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1. 发明申请

WO2020086406A3 ANTI-NPR1 ANTIBODIES AND USES THEREOF 审中-公开
公开(公告)号：WO2020086406A3
公开(公告)日：2020-04-30
申请号：PCT/US2019/057033
申请日：2019-10-18
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： DUNN, Michael , SU, Jia , MASTAITIS, Jason , GROMADA, Jesper , MORTON, Lori
IPC分类号： C07K16/28 , A61K39/395 , A61P9/12
摘要： The present invention provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to NPR1. In some embodiments, the antibodies of the invention are useful for activating NPR1 activity, thus providing a means of treating or preventing a disease, disorder or condition associated with NPR1 in humans.

2. 发明申请

WO2019195796A1 A LEPTIN RECEPTOR AGONIST ANTIBODY FOR USE IN TREATING A METABOLIC DYSFUNCTION OR HYPOLEPTINEMIA 审中-公开
公开(公告)号：WO2019195796A1
公开(公告)日：2019-10-10
申请号：PCT/US2019/026173
申请日：2019-04-05
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GROMADA, Jesper , STEVIS, Panayiotis , ALTAREJOS, Judith , MURPHY, Andrew J.
IPC分类号： A61K39/395 , A61P3/00 , A61P3/04 , A61P3/10
摘要： Provided herein are therapeutic methods of treatment using agonist leptin receptor (LEPR) antibodies, antigen-binding fragments thereof, or compositions comprising the LEPR antibodies or antigen-binding fragments thereof. Such therapeutic methods include treatment for conditions related to metabolic dysfunction, including for example, lipodystrophy, adiposity or obesity, reducing body weight, non-alcoholic fatty liver disease, hyperphagia, hyperglycemia, insulin resistance, dyslipidemia, hepatic steatosis, and infertility.

3. 发明申请

WO2018089532A1 ANTIGEN-BINDING PROTEINS THAT ANTAGONIZE LEPTIN RECEPTOR 审中-公开
标题翻译：抗约束蛋白受体的抗原结合蛋白
公开(公告)号：WO2018089532A1
公开(公告)日：2018-05-17
申请号：PCT/US2017/060690
申请日：2017-11-08
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GROMADA, Jesper , STEVIS, Panayiotis , ALTAREJOS, Judith
IPC分类号： C07K16/28 , A61K39/395
摘要： The present invention provides antibodies and antigen-binding fragments of antibodies that bind to leptin receptor (LEPR), and methods of using the same. According to certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR and antagonize LEPR signaling. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR in the presence or absence of leptin. In other embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that exhibit partial agonism of LEPR signaling. The antibodies and antigen-binding fragments of the present invention are useful for the treatment of various conditions, including but not limited to congestive heart failure cachexia, pulmonary cachexia and cancer cachexia, autoimmune disorders such as inflammatory bowel disease, lupus erythematosus, multiple sclerosis, psoriasis, cardiovascular diseases, elevated blood pressure, neurodegenerative disorders, depression, cancer such as hepatocellular carcinoma, melanoma, breast cancer, and other diseases and disorders associated with or caused by elevated leptin signaling.
摘要翻译：本发明提供了与瘦素受体（LEPR）结合的抗体和抗体的抗原结合片段及其使用方法。根据某些实施方案，本发明包括结合LEPR并拮抗LEPR信号传导的抗体和抗体的抗原结合片段。在某些实施方案中，本发明包括在存在或不存在瘦素的情况下结合LEPR的抗体和抗体的抗原结合片段。在其他实施方案中，本发明包括显示LEPR信号传递的部分激动作用的抗体和抗体的抗原结合片段。本发明的抗体和抗原结合片段可用于治疗各种病症，包括但不限于充血性心力衰竭恶病质，肺恶病质和癌症恶病质，自身免疫病症如炎症性肠病，红斑狼疮，多发性硬化症，牛皮癣，心血管疾病，血压升高，神经退行性疾病，抑郁症，癌症如肝细胞癌，黑素瘤，乳腺癌以及与瘦素信号升高相关或由其引起的其他疾病和病症。

4. 发明申请

WO2018023014A1 MICE COMPRISING MUTATIONS RESULTING IN EXPRESSION OF C-TRUNCATED FIBRILLIN-1 审中-公开
标题翻译：包含引起C-受体结合的FIBRILLIN-1表达的突变的小鼠
公开(公告)号：WO2018023014A1
公开(公告)日：2018-02-01
申请号：PCT/US2017/044409
申请日：2017-07-28
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： HUNT, Charleen , MASTAITIS, Jason , GONG, Guochun , LAI, Ka-Man Venus , GROMADA, Jesper , ECONOMIDES, Aris, N.
IPC分类号： A01K67/027
摘要： Provided are non-human animals comprising a mutation in the Fbnl gene to model neonatal progeroid syndrome with congenital lipodystrophy (NPSCL). Also provided are methods of making such non-human animal models. The non-human animal models can be used for screening compounds for activity in inhibiting or reducing NPSCL or ameliorating NPSCL- like symptoms or screening compounds for activity potentially harmful in promoting or exacerbating NPSCL as well as to provide insights in to the mechanism of NPSCL and potentially new therapeutic and diagnostic targets.
摘要翻译：提供包含Fbnl基因中的突变的非人动物以模拟具有先天性脂肪代谢障碍（NPSCL）的新生儿原病综合征。还提供了制造这种非人动物模型的方法。非人类动物模型可用于筛选化合物抑制或减少NPSCL或改善NPSCL样症状的活性或筛选化合物的活性，以促进或加剧NPSCL的潜在危害，并提供对NPSCL机制的见解和潜在的新的治疗和诊断目标。

5. 发明申请

WO2017066204A1 ANTIGEN-BINDING PROTEINS THAT ACTIVATE THE LEPTIN RECEPTOR 审中-公开
标题翻译：激活LEPTIN受体的抗原结合蛋白
公开(公告)号：WO2017066204A1
公开(公告)日：2017-04-20
申请号：PCT/US2016/056465
申请日：2016-10-11
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GROMADA, Jesper , STEVIS, Panayiotis , ALTAREJOS, Judith
IPC分类号： C07K16/28 , A61P3/00 , A61P3/10 , A61P25/28 , A61K39/395
CPC分类号： C07K16/2869 , A61K39/395 , A61K2039/505 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/565 , C07K2317/75 , C07K2317/92
摘要： The present invention provides antibodies and antigen-binding fragments of antibodies that bind to leptin receptor (LEPR), and methods of using the same. According to certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR and activate LEPR signaling. In other embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind to LEPR and enhance sensitization of LEPR to an antigen. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR in the presence and absence of leptin. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that induce signaling in cells expressing LEPR mutants that otherwise exhibit defective or impaired signaling in the presence of leptin. The antibodies and antigen-binding fragments of the present invention are useful for the treatment of lipodystrophies and other diseases and disorders associated with or caused by leptin deficiency or leptin resistance.
摘要翻译：本发明提供了与瘦素受体（LEPR）结合的抗体和抗体的抗原结合片段及其使用方法。根据某些实施方案，本发明包括结合LEPR并激活LEPR信号传导的抗体和抗体的抗原结合片段。在其他实施方案中，本发明包括结合LEPR并增强LEPR对抗原的敏化的抗体和抗体的抗原结合片段。在某些实施方案中，本发明包括在存在和不存在瘦素的情况下结合LEPR的抗体和抗体的抗原结合片段。在某些实施方案中，本发明包括在表达LEPR突变体的细胞中诱导信号传导的抗体和抗体的抗原结合片段，所述LEPR突变体否则在存在瘦素的情况下表现出缺陷或受损的信号传导。本发明的抗体和抗原结合片段可用于治疗与瘦素缺乏或瘦素抗性相关或由瘦素缺乏或瘦素抗性引起的脂肪营养不良和其他疾病和病症。

6. 发明申请

WO2022140219A1 NUCLEIC ACIDS ENCODING ANCHOR MODIFIED ANTIBODIES AND USES THEREOF 审中-公开
公开(公告)号：WO2022140219A1
公开(公告)日：2022-06-30
申请号：PCT/US2021/064263
申请日：2021-12-20
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： MASTAITIS, Jason , MURPHY, Andrew J. , MCWHIRTER, John , VORONINA, Vera , GROMADA, Jesper
IPC分类号： C07K14/58 , C07K14/72 , C07K16/28 , C07K16/46
摘要： Described herein are anchor-modified immunoglobulin polypeptides, wherein the anchor moors the immunoglobulin polypeptide to a receptor of interest. The anchor-modified immunoglobulin polypeptides are generally characterized at the N-terminus with an anchor, e.g., the receptor binding portion of a ligand that binds a receptor. Non-human animals genetically modified with recombinant immunoglobulin segments that encode the anchor-modified immunoglobulin polypeptides are capable of making the anchor-modified immunoglobulin polypeptides. Such non-human animals also provided, along with methods and compositions for making and using the non-human animals. Methods for producing anchor-modified immunoglobulins from non-human animals are also provided, as well as anchor-modified immunoglobulins generated therefrom.

7. 发明申请

WO2019126071A1 BISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND LEPTIN RECEPTOR AND/OR GP130, AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2019126071A1
公开(公告)日：2019-06-27
申请号：PCT/US2018/066075
申请日：2018-12-17
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： GROMADA, Jesper , STEVIS, Panayiotis , ALTAREJOS, Judith
IPC分类号： C07K16/28 , A61K39/395 , A61P3/04 , A61P3/10 , A61K39/00
CPC分类号： C07K16/2803 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61K2039/54 , A61P3/04 , A61P3/10 , A61P5/04 , C07K16/2866 , C07K16/2869 , C07K16/468 , C07K2317/21 , C07K2317/31 , C07K2317/33 , C07K2317/75 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to antigen-binding molecules, including bispecific antigen-binding molecules that bind human GP130 and/or human leptin receptor (LEPR), and the use of such antigen-binding molecules for the treatment of conditions and disorders related to leptin deficiency or leptin resistance. The bispecific antigen-binding molecules of the present invention can be, e.g., bispecific antibodies comprising a first antigen-binding domain that specifically binds human GP130 and a second antigen-binding domain that specifically binds human LEPR. The bispecific antigen-binding molecules of the present invention are useful in therapeutic applications where induced leptin and/or LEPR-mediated signaling would be beneficial, e.g., in the treatment of obesity, lipodystrophies and other diseases and disorders associated with or caused by leptin deficiency or leptin resistance.

8. 发明申请

WO2019075181A1 INHIBITION OF HSD17B13 IN THE TREATMENT OF LIVER DISEASE IN PATIENTS EXPRESSING THE PNPLA3 I148M VARIATION 审中-公开
公开(公告)号：WO2019075181A1
公开(公告)日：2019-04-18
申请号：PCT/US2018/055377
申请日：2018-10-11
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： XIN, Yurong , GROMADA, Jesper , CHENG, Xiping , DEWEY, Frederick , TESLOVICH DOSTAL, Tanya , SCHURMANN, Claudia
IPC分类号： C12Q1/6883
摘要： The disclosure provides methods of identifying a human subject as a candidate for treating or inhibiting a liver disease by inhibiting HSD17B13. The disclosure also provides methods of treating a subject who is PNPLA3 Ile148Met+ by administering an inhibitor of HSD17B13. The disclosure also provides method of detecting a PNPLA3 Ile148Met variant and functional HSD17B13 in a subject. The disclosure also provides method of identifying a subject having a protective effect against liver disease. The disclosure also provides inhibitors of HSD17B13 for use in the treatment of a liver disease.

9. 发明申请

WO2019060653A1 GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS AND USES THEREOF 审中-公开
公开(公告)号：WO2019060653A1
公开(公告)日：2019-03-28
申请号：PCT/US2018/052110
申请日：2018-09-21
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： WEI, Yang , OKAMOTO, Haruka , GROMADA, Jesper , DAVIS, Samuel , MURPHY, Andrew, J.
IPC分类号： C07K14/605 , A61K38/17 , C07K16/28
摘要： The present invention provides modified glucagon-like peptide 1 (GLP1) polypeptides, fusion proteins comprising modified GLP1 polypeptides, and methods of use thereof. In various embodiments of the invention, the fusion proteins are GLP1 receptor agonists that comprise a modified GLP1 fused to a stabilizing domain. In some embodiments, the fusion proteins comprising modified GLP1 are useful for treating or ameliorating a symptom or indication of a disorder such as obesity and diabetes.

10. 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。

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