"Any sufficiently advanced technology is indistinguishable from magic."
- Arthur C. Clarke, Profiles of the Future, 1962

The field of antibody therapeutics is indeed on a comeback trail. Following the early indication in 1982 of potentially significant therapeutic effect of mouse monoclonals (MAbs), and notwithstanding the disappointments during the subsequent years of the 1980s and early 1990s, the total number of therapeutic antibodies approved amounts to a total of ten, besides two additionally approved MAbs: one in Europe and an additional one in Germany only. There are also more than 100 antibodies currently at the various phases of clinical trials and hundreds more in preclinical development. While the first generation of therapeutic antibodies were primarily derived from rodent hybridomas, they mostly proved to be useless primarily due to their triggering of severe immune response to patients, otherwise known as HAMA (Human AntiMouse Antibody) response. Consequent humanization of mouse MAbs and more recent developments of generating complete human antibodies by phage display method and transgenic mouse systems are proving to be the driving forces behind the recent success story of the therapeutic antibodies.

Revenues generated from the sales of the approved MAbs topped $2 billion in 2000, which was an increase of 250% over that of 1998 sales. Also, a conservative estimate points to about 1,100 biotherapeutic products currently in preclinical studies. In addition to the excess of 100 MAbs in clinical trials, current activities in the genomics area and the efforts in proteomics research have further increased the possibility of discovering many MAbs and developing those for various unmet medical needs. Such a glut of MAbs in the clinical pipeline and many more other biotherapeutics are causing a bottleneck in production that may require years to open. While several companies have resorted to establishing larger production capabilities to cope up with their individual production needs, others are optioning to utilize contract manufacturing organizations (CMOs) to satisfy the needs of production, rather than taking the risk of establishing their own manufacturing facilities. This has created a good opportunity and market niche for the CMOs, since many companies with products in pipelines are scrambling to employ the services of such CMOs to move their drug candidates through various clinical phases. Indeed, the Contract Research Industry has experienced growth of 25 to 30% annually since 1995, and the overall value of the industry grew from $1.5 billion in 1995 to $4.5 billion in 1999.

Up until now, large-scale production of antibodies has been primarily achieved from cell culture systems. Alternative methods of production such as transgenic mammals and chickens, insect cells, and transgenic plants are being currently considered by various companies such that high yields of products at a potentially lower cost of goods than in mammalian cell culture can be obtained. However, manufacturing regulatory issues, and the questions of antibody modifications such as the presence of carbohydrate residues are becoming acute topics of concern when large-scale production systems are considered. It is also being realized that various separation technologies that may be quite successful on a small research scale may not meet the challenge of scaling-up to industrial levels.

While a large number of therapeutic antibody-based clinical trials are ongoing for diseases such as allergy, asthma, autoimmune, cancer, cardiovascular, transplantation, and viral infection, the revenues from the existing antibody therapeutics in the market are also increasing significantly over the years. In fact, it has been forecasted that the market could grow above $4 billion by 2002, and has the potential of arriving at $8 billion by 2004, provided the capacity gap between the existing manufacturing resources and potential future requirements is eliminated.

As the interest in the antibody field grows in both biotechnology and pharma sectors, primarily because of their versatility as therapeutics, diagnostics, and reagents in drug discovery research, so grows the legal rambling about intellectual property (IP) situations. While controversy about IP position is nothing new to the antibody field, the court rulings on these patent skirmishes will have far-reaching monetary and product development repercussions, since the companies involved in the lawsuits have major alliances with a large number of biotechnology and first-tier pharma companies.