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31. 发明授权

US08119783B2 FGF variants and methods for use thereof 有权
标题翻译： FGF变体及其使用方法
公开(公告)号：US08119783B2
公开(公告)日：2012-02-21
申请号：US12416435
申请日：2009-04-01
申请人： Oren Bogin , Avner Yayon
发明人： Oren Bogin , Avner Yayon
IPC分类号： C12N15/11 , C12N15/12 , A61K38/18
CPC分类号： A61K38/1825 , A61K38/22 , C07K14/50 , C07K14/501 , C07K14/503 , C07K14/575 , C12N5/0655 , C12N5/0658 , C12N2501/115 , C12N2506/1346
摘要： The present invention provides fibroblast growth factor variants demonstrating enhanced receptor subtype specificity and/or affinity. Preferred embodiments include both variants having enhanced activity that act as improved agonists and variants having reduced activity that act as antagonists. Methods of utilizing preferred FGF variants in preparation of medicaments for the treatment of skeletal disorders including skeletal dysplasia, osteoporosis and enhancing bone fracture healing and cartilage healing processes are provided.
摘要翻译：本发明提供证明增强的受体亚型特异性和/或亲和力的成纤维细胞生长因子变体。优选的实施方案包括具有增强活性的两种变体，其作为改善的激动剂和具有降低的作为拮抗剂的活性的变体。提供了利用优选的FGF变体在制备用于治疗骨骼障碍（包括骨骼发育不良，骨质疏松症和增强骨折愈合和软骨愈合过程）的药物中的方法。

32. 发明授权

US07714107B2 Freeze-dried fibrin matrices and methods for preparation thereof 有权
标题翻译：冻干纤维蛋白基质及其制备方法
公开(公告)号：US07714107B2
公开(公告)日：2010-05-11
申请号：US11190387
申请日：2005-07-26
申请人： Avner Yayon , Malkit Azachi , Micha Gladnikoff
发明人： Avner Yayon , Malkit Azachi , Micha Gladnikoff
IPC分类号： A61K35/14
CPC分类号： A61K9/0024 , A61F2/30756 , A61K9/2063 , A61K31/727 , A61K31/728 , A61K35/12 , A61K38/1825 , A61L27/225 , A61L27/3852 , A61L27/56 , C07K14/75 , C12N5/0068 , C12N5/0655 , C12N2533/56
摘要： The present invention relates to porous freeze-dried fibrin matrices substantially devoid of external anti-fibrinolytic agents, and methods of producing such matrices. Resilient matrices, also known as sponges, that are particularly beneficial for supporting three dimensional cell growth are obtained from plasma proteins substantially devoid of plasminogen or from partially purified plasma proteins, thus obviating the need for exogenous anti-fibrinolytic agents. Furthermore, incorporation of glycosaminoglycans and bioactive agents during the formation of the matrix results in a sponge having advantageous biological, mechanical and physical properties. The compositions of the present invention are useful clinically, without cells or as a cell bearing implants.
摘要翻译：本发明涉及基本上不含外部抗纤维蛋白溶解剂的多孔冷冻干燥的纤维蛋白基质，以及制备这种基质的方法。特别有利于支持三维细胞生长的弹性基质，也称为海绵，从基本上不含纤溶酶原的血浆蛋白质或部分纯化的血浆蛋白质中获得，从而避免需要外源性抗纤维蛋白溶解剂。此外，在形成基质期间掺入糖胺聚糖和生物活性剂可形成具有有利的生物，机械和物理性质的海绵。本发明的组合物在临床上是有用的，没有细胞或作为携带细胞的植入物。

33. 发明申请

US20100003222A1 METHODS FOR BONE REGENERATION USING ENDOTHELIAL PROGENITOR CELL PREPARATIONS 有权
标题翻译：使用内皮祖细胞制备的骨再生方法
公开(公告)号：US20100003222A1
公开(公告)日：2010-01-07
申请号：US12297417
申请日：2007-04-17
申请人： Avner Yayon , Dina Lewinson , Nimrod Rozen
发明人： Avner Yayon , Dina Lewinson , Nimrod Rozen
IPC分类号： A61K35/12 , A61P19/08
CPC分类号： A61L27/3808 , A61K35/28 , A61K35/44 , A61K38/1841 , A61K2035/124 , A61L27/12 , A61L27/54 , A61L2300/414 , A61L2300/64 , C12N5/0692 , C12N2500/38 , C12N2501/105 , C12N2501/11 , C12N2501/115 , C12N2501/165 , A61K2300/00
摘要： The present invention relates in general to orthopedics and to a method for promoting repair of large bone defects, in particular non-union or delayed union fractures. Specifically the invention concerns the use of endothelial progenitor cell preparations for bone repair.
摘要翻译：本发明一般涉及骨科和一种用于促进大骨缺损修复的方法，特别是非联合或延迟联合骨折。具体地，本发明涉及内皮祖细胞制剂用于骨修复的用途。

34. 发明授权

US07009039B2 Plasma protein matrices and methods for their preparation 有权
标题翻译：血浆蛋白质基质及其制备方法
公开(公告)号：US07009039B2
公开(公告)日：2006-03-07
申请号：US10761615
申请日：2004-01-20
申请人： Avner Yayon , Rachel Glicklis
发明人： Avner Yayon , Rachel Glicklis
IPC分类号： A61K35/14 , A61K38/00
CPC分类号： A61L27/3852 , A61K35/12 , A61L27/225 , A61L27/3839 , A61L27/56 , C12N5/0068 , C12N5/0655 , C12N2533/56
摘要： A freeze dried biocompatible matrix comprising plasma proteins, useful as implants for tissue engineering as well as in biotechnology, and methods of producing the matrix are provided. Mechanical and physical parameters can be controlled by use of auxiliary components or additives which may be removed after the matrix is formed in order to improve the biological properties of the matrix. The matrices according to the present invention may be used clinically per se, or as a cell-bearing implant.
摘要翻译：提供了包含血浆蛋白质的冷冻干燥生物相容性基质，其可用作组织工程和生物技术的植入物，以及生产基质的方法。机械和物理参数可以通过使用可以在形成基质之后除去的辅助组分或添加剂来控制，以改善基质的生物学性质。根据本发明的基质本身可以临床使用，或作为携带细胞的植入物。

35. 发明授权

US06730666B1 Pharmaceutical compositions comprising porphyrins and some novel porphyrin derivatives 失效
标题翻译：包含卟啉和一些新型卟啉衍生物的药物组合物
公开(公告)号：US06730666B1
公开(公告)日：2004-05-04
申请号：US09831305
申请日：2001-07-18
申请人： Avner Yayon , David Aviezer , Zeev Gross
发明人： Avner Yayon , David Aviezer , Zeev Gross
IPC分类号： A61K3841
CPC分类号： C07D487/22 , A61K31/409 , A61K31/4425 , A61K31/4439
摘要： Tertrapyrrolic macrocycles selected from 5,10,15,20-tetraaryl-porphyrins and 5,10,15-triaryl-corrloes, wherein said aryl radical is a carboaryl, a heteroaryl or a mixed carboaryl-heteroaryl radical and at least two of said aryl radicals are positively charged, inhibit growth factor (e.g. bFGF, VEGF) receptor tyrosine kinase activity, and are useful for inhibition of cell proliferation mediated by growth factor receptor tyrosine kinase activity for example for inhibition of angiogenesis, or vascular smooth muscle cell proliferation in disorders including atherosclerosis, hyperthrophic heart failure and postsurfical restenosis, and of cell proliferation and migration in the treatment of primary tumors and metastasis. Some of the 5,10,15,20-tetraaryl-prophyrins are novel compounds.
摘要翻译：选自5,10,15,20-四芳基卟啉和5,10,15-三芳基对aryl aryl aryl aryl aryl aryl aryl aryl aryl，，，，，，，，，，，，，，aryl aryl aryl aryl aryl aryl aryl aryl aryl aryl aryl aryl aryl 自由基是带正电荷的，抑制生长因子（例如bFGF，VEGF）受体酪氨酸激酶活性，并且可用于抑制由生长因子受体酪氨酸激酶活性介导的细胞增殖，例如用于抑制血管生成或血管平滑肌细胞增殖紊乱包括动脉粥样硬化，亢进性心力衰竭和术后再狭窄，以及原发性肿瘤和转移治疗中的细胞增殖和迁移。 5,10,15,20-四芳基卟啉中的一些是新化合物。

36. 发明授权

US5491220A Surface loop structural analogues of fibroblast growth factors 失效
标题翻译：成纤维细胞生长因子的表面环结构类似物
公开(公告)号：US5491220A
公开(公告)日：1996-02-13
申请号：US290373
申请日：1994-08-15
申请人： Andrew P. Seddon , Luyuan Li , Peter Bohlen , Magdalena Eisinger , Avner Yayon
发明人： Andrew P. Seddon , Luyuan Li , Peter Bohlen , Magdalena Eisinger , Avner Yayon
IPC分类号： A61K38/00 , C07K14/50 , C07K14/545 , C12N15/18
CPC分类号： C07K14/501 , C07K14/50 , C07K14/503 , C07K14/545 , A61K38/00
摘要： Structural analogues of fibroblast growth factors have an amino acid sequence replacement in the ninth or tenth .beta.-strand of the factor, or the sequence that corresponds to the surface loop that connects the ninth and tenth .beta.-strands, such that the folding of the molecule is not significantly perturbed. Preferred analogues have the amino acid sequence replacement in the surface loop that extends from the ninth .beta.-strand to the tenth .beta.-strand and have the overall secondary and tertiary structure of the original factor, and bind to heparin and a member or members of the fibroblast growth factor receptor family with high affinity. In some embodiments, the analogues are prepared by replacing the surface loop sequence that connects the ninth and tenth .beta.-strand with another amino acid sequence such as a loop sequence from another structurally related fibroblast growth factor or an interleukin. Preferred analogues exhibit different biological properties and/or receptor binding specificity profiles from native factors.
摘要翻译：成纤维细胞生长因子的结构类似物在该因子的第9或第10个β链中具有氨基酸序列替换，或者对应于连接第9和第10个β链的表面环的序列，使得分子的折叠没有明显的扰动。优选的类似物在表面循环中具有从第九个β链延伸到第十个β链的氨基酸序列替代物，并具有原始因子的总体二级结构和三级结构，并且结合肝素和成员成纤维细胞生长因子受体家族具有高亲和力。在一些实施方案中，通过将来自另一结构相关的成纤维细胞生长因子或白介素的另一个氨基酸序列例如环序列替换连接第九和第十个β链的表面环序列来制备类似物。优选的类似物表现出与天然因素不同的生物学特性和/或受体结合特异性谱。

37. 发明授权

US5270197A Cells expressing a substantial number of surface high affinity HBGF receptors but relatively few low affinity HBGF binding sites and system for assaying binding to HBGF receptor 失效
标题翻译：表达大量表面高亲和力HBGF受体但相对较少的低亲和力HBGF结合位点的细胞和用于测定与HBGF受体结合的系统
公开(公告)号：US5270197A
公开(公告)日：1993-12-14
申请号：US631717
申请日：1990-12-20
申请人： Avner Yayon , David M. Ornitz , Michael Klagsbrun , Philip Leder
发明人： Avner Yayon , David M. Ornitz , Michael Klagsbrun , Philip Leder
IPC分类号： C07K14/50 , C07K14/71 , C12N9/16 , G01N33/50 , G01N33/74 , C12N5/10 , C12N15/85 , C12P21/00 , G01N33/566
CPC分类号： G01N33/5008 , C07K14/503 , C07K14/71 , C12N9/16 , G01N33/74 , C07K2319/034 , C07K2319/32 , C07K2319/61 , G01N2500/00
摘要： A homogeneous population of cells having on average (1) a number of cell surface low-affinity heparin-binding growth factor (HBGF) sites per cell less than 20% of the number of such binding sites found on wild-type CHO-K1 cells (ATCC Accession No. CCL61), and at least three times the number of cell surface high-affinity HBGF receptors per cell found on such CHO-K1 cells; and an assay system utilizing such cells.
摘要翻译：平均每个细胞的细胞表面平均少量细胞表面低亲和力肝素结合生长因子（HBGF）位点的均匀群体少于在野生型CHO-K1细胞上发现的这种结合位点数目的20％（ATCC登录号CCL61），并且在这种CHO-K1细胞上发现的每个细胞的细胞表面高亲和力HBGF受体的数目的至少三倍; 以及利用这种细胞的测定系统。

38. 发明申请

US20140038892A1 Conjugates Of Carboxy Polysaccharides With Fibroblast Growth Factors And Variants Thereof 有权
标题翻译：羧基多糖与成纤维细胞生长因子及其变体的结合
公开(公告)号：US20140038892A1
公开(公告)日：2014-02-06
申请号：US14054300
申请日：2013-10-15
申请人： Avner Yayon , Roy Sirkis , Boaz Amit , Avraham Wortzel
发明人： Avner Yayon , Roy Sirkis , Boaz Amit , Avraham Wortzel
IPC分类号： A61K47/48 , A61K38/36 , A61K38/18 , C07K14/50
CPC分类号： A61K47/4823 , A61K9/19 , A61K31/728 , A61K38/1825 , A61K38/363 , A61K47/61 , C07K14/50
摘要： Conjugates of hydrophilic carboxy polysaccharides with protein members of the fibroblast growth factor (FGF) family and variants thereof. The conjugates provide a modified bioactivity and stability of FGFs for various therapeutic applications.
摘要翻译：亲水性羧基多糖与成纤维细胞生长因子（FGF）家族的蛋白质成员及其变体的缀合物。缀合物为各种治疗应用提供改善的生物活性和FGFs的稳定性。

39. 发明授权

US08298528B2 Methods for bone regeneration using endothelial progenitor cell preparations 有权
标题翻译：使用内皮祖细胞制剂的骨再生方法
公开(公告)号：US08298528B2
公开(公告)日：2012-10-30
申请号：US12297417
申请日：2007-04-17
申请人： Avner Yayon , Dina Lewinson , Nimrod Rozen
发明人： Avner Yayon , Dina Lewinson , Nimrod Rozen
IPC分类号： A01N63/00 , A61K48/00 , C12N5/00
CPC分类号： A61L27/3808 , A61K35/28 , A61K35/44 , A61K38/1841 , A61K2035/124 , A61L27/12 , A61L27/54 , A61L2300/414 , A61L2300/64 , C12N5/0692 , C12N2500/38 , C12N2501/105 , C12N2501/11 , C12N2501/115 , C12N2501/165 , A61K2300/00
摘要： The present invention relates in general to orthopedics and to a method for promoting repair of large bone defects, in particular non-union or delayed union fractures. Specifically the invention concerns the use of endothelial progenitor cell preparations for bone repair.
摘要翻译：本发明一般涉及骨科和一种用于促进大骨缺损修复的方法，特别是非联合或延迟联合骨折。具体地，本发明涉及内皮祖细胞制剂用于骨修复的用途。

40. 发明授权

US08193317B2 Freeze-dried fibrin matrices and methods for preparation thereof 有权
标题翻译：冻干纤维蛋白基质及其制备方法
公开(公告)号：US08193317B2
公开(公告)日：2012-06-05
申请号：US12731356
申请日：2010-03-25
申请人： Avner Yayon , Malkit Azachi , Micha Gladnikoff
发明人： Avner Yayon , Malkit Azachi , Micha Gladnikoff
IPC分类号： A61K35/14
CPC分类号： A61K9/0024 , A61F2/30756 , A61K9/2063 , A61K31/727 , A61K31/728 , A61K35/12 , A61K38/1825 , A61L27/225 , A61L27/3852 , A61L27/56 , C07K14/75 , C12N5/0068 , C12N5/0655 , C12N2533/56
摘要： Methods for producing porous freeze-dried fibrin matrices substantially devoid of external anti-fibrinolytic agents. Resilient matrices, also known as sponges, that are particularly beneficial for supporting three dimensional cell growth are obtained from plasma proteins substantially devoid of plasminogen or from partially purified plasma proteins, thus obviating the need for exogenous anti-fibrinolytic agents. Furthermore, incorporation of glycosaminoglycans and bioactive agents during the formation of the matrix results in a sponge having advantageous biological, mechanical and physical properties. The compositions made by the method of the present invention are useful clinically or as cell-bearing implants.
摘要翻译：制备基本上不含外部抗纤维蛋白溶解剂的多孔冻干纤维蛋白基质的方法。特别有利于支持三维细胞生长的弹性基质，也称为海绵，从基本上不含纤溶酶原的血浆蛋白质或部分纯化的血浆蛋白质中获得，从而避免需要外源性抗纤维蛋白溶解剂。此外，在形成基质期间掺入糖胺聚糖和生物活性剂可形成具有有利的生物，机械和物理性质的海绵。通过本发明的方法制备的组合物在临床上或作为细胞承载植入物是有用的。

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