Chymosin is an enzyme used in the food industry for cheese production. It is a protease that cleaves κ-casein in milk, leading to coagulation and curd formation. This enzyme was traditionally extracted from the stomachs of calves but is now primarily produced through recombinant DNA technology.

Bevacizumab (Brand name: Avastin)

Disease: Bevacizumab is used to treat various types of cancers, including colorectal cancer, lung cancer, and glioblastoma. The problem it addresses is tumor growth and angiogenesis, which are crucial for cancer progression.

b) Mechanism

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). VEGF promotes the formation of new blood vessels (angiogenesis), which tumors use to grow and metastasize. By inhibiting VEGF, Bevacizumab starves the tumor of the nutrients and oxygen it requires to grow, slowing its progression.

c) Manufacturer/Companies

• Genentech (a subsidiary of Roche)

• Roche

• Biocon

• Amgen (biosimilar producers)

Bevacizumab is produced using recombinant DNA technology. Specifically, it is synthesized in genetically engineered Chinese Hamster Ovary (CHO) cells. The production involves:

1. Insertion of the humanized monoclonal antibody gene into CHO cells.

2. Cultivation of these cells in bioreactors.

3. Harvesting and purification of the monoclonal antibody using chromatography techniques.

e) Business Outcome

• Global Patient Reach: As of recent years, Bevacizumab has been prescribed to millions of cancer patients worldwide.

• Revenue: Avastin generated approximately $7.1 billion in annual sales for Roche at its peak (2019).

• Market Reach: Approved in over 80 countries for multiple indications.

Information Summary for Chymosin

a) Problem

Low production rate in traditional methods: Chymosin was traditionally extracted from calf stomachs, which is costly, labor-intensive, and unsustainable given the growing global cheese demand.

b) Mechanism

Chymosin cleaves κ-casein in milk, leading to coagulation and curd formation, a crucial step in cheese production. Recombinant chymosin provides a consistent, high-quality alternative to traditional extraction methods.

c) Manufacturer/Companies

• Pfizer

• Novozymes

• Chr. Hansen

d) Production Method

Chymosin is produced using recombinant microbial technology:

1. The chymosin gene is inserted into yeast, bacteria (E. coli), or fungi (Aspergillus niger).

2. These microorganisms are cultured in controlled fermentation systems.

3. The enzyme is then extracted, purified, and formulated for commercial use.

e) Business Outcome

• Market Adoption: Recombinant chymosin accounts for approximately 90% of the world's cheese production.

• Profit Generation: The global cheese enzyme market is valued at $1.5 billion, with recombinant chymosin dominating the sector.