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1. 发明申请

WO2019006034A1 NON-HUMAN ANIMALS COMPRISING A HUMANIZED ASGR1 LOCUS 审中-公开
公开(公告)号：WO2019006034A1
公开(公告)日：2019-01-03
申请号：PCT/US2018/039864
申请日：2018-06-27
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： MUJICA, Alexander O. , GUSAROVA, Viktoria , WANG, Cheng , KYRATSOUS, Christos , POTOCKY, Terra , CYGNAR, Katherine , MARTIN, Joel
IPC分类号： A01K67/027 , C07K14/705 , C12N15/86
摘要： Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

2. 发明申请

WO2017151783A1 METHODS FOR TREATING PATIENTS WITH HYPERLIPIDEMIA BY ADMINISTERING A PCSK9 INHIBITOR IN COMBINATION WITH AN ANGPTL3 INHIBITOR 审中-公开
标题翻译：通过施用PCSK9抑制剂与ANGPTL3抑制剂组合治疗高脂血症患者的方法
公开(公告)号：WO2017151783A1
公开(公告)日：2017-09-08
申请号：PCT/US2017/020221
申请日：2017-03-01
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GUSAROVA, Viktoria , GROMADA, Jesper , MURPHY, Andrew J.
IPC分类号： A61P9/10 , A61K39/00 , C07K16/22 , C07K16/40
摘要： The present invention provides methods for treating patients suffering from hypercholesterolemia, wherein the patient is non-responsive to, inadequately controlled by, or intolerant to treatment with a standard lipid modifying therapy. The methods of the invention provide for lowering at least one lipid parameter in the patient by administering a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to proprotein convertase subtilisin/kexin type 9 (PCSK9) in combination with a therapeutically effective amount of an antibody that specifically binds to angiopoietin-like protein 3 (ANGPTL3). The combination of an anti-PCSK9 antibody with an anti-ANGPTL3 antibody is useful in treating diseases such as hypercholesterolemia, including familial hypercholesterolemia (FH), both heFH and hoFH, as well as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, chylomicronemia, and to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor, such as cardiovascular diseases.
摘要翻译：本发明提供了用于治疗患有高胆固醇血症的患者的方法，其中患者对标准的脂质修饰疗法的治疗无反应，控制不好或不耐受。本发明的方法通过施用治疗有效量的与原蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）特异性结合的抗体或其抗原结合片段与治疗有效地组合，从而降低患者的至少一种脂质参数有效量的特异性结合血管生成素样蛋白3（ANGPTL3）的抗体。抗PCSK9抗体与抗ANGPTL3抗体的组合可用于治疗诸如高胆固醇血症（包括家族性高胆固醇血症（FH），heFH和hoFH）以及高脂血症，高脂蛋白血症和血脂异常包括高甘油三酯血症，乳糜微粒血症和预防或治疗疾病或病症，脂质代谢异常是心血管疾病的风险因素。

3. 发明申请

WO2019006034A9 NON-HUMAN ANIMALS COMPRISING A HUMANIZED ASGR1 LOCUS 审中-公开
公开(公告)号：WO2019006034A9
公开(公告)日：2019-01-03
申请号：PCT/US2018/039864
申请日：2018-06-27
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： MUJICA, Alexander O. , GUSAROVA, Viktoria , WANG, Cheng , KYRATSOUS, Christos , POTOCKY, Terra , CYGNAR, Katherine , MARTIN, Joel
IPC分类号： A01K67/027 , C07K14/705 , C12N15/86
摘要： Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

4. 发明申请

WO2017177181A1 METHODS FOR TREATING HYPERLIPIDEMIA WITH AN ANGPTL8 INHIBITOR AND AN ANGPTL3 INHIBITOR 审中-公开
标题翻译：用ANGPTL8抑制剂和ANGPTL3抑制剂治疗高脂血症的方法
公开(公告)号：WO2017177181A1
公开(公告)日：2017-10-12
申请号：PCT/US2017/026679
申请日：2017-04-07
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GROMADA, Jesper , GUSAROVA, Viktoria , MURPHY, Andrew J.
IPC分类号： A61K39/00 , A61P3/06 , C07K16/22
摘要： The present invention provides methods for treating patients suffering from hyperlipidemia, wherein the patient is non-responsive to, inadequately controlled by, or intolerant to treatment with a standard lipid modifying therapy. The methods of the invention provide for lowering at least one lipid parameter in the patient by administering a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to angiopoietin-like protein 8 (ANGPTL8) in combination with a therapeutically effective amount of an antibody that specifically binds to angiopoietin-like protein 3 (ANGPTL3). The combination of an anti-ANGPTL8 antibody with an anti-ANGPTL3 antibody is useful in treating diseases such as hypercholesterolemia, including familial hypercholesterolemia (FH), both heFH and hoFH, as well as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, chylomicronemia, and to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor, such as cardiovascular diseases.
摘要翻译：本发明提供了用于治疗患有高脂血症的患者的方法，其中患者对标准的脂质修饰疗法的治疗无反应，控制不好或不耐受。本发明的方法通过给药治疗有效量的特异性结合血管生成素样蛋白8（ANGPTL8）的抗体或其抗原结合片段与治疗有效量的特异性结合血管生成素样蛋白3（ANGPTL3）的抗体。抗ANGPTL8抗体与抗ANGPTL3抗体的组合可用于治疗疾病，如高胆固醇血症，包括家族性高胆固醇血症（FH），heFH和hoFH，以及高脂血症，高脂蛋白血症和血脂异常，包括高甘油三酯血症，乳糜微粒血症和预防或治疗疾病或病症，脂质代谢异常是心血管疾病的风险因素。

5. 发明申请

WO2019217591A1 ANTI-MSR1 ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2019217591A1
公开(公告)日：2019-11-14
申请号：PCT/US2019/031383
申请日：2019-05-08
申请人： REGENERON PHARMACEUTICALS, INC. , KYRATSOUS, Christos , NITTOLI, Thomas , ZUMSTEG, Anna
发明人： KYRATSOUS, Christos , NITTOLI, Thomas , ZUMSTEG, Anna , GROMADA, Jesper , GUSAROVA, Viktoria , HAN, Amy , HAXHINASTO, Sokol , MURPHY, Andrew J. , OLSON, William , SLEEMAN, Matthew
IPC分类号： C07K16/28 , A61K47/68
摘要： Provided herein are antibodies and antigen-binding fragments that bind MSR1 and methods of use thereof. According to certain embodiments, the antibodies bind human MSR1 with high affinity. In certain embodiments, the antibodies bind MSR1 without blocking, or blocking less than 90%, of modified LDL binding to MSR1. In some embodiments, the antibodies bind cell surface expressed-MSR1 and are internalized. The antibodies of the invention may be fully human antibodies. The invention includes anti-MSR1 antibodies, or antigen-binding fragments thereof, conjugated to drugs or therapeutic compounds.

6. 发明申请

WO2018094112A1 METHODS OF TREATING OBESITY WITH ANTI-ANGPTL8 ANTIBODIES 审中-公开
公开(公告)号：WO2018094112A1
公开(公告)日：2018-05-24
申请号：PCT/US2017/062103
申请日：2017-11-16
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GUSAROVA, Viktoria , GROMADA, Jesper , MURPHY, Andrew, J.
IPC分类号： C07K16/22 , A61K39/00 , A61P3/06
摘要： The present invention provides antibodies that bind to ANGPTL8 and methods of using the same. According to certain embodiments, the invention includes methods of using anti-ANGPTL8 antibodies that bind human ANGPTL8 with high affinity to treat obesity, reduce body fat, reduce body weight, increase energy expenditure, and increase HDL-C, in a subject.

7. 发明申请

WO2017136712A1 NON-HUMAN ANIMALS HAVING AN ENGINEERED ANGPTL8 GENE 审中-公开
标题翻译：具有工程ANGPTL8基因的非人动物
公开(公告)号：WO2017136712A1
公开(公告)日：2017-08-10
申请号：PCT/US2017/016487
申请日：2017-02-03
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GUSAROVA, Viktoria , MURPHY, Andrew J. , GROMADA, Jesper , GUO, Dayong
IPC分类号： C07K14/515 , A01K67/027 , A61K49/00 , C07K16/22 , A61K39/00
CPC分类号： A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/206 , A01K2227/10 , A01K2227/105 , A01K2267/0306 , A01K2267/0375 , A61K49/0008 , A61K2039/505 , C07K14/515 , C07K16/22
摘要： Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an Angiopoietin- like protein 8 ( ANGPTL8 ) gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous ANGPTL8 locus so that said non-human animals express a human ANGPTL8 polypeptide.
摘要翻译：提供了非人动物以及用于制备和使用它们的方法和组合物，其中所述非人动物包含血管生成素样蛋白8（ANGPTL8）的人源化，基因）。在一些实施方案中，所述非人动物可被描述为具有对内源ANGPTL8基因座的遗传修饰，使得所述非人动物表达人ANGPTL8多肽。

8. 发明申请

WO2014197752A1 METHODS FO INHIBTING ATHEROSCLEROSIS BY ADMINISTERING AN INHIBITOR OF PCSK9 审中-公开
标题翻译：方法通过管理PCSK9的抑制剂抑制动脉粥样硬化
公开(公告)号：WO2014197752A1
公开(公告)日：2014-12-11
申请号：PCT/US2014/041204
申请日：2014-06-06
申请人： REGENERON PHARMACEUTICALS, INC. , SANOFI
发明人： SASIELA, William, J. , GUSAROVA, Viktoria , PEYMAN, Anusch , SCHAEFER, Hans-ludwig , SCHWAHN, Uwe
IPC分类号： C07K16/40 , A61K39/00
CPC分类号： C07K16/40 , A61K31/4015 , A61K39/3955 , A61K2039/505 , C07K14/4703 , C07K2317/21 , C07K2317/565 , C07K2317/76 , Y02A50/407
摘要： The present invention provides methods and compositions for inhibiting atherosclerotic plaque formation in a subject. In certain embodiments, the methods of the present invention comprise selecting a subject who has, or is at risk of developing, atherosclerosis, and administering to the subject a pharmaceutical composition comprising a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody, or antigen binding protein.
摘要翻译：本发明提供用于抑制受试者中动脉粥样硬化斑块形成的方法和组合物。在某些实施方案中，本发明的方法包括选择具有或具有发展动脉粥样硬化风险并且向受试者施用包含前体蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）抑制剂的药物组合物的受试者。在某些实施方案中，PCSK9抑制剂是抗PCSK9抗体或抗原结合蛋白。

9. 发明申请

WO2020106780A1 BIS-OCTAHYDROPHENANTHRENE CARBOXAMIDE DERIVATIVES AND PROTEIN CONJUGATES THEREOF FOR USE AS LXR AGONISTS 审中-公开
公开(公告)号：WO2020106780A1
公开(公告)日：2020-05-28
申请号：PCT/US2019/062302
申请日：2019-11-19
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GROMADA, Jesper , GUSAROVA, Viktoria , HAN, Amy , HAXHINASTO, Sokol , MURPHY, Andrew, J. , OLSON, William , SLEEMAN, Matthew
IPC分类号： C07D233/64 , A61K47/68 , A61K47/69 , C07C233/90 , C07D249/16 , C07H17/02 , C07K5/06 , C07K5/08
摘要： Provided herein are compounds or payloads, linker-payloads, antibody-drug conjugates, and compositions, and methods for the treatment of diseases and disorders associated with the liver X receptor, including bis-octahydrophenanthrene carboxamides and protein (e.g., antibody) drug conjugates thereof.

10. 发明申请

WO2019126194A1 ANGPTL8 ASSAY AND USES THEREOF 审中-公开
公开(公告)号：WO2019126194A1
公开(公告)日：2019-06-27
申请号：PCT/US2018/066266
申请日：2018-12-18
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GUSAROVA, Viktoria , GROMADA, Jesper , MURPHY, Andrew J.
IPC分类号： G01N33/74
CPC分类号： G01N33/74 , G01N2800/044
摘要： The present invention provides ELISA-based methods for detecting and/or quantifying ANGPTL8 in biological samples using anti-ANGPTL8 antibodies.

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