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1. 发明授权

US5877305A DNA encoding biosynthetic binding protein for cancer marker 失效
标题翻译：编码癌症标记物的生物合成结合蛋白的DNA
公开(公告)号：US5877305A
公开(公告)日：1999-03-02
申请号：US356786
申请日：1994-12-12
申请人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
发明人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
IPC分类号： C12N15/09 , A61K39/395 , A61K49/00 , A61K51/00 , A61K51/08 , A61P35/00 , C07H21/04 , C07K16/22 , C07K16/28 , C07K16/30 , C07K16/32 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12N15/62 , C12N15/66 , C12P21/02 , C12P21/08 , C12R1/19
CPC分类号： C07K16/32 , C07K16/22 , C07K16/30 , C07K16/3015 , C07K16/3069 , A61K2039/505 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/33 , C07K2319/55
摘要： Disclosed is DNA encoding a single-chain Fv (sFv) polypeptide defining a binding site which exhibits the immunological binding properties of an immunoglobulin molecule which binds c-erbB-2 or a c-erbB-2-related tumor antigen, the sFv includes at least two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each of the polypeptide domains includes a set of complementarity determining regions (CDRs) interposed between a set of framework regions (FRs), the CDRs conferring immunological binding to the c-erbB-2 or c-erbB-2-related tumor antigen.
摘要翻译：公开了编码单链Fv（sFv）多肽的DNA，其限定结合位点，其显示结合c-erbB-2或c-erbB-2相关肿瘤抗原的免疫球蛋白分子的免疫结合特性，sFv包括在通过跨越一个结构域的C末端与另一个结构域的N末端之间的距离的多肽连接体连接的至少两个多肽结构域，每个多肽结构域的氨基酸序列包括一组互补决定区（CDR），其插入在一组框架区域（FR）之间，CDRs赋予与c-erbB-2或c-erbB-2相关的肿瘤抗原的免疫学结合。

2. 发明授权

US5534254A Biosynthetic binding proteins for immuno-targeting 失效
公开(公告)号：US5534254A
公开(公告)日：1996-07-09
申请号：US133804
申请日：1993-10-07
申请人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
发明人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
IPC分类号： C12N15/09 , A61K39/395 , A61K49/00 , A61K51/00 , A61K51/08 , A61P35/00 , C07H21/04 , C07K16/22 , C07K16/28 , C07K16/30 , C07K16/32 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12N15/62 , C12N15/66 , C12P21/02 , C12P21/08 , C12R1/19 , A61K39/00
CPC分类号： C07K16/32 , C07K16/22 , C07K16/30 , C07K16/3015 , C07K16/3069 , A61K2039/505 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/33 , C07K2319/55
摘要： Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

3. 发明授权

US5837846A Biosynthetic binding proteins for immuno-targeting 失效
公开(公告)号：US5837846A
公开(公告)日：1998-11-17
申请号：US461386
申请日：1995-06-05
申请人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
发明人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
IPC分类号： C12N15/09 , A61K39/395 , A61K49/00 , A61K51/00 , A61K51/08 , A61P35/00 , C07H21/04 , C07K16/22 , C07K16/28 , C07K16/30 , C07K16/32 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12N15/62 , C12N15/66 , C12P21/02 , C12P21/08 , C12R1/19
CPC分类号： C07K16/32 , C07K16/22 , C07K16/30 , C07K16/3015 , C07K16/3069 , A61K2039/505 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/33 , C07K2319/55
摘要： Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

4. 发明授权

US5753204A Biosynthetic binding proteins for immunotargeting 失效
标题翻译：用于免疫靶向的生物合成结合蛋白
公开(公告)号：US5753204A
公开(公告)日：1998-05-19
申请号：US461838
申请日：1995-06-05
申请人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
发明人： James S. Huston , L. L. Houston , David B. Ring , Hermann Oppermann
IPC分类号： C12N15/09 , A61K39/395 , A61K49/00 , A61K51/00 , A61K51/08 , A61P35/00 , C07H21/04 , C07K16/22 , C07K16/28 , C07K16/30 , C07K16/32 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12N15/62 , C12N15/66 , C12P21/02 , C12P21/08 , C12R1/19
CPC分类号： C07K16/32 , C07K16/22 , C07K16/30 , C07K16/3015 , C07K16/3069 , A61K2039/505 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/33 , C07K2319/55
摘要： Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a preselected antigen by the binding site of each polypeptide chain when administered to a mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.
摘要翻译：公开了用于靶向在哺乳动物中表达的抗原上的表位的制剂。该制剂包含药学上可接受的载体以及用于结合至少一种预选抗原的二聚生物合成构建体。生物合成构建体含有两条多肽链，每条链定义单链Fv（sFv）结合蛋白，并具有促进两种sFv多肽交联的C末端尾。所得二聚体构建体具有允许预先选择的抗原通过每个多肽链的结合位点与哺乳动物施用时的结构。该制剂在体内成像和药物靶向实验中具有特别的用途。

5. 发明授权

US07105638B1 Product and process for the production, isolation, and purification of recombinant polypeptide 失效
标题翻译：用于生产，分离和纯化重组多肽的产物和方法
公开(公告)号：US07105638B1
公开(公告)日：2006-09-12
申请号：US08014096
申请日：1993-02-04
申请人： James S. Huston , Marc F. Charette , Charles M. Cohen , Roberto Crea , Peter C. Keck , Hermann Oppermann , David C. Rueger , Richard J. Ridge
发明人： James S. Huston , Marc F. Charette , Charles M. Cohen , Roberto Crea , Peter C. Keck , Hermann Oppermann , David C. Rueger , Richard J. Ridge
IPC分类号： C07K16/46
CPC分类号： C07K14/485 , C07K14/575 , C07K14/585 , C07K2319/00 , C07K2319/02 , C07K2319/036 , C07K2319/50 , C07K2319/75 , C12N15/62
摘要： Disclosed is a method for the isolation and purification of polypeptides expressed in host cells by recombinant DNA techniques. A fused polypeptide is produced containing a desired polypeptide fused to additional amino acids. The additional amino acids define a leader sequence having properties exploitable in purification, a hinge region, and a cleavage site. The hinge region is cysteine-free and has a secondary structure which serves to expose the cleavage site to a selected endopeptidase. The method of the invention involves the production of a fused polypeptide which may be efficiently isolated by exploiting the properties of the leader sequence, and then efficiently cleaved at the cleavage site in an appropriate aqueous environment by virtue of the influence of the hinge on the cleavage agent/cleavage site reaction and other properties of the fused polypeptide.
摘要翻译：公开了通过重组DNA技术分离和纯化在宿主细胞中表达的多肽的方法。产生融合的多肽，其含有与另外的氨基酸融合的所需多肽。另外的氨基酸定义具有在纯化中可利用的性质，铰链区和切割位点的前导序列。铰链区域是无半胱氨酸的并且具有用于将切割位点暴露于所选择的内肽酶的二级结构。本发明的方法涉及产生融合多肽，其可以通过利用前导序列的性质而有效分离，然后由于铰链对切割的影响，在合适的水性环境中的切割位点处有效地切割试剂/裂解位点反应和融合多肽的其他性质。

6. 发明授权

US5091513A Biosynthetic antibody binding sites 失效
标题翻译：生物合成抗体结合位点
公开(公告)号：US5091513A
公开(公告)日：1992-02-25
申请号：US636765
申请日：1991-01-02
申请人： James S. Huston , Hermann Oppermann
发明人： James S. Huston , Hermann Oppermann
IPC分类号： C07K16/00 , C07K16/46 , C12N15/62
CPC分类号： C12N15/62 , C07K16/00 , C07K16/464 , C07K2317/24 , C07K2317/622 , C07K2317/624 , C07K2319/00 , C07K2319/02 , C07K2319/705 , Y10S530/867
摘要： Disclosed are a family of synthetic proteins having affinity for a preselected antigen. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic V.sub.H and V.sub.L dimers, 2) V.sub.H -V.sub.L or V.sub.L -V.sub.H single chains wherein the V.sub.H and V.sub.L are attached by a polypeptide linker, or 3) individuals V.sub.H or V.sub.L domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.
摘要翻译：公开了对预选抗原具有亲和力的合成蛋白家族。蛋白质的特征在于构成表现为生物合成抗体结合位点（BABS）的区域的一个或多个氨基酸序列。所述位点包括1）非共价缔合或二硫键合的合成的VH和VL二聚体，2）VH-VL或VL-VH单链，其中VH和VL通过多肽接头连接，或3）个体VH或VL结构域。结合域包含连接的CDR和FR区，其可以衍生自单独的免疫球蛋白。蛋白质还可以包括其它多肽序列，其例如作为酶，毒素，结合位点或与固定化介质或放射性原子的连接位点起作用。公开了用于生产蛋白质的方法，用于设计具有可通过体内产生抗体引发的任何特异性的BABS和用于制备其类似物的方法。

7. 发明授权

US5084398A Selective removal of immune complexes 失效
标题翻译：选择性去除免疫复合物
公开(公告)号：US5084398A
公开(公告)日：1992-01-28
申请号：US601029
申请日：1990-10-23
申请人： James S. Huston , Lynn Baird , Charles Cohen , Hermann Oppermann
发明人： James S. Huston , Lynn Baird , Charles Cohen , Hermann Oppermann
IPC分类号： A61M1/36 , C07K14/31 , C07K17/06
CPC分类号： A61M1/3679 , C07K14/31 , C07K17/06
摘要： Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and inidivdual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.
摘要翻译：公开了一种可用于将血液中的免疫复合物优先地去除可溶性抗体的方法和一系列材料。该材料包含与免疫球蛋白Fc区结合的蛋白质的类似物。类似物通过截短或以其它方式改变结合蛋白的氨基酸序列来降低它们对Fc的亲和力而产生。在不溶性基质的表面附近设置的这种类似物的阵列具有在复合物中形成与多个Fc的多个连接点的能力，以便强烈地结合复合物，而仅在可溶性IgG的Fc区和 inidivdual类似物。优选的类似物是与蛋白A或蛋白G的结合部分与Fc结合的截短的蛋白质。可以使用材料和常规的血浆置换技术从全血或血清中除去复合物。

8. 发明授权

US5482858A Polypeptide linkers for production of biosynthetic proteins 失效
标题翻译：用于生物合成蛋白质的多肽接头
公开(公告)号：US5482858A
公开(公告)日：1996-01-09
申请号：US139171
申请日：1993-10-19
申请人： James S. Huston , Hermann Oppermann
发明人： James S. Huston , Hermann Oppermann
IPC分类号： C07K16/00 , C07K16/46 , C12N15/62 , C12P21/08 , C12N1/21 , C12N5/10 , C12N15/09
CPC分类号： C07K16/464 , C07K16/00 , C12N15/62 , C07K2317/24 , C07K2317/622 , C07K2317/624 , C07K2319/00 , C07K2319/02 , C07K2319/705 , Y10S424/80
摘要： Disclosed are a family of synthetic proteins having binding affinity for a preselected antigen, and multifunctional proteins having such affinity. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise V.sub.H -V.sub.L or V.sub.L -V.sub.H -like single chains wherein the V.sub.H and V.sub.L -like sequences are attached by a polypeptide linker, or individual V.sub.H or V.sub.L -like domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site for attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, for producing analogs thereof, and for producing multifunctional synthetic proteins which are self-targeted by virtue of their binding site region.
摘要翻译：公开了对预选抗原具有结合亲和力的合成蛋白质家族，以及具有这种亲和力的多功能蛋白质。蛋白质的特征在于构成表现为生物合成抗体结合位点（BABS）的区域的一个或多个氨基酸序列。所述位点包含VH-VL或VL-VH样单链，其中VH和VL样序列通过多肽接头或单独的VH或VL样结构域连接。结合域包含连接的CDR和FR区，其可以衍生自单独的免疫球蛋白。蛋白质还可以包括其它多肽序列，其功能例如作为酶，毒素，结合位点或用于附着到固定化介质或放射性原子的位点。公开了用于制备蛋白质的方法，用于设计具有可通过体内产生抗体引起的任何特异性的BABS，用于产生其类似物，以及用于生产通过其结合位点区域自身靶向的多功能合成蛋白质。

9. 发明授权

US5243040A DNA encoding a protein which enables selective removal of immune complexes 失效
标题翻译：编码能够选择性去除免疫复合物的蛋白质的DNA
公开(公告)号：US5243040A
公开(公告)日：1993-09-07
申请号：US787669
申请日：1991-11-04
申请人： James S. Huston , Lynn Baird , Charles Cohen , Hermann Oppermann
发明人： James S. Huston , Lynn Baird , Charles Cohen , Hermann Oppermann
IPC分类号： A61M1/36 , C07K14/31 , C07K17/06 , C12N15/31
CPC分类号： A61M1/3679 , C07K14/31 , C07K17/06
摘要： Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and individual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.
摘要翻译：公开了一种用于从血液中将免疫复合物优先地去除可溶性抗体的方法和一系列材料。该材料包含与免疫球蛋白Fc区结合的蛋白质的类似物。类似物通过截短或以其它方式改变结合蛋白的氨基酸序列来降低它们对Fc的亲和力而产生。在不溶性基质的表面附近设置的这种类似物的阵列具有在复合物中形成与多个Fc的多个连接点的能力，以便强烈地结合复合物，而仅在可溶性IgG的Fc区和个别类似物。优选的类似物是与蛋白A或蛋白G的结合部分与Fc结合的截短的蛋白质。可以使用材料和常规的血浆置换技术从全血或血清中除去复合物。

10. 发明授权

US5525491A Serine-rich peptide linkers 失效
标题翻译：富含丝氨酸的肽接头
公开(公告)号：US5525491A
公开(公告)日：1996-06-11
申请号：US257341
申请日：1994-06-09
申请人： James S. Huston , Hermann Oppermann , Serge N. Timasheff
发明人： James S. Huston , Hermann Oppermann , Serge N. Timasheff
IPC分类号： C07K16/00 , C12N15/62 , C07K16/46
CPC分类号： C07K16/00 , C12N15/62 , C07K2319/00 , C07K2319/35 , C07K2319/705
摘要： Disclosed are serine-rich peptide linkers for linking two or more protein domains to form a fused protein. The peptide linkers contains at least 40% serine residues and preferably have the formula (Ser, Ser,Ser,Ser,Gly).sub.y where y is .gtoreq.1. The resulting fused domains are biologically active together or individually, have improved solubility in physiological media, and improved resistance to proteolysis.
摘要翻译：公开了用于连接两个或多个蛋白质结构域以形成融合蛋白的丝氨酸丰富的肽接头。肽接头含有至少40％的丝氨酸残基，并且优选具有式（Ser，Ser，Ser，Ser，Gly）y，其中y为≥1。所得的融合结构域在一起或单独地具有生物活性，在生理介质中具有改善的溶解性，并且改善了对蛋白水解的抵抗力。

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