New stuff from the docket provides a little more color on the competing processes for copolymer manufacture. I dared to comment and to reference your thoughts re poly-glu:
>>Thanks to an anonymous benefactor, I've been given a look at MNTA/Sandoz' "Statement of Claims and Defenses." I gather you also have it and will post it and other recent documents relating to the mC litigation. My comments for what they are worth (remember they are free) . . .
I'm not sure I agree that MNTA's '187 patent bolsters their defense much. OK, they have a different method for analyzing process quality, but the manufacturing steps seem much the same. Interestingly, MNTA/Sandoz argue that because Teva does not disclose its source of quality for the HBr/Acetic Acid used in step 2, their patents are invalid ("lack of best mode"). Well, guess what? It's just as key in Momenta's process, and they don't disclose it, either! Further, I would think those skilled in the art could assess the quality of their hydrobromic acid in acetic acid, and that they'd want the best stuff. As with other reagents, impurities mess up your reaction times, among other things. I don't think that argument will fly.
However, they have other avenues that look more solid to me wrt indefiniteness. One is the lack of detail around the molecular weight analysis by size exclusion chromatography -- which is the only method mentioned. No info is given about the mobile phase, flow rate, or temperature standards. By contrast, MNTA's '187 patent supplies this kind of info.
While we're talking about pyro-glutamate residues . . . Biotech Jim noted that these can be immunogens if they cyclize during synthesis:
Message 26782535
Not good from a safety perspective. But then, I don't know what Teva does about that issue. Anyway, it's a regulatory one.
The "test reaction" appears to be the one in which rodents are tested, and toxic batches discarded. In this way it was determined that batches that weren't "cooked" within a specific time and temperature range messed up the rodents. MNTA's method of using pyro-glu fractions indeed should not infringe and is quite likely more precise.
I'm not sure what to make of the molar ratio issue. As exwannabe pointed out, the label differs from the patent claims on that metric. That seems pretty strong. Teva does say "approximately" but only in reference to the older version. A ratio for the lower tox version is not given in Teva's patents that I've looked at (though I haven't looked exhaustively). Somewhat puzzled that Teva didn't address this issue, as it seems like a biggie, and perhaps the easiest defense for MNTA/Sandoz to assert. But I must be missing something, because it seems so glaring that a summary judgement could have been tried on this issue, one of non-infringement. Perhaps Teva feels that the molecular weights are sufficient protection? Though everyone agrees getting the weights of the individual peptides is not happening, the weights for the copolymers are given in Teva's patents for their version. Frankly, I do not see why it would be impossible, as Sandoz asserts, to determine the molecular weight of its copolymer in the same way. Unless they are saying that because Teva doesn't properly show how its SEC method for determining these weights works, it's impossible. Anyone buy that idea? <<
You & others feel free to correct any scientific or legal deficiencies in the above. Throwing it out there as a starting point for discussion.
Cheers, Tuck |
