Corporation gives high priority to developing highly efficient therapeutics and their precursors, and providing improvement to the current approaches to the production of therapeutic agents.

   As part of the research and production biopharmaceutical complex “Bioran” in Puschino, a pilot facility K1 is to be constructed, the design of which is based on genetic engineering technology in biologics manufacture, for the development and production of bacterial substances for further use in modern drug manufacture.

   The primary research areas include:

  • Production of import-replacing insulin analogs
  • Design of therapeutics using genetic tools
  • Development of monoclonal antibody-based products
  • Production of import-replacing insulin analogs

   The designated laboratory in the pilot facility K1 will permit most challenging genetic manipulations with strains producing biologically active substances. The facility in compliance with GMP will provide the environment for the development of both laboratory and test output products, including insulin analogs and promising innovative products.

   Insulin products are nearly completely funded by the Russian government. The domestic market is dominated by products of foreign manufacturers imported in the country, and import-replacing therapeutics in this sector would be much beneficial for the country budget.

   Since 1996 insulin analogs have been widely used in clinical practice, different from the natural hormone by chemical modifications; i.e., very rapid-acting and long-acting insulins. Home-made insulin analogs are not yet available on the domestic market. Our Corporation is looking at the development and large scale production of home-made insulin analogs in complete cycle.

   Very rapid-acting insulins are human insulin analogs. Endogenous insulin in pancreatic β-cells and molecules of rapid-acting insulin filled in vials are polymerized and are in the form of a hexamer. Following subcutaneous injection hexamers are absorbed slowly, and the concentration peak of insulin after a meal in the blood similar to that of a healthy individual never occurs. The first ultra short-term insulin analog, which is absorbed from the adipose tissue 3-fold faster than native human insulin, was insulin lispro.

   Insulin lispro is a derivative from human insulin modified by reversing two amino acid residues in the insulin molecule (lysine in position 25 and proline in position 29 of the B-chain). This modification prevents the formation of hexamers and permits rapid absorption of the hormone in the blood. Nearly immediately following subcutaneous injection insulin hexamers rapidly break down into monomers and enter the bloodstream.

   Another insulin analog, insulin aspart, was produced by changing the proline residue in position B28 to negatively charged aspartic acid. Like Insulin lispro it also quickly breaks down into monomers after subcutaneous injection.

   In insulin glulisine, the substitution of the aspartic acid residue in human insulin in position В3 for a lysine residue and the lysine residue in position В29 for a glutamic acid residue also allow more rapid absorption. Ultra rapid-acting insulin analogs can be administered before meal initiation or after it.


   Long-acting insulins include insulin glargine, a human insulin analog, produced by using DNA recombinant techniques. It is the first insulin product that has a peakless profile. .

   Insulin glargine has two modifications in its molecule: the substitution of the aspartic acid residue in position 21 in the A-chain for glycine and the addition of two lysine residues to the C-terminal of the B-chain. The insulin is a transparent solution with a рН of 4. Acidic рН stabilizes hexamers and ensures long-term and predictable absorption from the adipose tissue. However, due to the acidic рН of insulin glargine it must not be mixed with rapid-acting insulins with neutral pH. A single injection of insulin glargine can offer a 24-h peakless glycemic control. Most insulin agents reach peak actions when the insulin level is greatest in the blood.. Insulin glargine has a peakless profile of action since it is released in the bloodstream at a relatively constant rate.

   Insulins with prolonged action are available in various pharmaceutical forms, giving a hypoglycemic effect with various duration (from 10 to 36 h). The prolonged action allows for a reduction in daily injections. They are available as suspensions injected only subcutaneously or intramuscularly. In diabetic coma and precomatose states long-acting insulins are not prescribed .

   Insulin detemir is a new soluble analog of basal insulin, showing a specific mode of prolonged action, which manifests itself as more predictable glucose control, lower risks of hypoglycemia and weight gain as compared to NPH insulin. Insulin detemir [LysB29-tertradecanoyl, des. (B30) human insulin] has the deletion of the amino acid threonine in position B30 and addition of a 14-carbon fatty acid (myristic fatty acid) to the lysine in position B29.

   Design of therapeutics using genetic tools.

   The therapeutics are intended for the treatment of impaired blood supply to organs and tissues. Research and advanced development will be completed by branch research institutes.

 

Arrangement of necessary testing, and establishment of production of substances and bulk products.

   Development of monoclonal antibody-based products

The world market of monoclonal antibodies (mAbs) exceeds $20 billion.

   No industrial production of mAbs-based products in Russia is conducted. Manufacturing processes for therapeutic mAbs will be developed by specialist from branch companies of our corporation  LLC «BioCloneTek» and LLC «BionA Farma».