公开(公告)号：US20180237541A1

公开(公告)日：2018-08-23

申请号：US15944505

申请日：2018-04-03

Applicant: AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION

Inventor： Yong Sung KIM ,  Hye Ji CHOI ,  Eun Sil SUNG

IPC: C07K16/46 ,  C07K16/28 ,  C07K16/00

CPC classification number: C07K16/46 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/2878 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/526 ,  C07K2317/622 ,  C07K2319/30

Abstract: Disclosed are a CH3 domain variant pair of an antibody, a method for preparing same, and a use thereof. A mutation is induced in the CH3 domain so as to improve a yield of forming a heterodimer heavy chain constant region of an antibody. The CH3 domain heterodimer forms a heterodimer heavy chain constant region with a high efficiency of 90 to 95% or more and also has outstanding heat stability. A heterodimer heavy chain constant region including the CH3 domain heterodimer can construct a bispecific monoclonal antibody which simultaneously recognizes two kinds of antigens. The CH3 domain heterodimer and the bispecific antibody or fusion protein of an antibody constant region comprising same can be usefully applied to the treatment or prevention of a disease associated with a target antigen or a target protein.

公开(公告)号：US20160130315A1

公开(公告)日：2016-05-12

申请号：US14893317

申请日：2014-05-22

Applicant: AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION

Inventor： Yong Sung KIM ,  Tae Hwan SHIN ,  Yae Jin KIM ,  Eun Sil SUNG

IPC: C07K14/47

CPC classification number: C07K14/4703 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/30

Abstract: A tumor tissue-penetrating peptide specifically binding to neuropilin, or a fusion protein, a small molecule drug, a nanoparticle, or a liposome having the peptide fused therein is provided, as well as a method for preparing the same and a pharmaceutical composition comprising the same for treating, diagnosing, or preventing cancer or angiogenesis-related diseases. The tumor tissue-penetrating peptide is fused to the C-terminus of an anticancer antibody heavy-chain constant region (Fc) and the fused antibody specifically binds to neuropilin, and specifically accumulates in tumor tissue, widens intercellular gaps between tumor vascular endothelial cells, promotes extravasation, increases infiltration within tumor tissue, and shows a remarkably increased in vivo tumor-suppressing activity. Furthermore, the tumor tissue-penetrating peptide is fused into a fusion protein and inhibits the angiogenic function of neuropilin coreceptors resulting from targeting of neuropilin, and is expected to have an alleviating effect on angiogenesis-related diseases.

Abstract translation: 提供了特异性结合神经纤维素的蛋白质组织穿透肽，或融合蛋白质，小分子药物，纳米颗粒或其中融合肽的脂质体，以及其制备方法和药物组合物，其包含 相同的治疗，诊断或预防癌症或血管生成相关疾病。 肿瘤组织穿透肽与抗癌抗体重链恒定区（Fc）的C末端融合，融合抗体特异性结合神经纤维蛋白，特异性地积聚在肿瘤组织中，扩大肿瘤血管内皮细胞之间的细胞间隙， 促进外渗，增加肿瘤组织内的浸润，并显示体内肿瘤抑制活性显着增加。 此外，将肿瘤组织穿透肽融合成融合蛋白，并抑制由神经丝氨酸靶向产生的神经丝氨酸共受体的血管生成功能，并且预期对血管发生相关疾病具有缓解作用。

公开(公告)号：US20150307628A1

公开(公告)日：2015-10-29

申请号：US14647480

申请日：2013-11-27

Applicant: AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION

Inventor： Yong Sung KIM ,  Hye Ji CHOI ,  Eun Sil SUNG

IPC: C07K16/46

CPC classification number: C07K16/46 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/2878 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/526 ,  C07K2317/622 ,  C07K2319/30

Abstract: Disclosed are a CH3 domain variant pair of an antibody, a method for preparing same, and a use thereof. A mutation is induced in the CH3 domain so as to improve a yield of forming a heterodimer heavy chain constant region of an antibody. The CH3 domain heterodimer forms a heterodimer heavy chain constant region with a high efficiency of 90 to 95% or more and also has outstanding heat stability. A heterodimer heavy chain constant region including the CH3 domain heterodimer can construct a bispecific monoclonal antibody which simultaneously recognizes two kinds of antigens. The CH3 domain heterodimer and the bispecific antibody or fusion protein of an antibody constant region comprising same can be usefully applied to the treatment or prevention of a disease associated with a target antigen or a target protein.

Abstract translation: 公开了抗体的CH3结构域变体对，其制备方法及其用途。 在CH3结构域中诱导突变，从而提高形成抗体的异源二聚体重链恒定区的产量。 CH3结构域异二聚体形成高效率为90〜95％以上的异源二聚体重链恒定区，热稳定性优异。 包含CH3结构域异源二聚体的异二聚体重链恒定区可以构建同时识别两种抗原的双特异性单克隆抗体。 包含其的抗体恒定区的CH3结构域异二聚体和双特异性抗体或融合蛋白可有效地应用于治疗或预防与靶抗原或靶蛋白相关的疾病。