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1. 发明授权

US11434271B2 Method for preparing physiologically active polypeptide complex 有权
公开(公告)号：US11434271B2
公开(公告)日：2022-09-06
申请号：US14356054
申请日：2012-11-02
申请人： HANMI SCIENCE CO., LTD
发明人： Dae Jin Kim , Myung Hyun Jang , Seung Su Kim , Jong Soo Lee , Jae Hyuk Choi , Se Chang Kwon
IPC分类号： C07K14/62 , C07K1/107 , C07K17/08 , A61K47/60
摘要： A method for preparing a conjugate of a physiologically active polypeptide and a non-peptide polymer by linking physiologically active polypeptide with non-peptide polymer through a covalent bond using an organic solvent is provided. A method for preparing a physiologically active polypeptide complex by linking the conjugate with a carrier is provided. The complex shows improved in vivo duration and stability of the physiologically active polypeptide. The method can prepare the conjugate at a lower production cost, and the resulting conjugate shows an extension of in vivo activity at a relatively high level and significantly increase in the blood half-life.

2. 发明授权

US10442848B2 Oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same 有权
公开(公告)号：US10442848B2
公开(公告)日：2019-10-15
申请号：US15675274
申请日：2017-08-11
申请人： HANMI SCIENCE CO., LTD
发明人： Sung Youb Jung , Myung Hyun Jang , Ling Ai Shen , Young Kyung Park , Young Jin Park , Se Chang Kwon
IPC分类号： A61K38/17 , A61K38/22 , A61K38/26 , A61K45/06 , C07K14/575 , C07K14/605 , C07K14/705 , A61P3/04 , A61K38/00
摘要： The present invention relates to a novel peptide showing more excellent activities on a glucagon like peptide-1 receptor and a glucagon receptor than native oxyntomodulin, and a composition for the prevention or treatment of obesity comprising the peptide as an active ingredient. Unlike native oxyntomodulin, the novel peptide of the present invention reduces food intake, suppresses gastric emptying, and facilitates lipolysis with reduced side-effects, and also shows excellent receptor-activating effects. Thus, it can be widely used in the treatment of obesity with safety and efficacy.

3. 发明申请

US20180326083A1 PROTEIN COMPLEX USING AN IMMUNOGLOBULIN FRAGMENT AND METHOD FOR THE PREPARATION THEREOF 审中-公开
公开(公告)号：US20180326083A1
公开(公告)日：2018-11-15
申请号：US16041263
申请日：2018-07-20
申请人： HANMI SCIENCE CO., LTD.
发明人： Young Min KIM , Dae Jin KIM , Sung Min BAE , Chang Ki LIM , Se Chang KWON , Gwan Sun LEE
IPC分类号： A61K47/68 , C07K16/46 , C07K14/61 , C07K14/56 , C07K14/535 , C07K14/505 , C07K19/00
CPC分类号： A61K47/68 , A61K47/6811 , A61K47/6813 , A61K47/6835 , C07K14/505 , C07K14/535 , C07K14/56 , C07K14/61 , C07K16/46 , C07K19/00 , C07K2317/52 , C07K2317/732 , C07K2317/734 , C07K2319/30
摘要： Disclosed are a protein conjugate with improved in vivo duration and stability and the use thereof. The protein conjugate includes a physiologically active polypeptide, a non-peptide polymer and an immunoglobulin Fc fragment. Since the three components are covalently linked, the protein conjugate has extended in vivo duration and enhanced stability for the physiologically active polypeptide. The protein conjugate maintains the in vivo activity at relatively high levels and remarkably increases the serum half-life for the physiologically active polypeptide, with less risk of inducing undesirable immune responses. Thus, the protein conjugate is useful for developing long-acting formulations of various polypeptide drugs.

4. 发明授权

US09981017B2 Insulin conjugate using an immunoglobulin fragment 有权
公开(公告)号：US09981017B2
公开(公告)日：2018-05-29
申请号：US15286871
申请日：2016-10-06
申请人： HANMI SCIENCE CO., LTD.
发明人： Dae Hae Song , Jae Hee Hee Shin , Young Jin Park , Dae Seong Im , Sung Min Bae , Se Chang Kwon
IPC分类号： A61K39/00 , A61K38/28 , A61K47/48
CPC分类号： A61K38/28 , A61K47/60 , A61K47/68 , A61K47/6883
摘要： An insulin conjugate having improved in vivo duration and stability is provided. The conjugate is prepared by covalently linking insulin with an immunoglobulin Fc region via a non-peptidyl polymer, a long-acting formulation comprising the same, and a preparation method thereof. The insulin conjugate of the present invention maintains in vivo activity of the peptide at a relatively high level and remarkably increases the serum half-life thereof, thereby greatly improving drug compliance upon insulin treatment.

5. 发明授权

US09750820B2 IgG Fc fragment for a drug carrier and method for the preparation thereof 有权
公开(公告)号：US09750820B2
公开(公告)日：2017-09-05
申请号：US14327120
申请日：2014-07-09
申请人： HANMI SCIENCE CO., LTD.
发明人： Sung Youb Jung , Jin Sun Kim , Geun Hee Yang , Se Chang Kwon , Gwan Sun Lee
IPC分类号： C07K19/00 , C07K14/50 , C07K14/61 , A61K47/48 , C07K14/505 , C07K14/535 , C07K14/56 , C07K16/46
CPC分类号： A61K47/68 , A61K47/6811 , A61K47/6813 , A61K47/6835 , C07K14/505 , C07K14/535 , C07K14/56 , C07K14/61 , C07K16/46 , C07K19/00 , C07K2317/52 , C07K2317/732 , C07K2317/734 , C07K2319/30
摘要： Disclosed is an IgG Fc fragment useful as a drug carrier. A recombinant vector expressing the IgG Fc fragment, a transformant transformed with the recombinant vector, and a method of preparing an IgG Fc fragment are disclosed. When conjugated to a certain drug, the IgG Fc fragment improves the in vivo duration of action of the drug and minimizes the in vivo activity reduction of the drug.

6. 发明申请

US20160051696A1 POLYPEPTIDE COMPLEX COMPRISING NON-PEPTIDYL POLYMER HAVING THREE FUNCTIONAL ENDS 审中-公开
标题翻译：包含具有三个功能末端的非肽聚合物的多肽复合物
公开(公告)号：US20160051696A1
公开(公告)日：2016-02-25
申请号：US14873321
申请日：2015-10-02
申请人： HANMI SCIENCE CO., LTD.
发明人： Dae Hae SONG , Jae Hee SHIN , Mi Ji LEE , Sung Hee HONG , Se Chang KWON , Gwan Sun LEE
IPC分类号： A61K47/48
CPC分类号： A61K47/48715 , A61K47/60 , A61K47/6811 , A61K47/6889 , C07K14/59 , C07K19/00 , C07K2319/31
摘要： Disclosed is a protein complex, comprising a physiologically active polypeptide, a dimeric protein and a non-peptidyl polymer having three functional ends (3-arm), with the linkage of both the physiologically active polypeptide and the dimeric protein to the 3-arm non-peptidyl polymer via respective covalent bonds. The protein complex guarantees the long acting activity and biostability of a physiologically active polypeptide. Having the ability to maintain the bioactivity of physiologically active polypeptides or peptides highly and to significantly improve the serum half life of the polypeptides or peptides, the protein complex can be applied to the development of sustained release formulations of various physiologically active polypeptide drugs. Also, it utilizes raw materials including the physiologically active polypeptides without significant loss, thereby increasing the production yield. Further, it can be easily purified.
摘要翻译：公开了一种蛋白质复合物，其包含生理活性多肽，二聚体蛋白质和具有三个功能性末端（3-臂）的非肽基聚合物，其具有生理活性多肽和二聚体蛋白质与3-臂非 - - 肽基聚合物。蛋白质复合物保证生理活性多肽的长效和生物稳定性。具有维持生理活性多肽或肽的生物活性以及显着改善多肽或肽的血清半衰期的能力，蛋白质复合物可用于开发各种生理活性多肽药物的持续释放制剂。此外，它利用包括生理活性多肽的原料，而不会显着损失，从而提高产量。此外，它可以容易地纯化。

7. 发明申请

US20150299247A1 AN IMPROVED PROCESS FOR PREPARATION OF PHYSIOLOGICALLY ACTIVE POLYPEPTIDE COMPLEX 审中-公开
标题翻译：用于制备生理活性多肽复合物的改进方法
公开(公告)号：US20150299247A1
公开(公告)日：2015-10-22
申请号：US14383334
申请日：2013-03-08
申请人： HANMI SCIENCE CO., LTD.
发明人： Myung Hyun JANG , Min Young KIM , Jong-soo LEE , Dae Jin KIM , Sung Min BAE , Se Chang KWON
IPC分类号： C07K1/107 , A61K47/48 , A61K38/28
CPC分类号： C07K1/1077 , A61K38/28 , A61K47/60 , A61K47/68 , A61K47/6883 , C07K1/1075 , C07K2319/30
摘要： Disclosed is a method for the preparation of a complex in which a physiologically active polypeptide is covalently bonded to an immunoglobulin constant region via a non-peptidyl linker. The method is characterized by the employment of a reducing agent, by which conventional problems of low production yield and modification of the polypeptide can be overcome. The physiologically active polypeptide-non-peptidyl polymer-immunoglobulin constant region complex can be produced with high purity and yield as well as at low cost. Thus, the method is industrially useful. Moreover, by exhibiting a prolonged action profile, the physiologically active polypeptide-non-peptidyl polymer-immunoglobulin constant region complex can be effectively used for developing long-acting formulations of physiologically active polypeptides which have improved drug compliance.
摘要翻译：公开了一种制备其中生理活性多肽通过非肽基连接体与免疫球蛋白恒定区共价结合的复合物的方法。该方法的特征在于使用还原剂，通过该还原剂可以克服生产产率低和多肽修饰的常规问题。生理活性多肽 - 非肽基聚合物 - 免疫球蛋白恒定区复合物可以以高纯度和产率以及低成本生产。因此，该方法在工业上是有用的。此外，通过显示延长的作用特征，生理活性多肽 - 非肽基聚合物 - 免疫球蛋白恒定区复合物可以有效地用于开发具有改善的药物依从性的生理活性多肽的长效制剂。

8. 发明申请

US20150056223A1 PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE 审中-公开
标题翻译：用于预防或治疗非酒精性脂肪肝疾病的药物组合物
公开(公告)号：US20150056223A1
公开(公告)日：2015-02-26
申请号：US14383954
申请日：2013-03-08
申请人： HANMI SCIENCE CO., LTD
发明人： Se Young Lim , Sung Hee Park , Ryoung Ae Shin , In Young Choi , Se Chang Kwon
IPC分类号： A61K47/48 , C07K14/605 , C07K16/18 , A61K38/26 , A61K39/395
CPC分类号： A61K47/48215 , A61K38/26 , A61K39/3955 , A61K47/60 , A61K47/6883 , A61K2039/505 , C07K14/605 , C07K16/18 , C07K2317/41 , C07K2317/75 , C07K2317/94
摘要： The present invention relates to a pharmaceutical composition for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), including a conjugate prepared by covalently linking an insulinotropic peptide, a non-peptidyl polymer and an immunoglobulin Fc region. The composition of the present invention maintains the in-vivo activity of the peptide at a relatively high level, and remarkably increases the blood half-life, thereby preventing triglyceride accumulation which is a typical feature of non-alcoholic fatty liver disease. Ultimately, it can be desirably employed for the prevention and treatment of non-alcoholic fatty liver disease.
摘要翻译：本发明涉及用于预防和治疗非酒精性脂肪肝疾病（NAFLD）的药物组合物，其包括通过共价连接促胰岛素肽，非肽基聚合物和免疫球蛋白Fc区而制备的缀合物。本发明的组合物将肽的体内活性维持在较高的水平，显着增加血液半衰期，从而防止作为非酒精性脂肪性肝病的典型特征的甘油三酯积聚。最终，可以理想地用于预防和治疗非酒精性脂肪性肝病。

9. 发明申请

US20150050692A1 METHOD OF CULTURING E. COLI CELLS FOR HIGH DENSITY 有权
标题翻译：培养高密度脂蛋白细胞的方法
公开(公告)号：US20150050692A1
公开(公告)日：2015-02-19
申请号：US14384015
申请日：2013-03-12
申请人： HANMI SCIENCE CO., LTD.
发明人： Yong Ho Huh , Euh Lim Oh , Sung Youb Jung , Se Chang Kwon
IPC分类号： C12P21/00
CPC分类号： C12P21/00 , C12N1/20
摘要： Disclosed is a method of culturing E. coli cells for high density, comprising a cell growth step and an expression induction step by which a maximum of cell mass can be obtained with the concomitant maximum expression of a recombinant protein. E. coli transformed to produce a recombinant protein of interest can be grown at a high concentration using the culturing method of the present invention. Therefore, the method increases the productivity of cells as well as the production yield of the recombinant protein, and can be widely applied to the effective production of recombinant proteins.
摘要翻译：公开了一种高密度培养大肠杆菌细胞的方法，包括细胞生长步骤和表达诱导步骤，通过该步骤可以通过重组蛋白的伴随最大表达获得最大的细胞团数。利用本发明的培养方法可以转化生产重组蛋白质的大肠杆菌以高浓度生长。因此，该方法提高了细胞的生产力以及重组蛋白的产量，可广泛应用于重组蛋白的有效生产。

10. 发明申请

US20140275534A1 METHOD FOR PREPARING 1-(4-(4-(3,4-DICHLORO-2-FLUOROPHENYLAMINO)-7-METHOXYQUINAZOLIN-6-YLOXY) PIPERIDIN-1-YL)-PROP-2-EN-1-ONE HYDROCHLORIDE AND INTERMEDIATES USED THEREIN 有权
标题翻译：制备1-（4-（4-（3,4-二氯-2-氟亚氨基）-7-甲氧基喹啉-6-基）哌嗪-1-基）丙-2-烯-1-酮氯化物和中间体的方法使用者
公开(公告)号：US20140275534A1
公开(公告)日：2014-09-18
申请号：US14349887
申请日：2012-10-05
申请人： HANMI SCIENCE CO., LTD.
发明人： Keuk Chan Bang , Young Ho Moon , Young Kil Chang
IPC分类号： C07D401/12 , C07D239/94
CPC分类号： C07D239/94 , A61K31/517 , C07D401/12
摘要： The present invention relates to an improved method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-prop-2-en-1-one hydrochloride, which selectively and effectively inhibits the growth of cancer cells induced by over-expression of an epidermal growth factor receptor (EGFR) and prevents the development of drug resistance caused by mutation of a tyrosine kinase, and intermediates used therein.
摘要翻译：本发明涉及一种制备1-（4-（4-（3,4-二氯-2-氟苯基氨基）-7-甲氧基喹唑啉-6-基氧基）哌啶-1-基） - 丙-2-烯 -1-盐酸盐，其选择性和有效地抑制由表皮生长因子受体（EGFR）的过表达诱导的癌细胞的生长，并且防止由酪氨酸激酶的突变引起的耐药性的发展及其中使用的中间体。

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