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Author: YoHo00 Two stars, 250 posts Old School Fool Add to my Favorite Fools Ignore this person (you won't see their posts anymore) Number: of 1856  
Subject: Re: ABGX & MEDX vs. CAT (LSE) Date: 5/25/2000 10:54 AM
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Kozbanky,

Wow, where to begin...The field of antibody humanization is very very complex, even for someone like myself with a PhD in the field.

Differences between these two technologies
CAT: uses a process called phage display in order to find recombinant antibody fragments called scFv (Single chains). Basically, CAT clones variable regions (the business end of the antibody) into cassettes that allow for display as an intact antibody fragment within a bacteria phage (virus that infects bacteria). This library of billions of different antibodies are then screened against a potential target and the nonbinders are washed away. The binders are amplified in bacteria, the sequence of the recombinant antibody determined and viola a new antibody...this is a very simplified version of what really happens so any other gurus please be gentle with me.

MEDX/ABGX: These companies use essentially genetically modified animals whose antibody system has been modified to contain human sequences. This technology is basically the same as using a normal mouse, i.e., innoculate with an antigen (target of the antibody), boost, clone out antibody producing B-cell, make cell line and viola antibody. This antibody also does not need to be "humanized" because the mouse antibody system was "humanized" from the get go...

Advan/Disadvan
Affinity:
Animals are much better at making antibodies with stronger affinities. (Advan)
In order to get high affinity antibodies in phage one needs to go through numerous steps of "affinity maturation." (Disadvan)

Specificity:
Animals will not make antibodies to "self." What I mean by this is the animal's immune system knows not to make a response to a protein that is normally found in the animal. (Disadvan)
Phage display is a completely artificial environment therefore, using phage display allows for the possibility of finding antibodies to targets that an animal would never create. (Advan)

Throughput:
With the impending onslaught of new targets coming from the functional genomics effort, there will be a serious need to find new antibodies to many targets very rapidly. The use of an artificial system such as phage display is clearly geared toward meeting that demand. (Advan)
I just can not see finding new antibodies to 80,000 new proteins one mouse at a time...(Disadvan)

Business:
MEDX and ABGX have cross licensed their technologies and are adding large numbers of corporate collaborators. They are the only game in town wrt this technology.
CAT holds almost all the intellectual property on the phage display system, and hence at this time they are the only game in town. However, from what I have heard they are difficult to work with...I will leave it at that...However, I said above (...at this time...), there are numerous other companies that claim to have IP in the phage display arena (Morphosys, etc.). Currently, Morphosys and CAT are locked in a very ugly suit in Europe over this exact topic and it should all be resolved by this fall.

Anyway, I have yammered on long enough on this, I hope this helps...

Yo.
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