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61. 发明授权

US07226911B2 Hair keratin-associated proteins 有权
标题翻译：头发角蛋白相关蛋白
公开(公告)号：US07226911B2
公开(公告)日：2007-06-05
申请号：US10846374
申请日：2004-05-13
申请人： Jun Kudo , Kazunori Shibuya , Nobuyoshi Shimizu
发明人： Jun Kudo , Kazunori Shibuya , Nobuyoshi Shimizu
IPC分类号： A61K38/08 , A61K38/17 , A61K8/64 , A61K8/65 , C07K7/06
CPC分类号： C07K14/47 , A01K2217/05 , A61K38/00 , A61K39/00 , A61K48/00 , C07K14/4741
摘要： The present invention relates to provide a protein group binding to keratin which is the major component of body hair, or genes encoding the same, particularly to keratin-associated proteins (KAP) which bind specifically and strongly to hair keratin or genes encoding the same. The base sequence of eurochromtic region of approximately 33.5 Mb of human chromosome 21 was determined, a dot-matrix analysis of the base sequence of the long arm region of chromosome 21 (21q22.3) was carried out, homology search was made to low frequency repetitive sequences and 16 KAP genes being expressed only in hair root cells were found. Moreover, the high frequency repetitive sequences present in the sequence spanning for approximately 1 Mb between CLDN8 gene and TIAM1 gene in the long arm region of chromosome 21(21q22.11) were masked, the presence or absence of short low frequency repetitive sequence was searched, and 22 KAP genes were found. Moreover, a group of functional peptide was designed from the above mentioned KAPs.
摘要翻译：本发明涉及提供与作为身体毛发的主要成分的角蛋白结合的蛋白质组，或编码其的基因，特别是与毛发角蛋白特异性强烈结合的角蛋白相关蛋白（KAP）或其编码基因的角蛋白相关蛋白（KAP）。测定21号染色体约33.5Mb的欧洲色素碱基序列，对21号染色体长臂区（21q22.3）的碱基序列进行点阵分析，对低频进行同源性检索发现重复序列和仅在发根细胞中表达的16个KAP基因。此外，染色体21（21q22.11）的长臂区域中CLDN8基因和TIAM1基因之间跨越约1Mb的序列中存在的高频重复序列被掩蔽，搜索是否存在短的低频重复序列，发现22个KAP基因。此外，从上述KAP设计了一组功能性肽。

62. 发明申请

US20040062793A1 Tissue defect dressings comprising proteinaceous networks 审中-公开
标题翻译：包含蛋白质网络的组织缺陷敷料
公开(公告)号：US20040062793A1
公开(公告)日：2004-04-01
申请号：US10411358
申请日：2003-04-10
发明人： Mark Van Dyke
IPC分类号： A61K038/17 , A61L015/00
CPC分类号： C08H1/06 , A61K38/015 , A61K38/39 , A61K47/65 , A61L26/0047 , C07K1/107 , C07K14/4741
摘要： Proteinaceous tissue defect dressings and methods for their use.
摘要翻译：蛋白质组织缺陷敷料及其使用方法。

63. 发明授权

US06706488B2 Apoptosis-related compounds and their use 有权
公开(公告)号：US06706488B2
公开(公告)日：2004-03-16
申请号：US09915374
申请日：2001-07-27
申请人： Viveka Björklund , Bertil Björklund , Peter Björklund , Marius Nap , Frans C. S. Ramaekers , Bert Schutte
发明人： Viveka Björklund , Bertil Björklund , Peter Björklund , Marius Nap , Frans C. S. Ramaekers , Bert Schutte
IPC分类号： G01N3353
CPC分类号： C07K5/1021 , A61K38/00 , C07K14/4741 , C07K14/4747 , C07K16/18
摘要： Apoptosis-related antigenic compounds comprising an exposed antigenic site having the amino acid sequence SEQ ID NO: 1: Glu Asp Phe Asn Leu Gly Asp Ala Leu Asp 1 5 10 or a functionally equivalent sequence comprising at least the sequence Ala Leu Asp are disclosed. Further, several applications and uses based on such compounds are included, such as use of the compounds in medicaments, nucleic acid sequences encoding the amino-acid sequence of such a peptide compound or protein fragment comprising the C-terminal amino acid sequence Ala Leu Asp, anti-sense nucleic acid sequence, vector comprising such a nucleic acid sequence, antibody or antigen-binding peptide recognizing such an antigenic compound and use thereof in a medicament, agents regulating the liberation of protein fragments comprising the amino-acid sequence SEQ ID NO: 1 or functionally equivalent sequences comprising the C-terminal amino acid sequence Ala Leu Asp, a method of determining the occurrence of cell apoptosis in a sample of biological material, especially in the diagnosis of degenerative diseases and cancer, or monitoring of the effect of therapy, a method of treating diseases with involvement of apoptosis, such as cancer and degenerative diseases, a method of creating cancer cells, and as carrier for prophylactic, therapeutic or diagnostic use.

64. 发明申请

US20030224052A1 Hydrogel with controllable merchanical, chemical, and biological properties and method for making same 有权
标题翻译：水凝胶具有可控制的机械，化学和生物学特性及其制备方法
公开(公告)号：US20030224052A1
公开(公告)日：2003-12-04
申请号：US10127523
申请日：2002-04-22
发明人： Mark E. Van Dyke
IPC分类号： A61K038/17 , A61K009/14 , C07K014/47
CPC分类号： C08H1/06 , A61K38/015 , A61K38/39 , A61K47/65 , A61L26/0047 , C07K1/107 , C07K14/4741 , C08G77/42 , C08G77/455 , Y10S530/842
摘要： Networks, hydrogels, and methods for networks and hydrogels comprising proteinaceous material consisting essentially of water soluble proteins and covalent interprotein crosslinks other than disulfide crosslinks.
摘要翻译：用于网络和水凝胶的网络，水凝胶和方法，其包含基本上由水溶性蛋白质组成的蛋白质材料和除二硫键交联以外的共价蛋白质交联。

65. 发明申请

US20010047082A1 Soluble keratin peptide 审中-公开
标题翻译：可溶性角蛋白肽
公开(公告)号：US20010047082A1
公开(公告)日：2001-11-29
申请号：US09899372
申请日：2001-07-02
发明人： Mark E. Van Dyke , Cheryl R. Blanchard , Scott F. Timmons , Arlene J. Siller-Jackson , Robert A. Smith
IPC分类号： C07K014/435
CPC分类号： C07K14/4741 , A61K8/02 , A61K8/0208 , A61K8/64 , A61K8/65 , A61K8/66 , A61K38/17 , A61Q19/00 , A61Q19/08
摘要： A peptide derived from keratin, which can be used as a wound-healing agent. In one method for making the peptide, a keratin source such as human hair is washed, dried, and treated with an oxidizing agent such as peracetic acid for a time and temperature sufficient to swell the keratin and oxidize some of the disulfide bonds to form sulfonic acid groups. The oxidation is believed to form a series of water-soluble peptides. The oxidized hair can be filtered, and the filtrate collected and concentrated under vacuum distillation to a viscous syrup, which can be neutralized with base. The concentrate can be mixed with an excess of a water-miscible organic solvent such as methanol, and the precipitate collected and dried to form the wound-healing agent. The wound-healing agent is believed to include peptides having a molecular weight centered around 850 daltons and having at least one ionizeable group such as sulfonic acid.
摘要翻译：衍生自角蛋白的肽，其可用作伤口愈合剂。在制备肽的一种方法中，将诸如人毛的角蛋白源洗涤，干燥，并用氧化剂如过乙酸处理足以使角蛋白溶胀并氧化一些二硫键形成磺酸的时间和温度酸性基团。据信氧化形成一系列水溶性肽。可以过滤氧化毛发，并将滤液收集并在减压蒸馏下浓缩成粘稠糖浆，其可用碱中和。浓缩物可以与过量的水混溶性有机溶剂如甲醇混合，收集沉淀并干燥形成伤口愈合剂。伤口愈合剂被认为包括分子量为850道尔顿左右并具有至少一个可离子化基团如磺酸的肽。

66. 发明授权

US06296850B1 Apoptosis-related compounds and their use 有权
标题翻译：凋亡相关化合物及其用途
公开(公告)号：US06296850B1
公开(公告)日：2001-10-02
申请号：US09162366
申请日：1998-09-29
申请人： Viveka Björklund , Bertil Björklund , Peter Björklund , Marius Nap , Frans C. S. Ramaekers , Bert Schutte
发明人： Viveka Björklund , Bertil Björklund , Peter Björklund , Marius Nap , Frans C. S. Ramaekers , Bert Schutte
IPC分类号： A61K3804
CPC分类号： C07K5/1021 , A61K38/00 , C07K14/4741 , C07K14/4747 , C07K16/18
摘要： Apoptosis-related antigenic compounds comprising an exposed antigenic site having the amino acid sequence SEQ ID NO: 1: Glu Asp Phe Asn Leu Gly Asp Ala Leu Asp 1 5 10 or a functionally equivalent sequence comprising at least the sequence Ala Leu Asp are disclosed. Further, several applications and uses based on such compounds are included, such as use of the compounds in medicaments, nucleic acid sequences encoding the amino-acid sequence of such a peptide compound or protein fragment comprising the C-terminal amino acid sequence Ala Leu Asp, anti-sense nucleic acid sequence, vector comprising such a nucleic acid sequence, antibody or antigen-binding peptide recognizing such an antigenic compound and use thereof in a medicament, agents regulating the liberation of protein fragments comprising the amino-acid sequence SEQ ID NO: 1 or functionally equivalent sequences comprising the C-terminal amino acid sequence Ala Leu Asp, a method of determining the occurrence of cell apoptosis in a sample of biological material, especially in the diagnosis of degenerative diseases and cancer, or monitoring of the effect of therapy, a method of treating diseases with involvement of apoptosis, such as cancer and degenerative diseases, a method of creating cancer cells, and as carrier for prophylactic, therapeutic or diagnostic use.
摘要翻译：公开了包含具有氨基酸序列的暴露的抗原位点或至少包含序列Ala Leu Asp的功能等同序列的凋亡相关抗原化合物。此外，包括基于这些化合物的几种应用和用途，例如在药物中使用化合物，编码这种肽化合物的氨基酸序列的核酸序列或包含C-末端氨基酸序列Ala Leu Asp的蛋白质片段，反义核酸序列，包含这种核酸序列的载体，识别这种抗原性化合物的抗体或抗原结合肽及其在药物中的用途，调节释放包含氨基酸序列SEQ ID NO ：1或包含C-末端氨基酸序列Ala Leu Asp的功能等同序列，确定生物材料样品中细胞凋亡发生的方法，特别是在退行性疾病和癌症的诊断中，或监测其作用治疗，涉及凋亡的疾病如癌症和退行性疾病的方法，一种产生癌症的方法细胞，以及作为预防，治疗或诊断用途的载体。

67. 发明授权

US06221843B1 Human keratins 失效
标题翻译：人角蛋白
公开(公告)号：US06221843B1
公开(公告)日：2001-04-24
申请号：US09360490
申请日：1999-07-23
申请人： Y. Tom Tang , Jennifer L. Hillman , Neil C. Corley , Mariah Baughn
发明人： Y. Tom Tang , Jennifer L. Hillman , Neil C. Corley , Mariah Baughn
IPC分类号： A61K3800
CPC分类号： C07K14/4741
摘要： The invention provides human keratins (KERT) and polynucleotides which identify and encode KERT. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of KERT.
摘要翻译：本发明提供鉴定和编码KERT的人角蛋白（KERT）和多核苷酸。本发明还提供表达载体，宿主细胞，抗体，激动剂和拮抗剂。本发明还提供用于诊断，治疗或预防与KERT表达相关的障碍的方法。

68. 发明授权

US6159495A Porous and bulk keratin bio-polymers 有权
标题翻译：多孔和体积角蛋白生物聚合物
公开(公告)号：US6159495A
公开(公告)日：2000-12-12
申请号：US362244
申请日：1999-07-28
申请人： Scott F. Timmons , Cheryl R. Blanchard , Robert A. Smith
发明人： Scott F. Timmons , Cheryl R. Blanchard , Robert A. Smith
IPC分类号： A61K9/70 , A61K35/36 , A61K38/17 , A61K38/39 , A61L15/32 , A61L26/00 , A61L27/22 , A61L27/34 , A61L27/60 , A61L31/04 , A61L31/10 , C07K14/47 , C08H1/06 , C12N5/00 , A61K13/00 , A61K38/00 , C08G63/48
CPC分类号： C12N5/0068 , A61K35/36 , A61K38/1709 , A61K38/39 , A61K9/70 , A61L15/32 , A61L26/0047 , A61L26/008 , A61L27/227 , A61L27/34 , A61L27/60 , A61L31/047 , A61L31/10 , C07K14/4741 , C08H1/06 , C12N2533/50 , Y10S530/842
摘要： Methods for producing thin keratin films, sheets, and bulk materials, and products formed using these methods. One method includes providing hair, reducing the hair such that the disulfide linkages are broken and free cysteine thiol groups formed, separating out a more soluble keratin fraction in solution, forming a thin layer from the more soluble fraction, and air drying the keratin fraction in the presence of oxygen, thereby forming new disulfide bonds imparting strength to the resulting thin keratin film. One method includes reducing hair by heating the hair under nitrogen in an ammonium hydroxide and ammonium thioglycolate solution followed by centrifuging and collecting the supernatant containing the more soluble keratin fraction. The more soluble keratin in this method is precipitated using HCl, removed, and resuspended in ammonium hydroxide. The keratin solution thus formed is poured onto a flat surface and allowed to air dry into a thin keratin film. The film may be used as a wound dressing, a tissue-engineering scaffold, a diffusion membrane, a coating for implantable devices, and as a cell encapsulant. In another method, the keratin solution thus formed is concentrated, poured into a mold, and allowed to air dry into a three dimensional keratin product. The resulting bulk product can be used as a cross-linked implantable biomaterial for soft and hard tissue replacement. In another method, a keratin solution is emulsified and freeze dried, forming a porous, open cell keratin material.
摘要翻译：用于生产薄角蛋白薄膜，片材和散装材料的方法以及使用这些方法形成的产品。一种方法包括提供毛发，减少头发，使得二硫键断裂，形成游离的半胱氨酸硫醇基团，在溶液中分离出更可溶的角蛋白级分，从较可溶级分形成薄层，并将角蛋白级分空气干燥氧的存在，从而形成新的二硫键，赋予所得薄的角蛋白薄膜强度。一种方法包括通过在氮气下在氢氧化铵和巯基乙酸铵溶液中加热头发，然后离心并收集含有较可溶性角蛋白级分的上清液来减少头发。该方法中较易溶解的角蛋白用HCl沉淀，除去，再悬浮于氢氧化铵中。将如此形成的角蛋白溶液倒入平坦表面，并使其干燥成薄的角蛋白膜。该膜可以用作伤口敷料，组织工程支架，扩散膜，用于可植入装置的涂层，以及作为细胞密封剂。在另一种方法中，将如此形成的角蛋白溶液浓缩，倒入模具中，并使其风干至三维角蛋白产品。所得到的散装产品可用作用于软组织和硬组织置换的交联可植入生物材料。在另一种方法中，将角蛋白溶液乳化并冷冻干燥，形成多孔的开放细胞角蛋白材料。

69. 发明授权

US6110487A Method of making porous keratin scaffolds and products of same 有权
标题翻译：制作多孔角蛋白支架及其制品的方法
公开(公告)号：US6110487A
公开(公告)日：2000-08-29
申请号：US198998
申请日：1998-11-24
申请人： Scott F. Timmons , Cheryl R. Blanchard , Robert A. Smith
发明人： Scott F. Timmons , Cheryl R. Blanchard , Robert A. Smith
IPC分类号： A61K9/70 , A61K35/36 , A61K38/17 , A61K38/39 , A61L15/32 , A61L26/00 , A61L27/22 , A61L27/34 , A61L27/60 , A61L31/04 , A61L31/10 , C07K14/47 , C08H1/06 , C12N5/00 , A61K9/00 , A61K38/00 , C08G63/48
CPC分类号： C12N5/0068 , A61K35/36 , A61K38/1709 , A61K38/39 , A61K9/70 , A61L15/32 , A61L26/0047 , A61L26/008 , A61L27/227 , A61L27/34 , A61L27/60 , A61L31/047 , A61L31/10 , C07K14/4741 , C08H1/06 , C12N2533/50 , Y10S530/842
摘要： Methods for producing thin keratin films, sheets, and bulk materials, and products formed using these methods. One method includes providing hair, reducing the hair such that the disulfide linkages are broken and free cysteine thiol groups formed, separating out a more soluble keratin fraction in solution, forming a thin layer from the more soluble fraction, and air drying the keratin fraction in the presence of oxygen, thereby forming new disulfide bonds imparting strength to the resulting thin keratin film. One method includes reducing hair by heating the hair under nitrogen in an ammonium hydroxide and ammonium thioglycolate solution followed by centrifuging and collecting the supernatant containing the more soluble keratin fraction. The more soluble keratin in this method is precipitated using HCl, removed, and resuspended in ammonium hydroxide. The keratin solution thus formed is poured onto a flat surface and allowed to air dry into a thin keratin film. The film may be used as a wound dressing, a tissue-engineering scaffold, a diffusion membrane, a coating for implantable devices, and as a cell encapsulant. In another method, the keratin solution thus formed is concentrated, poured into a mold, and allowed to air dry into a three dimensional keratin product. The resulting bulk product can be used as a cross-linked implantable biomaterial for soft and hard tissue replacement. In another method, a keratin solution is emulsified and freeze dried, forming a porous, open cell keratin material.
摘要翻译：用于生产薄角蛋白薄膜，片材和散装材料的方法以及使用这些方法形成的产品。一种方法包括提供毛发，减少头发，使得二硫键断裂，形成游离的半胱氨酸硫醇基团，在溶液中分离出更可溶的角蛋白级分，从较可溶级分形成薄层，并将角蛋白级分空气干燥氧的存在，从而形成新的二硫键，赋予所得薄的角蛋白薄膜强度。一种方法包括通过在氮气下在氢氧化铵和巯基乙酸铵溶液中加热头发，然后离心并收集含有较可溶性角蛋白级分的上清液来减少头发。该方法中较易溶解的角蛋白用HCl沉淀，除去，再悬浮于氢氧化铵中。将如此形成的角蛋白溶液倒入平坦表面，并使其干燥成薄的角蛋白膜。该膜可以用作伤口敷料，组织工程支架，扩散膜，用于可植入装置的涂层，以及作为细胞密封剂。在另一种方法中，将如此形成的角蛋白溶液浓缩，倒入模具中，并使其风干至三维角蛋白产品。所得到的散装产品可用作用于软组织和硬组织置换的交联可植入生物材料。在另一种方法中，将角蛋白溶液乳化并冷冻干燥，形成多孔的开放细胞角蛋白材料。

70. 发明授权

US5932552A Keratin-based hydrogel for biomedical applications and method of production 失效
公开(公告)号：US5932552A
公开(公告)日：1999-08-03
申请号：US979456
申请日：1997-11-26
申请人： Cheryl R. Blanchard , Scott F. Timmons , Robert A. Smith
发明人： Cheryl R. Blanchard , Scott F. Timmons , Robert A. Smith
IPC分类号： A61K38/17 , A61K38/39 , A61L26/00 , A61L27/22 , A61L27/34 , A61L27/52 , A61L27/60 , A61L31/04 , A61L31/10 , C07K14/47 , C08H1/06 , A61K38/00 , A61K7/06 , A61K9/70 , A61L15/00
CPC分类号： C08H1/06 , A61K38/1709 , A61K38/39 , A61K8/042 , A61K8/65 , A61L26/0047 , A61L26/008 , A61L27/227 , A61L27/34 , A61L27/52 , A61L27/60 , A61L31/047 , A61L31/10 , A61Q19/00 , C07K14/4741 , Y10S514/944 , Y10S530/842
摘要： A keratin hydrogel which can be used as a wound dressing and cell scaffolding. The keratin hydrogel is formed from clean, washed hair by partially oxidizing a significant percentage of disulfide linkages to form cysteic acid groups, while some disulfide linkages remain intact. The partially oxidized hair is treated with a reducing agent, thereby reducing most of the remaining disulfide linkages to cysteine-thioglycollate disulfide and cysteine groups. A soluble fraction of hair is collected and oxidized, such that the reduced sulfur groups are allowed to reform disulfide linkages, thereby binding the keratin together. The cysteic acid groups remain, providing hydrophilic sites within the hydrogel. A higher degree of partial oxidation results in a greater abundance of hydrophilic cysteic acid groups in the hydrogel.

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