AMP v. USPTO after Bilski v. Kappos

    By Kevin E. Noonan --

After issuing its decision in Bilski v. Kappos, the Supreme Court granted certiorari, vacated the Federal Circuit's decision below, and remanded to the appellate court two cases related to medical diagnostic claims:  Prometheus Laboratories, Inc.  v. Mayo Collaborative Services and Classen Immunotherapies, Inc. v. Biogen Idec.  These cases have the most-developed case law regarding the question of patent-eligibility for diagnostic method claims, and thus can be expected to provide the Federal Circuit with ample opportunity to craft the type of analytical framework envisioned by the Supreme Court when it left the development of the law in this area to the Federal Circuit (in the first instance, at least).

It is another case, however, that may provide the first instance for the Federal Circuit to "make law" under Bilski v. Kappos.  That case is Association of Molecular Pathology v. U.S. Patent and Trademark Office (aka the Myriad case).  As a reminder, method claims from the following U.S. Patents were invalidated by the District Court Judge Robert W. Sweet's decision:  U.S. Patent  Nos. 5,747,282; 5,709,999; 5,710,001; 5,753,441; and 6,033,857.  These patents are assigned to Myriad Genetics, the University of Utah Research Foundation, and the National Institutes of Health (the '282, '001 and '441 patents); Myriad Genetics, Centre de Recherche du Chul, and the Japanese Cancer Institute (the '999 patent); and Myriad Genetics, Endo Recherche, HCS R&D Ltd. Partnership, and the University of Pennsylvania (the '857 patent).  All but the '857 patent claims priority to an application filed August 12, 1994; all but the '857 patent will expire (upon timely payment of maintenance fees) in 2015 (the '857 patent expires March 2017).

The following method claims have (for now) been invalidated:

For the '282 patent:

20.  A method for screening potential cancer therapeutics which comprises:  growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.

For the '999 patent:

1.  A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1.

For the '001 patent:

1.  A method for screening a tumor sample from a human subject for a somatic alteration in a BRCA1 gene in said tumor which comprises comparing a first sequence selected form the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said tumor sample from the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said nontumor sample indicates a somatic alteration in the BRCA1 gene in said tumor sample.

For the '441 patent:

1.  A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject.

And for the '857 patent:

1.  A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequences identifies a mutant BRCA2 nucleotide sequence.

2.  A method for diagnosing a predisposition for breast cancer in a human subject which comprises comparing the germline sequence of the BRCA2 gene or the sequence of its mRNA in a tissue sample from said subject with the germline sequence of the wild-type BRCA2 gene or the sequence of its mRNA, wherein an alteration in the germline sequence of the BRCA2 gene or the sequence of its mRNA of the subject indicates a predisposition to said cancer.

If the Federal Circuit merely applies the rubrics (such as they may be) of the Supreme Court's Bilski decision to these claims, it seems that only claim 20 of the '282 patent clearly falls within the scope of the machine-or-transformation (MOT) test.  The claim requires growth of transformed human cell in the presence or absence of a test compound.  "Transformation" (or to put it another way, "the hand of man") could be found either in the production of a transformed eukaryotic host cell or the growth of such a cell in the presence of a test compound.  Since neither the transformed host cell (which should remain patentable per se under the Court's Chakrabarty decision) nor growth in the presence of a test compound would occur without human intervention, recitation of these elements in the claim could be enough for the Federal Circuit to reverse the District Court's decision based on principles enunciated by the Supreme Court in Bilski and other precedent.  This result would also serve not to "disturb the settled expectations of the patent community" (Festo Corp. v. Shoketsu Kinzoko Kogyo Kabutshiki Co., 122 S. Ct. 1831, 1841 (2002)), since such claims are not unique to this patent but form the basis for many screening method patents (see, for example, U.S. Patent Nos. 7,736,862; 7,727,731; 7,700,822; 6,960,558; 6,682,920; and 5,344,846, as well as 1760 other such patents).

The other claims may not fare as well, in view of language that tracks more closely with the claims in the patents at issue in the Classen and Laboratory Corp. v. Metabolite Labs., Inc. (LabCorp) cases (thereby raising issues relating to form and substance in determining whether an invention is patent-eligible).  Each of Myriad's remaining claims invalidated by the District Court recite "comparing" steps that are not expressly tied to determining the genetic sequence of an individual's BRCA1 or BRCA2 genes.  Specifically:

• "analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample" (claim 1, '999 patent)

• "comparing a first sequence selected form the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample" (claim 1, '001 patent)

• "comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA" (claim 1, '441 patent)

• "comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence" (claim 1, '857 patent)

• "comparing the germline sequence of the BRCA2 gene or the sequence of its mRNA in a tissue sample from said subject with the germline sequence of the wild-type BRCA2 gene or the sequence of its mRNA" (claim 2, '857 patent)

Arguments could certainly be made that in each case the patient sample sequence must be determined, which would involve the "transformative" steps of obtaining the sequence (involving inter alia cloning or amplifying patient-specific genomic or cDNA and sequencing the DNA, all involving multiple chemical transformations).  However, the question may be framed with regard to whether these claims require such transformative steps, or whether they are broad enough to encompass mere comparison of sequences previously obtained; under this analysis, the sequence steps may be viewed as mere "data gathering" and hence not satisfy the MOT test.

Alternatively, even if these claims are not sufficiently transformative to satisfy the MOT test, the Supreme Court's Bilski decision provides another avenue for the Federal Circuit to reverse the District Court's decision that these claims are not patent-eligible.  This analysis comes from the portion of the majority opinion (joined by Justice Scalia) instructing that its prior precedent (specifically the Benson/Flook/Diehr trilogy) reinforced the principle that abstract ideas are not patent-eligible subject matter.  The task for the Federal Circuit, then, would be to determine whether these Myriad claims were sufficiently broad to claim an abstract idea or a "broad concept" that would "wholly pre-empt" a law of nature, or as in Diehr be "an application of a law of nature" to a process and thus be worthy of patent protection.

One distinction that can be drawn in this regard is that in Bilski (and Diehr) the "law of nature" (hedging in Bilski, the Arrhenius equation in Diehr) were known in the prior art; indeed, the majority opinion in Bilski found that Bilski's claims were directed towards "basic concept of hedging, or protecting against risk: 'Hedging is a fundamental economic practice long prevalent in our system of commerce and taught in any introductory finance class,'" citing (now Chief) Judge Rader's dissent in In re Bilski, 545 F. 3d, at 1013.  In Myriad's claims the "law of nature," the presence of a specific mutation at a specific position in the nucleotide sequence of the BRCA1 or BRCA2 gene, was unknown prior to its elucidation by the Myriad inventors.  (On the other hand, a claim to a single nucleotide polymorphism (or SNP) itself could encompass the "natural phenomenon" or "law of nature" itself and have precisely the preclusive effect disparaged by the Court in Bilski and earlier precedent.)

It is clear that Myriad's method claims raise many of the same issues of patent-eligibility as in Classen and LabCorp.  How the Federal Circuit resolves those issues, and whether the Supreme Court is more willing to let the Federal Circuit make these decisions under Chief Judge Rader than it was under Chief Judge Michel, will determine the extent to which genetic diagnostic claims remain patent-eligible.  And consequently whether "unforeseen innovations," like personalized medicine, will be developed under the patent regime (with enabling disclosure attendant thereto) or be limited to alternative protections (such as trade secret) for which disclosure is antithetical and with all the resulting costs and disadvantages thereof.  Which path is taken will determine the rate, scope, and benefits of such new technology for at least a generation.

Comments

[QuestionBank]

Do we know when these cases are scheduled to be reviewed by the CAFC?

[EG]

Kevin,

A very concise but thorough analysis of what is now a muddled mess. I would suggest getting a Ouija board or maybe consulting the Oracle of Delphi to figure out what the Federal Circuit is going to do with the process/method claims in AMP, Classen and Prometheus in view of the pronouncements from our Judicial Mount Olympus. About the only thing I think is safe to say (with tongue in cheek) is that Sweet's basis for invalidating Myriad's method/process claims (MoT) isn't going to pass muster with the Federal Circuit now that our Judicial Mount Olympus has hurled its thunderbolts and smitten MoT as not the exclusive test.

Which gets me back to why 35 USC 101 is a lousy way to screen out the patent claim chaff from the wheat. After Bilski, we still have no clear and objective test for determining patent-eligible subject matter under 35 USC 101, certainly not from our Judicial Mount Olympus. Instead as Michael Risch has suggested and which I completely agree with, use 35 USC 112 as the initial screen for patent claims. The Bilski claims would have flunked 35 USC 112 under both paragraphs 1 and 2, and we would have avoided all this muddled rhetorical nonsense from our Judicial Mount Olympus that wouldn't know patent-eligible subject matter if it hit them square in the face.

[Sunny G.]

This may be an unsophisticated analysis, but I have been using it as a rough rule of thumb: if the entire method could be performed mentally (assuming one had enough processing capability ;) ) then it is suspect in my mind. For example, adding some sort of limitation in claim 1 of the '999 patent regarding the physical step required to "analyze" (e.g., using a nucletode probe or primer) would clearly solve the problem. It poses a challenge in terms of covering all of the possible technological solutions, but should pass muster as patent eligible. If no such steps are included, then the claim requires more scrutiny IMHO. Admitedly not a test that works well for the non-biotech arts though, but perhaps there is an equivalent solution there.

[Ken]

Kevin,

Why would a previously unknown SNP be different from a previously unknown mutation?

[funobama]

who takes away the patents to research MYGN no incentive for personalized medicine and judges must take this responsibility: put their money to continue the search.
intelligents or bandits?

[Courtenay]

I don't think you can draw a line between known and unknown laws of nature, etc., in view of the quote from Benson (quoted in Bilski) that "phenomena of nature, though just discovered . . . " are not patentable under 101.

[Kevin E. Noonan]

Dear Courtney:

Good point; I was unclear. What I meant to say with regard to the statement:
"the presence of a specific mutation at a specific position in the nucleotide sequence of the BRCA1 or BRCA2 gene"
in the context of a method claim is that the method of detecting this specific mutation for this specific purpose was not known. In Bilski, the method of hedging risk was known, and the application of it to commodities trading was straightforward.

I recognize that the method of detecting mutations associated with disease is also known, but the specific application of that method to detecting a risk for breast cancer by detecting the BRCA1 and BRCA2 polymorphisms was not, and the application to the general method is not straightforward (you need to have identified the mutation).

I recognize that one way of looking at this is that the mutation is a phenomenon of nature that was always there, but I think the Court's precedent supports the view that "phenomenon of nature" in the patent eligibility preclusive context is related to general phenomenon - the law of gravity or electromagnetism. Specific application of natural priciples is the only basis for any invention - "nature is all we have," after all.

Thanks for the comment.

[Kevin E. Noonan]

Dear Ken:

Obviously my day for being opaque. What I intended to convey was the contrast between claiming an application of a natural phenomenon (detecting a SNP for predicting a risk for a disease) and claiming the SNP itself - "a DNA fragment encoding residues xxx-yyy of SEQ ID NO. Z, wherein residue ### is (a mutant form)." Any mutation fits this bill.

Thank for the comment.

[Kevin E. Noonan]

Dear Question:

I don't think the court has set the briefing schedul for the AMP case yet, but we can expect the case to be fully briefed by the fall, with argument scheduled thereafter. Same should be true for Prometheus and Classsen.

When the cases are briefed and argued does not reliably predict when the decisions are rendered; it is possible the Federal Circuit could "talk amongst themselves" and issue all three on the same day in 2011.

Thanks for the comment.

[Kevin E. Noonan]

Dear Sunny:

I look at it similarly: if the claim could be practiced using only a computer, then it is overbroad for failing to recite any affirmative step in the "real" world. If you clone a gene and have it in a test tube, you have an invention. If you isolate and sequence DNA to detect a mutation, you have an invention. If your invention encompasses methods for extracting sequences from a database and comparing them, there had better be some software or other element of the claim that changes it from merely using genetic information, because the information per se isn't patenable. But a method for determining subpopulations of individuals at particular risk for a disease may be; it just isn't a biotech invention (so my ability to intelligently opine on it is much lower).

Thanks for the comment.

[6]

"in the context of a method claim is that the method of detecting this specific mutation for this specific purpose was not known."

Then the "not known" part is irrelevant for your analysis. Either the claim preempts an abstract idea or not.

At first glance I thought as you do Kev, but the more I look at the claim it appears to be nothing more than the abstract idea then had some post solution activity added on to limit it to the specific field of BRAC1 detection.

This is a tough call for me, not because the application of the abstract idea preemption test is hard, but because of my lack of a thorough understanding of the subject matter at hand and specifically what would be considered "post solution activity" in this art.

"and the application to the general method is not straightforward (you need to have identified the mutation)."

That is most likely irrelevant to the inquiry.