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.

Thursday, November 29, 2012

District Court Rejects Argument that Hatch-Waxman Safe Harbor Applies to Genetically Modified Crops

I noticed an interesting order issued on November 16 by the District Court hearing Monsanto v. E.I. DuPont De Nemours and Pioneer Hi-Bred International.  The case gathered quite a bit of attention last August when a jury awarded Monsanto a $1 billion verdict for infringement of a patent directed towards Monsanto’s  Roundup Ready gene.  Notably, DuPont had never brought the infringing product to market.  Under Monsanto's damages theory, DuPont is liable for $1 billion in "reasonable royalty"  damages to compensate for its  use of the patented technology in developing DuPont’s Optimum GAT soybean line (which includes both Monsanto’s Roundup Ready gene and the GAT gene, an alternative to the Roundup Ready gene that also confers resistance to glyphosate (trade name Roundup)).   The GAT gene is a synthetic gene developed by Maygen over a decade ago using DNA shuffling technology. The jury's decision was discussed widely on the Internet, for example on the Patently-O blog.

The recent order grants Monsanto’s motion to exclude evidence regarding DuPont's Hatch-Waxman safe harbor defense.  Most of the order is redacted, and I have not read any other rulings or filings the parties have made, but I presume that DuPont is arguing that it's infringement of Monsanto's patent in the development of recombinant Roundup Ready corn is "reasonably related" to the development and submission of information to obtain Federal marketing approval, and thus falls within the Hatch-Waxman safe harbor.  The safe harbor is normally invoked with respect to drugs and medical devices regulated by FDA.

To my knowledge, the Hatch-Waxman safe harbor has never been successfully invoked with respect to an agricultural product, and the conventional wisdom would have it that the safe harbor is limited to drugs and medical devices (see, for example, Dennis Crouch’s Patently-O blog post cited above). According to the court’s order, DuPont has argued for a broader interpretation of the safe harbor provision by relying on the following language from the Supreme Court's 2005 decision in Merck v. Integra: “[the] exemption from infringement extends to all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA." The District Court held that DuPont had taken the Supreme Court’s statement out of context, and that “Merck did not expand the coverage of the safe harbor provision beyond pharmaceuticals and medical devices.”

The Hatch-Waxman safe harbor, codified as 35 USC 271(e)(1), states:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States . . . a patented invention . . . solely for uses a reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological product.

Congress created the safe harbor in 1984 order to speed the approval of generic drugs, at least partially in response to Roche v. Bolar, a 1984 Federal Circuit decision which held that the common law "research use" exception does not apply to infringing activities by a generic company engaged in for the purpose of generating data necessary for FDA approval of the generic drug.  However, the courts have interpreted the statute more broadly, extending the safe harbor to non-drug products and to infringing activities not directed solely to obtaining FDA approval.

For example, in 1990, the Supreme Court held in Eli Lilly v. Medtronic that the safe harbor is not limited to drugs, but also extends to medical devices.  In assessing whether the safe harbor could also apply to an agricultural product like corn, it is informative to consider how the Supreme Court arrived at its holding in Medtronic.

To summarize, the Supreme Court found that Congress had enacted the Hatch-Waxman Act in order to eliminate to unintended distortions of the effective patent term resulting from the premarket approval required for certain products by the Food Drug and Cosmetics Act (FDCA). The first distortion was the reduction of the effective patent life caused by delays associated with obtaining FDA premarket approval. The second distortion was the de facto extension of effective patent life at the end of the patent term which resulted from the inability of a generic competitor to undertake activities necessary for obtaining FDA approval until after the patent expired. This second distortion was reinforced by the Federal Circuit's decision in Roche v. Bolar.

According to the Supreme Court, the Hatch-Waxman Act addresses the first of these distortions by providing patent term extension for patents claiming a "product" subject to regulatory delays caused by the FDA premarket approval process (codified under 35 USC 156). It addresses the second distortion by means of the safe harbor. Congress intended the safe harbor to allow competitors to begin the regulatory approval process while the patents are still in force, followed by market entry immediately upon patent expiration.

The scope of the safe harbor is determined largely by the interpretation of two critical terms in 35 USC 271(e)(1), "patented invention" and "reasonably related." In Medtronic, the Supreme Court concluded that the patent term extension and the safe harbor provisions are complementary, meant to address the two distortions, and tending to offset each other. Based on this conclusion, the Court interpreted the term "patented invention" in section 271(e)(1) to include all products listed in 35 USC 156(f) as eligible for patent term extension, including drugs, medical devices, food additives, and color additives. So while Medtronic explicitly held that the safe harbor extends to medical devices, the logic of the decision dictates that it should also extends to food additives. I haven't researched the question, but I am not aware of any judicial decisions explicitly holding that the safe harbor extends to food additives. Nevertheless, under my reading of Medtronic I think it should.

Whether or not DuPont is entitled to rely on the safe harbor could hinge largely on whether its product is a “food additive” is under 35 USC 156.  The infringement results from the unauthorized introduction of the Roundup Ready gene into DuPont’s soybean line. So the question becomes, is the Roundup ready gene (and its protein product) a food additive under 35 USC 156 that qualifies for the safe harbor under Medtronic?

I'm no expert on FDA regulation of genetically modified plants, and I have not researched the issue in any depth, but my sense is that there is no clear answer to the question of whether Roundup Ready corn should be treated as a food additive eligible for the safe harbor. Section 201(s) of the FDCA defines a “food additive” broadly to include all substances that may reasonably be expected to become components of food, but expressly excludes substances that are generally recognized as safe (“GRAS”). My understanding is that the FDA has taken the position that, with respect to foods derived from genetically modified plants, both the genetic construct and the protein expressed by the gene, could be considered food additives. However, it has also indicated that most foods derived from genetically modified plants are presumptively GRAS. According to a white paper published by the Pew Initiative on Food and Biotechnology, entitled Guide to US Regulation of Genetically Modified Food and Agricultural Biotechnology Products, the only genetically modified food that has triggered the food additive process is Calgene’s FLAVR SAVR tomato.  FDA approved the selectable marker gene used in the tomato, which encodes resistance to the antibiotic kanamycin and its gene product as a food additive in 1994. 59 Fed. Reg. 26,700.

Again, based on my understanding, it seems that the Roundup ready gene and its product are probably not food additives simply because Monsanto (and other developers of Roundup ready products) have represented to FDA that the gene and its product is GRAS, and FDA has acquiesced. But what if DuPont had chosen to treat the Roundup Ready gene as a food additive, and sought premarket approval from FDA? Wouldn't that make the Roundup ready gene a food additive, and hence eligible for the safe harbor? And is it too late for DuPont to seek FDA approval for Roundup ready as a food additive? Would not that render Roundup ready a food additive just like Calgene's kanamycin resistance gene?

Even if DuPont does not seek FDA approval of Roundup ready as a food additive, I think that Federal Circuit precedent does not rule out the possibility that Roundup Ready is nonetheless a food additive eligible for the safe harbor. To illustrate, in 1997 the Federal Circuit held in AbTox v. Exitron that the safe harbor applies to "all inventions" within 35 USC 156, regardless of whether the product qualifies for patent term extension. In particular, the safe harbor applies to Class II medical devices, even though these medical devices are ineligible for patent term extension (Medtronic involved a Class III medical device, a category of medical device that is eligible for patent term extension).   In other words, the Federal Circuit extended the range of safe harbor-eligible subject matter to include products lacking the symmetry of an offsetting patent term adjustment. I could imagine some judges on the Federal Circuit deciding that a recombinant trait such as Roundup ready is a food additive, even if the manufacturer did not seek pre-marketing approval as a food additive, based on the fact that FDA can regulate recombinant genes and their products as food additives, and apparently has done so at least once in the past.

Assuming for the sake of discussion that DuPont could establish that the Roundup ready trait in its soybean is a food additive  for purposes of the safe harbor, the safe harbor would only apply if DuPont’s infringing activity was "reasonably related" to potentially securing FDA approval. In 1992, the Federal Circuit held in Telectronics Pacing Systems v. Ventritrex that demonstrating a medical device at medical conferences was "reasonably related" to FDA approval because it facilitated the selection of clinical trial investigators. In 2005, the Supreme Court in Merck v. Integra held that "reasonably related" activity does not require actual submission of information to FDA, but also includes those situations in which a party has a "reasonable basis for believing that a patented compound may work, . . . and uses the compound in research that, if successful, would be appropriate to include in a submission to the FDA." On remand, the Federal Circuit held that the preclinical research in question was "reasonably related" to FDA approval. Perhaps DuPont could show that its pre-marketing activities developing the infringing Roundup ready soybean were reasonably related to the generation of data that might plausibly have been submitted to FDA.

Genetically modified agricultural products generally require pre-marketing approval from EPA and/or USDA.  This form of pre-marketing approval is outside the FDCA, and so does not appear to fall within the literal scope of the safe harbor statute, i.e., these are not Federal laws "which regulate the manufacture, use, or sale of drugs or veterinary biological products.”  However, with the imminent expiration of RoundupReady patents, there is a great deal of interest in providing a pathway for the approval of "generic" recombinant agricultural products. Congress could consider expanding the safe harbor, for example by removing the statutory limitation to laws which regulate drugs, to include other regulatory laws, such as those applicable non-drug technologies that require premarket approval, genetically modified plants for instance.


Monday, November 26, 2012

Life Technologies Sues Promega for Infringing Reissue Patent Claiming Fluorescence-Based Nucleic Acid Analysis


On November 19, Life Technologies Corporation and the California Institute of Technology sued Promega Corporation in the Central District of California for allegedly infringing US Patent Re-Issue No. 43,096, entitled "Tagged Extendable Primers and Extension Products."  RE43,096 issued on January 10, 2012, as a reissue of US patent number 6,200,748, which issued on March 13, 2001 and is based on an application filed June 7, 1995 (and hence eligible for a term of 17 years from the date of issuance). The application claims priority back to an application originally filed January 16, 1984, which has been the basis for multiple patents, including US patent number 5,821,058, which was recently the subject of an interference between Enzo Life Sciences and Life Technologies (the Board of Patent Appeals and Interferences decided the interference in favor of Life Technologies in 2010).

The patent came out the Caltech laboratory of Leroy Hood, and includes as inventors notable figures in the development of fluorescence-based automated DNA sequencing such as Prof. Hood and Michael Hunkapiller, the former president of Applied Biosystems who was recently named CEO of next-generation DNA sequencing company Pacific Biosciences. The reissue patent claims methods and reagents useful in fluorescence-based nucleic acid analysis. The complaint alleges that Promega infringes by offering various products for genetic assays and analysis, including those sold under the brands "PowerPlex,” “StemElite” and “CellID.”

According to the complaint, the predecessor of RE43,096, the ‘748 patent, it was the subject of prior litigation between the companies that commenced in 2001 and was ended by a settlement between the parties.  According to Life Technologies, as part of the settlement Prometa agreed to pay royalties on the sale of certain products after the reissuance of the ‘748 patent.  Life Technologies complains that Promega has refused to pay these royalties.

Monday, November 5, 2012

Jury Finds ABI’s Sale of DNA Sequencing Reagents and Products Infringed Enzo's Patent

On November 1, in the case of Enzo Biochem v. Applera (D. Conn. No. 04-00929), a jury found Applied Biosystems Incorporated (ABI) liable for directly infringing US Patent Number 5,449,767 by manufacturing and or selling reagent products used in DNA anaysis and sequencing. The jury also found ABI liable for inducing its customers to infringe the patent by selling DNA sequencing instruments and reagents. The jury found that ABI's infringement was not willful, but nonetheless awarded Enzo $48,587,500 in reasonable royalty damages.
The infringed patent claims certain chemical compounds useful as probes in DNA analysis, for example in DNA sequencing. The patent came out of research conducted in the Yale University laboratory of David Ward, and which the University exclusively licensed to Enzo. Initially, the District Court had on a motion for summary judgment ruled the patent invalid as anticipated by prior art, and indefinite based on the use of the claim language “covalently attached directly or through a linkage group that does not substantially interfere with the characteristic ability of the oligo- or polynucleotide to hybridize with a nucleic acid and does not substantially interfere with formation of the signalling moiety or detection of the detectable signal.”
However, in Enzo Biochem v. Applera, 599 F.3d 1325 (Fed. Cir. 2010) the Federal Circuit reversed, holding that with respect to anticipation Enzo had raised a genuine issue of material fact sufficient to survive a motion for summary judgment, and with respect to indefiniteness that the challenged claim language is not indefinite, and more particularly that the terms "hybridize" and “not interfering substantially” are not indefinite. This decision gained a lot of attention, with many people taking the position that the functional language used in the claim did not adequately apprise the public of the scope of these claims directed towards chemical compounds. It was thought that this case might be a good vehicle for the en banc Federal Circuit, or even the Supreme Court, to clarify the standard for satisfying the indefiniteness requirement, and perhaps raise the bar.
However, the petition for en banc rehearing and certiorari were both denied, and the case was sent back to the District Court for the jury to assess the validity and infringement of the patent. The jury found the claims not only to be infringed, but also rejected the anticipation and other validity challenges to Enzo's patent.



Tuesday, October 9, 2012

Bowman v. Monsanto: An Important Case for Agricultural Biotechnology

The Supreme Court recently granted certiorari in Bowman v. Monsanto, an important case for agricultural biotechnology. If the Supreme Court decides to overrule the Federal Circuit's decision in favor of Monsanto, it could seriously impact the ability of agricultural biotechnology companies to recoup their investment in developing traits for seeds that farmers can harvest and replant, such as soybeans.

Prior to agricultural biotechnology, there was little incentive to invest in the development of improved seeds, since farmers have historically been able to save and replant second-generation seeds, preventing seed innovators from recouping the value they create in their seeds. The exception has been hybrid corn, which cannot be saved for replanting without losing beneficial characteristics of the hybrid, effectively forcing farmers to buy new seed each year. This natural technological restriction on seed saving encouraged investment by seed companies such as Pioneer in the development of improved strains of hybrid corn.

In the 1990s scientists at USDA and Delta Pine Land, a cotton biotechnology company subsequently purchased by Monsanto, developed genetic use restriction technology (GURT). GURT allows for the production of seeds that germinate and produce second-generation seeds, but those second-generation seeds are sterile. In effect, this would allow a seed company like Monsanto to impose a technological restriction on the ability of farmers to save and replant seeds, analogous to the inherent restriction on the replanting of hybrid corn. It would also allay concerns that genetically modified crops might escape into the environment and cause environmental harm. However, anti-biotechnology activists learned of GURT and dubbed it "Terminator" technology, and made it a public relations disaster for agricultural biotechnology, and particularly Monsanto. Agricultural biotechnology companies like Monsanto have not used GURT in their products, but have instead relied upon patents to prevent farmers from saving and replanting seeds. In 1999, Monsanto pledged not to use GURT in its products.

Instead, Monsanto has relied upon patent and contract law to prevent replanting of second-generation patented seeds. Basically, purchasers of seeds containing a patented Monsanto trait, such as Roundup Ready soybean, are required to sign a contract agreeing not to save second-generation seeds for replanting. Farmers are of course able under the contract to harvest the seeds for use as food or feed. A number of farmers challenged the enforceability of this system on a variety of grounds, but in 2002 and 2006 the Federal Circuit issued decisions upholding the validity of the arrangement in Monsanto v. McFarling and Monsanto v. Scruggs, respectively. In those cases, the farmer saved and replanted seeds harvested from their own fields, which the Federal Circuit held to constitute infringement of Monsanto's patents.

In 2008, the Supreme Court's decision in Quanta v. LG Electronics cast some doubt on the ability of Monsanto to use patents to prevent replanting of second-generation seeds. In Quanta, the Supreme Court overturned the Federal Circuit's decision that patent owners could place conditions on sales, and held that the authorized sale of a patented product exhausts patent rights in the product. Arguably, Quanta could be interpreted as precluding Monsanto from claiming patent rights in the progeny of seed that had been the subject of an authorized sale, as discussed in a previous post.

In Monsanto v. Bowman, the Federal Circuit held that even post-Quanta Monsanto was not barred by the first sale doctrine from enforcing its patents against farmers who save and replant second-generation seeds. Vernon Bowman is a soybean farmer, and for years he has purchased and planted Roundup Ready soybean, and signed the agreement not to replant. However, he later began purchasing commodity soybeans from a grain elevator that he knew probably were Roundup Ready, planting those seeds, and then harvesting and replanting some of the second-generation seeds grown in his field. He apparently believed that since he did not sign agreement with respect to commodity seeds he was not barred from replanting them. He sprayed the soybeans twice during the season with Roundup, demonstrating that not only did he know that the seeds are Roundup Ready, but also that he was using the glyphosate-resistance properties of the plants.

The Federal Circuit rejected Bowman's argument that his activities were protected by the first sale doctrine. The court held that his purposeful planting and growing of the second-generation seeds constituted more than simply "using” the patented seed, but impermissibly "making" patented product in violation of Monsanto's patent.

In his petition for certiorari, Bowman argues that the ability to make second-generation seed is an inherent characteristic of seeds, and that his natural and foreseeable use of the seeds to produce second-generation seeds is permitted under the first sale doctrine, regardless of whether he sells the seed for use as feed or replants it.

The US solicitor general was invited to file Amicus brief in the case, and did so, advising the Supreme Court not to grant certiorari. The solicitor general agreed with Monsanto and the Federal Circuit that the first sale doctrine under Quanta does not extend to second-generation seed.  The Federal Circuit and solicitor general recognize that the interpretation of the first sale doctrine advocated by Bowman would severely limit the ability of biotechnology companies like Monsanto to recoup their sizable investment in developing agricultural traits.

The grant of certiorari is presumably cause for great concern to Monsanto and other agricultural biotechnology companies selling patented seed that can be saved and replanted. In recent years, when the Supreme Court has granted certiorari in patent cases it has tended to reverse the Federal Circuit, for example in Prometheus, Quanta, KSR, Bilski and Festo.  Because the Federal Circuit is generally the only Court of Appeals to decide patent cases, Supreme Court normally does not accept patent cases to resolve split between the circuits. The fact that it took the case suggests to me that at least some Justices question the Federal Circuit's decision in Monsanto v. Bowman. Of course, that does not necessarily mean the Court will reverse. For example, in LabCorp v. Metabolite (2006) the Supreme Court dismissed a petition for certiorari as improvidently granted, although three of the justices filed a dissent indicating they would have decided the case and overruled the Federal Circuit's decision.

Supporters of Bowman argue that they Federal Circuit's decision will end the long-standing practice of farmers saving and replanting seeds, and of grain elevator selling commodity seeds. They point out that today most of the soybeans collected by grain elevators and sold as commodity seeds contain the patented Roundup Ready trait, since most farmers are planting Roundup Ready soybeans. However, in this case Bowman clearly knew that the seeds he planted were Roundup Ready, since he sprayed the fields repeatedly with Roundup, which he would not have done if he thought he had planted non-glyphosate resistant seeds. I very much doubt whether Monsanto has sued any farmer who bought commodity seeds that happened to include the Roundup Ready trait, but who did not take advantage of the patented trait by using Roundup on his fields. Such a case of inadvertent infringement would clearly raise substantial policy issues, but those are not the facts of this case.

If the Supreme Court reverses the Federal Circuit and holds that companies like Monsanto cannot use their patents to prevent replanting a second-generation seeds, it would be analogous to interpreting the first sale doctrine in copyright as permitting anyone who buys a CD or DVD to make unlimited copies and sell those copies. Clearly the first sale doctrine does not go that far in copyright, and I don't think it should go that far in patent law with respect to self-replicating technologies like seeds. I don't think a farmer who innocently plants commodity seeds that happen to contain the patented Roundup Ready trait, and who does not take advantage of that trait by using Roundup on his fields, should be liable for patent infringement. But I don't think a farmer should be able to take advantage of the first sale doctrine to purposely acquire and grow patented seeds, benefit from the Roundup ready characteristics by using Roundup on the crops, and then use the first sale doctrine as a defense.

If the Supreme Court sides with Bowman in this case, I'm not sure what Monsanto and other agricultural biotechnology companies will do. They might have to alter their licensing practices, as discussed in a previous post. Perhaps they will have to reconsider the use of GURT or some other technological solution in lieu of patents.

Thursday, October 4, 2012

Momenta v. Amphastar:A Divided Federal Circuit Panel Addresses Scope of Hatch-Waxman Safe Harbor for Post-Approval Activities

Biosimilar legislation enacted as part of healthcare reform provides an abbreviated approval process for manufacturer’s of biosimilar biologic drugs. It provides even more benefits for a producer of an interchangeable biologic, including a period of market exclusivity for the first interchangeable brought to market. However, the chemical complexity of biologic drugs compared to traditional small molecule results in significant technical challenges for would-be providers of biosimilar or interchangeable products to demonstrate the chemical similarity required for FDA approval.

What happens if someone invents an analytical process for demonstrating biosimilarity and patents that process, particularly in a situation where there are no practicable alternative methods available for demonstrating biosimilarity? If the innovator company that brought the original biologic to market owns the patent, it could potentially prevent competitors from bringing a biosimilar to market, because they could not demonstrate biosimilarity required for FDA approval without infringing the patent. Alternatively, if a biosimilar manufacture had such a patent it could exclude other biosimilar manufacturers from bringing their products to market. That is, unless the Hatch-Waxman safe harbor under 35 USC 271(e)(1) applies.

A divided panel of the Federal Circuit actually addressed this issue on August 3, 2012, in Momenta Pharmaceuticals v. Amphastar Pharmaceuticals.  The particular drug in question, Lovenox (enoxaparin), it is technically not a biologic, but it is chemically complex and raises the same issues cited above in connection with demonstrating biosimilarity or interchangeability of a biosimilar.  Enoxaparin is a low molecular weight version of heparin, a naturally occurring polysaccharide. The chemical structure of heparin is chemically diverse, with molecules ranging in molecular weight between 5000 and 40,000 Da. There are also differences in disaccharide units and in the modifications to individual sugar units that vary from molecule to molecule.

In order to market a generic version of Lovenox, FDA requires the generic manufacturer to demonstrate a sufficient level of chemical similarity in terms of molecular weight and chemical structure between branded Lovenox and the generic enoxaparin. Establishing this similarity was apparently not trivial, and Momenta (a generic manufacturer) obtained a patent claiming a method of performing the analysis, US Patent Number 7,575,886. Momenta received FDA approval to market generic enoxaparin in July 2010, and begin generating sales revenue of $260 million per quarter.

In September 2011, Amphastar received FDA approval to market its own generic version of enoxaparin, and momenta sued Amphastar for  infringing its patent. Amphastar defended itself by arguing that its use of the patented method fell under the safe harbor of 35 USC 271(e)(1), which provides:

it shall not be enacted infringement to make, use, offer to sell, or so within the United States * * * a patented invention* * * solely for uses reasonably related to the development and submission of information under a federal law which regulates the manufacture, use, or sale of drugs ** * .

In particular, Amphastar argued that it was required to perform the tests to ensure that the product complies with FDA requirements, and that it retained the data so that it could submit it to FDA as necessary.

In response, Momenta argued that the safe harbor did not apply under the circumstances, since the product had already been approved and because Amphastar did not actually submit the information to FDA.

The District Court sided with Momenta, finding that the safe harbor did not apply under the circumstances, and issued a preliminary injunction. The Federal Circuit's 2011 opinion in Classen Immunotherapies v. BiogenicIDEC would seem to support this decision. In Classen, the panel stated that "[271(e)(1)] does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."

On appeal, a divided panel reversed and remanded, finding that the safe harbor does apply to Amphastar’s activities, essentially because the patented test is being used to confirm that its generic product meets the FDA requirement of similarity to branded Lovenox. The majority opinion is written by Judge Moore, who wrote a dissent in Classen arguing for a more expanded interpretation of the safe harbor that would encompass post-approval submissions to FDA.

In Momenta, Judge Moore found that a plain reading of the statute did not limit the safe harbor to pre-approval FDA submissions, and the legislative intent was to promote the availability of generic drugs. She also felt that the requirement that data be generated  for "submission" to FDA was satisfied in this case because FDA regulations required Amphastar to test the drugs for similarity and to maintain the records for one year so they would be available for FDA inspection.

Judge Moore acknowledged that the Classen decision is binding precedent, but she reads Classen as being limited to cases involving "routine submissions" to FDA. In the present case, she found that Amphastar’s actions are not routine, since the company is required to make the data available for FDA in order to maintain FDA approval, in contrast with the optional "routine submissions" at issue in Classen.

Judge Moore also rejected Momenta's argument that the safe harbor did not apply because there were alternate methods available for performing the necessary analysis. She found that the safe harbor applies even if FDA would accept the use of other, non-patented testing methods.

In a strongly worded dissent, Judge Rader (who wrote the majority opinion in Classen) argued that the safe harbor does not apply in this case, and under Classen should not be available for infringing activities relating solely to post-approval FDA submissions. He basically found Judge Moore's decision inconsistent with the majority opinion in Classen, but entirely consistent with her dissent.

Judge Rader adopts a fundamentally different characterization of the Amphastar’s infringing activity than the majority. While the majority finds that the patented test is used to generate data necessary to satisfy FDA regulatory requirements, Judge Rader finds that the method is also being used for the purpose of manufacturing the product. Neither characterization seems implausible to me. Of course the test is being used to analyze the product, but Judge Rader's point is that in order to manufacture FDA-approved generic enoxaparin, it is necessary to conduct the analytical test to ensure that the product meets specifications.

I think the outcome in the case hinges largely upon this distinction between analyzing a product and manufacturing a product. If we accept Judge Rader's view that the patent covers a method used in manufacturing the drug, then the patented invention fails to satisfy the statutory requirement of being used "solely for uses reasonably related to the development and submission of information" to FDA, and the safe harbor should not apply. However, if we characterize the patented method as a method of product analysis, Judge Moore's decision seems reasonable.

In any event, a significant aspect of the decision is that it apparently limits the ability of innovators and biosimilar manufacturers from using patents covering methods of product analysis to keep biosimilar competitors off the market.  This could be important as biosimilar manufacturers seek to enter the market in competition with innovators and other biosimilar companies.



Friday, August 17, 2012

Association for Molecular Pathology v. US PTO Decided on Remand

As reported in previous posts, on petition for certiorari the Supreme Court vacated the Federal Circuit's 2011 decision in Association for Molecular Pathology v. US PTO and remanded the case for further consideration in light of its decision in Mayo v. Prometheus. Yesterday, the Federal Circuit issued its decision on remand. Of course, this might not be the end of the story, since the plaintiffs will presumably petition for rehearing by the en banc Federal Circuit and/or certiorari by the Supreme Court. Some believe that the Supreme Court is likely to grant certiorari, based on the diverging opinions of the three Federal Circuit judges, and the arguably short shrift given by the majority to the relevance of Mayo to the Myriad claims.
Not surprisingly, the Mayo decision and the parties' subsequent re-briefing and re-arguing of the case did not alter the views of any of the three Federal Circuit judges deciding the case. As was the case in the first decision, the judges all agreed that the claims directed towards methods of testing for genetic variations in the BRCA genes are patent ineligible.  The majority (Judges Lourie and Moore) held the claims to isolated DNA molecules and the claim reciting a method for using a cell-based assay to screen for potential cancer drugs (claim 20) to be patent eligible. Judge Bryson, in dissent, agreed that claim 20 is patent eligible, but maintained his earlier position that the isolated DNA claims are patent ineligible, based largely on perceived policy concerns.

Writing for the majority, Judge Lourie noted that the only issue to be considered on remand was the applicability of the Supreme Court’s Mayo holding to the patent eligibility of the claims at issue.  He emphasized that the court was not addressing the overall patentability of the claims, only the eligibility of the claimed subject matter for patent protection, nor was the court addressing the policy concerns that had been raised with respect to "gene patents" and Myriads patent enforcement and licensing practices.
With respect to the isolated DNA claims, Judge Lourie found that Mayo "does not control," because the claims are directed towards compositions of matter, not methods. Recall that all of the claims at issue in Mayo were directed towards processes, not compositions of matter, and many  (including myself) have arguedthat Mayo is not applicable to composition of matter claims.

Judge Lourie appears to have adopted this position, explaining that “while Mayo and earlier decisions concerning method claim patentability provide valuable insights and illuminate broad, foundational principles, the "the Supreme Court’s decisions in Chakrabarty and Funk Brothers set out the primary framework for deciding the patent eligibility of compositions of matter, including isolated DNA molecules.” Based on this premise, he ruled that “the issue of patent-eligibility [with respect to composition of matter claims] remains, as it was on the first appeal to this court, whether they claim patent ineligible products of nature.” In the view of the majority, the claimed isolated DNA molecules are not found in nature, and hence are not products of nature, but rather patent eligible compositions of matter.

The majority also held that Mayo did not alter the outcome with respect to the method claims. The patent ineligibility of the method of diagnostic claims was a foregone conclusion  - as interpreted by the Federal Circuit, they could be infringed by merely comparing DNA sequence information, and hence lie much further down the spectrum of patent ineligibility than the claims at issue in Mayo, which at least involved a physical step of analyzing a blood sample taken from a patient.

The patent eligibility of claim 20 was more in doubt. Conceivably, the claim could have been found patent ineligible under a broad reading of Mayo. In fact, Eli Lilly submitted an amicus brief arguing that claim 20 was patent ineligible because it involved a step that could be performed in the mind. If the court had adopted Lilly’s radical theory of patent eligibility, it could have drastically constricted the range of patent eligible methods (and in doing so substantially eased the freedom to operate concerns of research pharmaceutical companies such as Eli Lilly). However, the court declined to go down this route, and did not even mention Lilly’s proposal.
Judge Lourie essentially held claim 20 to be patent eligible because the claimed method is based on a man-made, non-naturally occurring (and hence patent eligible) material, i.e., a cell transformed with a BRCA gene.  This is an interesting interpreation of Mayo. Recall that the method claims found to be patent ineligible in Mayo all center around the analysis of man-made, non-naturally occurring (and hence presumably patent eligible) drugs and drug breakdown products.  Judge Lourie chose not explain the distinction between claim 20 and the method claims at issue in Mayo.

Questions Remaining

The decision leaves unanswered a number of questions. For example, the majority's decision with respect to the isolated DNA claims seems to depend upon the chemical structural differences between the claimed isolated DNA and DNA that occurs naturally. In particular, Judge Lourie emphasized that the isolation of DNA molecules inherently involves the breaking of covalent bonds, and hence the isolated DNA molecule is chemically distinct from its natural counterpart. Where does that leave isolated natural products that are not chemically distinct from their natural counterpart, i.e., what if the isolation of a natural product does not inherently involve breaking covalent bonds?

Judge Lourie makes much of a perceived distinction between "isolation" and "purification" of DNA molecules, and seems to suggest that the mere purification of a natural product might not be sufficient for patent eligibility. This is concerning, because isolated natural products have long been considered patent eligible.  The amicus brief submitted by the Biotechnology Industry Organization provides numerous examples of non-DNA isolated natural products that have been patented, and that have proven highly beneficial to society.

There is also the important question of to what extent methods of diagnostic testing, and personalized medicine, or eligible for patent protection in view of Mayo.  The Myriad method of diagnostic claims held to be patent ineligible in this case were interpreted by the court to cover the mere mental comparison of genetic sequence information, and clearly such claims are patent ineligible. But the vast majority of diagnostic claims involve physical steps such as obtaining physical samples from patients, performing clinical tests on the sample, and/or using the information generated in the treatment of a patient. It is not clear at this point how these claims would fare under a Mayo analysis, but Judge Lourie's opinion with respect to claim 20 suggests he would interpret Mayo in a manner that would maintain patent eligibility of at least some diagnostic/personalized medicine claims, if drafted more narrowly than Myriad’s claims.

Saturday, June 16, 2012

BIO, AUTM and the Coalition for 21st Century Medicine file amicus brief in Myriad Remand

The Biotechnology Industry Organization (BIO), joined by the Association of University Technology Managers (AUTM) and the Coalition for 21st Century Medicine (representing diagnostic companies) has filed an amicus brief in the Myriad case, available here.

BIO et al. argue that Mayo  (a Supreme Court decision specifically addressing the patent eligibility of process claims) does not apply to manufacture or composition of matter claims, and thus should not alter the Federal Circuit’s original decision finding all of the challenged isolated DNA claims patent eligible. They also argue that were the court to rule that the isolated DNA claims are patent ineligible, it would have far-reaching negative consequences for innovation, pointing out many examples in which important innovations that have benefitted healthcare and the environment have been incentivized by patents on isolated DNA molecules and other isolated natural products.

With respect to claim 20, the cell-based assay claim, they argue that the claimed method is clearly patent eligible since it recites the use of a transformed (i.e., genetically modified) cell that would itself be patent eligible.

U.S. Governemnt Files Brief in Myriad

The U.S. has filed a brief in Myriad, available here, which argues that under Mayo “isolated but otherwise unmodified DNA molecules are not patent-eligible because they are products of nature, not human-made inventions.” The government also argues that under Mayo the claims are patent ineligible because they effectively preclude the public from using a product of nature, and because the need for financial incentives in a particular field does not alter the requirements of § 101.

The brief I filed is available here.

Friday, June 15, 2012

And Many More Myriad Briefs

And here are links to more Myriad briefs for those interested:

Supplemental Brief for Appellant (Myriad)

Brief of Amici Curiae The National Women’s Health Network, et al

Brief of Amici Curiae New York Intellectual Property Law Association

Brief of Amici Curiae American Medical Association, et al

Brief of Amici Curiae AARP, et al

Brief of Amici Curiae Intellectual Property Owners Association

Brief of Amici Curiae professor Eileen M. Kane in Support of Plaintiffs-Appellees and Affirmance

Brief of Amici Curiae Mark J. Gatschet, et al.

Brief for Amicus Curiae American Intellectual Property Law Association

More Myriad Briefs

Here are some more briefs recently filed in the remanded Myriad case.

ACLU and the Public Patent Foundation have filed their supplemental brief on behalf of plaintiffs, available here. Not surprisingly, they argue that the challenged isolated DNA claims, and claim 20 of the '282 patent (these cell based assay claim) are all patent ineligible under Prometheus, and for affirmance of the district court decision.

Knowledge Ecology International and Universities Allied for Essential Medicines have filed an amicus brief in support of the plaintiffs, available here. They argue that isolated DNA patents hinder science and harm healthcare, and that adequate non-patent incentives for pharmaceutical innovation are available (such as FDA data/marketing exclusivity), and ask the Federal Circuit to affirm the District Court's decision.

Gilead Sciences, Confluence Life Sciences and Euclises Pharmaceuticals have filed a joint amicus brief that focuses exclusively on claim 2 of the ‘282 patent, i.e., the cDNA claim, and argues that cDNA is clearly man-made patent eligible subject matter. The brief, available here, asks the Federal Circuit not to reverse its earlier decision.

Amicus Briefs In Remand of Myriad

Today is the deadline for filing amicus briefs for the Federal Circuit to consider when it decides the Myriad gene patent litigation, i.e. The Association for Molecular Pathology v. US Patent and Trademark Office, on remand. The first time the Federal Circuit heard the case, I joined with Robert Cook-Deegan in filing a brief arguing that the isolated DNA claims should not be declared patent ineligible, but rather that their validity should be assessed under the more conventional requirements of patentability, i.e., novelty, nonobviousness and enablement. This time I went it alone, and filed a brief on my own behalf, available here (I believe that Bob will also likely be filing his own brief).

In my latest brief, I focus largely on the nature of genomic DNA and cDNA, and the processes by which they are "isolated," and argue that the challenged isolated DNA claims (when properly interpreted) are limited to synthetic molecules that did not originate in the human body, and which are substantially different from naturally occurring chromosomal DNA both structurally and functionally. I also address an argument made by the US government in its amicus brief, i.e., that cDNA is fundamentally different from isolated genomic DNA, and as a result claims limited to isolated cDNA should be considered patent eligible, while claims encompassing isolated genomic DNA are not patent eligible. To the contrary, I argue that isolated genomic DNA and cDNA are quite analogous, and are not different in a way that would justify differential treatment under the patent eligibility doctrine.

I also point out that the Federal Circuit’s earlier decision includes a number of unfounded assumptions regarding the utility of isolated genomic DNA, and the impact of isolated DNA patents on genetic testing and whole genome sequencing. The brief concludes by observing that a determination 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.

Protein Sciences Corporation has filed its own Amicus brief, available here, which argues that:
Prometheus applies to method claims and does not change this Court’s correct decision as to the Representative Composition Claims, i.e., that isolated DNA molecules and cDNA are patent eligible subject matter under § 101; and that applying Prometheus to the Comparing or Analyzing Claims produces the same result as in Myriad, because the “transformed cells containing an altered BRCA1 gene causing cancer” are not naturally occurring cells, [and thus] the growing of those cells in the presence and absence of a putative cancer therapeutic in the Growth Rate Claim cannot be a method calling for applying a law of nature.
Eli Lilly has also submitted a brief, available here, which does not address the isolated DNA claims, but argues that claim 20 (the method claim reciting the use of BRCA gene in cell-based assay to screen for potential drug candidates) is patent ineligible if it includes a "mental step."

Tuesday, April 3, 2012

Computer-Implemented Method for Guiding Therapeutic Treatment Ruled Patent Ineligible under Mayo v. Prometheus

On March 30 the United States District Court for the District of Columbia dismissed a lawsuit between Plaintiff SmartGene, Inc., a North Carolina corporation and Defendant Advanced Biological Laboratories, SA, a company with its principal place of business in Luxembourg, after declaring the patents in dispute (U.S. Patent No. 6,081,786 (the “786 patent”) and U.S. Patent No. 6,188,988 B1 (the “988 patent”)) patent ineligible under 35 USC 101. (Click here for decision)

The plaintiff SmartGene brought the suit as a declaratory judgment action, after ABL filed a lawsuit alleging that “Smartgene’s IDNS™ HIV program incorporates at least one technology which infringes at least claim 1 of each [of] the ‘786 and ‘988 Patents.”

The court's analysis focused on Claim 1 of the ‘786 patent as exemplary of the subject matter covered by the patent dispute:

1. A method for guiding the selection of a therapeutic treatment regimen for a patient with a known disease or medical condition, said method comprising:
(a) providing patient information to a computing device comprising:
a first knowledge base comprising a plurality of different therapeutic treatment regimens for said disease or medical condition;
a second knowledge base comprising a plurality of expert rules for evaluating and selecting a therapeutic treatment regimen for said disease or medical condition;
a third knowledge base comprising advisory information useful for the treatment of a patient with different constituents of said different therapeutic treatment regimens; and
(b) generating in said computing device a ranked listing of available therapeutic treatment regimens for said patient; and
(c) generating in said computing device advisory information for one or more therapeutic treatment regimens in said ranked listing based on said patient information and said expert rules.

The district court began by observing that a recent Federal Circuit decision, MySpace, Inc. v. Graphon Corp., had cast doubt upon the use of § 101 subject matter inquiry as a threshold question, and cautioned that lower courts should avoid the “swamp of verbiage that is § 101 by exercising their inherent power to control the processes of litigation, . . . and insist that litigants initially address patent invalidity issues in terms of the conditions of patentability defenses as the statute provides, specifically §§ 102, 103, and 112.” However, the district court concluded that the Supreme Court's recent decision in Mayo v. Prometheus had unambiguously rejected this approach, and firmly established “the § 101 subject matter patentability inquiry as the threshold inquiry for patent validity.
The court's analysis focused on comparing the claims at issue to “Supreme Court caselaw ‘guideposts’ on the subject of patent subject matter eligibility [Benson, Diehr, Flook, Bilski, Prometheus]; and then examining whether the patents-in-dispute [] satisfy the MOT test, and [] constitute eligible subject matter irrespective of the MOT test.”

The court analyzed the claim under the approach used by the Supreme Court in Prometheus, i.e., by determining that the individual steps recited in the claim method are "routine, well understood and conventional." The court concluded that the steps of the claim “describe abstract ideas that are commonly performed by medical professionals in evaluating, considering and constructing treatment options for a patient presenting a specific medical condition. As with the claim examined in Prometheus, these ‘steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.’”

The machine or transformation test played a substantial role in the courts analysis. The court concluded that the claim failed the machine prong of the test because the “generic token reference of a ‘computing device’ in the claims [] does not identify any particular machine or provide any indication of what particular type of machine is to be used,” and because “the computing device referenced in the claims is incidental to the claimed invention and is not used for more than ‘insignificant postsolution activity’”.

Regarding the transformation prong of the test, the court held that “transformation must be central to the purpose of the claimed process” and the “mere manipulation or reorganization of data . . . does not satisfy the transformation prong.” The court concluded “that the defendants’ claims mirror the mental processes that a physician performs, and therefore embody the ‘basic tools of scientific and technological work’ that are free to all men and reserved exclusively to none.’”

Thanks to Docket Navigator for making me aware of this decision.

Friday, March 30, 2012

District Court Sees through Misleading Allegations in PubPat Lawsuit against Monsanto

In a recent post, I pointed out similarities between "fabrications" regarding conditions at factories in China manufacturing Apple products, and the misinformation being promulgated regarding gene patents and agricultural biotechnology. Some prime examples of this sort of misleading information are evident, I think, in the lawsuit filed last year by the Public Patent Foundation against Monsanto. In a post on the case, I pointed out that the plaintiffs in the case seemed to lack standing, and that there seemed to be no basis for PubPat’s allegation that Monsanto had sued involuntary/inadvertent infringers, or that there was any reasonable likelihood that the plaintiffs (organic farmers and the like) would be sued for infringing Monsanto patents on recombinant crops.

Fortunately, the district court saw through the exaggerated allegations raised by the Public Patent Foundation in the lawsuit against Monsanto, and dismissed the case last February. The court's decision specifically addresses some of these unfounded assertions.

For example, the complaint alleges that certain plaintiff farmers and seed distributors were afraid that their crops and seeds would be contaminated by recombinant Monsanto products. In rejecting this argument, the court pointed out that none of the plaintiffs claimed that contamination had actually occurred in any of the crops they had grown or seeds they have sold.

The complaint further alleged that organic farmers risked losing their organic certification if their fields became contaminated by recombinant product, but the court found “no evidence in the record that any farmer has ever been decertified as organic by the U.S. Department of Agriculture National Organic Program (the “NOP”) because of seed contamination.” In fact, according to the NOP, “[o]rganic certification is process based, and as a result, “[i]f all aspects of the organic production or handling process were followed correctly, the presence of a detectable residues from a genetically modified organism alone does not constitute a violation of this regulation.”

The complaint also alleged that the plaintiff farmers risk being sued for patent infringement based on inadvertent growth of crops with Monsanto's patented traits. However, the court found that Monsanto had never filed a patent infringement suit against a certified organic farm or handling operation over the presence of patented traits in its operations. In fact, during oral arguments Monsanto stated that they had never sued the party who did not “want to make use of the traits that are manifested in [defendants’] transgenic products.” The court noted that Monsanto had expressly declared that it is not their policy “to exercise [their] patent rights where trace amounts of our seed or traits are present in [a] farmer’s fields as a result of inadvertent means.” The court went on to find that although the complaint “alleges without specification that defendants have accused certain non-intentional users of Monsanto’s seed of patent infringement and threatened them with [litigation, no] plaintiffs claim to have been so threatened.”

The complaint alleged that the organic farmers feel threatened by the fact that between 1997 and 2010 Monsanto filed 144 patent infringement lawsuits against farmers. However, the court found that plaintiffs had overstated the magnitude of Monsanto's patent enforcement, since this "average of roughly 13 lawsuits per year is hardly significant when compared to the number of farms in the United States, approximately two million."

The plaintiffs alleged that Monsanto had filed patent infringement lawsuits against other farmers who did not want to grow patented crops, citing specific examples where this had allegedly occurred, but the court found that this assertion was:

“belied by the decisions in the suits against the referenced individuals. See Monsanto Co. v. Parr, 545 F. Supp. 2d 836, 842-44 (N.D. Ind. 2008) (defendant intentionally induced others to infringe Monsanto’s patents); Monsanto Co. v. Nelson, No. 4:00-CV-1636, 2001 U.S. Dist. LEXIS 25132, at *2 (E.D. Mo. Sept. 10, 2001) (Monsanto alleged that defendants had intentionally saved and replanted second generation seed with patented traits in violation of their licensing agreement); Monsanto Can. Inc. v. Schmeiser, 2001 FCT 256 [120] (Can.) (finding that the defendant saved and planted seed “he knew or ought to have known was Roundup tolerant”).”

I found it particularly gratifying that the court addressed the widely held misperception that Percy Schmeiser, a Canadian farmer who took Monsanto to the Canadian Supreme Court (and lost) and became somewhat of a folk hero in the process, was an innocent victim whose fields were contaminated by Monsanto product. If you actually read the decisions from the Canadian courts, it is very clear that the court was convinced that Schmeiser had actively selected for and cultivated Monsanto Roundup ready seeds on his property without authorization and without paying any licensing fee (see my previous post).

The court was particularly critical of the Public Patent Foundation’s characterization of an attempt by Monsanto to reassure organic farmers that they would not be sued for inadvertent infringement as an "implicit threat" by Monsanto. The Public Patent Foundation had written a letter to Monsanto basically asking for a blanket immunity for all the plaintiffs against ever being sued for patent infringement, even if they did intentionally engage in infringing activity. Monsanto responded with a statement of its policy, which it had previously published in other venues:

“It has never been, nor will it be[,] Monsanto policy to exercise its patent rights where trace amounts of our patented seeds or traits are present in [a] farmer’s fields as a result of inadvertent means.”

Amazingly, the Public Patent Foundation characterized Monsanto's statement as an implicit threat, and as such the basis for declaratory judgment action.

The court totally rejected this flawed logic, declaring it "objectively unreasonable for plaintiffs to read [the language of Monsanto statement] as a threat." The court also stated that,

"[i]ndeed, plaintiffs’ letter to defendants seems to have been nothing more than an attempt to create a controversy where none exists. This effort to convert a statement that defendants have no intention of bringing suit into grounds for maintaining a case, if accepted, would disincentivize patentees from ever attempting to provide comfort to those whom they do not intend to sue, behavior which should be countenanced and encouraged. In contrast, plaintiffs’ argument is baseless and their tactics not to be tolerated.”
It bears noting that critics of Myriad Genetics have repeatedly complained that Myriad should make an explicit statement that the company promises not to sue entities that infringe its BRCA patents in the context of research or non-commercial testing. But I've always maintained that Myriad is rightly concerned that such a statement could be used against them. Here we see a perfect example of this, with the Public Patent Foundation using Monsanto's attempt to reassure inadvertent infringers that they will not be sued as a weapon against Monsanto.

The district court in this case, fortunately, rejected the argument, and noted that public policy dictates that companies such as Monsanto should be encouraged to provide such reassurance, not punished, and that the Public Patent Foundation's tactic of using the statement against Monsanto is "not to be tolerated." But with all the advocacy groups out there gunning for Myriad, is it any wonder the company would be reluctant to open itself up to the negative unintended consequences of an explicit statement of immunity for some infringers?