公开(公告)号：US5770563A

公开(公告)日：1998-06-23

申请号：US487568

申请日：1995-06-07

Applicant: David D. Roberts ,  Philip J. Browning ,  Joseph L. Bryant ,  John K. Inman ,  Henry C. Krutzsch ,  Nenghua Guo

Inventor： David D. Roberts ,  Philip J. Browning ,  Joseph L. Bryant ,  John K. Inman ,  Henry C. Krutzsch ,  Nenghua Guo

IPC: A61K38/00 ,  C07K7/00 ,  C07K14/78 ,  C07K17/10 ,  A61K38/04 ,  C07K5/00

CPC classification number: C07K17/10 ,  C07K14/78 ,  A61K38/00 ,  C12N2533/50 ,  Y10S514/908

Abstract: This invention identifies a biologically active group of peptide sequences from Type I repeat units of the extracellular matrix protein, human thrombospondin-1, identical or homologous to the sequence, KRFKQDGGWSHWSPWSSC (SEQ ID NO:30). The biological activities residing with the full sequences, portions thereof, and variants of the full or partial sequences are disclosed. The invention describes how biological activity may be enhanced by covalently linking these peptides to suitable carriers, preferably a branched, water-soluble polymer of low (or absent) toxicity and immunogenicity, such as polysucrose (Ficoll.TM.). The invention describes (1) a method for preparing such conjugates, (2) the use of the defined peptides or their conjugates in blocking or modifying the action on cellular processes of heparin (e.g., proliferation, adhesion, motility, extravasation and neovascularization), sulfatides, related sulfated glycoconjugates, fibronectin, and basic fibroblast growth factor, involving malignant cell lines and normal endothelial cells. Use of the defined peptides, analogs or peptidomimetics and their conjugates for treatment of metastatic tumors, breast carcinomas, melanomas, Kaposi's sarcomas, hemangiomas, diabetic retinopathies, and various pathological conditions dependent upon neovascularization is also disclosed.

Abstract translation: 本发明鉴定了与序列KRFKQDGGWSHWSPWSSC（SEQ ID NO：30）相同或同源的细胞外基质蛋白I型重复单元的人类血小板反应蛋白-1的生物活性肽序列。 公开了其完整序列，部分和全部或部分序列的变体的生物活性。 本发明描述如何通过将这些肽共价连接到合适的载体，优选具有低（或不存在）毒性和免疫原性的支链水溶性聚合物如聚蔗糖（Ficoll TM）来增强生物活性。 本发明描述了（1）制备这种缀合物的方法，（2）使用所定义的肽或其缀合物来阻断或改变对肝素细胞过程的作用（例如增殖，粘附，运动，外渗和新生血管形成） 硫酸盐，相关的硫酸化糖缀合物，纤连蛋白和碱性成纤维细胞生长因子，涉及恶性细胞系和正常内皮细胞。 还公开了定义的肽，类似物或肽模拟物及其缀合物用于治疗转移性肿瘤，乳腺癌，黑素瘤，卡波西氏肉瘤，血管瘤，糖尿病视网膜病变以及依赖于新血管形成的各种病理状况的用途。

公开(公告)号：US5357041A

公开(公告)日：1994-10-18

申请号：US801812

申请日：1991-12-06

Applicant: David D. Roberts ,  Nenghua Guo ,  Henry C. Krutzsch

Inventor： David D. Roberts ,  Nenghua Guo ,  Henry C. Krutzsch

IPC: C07K5/10 ,  A61K38/00 ,  C07K5/103 ,  C07K5/107 ,  C07K7/06 ,  C07K7/08 ,  C07K14/78 ,  C07K17/10 ,  C12N5/00 ,  C12N5/06 ,  A61K37/00 ,  A61K37/02 ,  C07K5/00 ,  C07K7/00

CPC classification number: C07K17/10 ,  C07K14/78 ,  C12N5/0068 ,  A61K38/00 ,  C12N2533/50

Abstract: The present invention relates to peptides from the three type I repeats of human endothelial cell thrombospondin, which bind to sulfated glycoconjugates including heparin and sulfatide. Such peptides are useful in glycoconjugate binding pharmaceutical compositions and in a method for binding glycoconjugates in a subject.

Abstract translation: 本发明涉及来自人内皮细胞血小板反应蛋白的三个I型重复序列的肽，其与硫酸化糖缀合物（包括肝素和硫苷脂）结合。 这样的肽可用于糖缀合物结合药物组合物和用于结合受试者中糖缀合物的方法。

公开(公告)号：US08557788B2

公开(公告)日：2013-10-15

申请号：US13546941

申请日：2012-07-11

Applicant: Jeffrey S. Isenberg ,  David D. Roberts

Inventor： Jeffrey S. Isenberg ,  David D. Roberts

IPC: A61K48/00

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 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.

Abstract translation: 本文提供了用于预防，改善和/或减少由于局部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，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 动脉疾病，中风和影响其他条件，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。

公开(公告)号：US20120142751A1

公开(公告)日：2012-06-07

申请号：US13372361

申请日：2012-02-13

Applicant: MICHAEL L. PENDRAK ,  DAVID D. ROBERTS

Inventor： MICHAEL L. PENDRAK ,  DAVID D. ROBERTS

IPC: A61K31/409 ,  A61P25/28 ,  A61P29/00 ,  A61P35/00 ,  A61P9/00

CPC classification number: C12P17/165

Abstract: The present invention relates to compositions and methods for the production of biliverdin and methods of treatment and prevention. In particular, the invention concerns methods for producing biliverdin in yeast, especially Candida albicans, and other microorganisms.

Abstract translation: 本发明涉及用于生产胆红素的组合物和方法以及治疗和预防方法。 特别地，本发明涉及在酵母中产生胆色素的方法，特别是白色念珠菌和其它微生物。

公开(公告)号：US08114406B2

公开(公告)日：2012-02-14

申请号：US12824916

申请日：2010-06-28

Applicant: David D. Roberts ,  Henry C. Krutzsch

Inventor： David D. Roberts ,  Henry C. Krutzsch

IPC: A61K39/00

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, an 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 extracellular matrix, inhibiting α3β1-integrin-mediated cell motility, inhibiting α3β1-integrin mediated cell proliferation, promoting β3β1-integrin mediated cell proliferation and inhibiting angiogenesis utilizing the peptides of the invention.

Abstract translation: 本发明涉及包含序列R1-X1-X2-X3-X4-R2的肽，其中X1选自N，Q，D和S; X2选自V，I和L; X3选自R和K; X4选自V，I，L和F; R1是氢或1-6个氨基酸的肽，酰基或芳基; R2为1〜3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换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，以及血管移植物和人造血管，其包含 肽 - 底物组合。 本发明还涉及包含本发明的肽的药物组合物和肽缀合物。 本发明还涉及一种抑制α3和bgr1整联蛋白与细胞外基质粘附的方法，抑制α3和bgr1-整联蛋白介导的细胞运动，抑制α3和bgr1-整联蛋白介导的细胞增殖，促进和抑制3 - 整合素介导的细胞增殖并利用本发明的肽抑制血管生成。

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：US20090203762A1

公开(公告)日：2009-08-13

申请号：US12364054

申请日：2009-02-02

Applicant: MICHAEL L. PENDRAK ,  DAVID D. ROBERTS

Inventor： MICHAEL L. PENDRAK ,  DAVID D. ROBERTS

IPC: A61K31/4025 ,  C07D403/14 ,  A61P35/00

CPC classification number: C12P17/165

Abstract: The present invention relates to compositions and methods for the production of biliverdin. In particular, the invention concerns methods for producing biliverdin in yeast, especially Candida albicans, and other microorganisms.

Abstract translation: 本发明涉及用于生产胆红素的组合物和方法。 特别地，本发明涉及在酵母中产生胆色素的方法，特别是白色念珠菌和其它微生物。

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：US06255721B1

公开(公告)日：2001-07-03

申请号：US09353213

申请日：1999-07-14

Applicant: David D Roberts

Inventor： David D Roberts

IPC: H01L2972

CPC classification number: H01L21/67138 ,  B81C99/002

Abstract: A method of forming and handling an array of micro-devices such as thin film devices that enables simultaneous mass handling and processing of these thin film devices. A plurality of micro-devices and links are simultaneously formed on a wafer, with the links interconnecting the micro-devices for maintaining a unitary array structure. A matrix of magnetic strips is then formed to impart added overall tensile strength to the array. The magnetic strips are secured to the links and form a planar support grid therewith. The array of micro-devices is then released from the wafer and lifted therefrom by means of a magnetic pick-up tool. Using the pick-up tool, the array is transferred onto a magnetic chuck which securely retains the array. Conductive wires are bonded to a row of micro-devices which are then separated from the array into individual micro-devices.

Abstract translation: 一种形成和处理诸如薄膜器件的微器件阵列的方法，其能够同时进行质量处理和处理这些薄膜器件。 多个微器件和链节同时形成在晶片上，其中链节互连微器件以维持整体阵列结构。 然后形成磁条矩阵以赋予阵列增加的总拉伸强度。 磁条被固定到链节上并与其形成平面支撑格栅。 然后将微器件阵列从晶片释放并通过磁力拾取工具从其上提升。 使用拾取工具，将阵列转移到牢固地保持阵列的磁性卡盘上。 导电线结合到一排微器件，然后将其从阵列分离成单独的微器件。