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1. 发明申请

US20070077199A1 Humanized collagen antibodies and related methods 失效
标题翻译：人源化胶原抗体及相关方法
公开(公告)号：US20070077199A1
公开(公告)日：2007-04-05
申请号：US11486894
申请日：2006-07-14
申请人： Jeffry Watkins , William Huse , Ying Tang , Daniel Broek , Peter Brooks
发明人： Jeffry Watkins , William Huse , Ying Tang , Daniel Broek , Peter Brooks
IPC分类号： A61K51/00 , G01N33/574 , A61K39/395 , C07K16/30 , C07K16/46
CPC分类号： C07K16/30 , A61K47/6843 , A61K47/6851 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/565
摘要： The invention provides an antibody, or functional fragment thereof, a grafted antibody, or functional fragment thereof, comprising one or more complementarity determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the 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：本发明提供抗体或其功能片段，其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），其中抗体或其功能片段对隐窝胶原表位具有特异性结合活性。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。

2. 发明申请

US20050003469A1 Tumor specific human monoclonal antibodies and methods of use 审中-公开
标题翻译：肿瘤特异性人单克隆抗体及使用方法
公开(公告)号：US20050003469A1
公开(公告)日：2005-01-06
申请号：US10910124
申请日：2004-08-02
申请人： Jeffry Watkins , William Huse
发明人： Jeffry Watkins , William Huse
IPC分类号： A61K47/48 , C07K16/30 , G01N33/574 , C07K16/28
CPC分类号： C07K16/3069 , A61K47/6851 , A61K2039/505 , C07K16/3015 , C07K16/3023 , C07K2317/21 , C07K2317/565
摘要： The invention provides tumor-specific human monoclonal antibodies and functional fragments. Also provided are nucleic acids encoding tumor-specific human monoclonal antibodies and functional fragments. A method for reducing neoplastic cell proliferation is also provided. The method consists of administering an effective amount of a tumor-specific human monoclonal antibody or functional fragment. Also provided is a method of detecting a neoplastic cell in a sample. The method consists of contacting a cell with a tumor-specific monoclonal antibody or functional fragment and detecting the specific binding of the human monoclonal antibody or functional fragment to the sample.
摘要翻译：本发明提供肿瘤特异性人单克隆抗体和功能片段。还提供了编码肿瘤特异性人单克隆抗体和功能片段的核酸。还提供了减少肿瘤细胞增殖的方法。该方法包括施用有效量的肿瘤特异性人单克隆抗体或功能片段。还提供了检测样品中的肿瘤细胞的方法。该方法包括使细胞与肿瘤特异性单克隆抗体或功能片段接触并检测人单克隆抗体或功能片段与样品的特异性结合。

3. 发明申请

US20060269549A1 Tnf-alpha binding molecules 有权
标题翻译： Tnf-α结合分子
公开(公告)号：US20060269549A1
公开(公告)日：2006-11-30
申请号：US10541260
申请日：2004-01-08
申请人： Jeffry Watkins , Alain Vasserot , David Marquis , William Huse
发明人： Jeffry Watkins , Alain Vasserot , David Marquis , William Huse
IPC分类号： A61K48/00 , A61K39/395 , A61K38/17
CPC分类号： C07K16/241 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/565 , C07K2317/92
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).
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。

4. 发明申请

US20050064438A1 Heteromeric variable regions with unvaried human framework regions 审中-公开
公开(公告)号：US20050064438A1
公开(公告)日：2005-03-24
申请号：US10697400
申请日：2003-10-30
申请人： William Huse , Jeffry Watkins , Herren Wu
发明人： William Huse , Jeffry Watkins , Herren Wu
IPC分类号： C07K16/28 , C07K16/36 , C07K16/46 , C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C07K16/465 , C07K16/00 , C07K16/2878 , C07K16/36 , C07K16/464 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/92
摘要： The invention provides a method of conferring donor CDR binding affinity onto an antibody acceptor variable region framework. The method consists of: (a) constructing a population of altered antibody variable region encoding nucleic acids, said population comprising encoding nucleic acids for an acceptor variable region framework containing a plurality of different amino acids at one or more acceptor framework region amino acid positions and donor CDRs containing a plurality of different amino acids at one or more donor CDR amino acid positions; (b) expressing said population of altered variable region encoding nucleic acids, and (c) identifying one or more altered variable regions having binding affinity substantially the same or greater than the donor CDR variable region. The acceptor variable region framework can be a heavy or light chain variable region framework and the populations of heavy and light chain altered variable regions can be expressed alone to identify heavy or light chains having binding affinity substantially the same or greater than the donor CDR variable region. The populations of heavy and light chains additionally can be coexpressed to identify heteromeric altered variable region binding fragments. The invention also provides a method of simultaneously grafting and optimizing the binding affinity of a variable region binding fragment. The method consists of: (a) constructing a population of altered heavy chain variable region encoding nucleic acids comprising an acceptor variable region framework containing donor CDRs and a plurality of different amino acids at one or more framework region and CDR amino acid positions; (b) constructing a population of altered light chain variable region encoding nucleic acids comprising an acceptor variable region framework containing donor CDRs and a plurality of different amino acids at one or more framework regions and CDR amino acid positions; (c) coexpressing said populations of heavy and light chain variable region encoding nucleic acids to produce diverse combinations of heteromeric variable region binding fragments, and (d) identifying one or more heteromeric variable region binding fragments having affinity substantially the same or greater than the donor CDR heteromeric variable region binding fragment. A method of optimizing the binding affinity of an antibody variable region is also provided. The method consists of: (a) constructing a population of antibody variable region encoding nucleic acids, said population comprising two or more CDRs containing a plurality of different amino acids at one or more CDR amino acid positions; (b) expressing said population of variable region encoding nucleic acids, and (c) identifying one or more variable regions having binding affinity substantially the same or greater than the donor CDR variable region. The variable region populations can be heavy or light chains and can be expressed as individual populations or they can be coexpressed to produce heteromeric variable region binding fragments.

5. 发明申请

US20050003384A1 Surface expression libraries of heteromeric receptors 审中-公开
标题翻译：异聚受体的表面表达文库
公开(公告)号：US20050003384A1
公开(公告)日：2005-01-06
申请号：US10767869
申请日：2004-01-28
申请人： William Huse
发明人： William Huse
IPC分类号： C07K14/01 , C07K14/705 , C07K16/00 , C07K16/44 , C12N15/10 , C12N15/13 , C12N15/64 , C12N15/65 , C12N15/70 , C40B40/02 , C12Q1/70 , C12N5/06 , C12Q1/68 , G01N33/53
CPC分类号： C40B40/02 , C07K14/005 , C07K14/705 , C07K16/00 , C07K16/44 , C07K2319/00 , C12N15/1037 , C12N15/64 , C12N15/65 , C12N15/70 , C12N2795/10022 , C12N2795/14022
摘要： A composition of matter comprising a plurality of procaryotic cells containing diverse combinations of first and second DNA sequences encoding first and second polypeptides which form a heteromeric receptor exhibiting binding activity toward a preselected molecule, said heteromeric receptors being expressed on the surface of filamentous bacteriophage.
摘要翻译：一种包含多个原核细胞的组合物，其含有编码第一和第二多肽的第一和第二多肽的不同组合的组合，所述第一和第二DNA序列形成对预选分子具有结合活性的异聚受体，所述异聚受体在丝状噬菌体的表面上表达。

6. 发明授权

US5128256A DNA cloning vectors with in vivo excisable plasmids 失效
标题翻译：具有体内可切除质粒的DNA克隆载体
公开(公告)号：US5128256A
公开(公告)日：1992-07-07
申请号：US341261
申请日：1989-04-20
申请人： William Huse , Joseph A. Sorge , Jay M. Short
发明人： William Huse , Joseph A. Sorge , Jay M. Short
IPC分类号： C12N15/64 , C12N15/70
CPC分类号： C12N15/70 , C12N15/64
摘要： Vectors are described that circumvent traditional DNA cloning and subcloning procedures, and that contain a unique DNA cartridge that permits both cloning of DNA directly into DNA sequences present within the cartridge, and in vivo removal and circularization of the cartridge thereby yielding an autonomously replicating structure. Because the DNA cartridge can include a wide variety of functional DNA sequences, the cloned DNA can be subjected to a plethora of molecular biological procedures without having to remove the cloned DNA from the cartridge thereby obviating the need to perform additional subcloning techniques. A particularly useful example of this type of vector is bacteriophage lambda containing the DNA cartridge.
摘要翻译：描述了可以克服传统DNA克隆和亚克隆程序的载体，并且其含有独特的DNA柱，其允许将DNA直接克隆到存在于盒内的DNA序列中，并且在体内移除和环化圆筒，从而产生自主复制的结构。因为DNA盒可以包括多种功能性DNA序列，所以克隆的DNA可以经受大量的分子生物学过程，而不必从盒中除去克隆的DNA，从而避免进行附加亚克隆技术的需要。这种载体的特别有用的实例是含有DNA盒的噬菌体λ。

7. 发明申请

US20070207475A1 METHOD FOR PRODUCING POLYMERS HAVING A PRESELECTED ACTIVITY 失效
标题翻译：制备具有预定活性的聚合物的方法
公开(公告)号：US20070207475A1
公开(公告)日：2007-09-06
申请号：US11560769
申请日：2006-11-16
申请人： William Huse , Gregory Winter , Lutz Riechmann , Joseph Sorge , Richard Lerner
发明人： William Huse , Gregory Winter , Lutz Riechmann , Joseph Sorge , Richard Lerner
IPC分类号： C12Q1/68 , C07K16/00
CPC分类号： C07K16/005 , A61K38/00 , C07K16/00 , C07K16/44 , C07K16/468 , C07K2317/55 , C07K2317/56
摘要： The present invention relates to a method for isolating from the immunological gene repertoire a gene coding for a receptor having the ability to bind a preselected ligand. Receptors produced by the gene isolated by the method, particularly catalytic receptors, are also contemplated.
摘要翻译：本发明涉及从免疫基因库中分离编码具有结合预选配体的能力的受体的基因的方法。还考虑了通过该方法分离的基因产生的受体，特别是催化受体。

8. 发明授权

US5792456A Mutant BR96 antibodies reactive with human carcinomas 失效
标题翻译：突变型BR96抗体与人类癌反应
公开(公告)号：US5792456A
公开(公告)日：1998-08-11
申请号：US487860
申请日：1995-06-07
申请人： Dale Yelton , Scott Glaser , William Huse , Mae Joanne Rosok
发明人： Dale Yelton , Scott Glaser , William Huse , Mae Joanne Rosok
IPC分类号： G01N33/574 , A61K35/12 , A61K35/74 , A61K38/00 , A61K39/395 , A61K51/10 , A61P35/00 , C07K14/82 , C07K16/00 , C07K16/30 , C07K16/32 , C07K19/00 , C12N15/09 , C12N15/13 , C12P21/08 , C12R1/19 , G01N33/577
CPC分类号： C07K16/30 , A61K51/1045 , A61K38/00 , C07K2319/00
摘要： The present invention provides mutant BR96 polypeptides having a variable region comprising an amino acid sequence derived from the variable region of BR96.
摘要翻译：本发明提供具有可变区的突变体BR96多肽，其包含衍生自BR96可变区的氨基酸序列。

9. 发明申请

US20080004434A1 METHOD FOR TAPPING THE IMMUNOLOGICAL REPERTOIRE 失效
标题翻译：剥离免疫系统的方法
公开(公告)号：US20080004434A1
公开(公告)日：2008-01-03
申请号：US11558384
申请日：2006-11-09
申请人： William Huse , Gregory Winter , Lutz Riechmann , Joseph Sorge , Richard Lerner
发明人： William Huse , Gregory Winter , Lutz Riechmann , Joseph Sorge , Richard Lerner
IPC分类号： C07H21/02
CPC分类号： C07K16/00 , A61K38/00 , C07K16/468 , C07K2317/56
摘要： The present invention relates to a method for isolating from the immunological gene repertoire a gene coding for a receptor having the ability to bind a preselected ligand. Receptors produced by the gene isolated by the method, particularly catalytic receptors, are also contemplated.
摘要翻译：本发明涉及从免疫基因库中分离编码具有结合预选配体的能力的受体的基因的方法。还考虑了通过该方法分离的基因产生的受体，特别是催化受体。

10. 发明申请

US20060194254A1 Method for identifying optimal binding ligands to a receptor 审中-公开
公开(公告)号：US20060194254A1
公开(公告)日：2006-08-31
申请号：US11219519
申请日：2005-09-02
申请人： William Huse , Michael Freedman
发明人： William Huse , Michael Freedman
IPC分类号： C40B40/02 , C40B40/10
CPC分类号： G01N33/566
摘要： The present invention provides a method for determining binding of a receptor to one or more ligands. The method consists of contacting a collective receptor variant population with one or more ligands and detecting binding of one or more ligands to the collective receptor variant population. The collective receptor variant population can be further divided into two or more subpopulations, one or more of the two or more subpopulations can be contacted with one or more ligands and one or more receptor variant subpopulations having binding activity to one or more ligands can be detected. The steps of dividing, contacting and detecting can be repeated one or more times. The invention also provides methods for identifying a receptor variant having optimal binding activity to one or more ligands. The invention additionally provides a method for determining binding of a ligand to one or more receptors. The method consists of contacting a collective ligand variant population with one or more receptors and detecting binding of one or more receptors to the collective ligand variant population. As with the variant receptor population, the methods for determining binding of a ligand to one or more receptors can include the steps of further dividing, contacting and detecting one or more ligand variants having binding activity to one or more receptors. The invention also provides methods for identifying a ligand or ligand variant having optimal binding activity.

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