公开(公告)号：US11377485B2

公开(公告)日：2022-07-05

申请号：US16150164

申请日：2018-10-02

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu

IPC: C07K16/18 ,  C12P21/00 ,  C07K16/28

Abstract: Methods for making modified Fc regions of antibodies and antibody fragments, both human and humanized, and having enhanced stability and efficacy, are provided. Antibodies comprising Fc regions with core fucose residues removed, and attached to oligosaccharides comprising terminal sialyl residues, are provided. Antibodies comprising homogeneous glycosylation of Fc regions with specific oligosaccharides are provided. Fc regions conjugated with homogeneous glycoforms of monosaccharides and trisaccharides, are provided. Methods of preparing human antibodies with modified Fc using glycan engineering, are provided.

公开(公告)号：US10407673B2

公开(公告)日：2019-09-10

申请号：US16011622

申请日：2018-06-18

Applicant: CHO Pharma Inc. ,  Academia Sinica

Inventor： Nan-Horng Lin ,  Lin-Ya Huang ,  Sachin S Shivatare ,  Li-Tzu Chen ,  Chi-Huey Wong ,  Chung-Yi Wu ,  Ting Cheng

IPC: C12N9/42 ,  C12P21/00 ,  C07K16/28

Abstract: A mutant of EndoS2 includes one or more mutations in the sequence of a wild-type EndoS2 (SEQ ID NO:1), wherein the one or more mutations are in a peptide region located within residues 133-143, residues 177-182, residues 184-189, residues 221-231, and/or residues 227-237, wherein the mutant of EndoS2 has a low hydrolyzing activity and a high tranglycosylation activity, as compared to those of the wild-type EndoS2. A method for preparing an engineered glycoprotein using the mutant of EndoS2 includes coupling an activated oligosaccharide to a glycoprotein acceptor. The activated oligosaccharide is a glycan oxazoline.

公开(公告)号：US10336784B2

公开(公告)日：2019-07-02

申请号：US15453836

申请日：2017-03-08

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Sachin S. Shivatare

IPC: C07H5/06 ,  A61K31/702 ,  C12N9/10 ,  C07K16/10 ,  C12P19/04 ,  G01N33/50 ,  G01N33/532 ,  G01N33/68 ,  C08B37/00 ,  G01N33/569 ,  C12P19/28

Abstract: The present disclosure relates to novel modular methods for generating a diversity of N-glycans of high mannose, hybrid and complex types. The present disclosure also relates to exemplary arrays of the synthesized N-glycans spotted onto aluminium oxide coated slides. These arrays can be used to detect and analyze binding interactions between the synthesized N-glycans and glycan binding molecules, such as HIV-1 neutralizing antibodies. The present disclosure also relates to methods for identifying agents that bind to various types of molecules on the arrays and to defining the structural elements of the molecules on the arrays that bind to those agents. The arrays and methods provided herein may be used for general epitope identification, drug discovery and as analytical tools. The present disclosure also provides useful glycans and epitope determinants that are useful in detecting, diagnosing, recurrence monitoring and preventing pathological diseases such as HIV.

公开(公告)号：US20190177435A1

公开(公告)日：2019-06-13

申请号：US16184203

申请日：2018-11-08

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Tsui-Ling Hsu ,  Yi-Wei Lou ,  Chih-Wei Lin ,  Shih-Chi Yeh ,  Chung-Yi Wu ,  Han-Chung Wu

IPC: C07K16/44 ,  C07K16/30 ,  G01N33/574 ,  C07K16/18

Abstract: Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to globo H, SSEA3, and SSEA-4 are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cell surfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as those in brain, skin, bone, lungs, breast, esophagus, stomach, liver, bile duct, pancreas, colon, kidney, cervical, ovarian, and/or prostate cancer.

公开(公告)号：US20180369249A1

公开(公告)日：2018-12-27

申请号：US16075202

申请日：2017-02-03

Applicant: Academia Sinica ,  National Taiwan University

Inventor： Chi-Huey Wong ,  Pan-Chyr Yang ,  Jim-Min Fang ,  Szu-Hua Pan ,  Ting-Jen R. Cheng ,  Ling-Wei Li

IPC: A61K31/522 ,  A61K35/00

Abstract: The present disclosure provides compounds of Formulas (I′) and (I), and pharmaceutically acceptable salts thereof. The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses thereof for treating proliferative diseases.

公开(公告)号：US10130714B2

公开(公告)日：2018-11-20

申请号：US13836356

申请日：2013-03-15

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Kung-Cheng Liu ,  Jia-Tsrong Jan ,  Yih-Shyun E. Cheng ,  Ting-Jen R. Cheng

IPC: A61K31/351 ,  C07D309/28 ,  A61K47/55 ,  A61K47/48

Abstract: Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

公开(公告)号：US10086054B2

公开(公告)日：2018-10-02

申请号：US14392341

申请日：2014-06-26

Applicant: ACADEMIA SINICA

Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Hong-Yang Chuang ,  Chien-Tai Ren

IPC: C07H15/04 ,  A61K39/00 ,  A61K39/385 ,  A61K31/7028 ,  C07K14/47 ,  A61K49/00 ,  C07H15/10 ,  C07H15/14

Abstract: Described herein are synthetic glycan conjugates, immunogenic compositions thereof, vaccines thereof, and kits thereof. The present invention further provides methods of using the synthetic glycan conjugates, immunogenic compositions, or vaccines thereof to treat and/or prevent and/or diagnose proliferative diseases such as cancer. The provided glycan conjugate comprises a carrier and a glycan moiety of Formula (I-i) or Formula (I-ii): (structurally represented).

公开(公告)号：US10005847B2

公开(公告)日：2018-06-26

申请号：US14723181

申请日：2015-05-27

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu

IPC: C07K16/32 ,  C07K16/40 ,  A61K31/517 ,  A61K39/395 ,  C07K16/28 ,  C12P21/00

CPC classification number: C07K16/40 ,  A61K31/517 ,  A61K39/3955 ,  C07K16/283 ,  C07K16/32 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/40 ,  C07K2317/41 ,  C07K2317/732 ,  C07K2317/92 ,  C12P21/005 ,  C12Y302/01 ,  C12Y302/01051

Abstract: The present disclosure relates to a novel class of anti-HER2 monoclonal antibodies comprising a homogeneous population of anti-HER2 IgG molecules having the same N-glycan on each of Fc. The antibodies of the invention can be produced from anti-HER2 monoclonal antibodies by Fc glycoengineering. Importantly, the antibodies of the invention have improved therapeutic values with increased ADCC activity and increased Fc receptor binding affinity compared to the corresponding monoclonal antibodies that have not been glycoengineered.

公开(公告)号：US09982041B2

公开(公告)日：2018-05-29

申请号：US14599174

申请日：2015-01-16

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Tsui-Ling Hsu ,  Yi-Wei Lou ,  Chih-Wei Lin ,  Shih-Chi Yeh ,  Chung-Yi Wu ,  Han-Chung Wu

IPC: C07K16/18 ,  G01N33/574 ,  C07K16/30 ,  A61K39/00

CPC classification number: C07K16/18 ,  A61K2039/505 ,  C07K16/3053 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/734 ,  C07K2317/92 ,  G01N33/57407 ,  G01N33/57492 ,  G01N2800/52

Abstract: Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to SSEA-4 are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cell surfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as those in brain, lung, breast, mouse, esophagus, stomach, liver, bile duct, pancreas, colon, kidney, cervix, ovary, and/or prostate cancer.

公开(公告)号：US09914956B2

公开(公告)日：2018-03-13

申请号：US14422310

申请日：2013-08-16

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Yih-Shyun E. Cheng ,  Charng-Sheng Tsai

IPC: C12Q1/70 ,  C12Q1/40 ,  C12N9/96 ,  C08B37/00 ,  C12Q1/34 ,  C12Q1/04 ,  C07H13/04 ,  C07H13/12 ,  C07H5/00 ,  C12N9/24

CPC classification number: C12Q1/40 ,  C07H5/00 ,  C07H13/04 ,  C07H13/12 ,  C12N9/2402 ,  C12Q1/04 ,  C12Q1/34 ,  C12Q1/70 ,  C12Y302/01018 ,  G01N2333/11

Abstract: Provided herein are novel irreversible sialidase inhibitors. These compounds can be conjugated with a detectable tagging moiety such as azide-annexed biotin via CuAAC for isolation and identification of sialidases. The provided compounds and the corresponding detectable conjugates are useful for detecting sialidase-containing pathogens and imaging in situ sialidase activities under physiological conditions.