July 21, 2012

I just listened to yesterday’s oral arguments in ASSOCIATION FOR MOLECULAR PATHOLOGY (“AMP”) V. U.S. PATENT AND TRADEMARK OFFICE. Downlaod the AMP v USPTO Oral Argument mp3.

This case, about whether DNA claims are patentable subject matter, is a big deal. DNA claims have been around since shortly after the pioneering recombinant DNA patent, Cohen and Boyer, No. 4,237,224, issued 32 years ago. Cohen and Boyer claimed methods for “replicating a biologically functional DNA” then later a “cloned biologically functional circular recombinant DNA,” a DNA claim. Later patents would claim “isolated” nucleic acids having specific sequences. Needless to say, the entire Biotech industry rests on the bedrock of DNA claims.

Interestingly, the U.S. Patent office strongly favors DNA claims (having issued them for all these years) but the Justice Department, who is representing the USPTO, is against them. The Federal Circuit seems annoyed by this. They pointed out that Justice could have directed the agency to file a dissenting brief, but did not. (The Justice department not only disagrees with the USPTO, but says this case is not even close! So Patent Office, not only have you been wrong all these years, but you were clearly wrong, according to the Justice Department.)

The case is on remand from the Supreme Court, so another interesting aspect is that the Federal Circuit has already decided this case once (in favor of DNA claims) and so both parties know what each judge thinks of the case.

While there has been much written about this case (and read the Kevin Noonan piece here) I want to add my thoughts on a particular detail that arose during oral argument. It illustrates the mischief that can result from non-scientists addressing scientific topics. The problem is NOT that the science is too complicated or that the parties lack the intelligence to figure it out. The problem is misunderstood scientific jargon and parties taking advantage of a misunderstood word.

My example comes at a point about 19 minutes into oral argument. The parties discussed a method of screening for cancer drugs. The claim recites the steps: “growing a transformed eukaryotic host cell containing an altered BRCA1 gene” and then making a side by side comparison of the cell growth rates–with and without a candidate drug. A drug that significantly slows the cell growth rate is seen as a potential cancer therapeutic. If the drug slows growth of the cell in the method, then perhaps it will slow cancer in the body.

At one point AMP’s counsel argued the patent owner did not “transform” the cell but “bought it off the shelf” and that the cells were simply “test tubes.” Judge Bryson then asked, “In what respect has [the eukaryotic cell] been transformed prior to the insertion of the BRCA1 gene?”

AMP replied, “Neither the patent nor the specification explain the answer to that question.” AMP went on to argue that the claim is merely adding “anything” and “seeing what happens.” (AMP is arguing here that this method claim is non patentable subject matter because it is not significantly different from processes that go on in nature.) It mystified both J. Bryson and AMP. Just what had happened to that cell before the BRCA1 gene was inserted? What does it mean to be a “transformed” cell?

The problem here is quite simple. The court and AMP wrestled with the lay meaning for “transformed” but “transformed” is scientific jargon. To a scientist in the field, all is perfectly clear.

You microbiologists out there no doubt remember there are three ways to insert DNA into a cell: (1) Transformation, (2) Conjugation and (3) Transduction.

In transformation, a cell absorbs naked DNA. In conjugation a cell receives DNA from another cell. In transduction a cell receives DNA from a virus. Accordingly a “transformed cell” is simply a cell that received exogenous DNA directly, rather than through the actions of another cell or a virus. Another possible meaning of “transformed” is a cell that has become cancerous. The patent specification used “transformed” in both senses.

In either event, the claimed term means that a non-cancerous cell becomes cancerous because the BRCA1 gene is inserted. The answer to J. Bryson’s question is that in no sense is the cell “transformed” prior to insertion of the BRCA1 gene. The word “transformed” is simply referring to how the DNA got into the cell (by ‘transformation”). Alternatively, it means that the inserted gene has caused the cell to become cancerous. Either way, all is clear. The method uses cells in which the BRCA1 mutation is doing its thing. Once inserted into a normal cell it causes cancer, or at least increases cell grown rate.  This BRCA1 containing cell could now be used to screen for drugs that would slow down the growth rate. There is no “product of nature” here.  There is just two well intentioned, but uninformed, lawmen fumbling around with scientific jargon they do not understand–and deciding the fate of DNA patents.  I hope the bio tech community has a strong stomach.

There were other issues, such as comparing genetic engineering to coal mining(!) and cutting out someone’s kidney. But that’s for another post.