公开(公告)号：US20150344544A1

公开(公告)日：2015-12-03

申请号：US14723297

申请日：2015-05-27

Applicant: Academia Sinica

Inventor： Chi-Huey WONG ,  Chung-Yi Wu ,  Che Ma

IPC: C07K16/00 ,  C07K16/28 ,  C07K16/30 ,  C07K16/24 ,  C07K16/10 ,  A61K39/42 ,  A61K39/395 ,  A61K45/06 ,  C07K16/32

CPC classification number: C12P19/14 ,  A61K39/3955 ,  A61K39/42 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/1018 ,  C07K16/18 ,  C07K16/241 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/32 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C12N9/24 ,  C12Y302/01 ,  C12Y302/01051 ,  Y02A50/412 ,  Y02A50/466

Abstract: The present disclosure relates to glycoproteins, particularly monoclonal antibodies, comprising a glycoengineered Fc region, wherein said Fc region comprises an optimized N-glycan having the structure of Sia2(α2-6)Gal2GlcNAc2Man3GlcNAc2. The glycoengineered Fc region binds FcγRIIA or FcγRIIIA with a greater affinity, relative to comparable monoclonal antibodies comprising the wild-type Fc region. The monoclonal antibodies of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, autoimmune, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Abstract translation: 本公开涉及包含糖工程化Fc区的糖蛋白，特别是单克隆抗体，其中所述Fc区包含具有Sia2（α2-6）Gal2GlcNAc2Man3GlcNAc2结构的优化的N-聚糖。 相对于包含野生型Fc区域的可比较的单克隆抗体，糖工程化Fc区域以更高的亲和力结合FcγRIIA或FcγRIIIA。 本发明的单克隆抗体特别可用于预防，治疗或改善与需要由FcγR介导的效应细胞功能（例如，ADCC）增强的功效的疾病，病症或感染相关的一种或多种症状，例如， 癌症，自身免疫性，感染性疾病，以及提高其作用由ADCC介导的治疗性抗体的治疗功效。

公开(公告)号：US12085340B2

公开(公告)日：2024-09-10

申请号：US17933832

申请日：2022-09-20

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu

IPC: F27D1/12 ,  A61K39/12 ,  A61K49/00 ,  F27B3/14 ,  F27B3/24 ,  F27D11/08 ,  F27D9/00

CPC classification number: F27D1/12 ,  A61K39/12 ,  A61K49/00 ,  F27B3/14 ,  F27B3/24 ,  F27D11/08 ,  F27D2009/0021

Abstract: Immunogenic compositions comprising hemagglutinin (HA) variants and/or neuraminidase (NA) variants, which may be contained in an influenza A virus, and uses thereof for eliciting immune responses against influenza A virus.

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.

公开(公告)号：US10342858B2

公开(公告)日：2019-07-09

申请号：US14832993

申请日：2015-08-21

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu

IPC: C07H5/02 ,  C07H5/04 ,  C07H5/06 ,  A61K39/00 ,  C07H15/04 ,  C07H15/26 ,  C07K16/30 ,  C07K16/44 ,  C08B37/00 ,  A61K31/715 ,  A61K31/7028

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.

公开(公告)号：US10307470B2

公开(公告)日：2019-06-04

申请号：US14906663

申请日：2014-07-26

Applicant: ACADEMIA SINICA ,  Chi-Huey Wong ,  Chung-Yi Wu ,  Hsien-Yeh Hsu ,  Shih-Fen Liao ,  Chi-Hui Liang

Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Hsien-Yeh Hsu ,  Shih-Fen Liao ,  Chi-Hui Liang

IPC: A61K39/00 ,  A61K36/074

Abstract: Immunogenic compositions, cancer vaccines and methods for treating cancer comprising FMS, the fucose-enriched polysaccharide fraction from Reishi F3, are provided. Compositions comprise fucose-enriched Reishi polysaccharide fraction (FMS) MW=˜35 kDa, wherein the FMS is isolated by size-exclusion chromatography from Reishi F3, and the FMS comprises polysaccharides having primarily a backbone selected from 1,4-mannan and 1,6-α-galactan, wherein the backbone is linked to a terminal fucose-containing side-chain Immunogenic compositions comprising glycolipid adjuvants are provided. Antibodies generated by immunogenic compositions disclosed herein bind cancer cells comprising antigens Globo H, Globo H, Gb3, Gb4, Gb5 (SSEA-3) and SSEA-4 on the cell surface.

公开(公告)号：US10118969B2

公开(公告)日：2018-11-06

申请号：US15011544

申请日：2016-01-30

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Che Ma ,  Han-Chung Wu

IPC: C12N9/24 ,  C07K16/30 ,  C07K16/28 ,  A61K45/06 ,  C07K16/10 ,  C07K16/32 ,  C07K16/18 ,  C12P21/00

Abstract: The present disclosure relates to compositions and methods of use comprising antibodies or binding fragments thereof further comprising universal Fc glycoforms.

公开(公告)号：US09603913B2

公开(公告)日：2017-03-28

申请号：US14675838

申请日：2015-04-01

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Alice L. Yu ,  John Yu

IPC: A61K39/00 ,  C12N15/113

CPC classification number: A61K39/0011 ,  A61K2039/55511 ,  A61K2039/6037 ,  A61K2039/6081 ,  A61K2039/627 ,  C12N15/1137 ,  C12N2310/14

Abstract: An immunogenic composition containing a glycan conjugate including a carrier protein, and a glycan including Globo H, an immunogenic fragment thereof, or stage-specific embryonic antigen-4 (SSEA-4), wherein the glycan is conjugated with the carrier protein through a linker.

公开(公告)号：US20160274121A1

公开(公告)日：2016-09-22

申请号：US15005930

申请日：2016-01-25

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Sarah K.C. Cheung ,  Po-Kai Chuang ,  Tsui-Ling Hsu

IPC: G01N33/574 ,  C07K16/30

CPC classification number: G01N33/57492 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/3053 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/622 ,  C07K2317/734 ,  C07K2317/92 ,  G01N33/5073 ,  G01N33/57407 ,  G01N2333/70585 ,  G01N2333/70596 ,  G01N2405/10 ,  G01N2500/04 ,  G01N2500/10 ,  G01N2800/52

Abstract: The present disclosure relates to methods and compositions which can modulate the globoseries 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 globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. 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. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for disgnostic and therapeutic uses.

Abstract translation: 本公开涉及可以调节球形蛋白糖鞘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球形蛋白鞘糖脂SSEA-3 / SSEA-4 / 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酶在球形蛋白合成途径中。 另外，本公开还涉及靶向SSEA-3 / SSEA-4 / GLOBO H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，其引发可用于调节的抗体和/或结合片段产生 全球糖苷脂蛋白合成。 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。 此外，本公开还涉及用于预后和治疗用途的癌症干细胞生物标志物。

公开(公告)号：US20150344585A1

公开(公告)日：2015-12-03

申请号：US14723020

申请日：2015-05-27

Applicant: Academia Sinica

Inventor： Chi-Huey WONG ,  Chung-Yi Wu ,  Ming-Hung Tsai

IPC: C07K16/28 ,  C12P21/00

CPC classification number: C07K16/2887 ,  A61K2039/505 ,  A61K2039/54 ,  A61K2039/545 ,  C07K16/283 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/41 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C12P21/005 ,  C12Y302/01 ,  C12Y302/01051

Abstract: The present disclosure relates to a novel class of anti-CD20 monoclonal antibodies comprising a homogeneous population of anti-CD20 IgG molecules having the same N-glycan on each of Fc. The antibodies of the invention can be produced from anti-CD20 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.

Abstract translation: 本公开涉及一类新的抗CD20单克隆抗体，其包含在Fc上具有相同N-聚糖的均匀的抗CD20IgG分子群。 本发明的抗体可以通过Fc糖工程从抗CD20单克隆抗体产生。 重要的是，本发明的抗体具有改善的治疗价值，与尚未糖基化的相应单克隆抗体相比，具有增加的ADCC活性和增加的Fc受体结合亲和力。

公开(公告)号：US20150344551A1

公开(公告)日：2015-12-03

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

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.

Abstract translation: 本文公开了包含与SSEA-4结合的抗体或其抗原结合片段的药物组合物及其使用方法。 使用的方法包括但不限于癌症治疗和诊断。 本公开的抗体可以结合某些癌细胞表面。 本文公开的抗体的示例性靶标可以包括癌，例如脑，肺，乳腺，小鼠，食管，胃，肝，胆管，胰腺，结肠，肾，子宫颈，卵巢和/或前列腺癌中的那些。