Hanmi Pharm. Co., Ltd.

Hanmi Science Co., Ltd.

Other

Korea Institute of Industrial Technology

Hanmi Holdings Co., Ltd.

Sung Min Bae

Se Chang Kwon

Hyung Kyu Lim

Dae Jin Kim

Hyun Uk Kim

Sung H Hong

Jong Soo Lee

Sang Yun Kim

Dae Seong Im

Young Jin Park

Chang Ki Lim

Dae Hae Song

Sung Youb Jung

Gwan Sun Lee

Myung Hyun Jang

Min Young Kim

Jae Min Lee

Young Min Kim

Young Hoon Kim

Ho Taek Im

Jae Hee Shin

Byung Sun Lee

Sung Hee Hong

Jong Min Lee

Hwa Peoung Rim

Sung Hee Park

Chul Young Kim

Jung Kuk Kim

Mi Kyoung Lee

Mi Ji Lee

Hee Moon Kyung

Hye Jin Lee

Jae Hee Hee Shin

Nak Kyu Lee

Jung Han Song

Jeanho Park

Hyoung Wook Lee

Hyo Sang Park

Jong-soo Lee

Cha Soon Kim

Ki Doo Choi

A sustained release preparation of a human growth hormone conjugate is disclosed. The sustained release preparation contains a sustained release human growth hormone (hGH) conjugate resulting from conjugation between an immunoglobulin Fc region and a human growth hormone (hGH) as an active peptide; a buffer solution; a nonionic surfactant; and a sugar alcohol. A freeze dried preparation and a liquid preparation including the sustained release human growth hormone conjugate, a production method for the freeze dried preparation, a method of reconstituting the freeze dried preparation, and a kit containing the freeze dried preparation and a reconstituting solution are also disclosed.

Lyophilized formulation of long-acting human growth hormone immunoglobulin conjugate

Polyethylene glycol derivatives of the following formula I and uses thereof are disclosed. A method for manufacturing the polyethylene glycol derivatives is also disclosed.

Polyethylene glycol derivative and use thereof

The present invention relates to polyethylene glycol derivatives and use thereof.

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex prepared by the present invention may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

Protein complex by use of a specific site of an immunoglobulin fragment for linkage

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

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 a novel glucagon derivative peptide, and a composition for preventing or treating hypoglycemia containing the novel glucagon derivative peptide as an active ingredient. The glucagon derivative according to the present invention has improved physical properties due to the change in isoelectric point (pI) while being capable of maintaining an activity on glucagon receptors, and thus can improve patient compliance when used as a hypoglycemic agent, and is also suitable for administration in combination with other anti-obesity agents. Accordingly, the glucagon derivative according to the present invention can be effectively used for the prevention and treatment of hypoglycemia and obesity.

Glucagon derivatives with improved stability

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

The present invention relates to a sustained type human growth hormone conjugate preparation comprising: a sustained type human growth hormone (hGH) conjugate resulting from conjugation between the immunoglobulin Fc region and a human growth hormone (hGH) constituting a bioactive peptide; a buffer solution; a nonionic surfactant; and a sugar alcohol. More specifically, the present invention relates to a sustained type human growth hormone conjugate freeze dried preparation and liquid preparation, to a production method for the freeze dried preparation, to a method of reconstituting the freeze dried preparation, and to a kit comprising the freeze dried preparation and a reconstituting solution.

Liquid formulation of long-acting human growth hormone immunoglobulin conjugate

The present invention relates to a liquid formulation of long-acting insulin conjugate, comprising a pharmaceutically effective amount of a long-acting insulin conjugate, wherein a physiologically active peptide, which is an insulin, is linked to an immunoglobulin Fc region; and an albumin-free stabilizer, wherein the stabilizer comprises a buffer, a sugar alcohol, a non-ionic surfactant, and an isotonic agent, and a method for preparing the formulation. For preventing microbial contamination in multiple uses, a preservative can be added to the formulation. The liquid formulation of the present invention does not comprise a human serum albumin and potentially hazardous factors to body, and thus it has excellent storage stability for insulin conjugate without a risk of viral infection.

Liquid formulation of long-acting insulin conjugate

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.

Insulin conjugate using an immunoglobulin fragment

Provided is a long-acting pharmaceutical composition containing a conjugate comprising a physiologically active polypeptide linked to an immunoglobulin Fc fragment, wherein the composition contains a monomeric conjugate comprising one molecule of the physiologically active polypeptide linked to a single immunoglobulin Fc fragment, and optionally contains a multimeric conjugate comprising two or more molecules of the same physiologically active polypeptide linked to a single immunoglobulin Fc fragment, provided that the molar ratio of the monomeric conjugate to the multimeric conjugate in the composition is at least 19; a physiologically active polypeptide monomer-immunoglobulin Fc fragment conjugate that comprises a physiologically active polypeptide monomer linked via a non-peptidyl linker to an immunoglobulin Fc fragment, wherein the physiologically active polypeptide is linked via the non-peptidyl linker to the immunoglobulin Fc fragment in a monomeric form.

Conjugate of biologically active polypeptide monomer and immunoglobulin Fc fragment with reduced receptor-mediated clearance, and the method for preparing the same

Provided are a liquid formulation of long-acting insulinotropic peptide conjugate, containing a pharmaceutically effective amount of long-acting insulinotropic peptide conjugate consisting of a physiologically active peptide, insulinotropic peptide, and an immunoglobulin Fc region; and an albumin-free stabilizer, wherein the stabilizer comprises a buffer, a sugar alcohol, and a non-ionic surfactant, and a method for preparing the formulation. For the purpose of preventing microbial contamination, a preservative may be added. The liquid formulation of the present invention is free of human serum albumin and other potentially hazardous factors to body, having no risk of viral contamination, and thus can provide excellent storage stability for insulinotropic peptide conjugates at high concentration.

Liquid formulation of long acting insulinotropic peptide conjugate

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

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.

Protein complex using an immunoglobulin fragment and method for the preparation thereof

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Seongnam-si, South Korea

Sung Min Bae