Hi, from the press release it appears the licensing covers *one* humanized Ab. I agree that "primatized" and "humanized" Abs are two different potential solutions to the HAMA (Human-Anti-Mouse-Antibody) problem that has limited the use of MAbs in human therapy. Abs (of the IgG isotype, which are the ones most frequently used in therapy) have 4 polypeptide chains, 2 heavy chains and 2 light chains. The heavy chain has 4 so-called domains, 3 are "constant" and 1 is "variable." The light chain (LC) has just 2 domains, 1 constant, 1 variable. Each of the variable domains has about 100-125 amino acids. For a given "flavor" of IgG (there are subtypes like IgG1, IgG2, etc) and for a given individual the constant domains are indeed constant. A humanized IgG1 Ab, for example, and an primatized IgG1 Ab would have identical sequences for the all 4 constant domains (3 in HC and 1 in LC). In primatized Abs the entire V domains are usually taken *intact* from whatever the monkey made upon immunization. I think what IDEC's patent protection (when/if issued) would cover is the process of making the Abs in primates, extracting the V domain sequences and then "pasting" them with human C (constant) domain sequence to build a complete Ab. Abs made in this fashion from animal and human sequences are termed "chimeric"
Genentech has rights to a patent that cover this general ("chimeric") technology (in the old days the entire V domains came from the mouse; in fact, ReoPro, the Centocor Ab fragment and one of 2 or so Abs in approved clinical use in the US, is a chimeric of mouse V domains and human C domains). So, if primatized Abs infringe on anything, it would not be on PDL (whose technology involves modification of the V domains), but *maybe* on Genentech's patent rights. Now, IDEC and Genentech are codeveloping at least one drug, so one can probably assume that IDEC should be able to obtain a license to this in favorable terms (perhaps this is actually known; I have not checked thoroughly press releases, etc)
As for IDEC's competition with PDL, I see PDL's advantage in the possibility, in principle, of using their technology to "rescue" mouse Abs that showed early clinical (or pre-clinical) promise but were abandoned because of the HAMA problem mentioned above. Humanization can take those molecules and in principle make them less immunogenic. "Primatization" would involve creating completely brand new Abs (against the original target or antigen - Ag) by immunizing primates; this is a much longer process and there is no guarantee that one would recover an Ab with the same specificity as the original mouse (or rat) Ab. Humanization cannot make this a 100% guarantee, but the available data suggest that there is a very good chance of achieving or at least approaching this goal (of preserving the affinity and specificity of the mouse Ab).
Another issue is whether, all factors being equal, a humanized Ab is better or worse than a primatized Ab against the same target. This can only be addressed in the clinic (and eventually in the market place), and probably with great difficulty (not to mention the naivete of the "all factors being equal" statement above).
In summary, I see today's announcement as positive (but not unexpected) to PDL, and neutral to positive to IDEC(from the speculation of IDEC having one more very promising molecule on which they are willing to put more money upfront) . What's your take on this?
Max |
