Friday, March 15, 2013

Antibodies (mAbs) were 5 of top 8 best selling biologics

According to @CellCultureDish, 8 of 20 top selling drugs from last year were biologics.

#1. Humira (adalimumab)
#2. Remicade (infliximab)
#3. Enbrel (etanercept)
#4. ~not biologic~
#5. Rituxan (rituximab)
#6. Lantus (insulin glargine)
#7. Herceptin (trastuzumab)
#8.~not biologic~
#9. Avastin (bevacizumab)
#10.~not biologic~
#11.~not biologic~
#12. Neulasta (pegfilgrastim)

Source: Genetic Engineering and Biotechnology News

It's also interesting to point out that 5 of the 8 are monoclonal antibodies (mAbs). You can easily tell from the chemical name of the biologic because the chemical name ends with -mab.

Anatomy of the Antibody

For the non-biogeeks out there, monoclonal antibodies are Y-shaped molecules that are naturally produced by our immune systems to fight off foreign germs. Picture doing the "Y.M.C.A" dance and you're doing the "Y".

YMCA village people
The Village People emulating the shape of a monoclonal antibody

The significance of antibodies is that they are highly specific, meaning that they will bind to one target and only that target; it's possible because the antibody's molecular "hands" fit only one "glove" (specific antigen).

So the reason why monoclonal antibodies are so useful in medicine is because they can hit the targets that you want and nothing else... so-called, "Smart-bombs." And you'll see a lot of mAbs in cancer treatment (since you want to target only the cancerous cells, but not the healthy cells).

Equivalent of when an antibody comes across an antigen it doesn't recognize

mAbs can be divided into two regions: Fab and Fc.

Fab stands for fragment (antigen-binding). The part of the antibody that binds to the antigen. The Fab is basically everything from your shoulders up.

Fc stands for fragment constant: the rest of your body from your shoulders down to your legs. It's not really constant as it can be one of several classes in humans; but relatively, it's constant.

Early antibodies were engineered from mice. In very simplistic terms, you introduce a foreign biological molecule (antigen) to a mouse. The mouse's immune system will naturally fight off this foreign molecule by producing antibodies, and voila, you have yourself a mAb that can target your antigen. This mAb is 100% murine.

The problem with murine antibodies as medicine is that the human immune system recognizes it as foreign and will reject it. So to be useful, the antibody needs to be "humanized."

Humanizing an antibody means replacing mouse-Fc region with a human Fc region and then trying to make as much of the Fab region as human as possible.

mAb Nomenclature

There's actually a nomenclature for monoclonal antibodies that can tell you from the name, how much of the antibody is murine and how much is human:

diagram mab antibody

In the above diagram, the light-blue antibody is from a 100% murine (-omab). The darkish-red antibody is 100% human (-umab).

The genetically engineered antibodies are the ones that are mixed in color. A chimeric antibody (-ximab) is one where from the "elbow" down is human, and from the "elbow" to the fingertips is murine. Drugs like Remicade (infliximab) and Rituxan (rituximab) are chimeric.

A humanized-antibody (-zumab) is one where only the "fingers" are murine and the rest is human. Drugs like Herceptin (trastuzumab) and Avastin (bevacizumab) are humanized antibodies.

While the more humanized an antibody is, the less rejection it gets as a viable drug, there appears to be no obvious correlation from a revenue perspective (see list above).

What's this have to do with cell culture? Antibodies are secreted by genetically-engineered cells that are grown in cell cultures.

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