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1. 发明授权

US08062638B1 Prevention and treatment of diseases associated with blood coagulation 失效
标题翻译：预防和治疗与凝血相关的疾病
公开(公告)号：US08062638B1
公开(公告)日：2011-11-22
申请号：US10089501
申请日：2000-09-29
申请人： Hiroyuki Saito , Takehisa Kitazawa , Kazutaka Yoshihashi , Kunihiro Hattori
发明人： Hiroyuki Saito , Takehisa Kitazawa , Kazutaka Yoshihashi , Kunihiro Hattori
IPC分类号： A61K39/395 , C07K14/745 , C07K16/24
CPC分类号： G01N33/5008 , A01K67/0271 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/10 , A01K2227/106 , A01K2267/03 , A61K2039/505 , C07K16/36 , C07K2317/24 , C07K2319/00 , C12N15/8509 , G01N33/502 , G01N33/5094
摘要： Provided herein is an animal having a persistent hypercoagulable state by implanting a cell, for example a tumor cell, in which the gene of human tissue factor is implanted to an experimental animal such as a mouse and then growing the cell, thereby persistently supplying human tissue factor to the experimental animal. This animal model is useful for research and development of therapeutic agents for diseases having a persistent hypercoagulable state. Also provided are preventive or therapeutic agents for diseases having a persistent hypercoagulable state, a hypercoagulable state resulting from infections, venous thrombosis, arterial thrombosis, and diseases resulting from the hypertrophy of vascular media, the agent comprising an antibody against human tissue factor (human TF) as an active ingredient.
摘要翻译：本文提供了一种具有持续性高凝状态的动物，其通过将例如肿瘤细胞植入细胞，其中将人组织因子的基因植入到诸如小鼠的实验动物中，然后使细胞生长，从而持续地供应人体组织因子到实验动物。该动物模型对于具有持续性高凝状态的疾病的治疗剂的研究和开发是有用的。还提供了用于具有持续性高凝状态，由感染引起的高凝状态，静脉血栓形成，动脉血栓形成和由血管介质肥大引起的疾病的疾病的预防或治疗剂，所述药物包含针对人组织因子的抗体（人TF ）作为活性成分。

2. 发明申请

US20060233786A1 Agent neutralizint tissue factor inhibitor and agent neutralizing activated blood coagulation factor viii preparation 审中-公开
标题翻译：药剂中和组织因子抑制剂和药剂中和活化凝血因子viii制剂
公开(公告)号：US20060233786A1
公开(公告)日：2006-10-19
申请号：US10513491
申请日：2003-05-23
申请人： Takehisa Kitazawa , Kunihiro Hattori
发明人： Takehisa Kitazawa , Kunihiro Hattori
IPC分类号： A61K39/395
CPC分类号： A61K38/57 , A61K38/4846 , A61K2300/00
摘要： Formulations for neutralizing the anticoagulant action of a human tissue factor inhibitor, comprising a blood coagulation factor complex product or an activated blood coagulation factor VII product as an active ingredient; and formulations for neutralizing the blood coagulation-promoting action of an activated blood coagulation factor VII product, comprising a human tissue factor inhibitor as an active ingredient.
摘要翻译：用于中和人组织因子抑制剂的抗凝血作用的制剂，其包含凝血因子复合物产品或活化凝血因子VII产物作为活性成分; 以及用于中和包含人组织因子抑制剂作为活性成分的活化凝血因子VII产物的促凝血作用的制剂。

3. 发明申请

US20120237517A1 Antibody Substituting for Function of Blood Coagulation Factor VIII 审中-公开
标题翻译：抗体代替血液凝固因子VIII的功能
公开(公告)号：US20120237517A1
公开(公告)日：2012-09-20
申请号：US13434643
申请日：2012-03-29
申请人： Kunihiro Hattori , Tetsuo Kojima , Hiroyuki Saito , Taro Miyazaki , Tetsuhiro Soeda
发明人： Kunihiro Hattori , Tetsuo Kojima , Hiroyuki Saito , Taro Miyazaki , Tetsuhiro Soeda
IPC分类号： C07K16/36 , A61P7/02 , A61K39/395
CPC分类号： C07K16/36 , C07K16/40 , C07K16/468 , C07K2317/24 , C07K2317/31 , C07K2317/56 , C07K2317/622 , C07K2317/75
摘要： The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.
摘要翻译：本发明人生产了特异性结合F.IX / F两种的各种双特异性抗体。 IXa和F.X，并且功能上替代F.CⅧa，即具有辅因子功能以通过F.Ixa促进F.X活化。在这些抗体中，与未添加抗体时相比，抗体A44 / B26的凝固时间缩短了50秒以上。本发明人使用A44的L链从该抗体生产共同的L链抗体，并且表明尽管与原始抗体（A44HL-B26HL）相比，所得抗体的活性降低，但A44L可以用作共同的L链）。此外，通过适当的CDR改组，本发明人成功地制备了功能性替代凝血因子VIII的高活性多特异性抗体。

4. 发明申请

US20100003254A1 Antibody Substituting for Function of Blood Coagulation Factor VIII 审中-公开
标题翻译：抗体代替血液凝固因子VIII的功能
公开(公告)号：US20100003254A1
公开(公告)日：2010-01-07
申请号：US11910836
申请日：2006-03-31
申请人： Kunihiro Hattori , Tetsuo Kojima , Hiroyuki Saito , Taro Miyazaki , Tetsuhiro Soeda
发明人： Kunihiro Hattori , Tetsuo Kojima , Hiroyuki Saito , Taro Miyazaki , Tetsuhiro Soeda
IPC分类号： A61K39/395 , C07K16/00 , A61P7/00
CPC分类号： C07K16/36 , C07K16/40 , C07K16/468 , C07K2317/24 , C07K2317/31 , C07K2317/56 , C07K2317/622 , C07K2317/75
摘要： The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.
摘要翻译：本发明人生产了特异性结合F.IX / F两种的各种双特异性抗体。 IXa和F.X，并且功能上替代F.CⅧa，即具有辅因子功能以通过F.Ixa促进F.X活化。在这些抗体中，与未添加抗体时相比，抗体A44 / B26的凝固时间缩短了50秒以上。本发明人使用A44的L链从该抗体生产共同的L链抗体，并且表明尽管与原始抗体（A44HL-B26HL）相比，所得抗体的活性降低，但A44L可以用作共同的L链）。此外，通过适当的CDR改组，本发明人成功地制备了功能性替代凝血因子VIII的高活性多特异性抗体。

5. 发明授权

US08062635B2 Bispecific antibody substituting for functional proteins 有权
标题翻译：替代功能蛋白的双特异性抗体
公开(公告)号：US08062635B2
公开(公告)日：2011-11-22
申请号：US10575193
申请日：2004-10-08
申请人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda
发明人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda
IPC分类号： A61K39/395
CPC分类号： C07K16/36 , C07K16/2866 , C07K2317/24 , C07K2317/31 , C07K2317/622
摘要： The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.
摘要翻译：本发明人成功构建了结合凝血因子IX /活化凝血因子IX和血液凝固因子X两者的双特异性抗体，并且功能性地代替增强酶促反应的凝血因子VIII /活化凝血因子VIII。

6. 发明申请

US20070041978A1 Bispecific antibody substituting for functional proteins 有权
标题翻译：替代功能蛋白的双特异性抗体
公开(公告)号：US20070041978A1
公开(公告)日：2007-02-22
申请号：US10575193
申请日：2004-10-08
申请人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda
发明人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda
IPC分类号： A61K39/395 , C12N9/00 , C07K16/40
CPC分类号： C07K16/36 , C07K16/2866 , C07K2317/24 , C07K2317/31 , C07K2317/622
摘要： The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.
摘要翻译：本发明人成功构建了结合凝血因子IX /活化凝血因子IX和血液凝固因子X两者的双特异性抗体，并且功能性地代替增强酶促反应的凝血因子VIII /活化凝血因子VIII。

7. 发明授权

US5498698A Megakaryocyte potentiator 失效
标题翻译：巨核细胞增强剂
公开(公告)号：US5498698A
公开(公告)日：1996-03-12
申请号：US256133
申请日：1994-06-27
申请人： Nozomi Yamaguchi , Masayoshi Oh-Eda , Kunihiro Hattori
发明人： Nozomi Yamaguchi , Masayoshi Oh-Eda , Kunihiro Hattori
IPC分类号： A61K38/00 , A61P7/00 , A61P7/04 , C07K1/20 , C07K14/435 , C07K14/47 , C07K14/52 , C12N15/12 , C07K14/475
CPC分类号： C07K14/4705 , A61K38/00
摘要： A novel megakaryocyte potentiator (Meg-POT) of human origin is provided. This Meg-POT has a molecular weight of about 32,000 in SDS-PAGE. In addition, this megakaryocyte potentiator contains the following amino acid sequence in its molecule:Gly Glu Thr Gly Gln Glu Ala Ala Pro Leu Asp Gly Val Leu. (SEQ. I.D. No. 1)This Meg-POT is useful as a therapeutic preparation for disorders caused by decreased platelets or platelet hypofunction.
摘要翻译： PCT No.PCT / JP92 / 01689 Sec。 371日期1994年6月27日第 102（e）日期1994年6月27日PCT提交1992年12月24日PCT公布。公开号WO93 / 13132 日期：1994年7月8日。提供了一种人源的新型巨核细胞增强子（Meg-POT）。该Meg-POT在SDS-PAGE中的分子量约为32,000。此外，该巨核细胞增强剂在其分子中含有以下氨基酸序列：Gly Glu Thr Gly Gln Glu Ala Ala Pro Leu Asp Gly Val Leu。（SEQ.ID.D. No.1）该Meg-POT可用作由血小板减少或血小板功能减退引起的疾病的治疗剂。

8. 发明授权

US07732133B2 Screening methods for biologically active ligands 失效
标题翻译：生物活性配体的筛选方法
公开(公告)号：US07732133B2
公开(公告)日：2010-06-08
申请号：US10333103
申请日：2001-07-17
申请人： Naohiro Yabuta , Hideki Adachi , Yasushi Shimonaka , Kunihiro Hattori
发明人： Naohiro Yabuta , Hideki Adachi , Yasushi Shimonaka , Kunihiro Hattori
IPC分类号： G01Q1/68 , G01Q33/53 , G01N33/566 , C12P21/04 , C12N15/00
CPC分类号： G01N33/566 , G01N2500/00
摘要： In the case when there are two objective biological activities, and the aim is to isolate a compound having at least one biological activity, the present inventors developed an assay method wherein a common detection marker is utilized for separately detecting the presence or absence of each of the biological activities. The present inventors discovered that a compound having at least one of two or more distinct biological activities can be efficiently and conveniently detected by simultaneously assaying at least one test sample or more by the above-mentioned method. Furthermore, for a test sample that proved to be positive by the detection method, they found that it is possible to efficiently and conveniently screen for a test sample having an objective specific biological activity by combining with a method wherein an individual activity of a test sample can be detected to specify the biological activity.
摘要翻译：在存在两个目标生物活性的情况下，目的是分离具有至少一种生物活性的化合物时，本发明人开发了一种测定方法，其中使用常见的检测标记来分别检测每种化合物的存在或不存在生物活动。本发明人发现通过上述方法同时测定至少一种测试样品，可有效地方便地检测具有两种或更多种不同生物活性中至少一种的化合物。此外，对于通过检测方法证实为阳性的测试样品，他们发现可以通过结合其中测试样品的单独活性的方法有效和方便地筛选具有客观特异性生物活性的测试样品可以检测到指定生物活性。

9. 发明申请

US20080075712A1 Double Specific Antibodies Substituting For Functional Proteins 审中-公开
标题翻译：双功能抗体替代功能蛋白
公开(公告)号：US20080075712A1
公开(公告)日：2008-03-27
申请号：US10575905
申请日：2003-10-14
申请人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda , Chiaki Senoo , Osamu Natori , Keiko Kasutani , Shinya Ishii
发明人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda , Chiaki Senoo , Osamu Natori , Keiko Kasutani , Shinya Ishii
IPC分类号： A61K39/395 , A61P31/12 , A61P35/00 , A61P37/00 , A61P7/00 , C07K16/00 , C07K16/36
CPC分类号： C07K16/36 , C07K16/2866 , C07K2317/31 , C07K2317/622
摘要： The present inventors succeeded in separating bispecific antibodies that functionally substitute for ligands of type I interferon receptors comprising two types of molecules: AR1 chain and AR2 chain. Furthermore, the present inventors succeeded in producing bispecific antibodies that substitute for the enzyme reaction-accelerating function of blood coagulation factor VIII/activated blood coagulation factor VIII, which bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X.
摘要翻译：本发明人成功地分离了功能上代替包含两种类型的分子：AR1链和AR2链的I型干扰素受体的配体的双特异性抗体。此外，本发明人成功地制备了代替凝血因子VIII /活化凝血因子VIII的酶反应促进功能的双特异性抗体，其结合凝血因子IX /活化凝血因子IX和凝血因子X 。

10. 发明授权

US5723318A DNA coding for megakaryocyte potentiator 失效
标题翻译：编码巨核细胞增强子的DNA
公开(公告)号：US5723318A
公开(公告)日：1998-03-03
申请号：US426819
申请日：1995-04-21
申请人： Nozomi Yamaguchi , Tetsuo Kojima , Masayoshi Oh-eda , Kunihiro Hattori
发明人： Nozomi Yamaguchi , Tetsuo Kojima , Masayoshi Oh-eda , Kunihiro Hattori
IPC分类号： C07K14/475 , C07K14/52 , C12N15/19
CPC分类号： C07K14/475 , C07K14/52
摘要： Genes coding for a polypeptide having a human megakaryocyte potentiator activity, recombinant vectors containing said genes, host cells that have been transformed with said recombinant vectors, and a process for producing a polypeptide having a human megakaryocyte potentiator activity by first cultivating said transformed host cells and then isolating the desired polypeptide from the culture.
摘要翻译：编码具有人巨核细胞增强子活性的多肽的基因，含有所述基因的重组载体，已经用所述重组载体转化的宿主细胞，以及通过首先培养所述转化的宿主细胞产生具有人巨核细胞增强子活性的多肽的方法，以及然后从培养物中分离所需的多肽。

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