Supreme Court Denies Cert in Case Involving Post-Filing Evidence in Assessing Obviousness of Pharmaceutical Inventions

On January 20, 2015, Bristol-Myers Squibb petitioned for certiorari in Bristol-Myers Squibb v. Teva Pharmaceutical, asking whether an assessment of obviousness should "consider post-filing evidence showing the actual differences between a patented invention and the prior art.”  The Supreme Court denied the petition on May 4, but it remains an important issue, particularly for the biotechnology and pharmaceutical industries. Two concurring and two dissenting opinions followed by various combination of Federal Circuit judges in the denial of a petition for en banc rehearing highlight the confusion and divergence opinion among the members of that court.

In an article published in Biotechnology Law Report, I explained how the Federal Circuit panel’s ruling that post-filing date toxicity data is not probative of nonobviousness appears to run counter to a well-established body of Federal Circuit case law standing for the opposite proposition, i.e., that post-filing evidence can be used to establish the nonobviousness of an invention. The article also reviews some of the arguments made in support of the petition for certiorari by amici representing the biotechnology and pharmaceutical sectors, and critiques the highly divergent views of several Federal Circuit judges who have weighed in on the issue.

 

 

Agilent and Tecan Sued for Infringement of Patents Claiming Microarray Technology: The Back Story of an Apparently Non-Practicing Entity

On June 18, 2015, Gene Reader LLC sued Agilent and Tecan in the Eastern District of Texas, alleging infringement of United States Patent Nos. 6,545,758 (the "'758 patent") and 6,567,163 (the "'163 patent"), both entitled "Microarray Detector And Synthesizer." The allegedly infringing products include Agilent’s SureScan Microarray Scanner and Tecan’s PowerScanner.  According to the complaint, product features that contribute to the infringement include “a spatial light modulator capable of selectively optically interrogating a patterned microarray [,] a synchronous detector capable of detecting an optical signal obtained from the patterned microarray [and] a processor capable of performing repetitive comparative measurements of the optical signals from one or more sites on the patterned microarray.”

The patents have an interesting back story. Both patents issued from applications filed in 2000, and the sole named inventor is Perry Sandstrom. According to this article, Sandstrom was electrical engineer for the Wisconsin Center for Space Automation and Robotics at UW-Madison who first became interested in biotechnology in the 1980s based on “social contacts with graduate students in genetics.”  This interest led him to invent the SynchroGene Reader, described as a “simpler, faster, more cost-effective way of analyzing hybridization microarrays, otherwise known as DNA chips or biochips.”  He built his first DNA-chip readers in a “quiet basement electronics shop.” He eventually started a company called Able Signal LLC to commercialize the technology , and in 2003 he was awarded a $100,000 prize called the Wallace H. Coulter Award for Innovation and Entrepreneurship, which he used to fund the company.

Flash forward to 2015, and it appears that Able Signal LLC never succeeded in commercializing the technology, and the patents have been assigned to Gene Reader LLC.  By all indications, Gene Reader is a non-practicing entity established solely to license, and if necessary, enforce the patents. An Internet search revealed no other information about the company other than that it had filed these two lawsuits, and the complaint states that Gene Reader is a Texas LLC with a place of business located on the same street as the Eastern District of Texas courthouse (Preston Road). The Eastern District of Texas is a popular forum for patent litigation, and is perceived by many to be a relatively friendly venue for patent owners. These two lawsuits appear to be the first filed by Gene Reader, but future lawsuits would not surprise me.

Nonpracticing entities, sometimes referred to as patent trolls, are often maligned, and have been the target of certain "patent reform" efforts.  But the inventor of these patents seems to have invested time, effort, and money in an attempt to commercialize the patented technology, and the activities of Gene Reader might be characterized as an attempt to salvage some return on that investment. The ability of an innovator to sell its patents to a nonpracticing entity like Gene Reader could provide an additional incentive to invest in commercialization, since it provides an additional opportunity to recoup investment even if the startup company does not succeed in bringing its own product to market.

Kristen Osenga, a professor at the University of Richmond School of Law, and (along with myself) a Senior Fellow at the Center for Intellectual Property, recently published an interesting article on a related topic entitled “Formerly Manufacturing Entities -- Piercing the 'Patent Troll' Veil,” which uses case study analysis to focus on one type of patent troll – the formerly manufacturing entity, i.e., patent trolls that “used to make or do something in commerce, but now derive all or a significant portion of their income through licensing their intellectual property.”

 

 

 

Cephalon v. Abraxis: Abraxane Does Not Infringe Cephalon's Patent Claiming Porous Paclitaxel Matrices

On June 17, 2015, the Federal Circuit affirmed a district court’s determination in Cephalon v. Abraxis that Celgene’s Abraxane drug product, which contains a fast-dissolving form of paclitaxel, did not infringe Cephalon’s U.S. Reissued Patent No. RE40,493 (“the ’493 patent”), titled “Porous Paclitaxel Matrices and Methods of Manufacture Thereof.”  Paclitaxel is a type of taxane compound derived from the bark of the Pacific yew tree that, in the words of the patent, exhibits “extremely low solubility in water,”, making effective administration challenging.  The ’493 patent addresses the solubility problem by integrating paclitaxel into a “porous matrix form which forms nanoparticles and microparticles of paclitaxel when the matrix is contacted with an aqueous medium.”

Resolution of the dispute centered around the construction of the claim term “microparticles” and “nanoparticles.” The claims recite “nanoparticles and microparticles of a taxane, wherein the nanoparticles and microparticles have a mean diameter between about 0.01 and 5 μm.”  The district court construed “nanoparticles” to mean “particles that have a mean diameter of between about 1 to 1000 nanometers and less than that of microparticles,” and construed “microparticles” to mean “particles that have a diameter of between about 1 to 1000 microns and greater than that of nanoparticles.”  The patent owner argued that the two terms (“microparticles” and “nanoparticles”) should be construed as meaning exactly the same thing, namely, “particles of a taxane having a mean diameter between about 0.01 and 5 μm.” The patent owner stipulated to non-infringement under the district court’s interpretation of the terms.

In reviewing the district court’s claim construction, the Federal Circuit applied the relatively deferential “clear error” standard, as set forth in the Supreme Court’s Teva decision, after noting that that the terms “microparticles” and “nanoparticles” are technical words, and therefore that the “scientific community’s understanding of the terms” is a question of fact reviewable for clear error.

 A claim amendment during prosecution of the patent figured prominently in the Federal Circuit’s interpretation of the terms “nanoparticles” and “microparticles.” The claims originally recited “microparticles of a taxane, wherein the microparticles have a mean diameter between about 0.01 and 5 μm,” i.e., the original claims did not recite nanoparticles. The examiner rejected the claims in view of prior art that purportedly rendered the use of micron -sized particles obvious. The applicant responded by arguing that “[t]here are no nanoparticles” in the cited prior art, and by amending the claims to recite “nanoparticles and microparticles” rather than simply “microparticles.” The amendment did not alter size range of the particles (0.01 to 5 μm).

 
The Federal Circuit found that the amendment precluded the patent owner’s proposed claim construction, noting that under this construction:

[A] pharmaceutical composition could incorporate only micron-sized particles and still fall within the scope of the claims. Such a construction is inconsistent with [the patent owner’s] amendment adding “nanoparticles and” to overcome [the prior art’s] use of only microparticles. [The patent owner] does not offer an explanation of why the word “nanoparticles” was added during prosecution, stating only “the inventors tweaked their nomenclature” which it claims “was a matter of semantics, not substance.” This assertion, however, is unsupported by the prosecution history.

PTAB Institutes IPR of Alethia Biotherapeutics Patent Claiming Use of mAb to Treat Bone Disease

On June 15, 2015, the Patent Trial and Appeal Board (PTAB) instituted inter partes review (IPR) with respect to claims 1-6, 8-11, and 15-23 of US Patent Number 8,168,181 (Case IPR2015-00291).   The ’181 patent discloses "methods of modulating osteoclast differentiation, which may be useful in the treatment of bone loss or bone resorption in patients suffering or susceptible of suffering from a certain conditions such as osteoporosis."

Claim 1 is representative.

1. A method of impairing osteoclast differentiation in a mammal in need thereof, the method comprising administering an antibody or antigen binding fragment which specifically binds to human Siglec-15 (SEQ ID NO.:2) or murine Siglec-15 (SEQ ID NO.:108) to said mammal.

The patent owner is Alethia Biotherapeutics, a Montreal-based biotechnology company “[e]ngaged in the discovery and development of therapeutic mAbs against highly-disease tissue specific novel clinically-relevant targets.” The petitioner is Daichi Sankyo, a Japanese pharmaceutical company. According to Alethia Biotherapeutics, the two companies are developing competing products for treating bone disease based on anti-Siglec-15 antibodies that inhibit osteoclast differentiation.

The PTAB determined that there is a reasonable likelihood that Petitioner would prevail in demonstrating the unpatentability of the challenged claims as anticipated by a published PCT application, Yoshiharu Hiruma et al., WO 2009/048072.  The Hiruma reference is Daichi Sankyo's own PCT application, and the two companies appear to be attempting to patent similar same subject matter.

A critical issue in the case is whether the challenged claims are able to benefit from the filing date of a parent application.  The filing date of the ‘181 patent is October 16, 2009, but it claims priority to a continuation-in-part filed January 13, 2009, and a PCT application filed February 13, 2007. The prior art, Hiruma, published on April 16, 2009. Thus, If Alethia is able to claim priority to the earlier filed applications, then Hiruma is not prior art. But Daichi Sankyo argues that the earlier filed applications do not satisfy the written description and enablement requirements of Section 112 with respect to the challenged claims, and thus that the claims are entitled to a priority date “no earlier than April 16, 2009.”

In granting the petition, the PTAB found that “Petitioner has presented sufficient evidence, on the present record, to persuade us that the challenged claims of the ’181 patent are entitled to a priority date no earlier than April 16, 2009, on the basis of lack of adequate written description support and/or enablement of the claim subject matter in the Parent Application.

In its Preliminary Response, the Patent Owner argued that the petition should be denied because in related proceedings the PTO and PTAB have already addressed, or are currently addressing, petitioner’s arguments concerning the alleged lack of 112 support for the parent applications.  The Patent Owner also argued that Petitioner should be precluded from making arguments based on 112, i.e., lack of enablement and written description, because by statute IPR is limited to challenges based on 102 and 103, i.e., lack of novelty and obviousness. The PTAB rejected these arguments, at least for the purpose of deciding the question of whether the review should be instituted.

The PTAB decision points out that “Patent Owner does not dispute at this time that Hiruma discloses the limitations recited in the challenged claims.”  For strategic reasons, it is not uncommon for patent owners to hold back some of their best arguments at the Preliminary Response stage, saving them to use in their full Response, which is only necessary in the event IPR is instituted.  This could be what is going on here.

Denial of IPR Petition Sends Roche/Mayo Patent Back to District Court to Face Invalidation Under 101

On June 11, 2015, the Patent Trial and Appeal Board (PTAB) denied a petition for Inter Partes Review (IPR) filed by Cepheid against patent owners Roche Molecular Systems and Mayo Foundation for Medical Education and Research in connection with US patent number 5,643,723 (Case IPR2015-00255). The ’723 patent “is directed to methods based on the polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) and concurrent determination of its drug susceptibility, utilizing the appropriate oligonucleotide primers.” Claim 1 is representative.

1. A method for detecting Mycobacterium tuberculosis in a biological sample suspected of containing M. tuberculosis comprising:

(a) subjecting DNA from the biological sample to polymerase chain reaction using a plurality of primers under reaction conditions sufficient to simplify a portion of a M. tuberculosis rpoB gone to produce an amplification product, wherein the plurality of primers comprises at least one primer that hybridizes under hybridizing conditions to the amplified portion of the gone at a site comprising at least one position-specific M. tuberculosis signature nucleotide selected, with reference to FIG. 3 (SEQ D NO:1), from the group consisting :

a G at nucleotide position 2312,

a T at nucleotide position 2313,

an A at nucleotide position 2373,

a G at nucleotide position 2374,

an A at nucleotide position 2378,

a G at nucleotide position 2408,

a T at nucleotide position 2409,

an A at nucleotide position 2426,

a G at nucleotide position 2441,

an A at nucleotide position 2456, and

a T at nucleotide position 2465; and

(b) detecting the presence or absence of an amplification product, wherein the presence of an amplification product is indicative of the presence of M. tuberculosis in the biological sample and wherein the absence of the amplification product is indicative of the absence of M. tuberculosis in the biological sample.

The patent also includes product claims directed towards primers for use in this diagnostic method.

The petition for IPR was prompted by a lawsuit that Roche Molecular Systems filed on July 16, 2014, alleging that Cepheid’s XpertMTB/RIFAssay infringes the patent (Roche Molecular System v. Cepheid, Docket No. C-14-3228, N.D. Cal.). The district court stayed the litigation on January 7, 2015, pending the outcome of the IPR. The magistrate judge that entered the stay noted that the PTAB has invalidated at least one patent claim in approximately 84% of its final written decisions, and that this “data reflects a relatively high probability that at least some of the claims at issue in this litigation will be selected for IPR and eventually canceled. Accordingly, a stay has the potential to greatly simplify these Court proceedings, weighing in favor of a stay.”

Now that the stay will presumably be lifted and the infringement litigation resumed, the issue of patent eligibility will likely take center stage. IPR is limited by statute to invalidation challenges based on prior art, i.e., for lack of novelty or obviousness, and thus patent ineligibility under 101 cannot be raised as a basis to invalidate claims in IPR. However, the patent claims at issue in this case clearly implicate patent eligibility concerns.  Cepheid has already raised the issue of patent eligibility in the district court prior to the stay, arguing that the patent “contains claims that are not patent-eligible in light of the Supreme Court’s recent significant decision [in Myriad] that a naturally occurring DNA segment is a product of nature and not patentable.”

While Myriad calls into serious question the validity of the primer claims, it is the Supreme Court’s decision in Mayo v. Prometheus, and the Federal Circuit’s recent interpretation of Mayo in Ariosa, that will provide Cepheid with its strongest basis for arguing that the method claims are patent ineligible. Thus, somewhat ironically, there is a good change that one of Mayo’s own patents will be brought down by the Mayo decision.

Federal Circuit Decides Ariosa, and Its Not Good News for Innovation in the Life Sciences

On November 1, 2013, I reported on the district court decision in Aria Diagnostics v. Sequenom that invalidated diagnostic method claims under the Mayo v. Prometheus test for patent eligibility.  In that post, I predicted that if “the approach used by this court is upheld by the Federal Circuit and applied generally to diagnostic claims, it would seem to severely limit the availability of patent protection for diagnostics.  

The Federal Circuit’s decision came out today, and Ariosa Diagnostics v. Sequenom (Aria has changed its name to Ariosa) is indeed very bad news for the patenting of diagnostic methods, and in the life sciences generally.  The outcome appears to have been driven by unfortunate and unnecessarily broad language used by the Supreme Court in Mayo, as noted in a thoughtful concurring opinion by Judge Linn (discussed below).

Ariosa begins by setting forth the test for patent eligibility established in Mayo:

• Step 1 – Determine whether the claims at issue are directed to a patent ineligible concept. Id. at 1297. If the answer is yes, then proceed to Step 2.

• Step 2 - Determine whether additional claimed elements “transform the nature of the claim” into a patent-eligible application of the concept.

The Supreme Court has described the second step of this analysis as a search for an “inventive concept”—i.e., an element or combination of elements that is “sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the [ineligible concept] itself.”

The court then proceeded to apply the Mayo test to Sequenom’s claims.  The court found that the existence of cell free fetal DNA (“cffDNA”) in maternal plasma is a natural phenomenon, that the claims are directed to methods that begin and end with cffDNA, pointing out that “Sequenom does not contend that [the inventors] created or altered any of the genetic information encoded in the cffDNA, and it is undisputed that the location of the nucleic acids existed in nature before [the inventors] found them." After concluding that the claims are directed to “matter that is naturally occurring,” thereby satisfying Step 1 of the test, the court turned to Step 2.

In applying Step 2, the court found that none of the additional elements recited in the claims provided sufficient “inventive concept” to render the claims patent eligible. In particular, the claims recite steps of preparing, amplifying and detecting DNA, but the court held that all these techniques, such as PCR or detection of a specific chromosome, were “well-understood, routine, and conventional” at the time of the invention. The court states:

[I]n this case, appending routine, conventional steps to a natural phenomenon, specified at a high level of generality, is not enough to supply an inventive concept. Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art.

Sequenom argued that there are numerous other uses of cffDNA aside from those claimed in its patent, and thus, the patent does not preempt all uses of cffDNA. But the court rejected this argument, ruling that:

[A]lthough the Supreme Court “has made clear that the principle of preemption is the basis for the judicial exceptions to patentability, . . . the absence of complete preemption does not demonstrate patent eligibility. . . Where a patent’s claims are deemed only to disclose patent ineligible subject matter under the Mayo framework, as they are in this case, preemption concerns are fully addressed and made moot.

Sequenom and some of its supporting amici had urged the court to draw distinctions among natural phenomena based on whether or not their patenting would interfere significantly with innovation in other fields, now or in the future. The court rejected this policy argument, however, finding that the Supreme Court cases “ have not distinguished among different laws of nature or natural phenomenon according to whether or not the principles they embody are sufficiently narrow.”

In a thoughtful concurring opinion, Judge Linn states that he joined court’s opinion invalidating the claims of the Sequenom patent only because he felt “bound by the sweeping language of the test set out” by the Supreme Court in Mayo. Judge Linn expressed his view that Part 2 of the Mayo test is overly broad and was unnecessary to decide that case, and that the broad language of Mayo has had the “perhaps unintended” consequence of in this case "excluding a meritorious invention from the patent protection it deserves and should have been entitled to retain.”

Judge Linn found it “hard to deny that Sequenom’s invention is truly meritorious,” noting that prior to the invention prenatal diagnoses required invasive methods, which “present[ed] a degree of risk to the mother and to the pregnancy.” The available “techniques [we]re time consuming or require[d] expensive equipment.” He pointed out that the Royal Society had lauded the inventors’ discovery as “a paradigm shift in non-invasive prenatal diagnosis,” and that the commercial embodiment of the invention, the MaterniT21 test, was the first marketed non-invasive prenatal diagnostic test for fetal aneuploidies, such as Down’s syndrome, and presented fewer risks and a more dependable rate of abnormality detection than other tests.

According to Judge Linn, under “traditional” (pre-Mayo) standards of patentability, Sequenom’s patent would have been valid, since the inventors had “effectuate[d] a practical result and benefit not previously attained.”  His opinion concludes with the following observation: 

But for the sweeping language in the Supreme Court’s Mayo opinion, I see no reason, in policy or statute, why this breakthrough invention should be deemed patent ineligible.

I agree with Judge Linn on this point, and can only hope that the Federal Circuit can find some way to rein in the unnecessarily expansive language of Mayo.  But if the Federal Circuit is as constrained by Mayo as Judge Linn seems to believe, Congressional or Supreme Court intervention might be necessary to restore effective patent protection for important innovations as exemplified by the Sequenom test.

Celegene Fights Back Against Hayman Capital's Alleged Abuse of IPR Process

The Wall Street Journal recently reported that Hayman Capital, a hedge fund, has adopted a strategy of seeking to invalidate patents through inter partes review (IPR), while betting on a drop in the target’s share price.  In particular, the fund has targeted pharmaceutical patents that the head of Hayman Capital, Kyle Bass, says “have little value other than to drive a prescription drug prices.” According to the article, “his new fund bets against companies whose patents it believes are spurious, and invests in those that would profit if the patents are invalid.”

Mr. Bass has created an organization called Coalition for Affordable Drugs, and petitions for IPR have been filed on  behalf of Hayman Capital, the Coalition, and Mr. Bass personally (the "Coalition"). The first petition was filed in February 2015, targeting an Acorda Therapeutics patent (8,663,685). Since then the Coalition has filed a total of 16 IPR petitions, all of them targeting pharmaceutical patents owned by companies such as Biogen, Celgene, Shire, and Jazz Pharmaceuticals. As of yet, none of the petitions have resulted in the institution of IPR proceedings. Some have criticized the fund’s tactics, and called for stricter standing requirements in IPRs.

Celgene, one of the Coalition’s prime targets, recently struck back. On June 3, 2015, Celgene sent an email to the Patent Trial and Appeal Board (PTAB) requesting authorization to file a sanctions motion for dismissal of four petitions for IPR filed by the Coalition. In the email, Celgene states:

The identified real parties in interest (“RPI”) in these proceedings have stated publicly that they intend to use the IPR process for the purpose of affecting the value of public companies. This is not the purpose for which the IPR process was designed. Moreover, one or more of the identified RPI previously threatened to file IPRs against the challenge patents unless Celgene met their demands. When Celgene did not pay, the RPI -- apparently in furtherance of their efforts to abuse the IPR process for private financial gain -- filed the present petitions. Celgene respectfully requests authorization to file a sanctions motion to dismiss the petitions due to the real parties in interest’s abuse of process and misuse of the IPR proceedings.

On June 9, 2015, the PTAB issued an order authorizing Celgene’s motion for sanctions. The order states:

Based on the specific representations made [by Celgene during a] telephone conference, we [have] granted the requested authorization. Our decision was based on a determination that briefing will facilitate development of a complete record and, thereby, will promote the just resolution of the issues raised by [Celgene]. We emphasized that our grant of authorization to file a motion for sanctions is not a decision on the merits of Celgene’ allegation of abuse of process.

 

Generic Drug Companies Use IPR as Both an Alternative and Supplement to Paragraph IV Certification

The traditional mechanism by which generic drug companies challenge innovator patents is through the Paragraph IV certification process, as provided under the Hatch-Waxman Act. Recently, however, generic companies have begun to employ inter partes review (IPR), a new pathway for challenging patents created by the America Invents Act (AIA) of 2011, an alternative or supplement to Paragraph IV. The IPR route can be particularly attractive for a generic company that is not a first-filer, and thus ineligible for the 180 days of generic exclusivity provided under Hatch-Waxman for the first generic to succeed in a Paragraph IV challenge.

A recent example of this involves RESTASIS, an ophthalmic product for the treatment of dry eye manufactured and distributed by Allergan. FDA approved Allergan’s New Drug Application in December of 2002. On November 14, 2011 Actavis submitted an ANDA, with Paragraph IV certification, to FDA in order to obtain approval for a generic form of RESTASIS. On August 30, 2013, FDA informed Actavis that FDA had refused receipt of its ANDA based on certain deficiencies in the filing. On December 23, 2014, a judge in the Eastern District of Texas found Actavis’ ANDA filing insufficient to trigger infringement under § 271(e)(2), but declined to decide certain questions relating to Actavis’ status as a first filer.

On June 4, 2015, Apotex (another generic drug company) filed petitions for IPR of the five patents listed in the Orange Book with respect to RESTASIS, i.e., US patent numbers 8,633,162; 8,629,111; 8,685,930; 8,648,048; and 8,642,556. Apotex states in its petitions that there are no related matters, i.e., it is not involved in any other litigation with Allergan relating to these patents.

A generic company can also employ IPR concurrently with a paragraph IV challenge. For example, Mylan filed ANDAs, with paragraph IV certifications, seeking approval to market generic versions of AstraZeneca products ONGLYZA and KOMBIGLYZE.  In response, AstraZeneca sued Mylan (as well as other generic challengers) for allegedly infringing US patent numbers RE’44,186 and 8,628,799 under 35 USC (e)(2)(A).  On June 4, 2015 Mylan filed an IPR challenging RE’44,186.

 

Boston Heart Diagnostics Corporation Attempts to Navigate the Shoals between Patent Ineligibility and Divided Infringement

On June 2, 2015, Boston Heart Diagnostics Corporation (BHDX) sued Harmonyx Diagnostics in the Eastern District of Texas for infringement of US patent number 8,455,194. The patent is assigned to Isys Innovation Limited, a wholly owned subsidiary of the University of Oxford and the assignee of the diagnostic patents at issue in two other cases recently discussed in this blog, Arioso Diagnostics and Athena Diagnostics. BHDX represents that it is the exclusive licensee.  The patent is basically directed towards testing for the presence of a single nucleotide polymorphism (SNP) correlated with risk of statin -induced myopathy, and using that information to establish and administer the appropriate statin type and dosage to the patient. The patent recently emerged successfully from a reexamination that resulted in the amendment of some claims in the addition of some new claims. Here is a representative claim:

1.       A method, comprising: (a) assaying for the presence or absence of a C or T allele for single nucleotide polymorphism rs4149056 in the SLCO1B1 gene in a biological sample obtained from a patient in need of treatment with a statin; (b) correlating the identity of the allele of said polymorphism with risk of statin-induced myopathy; (c) establishing a statin type and dosage based on said patient's statin-induced myopathy risk; and (d) administering said statin type and dosage to said patient.

The patent raises interesting enforcement issues, since there appears to be no single party that directly performs all of the steps recited in the claims. In its recent Akamai v.Limelight decision, the Federal Circuit held that infringement of a method claim requires a single party to perform all of the steps of the method, either directly or through an agent or some other party contractually obligated to perform the steps. In Akamai, a divided panel of the Federal Circuit rejected “calls to expand the scope of direct infringement to include a wider allowance for joint-tortfeasors when parties collectively practice all of the elements of a claimed invention.”   This decision, combined with the Supreme Court’s earlier decision in Limelight v.Akamai which held that liability for induced infringement requires some party to directly infringe, creates difficulties for owners of diagnostic patents such as BHDX attempting to enforce the patents against competitors.

In particular, note that the representative claim includes steps of “assaying” for presence of an allele and “administering” a particular statin type and dosage to a patient based on the results of the assay.  The problem is, there appears to be no single party that is directly performing both the “assaying” and “administering” steps.

In its complaint, BHDX attempts to address this issue by alleging that Harmonyx directly infringes because it directly performs the “assaying” and “determining” steps, and that “Harmonyx acts in concert with performances and physicians, as a partner or joint venture, and this jointly performs the “administering” step of the patent method.” BHDX also alleges that “Harmonyx enters into written agreements with pharmacies pursuant to which the pharmacies offer the Harmonyx Test for Statins to customers, as an agent and under the direction and control of Harmonyx.” Clearly, BHDX is attempting to establish the contractual-agency relationship between Harmonyx and pharmacists necessary under Akamai to attribute the “administering” step two Harmonyx.

BHDX also alleges induced infringement in its complaint, but under Limelight the patent owner needs to establish that someone directly infringement forming all the steps. In particular, Harmonyx alleges that pharmacists and physicians directly infringe the patent, and that Harmonyx induces this infringement. BHDX attempts to address the divided infringement problem by alleging that Harmonyx performs the “assaying” steps of the patented method “under the control and direction of the pharmacists and physicians, pursuant to written agreements.”

This is a perfect example of the “caught between a rock and a hard place” problem facing diagnostic innovators as a consequence of recent developments in patent eligibility and divided infringement, as discussed in an earlier blog post and in this short article. Basically, the recent restrictive interpretation of patent eligibility seems to require the inclusion in diagnostic method claims of a step applying information derived from the diagnostic test, i.e., the administering step in BHDX’s claims, but the inclusion of such a step renders the claim vulnerable to circumvention when no single party performs all the steps, e.g., a diagnostic testing company performs the assaying and correlation steps but does not directly administer drug to a patient.

This would appear to be another interesting diagnostic method case to follow in light of the ongoing developments in patent eligibility and divided infringement.

 

Athena Diagnostics Sues Mayo in Case That Implicates Patent Eligibility Doctrine

On June 2, 2015, Athena Diagnostics sued Mayo Collaborative Services (the Mayo Clinic and its associated reference laboratory) in the District of Massachusetts for infringement of US patent number 7,267,820. On its face, the patent is assigned to two European entities, Isis Innovation Limited and Max-Planck, but Athena represents that it is the exclusive licensee of the patent.

The patent claims methods for detecting antibodies to a protein called muscle-specific tyrosine kinase (“MuSK”).  The method is useful as a diagnostic for certain rare forms of an autoimmune disorder, Myasthenia gravis, that is characterized by the presence of autoantibodies directed against the patient’s own MuSK. Athena offers quantitative testing for the presence of MuSK-associated autoantibodies.

According to the complaint, prior to May 19, 2015, medical practitioners associated with Mayo utilized Athena for quantitative detection of MuSK-associated antibodies. However, Mayo has developed its own in-house tests for the autoantibodies, and as of May 19, 2015 it has directed its practitioners to use its in-house test instead of Athena’s. This is analogous to what happened in the case of Prometheus v. Mayo, where Mayo originally utilized the patent owner’s diagnostic test but then, presumably as a cost-saving measure, switched over to their own internal testing procedure.

Patent eligibility could become a significant issue in this case. Athena is clearly cognizant of this fact, emphasizing in this complaint that its patented methods “involve using man-made chemical reagents capable of detecting antibodies to an epitope of” MuSK. The illustrative independent claim in the patent recites:

1.       A method for diagnosing neurotransmission or developmental disorders related to muscle specific tyrosine kinase (MuSK) in a mammal comprising the step of detecting in a bodily fluid of said mammal autoantibodies to an epitope of muscle specific tyrosine kinase (MuSK).

The claim seems to implicate patent eligibility concerns, particularly in the event a court were to find that the presence of autoantibodies to MuSK in a patient’s body fluid is a natural phenomenon, and that the claim does not include sufficient additional inventive attributes to qualify for patent protection. The patent also includes a number of dependent claims that recites methods of performing the test with a greater degree of specificity, including the use of labeled antibodies. However, if the court follows the path set by Myriad II and Ariosa Diagnostics, it could very well conclude that these methods for detecting the autoantibodies are too conventional, and not sufficiently inventive, to render the claims patent eligible.

Of course, we are still waiting to hear what the Federal Circuit has to say about the district court's decision in Ariosa Diagnostics. But the present lawsuit between Athena and Mayo is one to keep an eye on for those interested in the patent eligibility of diagnostic methods.

Do Biotech Patent Lawsuits Really “Overwhelmingly Lose?”: A Response to Our Divided Patent System

On October 14, 2014, Stanford’s Professor Mark Lemley tweeted “My new study with Allison & Schwartz shows that software and biotech patent lawsuits overwhelmingly lose.” The "study" he was referring to is Our Divided Patent System, an article co-authored by Lemley and two other prominent law professors, which found that biotech companies have only won with respect to 8% of the patents that have been taken to judgment.  

In order to better understand the basis for Lemley’s assertion, I reanalyzed the data underlying Our Divided Patent System, and found that the situation is not nearly as bleak as Lemley's tweet might suggest. For example, while Our Divided Patent System reported that biotech companies have only won with respect to 8% of the patents that have been taken to judgment, I looked at the same set of lawsuits and found that, out of a total of sixteen distinct biotech patent litigations, seven appear to result in favorable outcomes for the patent owner (44%).  Not only did biotech patent owners benefit from favorable outcomes in nearly half of the litigations, the magnitude of these favorable outcomes was often substantial. 

My full response to Our Divided Patent System, which originally appeared in Biotechnology Law Report, is available here.