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| Overview
of the Market for Monoclonal Antibodies & Antibody
Therapeutics |
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Michael Wijaranakula*
Staff Researcher, Infotix
Systems, Inc. - December 22, 2004
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To prevent and treat inflammatory and autoimmune disorders, cancer, rheumatoid arthritis and infectious diseases, biotech and biopharmaceutical companies are using
monoclonal antibodies (MAbs) that specifically target disease organisms
as well as other types of molecules found in the body
such as hormones, infectious substances, toxins, and
proteins on the
surface of normal cells or those uniquely present of the
surface of cancer cells. The specificity of MAbs
makes them promising agents for human therapy.
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According to Minneapolis, MN-based
Arrowhead Publishers, the revenues from sales of
monoclonal antibodies (MAb) and antibody therapies
accounted for over $5.1 billion last year and will
continue to grow at a phenomenal rate throughout the
next five years. By 2008, MAbs should account for 32
percent of all revenue in the biotech market, said the
research firm.
What
are MAbs and What is Needed to Make Them?
Antibodies
are very important parts of
the immune system that act primarily as a defense
against invasion by foreign substances called antigens.
Antibodies are
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produced by a type of white blood
cell
known as a B cell and are manufactured when the antigen
enters the body. Antibodies neutralize or mark antigens
for destruction with the help of other cells of the
immune system by attaching, or binding, to specific
parts of antigens. Only the antibodies created for a
specific antigen can attach to that antigen. After the
antibody is produced, it continues to circulate in the
blood to attack its targeted antigen the next time the
antigen invades the body.
The response of the immune system to any antigen is polyclonal, which means that the system manufactures a great range of antibodies. Even if one were to isolate a single antibody-secreting cell, and place it in culture, it would die out after a few generations because of the limited growth potential of all normal cells. This problem was solved in mice by the technique devised by
Milstein and Köhler to produce
MAbs.
In 1975, Argentine-born British immunologist César
Milstein and German immunologist Georges Köhler
discovered a technique to generate a quantity of white
blood cells that uniformly produced only one type of
antibody, known as monoclonal antibodies (MAbs),
targeting only one specific antigen to allow scientists
to tag one specific substance. In 1984, Milstein and Köhler
received the Nobel Prize in physiology or medicine for
their work.
The first step in the production of MAbs is to immunize a mouse with an antigen to increase the amount of antibodies in that mouse. When the mouse begins to produce antibodies to the antigen, its spleen is removed.
Antibody- producing B cells from the spleen are then fused with a myeloma, a cancerous B cell in the bone marrow that can grow indefinitely. This fusion creates a hybrid cell, called a hybridoma, that can live forever and produce an unlimited supply of the antibody secreted by the original, normal B cell. The new fused cell line is grown briefly in culture and then re-injected into another mouse's peritoneum, a membrane in the mouse near the abdomen. The fluid build up that is formed, called ascites, containing the monoclonal antibodies is then removed for research.
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Mouse and “Humanized” MAbs
- Since MAbs are created using mouse B cells, the main difficulty is that mouse (murine) antibodies are recognized by the human immune system as foreign proteins, and the human patient mounts an immune response against them, producing
HAMA ("human anti-mouse antibodies"), causing the MAbs to be attacked and neutralized.
Biotech and biopharmaceutical companies are currently using proprietary technology platform approaches in an attempt to reduce the problem of HAMA so that fully human monoclonal antibodies can
be developed and commercialized
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for a variety of disease targets. For example, chimeric antibodies, where the antigen-binding parts of the mouse antibody are fused to parts of a human antibody using genetic engineering but still contain mouse protein sequences (approx. 33%) and human protein sequences (approx. 66%), and
"humanized" antibodies (CDR grafted), where the amino acids responsible for making the antigen binding site are inserted into a human antibody molecule replacing its own regions.
In addition, these companies, including Abgenix (NASDAQ: ABGX), Protein Design Labs (NASDAQ: PDLI), and Medarex (NASDAQ: MEDX), build collaborative arrangements with other pharmaceutical, biotechnology and genomics companies to produce antibody therapeutic drugs to prevent and treat inflammatory and autoimmune disorders, cancer, rheumatoid arthritis, transplant-related conditions and infectious diseases.
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| About NMS
Research Analysis:
NMS Research Analysis is a private independent research entity of
Infotix Systems, since 1999, bridging the gap between cutting-edge
scientific research and the investment community. We offer in-depth
research analysis of companies and emerging technology in sectors
ranging from semiconductors, biotech, nanotechnology, novel
materials for aerospace and energy industries. At the time of
publication, Mr. Wijaranakula's portfolio holds long positions
or controls in AMGN, JNJ, PDLI and MEDX. *Mr. Wijaranakula is now with the Department of Immunology, University of Washington. |
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