公开(公告)号：USD793944S1

公开(公告)日：2017-08-08

申请号：US29543915

申请日：2015-10-29

申请人： Judy Genshaft ,  Paul R. Sanberg

设计人： Judy Genshaft ,  Paul R. Sanberg

公开(公告)号：US20170065643A1

公开(公告)日：2017-03-09

申请号：US15257315

申请日：2016-09-06

申请人： Cesario Venturina Borlongan ,  Paul R. Sanberg

发明人： Cesario Venturina Borlongan ,  Paul R. Sanberg

IPC分类号： A61K35/51 ,  A61K47/26

CPC分类号： A61K35/51 ,  A61K9/0019 ,  A61K47/26

摘要： Blood brain barrier (BBB) permeabilizers, such as mannitol, can facilitate the entry of stem cells from the periphery to the stroke brain. It is unknown whether BBB permeation in the chronic stage of the disease still facilitates the entry of stem cells from the periphery to the injured brain. Evidence herein shows BBB permeation in the chronic stage of stroke assisted in the entry of stem cells from the periphery to the stroke brain. Stroke models treated with human umbilical cord stem cells (hUCBC) only (2 million viable cells), mannitol or a combination. Results revealed that hUCBC alone or combined with mannitol displayed significant behavioral and histological deficits compared to control animals, with the HUCBC-mannitol combined treatment showing improvements over hUCBC only treatments in brain cell survival in the peri-infarct area. BBB permeation in chronic stroke also lowers the effective stem cell dose necessary to improve functional outcomes.

摘要翻译： 血脑屏障（BBB）渗透剂如甘露醇可以促进干细胞从外周进入脑卒中。 在慢性疾病阶段BBB渗透是否还有助于干细胞从外周进入受损脑。 本文的证据表明，BBB在慢性中风期的渗透有助于干细胞从外周进入脑卒中。 仅用人脐带干细胞（hUCBC）处理的中风模型（200万活细胞），甘露醇或组合。 结果显示，与对照动物相比，hUCBC单独或与甘露醇组合显示出显着的行为和组织学缺陷，HUCBC-甘露醇联合治疗显示出在脑梗死区域的脑细胞存活中仅用于hUCBC治疗的改善。 慢性脑卒中中的BBB渗透也降低了改善功能结果所需的有效干细胞剂量。

公开(公告)号：US09051386B2

公开(公告)日：2015-06-09

申请号：US14220714

申请日：2014-03-20

申请人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

发明人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

IPC分类号： C07K14/47 ,  A61K38/00

CPC分类号： C07K14/4703 ,  A61K38/00 ,  Y02A50/471

摘要： A method of treating inflammation by administering a therapeutically effective amount of a human immunosuppressant protein (HISP) to a subject is presented. The inventors have discovered a novel immunosuppressive protein purified from the supernatant of hNT cell culture. The immunosuppressant protein has a molecular weight of about 40-100 kDa, an isoelectric point of about 4.4, a net ionic charge and is capable of suppressing T-cell activation, T-cell proliferation and the production of IL-2. This protein can be used in treating inflammation, preventing graft rejection after transplantation, treating autoimmune diseases and suppressing allergic responses as well as other uses.

摘要翻译： 提出了通过向受试者施用治疗有效量的人免疫抑制蛋白（HISP）来治疗炎症的方法。 本发明人发现了从hNT细胞培养物的上清液中纯化的新型免疫抑制蛋白。 免疫抑制蛋白具有约40-100kDa的分子量，约4.4的等电点，净离子电荷，并且能够抑制T细胞活化，T细胞增殖和IL-2的产生。 该蛋白质可用于治疗炎症，预防移植后的移植排斥反应，治疗自身免疫疾病和抑制过敏反应以及其他用途。

公开(公告)号：US20140369983A1

公开(公告)日：2014-12-18

申请号：US14336621

申请日：2014-07-21

申请人： Paul R. Sanberg ,  Alison E. Willing

发明人： Paul R. Sanberg ,  Alison E. Willing

IPC分类号： A61K35/14 ,  C12N5/0786

CPC分类号： A61K35/15 ,  A61K35/44 ,  A61K35/51 ,  A61K2035/124 ,  C12N5/0634 ,  C12N5/0645

摘要： The present invention is directed to compositions and methods for treatment of ischemic diseases and conditions, particularly myocardial, CNS/brain and limb ischemia. More particularly, the present invention provides methods of treating disorders by administering monocytes obtained from blood, including umbilical cord blood, peripheral blood, or bone marrow to an individual in need of treatment, wherein the drug is administered to the individual at a time point specifically determined to provide therapeutic efficacy. In one embodiment, the cells are for injection into ischemic myocardium for the treatment of angina.

摘要翻译： 本发明涉及用于治疗缺血性疾病和病症，特别是心肌，CNS /脑和肢体缺血的组合物和方法。 更具体地，本发明提供了通过从需要治疗的个体施用从血液（包括脐带血，外周血或骨髓）获得的单核细胞来治疗疾病的方法，其中在具体时间点向个体施用药物 确定提供治疗功效。 在一个实施方案中，细胞用于注射到缺血心肌中用于治疗心绞痛。

公开(公告)号：US20080279835A1

公开(公告)日：2008-11-13

申请号：US12117197

申请日：2008-05-08

申请人： Robert J. Henning ,  Paul R. Sanberg

发明人： Robert J. Henning ,  Paul R. Sanberg

IPC分类号： A61K35/14 ,  A61P9/10

CPC分类号： A61K35/51

摘要： A method of treating acute myocardial infarction has the steps of providing human umbilical cord blood cells (HUCBC); and administering the HUCBC to the individual with the acute myocardial infarction at particular time intervals after said myocardial infarction. Preferably the intervals are about one to about three hours or about 12 to about 48 hours after the acute myocardial infarction.

摘要翻译： 治疗急性心肌梗死的方法有以下步骤：提供人脐血细胞（HUCBC）; 并在所述心肌梗塞后的特定时间间隔内将HUCBC给予患有急性心肌梗死的个体。 优选地，间隔在急性心肌梗塞后约1至约3小时或约12至约48小时。

公开(公告)号：US07388076B2

公开(公告)日：2008-06-17

申请号：US10621061

申请日：2003-07-16

申请人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

发明人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

IPC分类号： C07K1/36 ,  C12P21/00

CPC分类号： C07K14/4703 ,  A61K38/00 ,  Y02A50/471

摘要： A method for purifying an immunosuppressant protein (HISP) has the steps of obtaining supernatant from hNT cells; exposing the supernatant to preparative polyacrylamide gel electrophoresis to produce 20 isoelectric fractions, including active isoelectric fraction #10; placing the active isoelectric fraction on a Blue Sepharose column to bind albumin; and collecting the free fraction containing the concentrated, isolated HISP. Also disclosed is a method of treating inflammation, using an effective amount of an HISP. The HISP is anionic, has a molecular weight of 40-100 kDa, an isoelectric point of about 4.8 and is obtained from the supernatant of hNT cells, but not from NCCIT embryonal carcinoma cells, T98G glioblastoma cells or THP-1 monocytic leukemia cells. HISP can maintain T cells in a quiescent G0/G1 state without lowering their viability. HISP loses activity when treated with heat, pH2, pH11, or mixed with trypsin or carboxypeptidase, but not with neuraminidase. HISP can suppress proliferation of responder peripheral blood mononuclear cells in allogeneic mixed lymphocyte cultures; HISP can suppress T-cell proliferation and IL-2 production in response to phorbol 12-myristate 13-acetate (PMA), ionomycin and concanavalin-A. HISP does not bind to heparin-sepharose CL-B gel; or to albumin-binding resin Blue Sepharose. HISP is concentrated with YM10 ultrafiltration. HISP does not act through the T-cell receptor-CD3 complex or via altered accessory signal cells. A method of treating inflammation comprises administering an effective amount of hNT neuronal cells.

摘要翻译： 纯化免疫抑制蛋白（HISP）的方法具有从hNT细胞获得上清液的步骤; 将上清液暴露于制备型聚丙烯酰胺凝胶电泳以产生20个等电点，包括活性等电点＃10; 将活性等电点部分置于蓝色琼脂糖凝胶柱上以结合白蛋白; 并收集含有浓缩，分离的HISP的游离级分。 还公开了使用有效量的HISP治疗炎症的方法。 HISP是阴离子型的，分子量为40-100kDa，等电点约为4.8，从hNT细胞的上清液获得，而不是来自NCCIT胚胎癌细胞，T98G胶质母细胞瘤细胞或THP-1单核细胞白血病细胞。 HISP可以将T细胞维持在静止状态，而不降低其活力。 当用热，pH2，pH11处理或与胰蛋白酶或羧肽酶混合时，HISP失去活性，但不与神经氨酸酶混合。 HISP可以抑制同种异体混合淋巴细胞培养物中应答者外周血单核细胞的增殖; HISP可以抑制佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），离子霉素和伴刀豆素A的T细胞增殖和IL-2产生。 HISP不结合肝素 - 琼脂糖CL-B凝胶; 或白蛋白结合树脂蓝色琼脂糖。 HISP集中在YM10超滤。 HISP不通过T细胞受体-CD3复合物或通过改变的附属信号细胞起作用。 治疗炎症的方法包括施用有效量的hNT神经元细胞。

公开(公告)号：US5874099A

公开(公告)日：1999-02-23

申请号：US449837

申请日：1995-05-24

申请人： Keith E. Dionne ,  Dwaine F. Emerich ,  Diane Hoffman ,  Paul R. Sanberg ,  Lisa Christenson ,  Orion D. Hegre ,  David W. Scharp ,  Paul E. Lacy ,  Patrick Aebischer ,  Alfred V. Vasoohcellos ,  Michael J. Lysaght ,  Frank T. Gentile

发明人： Keith E. Dionne ,  Dwaine F. Emerich ,  Diane Hoffman ,  Paul R. Sanberg ,  Lisa Christenson ,  Orion D. Hegre ,  David W. Scharp ,  Paul E. Lacy ,  Patrick Aebischer ,  Alfred V. Vasoohcellos ,  Michael J. Lysaght ,  Frank T. Gentile

IPC分类号： A61F2/02 ,  A61K9/00 ,  A61K9/48 ,  A61K9/50 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/18 ,  A61K39/395 ,  A61K47/36 ,  A61K48/00 ,  A61L27/00 ,  C12N5/00 ,  C12N5/071 ,  C12N5/077 ,  A61K9/14

CPC分类号： A61K9/0092 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/185 ,  A61K48/00 ,  A61K9/0024 ,  A61K9/4816 ,  C12N5/0012 ,  C12N5/0062 ,  C12N5/0614 ,  C12N5/0656 ,  C12N5/0677 ,  A61K2035/126 ,  A61K2035/128 ,  C12N2510/02 ,  Y10S514/814 ,  Y10S514/866

摘要： A method of forming an implantable and retrievable immunoisolatory vehicles is disclosed, the method comprising the steps of first forming a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of providing a biologically active product or metabolic or immunologic function, said cells being dispersed in a biocompatible hydrogel or extracellular matrix, and then forming around the core a surrounding external biocompatible thermoplastic or hydrogel jacket free of said cells projecting externally thereof, said jacket having molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.

摘要翻译： 公开了一种形成可植入和可回收的免疫隔离剂的方法，所述方法包括以下步骤：首先形成包含至少1μl的体积和至少能够提供生物活性产物或代谢或免疫功能的至少104个细胞的核心， 所述细胞分散在生物相容的水凝胶或细胞外基质中，然后在核心周围形成周围的外部生物相容性热塑性或水凝胶套，所述周围的外部生物相容性热塑性或水凝胶护套不含外部突出的所述细胞，所述护套具有分子量截留允许分子通过和穿过芯通过 所述护套提供所述生物活性产品或功能。

公开(公告)号：US08784802B2

公开(公告)日：2014-07-22

申请号：US13063456

申请日：2009-09-14

申请人： Paul R. Sanberg ,  Nelson Americo Hossne, Jr. ,  Alison E. Willing ,  Adriana Invitti

发明人： Paul R. Sanberg ,  Nelson Americo Hossne, Jr. ,  Alison E. Willing ,  Adriana Invitti

IPC分类号： A61K35/14

CPC分类号： A61K35/15 ,  A61K35/44 ,  A61K2035/124 ,  C12N5/0634 ,  C12N5/0645

摘要： The present invention is directed to compositions and methods for treatment of ischemic diseases and conditions, particularly myocardial, CNS/brain and limb ischemia. More particularly, the present invention provides methods of treating disorders by administering monocytes obtained from blood, including umbilical cord blood, peripheral blood, or bone marrow to an individual in need of treatment, wherein the drug is administered to the individual at a time point specifically determined to provide therapeutic efficacy. In one embodiment, the cells are for injection into ischemic myocardium for the treatment of angina.

摘要翻译： 本发明涉及用于治疗缺血性疾病和病症，特别是心肌，CNS /脑和肢体缺血的组合物和方法。 更具体地，本发明提供了通过从需要治疗的个体施用从血液（包括脐带血，外周血或骨髓）获得的单核细胞来治疗疾病的方法，其中在具体时间点向个体施用药物 确定提供治疗功效。 在一个实施方案中，细胞用于注射到缺血心肌中用于治疗心绞痛。

公开(公告)号：US20080280812A1

公开(公告)日：2008-11-13

申请号：US12118675

申请日：2008-05-09

申请人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

发明人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

IPC分类号： A61K38/02 ,  A61P29/00

CPC分类号： C07K14/4703 ,  A61K38/00 ,  Y02A50/471

摘要： A method for purifying an immunosuppressant protein (HISP) has the steps of obtaining supernatant from hNT cells; exposing the supernatant to preparative polyacrylamide gel electrophoresis to produce 20 isoelectric fractions, including active isoelectric fraction #10; placing the active isoelectric fraction on a Blue Sepharose column to bind albumin; and collecting the free fraction containing the concentrated, isolated HISP. Also disclosed is a method of treating inflammation, using an effective amount of an HISP. The HISP is anionic, has a molecular weight of 40-100 kDa, an isoelectric point of about 4.8 and is obtained from the supernatant of hNT cells, but not from NCCIT embryonal carcinoma cells. T98G glioblastoma cells or THP-1 monocytic leukemia cells. HISP can maintain T cells in a quiescent G.sub.0/G.sub.1 state without lowering their viability. HISP loses activity when treated with heat, pH2, pH11, or mixed with trypsin or carboxypeptidase, but not with neuraminidase. HISP can suppress proliferation of responder peripheral blood mononuclear cells in allogeneic mixed lymphocyte cultures; HISP can suppress T-cell proliferation and IL-2 production in response to phorbol 12-myristate 13-acetate (PMA), ionomycin and concanavalin-A. HISP does not bind to heparin-sepharose CL-B gel; or to albumin-binding resin Blue Sepharose, HISP is concentrated with YM10 ultrafiltration. HISP does not act through the T-cell receptor-CD3 complex or via altered accessory signal cells. A method of treating inflammation comprises administering an effective amount of hNT neuronal cells.

摘要翻译： 纯化免疫抑制蛋白（HISP）的方法具有从hNT细胞获得上清液的步骤; 将上清液暴露于制备型聚丙烯酰胺凝胶电泳以产生20个等电点，包括活性等电点＃10; 将活性等电点部分置于蓝色琼脂糖凝胶柱上以结合白蛋白; 并收集含有浓缩，分离的HISP的游离级分。 还公开了使用有效量的HISP治疗炎症的方法。 HISP是阴离子型的，分子量为40-100kDa，等电点约为4.8，从hNT细胞的上清中获得，但不是来自NCCIT胚胎癌细胞。 T98G胶质母细胞瘤细胞或THP-1单核细胞白血病细胞。 HISP可以将T细胞维持在静止的G.sub.0 / G.sub.1状态，而不降低其活力。 当用热，pH2，pH11处理或与胰蛋白酶或羧肽酶混合时，HISP失去活性，但不与神经氨酸酶混合。 HISP可以抑制同种异体混合淋巴细胞培养物中应答者外周血单核细胞的增殖; HISP可以抑制佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），离子霉素和伴刀豆素A的T细胞增殖和IL-2产生。 HISP不结合肝素 - 琼脂糖CL-B凝胶; 或白蛋白结合树脂蓝色琼脂糖，HISP用YM10超滤浓缩。 HISP不通过T细胞受体-CD3复合物或通过改变的附属信号细胞起作用。 治疗炎症的方法包括施用有效量的hNT神经元细胞。

公开(公告)号：US06960351B2

公开(公告)日：2005-11-01

申请号：US10624081

申请日：2003-07-21

申请人： Keith E. Dionne ,  Dwaine F. Emerich ,  Diane Hoffman ,  Paul R. Sanberg ,  Lisa Christenson ,  Orion D. Hegre ,  David W. Scharp ,  Paul E. Lacy ,  Patrick Aebischer ,  Alfred V. Vasconcellos ,  Michael J. Lysaght ,  Frank T. Gentile

发明人： Keith E. Dionne ,  Dwaine F. Emerich ,  Diane Hoffman ,  Paul R. Sanberg ,  Lisa Christenson ,  Orion D. Hegre ,  David W. Scharp ,  Paul E. Lacy ,  Patrick Aebischer ,  Alfred V. Vasconcellos ,  Michael J. Lysaght ,  Frank T. Gentile

IPC分类号： A61F2/02 ,  A61K9/00 ,  A61K9/48 ,  A61K9/50 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/18 ,  A61K39/395 ,  A61K47/36 ,  A61K48/00 ,  A61L27/00 ,  C12N5/00 ,  C12N5/071 ,  C12N5/077 ,  A61F13/00 ,  A61F2/00 ,  A61F9/14 ,  A61F9/16 ,  A61F9/22

CPC分类号： A61K9/0092 ,  A61K9/0024 ,  A61K9/4816 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/185 ,  A61K48/00 ,  A61K2035/126 ,  A61K2035/128 ,  C12N5/0012 ,  C12N5/0062 ,  C12N5/0614 ,  C12N5/0656 ,  C12N5/0677 ,  C12N2510/02 ,  Y10S514/814 ,  Y10S514/866

摘要： An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process. A method for isolating cells within a biocompatible, immunoisolatory implantable vehicle, which protects the isolated cells from attack by the immune system of an individual in whom the vehicle is implanted. A method of providing a needed biological product or metabolic function to an individual, comprising implanting into the individual an immunoisolatory vehicle containing isolated cells which produce the product or provide the metabolic function.

摘要翻译： 用于植入到产生所需产品或提供所需代谢功能的细胞个体中的免疫分析载体。 载体由含有分离的细胞和足以维持细胞的材料的核心区域组成，以及不含分离细胞的选择性选择性生物相容的外周区域，所述细胞免疫分离核心，但提供分泌产物或代谢功能的递送， 个人 该载体特别适合于从朗格汉斯的免疫隔离胰岛递送胰岛素，并且还可有利地用于递送高分子量产物，例如大于IgG的产物。 在共挤出方法的第一实施方案中和在逐步方法的第二实施方案中制备生物相容的免疫隔离可植入载体的方法。 一种用于分离生物相容的免疫隔离可植入载体中的细胞的方法，其保护分离的细胞免受被植入其中的个体的免疫系统的攻击。 向个体提供所需的生物制品或代谢功能的方法，包括向个体植入包含产生产物或提供代谢功能的分离细胞的免疫隔离载体。