Thursday, December 20, 2012

DNA 2.0 Sues Genome Compiler Corp for Patent Infringement


Disclaimer: I have done some consulting work for DNA 2.0, but have not been involved with the lawsuit discussed in this post.

DNA 2.0 is a leading gene synthesis company, specializing in the custom synthesis of long and complex DNA sequences. DNA 2.0 provides a web-based DNA design tool called Gene Designer, which its customers can use to design, clone, validate and order custom designed DNA sequences.  Gene Designer includes an "intuitive drag-and-drop interface for moving sequence elements within or between constructs.”

Yesterday, DNA 2.0 sued Genome Compiler Corporation (GCC) in the Northern District of California for infringing US Patent Number 7,805,252. In its complaint, DNA 2.0 alleges that GCC infringes the patent directly and/or indirectly by developing, distributing and supporting Genome Compiler software. According to the GCC website, Genome Compiler is a DNA design program that features an "intuitive drag & drop, zoom in & out user interface” and enables its users to order their own synthetic DNA designs.

The ‘252 patent includes a single independent claim:

1. A computer program product for use in conjunction with a computer system, the computer program product comprising a tangible computer re adable storage medium and a computer program mechanism embedded therein, the computer program mechanism for designing and manipulating a set of sequence elements in order to design a design nucleic acid sequence, the computer program mechanism comprising:

(I) instructions for representing the set of sequence elements on a display, each sequence element representing an amino acid sequence segment or a nucleic acid sequence segment, wherein the set of sequence elements collectively encode the design nucleic acid sequence, wherein said instructions for representing said set of sequence elements comprise instructions for displaying a plurality of icons in a linear or a near linear arrangement on a display, each respective icon in said plurality of icons uniquely representing a corresponding sequence element in said set of sequence elements such that neighboring icons in said plurality of icons represent neighboring sequence elements in said plurality of sequence elements in said design nucleic acid sequence, and each said respective icon in said plurality of icons depicts a directional property for the corresponding sequence element in said set of sequence elements; and

(II) instructions for permitting a user to rearrange an order of the icons on a display thereby causing a corresponding change in the nucleic acid sequence of the design nucleic acid sequence.

Tuesday, December 18, 2012

Life Technologies Sues Promega for Declaratory Judgments Relating to Cell Line Authentication Kits


Last February, I reported that a district court had ordered Life Technologies to pay $52 million in damages to Promega, based on a finding that Life’s AmpFLSTR PCR kits infringe multiple Promega  patents.  These kits use single tandem repeat (STR) technology to produce genetic fingerprints, useful in a variety of applications, such as forensics and paternity testing.

In September, the court vacated the award of damages, finding that as a matter of law Promega had failed to present sufficient evidence proving that infringing products were made or sold in the United States, or imported into the United States (as summarized here) . The decision is currently on appeal to the Federal Circuit.

Yesterday, Life Technologies filed two declaratory judgment lawsuits seeking a ruling that the company will not be liable for infringing the same Promega patents based on the launch of a new line of Life Technologies product, which will be sold under the trade name AuthentiFiler.  According to the complaints, AuthentiFiler employs STR technology to authenticate/identify the origin of cell lines, providing important validation of cell lines used in biotechnology processes.

One of the lawsuits, filed in the Southern District of California, seeks a declaration that US Patent Numbers 5,843,660; 6,221,598; 6,479,235; and 7,008,771 are not infringed by AuthentiFiler. These are patents that were asserted in the AmpFLSTR lawsuit. According to the complaint, the AuthentiFiler products utilize a different set of STR loci than used in the AmpFLSTR products, and these loci "do not overlap with those required by the claims of the Patents-in-Suit.”

The second lawsuit was filed in the Central District of California, and involves another patent asserted in the AmpFLSTR litigation, Re37,984.  According to the complaint, this patent was exclusively licensed by Max-Planck-Gesellschaft to a company called Research Genetics pursuant to a 1993 license agreement. In 1996, Research Genetics granted Promega exclusive and nonexclusive rights under the patent in certain fields. According to the complaint, Research Genetics retained rights under the patent in other fields, including uses in cell line authentication/identification. Research Genetics was subsequently acquired by Life Technologies, and Life Technologies alleges that under the 1996 agreement the company retains the right to use the patented technology in the AuthentiFiler products. Promega evidently disputes this interpretation of the import of the license agreement.

In this second lawsuit, Life Technologies is asking the court to declare that Promega must agree to arbitrate the licensing dispute (pursuant to an arbitration clause in the agreement), and also for a declaration that, pursuant to the 1996 agreement, Life Technologies is licensed under the ‘984 patent to commercialize products for use in authentication/identification of cell lines, including the AuthentiFiler system.

Thursday, December 6, 2012

ArcticDx v. Sequenom: A Human Gene Patent Litigation Settles

On November 16, a court in the Eastern District of Texas issued a consent judgment and dismissal with prejudice in the case of ArcticDx v. Sequenom.   The patents at issue are what I would classify as gene patents - all of the patents include claims directed towards methods of identifying specific genetic variations associated with disease, particularly age-related macular degeneration (AMD). These method claims are analogous to the Myriad claims directed toward methods of identifying mutations in the BRCA genes, which the Federal Circuit recently held to be patent ineligible in Association for Molecular Pathology v. USPTO, i.e., the Myriad case. 
I think ArcticDx v. Sequenom illustrates some point I have raised in earlier posts to this blog, including a post earlier this week reporting on the Supreme Court's decision to grant certiorari in the Myriad case, i.e., claims to isolated DNA sequences are probably not that big of a deal, and gene patent claims are generally not nearly so preemptive of genetic testing as the ACLU and other critics of gene patents would have us believe.
The lawsuit was filed by ArcticDx earlier this year, alleging infringement of one of its patents, and seeking a declaratory judgment of non-infringement of five Sequenom patents.  None of the patents at issue in this case include a composition of matter claim, there are only method claims. Thus, the classic gene patent claim most people think about, i.e., the isolated DNA claim, is not represented in any of these patents. This is consistent with my view that, at least moving forward, isolated DNA claims are probably not that big of a deal. As I have explained on this blog, in articles I have published in venues such as Nature Biotechnology, and an Amicus brief I filed with the Federal Circuit in the Myriad case, there is good reason to think that few isolated DNA claims would be infringed by most genetic testing activities. Ironically, the Supreme Court granted certiorari solely for the purpose of assessing the patent eligibility of isolated DNA claims.
The five Sequenom patents are numbers 8,053,190; 7,867,727; 7,695,909; 7,351,524; and 8,088,579. The ArcticDx patent is number 8,114,592.
To provide a sense of the nature of the patent claims, claim 1 of the ‘579 patent recites:
A method of screening for susceptibility to developing age-related macular degeneration (AMD) in a subject by determining whether or not the subject's genome encodes a haplotype in the Complement Factor H (CFH) gene associated with reduced susceptibility to developing AMD, comprising determining whether or not a sequence encoding isoleucine at position 62 of the CFH protein is present at the polymorphic site rs800292 (SEQ ID NO:12) in the subject's genome, wherein the presence of said haplotype indicates the subject has reduced susceptibility to developing AMD.

Claim 1 of the 727 patent recites:
A screening method for determining a human subject's propensity to develop an abdominal aortic aneurysm and/or age-related macular degeneration (AMD) comprising: analyzing a biological sample from the subject to detect the presence or absence of a deletion of at least 1000 bp in the region of chromosome 1 between the 3' end of exon 22 of the complement factor H (CFI-1) gene and the 5' end of exon 1 of complement Factor H-related 4 (CFHR4) gene wherein the presence of a deletion indicates the subject is at increased risk of developing an abdominal aortic aneurysm and is at decreased risk of developing AMD.
For comparison, one of the Myriad method claims that was found patent ineligible is claim 1 of US patent number 6,033,857, which recites:
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 sequence identifies a mutant BRCA2 nucleotide sequence.

Note that the Sequenom claims are much narrower than Myriad’s, restricted to specific genetic variations like 1000 base deletion and isoleucine substitution recited in the exemplary claims. In contrast, the Myriad claim purports to cover detection of any mutation in the BRCA2 nucleotide sequence, including mutations that were not identified at the time the patent was filed. This scope, and particularly the apparent inclusion within the claim of genetic variations which had not been identified at the time the patent was filed, has been one of the primary criticisms of Myriad’s method claims.
The consent judgment and settlement between ArcticDx and Sequenom is based upon the parties’ agreement that ArcticDx's AMD testing products and related activities, including “Macula Risk,” do not test for the specific genetic variations recited in Sequenom’s claims, e.g., the specific 1000 base pair deletion or the isoleucine substitution.
I think it is worth noting the scope of the patent claims at issue in this case. In contrast with the Myriad claims, the ArcticDx and Sequenom claims appear to be quite narrow (and perhaps not overly preemptive of genetic testing). These two companies are currently competing in the market for AMD genetic testing, but based on the consent judgment the parties agree that ArcticDx does not need to test for any of the claimed genetic creations in order to provide services. Once again, I think this is consistent with the idea that gene patents, and particularly this sort of method of genetic diagnostic testing claim, is not necessarily as preemptive of genetic testing as some would have us believe.
As another observation, all of the patents at issue in the case are University patents – Sequenom’s patents were all assigned to the University of Iowa or the University of Pittsburgh, and ArcticDx's patent was assigned to Cambridge University. This is consistent with what I have found in studying gene patents, i.e., most of the gene patents which could have an impact on genetic testing come out of universities, including some of Myriads patents.



Monday, December 3, 2012

Supreme Court Grants Certiorari in Myriad Gene Patent Case

On November 30, the Supreme Court granted certiorari in AMP v. Myriad (commonly referred to as the "Myriad" case), as reported on other blogs such as Patently-O, Patent Docs and Pharmapatentblog. There were three questions presented in the plaintiff's petition for certiorari, but the Supreme Court granted the petition with respect to only one -"Are human genes patentable?"

The other questions presented in the petition, but not taken up by the Supreme Court, addressed the Federal Circuit's decision upholding the patent eligibility of Claim 20 (a method of using genetically modified cells to screen for drug candidates) and the issue of standing. The Courts decision to let the Federal Circuit's decision regarding claim 20 stand comes as welcome news, because were the Supreme Court to declare the claim patent ineligible it could have had potentially serious negative ramifications for innovation in health sciences.

It will be interesting to see what the Supreme Court does with the case. The manner in which the plaintiff's framed the question for appeal is somewhat misleading. It has long been well established that human genes per se (as they exist naturally in the human body) are not patent eligible.  The Myriad "gene patent" claims at issue in the case do not encompass human genes as they exist in the body, but rather are limited to "isolated" DNA molecules corresponding structure to naturally occurring gene sequences. So the question is, to what extent might the Supreme Court decide the case in a manner which imposes new constraints on patent eligibility relative to the conventional understanding of the patent office and most patent practitioners, i.e., that naturally occurring biomolecules, including DNA, are patent eligible in their isolated form.

The Supreme Court could find some of Myriad's isolated DNA patent claims patent ineligible without invalidating most issued isolated DNA claims. In particular, the US Solicitor General’s amicus brief at the Federal Circuit argued that claims encompassing isolated genomic DNA sequences are patent ineligible, while claims to isolated cDNA sequences should be considered patent eligible.  I have argued that the Solicitor General's distinction between isolated genomic DNA and cDNA is not supported by the science, but were the Court to adopt it, it would likely result in patent eligibility for most gene patent claims. I have conducted empirical research looking at hundreds of gene patents, and the vast majority of isolated DNA claims appear to be directed towards cDNA, not isolated genomic DNA.

Of course, the Supreme Court could go further, and find that not only isolated genomic DNA, but also isolated cDNA claims are patent ineligible. Or it could go further still, and find that claims to isolated/purified biomolecules in general are patent ineligible. As I have discussed previously, there are many important patents directed towards isolated proteins and other naturally occurring biological molecules. The Biotechnology Industry Organization (BIO) provided numerous examples in their amicus brief filed with the Federal Circuit. Under the rationale used by the District Court in finding Myriad’s isolated DNA claims patent ineligible, it would seem that mere purification/isolation of a naturally occurring molecule would be insufficient to render it patent eligible.

In Judge Lourie’s majority opinion for the Federal Circuit, he made a point of distinguishing between isolated DNA molecules and purified naturally occurring molecules. He found it significant that, according to his understanding, isolation of DNA inherently involves cleaving covalent bonds, rendering Myriad’s claimed isolated DNA structurally distinct from its naturally occurring counterpart. This allowed him to conclude that Myriad’s isolated DNA claims are patent eligible, while leaving undecided the question of whether purification of a naturally occurring molecule (without cleavage of covalent bond or other structural change) would be sufficient to render it patent eligible. I have suspected that perhaps he made this distinction in order to narrow the scope of his ruling, and hopefully avoid the Supreme Court taking the case. After the Prometheus decision, it would not surprise me if at least some Justices on the Supreme Court would reject the notion that purification of a naturally occurring molecule renders it patent eligible.

The irony is that, in my view, the whole furor over isolated DNA claims is something of a tempest in a teapot. In 2012, I just don't believe that claims to isolated human DNA are that relevant. In 2007, I published the results of a study I conducted which looked at all instances of human gene patent litigation in the United States (using a relatively broad definition of "human gene patent"). In that study, I only found two cases in which an isolated DNA claims was successfully asserted against an infringer. One of these cases was Amgen v. Chugai (claim 2 of US Patent No. 4,703,008), decided in 1993, and the other was Promega v. Lifecodes, a relatively obscure case from the 1990s with claims directed towards specific, non-protein encoding genomic sequences useful as "DNA fingerprints" for forensics and paternity testing (US Patent No. 4,963,663).

Significantly, in Amgen v. Chugai claims 4 and 6 were also found valid and infringed, and these claims are directed towards recombinant cells transformed or transfected with the claimed erythropoietin gene. In subsequent cases, Amgen again prevailed against competitors based on infringement of claims directed towards recombinant cells and vectors, the protein product of the gene, and methods of using and producing the product (see Amgen v. Hoechst Marion Roussel and Amgen v. Hoffman-La Roche).  In other words, the isolated DNA claim was probably not necessary in order for Amgen to effectively protect its invention.

Since I conducted my study, I have seen a few subsequently filed cases involving genetic testing and gene patents, but invariably the asserted patent claims are method claims, not isolated DNA claims. I think these method claims are much more relevant for innovation in diagnostics and personalized medicine. Of course, the patent eligibility of these sorts of methods has been called into question by the Supreme Court's recent decision in Prometheus.

As far as product claims go, it should be possible for innovators to draft claims that have some value and which would be patent eligible regardless of how the Supreme Court decides Myriad. For example, Amgen did not just obtain a patent claim to the isolated erythropoietin gene, but also to recombinant vectors comprising the gene, recombinant cells comprising the gene and/or vector, claims to the therapeutic protein product, and a variety of method claims, all of which will very likely remain patent eligible.

As Myriad has long pointed out, the publication of the sequence of the human genome and other developments since the last century will make it difficult going forward to obtain new patents claiming isolated human genes. Method claims will likely be much more important for protecting future genetic discoveries. Most of the human gene patents in existence probably arise from work conducted prior to the turn-of-the-century, and they are already beginning to expire. Despite the ongoing concern, there is little to suggest that isolated DNA claims of the type at issue in this case have been a problem, or will develop into a problem, warranting Supreme Court intervention. But it's not too surprising that the Court took the case, given the number of amicus briefs filed in support of the petition, by groups such as the National Woman's Health Network and American Medical Association, as discussed on a post to Patent Docs.