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    ANTIGEN-BINDING PROTEINS THAT ANTAGONIZE LEPTIN RECEPTOR
    3.
    发明申请
    ANTIGEN-BINDING PROTEINS THAT ANTAGONIZE LEPTIN RECEPTOR 审中-公开
    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

    Applicant: REGENERON PHARMACEUTICALS, INC.

    Inventor： GROMADA, Jesper ,  STEVIS, Panayiotis ,  ALTAREJOS, Judith

    IPC: C07K16/28 ,  A61K39/395

    Abstract: 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.

    Abstract translation: 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。

    MICE COMPRISING MUTATIONS RESULTING IN EXPRESSION OF C-TRUNCATED FIBRILLIN-1
    4.
    发明申请
    MICE COMPRISING MUTATIONS RESULTING IN EXPRESSION OF C-TRUNCATED FIBRILLIN-1 审中-公开
    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

    Applicant: REGENERON PHARMACEUTICALS, INC.

    Inventor： HUNT, Charleen ,  MASTAITIS, Jason ,  GONG, Guochun ,  LAI, Ka-Man Venus ,  GROMADA, Jesper ,  ECONOMIDES, Aris, N.

    IPC: A01K67/027

    Abstract: 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.

    Abstract translation: 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。

    ANTIGEN-BINDING PROTEINS THAT ACTIVATE THE LEPTIN RECEPTOR
    5.
    发明申请
    ANTIGEN-BINDING PROTEINS THAT ACTIVATE THE LEPTIN RECEPTOR 审中-公开
    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

    Applicant: REGENERON PHARMACEUTICALS, INC.

    Inventor： GROMADA, Jesper ,  STEVIS, Panayiotis ,  ALTAREJOS, Judith

    IPC: C07K16/28 ,  A61P3/00 ,  A61P3/10 ,  A61P25/28 ,  A61K39/395

    CPC classification number: C07K16/2869 ,  A61K39/395 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/75 ,  C07K2317/92

    Abstract: 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.

    Abstract translation: 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。

    NUCLEIC ACIDS ENCODING ANCHOR MODIFIED ANTIBODIES AND USES THEREOF
    6.
    发明申请
    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

    Applicant: REGENERON PHARMACEUTICALS, INC.

    Inventor： MASTAITIS, Jason ,  MURPHY, Andrew J. ,  MCWHIRTER, John ,  VORONINA, Vera ,  GROMADA, Jesper

    IPC: C07K14/58 ,  C07K14/72 ,  C07K16/28 ,  C07K16/46

    Abstract: 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.

    METHODS FOR TREATING PATIENTS WITH HYPERLIPIDEMIA BY ADMINISTERING A PCSK9 INHIBITOR IN COMBINATION WITH AN ANGPTL3 INHIBITOR
    10.
    发明申请
    METHODS FOR TREATING PATIENTS WITH HYPERLIPIDEMIA BY ADMINISTERING A PCSK9 INHIBITOR IN COMBINATION WITH AN ANGPTL3 INHIBITOR 审中-公开
    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

    Applicant: REGENERON PHARMACEUTICALS, INC.

    Inventor： GUSAROVA, Viktoria ,  GROMADA, Jesper ,  MURPHY, Andrew J.

    IPC: A61P9/10 ,  A61K39/00 ,  C07K16/22 ,  C07K16/40

    Abstract: 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.

    Abstract translation: 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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