University Of California | TARGETING K-RAS-MEDIATED SIGNALING PATHWAYS AND MALIGNANCY BY ANTI-hLIF ANTIBODIES |
| EP3173483A1 (en) * | 2015-11-27 | 2017-05-31 | Fundació Privada Institut d'Investigació Oncològica de Vall-Hebron | Agents for the treatment of diseases associated with undesired cell proliferation |
| US10583191B2 (en) * | 2016-12-19 | 2020-03-10 | Mosaic Biomedicals Slu | Antibodies against LIF and uses thereof |
| LT3555132T (lt) * | 2016-12-19 | 2024-02-26 | Medimmune Limited | Antikūnai prieš lif ir jų panaudojimas |
| SG11202009966SA (en) * | 2018-04-12 | 2020-11-27 | Medimmune Ltd | Combination of lif inhibitors and pd-1 axis inhibitors for use in treating cancer |
| KR20210024007A (ko) * | 2018-06-18 | 2021-03-04 | 메디뮨 리미티드 | 암이 있는 개체에서 항-lif 항체 치료에 대한 반응을 개선하기 위한 방법 |
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