Thursday, November 4, 2010

Summary of Myriad Patent Claims Under Attack in AMP v. PTO

Today I published a short article in Managing IP "discerning" Myriad's patent claims, currently under attack in AMP v. PTO . The article is available here for subscribers to Managing IP, along with other materials relating to the Myriad case.

The substance of my article is as follows:

As a preliminary matter, it bears noting that the precise contours of Myriad's patent claims are not entirely clear. Claim interpretation is a notoriously unpredictable exercise, and no court has ever formally construed the claims, or considered their scope in the context of infringement litigation. In fact, no US court has ever interpreted a human gene patent claim in a case involving genetic diagnostic testing. In an amicus brief filed with the Federal Circuit in AMP v. PTO, the author (Holman) and Robert Cook-Deegan explain that if the claims were ever enforced in an infringement suit there are reasons to believe that the claims would not be interpreted as broadly as many critics of gene patents have assumed. The following analysis is based on a facial reading of the claims in view of the patent specifications, as well as statements made by the district court and by Myriad.

The challenged patent claims recite subject matter falling under general three categories: isolated DNA molecules claimed as compositions of matter, methods of diagnostic testing, and cell-based assay methods. Importantly, none of the claims encompass DNA as it exists naturally in the human body, and none of the claims recite mere genetic information. Thus, popular allegations that the patent claims confer ownership on people's bodies, or can be used to prevent a doctor from communicating the existence of a genetic predisposition to cancer to a patient, would appear to be unfounded.

Isolated DNA claims
All of the composition of matter claims are limited to "isolated" DNA molecules, and hence clearly do not encompass genomic DNA as it exists naturally in the human body. This is consistent with long-standing patent office policy which requires claims directed to naturally occurring DNA molecules to be limited to isolated, purified and/or recombinant embodiments of the molecule, in order to prevent the patent from covering native genes in the human body

There is, however, some uncertainty with respect to exactly how broadly the term "isolated" should be interpreted. Myriad's patent specifications define the term to encompass any DNA sequence that has been “removed from its naturally occurring environment, and includes recombinant or cloned DNA isolates and chemically synthesized analogs or analog biologic synthesized by heterologous systems." Many in the biotechnology community have assumed that claims to "isolated" DNA molecules broadly encompass the claimed sequence in any context outside its native environment, such as residing in a recombinant DNA vector, cell or organism. However, there is little US case law directly addressing the proper interpretation of the term "isolated" in this context, and there is reason to believe that if litigated the term might be given a narrower construction, at least in some cases (depending, for example, on how the term "isolated" is used in the patent specification and in communications to the patent office during patent prosecution).

Some of the composition of matter claims encompass any isolated DNA that codes for a full length BRCA1 or BRCA2 protein. These claims are relatively broad in the sense that they would appear to cover any of the astronomical number of redundant DNA sequences that would encode the BRCA1 protein. They also arguably cover genomic DNA coding for the protein, i.e., the isolated gene as it exists in the human body. Assuming the courts gives the term "isolated" an expansive reading, the claims arguably cover very large recombinant molecules that comprise the BRCA coding sequence (i.e., large DNA vectors), as well as recombinant cells or organisms comprising the coding sequence in a non-native context.

Although many have assumed that claims directed towards DNA encoding full-length BRCA proteins can be used to block genetic diagnostic testing, in fact these claims would not appear to be infringed by standard genetic diagnostic testing. In conventional BRCA diagnostic testing, segments of the BRCA gene are amplified and sequenced, not the entire full-length genomic sequence. As a consequence, the full-length coding sequence is not made or used, and thus there would seem to be no infringement (see Holman/Cook-Deegan amici brief). The claim would however appear to cover a recombinant DNA molecule encoding a full-length BRCA protein, which could be used in drug discovery research or, potentially, gene-based therapy.

There are also a variety of narrower isolated DNA claims at issue. For example, some of the isolated DNA claims are limited to a specific cDNA molecule encoding a BRCA protein. These claims are relatively narrow, and could be readily circumvented in many instances by simply using a different DNA sequence that encodes the same protein (which is trivial given the redundancy of the genetic code and the general availability of whole gene synthesis). Although the district court found the cDNA claims patent ineligible, the government argues in its amicus brief that while isolated genomic DNA is patent ineligible, cDNA is patent eligible because it does not exist in nature (cDNA is essentially a DNA version of a naturally existing RNA molecule).

Some of the claims recite any isolated DNA having least 15 nucleotides of a DNA sequence encoding full-length BRCA protein. These claims appear on their face to be extremely broad, encompassing conventional BRCA genetic diagnostic testing (because the testing involves amplification of fragments of the BRCA gene exceeding 15 nucleotides in length). However, a recent bioinformatics study suggests that the breadth of these claims could render them invalid based on anticipation by genetic sequences published in GenBank more than one year before the patents’ filing dates (see Holman/Cook-Deegan amici brief).

Method of diagnosis claims
The method of diagnosis claims are generally directed towards processes of "analyzing" a person's BRCA gene sequence for the existence of a naturally occurring mutation or genetic variation, or “comparing” two BRCA sequences in order to identify the existence of a variation. Critics of gene patents have argued that these method claims broadly cover the mere mental process of analyzing or comparing genetic sequence information, and this was the interpretation of the district court in its summary judgment opinion. However, in their appellant brief Myriad argues for a narrower interpretation, explaining that when the claims are read in light of the specification it is clear that the claims require "extracting, processing and analyzing” DNA molecules, not merely an analysis or comparison of genetic information.

The scope of these method claims could be significant. For example, in the not-too-distant future it is predicted that many people will have their whole genome sequenced. With this information in hand, one could then look for medically significant genetic variations, such as variations in the BRCA gene. Under the district court's broad interpretation, the method claims might be infringed by a doctor or patient merely analyzing the genetic information, which is one of the fears voiced by critics of gene patents. On the other hand, under Myriad's proposed interpretation merely analyzing genetic information would not constitute infringement.

Cell-based assay methods
One of the challenged patent claims recite a method of using recombinant cells engineered to express a BRCA protein to screen for potential cancer drugs. This claim clearly has no implications for genetic testing, and it is unclear why the ACLU chose to challenge its patent eligibility.

1 comment:

patent litigation said...

Although some gene patent proponents argue that this patent litigation is about legal precedent and reliance, I honestly think that this is one of those issues that is largely about one's politics and policy. Whether or not human genes are legally patentable is a question rather like the "if a tree falls in the forest" hypo. I've noticed that most biotech proponents, in particular, base their pro-patenting contentions on policy arguments, rather than on legal ones -- perhaps because there is no real legal answer. That being the case, although I'd like to read a Supreme Court opinion deciding this issue, perhaps this is really one for Congress to deal with.