公开(公告)号：US20100092467A1

公开(公告)日：2010-04-15

申请号：US12444364

申请日：2007-10-05

Applicant: Jeffrey S. Isenberg ,  David D. Roberts ,  William A. Frazier

Inventor： Jeffrey S. Isenberg ,  David D. Roberts ,  William A. Frazier

IPC: A61K39/395 ,  C07K7/06 ,  C07K7/08 ,  C07H21/00 ,  A61K38/08 ,  A61K38/10 ,  A61K31/7052 ,  C07K16/00 ,  A61P9/12 ,  A61P9/10

CPC classification number: C07K16/18 ,  A61K39/3955 ,  A61K45/06 ,  A61K48/00 ,  A61K2039/505 ,  B01J21/063 ,  B01J21/12 ,  B01J23/002 ,  B01J23/30 ,  B01J27/188 ,  B01J37/0205 ,  B01J2523/00 ,  C07C45/002 ,  C07C45/52 ,  C07C51/235 ,  C07C51/252 ,  C07C253/26 ,  C07K14/78 ,  C07K2317/76 ,  G01N33/6887 ,  G01N33/6893 ,  G01N2333/705 ,  C07C47/22 ,  C07C57/04 ,  B01J2523/15 ,  B01J2523/51 ,  B01J2523/69 ,  B01J2523/41

Abstract: Provided herein are compositions and methods for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival. This in turn reduces or prevents tissue necrosis and death. The therapeutics identified herein allow for precise regulation of blood flow to tissues and organs which need it, while substantially avoiding systemic complications. Methods and compositions described herein can be used to increase tissue survival under conditions of trauma and surgery, as well as conditions of chronic vascular disease. Also disclosed are methods for the treatment of elderly subjects using agents that affect TSP1 and CD47 and thereby affect tissue perfusion. Additionally, provided herein are compositions and methods for influencing blood coagulation, allowing for controlled increased or decreased blood clotting. Additionally, provided herein are compositions and methods for decreasing blood flow, as in the case of cancer through mimicking the effects of TSP1 and CD47 on blood vessel diameter and blood flow.

Abstract translation: 本文提供的是用于预防，改善和/或减少由于缺血引起的组织缺血和/或组织损伤，增加血管直径，血流量和组织灌注的组合物和方法，所述血管疾病包括外周血管疾病，动脉粥样硬化性血管疾病 ，冠状动脉疾病，中风和影响其他病症，通过抑制CD47和/或阻断TSP1和/或CD47活性或相互作用。 影响CD47-TSP1在血管中的相互作用允许控制血管直径和血流量，并允许改变血压和心脏功能。 在血液流量减少的情况下，例如通过损伤或动脉粥样硬化，阻断TSP1-CD47相互作用使血管扩张并增加血流量，组织灌注和组织存活。 这又减少或预防组织坏死和死亡。 本文鉴定的治疗剂允许精确调节需要它的组织和器官的血流，同时基本上避免系统并发症。 本文描述的方法和组合物可用于在创伤和手术的条件下以及慢性血管疾病的病症中增加组织存活。 还公开了使用影响TSP1和CD47并因此影响组织灌注的试剂治疗老年受试者的方法。 此外，本文提供了影响血液凝固的组合物和方法，允许控制增加或减少血液凝固。 此外，本文提供的是通过模拟TSP1和CD47对血管直径和血流量的影响来降低血流量的组合物和方法，如在癌症的情况下。

公开(公告)号：US07618789B2

公开(公告)日：2009-11-17

申请号：US10474213

申请日：2002-04-03

Applicant: David D. Roberts ,  Henry C. Krutzsch ,  Christine Krutzsch, legal representative

Inventor： David D. Roberts ,  Henry C. Krutzsch

IPC: G01N33/574

CPC classification number: G01N33/57423 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/574 ,  G01N33/5743 ,  G01N33/57488 ,  G01N2333/47

Abstract: Method of diagnosing cancer in a male mammal comprising obtaining and assaying a test sample for an increased level of semenogelin; method of diagnosing cancer in a female mammal comprising obtaining and assaying a test sample for the presence of semenogelin; methods of prognosticating and assessing the effectiveness of treatment of a cancer in a mammal comprising measuring the level of semenogelin in a test sample; method of inducing an immune response to a cancer in a mammal comprising administering to the mammal a composition comprising (a) an immune-response inducing effective amount of (i) semenogelin or (ii) antibody thereto or (b) a recombinant vector encoding and expressing an immune-response inducing effective amount of (i) or (ii); and composition comprising a carrier and (a) an immune-response inducing effective amount of (i) a polypeptide of any of SEQ ID NOS:1-27 or (ii) antibody thereto or (b) a recombinant vector encoding and expressing an immune-response inducing effective amount of (i) or (ii).

Abstract translation: 诊断男性哺乳动物癌症的方法，包括获得和测定测试样品以增加精液蛋白的含量; 诊断女性哺乳动物癌症的方法，包括获得和测定样品中存在精液蛋白的方法; 预测和评估哺乳动物癌症治疗有效性的方法，包括测量测试样品中精液蛋白的水平; 诱导哺乳动物对癌症的免疫应答的方法，包括向哺乳动物施用组合物，其包含（a）诱导有效量的（i）精液蛋白或（ii）抗体的免疫应答或（b）编码和 表达免疫应答诱导有效量的（i）或（ii）; 和（a）免疫应答诱导有效量的（i）SEQ ID NO：1-27中任一项的多肽或（ii）抗体的组合物，或（b）编码和表达免疫的重组载体 - 反应诱导有效量的（i）或（ii）。

公开(公告)号：US07129052B1

公开(公告)日：2006-10-31

申请号：US10030735

申请日：2000-07-12

Applicant: David D. Roberts ,  Henry C. Krutzsch

Inventor： David D. Roberts ,  Henry C. Krutzsch

IPC: G01N33/53 ,  A61K38/04

CPC classification number: C07K7/06 ,  A61K38/00

Abstract: The present invention relates to a peptide comprising the sequence R1-X1-X2-X3-X4-R2, wherein X1 is selected from the group consisting of N, Q, D and S; X2 is selected from the group consisting of V, I and L; X3 is selected from the group consisting of R and K; and X4 is selected from the group consisting of V, I, L and F; R1 is a hydrogen or a peptide of 1 to 6 amino acids, and acyl or an aryl group; and R2 is a peptide of 1 to 3 amino acids, a hydroxide or an amide. The invention also relates to partial or full retro-inverso peptides comprising the above sequences. The invention also relates to peptide-substrate combination comprising a substrate suitable for cell growth and the peptide of the invention, and to a vascular graft and an artificial blood vessel comprising the peptide-substrate combination. The invention also relates to a pharmaceutical composition and a peptide conjugate comprising the peptide of the invention. The invention also relates to a method of inhibiting adhesion of a cell expressing α3β1 integrin to an cellular matrix, inhibiting α3β1-integrin-mediated cell motility, inhibiting α3β1-integrin mediated cell proliferation, promoting α3β1-integrin mediated cell proliferation and inhibiting angiogenesis utilizing the peptides of the invention.

Abstract translation: 本发明涉及包含序列R 1 -X 1 -X 2 -X 3 -X 3的肽， X 4 -R 2，其中X 1选自N，Q，D和S; X 2选自V，I和L; X 3选自R和K; 并且X 4选自V，I，L和F; R 1是氢或1至6个氨基酸的肽，酰基或芳基; R 2是1至3个氨基酸的肽，氢氧化物或酰胺。 本发明还涉及包含上述序列的部分或全部逆转肽。 本发明还涉及包含适合于细胞生长的底物和本发明的肽的肽 - 底物组合以及包含肽 - 底物组合的血管移植物和人造血管。 本发明还涉及包含本发明的肽的药物组合物和肽缀合物。 本发明还涉及抑制表达α3beta1整联蛋白的细胞粘附到细胞基质上的方法，抑制α3β1整联蛋白介导的细胞运动，抑制α3β1整联蛋白介导的细胞增殖，促进α3β1整联蛋白介导的细胞增殖并抑制血管生成 本发明的肽。

公开(公告)号：US06212047B1

公开(公告)日：2001-04-03

申请号：US08771468

申请日：1996-12-20

Applicant: Alexander P. Payne ,  William C. Cain ,  Michael E. Devillier ,  Harold J. Hamilton ,  Robert D. Hempstead ,  Darren T. Imai ,  Dimitre A. Latev ,  Mark A. Lauer ,  David D. Roberts

Inventor： Alexander P. Payne ,  William C. Cain ,  Michael E. Devillier ,  Harold J. Hamilton ,  Robert D. Hempstead ,  Darren T. Imai ,  Dimitre A. Latev ,  Mark A. Lauer ,  David D. Roberts

IPC: G11B539

CPC classification number: G11B5/6005 ,  G11B5/1278 ,  G11B5/3106 ,  G11B5/3176 ,  G11B5/3183 ,  G11B5/3967 ,  G11B5/6076

Abstract: An information storage system having a ring head in such close proximity to a rigid magnetic storage disk that the magnetic field felt by the media layer or layers of the disk has a larger perpendicular than longitudinal component so that data is stored in a perpendicular mode. Reading of data is accomplished with a magnetoresistive sensor which may be coupled to the magnetically permeable core of the ring head far from the poletips, which may contact the disk. The media preferably has a high perpendicular anisotropy, and may be formed in a plurality of films with crystalline structures traversing the films.

Abstract translation: 一种信息存储系统，其具有如此靠近刚性磁存储盘的环形头，所述刚性磁存储盘使得所述介质层感觉到的磁场或所述盘的层具有比纵向分量更大的垂直于垂直模式的数据。 数据读取是通过一个磁阻传感器实现的，该磁阻传感器可耦合到远离可以接触磁盘的引脚的环形头部的导磁芯。 介质优选具有高垂直各向异性，并且可以形成为具有穿过膜的结晶结构的多个膜。

公开(公告)号：US5389521A

公开(公告)日：1995-02-14

申请号：US3915

申请日：1993-01-13

Applicant: Howard C. Krivan ,  Victor Ginsburg ,  David D. Roberts

Inventor： Howard C. Krivan ,  Victor Ginsburg ,  David D. Roberts

IPC: A61K31/70 ,  G01N33/569

CPC classification number: G01N33/56911 ,  A61K31/70 ,  Y10S435/803 ,  Y10S435/851 ,  Y10S435/874 ,  Y10S435/882 ,  Y10S435/885

Abstract: The invention is a method for detecting pathogenic bacteria by specific binding of the bacteria to GalNAc.beta.1-4Gal sequences found in fucosyl-asialo GM1, asialo GM1 and asialo GM2. An agglutination reaction is disclosed comprising contacting a culture suspected of containing the bacteria with a suspension of a purified carbohydrate compound bound to an insoluble carrier and detecting the presence of perceptible agglutination of the carrier as an indication of the presence of the bacteria. Bacteria which can be detected using the claimed method include Pseudomonas, Haemophilus, Staphylococcus, Klebsiella and Streptococcus pneumoniae.

Abstract translation: 本发明是通过将细菌与岩藻糖基脱唾液酸GM1，脱ial GM1和唾液酸GM2中发现的GalNAcβ1-4Gal序列的特异性结合来检测病原菌的方法。 公开了一种凝集反应，包括将怀疑含有细菌的培养物与结合到不溶性载体的纯化碳水化合物混合物的悬浮液接触，并检测载体的可感知凝集物的存在，作为细菌存在的指示。 可以使用所要求保护的方法检测的细菌包括假单胞菌属，嗜血杆菌属，葡萄球菌属，克雷伯杆菌属和肺炎链球菌。

公开(公告)号：US5217715A

公开(公告)日：1993-06-08

申请号：US226445

申请日：1988-08-01

Applicant: Howard C. Krivan ,  Ginsburg Victor ,  David D. Roberts

Inventor： Howard C. Krivan ,  Ginsburg Victor ,  David D. Roberts

IPC: A61K31/70 ,  G01N33/569

CPC classification number: G01N33/56911 ,  A61K31/70 ,  Y10S435/803 ,  Y10S435/851 ,  Y10S435/874 ,  Y10S435/882 ,  Y10S435/885

Abstract: The invention is a carbohydrate receptor for pathogenic bacteria. The receptor is a purified carbohydrate compound that is a member selected from the group consisting of fucosyl-asialo GM1, asialo GM1, and asialo GM2. The invented receptor can be included in a composition having a pharmaceutically acceptable carrier. The invention includes methods for purifying, detecting, or removing bacteria from diseased tissue. The applicants have discovered a carbohydrate receptor for a variety of different species of disease-producing bacteria. The structure of the receptor is N-acetylgalactosamine-beta-1-4-galactose-beta-1-4-glucose, abreviated GalNAc.beta.1-4Gal.beta.1-4Glc. The receptor is present in human and animal tissues as complex molecules and can serve as the attachment site for bacterial infection. For example, fucosyl-asialo GM1, asialo GM1, and asialo GM2 are three biological molecules which occur in cell membranes and contain the carbohydrate receptor.

Abstract translation: 本发明是病原菌的碳水化合物受体。 受体是选自岩藻糖基 - 脱ial GM1，脱ial GM1和唾液酸GM2的成员的纯化碳水化合物化合物。 本发明的受体可以包含在具有药学上可接受的载体的组合物中。 本发明包括用于纯化，检测或从病变组织中除去细菌的方法。 申请人已经发现了多种不同种类的产生疾病的细菌的碳水化合物受体。 受体的结构是N-乙酰半乳糖胺-β-1-4-半乳糖-β-1-4-葡萄糖，缓解GalNAcβ1-4Galβ1-4Glc。 受体作为复合分子存在于人和动物组织中，并可作为细菌感染的附着位点。 例如，岩藻糖基唾液酸GM1，脱ial GM1和脱ial GM2是发生在细胞膜中并含有碳水化合物受体的三种生物分子。