ES2946083T3 - Proteínas de unión a antígeno para proproteína convertasa subtilisina kexina tipo 9 (PCSK9) - Google Patents
Proteínas de unión a antígeno para proproteína convertasa subtilisina kexina tipo 9 (PCSK9) Download PDFInfo
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- ES2946083T3 ES2946083T3 ES19207796T ES19207796T ES2946083T3 ES 2946083 T3 ES2946083 T3 ES 2946083T3 ES 19207796 T ES19207796 T ES 19207796T ES 19207796 T ES19207796 T ES 19207796T ES 2946083 T3 ES2946083 T3 ES 2946083T3
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- antigen
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| US1063008P | 2008-01-09 | 2008-01-09 | |
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Families Citing this family (235)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1283851B1 (en) | 2000-05-26 | 2012-03-28 | Immunex Corporation | Use of il-4r antibodies and compositions thereof |
| EP2835429B1 (en) | 2006-05-11 | 2017-12-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
| EP2083861A4 (en) | 2006-11-07 | 2010-11-24 | Merck Sharp & Dohme | ANTAGONISTS OF PCSK9 |
| EP2615114B1 (en) | 2007-08-23 | 2022-04-06 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
| JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
| CL2008002775A1 (es) | 2007-09-17 | 2008-11-07 | Amgen Inc | Uso de un agente de unión a esclerostina para inhibir la resorción ósea. |
| EP2245039A4 (en) * | 2008-01-31 | 2012-06-06 | Alnylam Pharmaceuticals Inc | OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN |
| AR070315A1 (es) * | 2008-02-07 | 2010-03-31 | Merck & Co Inc | Anticuerpos 1b20 antagonistas de pcsk9 |
| AR070316A1 (es) | 2008-02-07 | 2010-03-31 | Merck & Co Inc | Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9) |
| EP2641918A3 (en) | 2008-08-04 | 2014-03-05 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
| TWI445716B (zh) | 2008-09-12 | 2014-07-21 | Rinat Neuroscience Corp | Ｐｃｓｋ９拮抗劑類 |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| US20130064834A1 (en) | 2008-12-15 | 2013-03-14 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to pcsk9 |
| US8357371B2 (en) | 2008-12-15 | 2013-01-22 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to PCSK9 |
| NZ597504A (en) * | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
| WO2011028938A1 (en) * | 2009-09-02 | 2011-03-10 | Alnylam Pharmaceuticals, Inc. | Methods for lowering serum cholestrol in a subject using inhibition of pcsk9 |
| PT2473605T (pt) | 2009-09-03 | 2018-05-28 | Pfizer Vaccines Llc | Vacina pcsk9 |
| US20120219558A1 (en) * | 2009-09-25 | 2012-08-30 | Yan Ni | Antagonists of pcsk9 |
| US20120208209A1 (en) * | 2009-10-30 | 2012-08-16 | Marina Ichetovkin | Pcsk9 immunoassay |
| CN102639150A (zh) * | 2009-10-30 | 2012-08-15 | 默沙东公司 | Ax213和ax132 pcsk9拮抗剂和变体 |
| WO2011053759A1 (en) * | 2009-10-30 | 2011-05-05 | Merck Sharp & Dohme Corp. | Ax1 and ax189 pcsk9 antagonists and variants |
| AR079336A1 (es) * | 2009-12-11 | 2012-01-18 | Irm Llc | Antagonistas de la pro-proteina convertasa-subtilisina/quexina tipo 9 (pcsk9) |
| US20130058891A1 (en) | 2010-01-12 | 2013-03-07 | Jay K. Kolls | Kexin-Derived Vaccines to Prevent or Treat Fungal Infections |
| US9181538B1 (en) | 2010-01-12 | 2015-11-10 | Karen A. Norris | Kexin-based vaccines to prevent or treat fungal infections |
| AU2011225716A1 (en) * | 2010-03-11 | 2012-09-27 | Pfizer Inc. | Antibodies with pH dependent antigen binding |
| JO3756B1 (ar) | 2010-11-23 | 2021-01-31 | Regeneron Pharma | اجسام مضادة بشرية لمستقبلات الجلوكاجون |
| AR084938A1 (es) | 2011-01-28 | 2013-07-10 | Sanofi Sa | Anticuerpos humanos contra la proproteina convertasa subtilisina/kexina tipo 9 (anti pcsk9) para usar en metodos para tratar grupos de pacientes |
| EP2650016A1 (en) * | 2011-01-28 | 2013-10-16 | Sanofi | Human antibodies to PSCK9 for use in methods of treatment based on particular dosage regimens (11565) |
| US11998479B2 (en) | 2011-02-04 | 2024-06-04 | Seed Health, Inc. | Method and system for addressing adverse effects on the oral microbiome and restoring gingival health caused by sodium lauryl sulphate exposure |
| US11951139B2 (en) | 2015-11-30 | 2024-04-09 | Seed Health, Inc. | Method and system for reducing the likelihood of osteoporosis |
| US12257272B2 (en) | 2015-12-24 | 2025-03-25 | Seed Health, Inc. | Method and system for reducing the likelihood of developing depression in an individual |
| US9730967B2 (en) | 2011-02-04 | 2017-08-15 | Katherine Rose Kovarik | Method and system for treating cancer cachexia |
| US11951140B2 (en) | 2011-02-04 | 2024-04-09 | Seed Health, Inc. | Modulation of an individual's gut microbiome to address osteoporosis and bone disease |
| US10314865B2 (en) | 2011-02-04 | 2019-06-11 | Katherine Rose Kovarik | Method and system for treating cancer and other age-related diseases by extending the healthspan of a human |
| US12279989B2 (en) | 2011-02-04 | 2025-04-22 | Seed Health, Inc. | Method and system for increasing beneficial bacteria and decreasing pathogenic bacteria in the oral cavity |
| US11844720B2 (en) | 2011-02-04 | 2023-12-19 | Seed Health, Inc. | Method and system to reduce the likelihood of dental caries and halitosis |
| JP2014511378A (ja) * | 2011-02-11 | 2014-05-15 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｐｃｓｋ９アンタゴニスト |
| KR20230005405A (ko) | 2011-02-25 | 2023-01-09 | 추가이 세이야쿠 가부시키가이샤 | ＦｃγＲＩＩｂ 특이적 Ｆｃ 항체 |
| SI2702146T1 (sl) | 2011-04-28 | 2019-06-28 | The Board Of Trustees Of The Leland Stanford Junior University | Identifikacija polinukleotidov, povezanih z vzorcem |
| JP6081714B2 (ja) * | 2011-04-28 | 2017-02-15 | 株式会社ビー・エム・エル | 高コレステロール血症と動脈硬化の検出方法 |
| AR088782A1 (es) * | 2011-04-29 | 2014-07-10 | Sanofi Sa | Sistemas de ensayo y metodos para identificar y caracterizar farmacos hipolipemiantes |
| JOP20200043A1 (ar) * | 2011-05-10 | 2017-06-16 | Amgen Inc | طرق معالجة أو منع الاضطرابات المختصة بالكوليسترول |
| US20140004122A1 (en) * | 2011-05-10 | 2014-01-02 | Amgen Inc. | Methods for treating or preventing cholesterol related disorders |
| WO2012170607A2 (en) * | 2011-06-10 | 2012-12-13 | Novartis Ag | Use of pcsk9 antagonists |
| WO2012168491A1 (en) * | 2011-06-10 | 2012-12-13 | Novartis Ag | Pharmaceutical formulations of pcsk9 antagonists |
| CN103827300A (zh) | 2011-06-30 | 2014-05-28 | 中外制药株式会社 | 异源二聚化多肽 |
| EP2731623A1 (en) * | 2011-07-14 | 2014-05-21 | Pfizer Inc | Treatment with anti-pcsk9 antibodies |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| ES2773111T3 (es) | 2011-09-16 | 2020-07-09 | Regeneron Pharma | Inhibidor de la proproteína convertasa subtilisina/kexina 9 (PCSK9) para su uso en la reducción de los niveles de lipoproteína (a) |
| AR087715A1 (es) | 2011-09-16 | 2014-04-09 | Lilly Co Eli | Anticuerpos anti pcsk9 y usos de los mismos |
| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| LT3045187T (lt) | 2011-10-14 | 2019-07-10 | Amgen Inc. | Injekcijų įrenginys ir surinkimo būdas |
| US20140228539A1 (en) * | 2011-10-21 | 2014-08-14 | Tanvex Biologics Corp. | Separation of acetylated proteins from unacetylated proteins |
| RU2739792C1 (ru) | 2011-11-30 | 2020-12-28 | Чугаи Сейяку Кабусики Кайся | Содержащий лекарственное средство переносчик в клетку для формирования иммунного комплекса |
| JP6188681B2 (ja) | 2012-04-09 | 2017-08-30 | 第一三共株式会社 | 抗ｆｇｆｒ２抗体 |
| US9321681B2 (en) * | 2012-04-27 | 2016-04-26 | United States Gypsum Company | Dimensionally stable geopolymer compositions and method |
| EA039663B1 (ru) * | 2012-05-03 | 2022-02-24 | Амген Инк. | Применение антитела против pcsk9 для снижения сывороточного холестерина лпнп и лечения связанных с холестерином расстройств |
| US9255154B2 (en) * | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| WO2013170367A1 (en) * | 2012-05-17 | 2013-11-21 | The University Of British Columbia | Methods and uses for proprotein convert ase subtilisin kexin 9 (pcsk9) inhibitors |
| EP2667197B1 (en) | 2012-05-25 | 2015-09-16 | Zora Biosciences OY | Sensitive efficacy and specificity biomarkers for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition |
| JP2013253842A (ja) | 2012-06-06 | 2013-12-19 | Univ Of Tokyo | ｐＨ依存的に標的分子に結合するペプチドのスクリーニング方法 |
| AR091462A1 (es) * | 2012-06-15 | 2015-02-04 | Genentech Inc | Anticuerpos anti-pcsk9, formulaciones, dosificacion y metodos de uso |
| KR20150041662A (ko) * | 2012-08-13 | 2015-04-16 | 리제너론 파아마슈티컬스, 인크. | Ｐｈ-의존적 결합 특성을 갖는 항-ｐｃｓｋ9 항체 |
| SG10201709559PA (en) | 2012-08-24 | 2017-12-28 | Chugai Pharmaceutical Co Ltd | Fcγriib-specific fc region variant |
| UY35148A (es) | 2012-11-21 | 2014-05-30 | Amgen Inc | Immunoglobulinas heterodiméricas |
| PT2929031T (pt) | 2012-12-05 | 2018-01-19 | Alnylam Pharmaceuticals Inc | Composições de irna de pcsk9 e métodos de seu uso |
| KR102249779B1 (ko) | 2012-12-27 | 2021-05-07 | 추가이 세이야쿠 가부시키가이샤 | 헤테로이량화 폴리펩티드 |
| US10287317B2 (en) * | 2013-02-15 | 2019-05-14 | Srx Cardio, Llc | Proprotein convertase subtilisin kexin type 9 (PCSK9) allosteric binding ligands to modulate serum low density lipoprotein (LDL) levels |
| WO2014150983A2 (en) * | 2013-03-15 | 2014-09-25 | Amgen Inc. | Human antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 |
| WO2014144817A2 (en) | 2013-03-15 | 2014-09-18 | Amgen Inc. | Inhibitory polypeptides specific to wnt inhibitors |
| WO2014149699A1 (en) | 2013-03-15 | 2014-09-25 | Eli Lilly And Company | Bifunctional protein |
| CA2897825C (en) | 2013-03-22 | 2022-05-24 | Scott R. Gibson | Injector and method of assembly |
| CN105246914B (zh) | 2013-04-02 | 2021-08-27 | 中外制药株式会社 | Fc区变体 |
| US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
| JP6417118B2 (ja) * | 2013-05-31 | 2018-10-31 | 株式会社ビー・エム・エル | Ｐｃｓｋ９測定用標準物質 |
| EP2862877A1 (en) | 2013-10-18 | 2015-04-22 | Sanofi | Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9 |
| TW201534324A (zh) | 2013-06-07 | 2015-09-16 | Sanofi Sa | 藉由投與ｐｃｓｋ９抑制劑抑制動脈粥狀硬化的方法 |
| US20150004174A1 (en) * | 2013-06-28 | 2015-01-01 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolemia |
| JP6267792B2 (ja) * | 2013-06-28 | 2018-01-24 | アムジエン・インコーポレーテツド | ホモ接合性家族性高コレステロール血症の治療方法 |
| EP3041863A4 (en) | 2013-09-05 | 2017-08-16 | Amgen Inc. | Fc-containing molecules exhibiting predictable, consistent, and reproducible glycoform profiles |
| AU2014340171B2 (en) | 2013-10-24 | 2019-05-30 | Amgen Inc. | Injector and method of assembly |
| CN106062003A (zh) | 2013-11-12 | 2016-10-26 | 赛诺菲生物技术公司 | 用于与pcsk9抑制剂一起使用的给药方案 |
| DE202014010499U1 (de) | 2013-12-17 | 2015-10-20 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
| US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
| US8945560B1 (en) | 2014-07-15 | 2015-02-03 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
| WO2015092394A1 (en) * | 2013-12-17 | 2015-06-25 | Kymab Limited | Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations |
| US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
| GB2521356B (en) * | 2013-12-17 | 2018-10-10 | Kymab Ltd | Antibodies for use in treating conditions related to specific PCKS9 variants and associated diagnostic methods |
| US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
| US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
| US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
| FR3014695A1 (enExample) * | 2013-12-17 | 2015-06-19 | Kymab Ltd | |
| EP2975058A1 (en) * | 2014-07-15 | 2016-01-20 | Kymab Limited | Antibodies for use in treating conditions related to specific PCSK9 variants in specific patient populations |
| DE112014005975T5 (de) * | 2013-12-17 | 2016-09-15 | Kymab Limited | Menschliche Ziele |
| US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
| US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
| US9045545B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision medicine by targeting PD-L1 variants for treatment of cancer |
| EP2886557A1 (en) * | 2013-12-17 | 2015-06-24 | Kymab Limited | Antibodies for use in treating conditions related to specific PCSK9 variants in specific patient populations |
| US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
| US9067998B1 (en) | 2014-07-15 | 2015-06-30 | Kymab Limited | Targeting PD-1 variants for treatment of cancer |
| US12246043B2 (en) | 2013-12-20 | 2025-03-11 | Seed Health, Inc. | Topical application to treat acne vulgaris |
| US12329783B2 (en) | 2013-12-20 | 2025-06-17 | Seed Health, Inc. | Method and system to improve the health of a person's skin microbiome |
| US11833177B2 (en) | 2013-12-20 | 2023-12-05 | Seed Health, Inc. | Probiotic to enhance an individual's skin microbiome |
| US11969445B2 (en) | 2013-12-20 | 2024-04-30 | Seed Health, Inc. | Probiotic composition and method for controlling excess weight, obesity, NAFLD and NASH |
| US11839632B2 (en) | 2013-12-20 | 2023-12-12 | Seed Health, Inc. | Topical application of CRISPR-modified bacteria to treat acne vulgaris |
| US12005085B2 (en) | 2013-12-20 | 2024-06-11 | Seed Health, Inc. | Probiotic method and composition for maintaining a healthy vaginal microbiome |
| US11998574B2 (en) | 2013-12-20 | 2024-06-04 | Seed Health, Inc. | Method and system for modulating an individual's skin microbiome |
| US11826388B2 (en) | 2013-12-20 | 2023-11-28 | Seed Health, Inc. | Topical application of Lactobacillus crispatus to ameliorate barrier damage and inflammation |
| US11980643B2 (en) | 2013-12-20 | 2024-05-14 | Seed Health, Inc. | Method and system to modify an individual's gut-brain axis to provide neurocognitive protection |
| CN106460033B (zh) | 2013-12-30 | 2021-12-24 | 阿特雷卡公司 | 使用核酸条形码分析与单细胞缔合的核酸 |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| MX377275B (es) | 2014-05-16 | 2025-03-07 | Amgen Inc | Ensayo para detectar poblaciones celulares linfocitos t colaboradores 1 (th1) y linfocitos t colaboradores (th2). |
| WO2015200438A1 (en) * | 2014-06-24 | 2015-12-30 | Eleven Biotherapeutics, Inc. | High affinity antibodies against pcsk9 |
| AU2015289874A1 (en) | 2014-07-14 | 2017-02-02 | Amgen Inc. | Crystalline antibody formulations |
| US10611850B2 (en) | 2014-07-14 | 2020-04-07 | Amgen Inc. | Crystalline antibody formulations |
| DE202015009006U1 (de) | 2014-07-15 | 2016-08-19 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
| EP4328245A3 (en) * | 2014-07-15 | 2024-06-05 | Kymab Ltd. | Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations |
| EP3332790A1 (en) | 2014-07-15 | 2018-06-13 | Kymab Limited | Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations |
| US9150660B1 (en) | 2014-07-15 | 2015-10-06 | Kymab Limited | Precision Medicine by targeting human NAV1.8 variants for treatment of pain |
| US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
| KR20240017117A (ko) | 2014-07-16 | 2024-02-06 | 사노피 바이오테크놀로지 | 이형접합성 가족성 고콜레스테롤혈증(heFH) 환자의 치료방법 |
| US9982052B2 (en) | 2014-08-05 | 2018-05-29 | MabQuest, SA | Immunological reagents |
| PL3177644T3 (pl) | 2014-08-05 | 2021-06-14 | MabQuest SA | Immunologiczne reagenty wiążące do PD-1 |
| JP2017523980A (ja) | 2014-08-06 | 2017-08-24 | ライナット ニューロサイエンス コーポレイション | Ｌｄｌ−コレステロールを低下させるための方法 |
| WO2016020799A1 (en) | 2014-08-06 | 2016-02-11 | Rinat Neuroscience Corp. | Methods for reducing ldl-cholesterol |
| WO2016023916A1 (en) | 2014-08-12 | 2016-02-18 | Kymab Limited | Treatment of disease using ligand binding to targets of interest |
| US9657099B2 (en) | 2014-09-16 | 2017-05-23 | Regeneron Pharmaceuticals, Inc. | Anti-glucagon antibodies |
| WO2016046684A1 (en) | 2014-09-23 | 2016-03-31 | Pfizer Inc. | Treatment with anti-pcsk9 antibodies |
| AU2015335743B2 (en) | 2014-10-23 | 2020-12-24 | Amgen Inc. | Reducing viscosity of pharmaceutical formulations |
| WO2016071701A1 (en) | 2014-11-07 | 2016-05-12 | Kymab Limited | Treatment of disease using ligand binding to targets of interest |
| IL278014B2 (en) | 2014-12-19 | 2023-10-01 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variable FC regions and methods of use |
| CN107108729A (zh) | 2015-02-05 | 2017-08-29 | 中外制药株式会社 | 包含离子浓度依赖性的抗原结合结构域的抗体，fc区变体，il‑8‑结合抗体，及其应用 |
| CN105461809B (zh) * | 2015-02-11 | 2018-10-12 | 康融东方（广东）医药有限公司 | Pcsk9抗体、其药物组合物及其用途 |
| WO2016145139A1 (en) | 2015-03-10 | 2016-09-15 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind psma |
| EP3973958A3 (en) * | 2015-03-20 | 2022-06-22 | Aarhus Universitet | Inhibitors of pcsk9 for treatment of lipoprotein metabolism disorders |
| JP2018516624A (ja) * | 2015-04-15 | 2018-06-28 | コンシーヴァルブ エルエルシー | 自然心臓弁、ステント装着された心臓弁またはバイオプロテーゼの狭窄、閉塞または石灰化を抑制するためのデバイスおよび方法 |
| CN105037554B (zh) * | 2015-06-12 | 2019-04-12 | 成都贝爱特生物科技有限公司 | 抗人pcsk9抗体的制备及其用途 |
| EA201890519A1 (ru) | 2015-08-18 | 2018-07-31 | Ридженерон Фармасьютикалз, Инк. | Ингибирующие антитела против pcsk9 для лечения пациентов с гиперлипидемией, подвергающихся аферезу липопротеинов |
| AU2016332900C1 (en) | 2015-09-29 | 2024-07-04 | Amgen Inc. | ASGR inhibitors |
| WO2017055966A1 (en) | 2015-10-01 | 2017-04-06 | Pfizer Inc. | Low viscosity antibody compositions |
| CN106589127A (zh) * | 2015-10-16 | 2017-04-26 | 钜川生物医药 | 一种pcsk9抗体及其制备方法和应用 |
| CN105348390B (zh) * | 2015-10-26 | 2018-08-28 | 北京智仁美博生物科技有限公司 | 抗人pcsk9单克隆抗体 |
| US20180363000A1 (en) * | 2015-12-14 | 2018-12-20 | The Trustees Of The University Of Pennsylvania | Aav-anti pcsk9 antibody constructs and uses thereof |
| EP3394098A4 (en) | 2015-12-25 | 2019-11-13 | Chugai Seiyaku Kabushiki Kaisha | ANTI-MYOSTATIN ANTIBODIES AND METHODS OF USE |
| RU2739208C2 (ru) * | 2015-12-31 | 2020-12-21 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Анти-pcsk9 антитело, его антигенсвязывающий фрагмент и их медицинское применение |
| EP3401336A4 (en) | 2016-01-05 | 2020-01-22 | Jiangsu Hengrui Medicine Co., Ltd. | ANTI-PCSK9 ANTIBODIES, ASSOCIATED ANTIGEN BINDING FRAGMENT, AND ASSOCIATED MEDICAL APPLICATION |
| US11214617B2 (en) | 2016-01-22 | 2022-01-04 | MabQuest SA | Immunological reagents |
| EP3405497A2 (en) | 2016-01-22 | 2018-11-28 | Mabquest SA | Immunological reagents |
| GB201604124D0 (en) | 2016-03-10 | 2016-04-27 | Ucb Biopharma Sprl | Pharmaceutical formulation |
| WO2017163049A1 (en) | 2016-03-21 | 2017-09-28 | Kymab Limited | Anti-malarial antibodies that bind circumsporozoite protein |
| US11066464B2 (en) | 2016-03-21 | 2021-07-20 | Kymab Limited | Anti-malarial antibodies that bind circumsporozoite protein |
| CN107266575B (zh) * | 2016-04-07 | 2021-12-24 | 天士力生物医药股份有限公司 | 前蛋白转化酶枯草溶菌素kexin 9型的结合蛋白及其应用 |
| EP3458988B1 (en) | 2016-05-16 | 2023-10-18 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
| CN107474140B (zh) * | 2016-06-08 | 2022-06-03 | 常州博嘉生物医药科技有限公司 | Pcsk9特异性的结合蛋白mv072及其应用 |
| WO2018029474A2 (en) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anti-icos antibodies |
| CN116903741A (zh) | 2016-06-20 | 2023-10-20 | 科马布有限公司 | 特异性结合于pd-l1的抗体或其抗原结合片段及其用途 |
| TWI831965B (zh) | 2016-08-05 | 2024-02-11 | 日商中外製藥股份有限公司 | Il-8相關疾病之治療用或預防用組成物 |
| TWI782920B (zh) * | 2016-09-20 | 2022-11-11 | 中國大陸商上海藥明生物技術有限公司 | 新型抗-pcsk9抗體 |
| JP2020502991A (ja) * | 2016-09-20 | 2020-01-30 | ウーシー バイオロジクス アイルランド リミテッド | 新規抗ｐｃｓｋ９抗体 |
| US11459401B2 (en) | 2016-10-06 | 2022-10-04 | Amgen Inc. | Reduced viscosity protein pharmaceutical formulations |
| US20190248888A1 (en) | 2016-10-20 | 2019-08-15 | Regeneron Pharmaceuticals, Inc. | Methods of lowering blood glucose levels |
| WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| CN106822881A (zh) * | 2016-12-09 | 2017-06-13 | 四川大学 | 一种针对pcsk9的抗高血脂蛋白疫苗 |
| CN108239150A (zh) | 2016-12-24 | 2018-07-03 | 信达生物制药(苏州)有限公司 | 抗pcsk9抗体及其用途 |
| MX2019008432A (es) | 2017-01-17 | 2019-11-18 | Amgen Inc | Dispositivos de inyeccion y metodos relacionados de uso y ensamblaje. |
| CA3221995C (en) | 2017-02-08 | 2024-05-28 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
| US11752258B2 (en) | 2017-02-17 | 2023-09-12 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
| SG11201907646YA (en) | 2017-02-20 | 2019-09-27 | Dragonfly Therapeutics Inc | Proteins binding her2, nkg2d and cd16 |
| JP7377596B2 (ja) | 2017-02-22 | 2023-11-10 | アムジエン・インコーポレーテツド | 低粘度、高濃度エボロクマブ製剤及びそれらの製造方法 |
| US10093731B2 (en) | 2017-02-24 | 2018-10-09 | Kindred Biosciences, Inc. | Anti-IL31 antibodies for veterinary use |
| EP3596225A1 (en) | 2017-03-14 | 2020-01-22 | Amgen Inc. | Control of total afucosylated glycoforms of antibodies produced in cell culture |
| US12023041B2 (en) | 2017-03-21 | 2024-07-02 | Teleflex Medical Incorporated | Clip applier |
| EP3600082A4 (en) | 2017-03-21 | 2020-09-16 | Teleflex Medical Incorporated | SURGICAL STAPLE AND STAPLE APPLICATOR |
| EP3630157A4 (en) * | 2017-05-31 | 2021-01-13 | North Carolina Central University | OPTIMIZATION OF AN ACTIVE PCSK9 TEST |
| CN107029243A (zh) * | 2017-06-08 | 2017-08-11 | 厦门大学 | 一种多肽桥连的双酰腙连接键应用于醛衍生药物的递送 |
| GB201709970D0 (en) | 2017-06-22 | 2017-08-09 | Kymab Ltd | Bispecific antigen-binding molecules |
| EP3655063A1 (en) | 2017-07-21 | 2020-05-27 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
| EP3658203B2 (en) | 2017-07-25 | 2025-10-01 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
| US11484648B2 (en) | 2017-07-25 | 2022-11-01 | Amgen Inc. | Drug delivery device with container access system and related method of assembly |
| MA49897A (fr) | 2017-08-18 | 2020-06-24 | Amgen Inc | Injecteur sur-corps avec patch adhésif stérile |
| JP6913566B2 (ja) * | 2017-08-23 | 2021-08-04 | 協同油脂株式会社 | グリース組成物 |
| MA50611A (fr) | 2017-10-04 | 2020-08-12 | Amgen Inc | Adaptateur d'écoulement destiné à un dispositif d'administration de médicament |
| EP3703778A1 (en) | 2017-11-03 | 2020-09-09 | Amgen Inc. | System and approaches for sterilizing a drug delivery device |
| WO2019098212A1 (en) | 2017-11-14 | 2019-05-23 | Chugai Seiyaku Kabushiki Kaisha | Anti-c1s antibodies and methods of use |
| WO2019099324A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Door latch mechanism for drug delivery device |
| GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
| JP6639463B2 (ja) * | 2017-12-21 | 2020-02-05 | アムジエン・インコーポレーテツド | ホモ接合性家族性高コレステロール血症の治療方法 |
| US12110342B2 (en) * | 2018-01-31 | 2024-10-08 | The Wistar Institute Of Anatomy And Biology | Nucleic acid monoclonal antibodies targeting PCSK9 and methods of use |
| PT3749346T (pt) | 2018-02-08 | 2024-09-05 | Dragonfly Therapeutics Inc | Combinações de domínios variáveis de anticorpos dirigidas ao receptor nkg2d |
| KR20200118824A (ko) | 2018-02-08 | 2020-10-16 | 드래곤플라이 쎄라퓨틱스, 인크. | 자연 살해 세포를 활성화시키는 다중-특이성 결합 단백질을 수반하는 암의 병용 요법 |
| CA3091424A1 (en) | 2018-02-20 | 2019-08-29 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind cd33, nkg2d, and cd16, and methods of use |
| MX2020008683A (es) * | 2018-02-20 | 2020-12-07 | Dragonfly Therapeutics Inc | Dominios variables de anticuerpo que se dirigen a cd33 y sus usos. |
| CN111954719B (zh) | 2018-03-26 | 2025-07-18 | 美国安进公司 | 细胞培养物中产生的抗体的总去岩藻糖基化糖型 |
| IL316596A (en) | 2018-03-30 | 2024-12-01 | Amgen Inc | C-terminal antibody variants |
| JP2021532167A (ja) | 2018-06-05 | 2021-11-25 | アンジ ファーマ（ユーエス）エルエルシー | 膵炎を治療するための組成物及び方法 |
| AU2019318083A1 (en) | 2018-08-08 | 2021-02-25 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind BCMA, NKG2D and CD16, and methods of use |
| CA3108646A1 (en) | 2018-08-08 | 2020-02-13 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and a tumor-associated antigen |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| CN112839960B (zh) | 2018-08-10 | 2024-09-06 | 中外制药株式会社 | 抗cd137抗原结合分子及其应用 |
| EP3856047A4 (en) | 2018-09-26 | 2022-06-22 | Teleflex Medical Incorporated | STAPLER APPLICATOR WITH STABILIZING ELEMENT |
| BR112021009373A2 (pt) * | 2018-11-16 | 2021-08-17 | Memorial Sloan Kettering Cancer Center | anticorpos para mucina-16 e métodos de uso dos mesmos |
| GB201820687D0 (en) | 2018-12-19 | 2019-01-30 | Kymab Ltd | Antagonists |
| CN109776680B (zh) * | 2019-01-25 | 2020-05-12 | 浙江蓝盾药业有限公司 | 抗人pcsk9单克隆抗体及其用途 |
| JP2022532282A (ja) | 2019-05-15 | 2022-07-14 | 中外製薬株式会社 | 抗原結合分子、薬学的組成物、および方法 |
| US12264366B2 (en) | 2019-05-17 | 2025-04-01 | Regeneron Pharmaceuticals, Inc. | Genome-based methods for reducing cardiovascular risk |
| WO2021050989A1 (en) * | 2019-09-13 | 2021-03-18 | Duke University | Zika antibodies and their use |
| WO2021058597A1 (en) | 2019-09-24 | 2021-04-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of determining whether a subject is at risk of developing arterial plaques |
| GB201913846D0 (en) | 2019-09-25 | 2019-11-06 | King S College London | Biomarker |
| BR112022005583A2 (pt) | 2019-09-26 | 2022-09-20 | Amgen Inc | Métodos para a produção de composições de anticorpos |
| US20230312750A1 (en) * | 2019-11-18 | 2023-10-05 | Ad Pharmaceuticals Co., Ltd. | Anti-pcsk9 antibody and use thereof |
| MX2022006495A (es) | 2019-11-29 | 2022-09-07 | Kymab Ltd | Tratamiento para la sobrecarga fisiologica de hierro. |
| KR20210095781A (ko) | 2020-01-24 | 2021-08-03 | 주식회사 에이프릴바이오 | 항원결합 단편 및 생리활성 이펙터 모이어티로 구성된 융합 컨스트럭트를 포함하는 다중결합항체 및 이를 포함하는 약학조성물 |
| MX2022013944A (es) | 2020-05-06 | 2022-11-30 | Dragonfly Therapeutics Inc | Proteinas que se unen al receptor activador de celulas asesinas naturales grupo 2 miembro d (nkg2d), cumulo de diferenciacion (cd16) y miembro a de la familia de dominios de lectina tipo c 12 (clec12a). |
| US20230273126A1 (en) | 2020-06-04 | 2023-08-31 | Amgen Inc. | Assessment of cleaning procedures of a biotherapeutic manufacturing process |
| AU2021360897A1 (en) | 2020-10-15 | 2023-05-25 | Amgen Inc. | Relative unpaired glycans in antibody production methods |
| JP2024508894A (ja) | 2021-03-03 | 2024-02-28 | ドラゴンフライ セラピューティクス， インコーポレイテッド | Ｎｋｇ２ｄ、ｃｄ１６、及び腫瘍関連抗原に結合する多特異性結合タンパク質を使用して癌を治療する方法 |
| JP2024511853A (ja) | 2021-03-31 | 2024-03-15 | カイマブ・リミテッド | Ｇｄｆ１５シグナル伝達の治療的阻害剤 |
| WO2022207785A1 (en) | 2021-03-31 | 2022-10-06 | Kymab Limited | Antibodies to gfral |
| WO2022243378A1 (en) | 2021-05-18 | 2022-11-24 | Kymab Limited | Uses of anti-icos antibodies |
| GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
| AU2022289365A1 (en) | 2021-06-07 | 2023-12-14 | Amgen Inc. | Using fucosidase to control afucosylation level of glycosylated proteins |
| CN113480650B (zh) * | 2021-06-30 | 2022-01-28 | 徐州医科大学 | 一种全人源靶向cd276的car-t细胞的制备方法及应用 |
| WO2023059607A1 (en) | 2021-10-05 | 2023-04-13 | Amgen Inc. | Fc-gamma receptor ii binding and glycan content |
| WO2023076419A2 (en) * | 2021-10-27 | 2023-05-04 | Twist Bioscience Corporation | Sars-cov-2 antibodies and methods of use |
| CN116948030B (zh) | 2022-04-25 | 2024-11-19 | 武汉大学 | 抗asgr1单克隆抗体及其应用 |
| WO2023215725A1 (en) | 2022-05-02 | 2023-11-09 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
| US20250340641A1 (en) | 2022-05-18 | 2025-11-06 | Kymab Limited | Uses of anti-icos antibodies |
| WO2024220916A1 (en) | 2023-04-20 | 2024-10-24 | Amgen Inc. | Methods of determining relative unpaired glycan content |
| WO2025036347A1 (zh) * | 2023-08-14 | 2025-02-20 | 信立泰(成都)生物技术有限公司 | Pcsk9抑制剂用于治疗或预防胆固醇相关疾病的方法 |
| WO2025038600A1 (en) | 2023-08-14 | 2025-02-20 | Amgen Inc. | Methods for reducing yellow color |
| WO2025101820A1 (en) | 2023-11-08 | 2025-05-15 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
Family Cites Families (211)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US896507A (en) | 1908-04-06 | 1908-08-18 | Theodore J Asch | Sweat-band. |
| US1063008A (en) | 1913-03-15 | 1913-05-27 | William E Budd | Vehicle-tire. |
| US3180193A (en) | 1963-02-25 | 1965-04-27 | Benedict David | Machines for cutting lengths of strip material |
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS5612114B2 (enExample) | 1974-06-07 | 1981-03-18 | ||
| US4263428A (en) | 1978-03-24 | 1981-04-21 | The Regents Of The University Of California | Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same |
| US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4444784A (en) * | 1980-08-05 | 1984-04-24 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
| AU548996B2 (en) | 1980-02-04 | 1986-01-09 | Merck & Co., Inc. | Tetrahydro-2h-pyran-2-one derivatives |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| EP0088046B1 (de) | 1982-02-17 | 1987-12-09 | Ciba-Geigy Ag | Lipide in wässriger Phase |
| HUT35524A (en) | 1983-08-02 | 1985-07-29 | Hoechst Ag | Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance |
| EP0143949B1 (en) | 1983-11-01 | 1988-10-12 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Pharmaceutical composition containing urokinase |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| US4740461A (en) | 1983-12-27 | 1988-04-26 | Genetics Institute, Inc. | Vectors and methods for transformation of eucaryotic cells |
| DE3675588D1 (de) | 1985-06-19 | 1990-12-20 | Ajinomoto Kk | Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist. |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US4959455A (en) | 1986-07-14 | 1990-09-25 | Genetics Institute, Inc. | Primate hematopoietic growth factors IL-3 and pharmaceutical compositions |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| WO1988001649A1 (en) | 1986-09-02 | 1988-03-10 | Genex Corporation | Single polypeptide chain binding molecules |
| US4912040A (en) | 1986-11-14 | 1990-03-27 | Genetics Institute, Inc. | Eucaryotic expression system |
| GB8823869D0 (en) * | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| FI94339C (fi) | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| FR2664073A1 (fr) | 1990-06-29 | 1992-01-03 | Thomson Csf | Moyens de marquage d'objets, procede de realisation et dispositif de lecture. |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| EP0546091B1 (en) | 1990-08-29 | 2007-01-24 | Pharming Intellectual Property BV | Homologous recombination in mammalian cells |
| WO1992003918A1 (en) | 1990-08-29 | 1992-03-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| WO1992022670A1 (en) | 1991-06-12 | 1992-12-23 | Genpharm International, Inc. | Early detection of transgenic embryos |
| WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
| WO1992022645A1 (en) | 1991-06-14 | 1992-12-23 | Genpharm International, Inc. | Transgenic immunodeficient non-human animals |
| JP2648897B2 (ja) | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| DE69233745D1 (de) | 1991-12-02 | 2008-10-23 | Cambridge Antibody Tech | Herstellung von Autoantikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken |
| US5869619A (en) * | 1991-12-13 | 1999-02-09 | Xoma Corporation | Modified antibody variable domains |
| EP1291360A1 (en) | 1991-12-13 | 2003-03-12 | Xoma Corporation | Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof |
| WO1994000569A1 (en) | 1992-06-18 | 1994-01-06 | Genpharm International, Inc. | Methods for producing transgenic non-human animals harboring a yeast artificial chromosome |
| NZ255101A (en) | 1992-07-24 | 1997-08-22 | Cell Genesys Inc | A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor |
| US6066718A (en) | 1992-09-25 | 2000-05-23 | Novartis Corporation | Reshaped monoclonal antibodies against an immunoglobulin isotype |
| US5981175A (en) | 1993-01-07 | 1999-11-09 | Genpharm Internation, Inc. | Methods for producing recombinant mammalian cells harboring a yeast artificial chromosome |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625825A (en) | 1993-10-21 | 1997-04-29 | Lsi Logic Corporation | Random number generating apparatus for an interface unit of a carrier sense with multiple access and collision detect (CSMA/CD) ethernet data network |
| US5643763A (en) | 1994-11-04 | 1997-07-01 | Genpharm International, Inc. | Method for making recombinant yeast artificial chromosomes by minimizing diploid doubling during mating |
| WO1996034096A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| ATE483733T1 (de) | 1995-06-14 | 2010-10-15 | Univ California | Hochaffine humane antikörper gegen tumorantigene |
| US6127977A (en) | 1996-11-08 | 2000-10-03 | Cohen; Nathan | Microstrip patch antenna with fractal structure |
| EP0773288A3 (en) | 1995-08-29 | 1997-07-09 | Kirin Brewery | Chimera animal and its method of manufacture |
| GB9610992D0 (en) | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
| WO1998001119A2 (en) | 1996-07-09 | 1998-01-15 | Merck & Co., Inc. | Pharmaceutical compositions comprising simvastatin |
| EP0852951A1 (de) | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
| CA2722378C (en) | 1996-12-03 | 2015-02-03 | Amgen Fremont Inc. | Human antibodies that bind tnf.alpha. |
| US6133426A (en) | 1997-02-21 | 2000-10-17 | Genentech, Inc. | Humanized anti-IL-8 monoclonal antibodies |
| US20080103090A1 (en) * | 1997-03-07 | 2008-05-01 | Human Genome Sciences, Inc. | Human Secreted Proteins |
| US20070224663A1 (en) * | 1997-03-07 | 2007-09-27 | Human Genome Sciences, Inc. | Human Secreted Proteins |
| US20060223088A1 (en) * | 1997-03-07 | 2006-10-05 | Rosen Craig A | Human secreted proteins |
| US20060223090A1 (en) * | 1997-03-07 | 2006-10-05 | Rosen Craig A | Polynucleotides encoding human secreted proteins |
| US20070015696A1 (en) * | 1997-03-07 | 2007-01-18 | Rosen Craig A | 621 human secreted proteins |
| US7968689B2 (en) | 1997-03-07 | 2011-06-28 | Human Genome Sciences, Inc. | Antibodies to HSDEK49 polypeptides |
| US7411051B2 (en) * | 1997-03-07 | 2008-08-12 | Human Genome Sciences, Inc. | Antibodies to HDPPA04 polypeptide |
| US20060246483A1 (en) * | 1997-03-07 | 2006-11-02 | Rosen Craig A | 337 human secreted proteins |
| US20070055056A1 (en) * | 1997-03-07 | 2007-03-08 | Rosen Craig A | 251 human secreted proteins |
| US7368531B2 (en) * | 1997-03-07 | 2008-05-06 | Human Genome Sciences, Inc. | Human secreted proteins |
| US20050197285A1 (en) * | 1997-03-07 | 2005-09-08 | Rosen Craig A. | Human secreted proteins |
| US20070059302A1 (en) | 1997-04-07 | 2007-03-15 | Genentech, Inc. | Anti-vegf antibodies |
| US6252050B1 (en) | 1998-06-12 | 2001-06-26 | Genentech, Inc. | Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method |
| FR2784749B1 (fr) | 1998-10-14 | 2000-12-29 | Instruments Sa | Appareil de caracterisation optique de materiau en couche mince |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| GB2343233A (en) | 1998-10-28 | 2000-05-03 | Whitnash Plc | Torsional vibration damper. |
| NL1011069C2 (nl) | 1999-01-19 | 2000-07-20 | Well Engineering Partners B V | Werkwijze en installatie voor het inbrengen van een buis in een boorgat in de aardbodem. |
| US6833268B1 (en) | 1999-06-10 | 2004-12-21 | Abgenix, Inc. | Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions |
| EP1514933A1 (en) * | 1999-07-08 | 2005-03-16 | Research Association for Biotechnology | Secretory protein or membrane protein |
| US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
| US20030119038A1 (en) * | 1999-09-09 | 2003-06-26 | Bingham Brendan William | NARC1, novel subtilase-like homologs |
| US7029895B2 (en) * | 1999-09-27 | 2006-04-18 | Millennium Pharmaceuticals, Inc. | 27411, a novel human PGP synthase |
| US20100291099A1 (en) | 1999-09-27 | 2010-11-18 | Millennium Pharmaceuticals, Inc. | Novel 27411, 23413, 22438, 23553, 25278, 26212, narc sc1, narc 10a, narc 1, narc 12, narc 13, narc17, narc 25, narc 3, narc 4, narc 7, narc 8, narc 11, narc 14a, narc 15, narc 16, narc 19, narc 20, narc 26, narc 27, narc 28, narc 30, narc 5, narc 6, narc 9, narc 10c, narc 8b, narc 9, narc2a, narc 16b, narc 1c, narc 1a, narc 25, 86604 and 32222 molecules and uses therefor |
| US20110230392A1 (en) | 1999-10-22 | 2011-09-22 | Millennium Pharmaceuticals, Inc. | Novel narc sc1, narc 10a, narc 1, narc 12, narc 13, narc17, narc 25, narc 3, narc 4, narc 7, narc 8, narc 11, narc 14a, narc 15, narc 16, narc 19, narc 20, narc 26, narc 27, narc 28, narc 30, narc 5, narc 6, narc 9, narc 10c, narc 8b, narc 9, narc2a, narc 16b, narc 1c, narc 1a, and narc 25 molecules and uses therefor |
| WO2001031007A2 (en) | 1999-10-22 | 2001-05-03 | Millennium Pharmaceuticals, Inc. | Nucleic acid molecules derived from rat brain and programmed cell death models |
| US20020081679A1 (en) | 1999-10-22 | 2002-06-27 | Millennium Pharmaceuticals, Inc. | NARC8 programmed cell-death-associated molecules and uses thereof |
| AU2001241461A1 (en) | 2000-02-07 | 2001-08-14 | Millennium Pharmaceuticals, Inc. | Narc-1, novel subtilase-like homologs |
| JP3753917B2 (ja) | 2000-03-17 | 2006-03-08 | 茨木精機株式会社 | 包装体の整列搬出方法及びその装置 |
| AU2001259432B2 (en) | 2000-05-03 | 2005-04-21 | Amgen Inc. | Modified peptides, comprising an FC domain, as therapeutic agents |
| CA2411971A1 (en) | 2000-06-16 | 2001-12-27 | Incyte Genomics, Inc. | Proteases |
| AU2001280471A1 (en) | 2000-08-11 | 2002-02-25 | Eli Lilly And Company | Novel secreted proteins and their uses |
| ATE442862T2 (de) * | 2000-10-12 | 2009-10-15 | Genentech Inc | Niederviskose konzentrierte proteinformulierungen |
| US20050101529A1 (en) * | 2000-12-08 | 2005-05-12 | Henry Yue | Protein modification and maintenance molecules |
| WO2003038063A2 (en) | 2001-03-21 | 2003-05-08 | Human Genome Sciences, Inc. | Human secreted proteins |
| US20070173473A1 (en) | 2001-05-18 | 2007-07-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
| US20040023243A1 (en) * | 2001-06-13 | 2004-02-05 | Yue Henry | Proteases |
| IL159177A0 (en) | 2001-06-20 | 2004-06-01 | Prochon Biotech Ltd | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| US20040038242A1 (en) * | 2001-07-30 | 2004-02-26 | Edmonds Brian Taylor | Novel secreted proteins and their uses |
| JP2006503547A (ja) | 2002-02-11 | 2006-02-02 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 生物兵器防衛のための免疫療法 |
| US6875433B2 (en) | 2002-08-23 | 2005-04-05 | The United States Of America As Represented By The Secretary Of The Army | Monoclonal antibodies and complementarity-determining regions binding to Ebola glycoprotein |
| NZ538569A (en) | 2002-09-06 | 2009-02-28 | Amgen Inc | Therapeutic human anti-IL-1R1 monoclonal antibody |
| US7261893B2 (en) * | 2002-10-22 | 2007-08-28 | Wyeth | Neutralizing antibodies against GDF-8 and uses therefor |
| US20040191243A1 (en) | 2002-12-13 | 2004-09-30 | Bei Chen | System and method for stabilizing antibodies with histidine |
| US20050158303A1 (en) | 2003-04-04 | 2005-07-21 | Genentech, Inc. | Methods of treating IgE-mediated disorders comprising the administration of high concentration anti-IgE antibody formulations |
| EP1471152A1 (en) * | 2003-04-25 | 2004-10-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Mutations in the human PCSK9 gene associated to hypercholesterolemia |
| AU2004270103B2 (en) * | 2003-05-21 | 2012-02-23 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies against Bacillusanthracis protective antigen |
| US20050118625A1 (en) * | 2003-10-02 | 2005-06-02 | Mounts William M. | Nucleic acid arrays for detecting gene expression associated with human osteoarthritis and human proteases |
| JP2005130764A (ja) | 2003-10-30 | 2005-05-26 | Pharmaceuticals & Medical Devices Agency | Ｎａｒｃ−１遺伝子上の多型を利用した脂質代謝異常に起因する疾患の検査方法、および創薬のための用途 |
| PT1786472E (pt) | 2004-08-10 | 2013-03-06 | Genzyme Corp | Modulação anti-sentido de expressão de apolipoproteína |
| US20060147945A1 (en) * | 2005-01-06 | 2006-07-06 | Edmonds Brian T | Novel secreted proteins and their uses |
| WO2006081171A1 (en) | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
| US7682981B2 (en) * | 2005-01-27 | 2010-03-23 | Contour Semiconductor, Inc. | Topography transfer method with aspect ratio scaling |
| WO2006124269A2 (en) | 2005-05-16 | 2006-11-23 | Amgen Fremont Inc. | Human monoclonal antibodies that bind to very late antigen-1 for the treatment of inflammation and other disorders |
| JP5231810B2 (ja) | 2005-12-28 | 2013-07-10 | 中外製薬株式会社 | 抗体含有安定化製剤 |
| JP2009524434A (ja) | 2006-01-26 | 2009-07-02 | エイチエックス・ダイアグノスティックス・インコーポレイテッド | トリインフルエンザウイルス亜型ｈ５ヘマグルチニンに結合するモノクローナル抗体およびそれらの使用 |
| EP2348106B1 (en) | 2006-05-08 | 2014-07-02 | Adaerata, Limited Partnership | Chimeric proteins, cells comprising same, and assays using same |
| EP2835429B1 (en) * | 2006-05-11 | 2017-12-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
| US7572618B2 (en) | 2006-06-30 | 2009-08-11 | Bristol-Myers Squibb Company | Polynucleotides encoding novel PCSK9 variants |
| WO2008042383A1 (en) | 2006-10-02 | 2008-04-10 | Armstrong World Industries, Inc. | Process for preparing high molecular weight polyesters |
| US20100068194A1 (en) * | 2006-10-24 | 2010-03-18 | Dong-Ku Kim | Composition for in vivo transplantation for treatment of human cervical cancer comprising mononuclear cells derived from umbilical cord blood |
| EP2083859A4 (en) * | 2006-11-07 | 2010-11-24 | Merck Sharp & Dohme | PCSK9 ANTAGONISTS |
| WO2008133647A2 (en) * | 2006-11-07 | 2008-11-06 | Merck & Co., Inc. | Antagonists of pcsk9 |
| EP2083861A4 (en) | 2006-11-07 | 2010-11-24 | Merck Sharp & Dohme | ANTAGONISTS OF PCSK9 |
| EP2083860A4 (en) * | 2006-11-07 | 2010-05-26 | Merck Sharp & Dohme | PCSK9 ANTAGONISTS |
| FR2909092B1 (fr) | 2006-11-24 | 2012-10-19 | Pf Medicament | Nouveaux anticorps anti-proliferation |
| JP5086618B2 (ja) * | 2006-11-27 | 2012-11-28 | オリンパス株式会社 | カプセル型内視鏡 |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8084437B2 (en) | 2006-11-27 | 2011-12-27 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| AU2008204901A1 (en) | 2007-01-09 | 2008-07-17 | Wyeth | Anti-IL-13 antibody formulations and uses thereof |
| WO2008109871A2 (en) | 2007-03-08 | 2008-09-12 | Irm Llc | Crystal structure of proprotein convertase 9 (pcsk9) and uses thereof |
| CN101679527A (zh) * | 2007-04-13 | 2010-03-24 | 诺瓦提斯公司 | 用于调节前蛋白转化酶枯草杆菌蛋白酶/kexin9型(pcsk9)的分子和方法 |
| JP5749009B2 (ja) | 2007-08-13 | 2015-07-15 | バスジーン セラピューティクス, インコーポレイテッドVasgenetherapeutics, Inc. | ＥｐｈＢ４に結合するヒト化抗体を利用する癌治療剤 |
| US20130072665A1 (en) | 2007-08-23 | 2013-03-21 | Simon Mark Jackson | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9) |
| JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
| EP2615114B1 (en) | 2007-08-23 | 2022-04-06 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
| JP2011501952A (ja) | 2007-10-26 | 2011-01-20 | シェーリング コーポレイション | 脂質障害およびコレステロール障害を治療するための抗ｐｃｓｋ９および方法 |
| EP2245039A4 (en) | 2008-01-31 | 2012-06-06 | Alnylam Pharmaceuticals Inc | OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN |
| AR070315A1 (es) | 2008-02-07 | 2010-03-31 | Merck & Co Inc | Anticuerpos 1b20 antagonistas de pcsk9 |
| JP2011511638A (ja) | 2008-02-07 | 2011-04-14 | シェーリング コーポレイション | 抗ｔｓｌｐｒ抗体の設計製作 |
| AR070316A1 (es) * | 2008-02-07 | 2010-03-31 | Merck & Co Inc | Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9) |
| KR102269708B1 (ko) | 2008-04-11 | 2021-06-25 | 추가이 세이야쿠 가부시키가이샤 | 복수 분자의 항원에 반복 결합하는 항원 결합 분자 |
| WO2009131740A2 (en) | 2008-04-23 | 2009-10-29 | Amgen Inc. | Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof |
| DK2982695T3 (da) | 2008-07-09 | 2019-05-13 | Biogen Ma Inc | Sammensætninger, der omfatter antistoffer mod lingo eller fragmenter deraf |
| DE102008034203B4 (de) * | 2008-07-21 | 2018-04-26 | Airbus Helicopters Deutschland GmbH | Herstellung von Faserverbundbauteilen mit Formkernen |
| EP2641918A3 (en) | 2008-08-04 | 2014-03-05 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
| TWI445716B (zh) | 2008-09-12 | 2014-07-21 | Rinat Neuroscience Corp | Ｐｃｓｋ９拮抗劑類 |
| WO2010068526A1 (en) | 2008-12-12 | 2010-06-17 | Merck Sharp & Dohme Corp. | Pcsk9 immunoassay |
| US20130064834A1 (en) * | 2008-12-15 | 2013-03-14 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to pcsk9 |
| US8357371B2 (en) | 2008-12-15 | 2013-01-22 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to PCSK9 |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| AU2010221156A1 (en) | 2009-03-06 | 2011-09-22 | Genentech, Inc. | Antibody formulation |
| US8210622B2 (en) | 2009-03-13 | 2012-07-03 | Liberty Hardware Mfg. Corp. | Adjustable product display assembly |
| WO2011028938A1 (en) | 2009-09-02 | 2011-03-10 | Alnylam Pharmaceuticals, Inc. | Methods for lowering serum cholestrol in a subject using inhibition of pcsk9 |
| US20120219558A1 (en) | 2009-09-25 | 2012-08-30 | Yan Ni | Antagonists of pcsk9 |
| WO2011044637A1 (en) | 2009-10-15 | 2011-04-21 | Monash University | Affinity ligands and methods for protein purification |
| WO2011053759A1 (en) | 2009-10-30 | 2011-05-05 | Merck Sharp & Dohme Corp. | Ax1 and ax189 pcsk9 antagonists and variants |
| CN102639150A (zh) | 2009-10-30 | 2012-08-15 | 默沙东公司 | Ax213和ax132 pcsk9拮抗剂和变体 |
| WO2011053665A1 (en) | 2009-10-30 | 2011-05-05 | Merck Sharp & Dohme Corp. | Pcsk9 immunoassay |
| US20120208209A1 (en) | 2009-10-30 | 2012-08-16 | Marina Ichetovkin | Pcsk9 immunoassay |
| CN102770157B (zh) | 2009-11-20 | 2017-05-17 | 拜康有限公司 | 抗体的配制品 |
| AR079336A1 (es) | 2009-12-11 | 2012-01-18 | Irm Llc | Antagonistas de la pro-proteina convertasa-subtilisina/quexina tipo 9 (pcsk9) |
| AU2011225716A1 (en) | 2010-03-11 | 2012-09-27 | Pfizer Inc. | Antibodies with pH dependent antigen binding |
| EA022983B1 (ru) * | 2010-04-13 | 2016-04-29 | Бристол-Майерс Сквибб Компани | Белки на основе структурного домена фибронектина, связывающие pcsk9 |
| CN201712554U (zh) | 2010-07-14 | 2011-01-19 | 李辉 | 电动汽车热管理系统 |
| WO2012054438A1 (en) | 2010-10-22 | 2012-04-26 | Schering Corporation | Anti-pcsk9 |
| US9518132B2 (en) | 2010-11-09 | 2016-12-13 | Altimab Therapeutics, Inc. | Protein complexes for antigen binding and methods of use |
| US8613308B2 (en) | 2010-12-10 | 2013-12-24 | Uop Llc | Process for transferring heat or modifying a tube in a heat exchanger |
| US20120195910A1 (en) | 2010-12-22 | 2012-08-02 | Genentech, Inc. | Anti-pcsk9 antibodies and methods of use |
| EP2650016A1 (en) | 2011-01-28 | 2013-10-16 | Sanofi | Human antibodies to PSCK9 for use in methods of treatment based on particular dosage regimens (11565) |
| AR084938A1 (es) * | 2011-01-28 | 2013-07-10 | Sanofi Sa | Anticuerpos humanos contra la proproteina convertasa subtilisina/kexina tipo 9 (anti pcsk9) para usar en metodos para tratar grupos de pacientes |
| EP2481758A1 (en) | 2011-01-28 | 2012-08-01 | Sanofi | Human antibodies to PSCK9 for use in methods of treating particular groups of subjects (11566) |
| JP2014511378A (ja) | 2011-02-11 | 2014-05-15 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｐｃｓｋ９アンタゴニスト |
| US20140004122A1 (en) * | 2011-05-10 | 2014-01-02 | Amgen Inc. | Methods for treating or preventing cholesterol related disorders |
| JOP20200043A1 (ar) | 2011-05-10 | 2017-06-16 | Amgen Inc | طرق معالجة أو منع الاضطرابات المختصة بالكوليسترول |
| WO2012170607A2 (en) | 2011-06-10 | 2012-12-13 | Novartis Ag | Use of pcsk9 antagonists |
| WO2012168491A1 (en) | 2011-06-10 | 2012-12-13 | Novartis Ag | Pharmaceutical formulations of pcsk9 antagonists |
| JP2014519848A (ja) | 2011-06-20 | 2014-08-21 | ジェネンテック， インコーポレイテッド | Ｐｃｓｋ９結合ポリペプチドと使用方法 |
| EP2731623A1 (en) | 2011-07-14 | 2014-05-21 | Pfizer Inc | Treatment with anti-pcsk9 antibodies |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| ES2773111T3 (es) | 2011-09-16 | 2020-07-09 | Regeneron Pharma | Inhibidor de la proproteína convertasa subtilisina/kexina 9 (PCSK9) para su uso en la reducción de los niveles de lipoproteína (a) |
| AR087715A1 (es) | 2011-09-16 | 2014-04-09 | Lilly Co Eli | Anticuerpos anti pcsk9 y usos de los mismos |
| JP6170940B2 (ja) | 2011-12-20 | 2017-07-26 | アダエラータ、リミテッド パートナーシップＡｄａｅｒａｔａ， Ｌｉｍｉｔｅｄ Ｐａｒｔｎｅｒｓｈｉｐ | Ｐｃｓｋ９の阻害剤としての単一ドメイン抗体 |
| WO2013148284A1 (en) | 2012-03-29 | 2013-10-03 | Genentech, Inc. | Antibodies that bind to a pcsk9 cleavage site and methods of use |
| EA039663B1 (ru) * | 2012-05-03 | 2022-02-24 | Амген Инк. | Применение антитела против pcsk9 для снижения сывороточного холестерина лпнп и лечения связанных с холестерином расстройств |
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| US9401875B2 (en) | 2012-06-01 | 2016-07-26 | Nippon Telegraph And Telephone Corporation | Packet transfer processing method and packet transfer processing device |
| AR091462A1 (es) | 2012-06-15 | 2015-02-04 | Genentech Inc | Anticuerpos anti-pcsk9, formulaciones, dosificacion y metodos de uso |
| EP2703009A1 (en) | 2012-08-31 | 2014-03-05 | Sanofi | Combination treatments involving antibodies to human PCSK9 |
| EP2706070A1 (en) | 2012-09-06 | 2014-03-12 | Sanofi | Combination treatments involving antibodies to human PCSK9 |
| WO2014150983A2 (en) | 2013-03-15 | 2014-09-25 | Amgen Inc. | Human antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 |
| JP6071725B2 (ja) | 2013-04-23 | 2017-02-01 | カルソニックカンセイ株式会社 | 電気自動車の駆動力制御装置 |
| US20150004174A1 (en) | 2013-06-28 | 2015-01-01 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolemia |
| US9300829B2 (en) | 2014-04-04 | 2016-03-29 | Canon Kabushiki Kaisha | Image reading apparatus and correction method thereof |
| WO2016046684A1 (en) | 2014-09-23 | 2016-03-31 | Pfizer Inc. | Treatment with anti-pcsk9 antibodies |
| US11284893B2 (en) | 2019-04-02 | 2022-03-29 | Covidien Lp | Stapling device with articulating tool assembly |
| DE102023206495B3 (de) | 2023-07-07 | 2024-11-21 | Volkswagen Aktiengesellschaft | Integrierter Schaltkreis, Anordnung sowie Verfahren zum Einkoppeln von optischen Signalen in einen integrierten Schaltkreis |
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