公开(公告)号：US09701694B2

公开(公告)日：2017-07-11

申请号：US13132194

申请日：2009-12-02

Applicant: Paul Stephen Donnelly ,  Michelle Therese Ma ,  Denis Bernard Scanlon

Inventor： Paul Stephen Donnelly ,  Michelle Therese Ma ,  Denis Bernard Scanlon

IPC: A61K8/72 ,  C07D521/00 ,  A61K51/08 ,  A61K51/04 ,  A61K49/10 ,  A61K49/08 ,  A61K49/06 ,  A61K51/00 ,  A61K51/02

CPC classification number: C07D521/00 ,  A61K49/06 ,  A61K49/08 ,  A61K49/10 ,  A61K49/101 ,  A61K51/00 ,  A61K51/02 ,  A61K51/04 ,  A61K51/0482 ,  A61K51/082 ,  A61K51/088

Abstract: The present invention relates to compounds that are useful as metal ligands and which either contain a molecular recognition moiety or can be bound to a molecular recognition moiety and methods of making these compounds. Once the compounds that contain a molecular recognition moiety are coordinated with a suitable metallic radionuclide, the coordinated compounds are useful as radiopharmaceuticals in the areas of radiotherapy and diagnostic imaging. The invention therefore also relates to methods of diagnosis and therapy utilising the radiolabelled compounds of the invention.

公开(公告)号：US20170128572A1

公开(公告)日：2017-05-11

申请号：US15343580

申请日：2016-11-04

Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： Jamey Weichert ,  Anatoly Pinchuk ,  Wolfgang Axel Tomé

IPC: A61K41/00 ,  A61N5/10 ,  G01N33/60 ,  C07F9/10 ,  A61K51/04

CPC classification number: A61K41/009 ,  A61K49/085 ,  A61K49/10 ,  A61K49/106 ,  A61K51/0482 ,  A61K2039/505 ,  A61N5/1039 ,  A61N5/1048 ,  A61N5/1077 ,  A61N2005/109 ,  C07F9/091 ,  C07F9/10 ,  C07F9/11 ,  C07F9/6515 ,  C07F9/6524 ,  C07F9/6561 ,  G01N33/574 ,  G01N33/58 ,  G01N33/60 ,  G01N2458/15

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. R1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

公开(公告)号：US09623128B2

公开(公告)日：2017-04-18

申请号：US14671062

申请日：2015-03-27

Applicant: University of Virginia Patent Foundation

Inventor： Kimberly A. Kelly

IPC: A61K51/08 ,  A61K51/04 ,  A61K51/06 ,  C07K7/06 ,  C07K14/00 ,  A61K47/48 ,  A61K49/00 ,  G01N33/531 ,  G01N33/574

CPC classification number: A61K51/088 ,  A61K47/64 ,  A61K49/0002 ,  A61K51/0482 ,  A61K51/065 ,  C07K7/06 ,  C07K14/00 ,  G01N33/531 ,  G01N33/574 ,  G01N2333/4724

Abstract: The present invention provides compositions and methods useful for diagnostic and imaging techniques for detecting and localizing the biomarker Plectin-1. The present invention provides multimeric peptide ligand complexes for targeting Plectin-1, such as the multimeric peptide ligand complex having the formula (βAKTLLPTPGGS(PEG5000))4 KKKKDOTAβA-NH2, to which imaging agents and/or therapeutic agents can be conjugated.

公开(公告)号：US20170087258A1

公开(公告)日：2017-03-30

申请号：US15265158

申请日：2016-09-14

Applicant: The Regents of the University of California ,  The Research Foundation for The State University of New York

Inventor： Jose Manuel Mejia Oneto ,  Maksim Royzen

IPC: A61K51/06 ,  A61K31/43 ,  A61K51/12 ,  A61K38/12 ,  A61K31/7076 ,  A61K38/14 ,  A61K49/00

CPC classification number: A61K51/065 ,  A61K31/43 ,  A61K31/7076 ,  A61K38/12 ,  A61K38/14 ,  A61K47/54 ,  A61K47/542 ,  A61K47/545 ,  A61K47/61 ,  A61K47/665 ,  A61K47/6903 ,  A61K49/0041 ,  A61K49/0043 ,  A61K49/0052 ,  A61K49/0054 ,  A61K49/0073 ,  A61K51/0482 ,  A61K51/0495 ,  A61K51/1213 ,  C07D257/08 ,  C07D311/82 ,  C07D499/74 ,  C07H7/02 ,  C07H15/24 ,  C07H19/167 ,  C07H19/213

Abstract: The present invention provides a method for selective delivery of a therapeutic or diagnostic agent to a targeted organ or tissue by implanting a biocompatible solid support in the patient being linked to a first binding agent, and administering a second binding agent to the patient linked to the therapeutic or diagnostic agent, such that the therapeutic or diagnostic agent accumulates at the targeted organ or tissue.

公开(公告)号：US20170007724A1

公开(公告)日：2017-01-12

申请号：US15115457

申请日：2015-02-02

Applicant: WASHINGTON UNIVERSITY

Inventor： Samuel Achilefu ,  Nalinikanth Kotagiri

IPC: A61K49/00 ,  A61K41/00 ,  A61K51/04

CPC classification number: A61K49/0056 ,  A61K41/0038 ,  A61K41/0057 ,  A61K49/0013 ,  A61K49/0021 ,  A61K51/0474 ,  A61K51/0482

Abstract: The present disclosure discloses methods and compositions for A administering Cerenkov radiation-induced therapy (GRIT). In an aspect, the invention encompasses a composition comprising at least two radiation-sensitive molecules. In another aspect, the invention encompasses a composition comprising a radiation-sensitive molecule and a targeting agent. In still another aspect, the invention encompasses a method for administering Gerenkov radiation-induced therapy (GRIT) to a target tissue in a subject. The method comprises administering to the subject an effective amount of a composition B comprising at least one radiation-sensitive molecule and administering to the subject an amount of a Gerenkov radiation (GR)-emitting radionuclide effective to activate the radiation-sensitive molecule, thereby administering GRIT to the target tissue in the subject.

Abstract translation: 本公开公开了用于施用切伦科夫辐射诱导疗法（GRIT）的方法和组合物。 一方面，本发明包括包含至少两种辐射敏感分子的组合物。 在另一方面，本发明包括包含辐射敏感分子和靶向剂的组合物。 另一方面，本发明包括用于给受试者的靶组织施用格伦科夫辐射诱导疗法（GRIT）的方法。 该方法包括向受试者施用有效量的包含至少一种辐射敏感分子的组合物B，并向受试者施用一定量的有效激活辐射敏感分子的Gerenkov辐射（GR）发射放射性核素，由此施用 GRIT到受试者的靶组织。

公开(公告)号：US20160354497A1

公开(公告)日：2016-12-08

申请号：US15240836

申请日：2016-08-18

Applicant: The University of Melbourne

Inventor： Paul Donnelly ,  Brett Paterson

IPC: A61K51/04 ,  C07F1/08 ,  C07B59/00 ,  C07D487/08

CPC classification number: A61K51/0482 ,  A61K51/088 ,  C07B59/002 ,  C07B2200/05 ,  C07D487/08 ,  C07F1/08

Abstract: The present invention relates to compounds that are useful as metal ligands and which can be bound to a biological entity such as a molecular recognition moiety and methods of making these compounds. Once the compounds that are bound to a biological entity are coordinated with a suitable metallic radionuclide, the coordinated compounds are useful as radiopharmaceuticals in the areas of radiotherapy and diagnostic imaging. The invention therefore also relates to methods of diagnosis and therapy utilising the radiolabelled compounds of the invention.

Abstract translation: 本发明涉及可用作金属配体并可结合生物实体如分子识别部分的化合物和制备这些化合物的方法。 一旦与生物实体结合的化合物与合适的金属放射性核素配位，配位化合物可用作放射治疗和放射治疗成像领域的放射性药物。 因此，本发明还涉及使用本发明的放射性标记化合物的诊断和治疗方法。

公开(公告)号：US09492571B2

公开(公告)日：2016-11-15

申请号：US14400757

申请日：2013-05-27

Applicant: University of Massachusetts Medical School

Inventor： Brian D. Gray ,  Mary Rusckowski ,  Koon Y. Pak

IPC: A61K51/04 ,  A61K49/00 ,  C07D209/14 ,  C07B59/00 ,  C07D209/20 ,  C07D403/14 ,  G01N33/50 ,  G01N33/58

CPC classification number: A61K51/0485 ,  A61K49/0032 ,  A61K51/0446 ,  A61K51/0478 ,  A61K51/0482 ,  C07B59/002 ,  C07D209/14 ,  C07D209/20 ,  C07D403/14 ,  G01N33/5005 ,  G01N33/52 ,  G01N33/56966 ,  G01N33/582

Abstract: The invention relates to novel multi-modality probes for imaging, tracking and analyzing stem cells and related biological samples, and methods of preparation and use thereof. The molecular probes of the invention are constructed, for example, by utilizing (a) the high selectivity of long hydrocarbon chains for binding to plasma membranes of cells, (b) a near-infrared (NIR) dye for optical imaging, and (c) a radionuclide for PET or SPECT imaging. The in vitro and in vivo data of the optical and radiolabeled probes demonstrated their utility for detecting the presence of stem cells with multiple imaging modalities.

Abstract translation: 本发明涉及用于成像，跟踪和分析干细胞和相关生物样品的新型多模态探针及其制备和使用方法。 本发明的分子探针例如通过利用（a）长烃链的高选择性结合细胞质膜，（b）用于光学成像的近红外（NIR）染料和（c ）用于PET或SPECT成像的放射性核素。 光学和放射性标记的探针的体外和体内数据证明了它们用于以多种成像方式检测干细胞的存在。

公开(公告)号：US09422286B2

公开(公告)日：2016-08-23

申请号：US14606714

申请日：2015-01-27

Applicant: Washington University

Inventor： Liviu Mirica ,  Anuj Sharma ,  Jason Schultz

IPC: C07D471/18 ,  C07D417/10 ,  C07F1/00 ,  A61K51/04

CPC classification number: C07D471/18 ,  A61K51/0482 ,  A61K51/0497 ,  C07D417/10 ,  C07F1/005

Abstract: Metal-binding bifunctional compounds and their use as diagnostic agents for Alzheimer's disease and other beta amyloid disorders are disclosed. Also, radiolabeled metal complexes of these bifunctional compounds and their use as positron emission tomography (PET) imaging agents are provided.

Abstract translation: 公开了金属结合双功能化合物及其作为阿尔茨海默氏病和其他β淀粉样蛋白病症的诊断剂的用途。 此外，提供这些双功能化合物的放射性标记金属络合物及其作为正电子发射断层摄影（PET）成像剂的用途。

公开(公告)号：US09381261B2

公开(公告)日：2016-07-05

申请号：US14124669

申请日：2012-06-05

Applicant: Shawn P Iadonato ,  Eric J Tarcha

Inventor： Shawn P Iadonato ,  Eric J Tarcha

IPC: A61K38/16 ,  A61K38/00 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00 ,  C07K17/00 ,  C07K1/00 ,  B01L3/00 ,  G01N31/22 ,  G01N33/52 ,  A61K51/08 ,  C07K14/00 ,  A61K38/17 ,  C07K14/435 ,  A61K47/48 ,  A61K49/00 ,  B01L3/12 ,  B01L9/00 ,  B01L99/00

CPC classification number: A61K49/0004 ,  A61K38/00 ,  A61K38/16 ,  A61K38/1767 ,  A61K49/0002 ,  A61K51/0482 ,  A61K51/088 ,  B01L3/12 ,  B01L9/00 ,  B01L99/00 ,  C07K14/00 ,  C07K14/43504

Abstract: Disclosed herein are pharmaceutical compositions having the sequence Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Xaa-Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys (SEQ ID NO: 1). The disclosed compositions can include an acid or amide at the C-terminus of SEQ ID NO: 1 and the polypeptide can be attached to an organic or inorganic chemical entity that has an anionic charge. The polypeptide can be detectably labeled for diagnostic purposes. Methods of manufacturing and using the pharmaceutical compounds are also disclosed.

Abstract translation: 本文公开了具有序列Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Xaa- Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys（SEQ ID NO：1）。 所公开的组合物可以在SEQ ID NO：1的C末端包括酸或酰胺，并且多肽可以连接到具有阴离子电荷的有机或无机化学实体。 为了诊断目的，多肽可以被可检测地标记。 还公开了制备和使用药物化合物的方法。

公开(公告)号：US09371360B2

公开(公告)日：2016-06-21

申请号：US14362011

申请日：2012-11-30

Applicant: THE JOHNS HOPKINS UNIVERSITY

Inventor： Martin Gilbert Pomper ,  Sangeeta Ray ,  Ronnie C. Mease ,  Hassan Shallal

IPC: A61K51/00 ,  C07K5/097 ,  C07K5/02 ,  C07K5/09 ,  A61K38/06 ,  A61K45/06 ,  C07D249/04 ,  A61K51/08 ,  A61K51/04

CPC classification number: A61K51/088 ,  A61K38/00 ,  A61K38/06 ,  A61K45/06 ,  A61K51/0482 ,  C07D249/04 ,  C07K5/0217 ,  C07K5/0815 ,  C07K5/0821

Abstract: The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (α-, ε-)dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.

Abstract translation: 本发明提供二价和多价配体，以提高尿素类PSMA抑制剂的亲和性和药代动力学性质。 化合物及其合成可以推广到其他靶抗原的多价化合物。 因为它们呈现多个拷贝的药效团，所以多价配体可以以高亲合力和亲和力结合受体，从而作为强大的抑制剂。 在一个或多个实施方案中，本发明的模块化多价支架含有用于并入两个或更多个抗原结合部分（例如PSMA结合Lys-Glu尿素部分）的赖氨酸（α-，＆amp; 点击化学和一个或多个另外的赖氨酸残基用于随后用成像和/或治疗核素或细胞毒性配体进行肿瘤细胞杀伤的修饰。