Kyowa Hakko Develops a New Manufacturing Technology
for Amino Acid Dimers (di-peptides)
A Significant Play
in the Growing High Value-added Amino Acid Industry

 Kyowa Hakko Kogyo Co., Ltd. (Kyowa Hakko), one of Japan’s leading companies in the pharmaceutical and biotechnology industries, announced today it has developed a novel, efficient, and versatile process for manufacturing amino-acid dimers (di-peptides). The Company intends to begin the commercial production by 2006 of Alanyl-glutamine, a di-peptide composed of L-Alanine and L-Glutamine, using the new technology.

 Despite the nutritional effectiveness of L-glutamine, it has been inefficiently utilized as a component of infusions and enteral nutrients due to its poor stability and inferior solubility in aqueous solutions. Alanyl-glutamine is stable against both heat and acid, is highly soluble, and functions as a source of L-glutamine in the body. The newly developed low-cost production process can encourage wider use of the superior di-peptide, Alanyl-glutamine. Kyowa Hakko anticipates the Alanyl-glutamine market to be between 100 and 200 tons within a few years, and several hundred tons in the near future.

 Tomonori Yuji, Managing Director and Bio-Chemicals Company President, commented, "As the company who invented and first industrialized amino-acid fermentation, Kyowa Hakko intends to forge ahead with its newly developed di-peptide manufacturing technology. We believe we can create a new world of superior amino acids, and contribute to the health and welfare of people around the world."

 Chemical and/or enzymatic methods have been previously employed for di-peptide synthesis. As these prior methods require chemical modification(s) of amino acids for use as substrates and/or can be contaminated with by-products, they are associated with problems in terms of quality, efficacy, yield, and environmental issues.

 Kyowa Hakko discovered a novel enzyme that directly connects amino acids, and has applied it to develop an efficient manufacturing process for di-peptides without chemical modification. Since this enzyme reacts with a variety of amino acids to yield various di-peptides, it can also be applied to the manufacture of other di-peptides in addition to Alanyl-glutamine.

 The ready availability of di-peptides can broaden the use of many amino acids by overcoming physicochemical limitations and advantageously adding new functions specific to di-peptides. Thus, broadened application and use of amino acids can be expected. Kyowa Hakko is eager to collaborate with researchers and companies domestically and abroad to explore, expand and apply the advantages of di-peptides with a particular focus on medical and health care applications.

Glossary
Di-peptides: Two amino acids connected with a peptide bond, generated in the process of protein degradation in the body, and finally used as amino acids. Known for comprising unique properties and activities not found in single amino acids.
L-alanine: A type of amino acid, thought to play an important role in energy generation.
L-glutamine: A type of amino acid, thought to have a protective effect for the enteric canal and gastric mucosa, used as an anti-ulcer agent, and cited as an important source of energy in the multiplication of immune cells and cells in wound-sites.

About Kyowa Hakko
Kyowa Hakko, a Tokyo based company with special strengths in biotechnology, is dedicated to the creation of new value in the life science, especially pharmaceuticals and bio-products as it strives to contribute to the health and well-being of people around the world. Kyowa Hakko has achieved worldwide success with amino acids and the innovative therapeutic agents | Mitomycin for cancer, Benidipine for hypertension, and Olopatadine for allergies. Today's company strengths are in its state-of-the-art biotechnology to be utilized in drug discovery, including the field of antibody technology (http://www.potelligent.com), and creating high value added bio-products.
In addition, Kyowa Hakko is currently clinically developing some compounds to combat cancer, and has two other novel agents: KW-6002, an agent for the treatment of Parkinson's disease in Phase 3 clinical trials, and KW-7158, an agent for treating urinary incontinence in Phase 2 clinical trials.
For further information, please visit Kyowa Hakko’s English-language website at http://www.kyowa.co.jp/eng/