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1. 发明授权

US11473070B2 Increased polypeptide production yields of butyrylcholinesterase polypeptides for therapeutic use 有权
公开(公告)号：US11473070B2
公开(公告)日：2022-10-18
申请号：US17129736
申请日：2020-12-21
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Fang Zheng
IPC分类号： C12N9/18
摘要： The presently-disclosed subject matter describes fusion proteins comprising butyrylcholinesterase (BChE) having an improved production yield and biological half-life and nucleotides encoding the same.

2. 发明授权

US11325901B2 Prostaglandin E synthase inhibitors and methods for utilizing the same 有权
公开(公告)号：US11325901B2
公开(公告)日：2022-05-10
申请号：US16305386
申请日：2017-06-28
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Fang Zheng , Kai Ding , Ziyuan Zhou
IPC分类号： C07D417/06 , C07D417/04 , C07D403/06 , C07D207/452 , C07D231/12 , C07D251/20 , C07D277/34 , C07C205/42 , C07C255/41
摘要： Compounds and compositions are provided that can inhibit microsomal prostaglandin E synthase-1 (mPGES-1). The compounds and compositions can reduce inflammation in a subject, such as inflammation caused by an inflammation disorder or symptoms thereof. Pharmaceutical compositions comprising the compound are also provided. Furthermore, methods are provided for reducing inflammation and/or inhibiting mPGES-1. The methods can comprise administering an effective amount of the composition to a subject.

3. 发明申请

US20220031709A1 INHIBITION OF MICROSOMAL PROSTAGLANDIN E2 (PGE2) SYNTHASE-1 (MPGES-1) 有权
公开(公告)号：US20220031709A1
公开(公告)日：2022-02-03
申请号：US17393210
申请日：2021-08-03
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Fang Zheng , Shuo Zhou , Ziyuan Zhou
IPC分类号： A61K31/546 , A61K31/427 , A61P29/00 , A61P31/14 , A61P19/02 , A61P9/14
摘要： Disclosed methods of inhibiting microsomal prostaglandin E2 (PGE2) synthase-1 (mPGES-1) make use of ceftriaxone, aztreonam, cefotetan, pharmaceutically-acceptable salts thereof, and combinations thereof.

4. 发明授权

US11098296B2 Mutants of cocaine esterase 有权
公开(公告)号：US11098296B2
公开(公告)日：2021-08-24
申请号：US16230067
申请日：2018-12-21
申请人： The Trustees of Columbia University in the City of New York , University of Kentucky Research Foundation
发明人： Donald Landry , Chang-Guo Zhan
IPC分类号： C12N9/18 , A61K38/46 , A61K38/00
摘要： Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

5. 发明授权

US10772940B1 Cocaine hydrolase-FC fusion proteins for cocaine and methods for utilizing the same 有权
公开(公告)号：US10772940B1
公开(公告)日：2020-09-15
申请号：US14102977
申请日：2013-12-11
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Fang Zheng , Hsin-Hsiung Tai , Xiabin Chen , Liu Xue , Shurong Hou
IPC分类号： C12N9/14 , C12N9/18 , A61K38/46
摘要： The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.

6. 发明授权

US09365841B1 High activity mutants of butyrylcholinesterase for cocaine hydrolysis 有权
公开(公告)号：US09365841B1
公开(公告)日：2016-06-14
申请号：US14577778
申请日：2014-12-19
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Fang Zheng , Wenchao Yang , Liu Xue , Shurong Hou
IPC分类号： C12N9/18 , C12N9/16 , A61K38/46 , C07H21/04
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

7. 发明授权

US11123341B2 Butyrylcholinesterase inhibitors for treatment of opioid use disorder 有权
公开(公告)号：US11123341B2
公开(公告)日：2021-09-21
申请号：US16883291
申请日：2020-05-26
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Fang Zheng
IPC分类号： A61K31/485 , A61K31/5415 , A61P25/36
摘要： A method of treating opioid use disorder involves administering a selective butyrylcholinesterase (BChE) inhibitor.

8. 发明授权

US10160960B2 Mutants of cocaine esterase 有权
公开(公告)号：US10160960B2
公开(公告)日：2018-12-25
申请号：US14910446
申请日：2014-08-06
申请人： The Trustees of Columbia University in the City of New York , University of Kentucky Research Foundation
发明人： Donald Landry , Chang-Guo Zhan
IPC分类号： C12N9/18 , A61K38/46 , A61K38/00
摘要： Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

9. 发明授权

US09586946B2 Selective immunoproteasome inhibitors with non-peptide scaffolds 有权
标题翻译：选择性免疫蛋白酶体抑制剂与非肽支架
公开(公告)号：US09586946B2
公开(公告)日：2017-03-07
申请号：US15155627
申请日：2016-05-16
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Kyung Bo Kim , Vinod Kasam , Na-Re Lee
IPC分类号： C07D405/14
CPC分类号： C07D405/14
摘要： Compounds useful for inhibiting the immunoproteasome have the formula of Methods and compounds for inhibiting the immunoproteasome, particularly, immunoproteasome inhibitors with non-peptide scaffolds, are described.
摘要翻译：描述了用于抑制免疫蛋白酶体的方法和化合物，特别是用非肽支架的免疫蛋白酶体抑制剂。

10. 发明授权

US09206403B1 High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same 有权
标题翻译：用于可卡因水解的丁酰胆碱酯酶的高活性突变体及其产生方法
公开(公告)号：US09206403B1
公开(公告)日：2015-12-08
申请号：US14163376
申请日：2014-01-24
申请人： University of Kentucky Research Foundation
发明人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
IPC分类号： C12N9/16 , C12N9/18
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (−)-cocaine compared with wild-type BChE.
摘要翻译：提供了一种新颖的计算方法和用于可卡因水解的突变丁酰胆碱酯酶的产生。该方法包括对可能的BChE突变体进行分子建模，并进行分子动力学模拟和混合量子力学/分子机械计算，从而通过预测哪个突变体将导致速率确定步骤的更稳定的过渡状态来提供可能的BChE突变体的筛选方法。对于可能的BChE突变体，即与野生型BChE相比预测具有更高催化效率的突变体，对计算确定的突变体进行定点诱变，蛋白质表达和蛋白质活性。此外，突变体A199S / A328W / Y332G，A199S / F227A / A328W / Y332G，A199S / S287G / A328W / Y332G，A199S / F227A / S287G / A328W / Y332G和A199S / F227A / S287G / A328W / E441D都具有增强的催化（ - ） - 可卡因与野生型BChE相比有效。

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