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1. 发明申请

US20080044385A1 Novel Modified Galectin 8 Proteins and Use Thereof 审中-公开
标题翻译：新型修饰的Galectin 8蛋白及其用途
公开(公告)号：US20080044385A1
公开(公告)日：2008-02-21
申请号：US11629296
申请日：2005-05-13
申请人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Akio Ito
发明人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Akio Ito
IPC分类号： C07K14/42 , A61K31/7088 , A61K38/16 , C12N15/11 , C12N15/63 , C12N1/00 , A61K48/00
CPC分类号： C07K14/4726 , A61K38/00
摘要： Recombinant galectin 8 (rGal 8), produced in host Escherichia coli, exerts hemagglutinating activity, neutrophil adhesion inducing activity, integrin αM-binding activity, proMMP-9 binding activity, active form MMP-9 production promoting activity, superoxide production promoting activity, apoptosis inducing activity for a particular cell, suppressive or inhibitory activity against the metastasis/invasion of tumor cells, etc. In the rGal 8, however, a link domain linking two CRDs is highly susceptible to protease and, therefore, is very easily digestible with the enzyme, thereby losing the above activities. Thus, there is a need for a more stabilized molecule in view of further studies. Modification of the link domain linking two CRDs in galectin 8 provides a modified molecule having an elevated activity without any undesirable effects on the above activities.
摘要翻译：在宿主大肠杆菌中产生的重组半乳凝素8（rGal 8）发挥血凝活性，嗜中性粒细胞粘附诱导活性，整联蛋白αM结合活性，proMMP-9结合活性，活性形式MMP-9生产促进活性，超氧化物生成促进活性，特定细胞的细胞凋亡诱导活性，抑制或抑制肿瘤细胞转移/侵袭的活性等。然而，在rGal8中，连接两个CRD的连接域对蛋白酶非常敏感，因此，与酶易于消化，从而失去上述活性。因此，鉴于进一步研究，需要更稳定的分子。在半乳凝素8中连接两个CRD的连接结构域的修饰提供了具有升高的活性的修饰分子，而对上述活性没有任何不良影响。

2. 发明申请

US20060134119A1 Drugs containing galectin 9 审中-公开
标题翻译：含有半乳凝素的药物9
公开(公告)号：US20060134119A1
公开(公告)日：2006-06-22
申请号：US10543193
申请日：2003-08-21
申请人： Mitsuomi Hirashima , Nozomu Nishi , Akira Yamauchi , Naoko Yoshida , Masako Seki
发明人： Mitsuomi Hirashima , Nozomu Nishi , Akira Yamauchi , Naoko Yoshida , Masako Seki
IPC分类号： A61K48/00 , A61K38/17 , A61K39/395
CPC分类号： A61K38/1709 , C07K16/18
摘要： Galectin 9 exerts various functions depending on its localizations. On the other hand, galectin 9 is expected as participating in various biological functions. Thus, it has been required to clarify the detailed biological activities of galectin 9 and develop galectin 9-related techniques including development of drugs. Human galectin 9 shows a cytotoxic activity and an apoptosis-inducing activity on tumor cells but shows neither cytotoxic activity nor apoptosis-inducing activity on normal cells. Therefore, it is possible to employ galectin 9 proteins, galectin 9 agonists, galectin 9 antagonists, anti-galectin 9 binding protein antibodies, anti-galectin 9 binding sugar chain antibodies, galectin 9-producing, releasing or inducing substances, etc. as antitumor, antiallergic, immunosuppressive agents, drugs for autoimmune diseases, anti-inflammatory agents and active ingredients for adrenocortical steroid hormone alternatives.
摘要翻译： Galectin 9根据其定位具有各种功能。另一方面，半乳凝素9预期参与各种生物学功能。因此，需要阐明半乳凝素9的详细生物学活性，并开发包含药物开发的半乳凝素9相关技术。人半乳凝素9显示对肿瘤细胞的细胞毒活性和细胞凋亡诱导活性，但对正常细胞无细胞毒性活性或细胞凋亡诱导活性。因此，可以使用半乳凝素9蛋白，半乳凝素9激动剂，半乳凝素9拮抗剂，抗半乳凝素9结合蛋白抗体，抗半乳凝素9结合糖链抗体，半乳凝素-9产生，释放或诱导物质等作为抗肿瘤剂，抗过敏药，免疫抑制剂，自身免疫性疾病药物，抗炎药和肾上腺皮质激素替代物的活性成分。

3. 发明授权

US08580743B2 Modified galectin 9 proteins and methods of treatment using them 有权
标题翻译：修饰的半乳凝素9蛋白和使用它们的治疗方法
公开(公告)号：US08580743B2
公开(公告)日：2013-11-12
申请号：US13591366
申请日：2012-08-22
申请人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
发明人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
IPC分类号： A61K38/00 , A61K35/02 , A61K35/04 , C07K14/00 , C12P21/00
CPC分类号： C07K14/4726 , A61K38/00 , A61K48/00 , Y02A50/402 , Y02A50/406 , Y02A50/411 , Y02A50/463 , Y02A50/471 , Y02A50/475 , Y02A50/48
摘要： A recombinant galectin 9 (rGal 9) is provided which exhibits an immune system-mediated action and a direct action on tumor cells (i.e., activity of inducing the intercellular adhesion and apoptosis of the tumor cells), thereby potent in inducing the inhibition of cancer metastasis and reduction. Moreover, the rGal 9 exerts no efficacy on non-activated lymphocytes but can induce apoptosis in activated T cells, in particular, CD4-positive T cells causing an excessive immune response.
摘要翻译：提供了重组galectin 9（rGal 9），其表现出免疫系统介导的作用和对肿瘤细胞的直接作用（即，诱导肿瘤细胞的细胞间粘附和凋亡的活性），从而有效诱导癌症的抑制转移和还原。此外，rGal9对非活化淋巴细胞没有效力，但可以诱导活化的T细胞，特别是导致过度免疫应答的CD4阳性T细胞的细胞凋亡。

4. 发明申请

US20100203628A1 Novel modified galectin 9 proteins and use thereof 有权
标题翻译：新型改良的半乳凝素9蛋白及其用途
公开(公告)号：US20100203628A1
公开(公告)日：2010-08-12
申请号：US11547091
申请日：2005-03-29
申请人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
发明人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
IPC分类号： C12N5/00 , C07K14/435 , C12N15/12 , C12N15/63
CPC分类号： C07K14/4726 , A61K38/00 , A61K48/00 , Y02A50/402 , Y02A50/406 , Y02A50/411 , Y02A50/463 , Y02A50/471 , Y02A50/475 , Y02A50/48
摘要： It is suggested that recombinant galectin 9 (rGal 9), produced in host Escherichia coli, exhibits an immune system-mediated action and a direct action on tumor cells (i.e., activity of inducing the intercellular adhesion and apoptosis of the tumor cells), thereby potent in inducing the inhibition of cancer metastasis and reduction. Moreover, the rGal 9 exerts no efficacy on non-activated lymphocytes but can induce apoptosis in activated T cells, in particular, CD4-positive T cells causing an excessive immune response. The rGal 9 has a further potent apoptosis-inducing property on synovial cells participating in joint deformation in rheumatism, etc. In the rGal 9, however, a link domain linking two CRDs is highly susceptible to protease and, therefore, is very easily digestible with the enzyme, thereby losing the above activities. Thus, there is a need for a more stabilized molecule in view of further studies. Modification of the link domain linking two CRDs in galectin 9 provides a modified molecule having an elevated activity without any undesirable effects on the above activities.
摘要翻译：建议在宿主大肠杆菌中产生的重组半乳凝素9（rGal 9）表现出免疫系统介导的作用和对肿瘤细胞的直接作用（即，诱导肿瘤细胞的细胞间粘附和凋亡的活性），由此有效诱导癌症转移和还原的抑制。此外，rGal9对非活化淋巴细胞没有效力，但可以诱导活化的T细胞，特别是导致过度免疫应答的CD4阳性T细胞的细胞凋亡。 rGal9对参与风湿病关节变形的滑膜细胞具有更强的细胞凋亡诱导性质。然而，在rGal9中，连接两个CRD的连接域对蛋白酶非常敏感，因此很容易被消化该酶，从而失去上述活性。因此，鉴于进一步研究，需要更稳定的分子。连接半乳凝素9中两个CRD的连接结构域的修饰提供了具有升高活性的修饰分子，而对上述活性没有任何不良影响。

5. 发明申请

US20130017998A1 NOVEL MODIFIED GALECTIN 9 PROTEINS AND USE THEREOF 有权
标题翻译：新改良的GALECTIN 9蛋白及其用途
公开(公告)号：US20130017998A1
公开(公告)日：2013-01-17
申请号：US13591366
申请日：2012-08-22
申请人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
发明人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
IPC分类号： A61K38/17 , A61P19/02 , A61P35/00 , A61P29/00 , A61P19/08 , C07K14/435 , A61P37/08
CPC分类号： C07K14/4726 , A61K38/00 , A61K48/00 , Y02A50/402 , Y02A50/406 , Y02A50/411 , Y02A50/463 , Y02A50/471 , Y02A50/475 , Y02A50/48
摘要： A recombinant galectin 9 (rGal 9) is provided which exhibits an immune system-mediated action and a direct action on tumor cells (i.e., activity of inducing the intercellular adhesion and apoptosis of the tumor cells), thereby potent in inducing the inhibition of cancer metastasis and reduction. Moreover, the rGal 9 exerts no efficacy on non-activated lymphocytes but can induce apoptosis in activated T cells, in particular, CD4-positive T cells causing an excessive immune response.
摘要翻译：提供了重组galectin 9（rGal 9），其表现出免疫系统介导的作用和对肿瘤细胞的直接作用（即，诱导肿瘤细胞的细胞间粘附和凋亡的活性），从而有效诱导癌症的抑制转移和还原。此外，rGal9对非活化淋巴细胞没有效力，但可以诱导活化的T细胞，特别是导致过度免疫应答的CD4阳性T细胞的细胞凋亡。

6. 发明授权

US08268324B2 Modified galectin 9 proteins and use thereof 有权
标题翻译：改良的半乳凝素9蛋白及其用途
公开(公告)号：US08268324B2
公开(公告)日：2012-09-18
申请号：US11547091
申请日：2005-03-29
申请人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
发明人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi , Aiko Ito
IPC分类号： A61K39/00 , C07K14/00 , C12P21/00
CPC分类号： C07K14/4726 , A61K38/00 , A61K48/00 , Y02A50/402 , Y02A50/406 , Y02A50/411 , Y02A50/463 , Y02A50/471 , Y02A50/475 , Y02A50/48
摘要： It is suggested that recombinant galectin 9 (rGal 9), produced in host Escherichia coli, exhibits an immune system-mediated action and a direct action on tumor cells (i.e., activity of inducing the intercellular adhesion and apoptosis of the tumor cells), thereby potent in inducing the inhibition of cancer metastasis and reduction. Moreover, the rGal 9 exerts no efficacy on non-activated lymphocytes but can induce apoptosis in activated T cells, in particular, CD4-positive T cells causing an excessive immune response. The rGal 9 has a further potent apoptosis-inducing property on synovial cells participating in joint deformation in rheumatism, etc. In the rGal 9, however, a link domain linking two CRDs is highly susceptible to protease and, therefore, is very easily digestible with the enzyme, thereby losing the above activities. Thus, there is a need for a more stabilized molecule in view of further studies. Modification of the link domain linking two CRDs in galectin 9 provides a modified molecule having an elevated activity without any undesirable effects on the above activities.
摘要翻译：建议在宿主大肠杆菌中产生的重组半乳凝素9（rGal 9）表现出免疫系统介导的作用和对肿瘤细胞的直接作用（即，诱导肿瘤细胞的细胞间粘附和凋亡的活性），由此有效诱导癌症转移和还原的抑制。此外，rGal9对非活化淋巴细胞没有效力，但可以诱导活化的T细胞，特别是导致过度免疫应答的CD4阳性T细胞的细胞凋亡。 rGal9对参与风湿病关节变形的滑膜细胞具有更强的细胞凋亡诱导性质。然而，在rGal9中，连接两个CRD的连接域对蛋白酶非常敏感，因此很容易被消化该酶，从而失去上述活性。因此，鉴于进一步研究，需要更稳定的分子。连接半乳凝素9中两个CRD的连接结构域的修饰提供了具有升高活性的修饰分子，而对上述活性没有任何不良影响。

7. 发明申请

US20070042941A1 Galectin 9-inducing factors 审中-公开
标题翻译：半乳凝素9诱导因子
公开(公告)号：US20070042941A1
公开(公告)日：2007-02-22
申请号：US10554721
申请日：2004-04-28
申请人： Mitsuomi Hirashima , Nozomu Nishi , Akira Yamauchi , Naoko Yoshida , Masako Seki
发明人： Mitsuomi Hirashima , Nozomu Nishi , Akira Yamauchi , Naoko Yoshida , Masako Seki
IPC分类号： A61K38/17 , C07K14/47 , C07H21/04 , C12P21/06
CPC分类号： A61K38/1709 , C07K14/4726
摘要： It has been disclosed that Galectin 9, which is a physiologically active substance acting as a lectin, is expressed in various cells and a correlationship is observed between the expression level of galectin 9 and the metastatic ability of tumors. Therefore, it is presumed that galectin 9 would relate to various physiological phenomena. Thus, a substance allowing the control of galectin 9 production and release is expected as exerting an activity of inducing antitumor and/or anti-inflammatory actions, etc. Therefore, it is required to reveal the same. It has been found that a factor inducing the production and release of galectin 9, “galectin 9-inducing factor”, is contained in a certain solubilized tumor cell membrane fraction. This factor can be obtained as a concanavalin A-adsorbed fraction and as a concentrated active fraction by fractionation with an ion exchange column packed with Resource Q®, a hydroxyapatite column, etc. Assay reagents, drugs, assays, etc. can be developed by using the galectin 9-inducing activity of this factor.
摘要翻译：已经公开了作为凝集素的生理活性物质的半乳凝素9在各种细胞中表达，并且在半乳凝素9的表达水平与肿瘤的转移能力之间观察到相关性。因此，推测半乳凝素9与各种生理现象有关。因此，预期能够控制半乳凝素9的产生和释放的物质具有诱导抗肿瘤和/或抗炎作用的活性等。因此，需要显示它。已经发现，诱导半乳凝素9的产生和释放的因子“半乳凝素9诱导因子”被包含在某些溶解的肿瘤细胞膜级分中。可以通过用填充有Resource Q（R），羟基磷灰石柱等的离子交换柱进行分级，作为伴刀豆素A吸附级分和作为浓缩的活性级分获得该因子。可以使用测定试剂，药物，测定等通过使用该因子的半乳凝素9诱导活性开发。

8. 发明申请

US20100009908A1 Galectin 9-Polymer Conjugates 审中-公开
标题翻译： Galectin 9-聚合物缀合物
公开(公告)号：US20100009908A1
公开(公告)日：2010-01-14
申请号：US12309583
申请日：2007-07-18
申请人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi
发明人： Nozomu Nishi , Mitsuomi Hirashima , Akira Yamauchi
IPC分类号： A61K47/48
CPC分类号： C07K14/4726 , A61K38/00
摘要： Galectin 9, which is an immune function-controlling factor belonging to a new class that is different from known cytokines and is expected to be used as a therapeutic drug for various immune-related diseases such as an autoimmune disease, has disadvantages (such as high sensitivity to protease and poor solubility) to be solved in developing therapeutic drugs. Therefore, there is a need to overcome these disadvantages. Chemically modified galectin 9, prepared by conjugating a polymer (for example, poly(ethylene glycol: PEG) to galectin 9, in particular, stabilized galectin 9, is verified to exert higher solubility with improvements in pharmacodynamics and pharmacokinetics (for example, prolongation of action potential duration, such as prolongation of blood half-life and others) and in suppression of hemagglutination and thus has excellent characteristics as a drug.
摘要翻译：作为属于与已知细胞因子不同的新类别的免疫功能调节因子的半乳凝素9预期被用作各种免疫相关疾病如自身免疫性疾病的治疗药物，具有缺点（例如高对蛋白酶的敏感性和溶解性差）在开发治疗药物中得到解决。因此，需要克服这些缺点。验证通过将聚合物（例如，聚乙二醇：PEG）与半乳聚糖9（特别是稳定的半乳聚糖9）结合而制备的化学修饰的半乳凝素9，其药效学和药代动力学的改善（例如，动作电位持续时间，如血液半衰期延长等），抑制血细胞凝集，作为药物具有优异的特性。

9. 发明申请

US20090023143A1 Predicting agent for metastasis 审中-公开
标题翻译：转移预测剂
公开(公告)号：US20090023143A1
公开(公告)日：2009-01-22
申请号：US11905296
申请日：2007-09-28
申请人： Mitsuomi Hirashima , Akira Yamauchi , Toshiro Kageshita , Takanori Nakamura , Nozomu Nishi
发明人： Mitsuomi Hirashima , Akira Yamauchi , Toshiro Kageshita , Takanori Nakamura , Nozomu Nishi
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： C12Q1/6886 , C07K16/18 , C07K16/26 , C12Q2600/158 , G01N33/5011 , G01N33/574 , G01N33/57484 , G01N2333/4724
摘要： By disclosing part of metastasis mechanisms in cancer cells, the metastatic potential of cancer cells will be determinable. Anti-galectin-9 Ab against galectin-9 is contained as an effective component with or without others, thereby enabling the evaluation or detection of galectin-9 expression levels in cancer cells wherein the metastatic potential of the cancer cells can be assessed or detected.
摘要翻译：通过揭示癌细胞中转移机制的一部分，癌细胞的转移潜力是可以确定的。含有半乳凝素-9抗体的抗半乳凝素-9抗体作为有或无其他成分的有效成分被含有，从而能够评价或检测癌细胞中的半乳凝素-9表达水平，其中可以评估或检测癌细胞的转移潜力。

10. 发明申请

US20140048805A1 BONDING-SUBSTRATE FABRICATION METHOD, BONDING SUBSTRATE, SUBSTRATE BONDING METHOD, BONDING-SUBSTRATE FABRICATION APPARATUS, AND SUBSTRATE ASSEMBLY 有权
公开(公告)号：US20140048805A1
公开(公告)日：2014-02-20
申请号：US13982697
申请日：2012-01-30
申请人： Tadatomo Suga , Akira Yamauchi , Ryuichi Kondou
发明人： Tadatomo Suga , Akira Yamauchi , Ryuichi Kondou
IPC分类号： H01L21/322 , H01L29/04 , H01L29/36 , H01L21/263
CPC分类号： H01L21/3221 , B23K1/20 , B23K20/24 , B23K2101/36 , H01J37/317 , H01J2237/202 , H01J2237/3165 , H01L21/02046 , H01L21/2007 , H01L21/263 , H01L21/302 , H01L21/67092 , H01L21/67115 , H01L21/76251 , H01L29/04 , H01L29/36
摘要： [Problem] To provide a substrate bonding technique having a wide range of application. [Solution] A silicon thin film is formed on a bonding surface, and the interface with the substrate is surface-treated using energetic particles/metal particles.

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