Hanmi Science Co., Ltd.

Hanmi Pharm. Co., Ltd.

Myung Hyun Jang

Jin Young Kim

Se Chang Kwon

Sung Youb Jung

Young Jin Park

Dae Jin Kim

Young Kyung Park

Sung Min Bae

Ling Ai Shen

Hyung Kyu Lim

Sang Yun Kim

Sang Hyun Lee

In Young Choi

Jong Soo Lee

Hyun Uk Kim

Min Young Kim

Jin-Sun Kim

Jae Hyuk Choi

Seung Su Kim

Chang Ki Lim

Sang Youn Hwang

Young Eun Woo

Yong Ho Huh

Sung In Lim

Jong-soo Lee

Sung Hee Hong

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.

Method for preparing physiologically active polypeptide complex

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.

Process for preparation of physiologically active polypeptide complex

The present invention relates to an albumin-free liquid formulation comprising a long-lasting oxyntomodulin conjugate in which an oxyntomodulin peptide comprising a derivative, variant, precursor or fragment of oxyntomodulin is linked to an immunoglobulin Fc region, which can increase the duration of physiological activity of the long-lasting oxyntomodulin conjugate and maintain the in vivo stability thereof for an extended period of time, as compared to native oxyntomodulin, as well as a method for preparing the liquid formulation. The liquid formulation comprises a buffer, a sugar alcohol and a nonionic surfactant and does not contain a human serum albumin and factors that are potentially harmful to the human body, and thus is not susceptible to viral infection. In addition, the oxyntomodulin conjugate of the invention comprises oxyntomodulin linked to an immunoglobulin Fc region, and thus has a large molecular weight, prolonged physiological activity, and excellent storage stability, compared to native oxyntomodulin.

Liquid formulation of long-lasting protein conjugate comprising the oxyntomodulin and an immunoglobulin Fc region

A method for preparing a conjugate by linking a physiologically active polypeptide, a non-peptidyl polymer linker, and an immunoglobulin constant region via a covalent bond are disclosed. The method enables an efficient preparation of a physiologically active polypeptide conjugate, in which a salt is used in a coupling reaction to improve the problem of low production yield during preparation of the physiologically active polypeptide conjugate.

Preparation method for high-yield production of physiologically active polypeptide conjugate

The present invention relates to a composition for preventing or treating hyperlipidemia, fatty liver disease or arteriosclerosis, comprising an oxyntomodulin derivative as an active ingredient. The oxyntomodulin derivative has a high ability to activate GLP-1 receptor and glucagon receptor compared to native oxyntomodulin and has the effects of reducing the blood total cholesterol, low-density cholesterol and triglyceride levels that were increased by high-fat diet, and increasing high-density cholesterol levels and the high-density cholesterol/low-density cholesterol ratio. Thus, the oxyntomodulin derivative can be effectively used for the treatment of hyperlipidemia and related diseases.

Composition for treating hyperlipidemia comprising oxyntomodulin derivative

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.

Oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same

Liquid formulation of long-lasting protein conjugate comprising the oxyntomodulin and an immunoglobulin fragment

The present invention relates to a composition for the prevention or treatment of diabetes comprising a long-acting insulin conjugate and a long-acting insulinotropic peptide conjugate, and a therapeutic method for the treatment of diabetes, and more particularly, concurrent administration of the long-acting insulin conjugate and the long-acting insulinotropic peptide conjugate inhibits weight gain caused by insulin treatment, and vomiting and nausea caused by insulinotropic peptide treatment, and reduces the required dose of insulin, thereby remarkably improving drug compliance. Moreover, each of the long-acting insulin conjugate and the long-acting insulinotropic peptide conjugate of the present invention is prepared by linking insulin or insulinotropic peptide with an immunoglobulin Fc region via a non-peptidyl linker, thereby showing improved in-vivo duration of efficacy and stability.

Composition for treating diabetes comprising long-acting insulin conjugate and long-acting insulinotropic peptide conjugate

Provided are an insulin conjugate having improved insulin receptor binding affinity and increased activity, in which a non-peptidyl polymer and an immunoglobulin Fc region are site-specifically linked to an amino acid residue of the insulin beta chain excluding the N-terminus thereof via a covalent bond, a long-acting formulation including the same, and a preparation method thereof. The insulin conjugate of the present invention is used to provide an insulin formulation which exhibits a remarkably increased in vivo activity of the peptide.

Site-specific insulin conjugate

The present invention relates to a non-peptidyl polymer-insulin multimer comprising two or more of a non-peptidyl polymer-insulin conjugate prepared by linking a non-peptidyl polymer and insulin via a covalent bond, in which the conjugates are complexed with cobalt ion to form a multimer, a method and kit for the preparation of the multimer, a pharmaceutical composition for the prevention or treatment of diabetes comprising the multimer as an active ingredient, and a method for preventing or treating diabetes by administering the composition to a subject.

Non-peptidyl polymer-insulin multimer and method for producing the same

Disclosed are an albumin-free liquid formulation including a long-lasting oxyntomodulin conjugate in which an oxyntomodulin peptide comprising a derivative, variant, precursor or fragment of oxyntomodulin is linked to an immunoglobulin Fc region, which can increase the duration of physiological activity of the long-lasting oxyntomodulin conjugate and maintain the in vivo stability thereof for an extended period of time, as compared to native oxyntomodulin, and a method for preparing the liquid formulation. The liquid formulation contains a buffer, a sugar alcohol and a nonionic surfactant and does not contain a human serum albumin and factors that are potentially harmful to the human body, and thus is not susceptible to viral infection. The oxyntomodulin conjugate contains oxyntomodulin linked to an immunoglobulin Fc region, and thus has a large molecular weight, prolonged physiological activity, and excellent storage stability, compared to native oxyntomodulin.

Liquid formulation of protein conjugate comprising an oxyntomodulin derivative covalently linked to a non-peptidyl polymer to an immunoglobulin FC region

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Seoul, South Korea

Myung Hyun Jang