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61. 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。

62. 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.

63. 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。

64. 发明授权

US5258498A 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：US5258498A
公开(公告)日：1993-11-02
申请号：US955399
申请日：1992-10-01
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 , C07K15/00 , C12N15/09 , C12P21/00
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： PCT No.PCT / US88 / 01737 Sec。 371日期1989年1月23日 102（e）日期1989年1月23日PCT提交1988年5月19日PCT公布。出版物WO88 / 09344 日期为1988年12月1日。公开是对预选抗原具有结合亲和力的合成蛋白家族，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。位点包含VH和VL-样的单链，其中VH和VL样序列被连接通过多肽接头，或单独的VH或VL样结构域。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产生其类似物的任何特异性的BABS，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。

65. 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。

66. 发明授权

US07176284B2 Osteogenic proteins 失效
公开(公告)号：US07176284B2
公开(公告)日：2007-02-13
申请号：US10428997
申请日：2003-05-02
申请人： Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang
发明人： Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang
IPC分类号： C07K14/51
CPC分类号： A61L27/3683 , A61C8/0006 , A61F2310/00365 , A61K38/00 , A61L27/227 , A61L27/24 , A61L27/34 , A61L27/3608 , A61L27/365 , A61L27/3654 , A61L27/56 , A61L2430/02 , C07K14/51 , C08L89/06
摘要： Disclosed are (1) osteogenic devices comprising a matrix containing substantially pure natural-sourced mammalian osteogenic protein; (2) DNA and amino acid sequences for novel polypeptide chains useful as subunits of dimeric osteogenic proteins; (3) vectors carrying sequences encoding these novel polypeptide chains and host cells transfected with these vectors; (4) methods of producing these polypeptide chains using recombinant DNA technology; (5) antibodies specific for these novel polypeptide chains; (6) osteogenic devices comprising these recombinantly produced proteins in association with an appropriate carrier matrix; and (7) methods of using the osteogenic devices to mimic the natural course of endochondral bone formation in mammals.

67. 发明授权

US06586388B2 Method of using recombinant osteogenic protein to repair bone or cartilage defects 失效
标题翻译：使用重组成骨蛋白修复骨或软骨缺陷的方法
公开(公告)号：US06586388B2
公开(公告)日：2003-07-01
申请号：US08957425
申请日：1997-10-24
申请人： Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang
发明人： Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang
IPC分类号： A61K3816
CPC分类号： A61L27/3683 , A61C8/0006 , A61F2310/00365 , A61K38/00 , A61L27/227 , A61L27/24 , A61L27/34 , A61L27/3608 , A61L27/365 , A61L27/3654 , A61L27/56 , A61L2430/02 , C07K14/51 , C08L89/06
摘要： Disclosed are (1) osteogenic devices comprising a matrix containing substantially pure natural-sourced mammalian osteogenic protein; (2) DNA and amino acid sequences for novel polypeptide chains useful as subunits of dimeric osteogenic proteins; (3) vectors carrying sequences encoding these novel polypeptide chains and host cells transfected with these vectors; (4) methods of producing these polypeptide chains using recombinant DNA technology; (5) antibodies specific for these novel polypeptide chains; (6) osteogenic devices comprising these recombinantly produced proteins in association with an appropriate carrier matrix; and (7) methods of using the osteogenic devices to mimic the natural course of endochondral bone formation in mammals.
摘要翻译：公开的是（1）包含含有基本上纯天然来源的哺乳动物成骨蛋白质的基质的成骨装置; （2）可用作二聚成骨蛋白亚基的新型多肽链的DNA和氨基酸序列; （3）携带编码这些新型多肽链的序列的载体和用这些载体转染的宿主细胞; （4）使用重组DNA技术生产这些多肽链的方法; （5）对这些新型多肽链具有特异性的抗体; （6）包含这些重组产生的蛋白质与合适的载体基质相结合的成骨装置; 和（7）使用成骨装置来模拟哺乳动物软骨内骨形成的自然过程的方法。

68. 发明授权

US5958441A Devices comprising chondrogenic protein and methods of inducing endochondral bone formation therewith 失效
标题翻译：包含软骨形成蛋白的装置和诱导软骨内骨形成的方法
公开(公告)号：US5958441A
公开(公告)日：1999-09-28
申请号：US449699
申请日：1995-05-24
申请人： Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang
发明人： Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang
IPC分类号： A61C8/00 , A61F2/00 , A61K6/00 , A61K9/00 , A61K38/00 , A61K38/18 , A61L27/22 , A61L27/24 , A61L27/34 , A61L27/36 , A61L27/56 , C04B14/12 , C04B20/06 , C07K14/51
CPC分类号： A61K9/0024 , A61K38/1875 , A61L27/227 , A61L27/24 , A61L27/34 , A61L27/3604 , A61L27/3608 , A61L27/365 , A61L27/3654 , A61L27/3683 , A61L27/54 , A61L27/56 , C04B14/12 , C04B20/068 , C07K14/51 , A61C8/0006 , A61F2310/00365 , A61L2300/412 , A61L2430/02 , Y10S530/84
摘要： Disclosed are (1) osteogenic devices comprising a matrix containing substantially pure natural-sourced mammalian osteogenic protein; (2) DNA and amino acid sequences for novel polypeptide chains useful as subunits of dimeric osteogenic proteins; (3) vectors carrying sequences encoding these novel polypeptide chains and host cells transfected with these vectors; (4) methods of producing these polypeptide chains using recombinant DNA technology; (5) antibodies specific for these novel polypeptide chains; (6) osteogenic devices comprising these recombinantly produced proteins in association with an appropriate carrier matrix; and (7) methods of using the osteogenic devices to mimic the natural course of endochondral bone formation in mammals.
摘要翻译：公开的是（1）包含含有基本上纯天然来源的哺乳动物成骨蛋白质的基质的成骨装置; （2）可用作二聚成骨蛋白亚基的新型多肽链的DNA和氨基酸序列; （3）携带编码这些新型多肽链的序列的载体和用这些载体转染的宿主细胞; （4）使用重组DNA技术生产这些多肽链的方法; （5）对这些新型多肽链具有特异性的抗体; （6）包含这些重组产生的蛋白质与合适的载体基质相结合的成骨装置; 和（7）使用成骨装置来模拟哺乳动物软骨内骨形成的自然过程的方法。

69. 发明授权

US5814604A Methods for inducing endochondral bone formation comprising administering CBMP-2A, CBMP-2B, and/or virants thereof 失效
标题翻译：用于诱导软骨内骨形成的方法，包括施用CBMP-2A，CBMP-2B和/或其变体
公开(公告)号：US5814604A
公开(公告)日：1998-09-29
申请号：US417071
申请日：1995-04-04
申请人： Hermann Oppermann , Thangavel Kuberasampath , David C. Rueger , Engin Ozkaynak
发明人： Hermann Oppermann , Thangavel Kuberasampath , David C. Rueger , Engin Ozkaynak
IPC分类号： C12N15/02 , A61C8/00 , A61F2/00 , A61K9/00 , A61K38/00 , A61K39/395 , A61L27/00 , A61L27/22 , A61L27/24 , A61L27/34 , A61L27/36 , A61L27/56 , A61P1/02 , A61P43/00 , C07H21/04 , C07K1/20 , C07K1/22 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/51 , C07K14/78 , C07K16/00 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/12 , C12N15/18 , C12P21/02 , C12P21/08 , C12Q1/68 , C12R1/07 , C12R1/19 , C12R1/645 , C12R1/91 , A61K38/16
CPC分类号： A61K9/0024 , A61L27/227 , A61L27/24 , A61L27/34 , A61L27/3604 , A61L27/3608 , A61L27/365 , A61L27/3654 , A61L27/56 , C07K14/51 , A61C8/0006 , A61F2310/00365 , A61K38/00 , A61L2430/02
摘要： Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.
摘要翻译：公开的是1）包含含有成骨蛋白的基质的成骨装置和使用该装置在哺乳动物中诱导软骨内骨生长的方法; 2）氨基酸序列数据，氨基酸组成，溶解性，结构特征，同源性和各种其他数据表征成骨蛋白，3）使用重组DNA技术生产成骨蛋白的方法，以及4）成骨和软骨形成活性合成蛋白质构建体。

70. 发明授权

US5670336A Method for recombinant production of osteogenic protein 失效
标题翻译：重组生产成骨蛋白OP-1的方法
公开(公告)号：US5670336A
公开(公告)日：1997-09-23
申请号：US376731
申请日：1995-01-20
申请人： Hermann Oppermann , Thangavel Kuberasampath , David C. Rueger , Engin Ozkaynak
发明人： Hermann Oppermann , Thangavel Kuberasampath , David C. Rueger , Engin Ozkaynak
IPC分类号： A61C8/00 , A61F2/00 , A61K9/00 , A61K38/00 , A61L27/22 , A61L27/24 , A61L27/34 , A61L27/36 , A61L27/56 , C07K14/51 , C12N15/18 , C12N15/12 , C12N15/00
CPC分类号： A61K9/0024 , A61L27/227 , A61L27/24 , A61L27/34 , A61L27/3608 , A61L27/365 , A61L27/56 , C07K14/51 , A61C8/0006 , A61F2310/00365 , A61K38/00 , A61L2430/02
摘要： Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.
摘要翻译：公开的是1）包含含有成骨蛋白的基质的成骨装置和使用该装置在哺乳动物中诱导软骨内骨生长的方法; 2）氨基酸序列数据，氨基酸组成，溶解性，结构特征，同源性和各种其他数据表征成骨蛋白，3）使用重组DNA技术生产成骨蛋白的方法，以及4）成骨和软骨形成活性合成蛋白质构建体。

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