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61. 发明申请

US20050245431A1 Membrane, device and method for removing proteases from liquids 有权
标题翻译：从液体中去除蛋白酶的膜，装置和方法
公开(公告)号：US20050245431A1
公开(公告)日：2005-11-03
申请号：US10516405
申请日：2003-06-17
申请人： Wolfgang Demmer , Dietmar Nussbaumer , Hans-Heinrich Horl
发明人： Wolfgang Demmer , Dietmar Nussbaumer , Hans-Heinrich Horl
IPC分类号： B01D15/00 , B01D61/00 , B01D67/00 , B01D69/14 , B01J20/32 , C07K14/81 , A61K38/17 , C12N9/99
CPC分类号： C07K14/81 , B01D15/00 , B01D15/3814 , B01D61/00 , B01D67/0093 , B01D69/14 , B01J20/28033 , B01J20/2808 , B01J20/3212 , B01J20/3219 , B01J20/3255 , B01J20/3274 , C07K14/8107
摘要： The invention comprises a membrane and device and method for removing proteases from fluids, particularly from biological fluids and pharmaceutical solutions, which uses a microporous membrane body, whereby inhibitors that selectively bind proteases are coupled to the membrane body by chemically activated groups.
摘要翻译：本发明包括用于从流体，特别是从生物流体和药物溶液中去除蛋白酶的膜和装置和方法，其使用微孔膜体，由此通过化学活化的基团将选择性结合蛋白酶的抑制剂偶联到膜体上。

62. 发明申请

US20040253228A1 Methods for using compositions comprising heat shock proteins or alpha-2-macroglobulin in the treatment of cancer and infectious disease 审中-公开
标题翻译：使用包含热休克蛋白或α-2-巨球蛋白的组合物在治疗癌症和感染性疾病中的方法
公开(公告)号：US20040253228A1
公开(公告)日：2004-12-16
申请号：US10784012
申请日：2004-02-20
发明人： Pramod K. Srivastava
IPC分类号： A61K039/395 , A61K038/17
CPC分类号： C07K14/8107 , A61K38/1709 , A61K38/57 , A61K39/0011 , A61K2039/6043 , C07K14/47 , A61K2300/00
摘要： The present invention relates to methods and compositions for the prevention and treatment of infectious diseases, and cancers. The methods of the invention comprises administering (a) a composition comprising a population of complexes of antigenic proteins or antigenic peptides derived from antigenic cells or viral particles and one or more different heat shock proteins; and (b) a non-heat shock protein and non-alpha-2-macroglobulin-based treatment modality. The population or the protein preparation used to produce the antigenic peptides comprises at least 50% of the different proteins or at least 50 different proteins of the antigenic cells or viral particles. Methods for making antigenic peptides comprise digesting a protein preparation of antigenic cells, a cellular fraction thereof, or of viral particles with one or more proteases, or exposing the protein preparation to ATP, guanidium hydrochloride, and/or acidic conditions.
摘要翻译：本发明涉及用于预防和治疗感染性疾病和癌症的方法和组合物。本发明的方法包括施用（a）包含抗原蛋白或衍生自抗原性细胞或病毒颗粒和一种或多种不同热休克蛋白的抗原肽复合物群的组合物; 和（b）非热休克蛋白和非α-2-巨球蛋白的治疗方式。用于产生抗原肽的群体或蛋白质制剂包含至少50％的不同蛋白质或至少50种抗原性细胞或病毒颗粒的不同蛋白质。用于制备抗原肽的方法包括消化抗原性细胞的蛋白质制剂，其细胞级分或具有一种或多种蛋白酶的病毒颗粒，或将蛋白质制剂暴露于ATP，盐酸胍，和/或酸性条件。

63. 发明申请

US20030180722A1 Methods and materials relating to alpha-2-macroglobulin-like polypeptides and polynucleotides 失效
标题翻译：与α-2-巨球蛋白样多肽和多核苷酸有关的方法和材料
公开(公告)号：US20030180722A1
公开(公告)日：2003-09-25
申请号：US09756247
申请日：2001-01-08
发明人： Shubhada D. Godbole , Bryan J. Boyle , Nancy K. Mize , Cenhua Deng , Ryle W. Goodrich , Matthew C. Arterburn , Ping Zhou , Y. Tom Tang , Chenghua Liu , George Yeung , Radoje T. Drmanac
IPC分类号： C12Q001/68 , C07H021/04 , C12P021/02 , C12N005/06 , C07K014/795
CPC分类号： C12N9/6432 , A61K38/00 , C07K14/8107 , C07K16/00 , C12N9/16 , C12Y304/21006
摘要： The invention provides novel polynucleotides and polypeptides encoded by such polynucleotides and mutants or variants thereof that correspond to novel human secreted alpha-2-macroglobulin-like polypeptides. These polynucleotides comprise nucleic acid sequences isolated from cDNA library from fetal brain mRNA (Clontech) (SEQ ID NO: 1) and uterus mRNA (Clontech) (SEQ ID NO: 26). Other aspects of the invention include vectors containing processes for producing novel human secreted alpha-2-macroglobulin-like polypeptides, and antibodies specific for such polypeptides.
摘要翻译：本发明提供由这样的多核苷酸编码的新的多核苷酸和多肽，其对应于新型人分泌的α-2-巨球蛋白样多肽的突变体或其变体。这些多核苷酸包含从胎儿脑mRNA（Clontech）（SEQ ID NO：1）和子宫mRNA（Clontech）（SEQ ID NO：26）的cDNA文库中分离的核酸序列。本发明的其它方面包括含有产生新的人分泌的α-2-巨球蛋白样多肽的方法的载体和对这些多肽特异的抗体。

64. 发明申请

US20030096279A1 Novel nucleic acids and polypeptides 审中-公开
公开(公告)号：US20030096279A1
公开(公告)日：2003-05-22
申请号：US10233131
申请日：2002-08-29
发明人： Y. Tom Tang , Ping Zhou , Ryle Goodrich , Vinod Asundi , Qing A. Zhao , Jian-Rui Wang , Aidong J. Xue , Feiyan Ren , Dunrui Wang , Rui-Hong Chen , Radoje T. Drmanac
IPC分类号： C12Q001/68 , C07H021/04 , A61K039/395 , C12N009/00 , C12P021/02 , C12N005/06 , C07K016/40
CPC分类号： C07K14/47 , A61K38/00 , C07K14/8107
摘要： The present invention provides novel nucleic acids, novel polypeptide sequences encoded by these nucleic acids and uses thereof.

65. 发明申请

US20020192230A1 Therapeutic formulations using heat shock/stress protein-peptide complexes 审中-公开
标题翻译：使用热休克/应激蛋白 - 肽复合物的治疗剂型
公开(公告)号：US20020192230A1
公开(公告)日：2002-12-19
申请号：US10126368
申请日：2002-04-19
申请人： University of Connecticut Health Center
发明人： Pramod K. Srivastava
IPC分类号： A61K039/00
CPC分类号： C07K14/47 , A61K39/0011 , A61K2039/5154 , A61K2039/6031 , A61K2039/6043 , A61K2039/622 , C07K14/8107
摘要： The present invention relates to methods for making compositions comprising heat shock proteins or alpha (2) macroglobulin (nullnull2Mnull), which compositions are immunogenic against a type of cancer or an agent of an infectious disease, and the compositions produced by the methods described herein. The invention further relates to methods for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. Specifically, the present invention provides a method of eliciting an immune response comprise administering to an individual a composition made by mixing an amount of a purified first complex comprising a first heat shock protein or null2M complexed to a peptide which displays antigenicity of an antigen of said type of cancer or antigenicity of an antigen of an agent of said infectious disease; and an equal or greater amount of a second heat shock protein or null2M that is not complexed in vitro to a peptide which displays antigenicity of an antigen of said type of cancer or antigenicity of an antigen of an agent of said infectious disease, respectively; and is not in the form of a complex, said complex having been isolated as a complex from cancerous tissue of said type of cancer or cells infected with said agent of infectious disease, respectively. Optionally, the methods further comprise administering antigen presenting cells sensitized with hsp-peptide or null2M-peptide complexes comprising peptides antigenic to cancer cells or to an agent of an infectious disease.
摘要翻译：本发明涉及制备包含热休克蛋白或α（2）巨球蛋白（“α2M”）的组合物的方法，该组合物对一种类型的癌症或感染性疾病的药物具有免疫原性，并且通过所述方法制备的组合物这里。本发明还涉及引发免疫应答和预防和治疗原发性和转移性肿瘤性疾病和感染性疾病的方法。具体地，本发明提供了引发免疫应答的方法，包括向个体施用通过混合一定量的纯化的第一复合物制备的组合物，所述第一复合物包含第一热休克蛋白或与形成所述第一热休克蛋白的抗原的抗原性的肽复合的α2M 所述传染病药物的抗原类型或抗原性; 以及相等或更大量的体外不与显示所述类型的癌症的抗原的抗原性或所述感染性疾病的药物的抗原的抗原性的肽分别复合的第二热休克蛋白或α2M; 并且不是复合物的形式，所述复合物分别作为复合物从所述类型的癌症的癌组织或感染有感染性疾病的细胞的细胞中分离出来。任选地，所述方法还包括施用用hsp-肽或α2M-肽复合物敏化的抗原呈递细胞，所述复合物包含抗原性的癌细胞的肽或感染性疾病的药剂。

66. 发明授权

US06406902B1 Herpes virus proteinase and methods of assaying 失效
标题翻译：疱疹病毒蛋白酶和测定方法
公开(公告)号：US06406902B1
公开(公告)日：2002-06-18
申请号：US09586563
申请日：2000-06-02
申请人： D. Wade Gibson , Anthony R. Welch
发明人： D. Wade Gibson , Anthony R. Welch
IPC分类号： C12N950
CPC分类号： C12Q1/37 , A61K38/00 , C07K14/005 , C07K14/8107 , C12N9/503 , C12N2710/16122 , G01N2333/03 , G01N2333/045
摘要： A herpes virus proteinase has been found to be encoded by a member of a family of four nested genes in simian cytomegalovirus. Another member of the nested genes encodes the assembly protein precursor, which is a substrate for the proteinase. Homologous genes are found in other herpes viruses. Cleavage sites recognized by the proteinase are identified in cytomegalovirus and are found to be highly conserved in other herpes viruses. Substrates, inhibitors, assay kits, and methods of assaying are provided which rely on the proteinase and its activity.
摘要翻译：已发现疱疹病毒蛋白酶由猴巨细胞病毒中的四个嵌套基因家族的成员编码。嵌套基因的另一个成员编码组蛋白前体，其是蛋白酶的底物。同源基因存在于其他疱疹病毒中。在巨细胞病毒中鉴定出由蛋白酶识别的切割位点，并且发现其在其他疱疹病毒中高度保守。提供了依赖于蛋白酶及其活性的底物，抑制剂，测定试剂盒和测定方法。

67. 发明申请

US20020028462A1 Alpha-2-macroglobulin isotype diagnostic test for Alzheimer's disease 审中-公开
标题翻译：阿尔茨海默氏病的α-2-巨球蛋白同种型诊断试验
公开(公告)号：US20020028462A1
公开(公告)日：2002-03-07
申请号：US09925313
申请日：2001-08-10
申请人： The General Hospital Corporation
发明人： Rudolph E. Tanzi , Deborah L. Blacker
IPC分类号： C12Q001/68 , C12P019/34
CPC分类号： C07K14/8107 , C12Q1/6883 , C12Q2600/156 , C12Q2600/172 , G01N33/6896 , G01N2800/2821
摘要： The disclosed invention relates to a diagnostic method for Alzheimer's disease based on genotyping the Alpha-2-Macroglobulin locus. A statistically significant correlation was found between inheritance of particular alleles of the Alpha-2-Macroglobulin gene and the occurrence of Alzheimer's disease. The diagnostic method involves the isolation of nucleic acid from an individual and subsequent genotyping by means such as sequencing or restriction fragment length polymorphism analysis. The invention also provides a means of genotype analysis through protein isotyping Alpha-2-Macroglobulin variant proteins. Finally, kits for nucleic acid analysis or protein analysis are taught.
摘要翻译：所公开的发明涉及基于α-2-巨球蛋白基因座的基因分型的阿尔茨海默病的诊断方法。发现α-2-巨球蛋白基因特异性等位基因遗传与阿尔茨海默病发生之间有统计学意义的相关性。诊断方法包括通过诸如测序或限制性片段长度多态性分析的方法从个体和随后的基因分型中分离核酸。本发明还提供通过蛋白质同种型分析α-2-巨球蛋白变体蛋白的基因型分析方法。最后，教导了用于核酸分析或蛋白质分析的试剂盒。

68. 发明授权

US6022855A Methods and reagents for inhibiting furin endoprotease 失效
标题翻译：用于抑制弗林蛋白酶内蛋白酶的方法和试剂
公开(公告)号：US6022855A
公开(公告)日：2000-02-08
申请号：US481534
申请日：1995-09-14
申请人： Gary Thomas , Eric D. Anderson , Laurel Thomas , Joel S. Hayflick
发明人： Gary Thomas , Eric D. Anderson , Laurel Thomas , Joel S. Hayflick
IPC分类号： C12N15/09 , A61K31/70 , A61K38/00 , A61K38/21 , A61K48/00 , A61P31/04 , A61P31/12 , C07H21/04 , C07K5/11 , C07K14/81 , C12N5/00 , C12N5/10 , C12N9/99 , C12N15/15 , C12R1/91 , A61K38/55 , C07K4/12 , C07K5/10
CPC分类号： C07K14/8107 , A61K38/00
摘要： This invention relates to method and reagents for inhibiting furin endoprotease activity and specifically for inhibiting furin endoprotease-mediated maturation of bioactive proteins in vivo and in vitro. The invention specifically provides proteins capable of inhibiting furin endoprotease activity. Particularly provided are .alpha..sub.1 -antitrypsin variants that specifically inhibit furin endoprotease activity. Methods for using furin endoprotease inhibition to attenuate or prevent viral protein maturation, and thereby alleviate viral infections, are provided. Also provided are methods for using furin endoprotease inhibition to attenuate or prevent proteolytic processing of bacterial toxins, thereby alleviating bacterial infections. Methods are also provided to inhibit proteolytic processing of biologically active proteins and peptides. The invention also provides pharmaceutically acceptable compositions of therapeutically effective amounts of furin endoprotease inhibitors.
摘要翻译： PCT No.PCT / US94 / 00247 Sec。 371 1995年9月14日第 102（e）1995年9月14日PCT PCT 1994年1月7日PCT公布。第WO94 / 16073号公报日期1994年7月21日本发明涉及抑制弗林蛋白酶内切蛋白酶活性的方法和试剂，特别涉及体内和体外抑制弗林蛋白酶内切蛋白酶介导的生物活性蛋白质成熟。本发明特别提供能够抑制弗林蛋白酶内切蛋白酶活性的蛋白质。特别提供了特异性抑制弗林蛋白酶内切蛋白酶活性的α1-抗胰蛋白酶变体。提供了使用弗林蛋白酶内蛋白酶抑制来减弱或预防病毒蛋白质成熟并由此减轻病毒感染的方法。还提供了使用弗林蛋白蛋白内切蛋白酶抑制来减弱或防止细菌毒素的蛋白水解加工的方法，从而减轻细菌感染。还提供了抑制生物活性蛋白质和肽的蛋白水解加工的方法。本发明还提供治疗有效量的弗林蛋白酶内切蛋白酶抑制剂的药学上可接受的组合物。

69. 发明授权

US5917018A Iterative method of at least five cycles for the refolding of proteins 失效
标题翻译：用于蛋白重折叠的至少5个循环的迭代方法
公开(公告)号：US5917018A
公开(公告)日：1999-06-29
申请号：US469658
申请日：1995-09-18
申请人： Christian Th.o slashed.gersen , Thor Las Holtet , Michael Etzerodt
发明人： Christian Th.o slashed.gersen , Thor Las Holtet , Michael Etzerodt
IPC分类号： C12N15/09 , C07D413/14 , C07D471/04 , C07K1/00 , C07K1/04 , C07K1/113 , C07K1/14 , C07K14/005 , C07K14/47 , C07K14/61 , C07K14/705 , C07K14/74 , C07K14/745 , C07K14/81 , C07K16/00 , C07K16/24 , C07K16/46 , C12N9/00 , C12N9/64 , C12N9/68 , C12N15/62 , C12N15/70 , C12P21/02 , C12R1/19 , C07K14/00 , C12P21/00
CPC分类号： C12N9/6435 , C07K1/1136 , C07K1/14 , C07K14/47 , C07K14/61 , C07K14/705 , C07K14/70539 , C07K14/70596 , C07K14/8107 , C07K16/241 , C12N15/62 , C12N15/70 , C12N9/6432 , C12Y304/21006 , C12Y304/21007 , C07K2319/50 , C07K2319/75 , C12N2310/1241 , C12N2310/127
摘要： A novel, generally applicable method for producing correctly folded proteins from a mixture of misfolded proteins, e.g. bacterial inclusion-body aggregates. A major new aspect of the method is that over-all efficiency is achieved by subjecting proteins to a time-sequence of multiple denaturation-renaturation cycles, resulting in gradual accumulation of the correctly folded protein. The method has proven efficient for a variety of recombinant proteins. Also provided are novel encrypted recognition sites for bovine coagulation factor X.sub.a. The encrypted recognition sites described may be activated in vitro by controlled oxidation or by reversible derivatization of cysteine residues and thereby generate new cleavage sites for factor X.sub.a. Two new recombinant serine protease exhibiting narrow substrate specificity for factor X.sub.a recognition sites are also provided. They may replace natural coagulation factor X.sub.a for cleavage of chimeric proteins.
摘要翻译：用于从错误折叠的蛋白质的混合物中产生正确折叠的蛋白质的新颖的，普遍适用的方法，例如。细菌包涵体聚集体。该方法的一个主要新方面是通过使蛋白质经历多个变性 - 复性循环的时间序列来实现全部效率，导致正确折叠的蛋白质的逐渐积累。该方法已被证明对多种重组蛋白有效。还提供了用于牛凝血因子Xa的新型加密识别位点。所描述的加密识别位点可以通过受控氧化或通过半胱氨酸残基的可逆衍生化在体外被激活，从而为因子Xa产生新的切割位点。还提供了两种对因子Xa识别位点具有窄底物特异性的重组丝氨酸蛋白酶。它们可以代替天然凝血因子Xa来切割嵌合蛋白质。

70. 发明授权

US5902787A Chemically modified a-macroglobulins, methods of making, and methods of using the same in anti-cytokine therapy 失效
标题翻译：化学修饰的a-巨球蛋白，制备方法，以及在抗细胞因子治疗中使用它们的方法
公开(公告)号：US5902787A
公开(公告)日：1999-05-11
申请号：US885764
申请日：1997-06-30
申请人： Steven L. Gonias , Donna J. Webb
发明人： Steven L. Gonias , Donna J. Webb
IPC分类号： A61K38/00 , C07K14/81 , G01N33/68 , C07K14/00 , A61K38/02
CPC分类号： C07K14/8107 , G01N33/6863 , A61K38/00
摘要： Chemically modified .alpha.-macroglobulin is conformationally locked by cross-linking .alpha..sub.2 M with a bi-functional peptide crosslinker, and then modified with methylamine, to provide conformational intermediates with limited conformational change. These modified compounds have a high binding affinity for inflammatory cytokines including TNF-.alpha. and IL-1.beta.. When administered in vivo, the modified .alpha..sub.2 M (MAC) protects against development of septic shock, and is an effective treatment aid in treating mammals with established septic shock.
摘要翻译：化学修饰的α-巨球蛋白通过将α2M与双功能肽交联剂交联而构象锁定，然后用甲胺修饰，以提供具有有限构象变化的构象中间体。这些修饰的化合物对炎性细胞因子（包括TNF-α和IL-1β）具有高结合亲和力。当在体内施用时，修饰的α2M（MAC）可防止败血性休克的发生，并且是治疗已建立的败血性休克的哺乳动物的有效治疗辅助物质。

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