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1. 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。

2. 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。

3. 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。

4. 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。

5. 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。

6. 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

7. 发明专利

JP2012097107A Antibody ultrahumanization by predicted mature cdr blasting and cohort library generation and screening 有权
标题翻译：通过预测成像进行抗体超声心动图扫描和联合图书馆生成和筛选
公开(公告)号：JP2012097107A
公开(公告)日：2012-05-24
申请号：JP2011288823
申请日：2011-12-28
申请人： Bioren Inc , バイオレン・インク
发明人： CAPPUCILLI GUIDO , CREA ROBERTO , BAYEZ NURTEN , TAKEUCHI TOSHIHIKO , SHEN RANDY , BHATT RAMESH
IPC分类号： C07K14/705 , C40B30/04 , C40B40/06 , C40B40/10 , G01N33/53
CPC分类号： C07K16/005 , C07K16/22 , C07K16/241 , C07K2317/21 , C07K2317/565 , C07K2317/622
摘要： PROBLEM TO BE SOLVED: To provide 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.SOLUTION: 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. Methods for making and screening such cohort libraries for isolating therapeutics suitable for treating disease are also disclosed.
摘要翻译：要解决的问题：提供针对改进的通用抗体文库的方法和组合物，其合理地利用包含在参考抗体文库（例如通用抗体文库）内的人类多样性信息。解决方案：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类抗体多样性并入队列文库。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。版权所有（C）2012，JPO＆INPIT

8. 发明专利

CA2627075A1 ANTIBODY ULTRAHUMANIZATION BY PREDICTED MATURE CDR BLASTING AND COHORT LIBRARY GENERATION AND SCREENING 未知
公开(公告)号：CA2627075A1
公开(公告)日：2007-05-18
申请号：CA2627075
申请日：2006-11-10
申请人： BIOREN INC
发明人： BHATT RAMESH , CAPPUCILLI GUIDO , SHEN RANDY , CREA ROBERTO , BAYEZ NURTEN , TAKEUCHI TOSHIHIKO
IPC分类号： C12N15/10 , G01N33/53 , G06F17/00
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.

9. 发明专利

ES2402576T3 Ultrahumanización de anticuerpos por generación y selección de bibliotecas cohorte y blast de cdr maduras previstas 未知
公开(公告)号：ES2402576T3
公开(公告)日：2013-05-06
申请号：ES06809242
申请日：2006-11-10
申请人： BIOREN INC
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
摘要： Un procedimiento para producir una biblioteca de pUn procedimiento para producir una biblioteca de polinucleótidos que codifica al menos una región deolinucleótidos que codifica al menos una región determinantede la complementariedad (CDR) en la que terminantede la complementariedad (CDR) en la que el procedimiento comprende: (a) determinar la variel procedimiento comprende: (a) determinar la variación de secuencia de aminoácidos de la CDR presenación de secuencia de aminoácidos de la CDR presente en una biblioteca de anticuerposde referencia qte en una biblioteca de anticuerposde referencia que consiste en las CDR naturales como se define deue consiste en las CDR naturales como se define de acuerdo con el Índice EU, Kabat, Chothia odefinic acuerdo con el Índice EU, Kabat, Chothia odefinición de punto de contacto, en el que la variación dión de punto de contacto, en el que la variación de secuencia CDR se determina en cada posición deree secuencia CDR se determina en cada posición deresto de aminoácido de la CDR; (b) alinear una secuesto de aminoácido de la CDR; (b) alinear una secuencia peptídica CDR problema de un anticuerpo contrncia peptídica CDR problema de un anticuerpo contra un antígeno diana con lassecuencias CDR de la bia un antígeno diana con lassecuencias CDR de la biblioteca de anticuerpo de referencia; y (c) sintetblioteca de anticuerpo de referencia; y (c) sintetizar una biblioteca de polinucleótidos que codificizar una biblioteca de polinucleótidos que codifica secuencias CDR, en la que(i) el resto de aminoáca secuencias CDR, en la que(i) el resto de aminoácido codificado en cualquier posición simple dentroido codificado en cualquier posición simple dentro de una secuencia CDR esidéntico a un resto de ami de una secuencia CDR esidéntico a un resto de aminoácido en la posición alineada correspondiente denoácido en la posición alineada correspondiente de la secuencia peptídica de laCDR problema de un an la secuencia peptídica de laCDR problema de un anticuerpo dirigido contra un antígeno candidato; o ticuerpo dirigido contra un antígeno candidato; o (ii) es un resto, o restos, de aminoácido predeter(ii) es un resto, o restos, de aminoácido predeterminado si un resto de aminoácido idéntico para lasminado si un resto de aminoácido idéntico para lasecuencia peptídica de CDR problema en la posición ecuencia peptídica de CDR problema en la posición que se alinea no aparece en la biblioteca derefereque se alinea no aparece en la biblioteca dereferencia, por lo que se proporciona una biblioteca de ncia, por lo que se proporciona una biblioteca de polinucleótidos que codifica análogos de CDR de lapolinucleótidos que codifica análogos de CDR de la secuencia peptídicade CDR problema de un anticuer secuencia peptídicade CDR problema de un anticuerpo contra un antígeno diana, enriqueciéndose los apo contra un antígeno diana, enriqueciéndose los análogos de CDR deaminoácidos que existen en estadonálogos de CDR deaminoácidos que existen en estado natural en una o más posiciones de restos. natural en una o más posiciones de restos.

10. 发明专利

CA2605697A1 METHOD OF PRODUCING HUMAN IGG ANTIBODIES WITH ENHANCED EFFECTOR FUNCTIONS 未知
公开(公告)号：CA2605697A1
公开(公告)日：2006-11-02
申请号：CA2605697
申请日：2006-04-26
申请人： BIOREN INC
发明人： TAKEUCHI TOSHI , RAJPAL ARVIND , BHATT RAMESH , SHEN RANDY , CREA ROBERTO , CAPPUCCILLI GUIDO
IPC分类号： C07K16/00 , C12N15/10
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 o f 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 F c receptor or other Fc-binding protein. The selected mutations may be used, in turn, to guide the selection of multiple substitutions in the construction o f 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.

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