公开(公告)号：US07560102B2

公开(公告)日：2009-07-14

申请号：US10810653

申请日：2004-03-29

申请人： Michal Eisenbach-Schwartz ,  Ehud Hauben ,  Irun R. Cohen ,  Pierre Beserman ,  Alon Monsonego ,  Gila Moalem

发明人： Michal Eisenbach-Schwartz ,  Ehud Hauben ,  Irun R. Cohen ,  Pierre Beserman ,  Alon Monsonego ,  Gila Moalem

IPC分类号： A61K38/04 ,  A61K38/17 ,  C12N5/00 ,  C07K14/435 ,  C07K7/00

CPC分类号： A61K38/1709 ,  A61K39/00 ,  A61K39/0007 ,  A61K48/00 ,  A61K2039/5158 ,  C07K14/47 ,  C07K14/705

摘要： Compositions and methods to promote nerve regeneration or to confer neuroprotection and prevent or inhibit neuronal degeneration within the nervous system, either the central nervous system or the peripheral nervous system, are provided. Treatment involves administering NS-specific activated T cells, or an NS-specific antigen or analog thereof, a peptide derived therefrom or an analog or derivative of said peptide, or a nucleotide sequence encoding such an antigen or peptide, or any combination thereof.

摘要翻译： 提供了促进神经再生或赋予神经保护作用并预防或抑制神经系统（中枢神经系统或周围神经系统）神经元变性的组合物和方法。 治疗涉及施用NS-特异性活化的T细胞或NS-特异性抗原或其类似物，由其衍生的肽或所述肽的类似物或衍生物，或编码这种抗原或肽的核苷酸序列或其任何组合。

公开(公告)号：US20080279869A1

公开(公告)日：2008-11-13

申请号：US11563630

申请日：2006-11-27

申请人： Michal Eisenbach-Schwartz ,  Ehud Hauben

发明人： Michal Eisenbach-Schwartz ,  Ehud Hauben

IPC分类号： A61K39/00 ,  A61P25/28 ,  A61P9/10 ,  A61P25/02

CPC分类号： A61K38/39 ,  A61K39/0007

摘要： Compositions are provided for promoting nerve regeneration or reducing or inhibiting degeneration in the CNS or PNS to ameliorate the effects of injury or disease. The composition includes an active ingredient selected from:(a) a peptide obtained by modification of a self-peptide derived from a CNS-specific antigen, which modification consists in the replacement of one or more amino acid residues of the self-peptide by different amino acid residues, such modified CNS peptide still being capable of recognizing the T-cell receptor recognized by the self-peptide but with less affinity; (b) a nucleotide sequence encoding such a peptide; (c) T cells activated by such peptide; and (d) any combination of (a)-(c). The peptide is preferably obtained by modification of the self-peptide p87-99 of MBP, more preferably, by replacing lysine 91 with glycine (G91) or alanine (A91) or by replacing proline 96 with alanine (A96).

摘要翻译： 提供组合物用于促进神经再生或减少或抑制CNS或PNS中的变性，以改善损伤或疾病的影响。 该组合物包括选自以下的活性成分：（a）通过修饰衍生自CNS特异性抗原的自身肽获得的肽，该修饰是由不同的自身肽的一个或多个氨基酸残基取代 氨基酸残基，这种修饰的CNS肽仍然能够识别由自身肽识别但具有较小亲和力的T细胞受体; （b）编码这种肽的核苷酸序列; （c）由该肽激活的T细胞; 和（d）（a） - （c）的任何组合。 肽优选通过修饰MBP的自身肽p87-99，更优选通过用甘氨酸（G91）或丙氨酸（A91）代替赖氨酸91或用丙氨酸（A96）代替脯氨酸96来获得。

公开(公告)号：US07399740B2

公开(公告)日：2008-07-15

申请号：US10807414

申请日：2004-03-24

申请人： Michal Eisenbach-Schwartz ,  Ester Yoles ,  Ehud Hauben

发明人： Michal Eisenbach-Schwartz ,  Ester Yoles ,  Ehud Hauben

IPC分类号： A61K38/02

CPC分类号： A61K38/02 ,  A61K39/00 ,  A61K39/0007 ,  A61K2039/5158

摘要： Methods and compositions are provided for preventing or inhibiting neuronal degeneration, or for promoting nerve regeneration, in the central nervous system (CNS) or peripheral nervous system (PNS), or for protecting nerves from glutamate toxicity, which comprises administering to an individual in need thereof an effective amount of the copolymer poly-Glu,Tyr.

摘要翻译： 提供了用于在中枢神经系统（CNS）或周围神经系统（PNS）中预防或抑制神经元变性或促进神经再生或用于保护神经免受谷氨酸毒性的方法和组合物，其包括向有需要的个体施用 的有效量的共聚物聚-Glu，Tyr。

公开(公告)号：US06835711B2

公开(公告)日：2004-12-28

申请号：US09893344

申请日：2001-06-28

申请人： Michal Eisenbach-Schwartz ,  Ester Yoles ,  Ehud Hauben

发明人： Michal Eisenbach-Schwartz ,  Ester Yoles ,  Ehud Hauben

IPC分类号： A61K3800

CPC分类号： A61K39/00 ,  A61K35/17 ,  A61K38/02 ,  A61K39/0007 ,  A61K2039/5158

摘要： Methods and compositions are provided for preventing or inhibiting neuronal degeneration, or for promoting nerve regeneration, in the central nervous system (CNS) or peripheral nervous system (PNS), or for protecting CNS cells from glutamate toxicity, comprising an effective amount of an agent selected from the group consisting of (a) poly-Glu,Tyr and (b) T cells which have been activated by poly-Glue,Tyr.

摘要翻译： 提供了用于预防或抑制中枢神经系统（CNS）或周围神经系统（PNS）中的神经元变性或促进神经再生或用于保护CNS细胞免于谷氨酸毒性的方法和组合物，其包含有效量的药剂 选自（a）聚-Gu，Tyr和（b）已经被聚胶Tyr激活的T细胞。

公开(公告)号：US07407936B2

公开(公告)日：2008-08-05

申请号：US11034262

申请日：2005-01-13

申请人： Michal Eisenbach-Schwartz ,  Irun R Cohen ,  Michael Sela ,  Eti Yoles ,  Jonathan Kipnis

发明人： Michal Eisenbach-Schwartz ,  Irun R Cohen ,  Michael Sela ,  Eti Yoles ,  Jonathan Kipnis

IPC分类号： A01N37/18

CPC分类号： A61K38/1709 ,  A61K38/16 ,  A61K39/0008 ,  A61K2039/5158

摘要： Methods are provided for treating injury to or disease of the central or peripheral nervous system. In one embodiment, treatment is effected by administering activated T cells that recognize an antigen of Cop 1 or a Cop 1-related peptide or polypeptide to promote nerve regeneration or to prevent or inhibit neuronal degeneration within the nervous system. In another embodiment, treatment involves administering Cop 1 or a Cop 1-related peptide or polypeptide to promote nerve regeneration or to prevent or inhibit neuronal degeneration in the nervous system, either the central nervous system or the peripheral nervous system. The activated T cells, which have been activated by the presence of Cop 1 or a Cop 1-related peptide or polypeptide, can be administered alone or in combination with Cop 1 or a Cop 1-related peptide or polypeptide.

摘要翻译： 提供用于治疗中枢或周围神经系统的损伤或疾病的方法。 在一个实施方案中，通过施用识别Cop1或Cop1相关肽或多肽的抗原以激活神经再生或预防或抑制神经系统内神经元变性的活化T细胞进行治疗。 在另一个实施方案中，治疗包括施用Cop1或Cop1相关肽或多肽以促进神经再生或预防或抑制神经系统，即中枢神经系统或周围神经系统中的神经元变性。 已经通过存在Cop1或Cop1相关肽或多肽而被活化的活化的T细胞可单独或与Cop 1或Cop 1相关的肽或多肽组合施用。

公开(公告)号：US06844314B2

公开(公告)日：2005-01-18

申请号：US09765644

申请日：2001-01-22

申请人： Michal Eisenbach-Schwartz ,  Irun R. Cohen ,  Michael Sela ,  Eti Yoles ,  Jonathan Kipnis

发明人： Michal Eisenbach-Schwartz ,  Irun R. Cohen ,  Michael Sela ,  Eti Yoles ,  Jonathan Kipnis

IPC分类号： A61K38/00 ,  A61K35/14 ,  A61K38/16 ,  A61K38/17 ,  A61K39/00 ,  A61P3/02 ,  A61P25/02 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P27/06 ,  A61P43/00 ,  A01N37/18

CPC分类号： A61K38/1709 ,  A61K38/16 ,  A61K39/0008 ,  A61K2039/5158

摘要： Methods are provided for treating injury to or disease of the central or peripheral nervous system. In one embodiment, treatment is effected by administering activated T cells that recognize an antigen of Cop 1 or a Cop 1-related peptide or polypeptide to promote nerve regeneration or to prevent or inhibit neuronal degeneration within the nervous system. In another embodiment, treatment involves administering Cop 1 or a Cop 1-related peptide or polypeptide to promote nerve regeneration or to prevent or inhibit neuronal degeneration in the nervous system, either the central nervous system or the peripheral nervous system. The activated T cells, which have been activated by the presence of Cop 1 or a Cop 1-related peptide or polypeptide, can be administered alone or in combination with Cop 1 or a Cop 1-related peptide or polypeptide.

公开(公告)号：US6126939A

公开(公告)日：2000-10-03

申请号：US864301

申请日：1997-05-28

申请人： Michal Eisenbach-Schwartz ,  Pierre Beserman ,  David L. Hirschberg

发明人： Michal Eisenbach-Schwartz ,  Pierre Beserman ,  David L. Hirschberg

IPC分类号： A61K9/08 ,  A61K38/00 ,  A61P1/04 ,  A61P9/00 ,  A61P11/00 ,  A61P11/06 ,  A61P13/12 ,  A61P17/00 ,  A61P19/02 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P27/00 ,  A61P27/16 ,  A61P29/00 ,  A61P37/06 ,  A61P37/08 ,  C07K4/12 ,  C07K5/06 ,  C07K5/072 ,  C07K5/08 ,  A61K38/05 ,  A61K51/08

CPC分类号： C07K5/08 ,  C07K5/06095 ,  C07K5/06104 ,  C07K5/06165 ,  C07K5/081 ,  C07K5/0815 ,  C07K5/123 ,  A61K38/00

摘要： The present invention is directed to peptides of the formulas (i) Xaa-Yaa-Arg, wherein either Xaa is any amino acid residue and Yaa is Glu or Xaa is absent and Yaa is any amino acid residue with the exception of Pro; (ii) Arg-Yaa-Xaa, wherein either Xaa is any amino acid residue and Yaa is Glu or Xaa is absent and Yaa is any amino acid residue with the exception of Asn; (iii) Xaa-Arg-Yaa, wherein Xaa is any amino acid residue and Yaa is Glu; and (iv) Yaa-Arg-Xaa, wherein Xaa is any amino acid residue and Yaa is Glu, and to derivatives thereof, which exert an inhibitory effect on macrophage migration and/or macrophage phagocytic activity. In addition, the peptides and derivatives thereof exert an inhibitory effect on the ability of macrophages and T cells to adhere to extracellular matrix and/or fibronectin. The peptides and derivatives thereof exert an inhibitory effect on a humoral and/or cellular immune response. The invention is also directed to methods for use of the peptides and derivatives thereof and compositions containing them for the inhibition of inflammation, including but not limited to, inflammation at a joint, in the central nervous system generally, at specific lesions in the central nervous system, and other immune privileged sites.

摘要翻译： 本发明涉及式（i）Xaa-Yaa-Arg的肽，其中Xaa是任何氨基酸残基，Yaa是Glu或Xaa不存在，Yaa是任何氨基酸残基，Pro除外; （ii）Arg-Yaa-Xaa，其中Xaa是任何氨基酸残基，Yaa是Glu或Xaa不存在，Yaa是除Asn之外的任何氨基酸残基; （iii）Xaa-Arg-Yaa，其中Xaa是任何氨基酸残基，Yaa是Glu; 和（iv）Yaa-Arg-Xaa，其中Xaa是任何氨基酸残基，Yaa是Glu，其衍生物对巨噬细胞迁移和/或巨噬细胞吞噬活性具有抑制作用。 此外，肽及其衍生物对巨噬细胞和T细胞粘附于细胞外基质和/或纤连蛋白的能力发挥抑制作用。 肽及其衍生物对体液和/或细胞免疫应答具有抑制作用。 本发明还涉及使用肽及其衍生物的方法和含有它们的组合物用于抑制炎症，包括但不限于在关节中的炎症，中枢神经系统中通常在中枢神经中的特定病变 系统和其他免疫特权站点。

公开(公告)号：US08377692B2

公开(公告)日：2013-02-19

申请号：US10496352

申请日：2002-11-21

申请人： Valentin Fulga ,  Ronit Kleiner Bakimer ,  Issar Ash ,  Michal Eisenbach-Schwartz

发明人： Valentin Fulga ,  Ronit Kleiner Bakimer ,  Issar Ash ,  Michal Eisenbach-Schwartz

IPC分类号： C12N5/00

CPC分类号： C12N5/0645 ,  A61K2035/124 ,  C12N2502/1323

摘要： A process for the manufacture of human mononuclear phagocytic leukocytes comprises incubating monocytes isolated from a blood sample of an individual and skin segments from the same individual, removing the dermis segments from the incubation mixture and sedimenting the obtained activated mononuclear phagocytic leukocytes by centrifugation, washing and resuspending the activated phagocytic leukocytes in the medium, and evaluating the culture for its suitability for human administration. Cellular therapy products are made from the obtained cultures and are useful for promoting axonal regeneration in the CNS, wound healing and treatment of myocardial infarction.

摘要翻译： 一种制造人单核吞噬白细胞的方法包括将来自同一个体的单个血液样品和皮肤片段分离的单核细胞孵育，从孵育混合物中除去真皮段，并通过离心，洗涤和沉淀获得的活化单核吞噬白细胞， 将活化的吞噬白细胞重新悬浮在培养基中，并评估培养物是否适合人类施用。 细胞治疗产品由获得的培养物制成，可用于促进CNS中的轴突再生，伤口愈合和心肌梗死的治疗。

公开(公告)号：US20110206706A1

公开(公告)日：2011-08-25

申请号：US13097427

申请日：2011-04-29

申请人： Michal Eisenbach-Schwartz ,  Ester Yoles ,  Oleg Butovsky ,  Jonathan Kipnis

发明人： Michal Eisenbach-Schwartz ,  Ester Yoles ,  Oleg Butovsky ,  Jonathan Kipnis

IPC分类号： A61K39/00 ,  A61P25/28

CPC分类号： A61K39/0007 ,  A61K39/00 ,  A61K39/0008 ,  A61K2039/5158

摘要： Methods and compositions are provided for treatment of neurodegenerative diseases in which there is accumulation of misfolded and/or aggregated proteins, excluding prion diseases. In particular, the invention relates to treatment of the neurodegenerative diseases Huntington's disease (HD), Alzheimer's disease (AD) or Parkinson's disease (PD), by administration of an agent selected from the group consisting of (i) Copolymer 1, (ii) a Copolymer 1-related peptide, (iii) a Copolymer 1-related polypeptide, and (iv) T cells activated with (i), (ii) or (iii).

摘要翻译： 提供方法和组合物用于治疗除了朊病毒疾病之外存在错误折叠和/或聚集蛋白质积累的神经变性疾病。 特别地，本发明涉及治疗神经退行性疾病亨廷顿病（HD），阿尔茨海默病（AD）或帕金森病（PD）），通过施用选自（i）共聚物1，（ii） 共聚物1相关肽，（iii）共聚物1相关多肽，和（iv）用（i），（ii）或（iii）活化的T细胞。

公开(公告)号：US20110033488A1

公开(公告)日：2011-02-10

申请号：US12988053

申请日：2009-04-16

申请人： Michal Eisenbach-Schwartz ,  Gil M. Lewitus

发明人： Michal Eisenbach-Schwartz ,  Gil M. Lewitus

IPC分类号： A61K39/00 ,  A61K38/16 ,  A61K35/14 ,  A61P25/22 ,  A61P25/00

CPC分类号： A61K38/1709 ,  A61K39/0007 ,  A61K2039/5158

摘要： Peptides derived from CNS-specific antigens, altered peptide ligands (APL) analogues of said peptides, T cells activated by such peptides, poly-YE, and any combination of said agents are useful for prevention, treatment and/or alleviation of anxiety disorders, particularly post-traumatic stress disorder, and for restoring BDNF levels in the brain of an individual after reduction of BDNF expression induced by stress.

摘要翻译： 衍生自CNS特异性抗原的肽，所述肽的改变的肽配体（APL）类似物，由这些肽激活的T细胞，聚-YE和所述药物的任何组合可用于预防，治疗和/或减轻焦虑症， 特别是创伤后应激障碍，以及在应激诱导的BDNF表达降低后恢复个体脑中BDNF水平。