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    NOVEL GLYCAN CONJUGATES AND METHODS OF USE THEREOF
    52.
    发明申请
    NOVEL GLYCAN CONJUGATES AND METHODS OF USE THEREOF 审中-公开
    新型糖果混合物及其使用方法

    公开(公告)号：US20160213763A1

    公开(公告)日：2016-07-28

    申请号：US14832993

    申请日：2015-08-21

    Applicant: Academia Sinica

    Inventor： Chi-Huey Wong ,  Chung-Yi Wu

    IPC: A61K39/00 ,  C07H7/02 ,  C07H15/04 ,  C07K16/30

    CPC classification number: A61K39/0011 ,  A61K31/7028 ,  A61K31/715 ,  A61K2039/55511 ,  A61K2039/6037 ,  A61K2039/627 ,  C07H5/02 ,  C07H5/04 ,  C07H5/06 ,  C07H15/04 ,  C07H15/26 ,  C07K16/3076 ,  C07K16/44 ,  C08B37/006

    Abstract: The present disclosure is directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA3/SSEA4/GloboH associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globo-series glycosphingolipid synthesis. The present disclosure relates to methods and compositions which can modulate the globo-series glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globo-series glycosphingolipid SSEA3/SSEA4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globo-series synthetic pathway. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions.

    Abstract translation: 本公开涉及针对SSEA3 / SSEA4 / GloboH相关表位（天然和修饰）的疫苗，抗体和/或免疫原性缀合物组合物，其引发可用于调节globo系列鞘糖脂合成的抗体和/或结合片段生产。 本公开涉及可以调节globo系列鞘糖脂合成的方法和组合物。 特别地，本公开涉及可以调节生物合成途径中的globo系列鞘糖脂SSEA3 / SSEA4 / GloboH的合成的糖酵母抑制剂化合物及其组合物和使用方法; 特别是糖酵解抑制剂靶向α-4GalT; β-4GalNAcT-I; 或β-3GalT-V酶在globo系列合成途径中。 此外，本公开还涉及使用本文所述的组合物治疗或检测过度增殖性疾病和/或病症的方法。

    ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY
    53.
    发明申请
    ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY 审中-公开
    增强与抗炎活性相关的抗感染药物

    公开(公告)号：US20130274229A1

    公开(公告)日：2013-10-17

    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: A61K47/48

    CPC classification number: C07D309/28 ,  A61K31/351 ,  A61K47/55

    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.

    Abstract translation: 公开了通过与抗炎剂缀合形成的新型双靶向双功能抗流感药物。 根据本发明的示例性药物包括用于同时抑制的咖啡酸（CA） - 扎尼米韦（ZA）缀合物ZA-7-CA（1），ZA-7-CA-酰胺（7）和ZA-7-Nap（43） 的流感病毒神经氨酸酶和抑制促炎细胞因子。 提供了制备这些增强型抗流感病毒缀合物药物的合成方法。 合成双功能ZA缀合物协同作用以保护由H1N1或H5N1流感病毒致死的小鼠。 ZA-7-CA，ZA-7-CA-酰胺和ZA-7-Nap缀合物的功效远远大于ZA与抗炎剂的组合疗法。

    Coronavirus vaccine
    54.
    发明授权
    Coronavirus vaccine 有权

    公开(公告)号：US12257298B2

    公开(公告)日：2025-03-25

    申请号：US18005573

    申请日：2022-04-12

    Applicant: ACADEMIA SINICA

    Inventor： Che Ma ,  Chi-Huey Wong ,  Han-Yi Huang

    IPC: A61K39/215 ,  A61P31/04 ,  A61K39/00

    Abstract: The present disclosure provides a glycoengineered SARS-CoV-2 spike protein which is capable of eliciting an enhanced immune response relative to a native spike protein of SARS-CoV-2 and its variants. The glycoengineered spike protein exposes the glycosylation sites and at the same time preserves the tertiary structure of the spike protein. The present disclosure therefore provides improved immunogens, vaccines, and methods for better prevention and treatment of the emerging coronavirus infections.

    Methods of using 4(1
    55.
    发明授权
    Methods of using 4(1 有权

    公开(公告)号：US12109207B2

    公开(公告)日：2024-10-08

    申请号：US18184364

    申请日：2023-03-15

    Applicant: Academia Sinica

    Inventor： Rong-Jie Chein ,  Pan-Chyr Yang ,  Chi-Huey Wong ,  Ming-Shiu Lin ,  Ting-Jen Cheng ,  Ting-Hung Rachel Chou

    IPC: A61K31/47 ,  A61K45/06 ,  A61P35/00 ,  C07D215/233

    CPC classification number: A61K31/47 ,  A61K45/06 ,  A61P35/00 ,  C07D215/233 ,  A61K31/47 ,  A61K2300/00

    Abstract: Provided herein are compounds of Formula (I). The disclosure provides new compounds, compositions, and methods for treating, delaying, and/or preventing the adverse effects of proliferative diseases, such as cancers including, for example, lung cancer, breast cancer, ovarian cancer, prostate cancer, head cancer, neck cancer, head and neck cancer, or leukemia (e.g., cancer resistant to treatment by one or more microtubule-targeting agents (e.g., cancer resistant to multiple drugs associated with P-glycoprotein (P-gp) overexpression)). Provided are methods of inhibiting polymerization of a cancer cell microtubule in a subject in need thereof or a cell, tissue, or biological sample, binding β-tubulin, inhibiting microtubule assembly and, inducing apoptosis in a cancer cell resistant to multiple drugs in a tissue, biological sample, or subject. Also provided in the present disclosure are pharmaceutical compositions, kits, and methods of using the compounds for treating any of the target diseases described herein.

    Compounds and methods for treating osteoarthritis
    58.
    发明授权
    Compounds and methods for treating osteoarthritis 有权

    公开(公告)号：US11332490B1

    公开(公告)日：2022-05-17

    申请号：US17182156

    申请日：2021-02-22

    Applicant: Academia Sinica

    Inventor： Shang-Cheng Hung ,  Chi-Huey Wong ,  Ting-Jen Cheng

    IPC: C07H7/02

    Abstract: Disclosed herein are substrates and/or inhibitors of endo-O-sulfatase 1 (Sulf-1). According to some embodiments, the substrates and/or inhibitors of Sulf-1 are compounds of formula (I) or (II), In formula (I) or (II), n is 2 or 3; X is methylene, O, or N; R1 is —SO3M, or —SO2NH2; R2 is C1-6 alkyl or C1-6 alkylamine; and M is a monovalent cation selected from the group consisting of lithium, sodium, potassium, and ammonium. Also encompasses herein are methods of identifying and treating a subject having or suspected of having osteoarthritis. The method includes steps of (a) mixing a urine sample of the subject with 4-methylumbelliferyl sulfate (4-MUS) and a Sulf-1 inhibitor of formula (I) or (II); (b) determining a fluorescence intensity of the mixture of the step (a); and (c) treating the subject with an analgesic, a non-steroidal anti-inflammatory drug (NSAID), or a corticosteroid when the determined fluorescence intensity of the step (b) is smaller than that of a control sample, which is a mixture of the urine sample and 4-MUS.

    Methods for modifying human antibodies by glycan engineering
    59.
    发明授权
    Methods for modifying human antibodies by glycan engineering 有权

    公开(公告)号：US11267870B2

    公开(公告)日：2022-03-08

    申请号：US16150190

    申请日：2018-10-02

    Applicant: Academia Sinica

    Inventor： Chi-Huey Wong ,  Chung-Yi Wu

    IPC: C07K16/00 ,  C12P21/00

    Abstract: Modified Fc regions of antibodies and antibody fragments, both human and humanized, and having enhanced stability and efficacy, are provided. 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.

    Human iNKT cell activation using glycolipids with altered glycosyl groups
    60.
    发明授权
    Human iNKT cell activation using glycolipids with altered glycosyl groups 有权

    公开(公告)号：US10918714B2

    公开(公告)日：2021-02-16

    申请号：US16175504

    申请日：2018-10-30

    Applicant: Academia Sinica

    Inventor： Chi-Huey Wong ,  Alice L. Yu ,  Kun-Hsien Lin ,  Tai-Na Wu

    IPC: A61K39/39 ,  C07H15/18 ,  A61K39/00

    Abstract: Glycosphingolipids (GSLs) bearing α-glucose (α-Glc) that preferentially stimulate human invariant NKT (iNKT) cells are provided. GSLs with α-glucose (α-Glc) that exhibit stronger induction in humans (but weaker in mice) of cytokines and chemokines and expansion and/or activation of immune cells than those with α-galactose (α-Gal) are disclosed. GSLs bearing α-glucose (α-Glc) and derivatives of α-Glc with F at the 4 and/or 6 positions are provided. Methods for iNKT-independent induction of chemokines by the GSL with α-Glc and derivatives thereof are disclosed. Methods for immune stimulation in humans using GSLs with α-Glc and derivatives thereof are provided.

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