公开(公告)号：US07977361B2

公开(公告)日：2011-07-12

申请号：US12836926

申请日：2010-07-15

Applicant: Thomas Lee Collier ,  Brian A. Duclos ,  Umesh B. Gangadharmath ,  Zhiyong Gao ,  Farhad Karimi ,  Dhanalakshmi Kasi ,  Hartmuth C. Kolb ,  Qianwa Liang ,  Henry Clifton Padgett ,  Joseph C. Walsh ,  Tieming Zhao

Inventor： Thomas Lee Collier ,  Brian A. Duclos ,  Umesh B. Gangadharmath ,  Zhiyong Gao ,  Farhad Karimi ,  Dhanalakshmi Kasi ,  Hartmuth C. Kolb ,  Qianwa Liang ,  Henry Clifton Padgett ,  Joseph C. Walsh ,  Tieming Zhao

IPC: C07D249/04 ,  A61K31/4192

CPC classification number: C07D403/06 ,  C07B59/002 ,  C07D403/12

Abstract: The present invention relates to novel radioactively labeled bioreducible tracers of Formula I useful for detecting hypoxic tumors or ischemic tissue in vivo. In one embodiment, the tracers consist of a 2-nitroimidazole moiety, a triazole, metabolically stable linker with pharmacokinetics enhancing substituents, and a radioisotope. The preferred in vivo imaging modality is positron emission tomography.

Abstract translation: 本发明涉及用于体内检测缺氧性肿瘤或缺血组织的式I的新型放射性标记的生物可降解示踪剂。 在一个实施方案中，示踪剂由2-硝基咪唑部分，三唑，具有药代动力学增强取代基的代谢稳定接头和放射性同位素组成。 优选的体内成像模式是正电子发射断层摄影。

公开(公告)号：US20110091382A1

公开(公告)日：2011-04-21

申请号：US12372717

申请日：2009-02-17

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Qianwa Liang ,  Brian A. Duclos ,  Wei Zhang ,  Peter J.H. Scott ,  Kai Chen ,  Zhiyong Gao ,  Tieming Zhao ,  Vani P. Mocharla ,  Dhanalakshmi Kasi ,  Gang Chen ,  Eric Wang ,  Anjana Sinha ,  Chunfang Xia ,  Henry Clifton Padgett ,  Farhad Karimi

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Qianwa Liang ,  Brian A. Duclos ,  Wei Zhang ,  Peter J.H. Scott ,  Kai Chen ,  Zhiyong Gao ,  Tieming Zhao ,  Vani P. Mocharla ,  Dhanalakshmi Kasi ,  Gang Chen ,  Eric Wang ,  Anjana Sinha ,  Chunfang Xia ,  Henry Clifton Padgett ,  Farhad Karimi

IPC: A61K51/04 ,  C07D209/82 ,  C07D311/20 ,  C07D403/12 ,  C07D405/12 ,  C07D471/04 ,  A61P25/28 ,  A61P25/00 ,  A61P25/22 ,  A61P25/24 ,  A61P25/18

CPC classification number: C07B59/002

Abstract: Disclosed here in are compounds and methods of diagnosing Alzheimer's Disease or a predisposition thereto in a mammal, the method comprising administering to the mammal a diagnostically effective amount of a radiolabeled compound, wherein the compound is selected from the group consisting of radiolabeled flavones, coumarins, carbazoles, quinolinones, chromenones, imidazoles and triazoles derivatives, allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing Alzheimer's Disease.

Abstract translation: 本文公开了在哺乳动物中诊断阿尔茨海默病或其倾向的化合物和方法，所述方法包括向哺乳动物施用诊断有效量的放射性标记的化合物，其中所述化合物选自放射性标记的黄酮，香豆素，咔唑 ，喹啉酮，色烯酮，咪唑和三唑衍生物，使化合物分布到脑组织中，并使脑组织成像，其中与正常对照结合水平相比，化合物与脑组织的结合增加指示哺乳动物 患有或有发生阿尔茨海默病的风险。

公开(公告)号：US20110008215A1

公开(公告)日：2011-01-13

申请号：US12803862

申请日：2010-07-08

Applicant: Arkadij M. Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  Reza Miraghaie ,  Todd Graves ,  Artem Lebedev

Inventor： Arkadij M. Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  Reza Miraghaie ,  Todd Graves ,  Artem Lebedev

IPC: G21C1/00

CPC classification number: B01J19/0093 ,  B01J2219/0081 ,  B01J2219/00826 ,  B01J2219/0086 ,  B01J2219/00871 ,  B01J2219/00936

Abstract: Macro- and microfluidic devices and related technologies, and chemical processes using such devices. More specifically, the devices may be used for a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in an efficient, compact and safe to the operator manner. In particular, embodiments of the present invention relate to an automated, multi-run, microfluidic instrument for the multi-step synthesis of radiopharmaceuticals, such as PET probes, comprising a remote shielded mini-cell containing radiation-handing components.

Abstract translation: 宏观和微流体装置及相关技术以及使用这种装置的化学过程。 更具体地，这些装置可以用于以有效，紧凑和安全的操作者方式全面自动化合成用于成像的放射性化合物，例如通过正电子发射断层摄影（PET）。 特别地，本发明的实施例涉及一种用于多步合成放射性药物的自动化，多运行微流控仪器，例如PET探针，其包括含有辐射递送部件的远程屏蔽微型电池。

公开(公告)号：US07829063B2

公开(公告)日：2010-11-09

申请号：US12099135

申请日：2008-04-07

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Bing Wang ,  Umesh B. Gangadharmath ,  Brian A. Duclos ,  Kai Chen ,  Wei Zhang ,  Gang Chen ,  Henry Clifton Padgett ,  Farhad Karimi ,  Peter J. H. Scott ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Tieming Zhao ,  Chunfang Xia

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Bing Wang ,  Umesh B. Gangadharmath ,  Brian A. Duclos ,  Kai Chen ,  Wei Zhang ,  Gang Chen ,  Henry Clifton Padgett ,  Farhad Karimi ,  Peter J. H. Scott ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Tieming Zhao ,  Chunfang Xia

IPC: A61K51/00 ,  C07D343/00

CPC classification number: C07D417/04 ,  C07D249/04 ,  C07D249/06 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14 ,  C12Q1/485 ,  G01N2500/04 ,  G01N2500/10

Abstract: The present application discloses methods for identifying inhibitors with high binding-affinity for the carbonic anhydrase-IX (CA-IX) enzyme using click chemistry and uses the candidates thereof as positron emission tomography (PET) imaging agents.

Abstract translation: 本申请公开了使用点击化学法鉴定对碳酸酐酶IX（CA-IX）酶具有高结合亲和力的抑制剂的方法，并将其候选用作正电子发射断层摄影（PET）成像剂。

公开(公告)号：US07807394B2

公开(公告)日：2010-10-05

申请号：US12098390

申请日：2008-04-04

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Umesh B. Gangadharmath ,  Farhad Karimi ,  Henry Clifton Padgett ,  Dhanalakshmi Kasi ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Brian A. Duclos ,  Tieming Zhao

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Umesh B. Gangadharmath ,  Farhad Karimi ,  Henry Clifton Padgett ,  Dhanalakshmi Kasi ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Brian A. Duclos ,  Tieming Zhao

IPC: C07D233/00 ,  C07D249/00 ,  G01N33/48 ,  G01N33/574

CPC classification number: C07D403/06 ,  C07B59/002 ,  C07D403/12

Abstract: The present invention relates to novel radioactively labeled bioreducible tracers of Formula I useful for detecting hypoxic tumors or ischemic tissue in vivo. In one embodiment, the tracers consist of a 2-nitroimidazole moiety, a triazole, metabolically stable linker with pharmacokinetics enhancing substituents, and a radioisotope. The preferred in vivo imaging modality is positron emission tomography.

Abstract translation: 本发明涉及用于体内检测缺氧性肿瘤或缺血组织的式I的新型放射性标记的生物可降解示踪剂。 在一个实施方案中，示踪剂由2-硝基咪唑部分，三唑，具有药代动力学增强取代基的代谢稳定接头和放射性同位素组成。 优选的体内成像模式是正电子发射断层摄影。

公开(公告)号：US20100239496A1

公开(公告)日：2010-09-23

申请号：US12661777

申请日：2010-03-23

Applicant: Umesh B. Gangadharmath ,  Hartmuth C. Kolb ,  Peter J.H. Scott ,  Joseph C. Walsh ,  Wei Zhang ,  Anna Katrin Szardenings ,  Anjana Sinha ,  Gang Chen ,  Eric Wang ,  Vani P. Mocharia ,  Chul Yu ,  Changhui Liu ,  Daniel Kurt Cashion ,  Dhanalakshmi Kasi

Inventor： Umesh B. Gangadharmath ,  Hartmuth C. Kolb ,  Peter J.H. Scott ,  Joseph C. Walsh ,  Wei Zhang ,  Anna Katrin Szardenings ,  Anjana Sinha ,  Gang Chen ,  Eric Wang ,  Vani P. Mocharia ,  Chul Yu ,  Changhui Liu ,  Daniel Kurt Cashion ,  Dhanalakshmi Kasi

IPC: A61K51/04 ,  C07D401/04 ,  C07D215/06 ,  C07D413/10 ,  C07D235/18 ,  C07D405/04 ,  C07D409/04 ,  C07D413/14 ,  C07D497/04 ,  C12Q1/02

CPC classification number: A61K51/0455 ,  A61K51/04 ,  A61K51/0453 ,  A61K51/0459 ,  A61K51/0463 ,  C07B59/002 ,  C07D215/06 ,  C07D235/14 ,  C07D277/62 ,  C07D401/04 ,  C07D403/06 ,  C07D413/10 ,  C07D413/14 ,  C07D487/04

Abstract: Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formula (I) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.

Abstract translation: 式（I）的成像剂和用于检测神经障碍的方法包括向需要的患者施用能够结合tau蛋白和β-淀粉样蛋白肽的式（I）化合物。 本发明还涉及成像A＆bgr的方法; 和tau聚集体，其包括引入可检测量的包含放射性标记的式（I）化合物的药物制剂，并检测患者中与淀粉样蛋白沉积物和/或tau蛋白相关的标记化合物。 这些方法和组合使得临床前诊断和监测AD和其他神经障碍的进展。

公开(公告)号：US20100098634A1

公开(公告)日：2010-04-22

申请号：US12509259

申请日：2009-07-24

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Wei Zhang ,  Umesh B. Gangadharmath ,  Dhanalakshmi Kasi ,  Kai Chen ,  Anjana Sinha ,  Eric Wang ,  Gang Chen ,  Peter J.H. Scott ,  Henry Clifton Padgett ,  Qianwa Liang ,  Zhiyong Gao ,  Tieming Zhao ,  Chunfang Xia

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Wei Zhang ,  Umesh B. Gangadharmath ,  Dhanalakshmi Kasi ,  Kai Chen ,  Anjana Sinha ,  Eric Wang ,  Gang Chen ,  Peter J.H. Scott ,  Henry Clifton Padgett ,  Qianwa Liang ,  Zhiyong Gao ,  Tieming Zhao ,  Chunfang Xia

IPC: A61K51/04 ,  C07D277/02 ,  C07D495/02 ,  C07D209/34 ,  C07D221/02 ,  C07D455/00 ,  C07D417/00 ,  C07D487/00 ,  C07D401/02 ,  C07D471/00 ,  C07D209/82 ,  C07D307/91 ,  A61P25/28 ,  G01N33/53

CPC classification number: C07D417/14 ,  A61K51/0406 ,  A61K51/0453 ,  A61K51/0455 ,  A61K51/0459 ,  C07D277/64 ,  C07D277/68 ,  C07D417/04 ,  C07D471/04 ,  C07D498/14 ,  C07D513/04 ,  C07D513/14

Abstract: Provided herein are compounds and compositions which comprise the formulae as disclosed herein, wherein the compound is an amyloid binding compound. An amyloid binding compound according to the invention may be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits, and distinguish between neurological tissue with amyloid deposits and normal neurological tissue. Amyloid probes of the invention may be used to detect and quantitate amyloid deposits in diseases including, for example, Down's syndrome, familial Alzheimer's Disease. In another embodiment, the compounds may be used in the treatment or prophylaxis of neurodegenerative disorders. Also provided herein are methods of allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing a neurodegenerative disease.

Abstract translation: 本文提供了包含本文公开的式的化合物和组合物，其中所述化合物是淀粉样蛋白结合化合物。 根据本发明的淀粉样蛋白结合化合物可以以适于淀粉样蛋白沉积物的体内成像的量施用于患者，并且可以区分具有淀粉样沉积物的神经组织和正常神经组织。 本发明的淀粉样蛋白探针可用于检测和定量疾病中的淀粉样蛋白沉积物，包括例如唐氏综合症，家族性阿尔茨海默氏病。 在另一个实施方案中，所述化合物可用于治疗或预防神经变性疾病。 本文还提供了允许化合物分布到脑组织中并对脑组织成像的方法，其中与正常对照结合水平相比，化合物与脑组织的结合增加指示哺乳动物患有或 有发展神经变性疾病的风险。

公开(公告)号：US20100074910A1

公开(公告)日：2010-03-25

申请号：US12455346

申请日：2009-06-01

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Kai Chen ,  Dhanalakshmi Kasi ,  Umesh B. Gangadharmath ,  Peter J.H. Scott ,  Gang Chen ,  Vani P. Mocharla

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Kai Chen ,  Dhanalakshmi Kasi ,  Umesh B. Gangadharmath ,  Peter J.H. Scott ,  Gang Chen ,  Vani P. Mocharla

IPC: A61K39/395 ,  C07K14/00 ,  C07K16/00 ,  A61K38/16 ,  A61P35/00

CPC classification number: A61K51/088 ,  A61K51/082

Abstract: The present disclosure provides methods for treating cancer in a patient in need of such treatment, the method includes prequalifying a patient's therapeutic treatment by performing a molecular imaging procedure to the patient using a labeled biomarker specific for a cancer target at the tumor site; and administering a therapeutic effective amount of a compound comprising a targeting agent linked to a chemotherapeutic or a targeting agent linked to an antibody. Embodiments of the present invention also include compounds and compositions for using such methods.

Abstract translation: 本公开提供了在需要这种治疗的患者中治疗癌症的方法，所述方法包括通过使用在肿瘤部位对癌症靶标特异的标记的生物标志物向患者进行分子成像程序来资格评估患者的治疗性治疗; 以及施用治疗有效量的包含连接于与抗体连接的化学治疗剂或靶向剂的靶向剂的化合物。 本发明的实施方案还包括使用这些方法的化合物和组合物。

公开(公告)号：US07666392B2

公开(公告)日：2010-02-23

申请号：US11901730

申请日：2007-09-17

Applicant: Hartmuth C. Kolb ,  Kai Chen ,  Joseph C. Walsh ,  Qianwa Liang ,  Henry Clifton Padgett ,  Farhad Karimi

Inventor： Hartmuth C. Kolb ,  Kai Chen ,  Joseph C. Walsh ,  Qianwa Liang ,  Henry Clifton Padgett ,  Farhad Karimi

IPC: A61K49/00

CPC classification number: A61K51/088 ,  A61K51/082

Abstract: The present application is directed to radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Abstract translation: 本申请涉及放射性标记的环状多肽，包含放射性标记的环状多肽的药物组合物，以及使用放射性标记的环状多肽的方法。 这样的多肽可用于成像研究，例如正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）。

公开(公告)号：US20080170992A1

公开(公告)日：2008-07-17

申请号：US11901730

申请日：2007-09-17

Applicant: Hartmuth C. Kolb ,  Kai Chen ,  Joseph C. Walsh ,  Qianwa Liang ,  Henry Clifton Padgett ,  Farhad Karimi

Inventor： Hartmuth C. Kolb ,  Kai Chen ,  Joseph C. Walsh ,  Qianwa Liang ,  Henry Clifton Padgett ,  Farhad Karimi

IPC: A61K51/00 ,  A61K38/12

CPC classification number: A61K51/088 ,  A61K51/082

Abstract: The present application is directed to radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Abstract translation: 本申请涉及放射性标记的环状多肽，包含放射性标记的环状多肽的药物组合物，以及使用放射性标记的环状多肽的方法。 这样的多肽可用于成像研究，例如正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）。