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1. 发明申请

WO2007054816A3 ANTIBODY ULTRAHUMANIZATION BY PREDICTED MATURE CDR BLASTING AND COHORT LIBRARY GENERATION AND SCREENING 审中-公开
标题翻译：预测成熟CDR爆破和排放库的生成和筛选进行抗体超声波化
公开(公告)号：WO2007054816A3
公开(公告)日：2007-10-04
申请号：PCT/IB2006003288
申请日：2006-11-10
申请人： BIOREN INC , CAPPUCILLI GUIDO , CREA ROBERTO , BAYEZ NURTEN , TAKEUCHI TOSHIHIKO , SHEN RANDY , BHATT RAMESH
发明人： CAPPUCILLI GUIDO , CREA ROBERTO , BAYEZ NURTEN , TAKEUCHI TOSHIHIKO , SHEN RANDY , BHATT RAMESH
IPC分类号： C12N15/10 , G01N33/53 , G06F17/00
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，其合理利用参考抗体文库（例如通用抗体文库）中包含的人类多样性信息。所公开的方法涉及使用查询CDR序列来指导参考文库内存在的人抗体多样性并入本发明的群组文库。还公开了制备和筛选这种用于分离适合治疗疾病的治疗剂的群组文库的方法。

2. 发明申请

WO2006114700A3 METHOD OF PRODUCING HUMAN IGG ANTIBODIES WITH ENHANCED EFFECTOR FUNCTIONS 审中-公开
标题翻译：生产具有增强效应功能的人IGG抗体的方法
公开(公告)号：WO2006114700A3
公开(公告)日：2007-04-26
申请号：PCT/IB2006001030
申请日：2006-04-26
申请人： BIOREN INC , CREA ROBERTO , CAPPUCCILLI GUIDO , TAKEUCHI TOSHI , RAJPAL ARVIND , BHATT RAMESH , SHEN RANDY
发明人： CREA ROBERTO , CAPPUCCILLI GUIDO , TAKEUCHI TOSHI , RAJPAL ARVIND , BHATT RAMESH , SHEN RANDY
IPC分类号： C07K16/00 , C12N15/10
CPC分类号： C07K16/00 , C07K2317/72 , C07K2319/30 , C07K2319/33 , C12N15/1051 , C12N15/1086
摘要： A method for generating human IgG 1 antibodies with enhanced Fc effector function is disclosed. In practicing the method, an IgG 1 Fc look-through mutagenesis (LTM) coding library directed at four receptor-contact regions of the Fc C H 2 portion of in human IgG 1 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：公开了一种产生具有增强的Fc效应子功能的IgG1抗体的方法。在实施该方法中，针对人IgG中Fc C H 2部分的四个受体 - 接触区域的IgG1C1直观诱变（LTM）编码文库 Fc表达在其中突变的Fc片段显示在表达细胞的表面上的系统中。然后筛选片段以改变与选定的Fc受体或其他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。

3. 发明申请

WO2011035202A3 UNIVERSAL FIBRONECTIN TYPE III BINDING-DOMAIN LIBRARIES 审中-公开
标题翻译：通用FIBRONECTIN III型绑定库
公开(公告)号：WO2011035202A3
公开(公告)日：2011-05-12
申请号：PCT/US2010049391
申请日：2010-09-17
申请人： PROTELIX INC , CAPPUCCILLI GUIDO , CREA ROBERTO , SHEN RANDY , HOKANSON CRAIG A , KIRK PETER B , LISTON DAVID R
发明人： CAPPUCCILLI GUIDO , CREA ROBERTO , SHEN RANDY , HOKANSON CRAIG A , KIRK PETER B , LISTON DAVID R
IPC分类号： C07K14/00 , G01N33/53
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 AxI proteins.
摘要翻译：描述了纤连蛋白III型（FN3）多肽文库，以及它们用于鉴定对于VEGFR2或AxI蛋白具有hign结合亲和力（例如大于300nM）的纤连蛋白型结合肽。

4. 发明申请

WO2007051036A8 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：WO2007051036A8
公开(公告)日：2007-11-29
申请号：PCT/US2006042411
申请日：2006-10-26
申请人： PROTELIX INC , CREA ROBERTO , GENERO MARIO H , CAPPUCCILLI GUIDO , SHEN RANDY
发明人： CREA ROBERTO , GENERO MARIO H , CAPPUCCILLI GUIDO , SHEN RANDY
IPC分类号： A61K39/00 , A61K39/12 , A61K39/145 , A61K39/21 , A61K39/295
CPC分类号： C07K14/005 , A61K39/12 , A61K39/145 , A61K2039/543 , A61K2039/55566 , A61K2039/70 , C12N2760/16122 , C12N2760/16134

5. 发明申请

WO2006014498A3 UNIVERSAL ANTIBODY LIBRARIES 审中-公开
标题翻译：通用抗体库
公开(公告)号：WO2006014498A3
公开(公告)日：2007-03-01
申请号：PCT/US2005024002
申请日：2005-07-06
申请人： BIOREN INC , CREA ROBERTO
发明人： CREA ROBERTO
IPC分类号： C07H21/02 , C07H21/00 , C07K1/00 , C12P19/34
CPC分类号： C07K16/00 , C07K2317/21 , C07K2317/565 , C07K2317/567 , C07K2317/622
摘要： Universal antibody libraries are described which are synthetic and derived from expressed human antibody sequences selected accordingly to certain criteria, for example, that the sequences are derived from naturally-occurring antibodies expressed in response to a certain antigen class (e.g., small molecule, polysaccharide, peptide, or protein) and having CDR regions engineered for optimal diversity. Methods for making and screening such libraries for isolating therapeutics suitable for treating disease are also disclosed.
摘要翻译：描述了通用抗体文库，其是合成的，并且衍生自相应于某些标准的表达的人抗体序列，例如，所述序列衍生自响应某一抗原类别（例如小分子，多糖，肽或蛋白质）并且具有被设计用于最佳多样性的CDR区域。还公开了用于制备和筛选用于分离适合治疗疾病的治疗剂的文库的方法。

6. 发明申请

WO2006023144A3 LOOK-THROUGH MUTAGENESIS FOR DEVELOPING ALTERED POLYPEPTIDES WITH ENHANCED PROPERTIES 审中-公开
标题翻译：突变致突变体用于增强特性开发修饰多肽
公开(公告)号：WO2006023144A3
公开(公告)日：2006-08-17
申请号：PCT/US2005024140
申请日：2005-07-06
申请人： BIOREN INC , CREA ROBERTO
发明人： CREA ROBERTO
IPC分类号： C07H21/02 , C07K16/00
CPC分类号： C12N15/102 , C07K16/00 , C07K16/18 , C07K2317/565 , C07K2317/622 , C07K2317/92 , C12N15/1093 , G01N33/6854 , G01N33/6857
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 polypeptide to produce a library of polypeptide analogs is disclosed. The method is based on the premise that certain amino acids play a crucial role in the structure and function of proteins and thus is capable of identifying and distinguishing functional amino acid residues ("hot spots") from non-functional amino acids residues ("cold spots") within a polypeptide or portion thereof. Libraries can be generated which contain only desired polypeptide analogs and are of reasonable size for screening. The libraries can be used to study the role of specific amino acids in polypeptide structure and function and to develop new or improved polypeptides such as antibodies, antibody fragments, single chain antibodies, enzymes, and ligands.
摘要翻译：公开了一种诱变方法，通过该方法将预定氨基酸引入多肽的预选区域（或多个不同区域）中选定位置组的每个位置以产生多肽类似物文库。该方法基于这样的前提：某些氨基酸在蛋白质的结构和功能中起关键作用，因此能够从非功能性氨基酸残基（“冷的（cold））中鉴别和区分功能性氨基酸残基（”热点“ 点“）在多肽或其部分内。可以产生仅包含期望的多肽类似物并且具有合理大小用于筛选的文库。文库可用于研究特定氨基酸在多肽结构和功能中的作用，并开发新的或改进的多肽，如抗体，抗体片段，单链抗体，酶和配体。

7. 发明申请

WO2009023184A3 UNIVERSAL FIBRONECTIN TYPE III BINDING-DOMAIN LIBRARIES 审中-公开
标题翻译：通用纤连蛋白III型结合域文库
公开(公告)号：WO2009023184A3
公开(公告)日：2009-07-09
申请号：PCT/US2008009617
申请日：2008-08-11
申请人： PROTELIX INC , CAPPUCCILLI GUIDO , CREA ROBERTO , SHEN RANDY , HOKANSON CRAIG A , KIRK PETER B , LISTON DAVID R
发明人： CAPPUCCILLI GUIDO , CREA ROBERTO , SHEN RANDY , HOKANSON CRAIG A , KIRK PETER B , LISTON DAVID R
IPC分类号： C12N15/10 , C07K14/78 , C07K16/18 , C07K16/22 , C07K16/24 , C12N9/00
CPC分类号： C07K16/241 , C07K14/78 , C07K16/18 , C07K16/22 , C07K2317/21 , C07K2317/52 , C07K2318/20 , C07K2319/30 , 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：描述了步行诱变和天然变体组合型纤连蛋白III型（FN3）多肽文库以及它们的构建和使用方法。还公开了通过筛选文库针对各种选择的抗原选择的许多高结合亲和性多肽。

8. 发明申请

WO2007127290A3 METHOD FOR PRODUCING VIRAL VACCINE AND THERAPEUTIC PEPTIDE ANTIGENS 审中-公开
标题翻译：生产病毒和治疗肽抗原的方法
公开(公告)号：WO2007127290A3
公开(公告)日：2008-08-07
申请号：PCT/US2007010106
申请日：2007-04-24
申请人： PROTELIX INC , CREA ROBERTO , CAPPUCCILLI GUIDO , SHEN RANDY , GENERO MARIO H
发明人： CREA ROBERTO , CAPPUCCILLI GUIDO , SHEN RANDY , GENERO MARIO H
IPC分类号： C07K5/00 , A61K39/00 , C12N15/00
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/145 , C12N2760/16122 , C12N2760/16134
摘要： A method of producing viral antigens for use in a vaccine or therapeutic composition against infection by a virus, and a composition produced thereby, are disclosed. The method is applicable to viruses having a plurality of subtypes whose protein sequences for at least one viral protein or polyprotein are known. Regions of a selected viral protein that (i) are known or predicted to bind to MHC proteins in host antigen-presenting cells, and (ii) have a moderate amino acid variability within the virus subtypes are systematically varied in amino acid sequence, and tested for enhanced binding to MHC proteins. The composition includes those peptides having the highest binding affinity for MHC proteins.
摘要翻译：公开了一种用于疫苗或治疗组合物中用于病毒感染的病毒抗原的方法，以及由此产生的组合物。该方法适用于具有多个亚型的病毒，其具有至少一种病毒蛋白或多蛋白的蛋白质序列是已知的。所选择的病毒蛋白的区域（i）已知或预测与宿主抗原呈递细胞中的MHC蛋白结合，和（ii）在病毒亚型中具有中等氨基酸变异性在氨基酸序列中系统地变化，并进行测试用于增强与MHC蛋白的结合。该组合物包括对MHC蛋白具有最高结合亲和力的那些肽。

9. 发明申请

WO2006014477A9 HIGH AFFINITY ANTI-TNF-a ANTIBODIES AND METHOD 审中-公开
标题翻译：高亲和力抗TNF-α抗体和方法
公开(公告)号：WO2006014477A9
公开(公告)日：2006-03-16
申请号：PCT/US2005023957
申请日：2005-07-06
申请人： BIOREN INC , CREA ROBERTO , RAJPAL ARVIND , TAKEUCHI TOSHI , CAPPUCCILLI GUIDO , JONES JENNIFER
发明人： CREA ROBERTO , RAJPAL ARVIND , TAKEUCHI TOSHI , CAPPUCCILLI GUIDO , JONES JENNIFER
IPC分类号： C07K16/24 , A61K39/395
CPC分类号： C07K16/241 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/92
摘要： An isolated human anti-TNF-a antibody, or antigen-binding portion thereof, containing at least one high-affinity V
摘要翻译：包含至少一个高亲和力V亚基的分离的人抗TNF-α抗体或其抗原结合部分

10. 发明专利

JP2003135084A WALK-THROUGH MUTAGENESIS 审中-公开
公开(公告)号：JP2003135084A
公开(公告)日：2003-05-13
申请号：JP2002296049
申请日：2002-10-09
申请人： CREA ROBERTO
发明人： CREA ROBERTO
IPC分类号： C07K14/155 , A61K38/00 , C07K14/00 , C07K16/00 , C07K16/18 , C12M1/00 , C12N9/00 , C12N9/50 , C12N15/09 , C12N15/10 , C12P21/02 , C12P21/08 , C12R1/19
摘要： PROBLEM TO BE SOLVED: To provide a method for mutagenesis by introducing a predetermined amino acid into each and every position of a selected set of positions in a preselected region (or several different regions) of a protein to produce a library of mutants. SOLUTION: The method is based on the premise that a certain kind of amino acid plays an important role in the structure and function of a protein. A library containing the desired mutant at a high ratio and having a rational size for screening can be produced by the method. These libraries are useful for the investigation of the role of a specific amino acid in the structure and function of a protein and the formation of new or improved proteins or polypeptides such as enzymes, antibodies, single-stranded antibodies and antibodies of catalysts.

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