Debunking the Gene Patent Mythology: Professor Holman’s Supplemental Brief in the AMP Remand*

The supplemental briefs for the parties and amicus are now finally in for the remand of the AMP v. USPTO case to the Federal Circuit.  As I’ve previously stated, the Supreme Court’s reasoning in Mayo Collaborative Services v. Prometheus Laboratories, Inc., which caused this remand should not change the fact that Myriad’s isolated DNA sequence claims are patent-eligible under 35 U.S.C. § 101.  That’s based on the Supreme Court’s 1980 decision in Diamond v. Chakrabarty (man-made living organism is patent-eligible) being the controlling precedent, not Mayo Collaborative Services.  See Chakrabarty Controls on Isolated DNA Sequences, not Mayo*

Not surprisingly, the ACLU and PubPat’s supplemental brief assert that these Myriad’s isolated DNA sequence claims are patent-ineligible in view of Mayo Collaborative Services, arguing that these claims “patent laws of nature and products of nature.”  This further mischaracterization of Myriad’s isolated DNA sequence claims perpetuates the unfortunate “myth” by the ACLU and PubPat that this case “is about the validity of certain patent claims on human genes.”  See page 8 of Brief for Appellees that filed for the original Federal Circuit panel decision.  But what the Federal Circuit panel should especially take note of in the remand of the AMP case is the supplemental amicus brief filed by Professor Christopher Holman of the University of Missouri-Kansas City School of Law.

Professor Holman not only teaches patent law at UMKC, but has a Ph.D. in biochemistry and molecular biology, as well as well as some post-doctoral drug discovery research experience.  In other words, Professor Holman speaks as one who understands both the patent law and the technology involved in the AMP case.  And what Professor Holman’s supplemental brief does is debunk the “gene patent mythology” fabricated by ACLU, PubPat, (and others), as well as “ a number of assumptions regarding the nature of the claimed subject matter” made by the original Federal Circuit panel which he characterizes as “unsupported at best, and in some instances clearly mistaken.”

At the outset, Professor Holman states that he is filing his supplemental brief “in the hope that this Court will not decide the patent eligibility of the isolated DNA claims based on unfounded assumptions as to the nature of the claimed subject matter and the potential impact of the claims (and so-called ‘gene patents’ in general) on research and diagnostic testing.”  He also makes the very astute observation that the AMP case “has serious ramifications extending well beyond the context of genetic diagnostic testing, particularly with respect to biotherapeutics.”

[Bio-Pharma]

But given these “serious ramifications,” Professor Holman also alarmingly observes that “[t]here has been no specific allegation that any particular[] technology infringes any of the challenged claims, and in fact my research indicates that no US court has ever addressed the question of whether an isolated DNA claim would be infringed by any form of DNA sequencing or diagnostic testing.”  Even more disconcerting is his observation that Myriad’s “claims have yet to be adequately construed, and their purported preemptive effect remains entirely speculative.”  Put differently, the patent-eligibility of Myriad’s isolated DNA sequence claims under 35 U.S.C. § 101 may unfortunately be judged by the Federal Circuit on remand without a sufficient “claim construction” record.

Professor Holman’s supplemental brief starts with the fundamental proposition that “isolated” DNA is not simply DNA which has been “cleaved” and “extracted” from native chromosomal DNA.  Or as Professor Holman further explains his proposition in more detail:

[S]ome members of this Court are under the impression that the claims encompass native genomic DNA that has been simply “cleaved” from the chromosome and “extracted” from the cell, in a process analogous to separating cotton fiber from cottonseed, or purifying human adrenaline from human tissue.  While the imagery of cleaving a piece of DNA out of the chromosome might serve as a useful metaphor for explaining difficult concepts to non-biologists, like the “magic microscope” it misrepresents the biology and obscures the very real distinction between the claimed DNA and native chromosomal DNA.  Properly construed, the challenged claims are limited to synthetic DNA molecules that are structurally and functionally distinguishable from their native counterparts.

So much also for the inapt analogy disingenuously propagated by the ACLU and PubPat that Myriad’s claimed isolated DNA sequences are equivalent to “plucking a leaf.”

Particularly important to Professor Holman’s proposition is that the “isolation of genomic DNA” according to Myriad’s patents “is fundamentally different from the isolation of other biomolecules, such as proteins, lipids, or the purified adrenalin claimed in” the 1928 case of Parke-Davis & Co. v. H. K. Wolford Co.  In fact, Professor Holman points out the highly synthetic (i.e., man-made) nature of the process for preparing such “isolated” genomic DNA:  (1) extracting chromosomal DNA from a cell sample; (2) cleaving the long chromosomal DNA into shorter fragments; (3) inserting these DNA fragments into DNA vectors capable of replicating in a host cell; (4) introducing these altered DNA vectors into, for example, bacterial or yeast host cells which are then cultured to multiply and create a collection of vector-containing cells known as the “genomic DNA library”; (5) screening this “genomic DNA library” to indentify cells containing the desired genomic DNA; and (6) isolating the cells containing the desired genomic DNA from the mixture of cells in the “genomic DNA library.”  Further copies of the desired “isolated” DNA sequence may then synthesized (replicated) by using, for example, conventional polymerase chain reaction (PCR) techniques.

Contrary to what the ACLU and PubPat suggest, nothing in “nature” (other than the host cells used essentially as “factories” for replicating DNA they don’t “natively” contain) makes these synthesized copies of the “isolated” DNA sequence a “product of nature.”  As Professor Holman further says in his supplemental brief, Myriad’s ‘282 patent “does not describe isolating DNA by extracting it directly from native human chromosome, and to do so would make little sense, since that is simply not how DNA was, or is isolated.”  Other than the initial isolation of the BRAC genes when extracting native chromosomal DNA from human cells and cleavage of that DNA into fragments which Professor Holman characterizes as “intermediate steps in the preparation of the genomic library,” that is close as Myriad’s claimed isolated DNA sequences get to “nature.”

In relying upon Mayo Collaborative Services, a key argument made by the ACLU and PubPat is that Myriad’s claimed isolated DNA sequences “are unduly preemptive of laws/products of nature.”  See page 6 of the Supplemental Brief for the Appellees.  Professor Holman’s supplemental brief does say that literal reading of Myriad’s claimed isolated DNA sequences might lead one to believe that the “claims would cover bulk extracted chromosomal DNA, or fragments of native DNA used in the preparation of a library, since they would inherently include a BRCA gene.”  But Professor Holman then says that giving Myriad’s isolated DNA sequence claims such a broad interpretation “would render them anticipated by the extraction and cleavage of chromosomal DNA, and the preparation of genomic DNA libraries, activities that were routine and widely described in printed publications long before the isolation of” the BRAC genes.  Instead, Professor Holman states that not only does Myriad’s claimed isolated DNA sequences “originate outside the body,” but that these claimed sequences also have “functional and structural characteristics that distinguish [them] from native genomic DNA.”  In particular, Professor Holm notes that the “methylation of genomic DNA, along with other epigenetic modifications, are not retained by the isolated DNA” such that Myriad’s claimed isolated DNA sequences do not “originate from a native source” and are “structurally different in a way that significantly affects function.”

One particular “myth” at the heart of the ACLU and PubPat argument that Myriad’s claimed isolated DNA sequences are “unduly preemptive” (and unfortunately bought into by Judge Bryson’s partial dissenting opinion in the original panel decision) is that these claimed sequences “effectively preempt any attempt to sequence the BRCA genes, including whole-genome sequencing.”  Professor Holman’s supplemental brief exposes that “myth” for what is:  uninformed belief having no factual support.  Professor Holman observes that there are “many alternate methodologies for sequencing DNA” that do not necessitate “any isolation of the specific DNA sequences.”  In fact, Professor Holman astutely observes that Judge Bryson’s partial dissenting opinion “provides no explanation as to how the challenged claims would necessarily be infringed by any, let alone all of these methodologies.”

Professor Holman also correctly reminds the Federal Circuit panel that “the name of the game is the claim,” despite all the “hand waving” by the ACLU, PubPat, and others, including Justice Breyer with his snide remark in Mayo Collaborative Services about the “draftman’s art.”  As Professor Holman astutely observes, without determining what is “within the scope” of Myriad’s isolated DNA sequence claims, “many critics of gene patents incorrectly assume that any patent claim that recites a gene sequence necessarily forecloses any research or diagnosis relating to that gene.”  Professor Holman then reemphasizes the point he made in his original amicus brief (co-authored with Professor Robert Cook-Deegan) that “there is no basis for assuming that all forms of DNA sequencing, especially next-generation single molecule methods, would necessarily entail the production of isolated DNA falling within the scope of the properly construed claims.”  Put differently, without understanding what Myriad’s isolated DNA sequence claims actually do (or do not) cover, any argument about “preemption” is completely divorced from reality.

Another “myth” present in the ACLU and PubPat’s “preemption” argument is that Myriad’s isolated DNA sequence claims will “curtail the ability of scientists to examine human genes.”  See page 11 of the Supplemental Brief for the Appellees.  Indeed, another “assumption” made by Judge Bryson in the original Federal Circuit panel decision is that, “unless this Court declares the broader isolated DNA claims patent ineligible whole genome sequencing will be impeded by thousands of gene patents.”  But as Professor Holman correctly observes, that “assumption” may be based on “the widespread perception that 20% of human genes are patented,” which he also correctly characterizes as “a myth based upon the misreading of” the Jensen and Murray study reported in a 2005 Science article entitled “Intellectual Property Landscape of the Human Genome.”

This Jensen and Murray study stated that “20% of human genes are explicitly claimed as US IP.”  In reference to this study, Professor Holman directs the Federal Circuit to consider two 2012 articles he wrote.  One of those 2012 articles entitled “Will Gene Patents Derail the Next-Generation of Genetic Technologies?:  A Reassessment of the Suggests Not” factually analyzed the evidentiary basis for this statement by the Jensen and Murray study, and concluded that “it should be quite apparent that the [Jensen and Murray study] provides absolutely no basis to infer that 20%, or for that matter any defined percent of human genes are covered by patents that would be infringed by sequencing the gene, or for that matter studying or using the gene (emphasis added).”  I would strongly suggest that the Federal Circuit panel (and especially Judge Bryson) read Professor Holman’s 2012 article before making any further “assumptions” about what “research of human genes” might be impeded by Myriad’s isolated DNA sequence claims.

In concluding his supplemental brief, Professor Holman states that a “determination by this court that any of the challenged isolated DNA claims is patent ineligible could cause serious unintended collateral damage to biotechnology, and should not be made cavalierly based on an overly simplistic and imprecise interpretation of the claims and speculation as to their potential preemptive effect.”  The Federal Circuit needs to heed this “warning” by Professor Holman very carefully in the context of what Myriad’s isolated DNA sequence claims actually cover, and without factually unsupported “speculation” or “assumptions” as to what “their potential preemptive effect” might be.  The ACLU, PubPat, and others have unfortunately fabricated the story that the AMP case is about “patents on human genes.”  But Professor Holman’s supplemental brief has carefully and factually exposed this fabricated story as being nothing more than “gene patent mythology.”

*© 2012 Eric W. Guttag.  Posted June 22, 2012 on IPWatchdog.com.