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1. 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。

2. 发明授权

US09248164B2 Growth factor anchoring type bone graft material, method for producing growth factor anchoring type bone graft material, kit for producing growth factor anchoring type bone graft material, and method for forming bone 有权
标题翻译：生长因子锚定型骨移植材料，生长因子锚定型骨移植物材料的制备方法，生长因子锚定型骨移植材料的制备方法，骨形成方法
公开(公告)号：US09248164B2
公开(公告)日：2016-02-02
申请号：US14117599
申请日：2012-03-26
申请人： Kentaro Uchida , Koji Naruse , Masashi Takaso , Takehiko Mima , Osamu Matsushita , Takashi Haraguchi , Nozomu Nishi
发明人： Kentaro Uchida , Koji Naruse , Masashi Takaso , Takehiko Mima , Osamu Matsushita , Takashi Haraguchi , Nozomu Nishi
IPC分类号： A61K38/18 , A61K9/70 , A61K47/42 , A61L27/54 , A61K38/48 , A61L27/36 , C07K14/33 , C07K14/485 , C12N9/52
CPC分类号： A61K38/1825 , A61K38/1808 , A61K38/4886 , A61L27/3608 , A61L27/54 , A61L2300/252 , A61L2300/414 , A61L2430/02 , C07K14/33 , C07K14/485 , C07K2319/00 , C07K2319/03 , C07K2319/70 , C12N9/52
摘要： Provided is a growth factor anchoring type bone graft material, wherein a bone graft substrate exposing at least a collagen fiber is bound to a collagen-binding-site-containing growth factor which contains a growth factor receptor agonist peptide and a collagen-binding peptide. The same can be produced by mixing a bone graft substrate and a collagen-binding-site-containing growth factor which contains a growth factor receptor agonist peptide and a collagen-binding peptide, and is also superior in osteogenic ability.
摘要翻译：提供了一种生长因子锚定型骨移植材料，其中暴露至少胶原纤维的骨移植基质与含有生长因子受体激动剂肽和胶原结合肽的含胶原结合位点的生长因子结合。通过混合骨移植基质和含有生长因子受体激动剂肽和胶原结合肽的含有胶原结合位点的生长因子，也可以产生同样的效果，并且成骨能力也优异。

3. 发明申请

US20110281351A1 PROCESS FOR PRODUCING LAMINATED HIGH-DENSITY CULTURED ARTIFICIAL TISSUE, AND LAMINATED HIGH-DENSITY CULTURED ARTIFICIAL TISSUE 审中-公开
标题翻译：生产层压高密度人造纤维组织的方法和层压高密度培养人造纤维组织
公开(公告)号：US20110281351A1
公开(公告)日：2011-11-17
申请号：US13146367
申请日：2010-01-28
申请人： Eijiro Adachi , Osamu Matsushita , Hironobu Iwashiro , Satoshi Hosoya , Nozomu Nishi
发明人： Eijiro Adachi , Osamu Matsushita , Hironobu Iwashiro , Satoshi Hosoya , Nozomu Nishi
IPC分类号： C12N5/071
CPC分类号： A61L27/60 , A61L27/3633 , A61L27/3895
摘要： Disclosed is a process for producing an artificial tissue, which comprises a step of providing a liquid flow control member and a mesh member in a flow path through which a cell culture liquid comprising at least one type of animal cells, a collagen-binding cell growth factor and an extracellular matrix component is circulated and cultured to accumulate the extracellular matrix molecule and the animal cells on the surface of the liquid flow control member at a high density, thereby forming a high-density cultured tissue, wherein the liquid flow control member and the mesh member are so arranged in the flow path that these members are in contact with each other or in proximity to each other, and wherein the mesh member is arranged on the back side of the liquid flow control member relative to the direction of the liquid flow. Also disclosed is an artificial tissue produced by the process.
摘要翻译：公开了一种生产人造组织的方法，其包括在流路中提供液体流动控制构件和网状构件的步骤，通过该流路将包含至少一种类型的动物细胞的细胞培养液，胶原结合细胞生长循环和培养细胞因子和细胞外基质组分，以高密度积聚细胞外基质分子和液体流量控制部件表面上的动物细胞，从而形成高密度培养组织，其中液体流动控制部件和网状构件在流路中被布置成使得这些构件彼此接触或彼此接近，并且其中网状构件相对于液体的方向布置在液体流动控制构件的背面上流。还公开了通过该方法生产的人造组织。

4. 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。

5. 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。

6. 发明申请

US20140335146A1 GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, METHOD FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, KIT FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, AND METHOD FOR FORMING BONE 有权
标题翻译：生长因子锚定型骨质量材料，生产生长因子锚定型骨质材料的方法，用于生产生长因子锚定型骨折材料的工具，以及用于形成骨的方法
公开(公告)号：US20140335146A1
公开(公告)日：2014-11-13
申请号：US14117599
申请日：2012-03-26
申请人： Kentaro Uchida , Koji Naruse , Masashi Takaso , Takehiko Mima , Osamu Matsushita , Takashi Haraguchi , Nozomu Nishi
发明人： Kentaro Uchida , Koji Naruse , Masashi Takaso , Takehiko Mima , Osamu Matsushita , Takashi Haraguchi , Nozomu Nishi
IPC分类号： A61K38/18 , A61K38/48
CPC分类号： A61K38/1825 , A61K38/1808 , A61K38/4886 , A61L27/3608 , A61L27/54 , A61L2300/252 , A61L2300/414 , A61L2430/02 , C07K14/33 , C07K14/485 , C07K2319/00 , C07K2319/03 , C07K2319/70 , C12N9/52
摘要： Provided is a growth factor anchoring type bone graft material, wherein a bone graft substrate exposing at least a collagen fiber is bound to a collagen-binding-site-containing growth factor which contains a growth factor receptor agonist peptide and a collagen-binding peptide. The same can be produced by mixing a bone graft substrate and a collagen-binding-site-containing growth factor which contains a growth factor receptor agonist peptide and a collagen-binding peptide, and is also superior in osteogenic ability.
摘要翻译：提供了一种生长因子锚定型骨移植材料，其中暴露至少胶原纤维的骨移植基质与含有生长因子受体激动剂肽和胶原结合肽的含胶原结合位点的生长因子结合。通过混合骨移植基质和含有生长因子受体激动剂肽和胶原结合肽的含有胶原结合位点的生长因子，也可以产生同样的效果，并且成骨能力也优异。

7. 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。

8. 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。

9. 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。

10. 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。

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