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1. 发明授权

US6140484A Bax .omega. protein and methods 失效
标题翻译： Bax omega蛋白和方法
公开(公告)号：US6140484A
公开(公告)日：2000-10-31
申请号：US37742
申请日：1998-03-10
申请人： Catherine Mastroni Bitler , Stephen Scott Bowersox , Roberto Crea , Susan Dunham Demo , William A. Horne , Mei Zhou
发明人： Catherine Mastroni Bitler , Stephen Scott Bowersox , Roberto Crea , Susan Dunham Demo , William A. Horne , Mei Zhou
IPC分类号： A61K38/00 , A61K48/00 , C07K14/47 , C12N15/12 , C07H21/02
CPC分类号： C07K14/4747 , A61K38/00 , A61K48/00 , C07K2319/00
摘要： Bax-.omega. polynucleotides and polypeptides, and compositions effective to hybridize to Bax-.omega. polynucleotides are disclosed. Also disclosed are methods for altering apoptosis in cells, for promoting cell survival and for identifying compounds capable of affecting the binding of Bax-.omega. to other proteins involved in apoptosis.
摘要翻译：公开了Bax-ω多核苷酸和多肽，以及有效与Bax-ω多核苷酸杂交的组合物。还公开了用于改变细胞凋亡，促进细胞存活和鉴定能够影响Bax-ω与参与凋亡的其它蛋白结合的化合物的方法。

2. 发明授权

US5770690A Bax omega protein and methods 失效
公开(公告)号：US5770690A
公开(公告)日：1998-06-23
申请号：US616732
申请日：1996-03-15
申请人： Catherine Mastroni Bitler , Stephen Scott Bowersox , Roberto Crea , Susan Dunham Demo , William A. Horne , Mei Zhou
发明人： Catherine Mastroni Bitler , Stephen Scott Bowersox , Roberto Crea , Susan Dunham Demo , William A. Horne , Mei Zhou
IPC分类号： A61K38/00 , A61K48/00 , C07K14/47 , C12N15/12 , C07K14/00 , C07K7/00
CPC分类号： C07K14/4747 , A61K38/00 , A61K48/00 , C07K2319/00
摘要： Bax-.omega. polynucleotides and polypeptides, and compositions effective to hybridize to Bax-.omega. polynucleotides are disclosed. Also disclosed are methods for altering apoptosis in cells, for promoting cell survival and for identifying compounds capable of affecting the binding of Bax-.omega. to other proteins involved in apoptosis.

3. 发明授权

US08680019B2 Universal fibronectin Type III binding-domain libraries 有权
标题翻译：通用纤连蛋白III型结合域文库
公开(公告)号：US08680019B2
公开(公告)日：2014-03-25
申请号：US12562992
申请日：2009-09-18
申请人： Guido Cappuccilli , Roberto Crea , Randy Shen , Craig A. Hokanson , Peter B. Kirk , David R. Liston
发明人： Guido Cappuccilli , Roberto Crea , Randy Shen , Craig A. Hokanson , Peter B. Kirk , David R. Liston
IPC分类号： C40B40/10
CPC分类号： C07K14/78 , C07K16/18 , C07K16/22 , C07K16/241 , C07K2317/21 , C07K2317/52 , C07K2318/20 , C12N15/1044
摘要： Walk-through mutagenesis and natural-variant combinatorial fibronectin Type III (FN3) polypeptide libraries are described, along with their method of construction and use. Also disclosed are a number of high binding affinity polypeptides selected by screening the libraries against a variety of selected antigens.
摘要翻译：描述了直通诱变和自然变体组合纤连蛋白III（FN3）多肽文库以及它们的构建和使用方法。还公开了通过针对多种选择的抗原筛选文库而选择的多种高结合亲和力多肽。

4. 发明申请

US20140011756A1 Method for Treatment of Inflammation 审中-公开
标题翻译：治疗炎症的方法
公开(公告)号：US20140011756A1
公开(公告)日：2014-01-09
申请号：US13544943
申请日：2012-07-09
申请人： Roberto Crea
发明人： Roberto Crea
IPC分类号： A61K31/7048 , A61P25/00 , A61P31/14
CPC分类号： A61K31/05 , A61K31/7048 , A61K2300/00
摘要： A method of treating inflammation, an inflammatory condition, or AIDS-associated neurological disorder in a subject in need of such treatment is disclosed. The method includes administering to said subject a pharmaceutically effective amount of substantially purified hydroxytyrosol or a substantially purified mixture of hydroxytyrosol and oleuropein. Also disclosed are compositions for use in practicing the method.
摘要翻译：公开了一种在需要这种治疗的受试者中治疗炎症，炎性病症或AIDS相关神经障碍的方法。所述方法包括向所述受试者施用药学有效量的基本纯化的羟基酪醇或基本上纯化的羟基酪醇和橄榄苦蛋白的混合物。还公开了用于实施该方法的组合物。

5. 发明申请

US20110021746A1 UNIVERSAL FIBRONECTIN TYPE III BINDING-DOMAIN LIBRARIES 有权
标题翻译：通用FIBRONECTIN III型绑定库
公开(公告)号：US20110021746A1
公开(公告)日：2011-01-27
申请号：US12820018
申请日：2010-06-21
申请人： Guido Cappuccilli , Roberto Crea , Randy Shen , Craig A. Hokanson , Peter B. Kirk , David R. Liston
发明人： Guido Cappuccilli , Roberto Crea , Randy Shen , Craig A. Hokanson , Peter B. Kirk , David R. Liston
IPC分类号： C07K14/00
CPC分类号： C07K14/78 , C07K16/18 , C07K16/22 , C07K16/241 , C07K2317/21 , C07K2317/52 , C07K2318/20 , C12N15/1044 , C40B40/10
摘要： Fibronectin Type III (FN3) polypeptide libraries are described, along with their use in identifying fibronectin-type binding peptides having hign binding affinities, e.g., greater than 300 nM, for VEGFR2 or Axl proteins.
摘要翻译：描述了纤连蛋白III（FN3）多肽文库以及它们用于鉴定对于VEGFR2或Ax1蛋白具有hign结合亲和力（例如大于300nM）的纤连蛋白型结合肽。

6. 发明申请

US20090318297A1 Antibody Ultrahumanization by Predicted Mature CDR Blasting and Cohort Library Generation and Screening 有权
标题翻译：通过预测成熟的CDR爆破和队列库生成和筛选的抗体超人性化
公开(公告)号：US20090318297A1
公开(公告)日：2009-12-24
申请号：US12085175
申请日：2006-11-10
申请人： Guido Cappucilli , Roberto Crea , Takeuchi Toshihilo , Randy Shen , Rarnesh Bhatt , Nurten Beyaz-Kavuncu
发明人： Guido Cappucilli , Roberto Crea , Takeuchi Toshihilo , Randy Shen , Rarnesh Bhatt , Nurten Beyaz-Kavuncu
IPC分类号： C40B10/00 , C40B40/10 , C40B30/04 , C40B40/08
CPC分类号： C07K16/005 , C07K16/22 , C07K16/241 , C07K2317/21 , C07K2317/565 , C07K2317/622
摘要： Methods and compositions directed to improved universal antibody libraries that rationally exploit human diversity information contained within reference antibody libraries, such as universal antibody libraries, are disclosed. The disclosed processes involve use of a query CDR sequence to guide incorporation of human antibody diversity present within the reference library into cohort libraries of the invention. Methods for making and screening such cohort libraries for isolating therapeutics suitable for treating disease are also disclosed.
摘要翻译：公开了针对改进的通用抗体文库的方法和组合物，其合理开发参考抗体文库（例如通用抗体文库）中所含的人类多样性信息。所公开的方法涉及使用查询CDR序列来引导参与文库中存在的人抗体多样性的并入本发明的队列文库。还公开了用于制备和筛选这种用于分离适合治疗疾病的治疗剂的队列文库的方法。

7. 发明申请

US20090215639A1 Method of Producing Human IgG Antibodies with Enhanced Effector Functions 审中-公开
标题翻译：用增强效应功能生产人IgG抗体的方法
公开(公告)号：US20090215639A1
公开(公告)日：2009-08-27
申请号：US11912568
申请日：2006-04-26
申请人： Roberto Crea , Arvind Rajpal , Guido Cappuccilli , Toshihiko Takeuchi , Ramesh Bhatt , Randy Shen
发明人： Roberto Crea , Arvind Rajpal , Guido Cappuccilli , Toshihiko Takeuchi , Ramesh Bhatt , Randy Shen
IPC分类号： C40B30/04 , C40B30/00 , C12P19/34
CPC分类号： C07K16/00 , C07K2317/72 , C07K2319/30 , C07K2319/33 , C12N15/1051 , C12N15/1086
摘要： A method for generating human IgG1 antibodies with enhanced Fc effector function is disclosed. In practicing the method, an IgG1 Fc look-through mutagenesis (LTM) coding library directed at four receptor-contact regions of the Fc CH2 portion of in human IgG1 Fc is expressed in a system in which the mutated Fc fragments are displayed on the surfaces of the expression cells. The fragments are then screened for altered binding affinity to a selected Fc receptor or other Fc-binding protein. The selected mutations may be used, in turn, to guide the selection of multiple substitutions in the construction of a walk-through mutation (WTM) library, for generating additional Fc fragment mutations with desired binding properties. The antibodies so produced have a variety of therapeutic and diagnostic applications.
摘要翻译：公开了产生具有增强的Fc效应子功能的人IgG1抗体的方法。在实施该方法中，针对人IgG1 Fc中的Fc CH2部分的四个受体 - 接触区域的IgG1 Fc直通诱变（LTM）编码文库在其中突变的Fc片段显示在表面上的系统中表达的表达细胞。然后筛选片段以改变与选定的Fc受体或其它Fc结合蛋白的结合亲和力。可以使用选定的突变来指导在构建穿越突变（WTM）文库中的多个取代的选择，以产生具有期望的结合性质的另外的Fc片段突变。所产生的抗体具有多种治疗和诊断应用。

8. 发明申请

US20090169576A1 INFLUENZA COMBINATORIAL ANTIGEN VACCINE 审中-公开
标题翻译：流感组合抗原疫苗
公开(公告)号：US20090169576A1
公开(公告)日：2009-07-02
申请号：US12091423
申请日：2006-10-26
申请人： Roberto Crea , Mario H. Genero , Guido Cappuccilli , Randy Shen
发明人： Roberto Crea , Mario H. Genero , Guido Cappuccilli , Randy Shen
IPC分类号： A61K39/145 , A61P31/16 , A61P37/04
CPC分类号： C07K14/005 , A61K39/12 , A61K39/145 , A61K2039/543 , A61K2039/55566 , A61K2039/70 , C12N2760/16122 , C12N2760/16134
摘要： The invention provides a combinatorial influenza vaccine composition for use in providing prophylactic protection in humans against influenza viruses or animals, and a method of producing the vaccine.
摘要翻译：本发明提供了一种组合型流感疫苗组合物，其用于在人类中提供针对流感病毒或动物的预防性保护，以及一种生产该疫苗的方法。

9. 发明授权

US06649340B1 Walk-through mutagenesis 失效
标题翻译：直通诱变
公开(公告)号：US06649340B1
公开(公告)日：2003-11-18
申请号：US08453623
申请日：1995-05-30
申请人： Roberto Crea
发明人： Roberto Crea
IPC分类号： C12Q168
CPC分类号： C07K16/18 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/034 , C12N9/0002 , C12N9/506 , C12N15/102
摘要： A method of mutagenesis by which a predetermined amino acid is introduced into each and every position of a selected set of positions in a preselected region (or several different regions) of a protein to produce library of mutants. The method is based on the premise that certain amino acids play crucial role in the structure and fuction of proteins. Libraries can be generated which contain a high proportion of the desired mutants and are of reasonable size for screening. This libraries can be used to study the role of specific amino acids in protein structure and function and to develop new or improved proteins and polypeptides such as enzymes, antibodies, single chain antibodies and catalytic antibodies.
摘要翻译：将预定氨基酸引入到蛋白质的预选区域（或几个不同区域）中所选择的一组位置的每个位置以产生突变体文库的诱变方法。该方法基于某些氨基酸在蛋白质的结构和功能上起关键作用的前提。可以生成含有高比例的所需突变体并且筛选合理大小的文库。该文库可用于研究特定氨基酸在蛋白质结构和功能中的作用，并开发新的或改进的蛋白质和多肽，如酶，抗体，单链抗体和催化抗体。

10. 发明授权

US5700677A Protein analogues of tissue plasminogen activator 失效
标题翻译：组织纤溶酶原激活物蛋白类似物
公开(公告)号：US5700677A
公开(公告)日：1997-12-23
申请号：US799769
申请日：1991-11-27
申请人： Roberto Crea , Roy Hoi Loi Pang , Hermann Oppermann , Peter C. Keck , Gabriel Alvarado-Urbina , Gay-May Wu , Charles M. Cohen
发明人： Roberto Crea , Roy Hoi Loi Pang , Hermann Oppermann , Peter C. Keck , Gabriel Alvarado-Urbina , Gay-May Wu , Charles M. Cohen
IPC分类号： C12N9/64 , A61K38/00 , A61K38/46 , A61P7/02 , C07K14/00 , C07K14/31 , C12N1/20 , C12N9/72 , C12N15/00 , C12N15/09 , C12P21/02 , C12R1/19 , A61K38/49 , C07K14/745
CPC分类号： C07K14/31 , C12N9/6459 , C12Y304/21069 , A61K38/00
摘要： Protein analogues of tissue plasminogen activator (tPA) are described. The analogues exhibit the proteolytic function of natural tPA and optionally fibrin binding activity, but are molecules, generally of lower molecular weight than natural tPA, designed for efficient expression in prokaryotic host cell systems. The analogues can comprise a catalytic fragment of tPA or a catalytic fragment of tPA linked to a polypeptide which stabilizes the catalytic fragment, provides for efficient expression of the fragment or confers a fibrin binding capability. Fibrin binding polypeptides can be a polypeptide fragments derived from tPA which embody the fibrin binding domain(s) of natural tPA or they can be an exogenous (non-tPA) polypeptides of eukaryotic or prokaryotic origin which exhibit fibrin binding affinity such as the antigen binding fragment of an antifibrin immunoglobulin or the B domain of protein A. Genetic constructs for expression of the analogues are also provided.
摘要翻译：描述了组织纤溶酶原激活物（tPA）的蛋白质类似物。类似物表现出天然tPA和任选的纤维蛋白结合活性的蛋白水解功能，但是通常具有比天然tPA低的分子量的分子，其设计用于在原核宿主细胞系统中有效表达。类似物可以包含tPA的催化片段或与稳定催化片段的多肽连接的tPA的催化片段，提供片段的有效表达或赋予纤维蛋白结合能力。纤维蛋白结合多肽可以是衍生自tPA的多肽片段，其表现为天然tPA的纤维蛋白结合结构域，或者它们可以是表现出纤维蛋白结合亲和力的真核或原核来源的外源（非tPA）多肽，例如抗原结合抗纤维蛋白免疫球蛋白的片段或蛋白质B的B结构域。还提供了用于表达类似物的遗传构建体。

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