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    PC33718E
    3.
    发明申请
    PC33718E 审中-公开

    公开(公告)号：US20160096898A1

    公开(公告)日：2016-04-07

    申请号：US14864750

    申请日：2015-09-24

    Applicant: RINAT NEUROSCIENCE CORP. ,  Pfizer Inc.

    Inventor： Hong LIANG ,  Yasmina Noubia ABDICHE ,  Javier Fernando CHAPARRO RIGGERS ,  Bruce Charles GOMES ,  Julie Jia Li HAWKINS ,  Jaume PONS ,  Xiayang QIU ,  Pavel STROP ,  Yuli WANG

    IPC: C07K16/40

    CPC classification number: C07K16/40 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K2299/00 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/76 ,  C07K2317/92

    Abstract: The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

    Abstract translation: 本发明提供了与抗蛋白转化酶枯草杆菌蛋白酶Kexin 9型（PCSK9）结合的拮抗抗体，其抗原结合部分和适体。 还提供了针对肽的抗体，其中抗体结合PCSK9。 本发明还提供了获得这样的抗体和抗体编码核酸的方法。 本发明还涉及使用这些抗体及其抗原结合部分来降低LDL-胆固醇水平和/或用于治疗和/或预防心血管疾病（包括治疗高胆固醇血症）的治疗方法。

    ANTIBODIES WITH pH DEPENDENT ANTIGEN BINDING
    7.
    发明申请
    ANTIBODIES WITH pH DEPENDENT ANTIGEN BINDING 审中-公开

    公开(公告)号：US20200024366A1

    公开(公告)日：2020-01-23

    申请号：US16296852

    申请日：2019-03-08

    Applicant: Pfizer Inc. ,  RINAT NEUROSCIENCE CORP.

    Inventor： Jaume PONS ,  Jeffrey Raymond CHABOT ,  Javier Fernando CHAPARRO RIGGERS ,  Bruce Charles GOMES ,  Hong LIANG ,  KapiI MAYAWALA ,  Jerome Thomas METTETAL, II ,  Arvind RAJPAL ,  David Louis SHELTON

    IPC: C07K16/42 ,  C07K16/40 ,  C07K16/28

    Abstract: The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the KD or koff ratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent KDs at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present at high levels (e.g., IgE, DKK1, C5 and SOST). In addition, such antibodies can increase antigen half life when the antigen is a receptor and the receptor has increased clearance when bound to antibody (e.g., GMCSF receptor).

    ANTIBODIES SPECIFIC FOR DKK-1 AND THEIR USES
    10.
    发明申请
    ANTIBODIES SPECIFIC FOR DKK-1 AND THEIR USES 失效
    DKK-1特异性抗体及其用途

    公开(公告)号：US20130071921A1

    公开(公告)日：2013-03-21

    申请号：US13680569

    申请日：2012-11-19

    Applicant: PFIZER INC. ,  RINAT NEUROSCIENCE CORP.

    Inventor： Vishwas Madhav PARALKAR ,  Donna Marie STONE ,  Mei LI ,  Jaume PONS

    IPC: C07K16/28 ,  C12N15/85 ,  C12N15/70

    CPC classification number: C07K16/28 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92 ,  C12N15/70 ,  C12N15/85

    Abstract: The present invention provides antibodies and fragments thereof that bind to Dkk-1 and, in particular, to humanized antibodies and fragments thereof that bind to Dkk-1 and, even more particularly to fully humanized antibodies and immunologically functional fragments that bind to Dkk-1. Also provided are antibodies and fragments thereof which compete with the binding of an anti-mouse Dkk-1 monoclonal antibody for binding to Dkk-1+ cells. Also provided are nucleic acids encoding anti-Dkk-1 antibodies or fragments thereof, as well as expression vectors and host cells incorporating these nucleic acids for the recombinant expression of anti-Dkk-1 antibodies and fragments thereof. Also provided are methods of preparing the antibodies and fragments thereof of the invention. Also provided are bone anabolic agents. Pharmaceutical compositions comprising the antibodies or fragments thereof of the invention are also provided. Further provided are methods of treating diseases, conditions and disorders, such as bone disorders, which result in a loss of bone. Methods of treating or preventing a loss of bone mass, methods of inducing increased bone mass, and methods of inducing Wnt activity are also provided.

    Abstract translation: 本发明提供了与Dkk-1结合的抗体及其片段，特别是结合Dkk-1的人源化抗体及其片段，更具体地，涉及与Dkk-1结合的完全人源化抗体和免疫功能片段 。 还提供了与抗小鼠Dkk-1单克隆抗体与Dkk-1 +细胞的结合竞争的抗体及其片段。 还提供了编码抗-Dkk-1抗体或其片段的核酸，以及掺入这些核酸用于重组表达抗-Dkk-1抗体及其片段的表达载体和宿主细胞。 还提供了制备本发明的抗体及其片段的方法。 还提供骨合成代谢剂。 还提供了包含本发明的抗体或其片段的药物组合物。 还提供了治疗导致骨丢失的疾病，病症和障碍（例如骨骼疾病）的方法。 还提供了治疗或预防骨量丧失的方法，诱导骨量增加的方法和诱导Wnt活性的方法。

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