公开(公告)号：US4137401A

公开(公告)日：1979-01-30

申请号：US698548

申请日：1976-06-21

申请人： Raymond U. Lemieux ,  David R. Bundle ,  Donald A. Baker

发明人： Raymond U. Lemieux ,  David R. Bundle ,  Donald A. Baker

IPC分类号： C07H3/04 ,  C07H3/06 ,  C07H13/06

CPC分类号： C07H3/06 ,  C07H3/04 ,  Y10S530/807

摘要： Carbohydrate antigenic determinants containing a glycosidically linked bridging arm are synthesized and coupled to carrier molecules to form artificial antigens, and to solid supports to form immunoabsorbants. These artificial antigens are used to detect antibodies to the carbohydrate haptens, and to raise antisera specific for the carbohydrate antigenic determinants. The immunoabsorbants are used to purify or remove antibodies to the carbohydrate haptens. Specific examples are given to the synthesis of the Lewis-a, Lewis-b, B, and H(O) blood group antigens; to the preparation of antisera to these artificial antigens, and to the preparation of immunoabsorbants specific for antibodies to these antigens.

摘要翻译： 合成含有糖基连接的桥连臂的碳水化合物抗原决定簇，并与载体分子偶联以形成人造抗原，并与固体支持物形成免疫吸附剂。 这些人造抗原用于检测对碳水化合物半抗原的抗体，并且提高对碳水化合物抗原决定簇特异性的抗血清。 免疫吸附剂用于纯化或去除对碳水化合物半抗原的抗体。 具体实例列举了Lewis-a，Lewis-b，B和H（O）血型抗原的合成; 制备这些人造抗原的抗血清，以及制备对这些抗原的抗体特异性的免疫吸附剂。

公开(公告)号：US07722890B2

公开(公告)日：2010-05-25

申请号：US10512216

申请日：2003-04-25

申请人： David R. Bundle ,  Mark Nitz ,  Jim E. Cutler

发明人： David R. Bundle ,  Mark Nitz ,  Jim E. Cutler

IPC分类号： A61K39/00

CPC分类号： A61K47/646 ,  A61K47/65

摘要： The present invention provides methods of making and using immunogenic oligosaccharide compositions comprising native O-linked and S-linked oligosaccharides coupled to a protein carrier, wherein the resultant conjugate elicits a protectively immunogenic response. These compositions may be useful in vaccines against pathogenic Candida species.

摘要翻译： 本发明提供了制备和使用免疫原性寡糖组合物的方法，所述组合物包含与蛋白质载体偶联的天然O-连接和S-连接的寡糖，其中所得的缀合物引起保护性免疫原性应答。 这些组合物可用于抗病原体假丝酵母属物种的疫苗中。

公开(公告)号：US5955379A

公开(公告)日：1999-09-21

申请号：US845659

申请日：1997-04-24

申请人： R. Bruce Lennox ,  Robert S. Hodges ,  Randall T. Irvin ,  Glen Armstrong ,  David R. Bundle ,  Pavel Kitov ,  Craig Railton

发明人： R. Bruce Lennox ,  Robert S. Hodges ,  Randall T. Irvin ,  Glen Armstrong ,  David R. Bundle ,  Pavel Kitov ,  Craig Railton

IPC分类号： C12Q1/00 ,  G01N33/543 ,  G01N33/533

CPC分类号： G01N33/5438 ,  C12Q1/003 ,  B01J2219/00653 ,  Y10S436/806 ,  Y10S436/807 ,  Y10S436/904

摘要： A biosensor apparatus for detecting a binding event between a ligand and receptor. The apparatus includes an electrode substrate coated with a high-dielectric hydrocarbon-chain monolayer, and having ligands attached to the exposed monolayer surface. Binding of a receptor to the monolayer-bound ligand, and the resultant perturbation of the monolayer structure, causes ion-mediated electron flow across the monolayer. In one embodiment, the monolayers have a coil--coil heterodimer embedded therein, one subunit of which is attached to the substrate, and the second of which carries the ligand at the monolayer surface.

公开(公告)号：US4831126A

公开(公告)日：1989-05-16

申请号：US705914

申请日：1985-02-26

申请人： David R. Bundle ,  Malcolm B. Perry ,  John W. Cherwonogrodzky ,  J. Robert Duncan ,  Martine G. Caroff

发明人： David R. Bundle ,  Malcolm B. Perry ,  John W. Cherwonogrodzky ,  J. Robert Duncan ,  Martine G. Caroff

IPC分类号： C07K16/12 ,  C12P19/04

CPC分类号： A61K39/098 ,  A61K39/025 ,  C07K16/1221 ,  C07K16/1228 ,  C12P19/04 ,  A61K2039/521 ,  G01N2333/23 ,  G01N2333/24 ,  G01N2400/50 ,  Y10S435/822

摘要： The antigenic O-chain polysaccharides from Brucella abortus and Yersinia enterocolitica serotype 0:9 have similar structure, i.e. 1-2 linked 4,6-dideoxy-4-formamido-.alpha.-D-mannopyranosyl units. The antigen is more readily isolated from the Yersinia and may be chemically modified to have a hydrophobic moiety attached thereto. The antigen can be adsorbed or coupled to carriers suitable for immunoassay use such as ELISA and RIA. A monoclonal antibody capable of specifically binding to B. abortus and Y. enterocolitica, has been produced. Assay procedures and kits therefor, are described.

摘要翻译： 来自流产布鲁杆菌和小肠结肠炎耶尔森氏菌血清型0：9的抗原性O链多糖具有相似的结构，即1-2个连接的4,6-二脱氧-4-甲酰氨基-α-甘露吡喃糖基单元。 抗原更容易从耶尔森氏菌中分离出来，并且可以被化学修饰以具有与其连接的疏水部分。 抗原可以吸附或偶联到适合免疫测定使用的载体，如ELISA和RIA。 已经制备了能够特异性结合流产流产和肠杆菌的肠杆菌的单克隆抗体。 描述了测定程序和试剂盒。

公开(公告)号：US20140037641A1

公开(公告)日：2014-02-06

申请号：US14112561

申请日：2012-04-20

申请人： Jim E. Cutler ,  Hong Xin ,  David R. Bundle ,  Sebastian Dziadek

发明人： Jim E. Cutler ,  Hong Xin ,  David R. Bundle ,  Sebastian Dziadek

IPC分类号： C07K16/14

CPC分类号： C07K16/14 ,  A61K39/0002 ,  A61K47/6415 ,  A61K47/646 ,  A61K2039/505 ,  A61K2039/5158 ,  A61K2039/55505 ,  A61K2039/55566 ,  A61K2039/55572 ,  A61K2039/6037 ,  C07K14/40 ,  C07K16/40 ,  C07K2319/00

摘要： Several new peptides have been developed that show effectiveness as vaccines against candidiasis and other fungal diseases. A new conjugate vaccine of a β-mannotriose linked to a fungal peptide linked to tetanus toxin has been shown to be effective as a vaccine with or without use of an adjuvant. In addition, a monoclonal antibody has been identified that offers protection from a Candida infection.

摘要翻译： 已经开发了几种新的肽，其显示出作为针对念珠菌病和其它真菌疾病的疫苗的有效性。 已经显示与连接到破伤风毒素的真菌肽连接的β-甘露三糖的新缀合疫苗作为具有或不使用佐剂的疫苗是有效的。 此外，已经鉴定出提供针对念珠菌感染的保护的单克隆抗体。

公开(公告)号：US20100209448A1

公开(公告)日：2010-08-19

申请号：US12750329

申请日：2010-03-30

申请人： David R. Bundle ,  Mark Nitz ,  Jim E. Cutler

发明人： David R. Bundle ,  Mark Nitz ,  Jim E. Cutler

IPC分类号： A61K39/385 ,  A61P31/10

CPC分类号： A61K47/646 ,  A61K47/65

摘要： The present invention provides methods of making and using immunogenic oligosaccharide compositions comprising native O-linked and S-linked oligosaccharides coupled to a protein carrier, wherein the resultant conjugate elicits a protectively immunogenic response. These compositions may be useful in vaccines against pathogenic Candida species.

摘要翻译： 本发明提供了制备和使用免疫原性寡糖组合物的方法，所述组合物包含与蛋白质载体偶联的天然O-连接和S-连接的寡糖，其中所得的缀合物引起保护性免疫原性应答。 这些组合物可用于抗病原体假丝酵母属物种的疫苗中。

公开(公告)号：US06420552B1

公开(公告)日：2002-07-16

申请号：US09650162

申请日：2000-08-29

申请人： Om Srivastava ,  Geeta Srivastava ,  Minghui Du ,  Ole Hingsgaul ,  David R. Bundle

发明人： Om Srivastava ,  Geeta Srivastava ,  Minghui Du ,  Ole Hingsgaul ,  David R. Bundle

IPC分类号： C07H100

CPC分类号： C07H15/04 ,  C07H7/027

摘要： The present invention provides improved method of preparing a 4-O-alkyl chromogenic ketoside of N-acetylneuraminic acid (Neu5Ac) and a 7-O-alkyl chromogenic ketoside of N-acetylneuraminic acid (Neu5Ac) for use in the selective detection of various influenza viruses and parainfluenza viruses. The ketosides are substrates that are selectively cleaved by a neuraminidase on the virus to be detected, but not by neuraminidases found on other viruses or on bacteria, or on the cells of the host. The syntheses are efficient and provide large quantities of the ketosides for commercial development. The synthesis includes a step of alkylating the 4- or 7-hydroxyl groups of a protected alkyl ester alkyl ketoside derivative of Neu5Ac by processes that include contacting the derivative with a composition comprising an alkyl halide to form a 4- or a 7-O-alkyl protected alkyl ester alkyl ketoside derivative of Neu5Ac. The syntheses alternatively include protecting the 8- and 9-hydroxyl groups of an alkyl ester alkyl ketoside derivative of Neu5Ac by forming an 8,9-ketal or an 8,9-epoxide protected alkyl ester alkyl ketoside derivative of Neu5Ac.

摘要翻译： 本发明提供了制备用于选择性检测各种流感的N-乙酰神经氨酸（Neu5Ac）的4- O-烷基显色酮面和N-乙酰神经氨酸（Neu5Ac）的7- O-烷基显色酮二酮的改良方法 病毒和副流感病毒。 酮氧化物是被待检测的病毒上的神经氨酸酶选择性地切割而不是其它病毒或细菌或宿主细胞上发现的神经氨酸酶的底物。 合成是有效的，并提供大量用于商业开发的酮基。 合成包括通过包括使衍生物与包含烷基卤化物的组合物接触以形成4-或7- O-O-的方法使Neu5Ac的被保护的烷基酯烷基酮酮衍生物的4-或7-羟基烷基化的步骤 烷基保护的烷基酯Neu5Ac的烷基酮基衍生物。 所述合成交替包括通过形成Neu5Ac的8,9-缩酮或8,9-环氧化物保护的烷基酯酮基衍生物来保护Neu5Ac的烷基酯烷基酮内酯衍生物的8-和9-羟基。

公开(公告)号：US06310043B1

公开(公告)日：2001-10-30

申请号：US09317290

申请日：1999-05-24

申请人： David R. Bundle ,  Pavel Kitov ,  Randy J. Read ,  Hong Ling ,  Glen Armstrong

发明人： David R. Bundle ,  Pavel Kitov ,  Randy J. Read ,  Hong Ling ,  Glen Armstrong

IPC分类号： A61K3170

CPC分类号： C07H15/04 ,  A61K47/549 ,  A61K47/59 ,  C07H3/04 ,  C07H3/06 ,  Y10S424/16

摘要： Compounds which bind to toxins associated with enteric bacterial infection, compositions including the compounds, methods for the neutralization of toxins in a patient, and methods for the diagnosis of bacterial and viral infections are disclosed. Toxins which can be bound by the compounds include pentameric toxins, for example SLTs, such as those from salmonella, camylobacter and other bacteria, verotoxins from E. coli, cholera toxin, clostridium difficile toxins A and B, bacterial pili from enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) and viral lectins such as viral hemagglutinins. The compounds include a core molecule bound to a plurality of linker arms, which in turn are bound to a plurality of bridging moieties, which in turn are bound to at least one, and preferably, two or more ligands which bind to the toxin. The presence of a plurality of bridged dimers of the ligands is responsible for the increased binding affinity of the compounds relative to the ligands themselves. In one embodiment, the compounds, when administered in a timely fashion to a patient suffering from enteric E. coli infection, inhibit progression of this infection into hemolytic uremic syndrome (HUS).

摘要翻译： 公开了结合与肠细菌感染相关的毒素的化合物，包括该化合物的组合物，用于中和患者中的毒素的方法，以及诊断细菌和病毒感染的方法。 可以被化合物结合的毒素包括五聚体毒素，例如SLT，例如来自沙门氏菌属，弯孢杆菌属和其他细菌的那些，来自大肠杆菌的肠毒素，霍乱毒素，艰难梭菌毒素A和B，来自肠致病性大肠杆菌的细菌 （EPEC）和肠毒素性大肠杆菌（ETEC）和病毒凝集素如病毒血凝素。 化合物包括与多个连接臂结合的核心分子，其又结合到多个桥连部分，其又结合至少一个，优选两个或更多个与毒素结合的配体。 配体的多个桥连二聚体的存在导致化合物相对于配体本身的增加的结合亲和力。 在一个实施方案中，当及时给予患有肠道大肠杆菌感染的患者时，化合物抑制该感染进入溶血性尿毒综合征（HUS）。

公开(公告)号：US4238473A

公开(公告)日：1980-12-09

申请号：US5579

申请日：1979-01-22

申请人： Raymond U. Lemieux ,  David R. Bundle ,  Donald A. Baker

发明人： Raymond U. Lemieux ,  David R. Bundle ,  Donald A. Baker

IPC分类号： C07H3/04 ,  C07H3/06 ,  A61K35/14 ,  C07H13/06

CPC分类号： C07H3/06 ,  C07H3/04 ,  Y10S530/807

摘要： Carbohydrate antigenic determinants containing a glycosidically linked bridging arm are synthesized and coupled to carrier molecules to form artificial antigens, and to solid supports to form immunoadsorbents. Various artificial antigens of the blood group type are prepared and applications shown. Specific examples are given to the synthesis of the Lewis-a, Lewis-b, A, B, and H(O) blood group antigens; to the preparation of antisera to these artificial antigens, to the preparation of immunoadsorbents specific for antibodies to these antigens, and to the detection of such antigens wherever they occur.

摘要翻译： 合成含有糖基连接的桥连臂的碳水化合物抗原决定簇，并与载体分子偶联形成人造抗原，并与固体支持物形成免疫吸附剂。 制备血型的各种人造抗原并显示应用。 给出Lewis-a，Lewis-b，A，B和H（O）血型抗原合成的具体实例。 制备这些抗原的抗血清，制备对这些抗原的抗体特异性的免疫吸附剂，以及在发生这些抗原的情况下检测这些抗原。

公开(公告)号：US20100166695A1

公开(公告)日：2010-07-01

申请号：US12530814

申请日：2008-03-20

申请人： David R. Bundle ,  Pavel kitov

发明人： David R. Bundle ,  Pavel kitov

IPC分类号： A61K31/70 ,  C07H15/08 ,  C08B37/02 ,  C08F251/00 ,  A61K31/74

CPC分类号： C08G69/48 ,  A61K47/549 ,  A61K47/58 ,  A61K51/065 ,  G16C10/00 ,  G16C20/50 ,  Y02A90/26

摘要： Designed herein are multivalent heterobifunctional polymers for binding to a biological target exhibiting biological activity and to an effector template which can affect the biological activity of the biological target or detect the presence of the biological target. The polymers comprise a plurality of pre-arranged heterobifunctional ligands connected thereto, and each heterobifunctional ligand comprises a first functionality capable of binding to the biological target, and a second functionality capable of binding to the effector template. The heterobifunctional ligands are pre-arranged on the polymer so as to form a ternary complex between the polymer, the biological target and the effector template. The polymers, methods and compositions described herein provide an approach for the design and production of new therapeutic agents as well as agents useful in a variety of non-therapeutic applications.

摘要翻译： 本文设计的是用于结合表现生物活性的生物靶标的多价异双功能聚合物和可影响生物靶标的生物活性或检测生物靶标存在的效应器模板。 聚合物包含与之连接的多个预先布置的异双功能配体，并且每个异双功能配体包括能够结合生物靶标的第一官能团和能结合效应子模板的第二官能团。 将异双功能配体预先排列在聚合物上，以便在聚合物，生物靶和效应模板之间形成三元复合物。 本文所述的聚合物，方法和组合物提供了用于设计和生产新的治疗剂以及可用于各种非治疗应用的试剂的方法。