Complex comprising both heparin binding proteins and heparin-hydroxyalkyl starch conjugates

A technology for complexes and conjugates, applied in the field of preparing the complexes, capable of solving problems such as incomplete, uneven connection, inactivation, etc.

Inactive Publication Date: 2011-06-01
OCTAPHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, linking of polymers can lead to decreased drug activity
Additionally, certain reagents used to conjugate polymers to proteins are not reactive enough, thus requiring long reaction times during which denaturation and / or inactivation of the protein can occur
Also, incomplete or inhomogeneous linkage leads to the formation of a mixed population of compounds with different properties

Method used

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  • Complex comprising both heparin binding proteins and heparin-hydroxyalkyl starch conjugates
  • Complex comprising both heparin binding proteins and heparin-hydroxyalkyl starch conjugates
  • Complex comprising both heparin binding proteins and heparin-hydroxyalkyl starch conjugates

Examples

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Embodiment 1

[0183] Example 1: Synthetic chemistry: HES-heparanoid-conjugates

[0184] One approach to prolonging the in vivo half-life of recombinant Factor VIII is based on hydroxyethyl starch as a macromolecular carrier non-covalently attached via selective binding sites on Factor VIII. For such non-covalently linked heparins, derivatives or mimetics thereof can be used as binding molecules for Factor VIII. HES binds to these heparanoids to form large complexes that cover and protect parts of the protein surface.

[0185] The proof of principle was evaluated by a factor VIII binding study performed by surface plasmon resonance followed by a large-scale in vivo study using a covalent conjugate of heparinoid and hydroxyethyl starch (1:1) . figure 2 The three-dimensional structure of Factor VIII in a complex containing heparan-HES (1:1) conjugate is shown.

[0186] To obtain this 1:1 conjugate, both heparin and HES were chemically modified at only one position with a complementary fu...

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Abstract

A complex comprises at least one target protein and at least one binding molecule having a binding affinity for said target protein, wherein said molecule having a binding affinity is covalently or non-covalently bound to at least one water-soluble polymer.

Description

technical field [0001] The present invention relates to complexes of target proteins, binding molecules and polymers. The invention further discloses the method for preparing the compound and the application of the compound. Background technique [0002] The use of polypeptides, such as proteins, for therapeutic purposes has expanded in recent years, largely due to advances in knowledge of the molecular biological principles underlying many diseases, and the availability of improved recombinant expression and drug delivery systems for human polypeptides. Peptide therapy is mainly used for diseases caused by a certain natural polypeptide defect or deletion in the patient's body, especially for diseases caused by genetic defects. [0003] For example, hemophilia is a disease caused by a deficiency of a certain plasma protein. Hemophiliacs suffer from bleeding disorders caused by dysfunction of the protein components of the coagulation cascade. Two types of hemophilia can be...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61P7/00
CPCA61K47/48176A61K47/48215A61K47/4823A61K47/60A61K47/58A61K47/61A61P7/00A61P7/04A61K47/50A61K38/17A61K38/19
Inventor 乌多·哈伯尔汉斯-格奥尔格·弗兰克安迪·波特根斯马克·埃姆跟布洛赫安德烈亚斯·里巴卡卡罗拉·施罗德克里斯托夫·卡尼克特奥拉夫·沃尔特
Owner OCTAPHARMA
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