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1. 发明申请

WO2006046935A1 METHODS OF OPTIMIZING ANTIBODY VARIABLE REGION BINDING AFFINITY 审中-公开
标题翻译：优化抗变性区域结合亲和力的方法
公开(公告)号：WO2006046935A1
公开(公告)日：2006-05-04
申请号：PCT/US2004/032772
申请日：2004-10-28
申请人： APPLIED MOLECULAR EVOLUTION, INC , WATKINS, Jeffry, Dean , HUSE, William, D. , VASSEROT, Alain, Philippe , MARQUIS, David , SMITH, Eric
发明人： WATKINS, Jeffry, Dean , HUSE, William, D. , VASSEROT, Alain, Philippe , MARQUIS, David , SMITH, Eric
IPC分类号： C07K16/46
CPC分类号： C07K16/2878 , C07K16/36 , C07K16/464 , C07K16/465 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/92
摘要： The present invention provides optimized heteromeric variable region binding fragments and antibodies comprising optimized heteromeric variable region binding fragments. Preferably, the optimized heteromeric variable region binding fragments exhibit optimized activity compared to donor heteromeric variable regions and have unvaried human frameworks. The present invention also provides methods of making the optimized heteromeric variable region binding fragments.
摘要翻译：本发明提供了优化的异源可变区结合片段和包含优化的异聚可变区结合片段的抗体。优选地，优化的异聚可变区结合片段与供体异聚体可变区相比表现出优化的活性并且具有不变的人框架。本发明还提供了制备优化的异源可变区结合片段的方法。

2. 发明申请

WO1990014443A1 CO-EXPRESSION OF HETEROMERIC RECEPTORS 审中-公开
标题翻译：共表达异位受体
公开(公告)号：WO1990014443A1
公开(公告)日：1990-11-29
申请号：PCT/US1990002890
申请日：1990-05-15
申请人： HUSE, William, D.
IPC分类号： C12Q01/70
CPC分类号： C07K16/00 , A61K38/00 , C07K16/468 , C07K2317/56
摘要： The invention provides a composition of matter comprising a plurality of procaryotic cells containing diverse combinations of first and second DNA sequences encoding first and second polypeptides that can be expressed and which form heteromeric receptors and at least one of the plurality of procaryotic cells expressing heteromer exhibiting binding activity towards a preselected molecule.
摘要翻译：本发明提供了一种包含多个原核细胞的组合物，所述原核细胞含有编码可被表达的第一和第二多肽的第一和第二DNA序列的不同组合，并且其形成异聚受体和表达具有结合性的异源异构体的多个原核细胞中的至少一个对预选分子的活性。

3. 发明申请

WO0244361A8 EUKARYOTIC EXPRESSION LIBRARIES BASED ON DOUBLE LOX RECOMBINATION AND METHODS OF USE 审中-公开
标题翻译：基于双重LOX重组的原始表达图书馆和使用方法
公开(公告)号：WO0244361A8
公开(公告)日：2003-10-30
申请号：PCT/US0144600
申请日：2001-11-28
申请人： APPLIED MOLECULAR EVOLUTION , HUSE WILLIAM D
发明人： HUSE WILLIAM D
IPC分类号： G01N33/50 , C12N1/15 , C12N5/02 , C12N5/10 , C12N15/09 , C12N15/10 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/53 , G01N33/566 , G01N33/68 , C12N5/06
CPC分类号： C12N15/1086 , C12N15/1034 , C12N15/1082 , G01N33/68
摘要： The invention provides a cell composition comprising a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids, each of the variant nucleic acids being expressed in a different cell and located within each cell at an identical site in the genome. The invention also provides a method of identifying a polypeptide exhibiting optimized activity by sceening a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids for an activity associated with a parent polypeptide of a diverse population of variant polypeptides encoded by the variant nucleic acids; and identifying a variant polypeptide exhibiting an optimized activity relative to the parent polypeptide.
摘要翻译：本发明提供了一种细胞组合物，其包含含有不同种群的变体核酸的非酵母真核细胞群，每个变体核酸在不同的细胞中表达并位于基因组中相同位点的每个细胞内。本发明还提供了通过收集含有不同种群的变体核酸的非酵母真核细胞群体来鉴定表现出优化的活性的多肽的方法，用于与变体编码的不同变体多肽群体的亲本多肽相关的活性核酸; 并鉴定相对于亲本多肽显示优化的活性的变体多肽。

4. 发明申请

WO1998025218A1 METHOD AND MEANS FOR SYNTHESIS-BASED SIMULATION OF CHEMICALS HAVING BIOLOGICAL FUNCTIONS 审中-公开
标题翻译：用于基于合成模拟具有生物功能的化学品的方法和手段
公开(公告)号：WO1998025218A1
公开(公告)日：1998-06-11
申请号：PCT/US1997022106
申请日：1997-11-25
申请人： IXSYS, INC. , HUSE, William, D. , HE, Zhengxu , WANG, Yifeng
发明人： IXSYS, INC.
IPC分类号： G06F17/50
CPC分类号： C07K1/00 , G06F19/702 , G06F19/709
摘要： Using a programmed, general purpose digital computer, biological effectiveness of synthesized chemicals is simulated. The synthesized chemicals are modelled by data structures that embody a relationship between chemicals of which the product chemicals are composed and reaction sequences under which the chemicals are combined to produce the synthesized chemicals. The modelling includes models in the form of data structures that represent experimentally performed or hypothetically specified synthesis procedures. The models are subjected to a simulation function that predicts feasibility of a specified synthesis procedure and the biological function of chemicals produced by the specified synthesis procedure. The simulation function operates on the models to produce simulation results. One or more product chemicals are synthesized according to the hypothetically specified synthesis procedures and are assayed to produce actual assay results. The simulated results are compared to the actual assay results while referencing a tolerance limit. The simulation function is changed until the comparison has a predetermined acceptability relationship with the tolerance limit.
摘要翻译：使用编程的通用数字计算机，模拟合成化学品的生物有效性。合成的化学物质由数据结构建模，该数据结构体现了产品化学品组成的化学品与化学物质结合产生合成化学品的反应顺序之间的关系。该模型包括表示实验执行或假设指定的合成过程的数据结构形式的模型。模型受到预测指定合成程序的可行性和由指定的合成程序产生的化学品的生物学功能的模拟功能。模拟功能在模型上运行，以产生模拟结果。根据假设规定的合成方法合成一种或多种产品化学品，并进行测定以产生实际的测定结果。将模拟结果与实际测定结果进行比较，同时参考公差极限。改变模拟功能，直到比较与公差极限之间具有预定的可接受性关系。

5. 发明申请

WO03046204A8 HUMANIZED COLLAGEN ANTIBODIES AND RELATED METHODS 审中-公开
标题翻译：人源化胶原抗体及相关方法
公开(公告)号：WO03046204A8
公开(公告)日：2004-07-08
申请号：PCT/US0238147
申请日：2002-11-26
申请人： CELL MATRIX INC , WATKINS JEFFRY D , HUSE WILLIAM D , TANG YING , BROEK DANIEL , BROOKS PETER C
发明人： WATKINS JEFFRY D , HUSE WILLIAM D , TANG YING , BROEK DANIEL , BROOKS PETER C
IPC分类号： C12N15/09 , A61K39/395 , A61K47/48 , A61P9/00 , A61P35/00 , A61P35/04 , C07K16/18 , C07K16/30 , C12P21/08 , C12Q
CPC分类号： C07K16/30 , A61K47/6843 , A61K47/6851 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/565
摘要： The invention provides a grafted antibody, or functional fragment thereof, comprising one or more complementarily determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the grafted antibody or functional fragment thereof has specific binding activity for a cryptic collagen epitope. The invention also provides methods of using an antibody having specific binding activity for a cryptic collagen epitope, including methods of inhibiting angiogenesis, tumor growth, and metastasis.
摘要翻译：本发明提供了移植抗体或其功能片段，其包含在重链CDR的一个或多个CDR中具有至少一个氨基酸取代的一个或多个互补决定区（CDR），其中移植抗体或其功能片段具有特异性对神经胶原表位的结合活性。本发明还提供了将具有特异性结合活性的抗体用于神经胶原表位的方法，包括抑制血管生成，肿瘤生长和转移的方法。

6. 发明申请

WO0236615A3 METHODS FOR PRODUCING AND IMPROVING THERAPEUTIC POTENCY OF BINDING POLYPEPTIDES 审中-公开
标题翻译：生产和改善结合多糖治疗疗法的方法
公开(公告)号：WO0236615A3
公开(公告)日：2003-08-21
申请号：PCT/US0146248
申请日：2001-10-30
申请人： APPLIED MOLECULAR EVOLUTION , HUSE WILLIAM D
发明人： HUSE WILLIAM D
IPC分类号： A61K38/00 , A61K38/22 , A61K38/28 , A61K38/43 , A61K38/44 , A61K38/45 , A61K38/46 , A61K39/395 , C07K1/00 , C07K14/00 , C07K16/00 , C12N9/18 , G01N33/557 , G01N33/68
CPC分类号： C12N9/18 , A61K38/00 , G01N33/557
摘要： The invention provides a binding polypeptide, or functional fragment thereof, comprising a kon of at least about 9 x 10 M s for associating with a ligand and having therapeutic potency. The invention also provides a method of determining the therapeutic potency of a binding polypeptide. The methods consist of (a) contacting a binding polypeptide with a ligand; (b) measuring association rate for binding between the binding polypeptide and the ligand, and (c) comparing the association rate for the binding polypeptide to an association rate for a therapeutic control, the relative association rate for the binding polypeptide compared to the association rate for the therapeutic control indicating that the binding polypeptide wil exhibit a difference in therapeutic potency correlative with the difference between the association rates.
摘要翻译：本发明提供了结合多肽或其功能片段，其包含与配体缔合并具有治疗效力的至少约9×10 -7 M -1的kon。本发明还提供了确定结合多肽的治疗效力的方法。方法包括（a）使结合多肽与配体接触; （b）测量结合多肽和配体之间结合的结合速率，和（c）将结合多肽的结合速率与治疗对照的结合速率进行比较，结合多肽相对于结合速率的相对关联速率用于治疗控制，表明结合性多肽与治疗效力之间的差异表现出与治疗效力的差异。

7. 发明申请

WO2004063335A3 TNF-α BINDING MOLECULES 审中-公开
公开(公告)号：WO2004063335A3
公开(公告)日：2004-07-29
申请号：PCT/US2004/000290
申请日：2004-01-08
申请人： APPLIED MOLECULAR EVOLUTION , WATKINS, Jeffry, D. , VASSEROT, Alain, P. , MARQUIS, David , HUSE, William, D.
发明人： WATKINS, Jeffry, D. , VASSEROT, Alain, P. , MARQUIS, David , HUSE, William, D.
IPC分类号： A61K39/395 , C07K16/22
摘要： The present invention relates to TNF-α binding molecules and nucleic acid sequences encoding TNF-α binding molecules. In particular, the present invention relates to TNF-α binding molecules with a high binding affinity, a high association rate, a low dissociation rate with regard to human TNF-α and that are capable of neutralizing TNF-α at low concentrations. Preferably, the TNF-α binding molecules of the present invention comprise light and/or heavy chain variable regions with fully human frameworks (e.g. human germline frameworks).

8. 发明申请

WO2004063335A2 TNF-alpha BINDING MOLECULES 审中-公开
标题翻译： TNF-α结合分子
公开(公告)号：WO2004063335A2
公开(公告)日：2004-07-29
申请号：PCT/US2004000290
申请日：2004-01-08
申请人： APPLIED MOLECULAR EVOLUTION , WATKINS JEFFRY D , VASSEROT ALAIN P , MARQUIS DAVID , HUSE WILLIAM D
发明人： WATKINS JEFFRY D , VASSEROT ALAIN P , MARQUIS DAVID , HUSE WILLIAM D
IPC分类号： C07K16/24 , C12N
CPC分类号： C07K16/241 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N2333/525
摘要： The present invention relates to TNF-alpha binding molecules and nucleic acid sequences encoding TNF-alpha binding molecules. In particular, the present invention relates to TNF-alpha binding molecules with a high binding affinity, a high association rate, a low dissociation rate with regard to human TNF-alpha and that are capable of neutralizing TNF-alpha at low concentrations. Preferably, the TNF-alpha binding molecules of the present invention comprise light and/or heavy chain variable regions with fully human frameworks (e.g. human germline frameworks).
摘要翻译：本发明涉及TNF-α结合分子和编码TNF-α结合分子的核酸序列。特别地，本发明涉及具有高结合亲和力，高缔合率，相对于人TNF-α的低解离速率且能够以低浓度中和TNF-α的TNF-α结合分子。优选地，本发明的TNF-α结合分子包含具有完全人框架（例如人种系框架）的轻链和/或重链可变区。

9. 发明申请

WO03046204A2 HUMANIZED COLLAGEN ANTIBODIES AND RELATED METHODS 审中-公开
标题翻译：人类胶原抗体及相关方法
公开(公告)号：WO03046204A2
公开(公告)日：2003-06-05
申请号：PCT/US0238147
申请日：2002-11-26
申请人： CELL MATRIX INC , WATKINS JEFFRY D , HUSE WILLIAM D , TANG YING , BROEK DANIEL , BROOKS PETER C
发明人： WATKINS JEFFRY D , HUSE WILLIAM D , TANG YING , BROEK DANIEL , BROOKS PETER C
IPC分类号： C12N15/09 , A61K39/395 , A61K47/48 , A61P9/00 , A61P35/00 , A61P35/04 , C07K16/18 , C07K16/30 , C12P21/08 , C12Q
CPC分类号： C07K16/30 , A61K47/6843 , A61K47/6851 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/565
摘要： The invention provides a grafted antibody, or functional fragment thereof, comprising one or more complementarily determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the grafted antibody or functional fragment thereof has specific binding activity for a cryptic collagen epitope. The invention also provides methods of using an antibody having specific binding activity for a cryptic collagen epitope, including methods of inhibiting angiogenesis, tumor growth, and metastasis.
摘要翻译：本发明提供了接枝抗体或其功能片段，其包含一个或多个在重链CDR的一个或多个CDR中具有至少一个氨基酸取代的互补决定区（CDR），其中所述接枝抗体或其功能片段具有特异性隐形胶原表位的结合活性。本发明还提供了使用具有对神经胶原表位具有特异性结合活性的抗体的方法，包括抑制血管发生，肿瘤生长和转移的方法。

10. 发明申请

WO0244361A3 EUKARYOTIC EXPRESSION LIBRARIES BASED ON DOUBLE LOX RECOMBINATION AND METHODS OF USE 审中-公开
标题翻译：基于双重LOX重组的原始表达图书馆和使用方法
公开(公告)号：WO0244361A3
公开(公告)日：2002-08-22
申请号：PCT/US0144600
申请日：2001-11-28
申请人： APPLIED MOLECULAR EVOLUTION , HUSE WILLIAM D
发明人： HUSE WILLIAM D
IPC分类号： G01N33/50 , C12N1/15 , C12N5/02 , C12N5/10 , C12N15/09 , C12N15/10 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/53 , G01N33/566 , G01N33/68 , C12N5/06
CPC分类号： C12N15/1086 , C12N15/1034 , C12N15/1082 , G01N33/68
摘要： The invention provides a cell composition comprising a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids, each of the variant nucleic acids being expressed in a different cell and located within each cell at an identical site in the genome. The invention also provides a method of identifying a polypeptide exhibiting optimized activity by sceening a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids for an activity associated with a parent polypeptide of a diverse population of variant polypeptides encoded by the variant nucleic acids; and identifying a variant polypeptide exhibiting an optimized activity relative to the parent polypeptide.
摘要翻译：本发明提供了一种细胞组合物，其包含含有不同种群的变体核酸的非酵母真核细胞群，每个变体核酸在不同的细胞中表达并位于基因组中相同位点的每个细胞内。本发明还提供了通过收集含有不同种群的变体核酸的非酵母真核细胞群体来鉴定表现出优化的活性的多肽的方法，用于与变体编码的不同变体多肽群体的亲本多肽相关的活性核酸; 并鉴定相对于亲本多肽显示优化的活性的变体多肽。

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