公开(公告)号：US11078166B2

公开(公告)日：2021-08-03

申请号：US15752340

申请日：2016-08-15

申请人： THE JOHNS HOPKINS UNIVERSITY

发明人： Martin G. Pomper ,  Ying Chen ,  Xing Yang ,  Ronnie C. Mease ,  Sangeeta Ray

IPC分类号： C07D249/04 ,  A61K51/04 ,  C07B59/00

摘要： Triazole conjugated urea-based and thiourea-based scaffolds that have high binding affinity to PSMA are disclosed. These scaffolds can be radiolabeled and used to image cells and tumors that express PSMA. Methods of synthesizing radiofluorinated triazole conjugated urea-based and thiourea-based scaffolds also are disclosed.

公开(公告)号：US10857246B2

公开(公告)日：2020-12-08

申请号：US15578473

申请日：2016-06-01

申请人： THE JOHNS HOPKINS UNIVERSITY

发明人： Xing Yang ,  Il Minn ,  Steven Rowe ,  Sangeeta Ray ,  Ronnie C. Mease ,  Michael Gorin ,  Mohamad Allaf ,  Martin G. Pomper

IPC分类号： A61K51/04 ,  C07D417/14 ,  C07D417/12 ,  A61P35/00

摘要： Highly potent and selective radionuclide-based imaging and therapy agents targeting carbonic anhydrase IX with minimum non-specific organ uptake are disclosed. Methods of imaging and/or treating carbonic anhydrase IX-expressing cells or tumors also are disclosed.

公开(公告)号：US20200330613A1

公开(公告)日：2020-10-22

申请号：US16908218

申请日：2020-06-22

申请人： The Johns Hopkins University

发明人： Sangeeta Ray ,  Xing Yang ,  Xiaolei Song ,  Michael T. McMahon ,  Martin G. Pomper

IPC分类号： A61K49/00 ,  C07F19/00 ,  C07F1/04 ,  C08F222/38 ,  A61K49/08 ,  A61K49/12 ,  C07F5/00 ,  C07F5/02 ,  A61K51/06 ,  A61K49/14

摘要： Salicylic acid-based polymeric CEST contrast agents targeting prostate-specific membrane antigen, pharmaceutical composition comprising the same and methods of use thereof are disclosed.

公开(公告)号：US10369113B2

公开(公告)日：2019-08-06

申请号：US15209352

申请日：2016-07-13

申请人： The Johns Hopkins University

发明人： Sachin S. Chandran ,  Sangeeta Ray ,  Martin G. Pomper ,  Samuel R. Denmeade ,  Ronnie C. Mease

IPC分类号： A61K9/51 ,  C07C275/16

摘要： The invention provides a nanoparticle composition that is decorated with a urea-based small-molecule peptidomimetic inhibitor of prostate specific membrane antigen (PSMA), which is expressed by almost all solid tumors. This strategy takes advantage of both the avidity of the functionalized nanoparticle for binding to PSMA and the ability of the nanoparticle to be retained for longer periods of time in the tumor due to enhanced leakage via EPR into the tumor interstitium and poor clearance due to underdeveloped or non-existent lymphatics within the tumor.

公开(公告)号：US20140341804A1

公开(公告)日：2014-11-20

申请号：US14362011

申请日：2012-11-30

申请人： THE JOHNS HOPKINS UNIVERSITY

发明人： Martin Gilbert Pomper ,  Sangeeta Ray ,  Ronnie C. Mease

IPC分类号： C07K5/097 ,  C07D249/04 ,  A61K45/06 ,  A61K38/06 ,  A61K51/04

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

摘要： 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.

摘要翻译： 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。

公开(公告)号：US20240140971A1

公开(公告)日：2024-05-02

申请号：US18209798

申请日：2023-06-14

申请人： The Johns Hopkins University ,  Duke University

发明人： Martin G. Pomper ,  Ronnie C. Mease ,  Ying Chen ,  Sangeeta Ray ,  Michael Zalutsky ,  Ganesan Vaidyanathan

IPC分类号： C07F13/00 ,  A61P35/00

CPC分类号： C07F13/00 ,  A61P35/00 ,  C07B2200/05

摘要： PSMA binding scaffolds with radioiodinated, radiobrominated and radioastatinated labeled prosthetic groups are disclosed. Pharmaceutical compositions and methods of treating PSMA expressing cells or tumors also are disclosed.

公开(公告)号：US11871895B2

公开(公告)日：2024-01-16

申请号：US15778236

申请日：2016-11-23

申请人： THE JOHNS HOPKINS UNIVERSITY

发明人： Ming Li ,  Ishan Barman ,  Martin Pomper ,  Sangeeta Ray

IPC分类号： A61B5/00 ,  G01N33/574 ,  A61K49/00 ,  A61B1/06 ,  G01N21/65 ,  G01N33/543 ,  B82Y15/00

CPC分类号： A61B5/0071 ,  A61B1/063 ,  A61B5/0084 ,  A61B5/4381 ,  A61K49/00 ,  G01N21/658 ,  G01N33/54346 ,  G01N33/574 ,  G01N33/57434 ,  B82Y15/00

摘要： The present invention provides a targeted nanoplex platform for in vivo imaging and theranostic imaging of cancer to simultaneously provide non-invasive assessment of tumor burden and cancer-selective treatments.

公开(公告)号：US20220135529A1

公开(公告)日：2022-05-05

申请号：US17575235

申请日：2022-01-13

申请人： The Johns Hopkins University ,  Northwestern University

发明人： Sangeeta Ray ,  Martin G. Pomper ,  Thomas J. Meade ,  Ronnie C. Mease ,  Ying Chen ,  Xing Yang ,  Matthew Rotz

IPC分类号： C07D257/02 ,  A61K49/10 ,  A61K51/04 ,  C07D403/14 ,  A61K49/12 ,  A61K51/06 ,  A61K49/00

摘要： Low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA-specific T1-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific T1 contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA-targeted imaging in vivo. 86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics.

公开(公告)号：US20210308286A1

公开(公告)日：2021-10-07

申请号：US17264220

申请日：2019-07-30

申请人： The Johns Hopkins University ,  University Health Network

发明人： Martin G. Pomper ,  Ronnie C. Mease ,  Ying Chen ,  Sangeeta Ray ,  Juan Chen ,  Marta Overchuk ,  Kara Harmatys ,  Gang Zheng

IPC分类号： A61K51/08 ,  A61K41/00 ,  A61P35/00 ,  A61K49/00 ,  A61K47/65

摘要： Theranostic probes comprising a porphyrin-based photosensitizer, a D-peptide linker, and a urea-based PSMA-targeting ligand and methods of their use for treating and/or imaging PMSA-expressing tumors are disclosed.

公开(公告)号：US10683272B2

公开(公告)日：2020-06-16

申请号：US15309009

申请日：2015-05-06

申请人： THE JOHNS HOPKINS UNIVERSITY ,  NORTHWESTERN UNIVERSITY

发明人： Sangeeta Ray ,  Martin G. Pomper ,  Thomas J. Meade ,  Ronnie C. Mease ,  Ying Chen ,  Xing Yang ,  Matthew Rotz

IPC分类号： A61K51/00 ,  A61M36/14 ,  C07D257/02 ,  A61K49/10 ,  A61K51/04 ,  C07D403/14 ,  A61K49/12 ,  A61K51/06 ,  A61K49/00

摘要： Low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA-specific Ti-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific Ti contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA-targeted imaging in vivo. 86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics.