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1. 发明申请

US20170313787A1 ENGINEERED POLYPEPTIDE CONJUGATES AND METHODS FOR MAKING THEREOF USING TRANSGLUTAMINASE 审中-公开
公开(公告)号：US20170313787A1
公开(公告)日：2017-11-02
申请号：US15593259
申请日：2017-05-11
申请人： PFIZER INC. , RINAT NEUROSCIENCE CORP.
发明人： Pavel STROP , Magdalena Grazyna DORYWALSKA , Arvind RAJPAL , David SHELTON , Shu-Hui LIU , Jaume PONS , Russell DUSHIN
IPC分类号： C07K17/02 , C07K16/30
CPC分类号： C07K17/02 , A61K47/68 , A61K47/6803 , A61K47/6851 , A61K47/6889 , C07K16/30 , C07K2317/31 , C07K2317/73
摘要： The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

2. 发明申请

US20160096898A1 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
申请人： RINAT NEUROSCIENCE CORP. , Pfizer Inc.
发明人： 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分类号： C07K16/40
CPC分类号： C07K16/40 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2299/00 , C07K2317/24 , C07K2317/33 , C07K2317/76 , C07K2317/92
摘要： 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.
摘要翻译：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。

3. 发明申请

US20130273069A1 PCSK9 ANTAGONISTS 审中-公开
公开(公告)号：US20130273069A1
公开(公告)日：2013-10-17
申请号：US13857063
申请日：2013-04-04
申请人： Pfizer Inc. , Rinat Neuroscience Corp.
发明人： 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分类号： C07K16/40 , A61K45/06 , A61K39/395
CPC分类号： C07K16/40 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2299/00 , C07K2317/24 , C07K2317/33 , C07K2317/76 , C07K2317/92
摘要： 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.
摘要翻译：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。

4. 发明申请

US20200024366A1 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
申请人： Pfizer Inc. , RINAT NEUROSCIENCE CORP.
发明人： 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分类号： C07K16/42 , C07K16/40 , C07K16/28
摘要： 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).

5. 发明申请

US20210115159A1 ENGINEERED POLYPEPTIDE CONJUGATES AND METHODS FOR MAKING THEREOF USING TRANSGLUTAMINASE 有权
公开(公告)号：US20210115159A1
公开(公告)日：2021-04-22
申请号：US16951003
申请日：2020-11-18
申请人： PFIZER INC. , RINAT NEUROSCIENCE CORP.
发明人： Pavel STROP , Magdalena Grazyna DORYWALSKA , Arvind RAJPAL , David SHELTON , Shu-Hui LIU , Jaume PONS , Russell DUSHIN
IPC分类号： C07K17/02 , C07K16/30 , A61K47/68
摘要： The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

6. 发明申请

US20150266974A1 ANTIBODIES WITH pH DEPENDENT ANTIGEN BINDING 审中-公开
标题翻译：具有pH依赖性抗原结合的抗体
公开(公告)号：US20150266974A1
公开(公告)日：2015-09-24
申请号：US14677983
申请日：2015-04-03
申请人： RINAT NEUROSCIENCE CORP. , PFIZER INC.
发明人： Jaume PONS , Jeffrey Raymond CHABOT , Javier Fernando CHAPARRO RIGGERS , Bruce Charles GOMES , Hong LIANG , Kapil MAYAWALA , Jerome Thomas METTETAL, II , Arvind RAJPAL , David Louis SHELTON
IPC分类号： C07K16/42 , C07K16/40 , C07K16/28
CPC分类号： C07K16/4291 , C07K16/28 , C07K16/40 , C07K2317/56 , C07K2317/565 , C07K2317/70 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/92 , C07K2317/94 , C07K2319/21
摘要： 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).
摘要翻译：本发明涉及与其抗原具有pH依赖性结合的抗体，使得在生理pH（即pH 7.4）下抗原结合的亲和力大于内体pH（即pH6.0或5.5）时的亲和力。换句话说，pH5.5 / pH7.4或pH6.0 / pH7.4下的KD或koff比大于或等于2,3,4,8,10,16,20,30,40或100 或者更多。这种pH依赖性抗体优先从内体中的抗原解离。与抗原为经过抗原介导的清除（例如，PCSK9）的抗原相比，与具有pH 7.4但具有pH依赖性结合的等效KD的抗体相比，可以增加抗体半衰期。当与抗体（例如IL6）结合时，当抗原经历减少的清除时，具有pH依赖性结合的抗体可降低总抗原半衰期。具有pH依赖性结合的抗体也可以延长不抗体结合的抗原的降低。当拮抗通常以高水平存在的靶抗原（例如IgE，DKK1，C5和SOST）时，这可能是重要的。此外，当抗原是受体时，这种抗体可以增加抗原半衰期，并且当与抗体（例如，GMCSF受体）结合时，该受体具有增加的清除能力。

7. 发明申请

US20130071921A1 ANTIBODIES SPECIFIC FOR DKK-1 AND THEIR USES 失效
标题翻译： 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
申请人： PFIZER INC. , RINAT NEUROSCIENCE CORP.
发明人： Vishwas Madhav PARALKAR , Donna Marie STONE , Mei LI , Jaume PONS
IPC分类号： C07K16/28 , C12N15/85 , C12N15/70
CPC分类号： C07K16/28 , A61K2039/505 , C07K16/18 , C07K2317/24 , C07K2317/33 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C12N15/70 , C12N15/85
摘要： 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.
摘要翻译：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。

8. 发明申请

US20170342143A1 ANTI-NGF ANTIBODIES AND METHODS USING SAME 审中-公开
公开(公告)号：US20170342143A1
公开(公告)日：2017-11-30
申请号：US15622551
申请日：2017-06-14
申请人： Rinat Neuroscience Corp.
发明人： Jaume PONS , Arnon ROSENTHAL
IPC分类号： C07K16/22 , A61K39/00
CPC分类号： C07K16/22 , A61K2039/505 , C07K2317/21 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92
摘要： The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

9. 发明申请

US20130236451A1 ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAME 审中-公开
标题翻译：针对AMYLOID-BETA肽的抗体和使用其的方法
公开(公告)号：US20130236451A1
公开(公告)日：2013-09-12
申请号：US13767222
申请日：2013-02-14
申请人： RINAT NEUROSCIENCE CORP.
发明人： Arnon ROSENTHAL , Jaume PONS , Wei-Hsien HO
IPC分类号： C07K16/28
CPC分类号： C07K16/18 , A61K2039/505 , C07K16/28 , C07K2317/14 , C07K2317/21 , C07K2317/41 , C07K2317/52 , C07K2317/522 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/92
摘要： Antibodies directed to the C-terminal side of β-amyloid peptide and methods of using these antibodies for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described.
摘要翻译：描述了针对β-淀粉样蛋白肽的C末端侧的抗体以及使用这些抗体诊断和治疗阿尔茨海默病和Aβ肽相关疾病的方法。

10. 发明申请

US20220332850A1 HETERODIMERIC PROTEINS AND METHODS FOR PRODUCING AND PURIFYING THEM 有权
公开(公告)号：US20220332850A1
公开(公告)日：2022-10-20
申请号：US17846933
申请日：2022-06-22
申请人： RINAT NEUROSCIENCE CORP.
发明人： Weihsien HO , Jaume PONS , Arvind RAJPAL , Pavel STROP
IPC分类号： C07K16/46 , C07K16/28 , C07K16/30
摘要： The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglubulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

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