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1. 发明申请

US20070298031A1 Methods for preventing or treating neuromuscular or muscular conditions by peripherally administered erythropoietin 审中-公开
标题翻译：通过外周给予的促红细胞生成素预防或治疗神经肌肉或肌肉状况的方法
公开(公告)号：US20070298031A1
公开(公告)日：2007-12-27
申请号：US11881759
申请日：2007-07-26
申请人： Michael Brines , Anthony Cerami , Carla Cerami Hand
发明人： Michael Brines , Anthony Cerami , Carla Cerami Hand
IPC分类号： A61K38/19 , A61K35/00 , A61K39/395 , A61P21/00 , A61P29/00 , A61P9/10
CPC分类号： A61K38/1816
摘要： Methods and compositions are provided for protecting or enhancing excitable tissue function in mammals by systemic administration of an erythropoietin receptor activity modulator, such as erythropoietin, which signals via an EPO-activated receptor to modulate the function of excitable tissue. Excitable tissues include central neuronal tissues, such as the brain, peripheral neuronal tissues, retina, and heart tissue. Protection of excitable tissues provides treatment of hypoxia, seizure disorders, neurodegenerative diseases, hypoglycemia, and neurotoxin poisoning. Enhancement of function is useful in learning and memory. The invention is also directed to compositions and methods for facilitating the transport of molecules across endothelial cell tight junction barriers, such as the blood-brain barrier, by association of molecules with an erythropoietin receptor activity modulator, such as an erythropoietin.
摘要翻译：通过全身给予促红细胞生成素受体活性调节剂如红细胞生成素，通过EPO激活的受体信号调节可兴奋组织的功能，提供了用于保护或增强哺乳动物可激发组织功能的方法和组合物。可兴奋组织包括中枢神经元组织，如脑，周围神经元组织，视网膜和心脏组织。保护可兴奋组织提供治疗缺氧，癫痫发作，神经退行性疾病，低血糖症和神经毒素中毒。功能的增强在学习和记忆中是有用的。本发明还涉及通过分子与促红细胞生成素受体活性调节剂如红细胞生成素的缔合促进分子穿过内皮细胞紧密连接屏障（例如血脑屏障）的转运的组合物和方法。

2. 发明申请

US20090004202A1 METHODS FOR TREATMENT OF NEURODEGENERATIVE CONDITIONS BY PERIPHERALLY ADMINISTERED ERYTHROPOIETIN 审中-公开
标题翻译：通过外周血管内皮细胞生长因子治疗神经营养因子的方法
公开(公告)号：US20090004202A1
公开(公告)日：2009-01-01
申请号：US12123828
申请日：2008-05-20
申请人： MICHAEL BRINES , Anthony Cerami , Carla Cerami Hand
发明人： MICHAEL BRINES , Anthony Cerami , Carla Cerami Hand
IPC分类号： A61K39/395 , A61K31/7048
CPC分类号： A61K38/1816
摘要： Methods and compositions are provided for protecting or enhancing excitable tissue function in mammals by systemic administration of an erythropoietin receptor activity modulator, such as erythropoietin, which signals via an EPO-activated receptor to modulate the function of excitable tissue. Excitable tissues include central neuronal tissues, such as the brain, peripheral neuronal tissues, retina, and heart tissue. Protection of excitable tissues provides treatment of hypoxia, seizure disorders, neurodegenerative diseases, hypoglycemia, and neurotoxin poisoning. Enhancement of function is useful in learning and memory. The invention is also directed to compositions and methods for facilitating the transport of molecules across endothelial cell tight junction barriers, such as the blood-brain barrier, by association of molecules with an erythropoietin receptor activity modulator, such as an erythropoietin.
摘要翻译：通过全身给予促红细胞生成素受体活性调节剂如红细胞生成素，通过EPO激活的受体信号调节可兴奋组织的功能，提供了用于保护或增强哺乳动物可激发组织功能的方法和组合物。可兴奋组织包括中枢神经元组织，如脑，周围神经元组织，视网膜和心脏组织。保护可兴奋组织提供治疗缺氧，癫痫发作，神经退行性疾病，低血糖症和神经毒素中毒。功能的增强在学习和记忆中是有用的。本发明还涉及通过分子与促红细胞生成素受体活性调节剂如红细胞生成素的缔合促进分子穿过内皮细胞紧密连接屏障（例如血脑屏障）的转运的组合物和方法。

3. 发明申请

US20100298219A1 METHOD OF TREATING CANCER, NEOPLASTIC DISORDERS, AND SYMPTOMS THEREOF WITH COMPOUNDS 审中-公开
标题翻译：治疗癌症，神经性疾病的方法及其与化合物的症状
公开(公告)号：US20100298219A1
公开(公告)日：2010-11-25
申请号：US12863915
申请日：2009-01-22
申请人： Anthony Cerami , Michael Brines
发明人： Anthony Cerami , Michael Brines
IPC分类号： A61K38/18 , A61P35/00 , A61P35/02 , A61P35/04
CPC分类号： A61K38/1816 , C07K14/505
摘要： The present invention is directed to the use of tissue protective compounds for the prevention, treatment, amelioration or management of cancer, neoplastic diseases, their symptoms and side-effects associated with the treatment of these indications, i.e. chemotherapy or radiation therapy. In particular, these compounds may be chemically modified erythropoietin peptides or recombinant derivatives of erythropoietin, and preferably these compounds lack erythropoietic activity or have substantially reduced erythropoietic activity.
摘要翻译：本发明涉及组合保护性化合物用于预防，治疗，改善或治疗癌症，肿瘤性疾病，其症状和与治疗这些适应症（即化疗或放射治疗）相关的副作用。特别地，这些化合物可以是化学修饰的红细胞生成素肽或促红细胞生成素的重组衍生物，并且优选地，这些化合物缺乏红细胞生成活性或具有显着降低的红细胞生成活性。

4. 发明申请

US20060216757A1 Tissue protective cytokine receptor complex, assays for identifying tissue protective compounds and uses thereof 审中-公开
标题翻译：组织保护性细胞因子受体复合物，用于鉴定组织保护性化合物的测定及其用途
公开(公告)号：US20060216757A1
公开(公告)日：2006-09-28
申请号：US11259326
申请日：2005-10-25
申请人： Michael Brines , Anthony Cerami , Thomas Coleman
发明人： Michael Brines , Anthony Cerami , Thomas Coleman
IPC分类号： C40B40/10 , G01N33/567 , G01N33/53
CPC分类号： A61K38/19 , A61K38/1793 , A61K38/1816 , C40B40/10 , G01N33/5032 , G01N2333/575 , G01N2333/72 , G01N2500/10 , G01N2500/20 , G01N2800/70 , A61K2300/00
摘要： The present invention is directed methods for identifying compounds that have a tissue protective activity using a heteromultimer receptor complex that mediates the tissue protective activities. The complex consists of at least one EPO-R in complex with at least one βc Receptor. These compounds used in the assays to identify tissue protective compounds include, but are not limited to, small molecules and biologics. The compounds identified using these assays can be used to treat or prevent various diseases, disorders, or conditions of the central and peripheral nervous systems as well as those of other erythropoietin-responsive or excitable cells, tissues, and organs.
摘要翻译：本发明涉及使用介导组织保护活性的异源多聚体受体复合物来鉴定具有组织保护活性的化合物的方法。复合物由至少一个与至少一个β受体复合物的EPO-R组成。用于鉴定组织保护性化合物的测定中使用的这些化合物包括但不限于小分子和生物制剂。使用这些测定法鉴定的化合物可用于治疗或预防中枢和周围神经系统以及其它促红细胞生成素反应或兴奋细胞，组织和器官的各种疾病，病症或病症。

5. 发明授权

US08716245B2 Tissue protective peptides and uses thereof 有权
标题翻译：组织保护肽及其用途
公开(公告)号：US08716245B2
公开(公告)日：2014-05-06
申请号：US13278131
申请日：2011-10-20
申请人： Anthony Cerami , Michael Brines , Thomas Coleman
发明人： Anthony Cerami , Michael Brines , Thomas Coleman
IPC分类号： C07K7/08 , A61K38/10 , A61K48/00
CPC分类号： C07K14/505 , A61K38/00 , C07K14/435 , C07K14/575 , C07K14/71 , C07K2319/00
摘要： Provided herein are tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are generally located on or within the region of the cytokine receptor ligand that faces away from a receptor complex while the ligand is bound to the receptor. Also provide herein are fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO; methods for treating or preventing a disease or disorder using tissue protective peptides; and methods for enhancing excitable tissue function using tissue protective peptides.
摘要翻译：本文提供了组织保护肽，其衍生自或与共同序列共享，其中部分细胞因子受体配体包括促红细胞生成素（EPO），其通常位于远离受体复合物的细胞因子受体配体的区域上或内侧，而配体为与受体结合。本文还提供了片段，嵌合体以及旨在模拟组织保护性受体配体例如EPO中的关键氨基酸残基的空间定位的肽; 使用组织保护肽治疗或预防疾病或病症的方法; 以及使用组织保护肽增强可兴奋组织功能的方法。

6. 发明授权

US08071554B2 Tissue protective peptides and uses thereof 有权
标题翻译：组织保护肽及其用途
公开(公告)号：US08071554B2
公开(公告)日：2011-12-06
申请号：US11997898
申请日：2006-08-07
申请人： Anthony Cerami , Michael Brines
发明人： Anthony Cerami , Michael Brines
IPC分类号： A61K38/08 , A61K38/16 , C07K17/08
CPC分类号： C07K14/505 , A61K38/00 , C07K14/435 , C07K14/575 , C07K14/71 , C07K2319/00
摘要： The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor. The invention is further directed to the consensus sequences for use in engineering a synthetic tissue protective peptide. These tissue protective peptides also include fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO. The invention further encompasses methods for treating or preventing a disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.
摘要翻译：本发明涉及新型组织保护肽。本发明的组织保护肽可以结合组织保护性受体复合物。特别地，本发明涉及来源于或共享共有序列的组织保护肽，其中部分细胞因子受体配体包括促红细胞生成素（EPO），其不参与配体与受体复合物的结合，例如与 EPO受体同二聚体。因此，本发明的组织保护肽衍生自通常位于与受体复合体相反的配体蛋白的区域上或内部的细胞因子受体配体的区域的氨基酸序列，即通常衍生自氨基当配体与受体结合时，配体蛋白的表面远离受体复合物的酸序列。本发明还涉及用于工程化合成组织保护肽的共有序列。这些组织保护肽还包括片段，嵌合体以及旨在模拟组织保护性受体配体例如EPO内的关键氨基酸残基的空间定位的肽。本发明还包括使用本发明的组织保护肽治疗或预防疾病或病症的方法。本发明还包括使用本发明的组织保护肽增强可兴奋组织功能的方法。

7. 发明申请

US20110263504A1 TISSUE PROTECTIVE PEPTIDES AND PEPTIDE ANALOGS FOR PREVENTING AND TREATING DISEASES AND DISORDERS ASSOCIATED WITH TISSUE DAMAGE 有权
标题翻译：用于预防和治疗与组织损伤相关的疾病和病症的组织保护肽和肽类似物
公开(公告)号：US20110263504A1
公开(公告)日：2011-10-27
申请号：US12863973
申请日：2009-01-22
申请人： Anthony Cerami , Michael Brines
发明人： Anthony Cerami , Michael Brines
IPC分类号： A61K38/16 , C07K7/08 , C07K14/00 , A61K38/08 , A61K38/10 , C12N15/12 , C12N15/63 , C12N1/21 , C12N5/07 , C12N5/04 , C12P21/00 , A61P35/00 , A61P29/00 , A61P9/00 , A61P11/00 , A61P13/12 , A61P13/02 , A61P15/00 , A61P19/08 , A61P17/00 , A61P1/00 , A61P5/00 , A61P3/00 , A61P25/00 , C07K7/06
CPC分类号： A61K38/1816 , A61K38/00 , A61K38/10 , C07K7/06 , C07K14/505
摘要： The present invention provides peptides and peptide analogs that have tissue protective activities while having little or no potentially undesirable hematopoietic effects. The peptides and peptide analogs are useful in preventing and treating a variety of diseases and disorders associated with tissue damage.
摘要翻译：本发明提供具有组织保护活性同时具有很少或没有潜在的不期望的造血作用的肽和肽类似物。肽和肽类似物可用于预防和治疗与组织损伤相关的各种疾病和病症。

8. 发明申请

US20110245169A1 PROTECTION, RESTORATION AND ENHANCEMENT OF ERYTHROPOIETIN RESPONSIVE CELLS, TISSUES AND ORGANS 审中-公开
标题翻译：保护，恢复和增强ERYTHROPOIETIN反应细胞，组织和器官
公开(公告)号：US20110245169A1
公开(公告)日：2011-10-06
申请号：US13036638
申请日：2011-02-28
申请人： Michael Brines , Anthony Cerami , Carla Cerami
发明人： Michael Brines , Anthony Cerami , Carla Cerami
IPC分类号： A61K38/18 , A61P25/00 , A61P27/02 , A61P9/00 , A61P13/12
CPC分类号： C07K14/505 , A61K38/1816
摘要： Methods and compositions are provided for protecting or enhancing an erythropoietin-responsive cell, tissue, organ or body part function or viability in vivo, in situ or ex vivo in mammals, including human beings, by systemic or local administration of an erythropoietin receptor activity modulator, such as an erythropoietin or a modified erythropoietin.
摘要翻译：提供了通过全身或局部施用促红细胞生成素受体活性调节剂，在哺乳动物（包括人）中原位或离体保护或增强促红细胞生成素反应性细胞，组织，器官或身体部位功能或活体活性的方法和组合物，例如促红细胞生成素或修饰的红细胞生成素。

9. 发明申请

US20080305990A1 Method of Producing Fully Carbamylated Erythropoietin 审中-公开
标题翻译：全谷氨酰化促红细胞生成素的生产方法
公开(公告)号：US20080305990A1
公开(公告)日：2008-12-11
申请号：US11631458
申请日：2005-07-01
申请人： Michael Brines , Anthony Cerami , Carla Hand , Qiao-wen Xie
发明人： Michael Brines , Anthony Cerami , Carla Hand , Qiao-wen Xie
IPC分类号： A61K38/22 , C07K14/575 , A61P1/16 , A61P9/00 , A61P27/02
CPC分类号： C07K14/505 , A61K38/00
摘要： The present invention relates to a method of carbamylating an erythropoietin such that the resulting carbamylated erythropoietin has less that about 10% free primary amines on the lysines and the N-terminal amino acids, is not digested when exposed to Lys-C proteolysis, exhibits no erythropoietic activity in a TF-1 or UT-7/EPOR cell viability assay at a concentration of 1 μg/ml, and demonstrates a static sciatic index of less than about 0.65 within a Sciatic Nerve Assay. Additionally, the invention is related to pharmaceutical compositions containing carbamylated erythropoietins of the invention and the use of the pharmaceutical compositions for the treatment of conditions and diseases of excitable tissues.
摘要翻译：本发明涉及一种氨基甲酰化促红细胞生成素的方法，使得所得到的氨基甲酰化促红细胞生成素在赖氨酸和N-末端氨基酸上具有少于约10％的游离伯胺，当暴露于Lys-C蛋白水解时不被消化，在1μg/ ml浓度的TF-1或UT-7 / EPOR细胞存活力测定中的红细胞生成活性，并且在Sciatic神经测定中显示小于约0.65的静态坐骨指数。另外，本发明涉及含有本发明的氨基甲酰化促红细胞生成素的药物组合物和药物组合物用于治疗可兴奋组织的病症和疾病的用途。

10. 发明申请

US20120142589A1 TISSUE-PROTECTIVE CYTOKINES FOR THE PROTECTION, RESTORATION AND ENHANCEMENT OF RESPONSIVE CELLS, TISSUES AND ORGANS 审中-公开
标题翻译：用于保护，恢复和增强反应性细胞，组织和器官的组织保护性细胞因子
公开(公告)号：US20120142589A1
公开(公告)日：2012-06-07
申请号：US13195757
申请日：2011-08-01
申请人： Michael Brines , Anthony Cerami , Carla Cerami
发明人： Michael Brines , Anthony Cerami , Carla Cerami
IPC分类号： A61K38/19 , A61P39/00
CPC分类号： A61K31/00 , A61K31/5377 , A61K31/573 , A61K31/65 , A61K31/66 , A61K38/00 , A61K45/06 , C07K14/505 , A61K2300/00
摘要： Methods and compositions are provided for protecting or enhancing a responsive cell, tissue, organ or body part function or viability in vivo, in situ or ex vivo in mammals, including human beings, by systemic or local administration of a tissue protective cytokine.
摘要翻译：提供了通过全身或局部施用组织保护性细胞因子，在哺乳动物（包括人）中原位或离体保护或增强体内反应性细胞，组织，器官或身体部位功能或活力的方法和组合物。

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