Wednesday, December 2, 2015

Federal Circuit Denies En Banc Rehearing of Ariosa v. Sequenom, But Some Judges Urge Supreme Court to Fix Flawed Patent Eligibility Precedent

Today the Federal Circuit issued an order (available here) denying en banc rehearing of Ariosa v. Sequenom, an important patent eligibility decisions discussed in earlier posts.  I filed a brief on behalf of the Biotechnology Industry Organization (BIO) and Pharmaceutical Research and Manufacturers of America (PhRMA) arguing in favor of en banc rehearing, and discussing the negative implications of the decision for patenting in biotechnology, particularly as related to diagnostics and personalized medicine.  The decision to deny rehearing was accompanied by two concurring and one dissenting opinions filed by a total of four judges (Lourie and Moore, Dyk, and Newman), which provide some very interesting insight into their views on the current state of patent eligibility jurisprudence, particularly as it relates to the life sciences.

There was some substantial overlap in the opinions of all four judges.  For example, they all appeared to agree that the decision invalidating Sequenom’s method was both ill-advised as a matter of policy and not compelled by the language of the patent statute.  All of the judges seemed to recognize that Ariosa’s interpretation and application of the Mayo framework threatened the availability of effective patent protection for a broad swath of biotechnological innovation, particularly in the area of diagnostics.  Lourie and Moore, for example, found “some truth” in concerns raised by Sequenom and their amici “that a crisis of patent law and medical innovation may be upon us,” and that a broad range of claims appear to be in serious jeopardy, particularly diagnostic claims.

The judges recognized that the claims might raises concerns regarding overbreadth and/or indefiniteness, but suggested more measured approaches to address these concerns rather than the blunt instrument of the Supreme Court’s new patent eligibility jurisprudence.  Lourie and Moore suggested that “the finer filter of Section 112 [i.e., the enablement and definiteness requirement] might be better suited to treating these [concerns] as questions of patentability, rather than reviewing them under the less-defined eligibility rules.” In contrast, Judge Dyk opined that these other statutory requirements of patentability might not be entirely up to the task, but instead proposed a novel alternative approach to patent eligibility analysis that would have likely salvage some patent protection for a company like Sequenom, albeit at the cost of substantially narrower claim scope.  His suggested approach is discussed in more detail below.

The concurrence by Lourie and Moore found that while the blood fractionation and DNA analysis steps recited in the claims are individually well known, “the innovative aspect of the claims appears to be the improvement in the method of determining fetal genetic characteristics [] consisting of use of the non-cellular fraction of fetal DNA obtained from maternal blood sample.”  The result is a novel, innovative and practical method of diagnosis that constitute a substantial improvement over the highly intrusive means use prior to the invention.

Lourie and Moore went on to find that the claims would not preempt the asserted natural phenomenon, since there exist “other uses for cffDNA and other methods of prenatal diagnostic testing using cffDNA that do not involve the steps recited in the various claims,” and that this “fact should sufficiently address the concern of improperly tying up future use of natural phenomena and laws.”  In other words, these judges appear to support the notion that a claim only raises patent ineligibility concerns if it preempts all applications of a natural phenomenon.  This is in stark contrast to the approach of the panel that decided Ariosa - they treated the question of preemption as essentially irrelevant to the determination of patent eligibility.

Dyk’s concurring opinion largely tracked Lourie and Moore, agreeing that the language of Mayo, while unfortunate, compelled the panel decision in Ariosa.  But Dyk goes on to suggest that in assessing patent eligibility courts should distinguish between a patent eligible concept that is well known and long-standing at the time of invention as opposed to one that is newly discovered.  In his view:
Mayo did not fully take into account the fact that an inventive concept can come not just from creative, unconventional application of a natural law, but also from the creativity and novelty of the discovery of law itself.  This is especially true in the life sciences, or development of useful new diagnostic and therapeutic methods is driven by investigation of complex biological systems.  I worry that method claims that apply newly discovered natural laws and phenomena in some conventional ways are screened out by the Mayo test.  In this regard I think that Mayo may not be entirely consistent with the Supreme Court’s decision in Myriad.

I think Judge Dyk raises a very interesting and insightful point regarding Myriad.  In that case, the Supreme Court found that the genetic sequence of the BRCA genes was a natural phenomenon, but that the corresponding cDNA sequences were nonetheless patent eligible, in spite of the fact that nothing could be more routine and conventional than to synthesize cDNA based on the discovery of a naturally occurring gene.  Judge Dyk inferred that Myriad “recognize[d] that an inventive concept can sometimes come from discovery of an unknown natural phenomenon, not just from unconventional application of the phenomenon.”  He went on to propose a refinement of the Supreme Court’s test for patent eligibility, whereby “the novelty of the discovery [of a natural phenomenon] should be enough to supply the necessary inventive concept.”

Significantly, under Dyk’s proposed approach, an inventor would only be able to claim applications of a newly discovered natural phenomenon that had been “actually reduced practice, not merely ‘constructively” reduced to practice by filing of a patent application replete with prophetic examples.”  According to Dyk, the resulting claims would be narrow in scope and “would allow the inventor to enjoy an exclusive right to what he himself has invented and put into practice, but not to prevent new applications of the natural law by others.”  In other words, the narrow scope of the claims would obviate the preemption concerns underlying the patent eligibility doctrine.

Dyk’s concurrence concludes by suggesting that:
A future case is likely to present a patent claim where the inventive concept resides the newly discovered law of nature or natural phenomenon, but the claims narrowly drawn and actually reduced practice.  That case will, I hope, provide the Supreme Court with an opportunity to revisit the Mayo/Alice framework in this one limited aspect.

The third opinion was a dissent by Judge Newman.  Not surprisingly, she agreed with the other judges that the decision below was wrongly decided, but she did not “share their view that this incorrect decision is required by Supreme Court precedent.”  She found that the facts of Ariosa diverge significantly from those in Mayo and Myriad, and that the patent eligibility of Sequenom’s claims could be upheld without contravening Supreme Court precedent.






Tuesday, November 24, 2015

The Cleveland Clinic Foundation v. True Health Diagnostics: Judge Denies Preliminary Injunction Based on Likelihood That Diagnostic Testing Method Is Patent Ineligible

On December 18, 2015, in The Cleveland Clinic Foundation v. True Health Diagnostics, LLC, a district court judge in Ohio issued an order denying the Cleveland Clinic Foundation’s (“CCF’s”) Motion for Temporary Restraining Order and Preliminary Injunction after concluding that CCF had failed to establish a likelihood of success on the merits.  In particular, the court found that CCF had “fail[ed] to make a clear showing that the patents-in-suit” are directed towards patent eligible subject matter.  This is yet another example of the challenges facing the developers of diagnostic tests in the wake of Mayo v. Prometheus.

The patents at issue in the case, U.S. Patent No. 7,223,552 (“the ’552 patent”); U.S. Patent No. 7,459,286 (“the ’286 patent”); and U.S. Patent No. 8,349,581 (“the ’581 patent”), relate to methods of analyzing Myeloperoxidase (“MPO”) biomarkers in a patient’s blood sample to predict a patient’s potential for heart disease, by comparing the level of MPO found in the patient’s blood sample with levels of MPO in control subjects to see if the patient has elevated levels of MPO.  MPO is an enzyme released by white blood cells when an artery wall is damaged or becomes inflamed, and its presence is thus an early symptom of many types of cardiovascular disease (“CVD”).

Applying the Mayo/Alice two-step test for patent eligibility, the court concluded that “it appears that the correlation between MPO levels and cardiovascular disease is more akin to a law of nature,” and that, “[m]easuring a sample of blood or blood product1 appears to be a “’well-understood, routine and conventional activity’ known in the scientific community.”  As a consequence, at least “at this point in the litigation,” the court was “not convinced that plaintiff has demonstrated that the patents-in-suit contain ‘an element or combination of elements’ sufficient to satisfy step two of the Mayo/Alice test.” The court rejected CCF’s argument that its patents require “measurement of a closed set of specific bodily samples” and, therefore, that its patents apply a “phenomenon in a combination of steps that has never been done before.”

Interestingly, the judge’s Order denying preliminary relief expounds in great detail on the important role the patents played in allowing CCF to translate the patented discovery into a successful commercial product.   It describes how in 2009, CCF launched HeartLab as the exclusive licensee of the patents to commercialize MPO testing.  CCF and HeartLab reportedly invested millions of dollars in their effort to build the MPO testing market, which has involved conducting ongoing medical and scientific studies, application for FDA approvals, and establishment of Medicare reimbursement status for MPO testing.  In addition, they “have focused considerable effort on developing stringent manufacturing and quality standards and also invested in educational programs about MPO testing.”

To illustrate the success of CCF’s and HeartLab’s efforts to develop and commercialize MPO testing, the Order notes that at its “inception, HeartLab had eight employees who performed only a few hundred MPO tests. It now has 140 employees who will perform hundreds of thousands of MPO tests in 2015.”

Thursday, November 19, 2015

Endo v. Actavis: Court Adopts Magistrate's Recommendation Finding Drug Method of Use Claims Facially Invalid Under 35 USC 101

In a September 28, 2015 post I reported on Endo v. Actavis, wherein a magistrate judge’s Report and Recommendation from a magistrate judge in the District of Delaware recommending invalidation of a drug method of treatment patent for patent ineligibility on a motion to dismiss under Rule 12(b)(6).  The magistrate judge essentially found the claim to be highly analogous to method of treatment claims found to be patent ineligible by the Supreme Court in Mayo v. Prometheus, and in my post I explained why the decision was consistent with my long-standing concern that an expansive interpretation of the literal language of Mayo threatened the validity of drug method of use claims in general.

In a November 17, 2015, Order Adopting Report and Recommendation, the district court judge hearing the case adopted the magistrate judge’s recommendation in its entirety and dismissed Endo’s Counts relating to infringement of U.S. Patent No. 8,808,737 (the '"737 patent"), finding the patent to be “facially invalid.”

 The district court judge rejected several arguments made by Endo in support of patent eligibility of the claims.

Of particular significance to the patentability of method of use claims in general, Endo argued “that the Magistrate Judge's reliance on the similarities between the '737 patent's representative claim and the claim involved in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012), was in error because the claim at issue in Mayo did not require that anyone act upon or apply the method in a tangible way, while claim 1 of the '737 patent actually requires that the lower dose be administered.”  As I mentioned in my previous post, many of us have held out hope that even post-Mayo a method of treatment claim that explicitly recites administration of the drug to a patient would remain patent eligible.  The district court judge, however, agreed with the magistrate judge’s conclusion that “limitations at issue in Mayo do in fact mirror the analogous limitations of Claim 1 of the '737patent.” 

The court considered the following side-by-side comparison of the language of the Mayo and Endo claims: "indicates a need to [increase/decrease] the amount of said drug subsequently administered to said subject"(Mayo) vs. "orally administering to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief"(Endo), and concluded that the “slight difference in phrasing is immaterial, because neither formulation provides any sort of 'inventive concept.'"

The court further found Endo’s argument that the '737 patent does not claim a law of a nature, but rather"a new and useful process," to be “thoroughly unconvincing.”  The district court found that Endo had essentially admitted in their briefing that the '737 patent claims a natural law as its invention based on the following statement by Endo: “[I]t is true that the claimed inventions relate to the unexpected discovery that the bioavailability of oxymorphone is increased in patients with renal impairment.”
This is troubling, because while the patent statute explicitly states that a “discovery” can be patented, this court apparently construes a patent owner’s use of the term “discovery” as an admission that the “discovery” is a natural phenomenon.  If anything that can be discovered is a natural phenomenon, the availability of patent protection for innovation in the life sciences would appear to be extremely limited post-Mayo.

Endo made the policy argument “that the reasoning employed by the Magistrate Judge's Report and Recommendation would in effect invalidate all pharmaceutical method-of treatment patents using an existing, well-known compound.”  The district court responded that “this case is hardly the poster child for [such] a policy argument,” and speculated that patent protection would still be available for method of use claims are directed towards an invention embodying “creative steps or inventive leaps aside from the discovery of a natural law.”

But if the discovery that a chemical compound has therapeutic effect on a patient is to be considered a “natural law,” which appears to be the case under the rationale of this decision, how successful will a pharmaceutical company be in arguing that use of that chemical compound for its therapeutic effect constitutes a sufficient “inventive leap” to satisfy the new post-Mayo patent eligibility standard?

Tuesday, November 17, 2015

The Medicines Company v. Hospira: Federal Circuit Will Reconsider "Suppliers Exception" to 102(b) On-Sale Bar

In a previous post I reported on the Federal Circuit’s July 2, 2015, decision in the The Medicines Company v. Hospira, wherein a panel of the Federal Circuit held that a patent owner’s use of a contract manufacturer to prepare three “validation batches” of a drug formulation embodying the claimed invention created an invalidating on-sale bar, even though the contract was for manufacturing service, not for the sale of product, and title to the drug always resided with the patent owner, and even though the batches were produced for the purpose of demonstrating to FDA that the invention resulted in a formulation that satisfied FDA specifications.  In the post I pointed out that the decision illustrates the risk of using a contract manufacturer prior to filing a patent application, particularly now that the AIA has called into question the availability of the one year grace period previously available under pre-AIA 102(b).

On November 13, 2015, the Federal Circuit granted The Medicine Company’s petition for rehearing en banc and vacated the panel’s decision.  The court requested that the parties file new briefs addressing the following issues:

(a)    Do the circumstances presented here constitute a commercial sale under the on-sale bar of 35 USC 102(b)?

(i)                 Was the resale for the purpose of 102(b) despite the absence of a transfer of title?

(ii)               Was the sale commercial in nature for the purpose of 102(b) or an experiment to use?

(b)   Should this court overrule or revise the principle in Special Devices, Inc. v. OEA, Inc., 270 F.3d 1353 (Fed. Cir. 2001), that there is no “supplier exception” to the on-sale bar of 35 USC 102(b)?

In Special Devices the court rejected the patent owner’s policy-based argument urging the Federal Circuit to create a “supplier exception” to the 102(b) on-sale bar, concluding that the text of section 102(b) itself “makes no room for” such an exception.
Of course, for that matter the experimental use exception likewise finds no support in the language of the statute, and there is nothing to prevent the court from creating another judge-made exception to the 102(b) on-sale bar. Such an exception would seem to be justified on policy grounds, given that without a "supplier exception" an inventor, faces a loss of patent rights based solely on a decision to contract out manufacturing rather than manufacture in-house. This could be particularly problematic for a small or underfunded inventor lacking the resources to manufacture its invention itself.

Wednesday, November 11, 2015

Court Dismisses “Disaffected” Professor’s Attempt to Change Inventorship on Johns Hopkins Patent

Peter Pedersen, a professor in the Department of Biological Chemistry at The Johns Hopkins University School of Medicine is one of three named inventors on US Patent Nos. 7,547,673 and 8,119,116.  The patents are directed towards chemotherapeutic uses of certain adenosine triphosphate (“ATP”) inhibitors, particularly 3-bromopyruvate.  The patents have been exclusively licensed to a company called PreScience Labs.  According to the company’s webpage, “PreScience Labs has successfully completed preclinical mechanistic, in–vitro and animal testing using the intro–arterial delivery of its proprietary drug 3–bromopyruvate ( “3–BrPA” or “PSL-001” ), and FDA has authorized Phase I testing.

One of the other named inventors on the patent is Young Hee Ko.  According to court documents, Ko and Pedersen “have a lengthy professional history:  Ko joined Plaintiff’s laboratory in 1991 and the two worked together until Ko’s resignation from JHU in 2006.  The two also appear to have had some sort of domestic arrangement: Ko acknowledged in a 2006 deposition that she sometimes stayed overnight at Plaintiff’s house and that she co-owned a vehicle with plaintiff.”

The third named inventor on the patents is Jean-Francois Geschwind, a former member of The Johns Hopkins University School of Medicine Department of Radiology.  He is currently identified on the PreScience Labs website as Founder and CEO.

On June 11, 2015, Pedersen filed a lawsuit in the District of Maryland seeking a (1) declaration under 35 USC 256 that Ko is the sole inventor of both patents and (2) an order directing the United States Patent and Trademark Office (USPTO) to issue a Certificate of Correction accordingly.
Even though Pedersen initiated the patenting process in 2001 by executing an invention disclosure with the Johns Hopkins Office of Technology Licensing identifying all three of them as inventors of the subject matter, he claims that at the time did not understand the distinction between inventorship and authorship.  He now claims that Geschwind’s sole contribution during the experimentation phase of the invention was to “guide the catheter into the hepatic arteries” of laboratory animals and “push the plunger,” and that Geschwind “did not even know what 3-BrPA was before Ko educated him.”

On October 27, 2015, the court issued an order granting Defendants’ (Johns Hopkins and Geschwind) motion to dismiss.  The court found that Pedersen lacked standing under Article III of the Constitution because he had failed to identify a “cognizable injury redressable by the section 256 relief that he seeks.” 
In particular, the court rejected his argument that his status as “named inventor” was enough to allow him to sue the University for change inventorship.  According to the court, “Plaintiff cannot seriously contend that he has standing to sue in federal court simply because he is unhappy with the manner in which a bona fide assignee of a patent chooses to deploy or license its interest.  Such a theory would confer near-limitless standing on disaffected scientists, well beyond the bounds of the particularized injury that Article III mandates.”

The court also rejected Pedersen’s argument that he had financial interest in the matter sufficient to establish standing, pointing out that Pedersen currently enjoyed a financial interest equal to one-third of the 35% “inventors’ personal share” provided by the Johns Hopkins IP Policy, which he would lose if he succeeded in removing himself as an inventor on the patents.
Pedersen also argued for standing based purely on “reputational interest,” asserting that his status as a “fair and honest academician is and will be adversely affected by the inclusion of himself and Geschwind as co-inventors.”  The court acknowledged the fact that a recent Federal Circuit decision held that “concrete and particularized reputational injury can give rise to Article III standing” (citing Shukh v. Seagate Technologies (decided October 2, 2015)).  However, Shukh involved a plaintiff who argued he has been wrongfully omitted as an inventor.  In contrast, the District Court characterized as “conclusory and speculative” Pedersen’s allegation that his reputation has been harmed by being wrongly included as a named inventor on the patents.


Tuesday, October 27, 2015

PTAB Upholds Validity of Herceptin Patent

Today the Patent Trial and Appeal Board issued a unanimous decision in Phigenix, Inc. v. ImmunoGen, Inc., upholding the validity of Immunogen’s US Patent Number 8,337,856.  The petition for inter partes review (IPR) was filed by Phigenix, Inc..  Genentech is a real party-in-interest in the proceedings.

 The ’856 patent claims “[a]n immunoconjugate comprising an anti-ErbB2 antibody conjugated to a maytansinoid, wherein the antibody is [HERCEPTIN].”  Herceptin is a biologic developed by Genentech for the treatment of some forms of breast cancer and gastric cancer.

Phigenix cited several prior art references which allegedly rendered the claims obvious and thus invalid under 35 USC 103.  One of the primary references, Chari 1992, describes immunoconjugates comprising an anti-ErbB2 mouse monoclonal antibody chemically coupled to a maytansinoid toxin (DMI).  The other primary reference was the HERCEPTIN label itself.  A Phigenix expert (Rosenblum) submitted a declaration which, according to Phigenix, established that it would have been obvious to substitute HERCEPTIN for the mouse antibody described in Chari 1192 “based on the teachings of Chari 1992 and HERCEPTIN label, as well as the general knowledge in the art at the time.”

The PTAB rejected petitioner’s argument, however, finding that the patent owner had provided persuasive evidence that at the time the patent was filed “prior art indicated that HERCEPTIN®-maytansinoid immunoconjugates would have been expected to exhibit unacceptable levels of antigen-dependent toxicity in normal human liver tissue in patients.”  The PTAB went on to find persuasive evidence in support of patent owner’s argument that ordinary artisans would not have had a reasonable expectation that any immunoconjugate, much less the claimed Herceptin®-maytansinoid immunoconjugate in particular, would be useful to treat solid tumors in humans,” given that “[r]esearchers had targeted tumors with immunoconjugates for about 40 years before the ’856 patent” without success and in view of evidence “indicating that preparing any antibody-toxin immunoconjugate for use in the treatment of human tumors was difficult and unpredictable.”

Previously, the PTAB declined to Institute review in a separate case involving a related patent, US Patent Number 7,575,748.  Phigenix, Inc. v. Genentech, Inc. and ImmunoGen, Inc., Case IPR2014-00842 (PTAB Dec. 9, 2014) (Paper 10).


Monday, October 5, 2015

Apotex Dances the BPCIA Patent Dance with Amgen, But Claims It Does Not Need to Provide 180-Day Notice of Commercial Marketing

The Federal Circuit held in Amgen v. Sandoz that the so-called “patent dance” is optional for applicants  seeking approval of a biosimilar product under the abbreviated BPCIA pathway, as discussed here.  Indeed, biosimilar applicants have in a number of cases chosen not to participate in the “patent dance.”  This occurred, for example, in a recent lawsuit filed by Amgen against Hospira in connection with Hospira’s plan to bring a biosimilar version of Epogen to market, as described in an earlier post.  In fact, until today I was personally unaware of any case in which a biosimilar applicant actually did participate in the patent dance with a reference sponsor, but that has changed with Amgen’s filing of a lawsuit against Apotex on October 2, 2015.

Amgen v. Apotex was filed in the Southern District of Florida, and alleges that Apotex has infringed, or will infringe, US Patent Numbers 8,952,138 and 6,162,427 by seeking approval under the abbreviated BPCIA pathway for a biosimilar version of filgrastim (which is sold by Amgen under the trade name Neupogen).  The complaint is available here.

According to the complaint, Apotex participated in the exchange of information set forth in the BPCIA, i.e., the patent dance, which included providing Amgen with a copy of its abbreviated Biologic License Application (aBLA), and as a result of these exchanges the parties agreed to the inclusion of these two US patents in the lawsuit.  The ‘138 patent “covers improved redox chemistry-based methodologies for efficiently refolding cysteine -containing proteins expressed in non-mammalian cells at high protein frustrations.”  Presumably Amgen believes the patent will be infringed by the processes Apotex will use to manufacture the biosimilar filgrastim.  

The ‘427 patent is directed towards a method that “employs a combination of G-CSF and a chemotherapeutic agent to mobilize stem cells more efficiently from the bone marrow to peripheral blood in a patient in need of a peripheral stem cell transplant.”  Amgen alleges that if FDA approves the Apotex product for the same indications as Amgen’s Neupogen product (which is what FDA did with respect to Zarxio, Sandoz’s biosimilar version of Neupogen), or if FDA requires Apotex’s label to contain the same information as Amgen’s Neupogen, then this will induce infringement of the ‘427 patent.  According to Amgen, “absent a legally cognizable and enforceable commitment by Apotex preventing Apotex from marketing its filgrastim product with a label that includes the same information regarding clinical trials, dosage and standard of care as Neupogen label… an actual controversy exists between the parties.”

The BPCIA also requires that biosimilar applicants “shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the” biosimilar product.  In Amgen v. Sandoz, the Federal Circuit interpreted this language as requiring that a biosimilar applicant “only give effective notice of commercial marketing after FDA has licensed its product.”  According to the complaint, Apotex sent Amgen a letter purporting to be Apotex’s Notice of Commercial Marketing on April 17, 2015.  Amgen seeks a declaratory judgment that the notice provided by Apotex on April 17, 2015 is invalid because at that time Apotex’s product had not been approved for licensure by FDA.
For its part, Apotex has reportedly taken the position, in a letter to Amgen dated August 24, 2015, that “because Apotex followed the pathway and provided Amgen with its application and manufacturing information, providing a notice of commercial marketing is not mandatory.”  Significantly, the Federal Circuit decided Amgen v. Sandoz on July 21, 2015, i.e., prior to Apotex’s letter, and held that notice of commercial marketing after licensure is mandatory.  I do not understand the basis for Apotex’s argument that notice of commercial marketing is not mandatory if the biosimilar applicant has participated in the patent dance, but it will likely be interesting to see how this plays out in the courts.





Monday, September 28, 2015

Magistrate Judge Finds Drug Method of Treatment Claim Patent Ineligible in Endo Pharmaceuticals v. Actavis

In 2009, I filed an amici brief on behalf of myself and several other law professors in Prometheus v.  Mayo, which was the first time the Federal Circuit heard the case.  In the decision below, the district court held that the interaction of a synthetic, non-naturally occurring pharmaceutical compound with the human body is a “natural phenomenon.”  In our brief, we basically argued that the interaction of a synthetic compound with the human body is not a natural phenomenon, but that if the definition of “natural phenomena” is interpreted so broadly as to encompass the interaction of human-made drugs with the human body, then by implication drug method of treatment claims seemed vulnerable to invalidation under 101 for encompassing patent ineligible subject matter.

Nonetheless, the Federal Circuit and the Supreme Court invalidated the Prometheus claims based on an assumption that the interaction of the pharmaceutical agent (the metabolic breakdown product of a drug) with the human body is a natural phenomenon.  In the Supreme Court’s decision, Mayo v. Prometheus, Justice Breyer seemed cognizant of this concern, and affirmatively stated that drug method of treatment claims should not be threatened by the holding in Mayo.  Still, I have continued to wonder how secure drug method of use claims are post-Mayo, particularly given the expansive interpretation of the Mayo/Alice by the district court’s and the Federal Circuit in decisions such as Ariosa (discussed in a previous post).

Thus, it came as no surprise when I saw a September 23, 2015 Report and Recommendation from a magistrate judge in the District of Delaware recommending invalidation of a drug method of treatment patent for patent ineligibility on a motion to dismiss under Rule 12(b)(6).  The case, Endo Pharmaceuticals v.  Actavis, is an ANDA litigation brought by Endo Pharmaceuticals against Actavis in connection with a Generic Oxymorphone ER Tablets.   The Report and Recommendation is available here.
The patent is US Patent Number 8,871,779, and representatives of claim one recites:

1. A method of treating pain in a renally impaired patient, comprising the steps of:

a. providing a solid oral controlled release dosage form, comprising: i. about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient; and ii. a controlled release matrix;

b. measuring a creatinine clearance rate of the patient and determining it to be (a) less than about 30 ml/min, (b) about 30 mL/min to about 50 mL/min, (c) about 51 mL/min to about 80 mL/min, or (d) above about 80 mL/min; and

c. orally administering to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief;

wherein after said administration to said patient, the average AUC of oxymorphone over a 12-hour period is less than about 21 nghr/mL.

The magistrate judge applied the Mayo/Alice two-part test for patent eligibility.  The first step is to determine whether the claims at issue are “directed to a patent-eligible concept,” in this case a natural law.  The magistrate judge notes that the “Mayo court provided a broad definition for a law of nature: ‘[a] patent that… describes a relationship that is the consequence of entirely natural processes sets forth a natural law.’”  The judge went on to conclude that “the connection between the severity of renal impairment and the bioavailability of oxymorphone” was the relevant natural law to which the claims are directed.

The second step is to determine whether the claims “add enough” to the “natural law” to render the claim patent eligible.  The magistrate judge essentially determined that the “providing,” “measuring,” and “administering” steps were analogous to the steps in the claims held to be patent ineligible in Mayo, and thus did not provide “enough” extra. 

The claims at issue in Mayo essentially recited a method of performing a diagnostic test and determining the optimal dosage of drug for a patient.  The claim did not recite a step of actually administering the optimized dosage to a patient, and many have held out the hope that in the future a claim that included this additional step of actually applying the information derived from the diagnostic test would be found patent eligible.

But note that Endo’s claim does expressly recite administering a lower dosage of drug to a patient based on the results of the diagnostic test, i.e., the claim does include the extra step that many thought would have rendered the claims in Mayo patent ineligible.  But, at least in the view of this magistrate judge, the inclusion of this extra step was not sufficient to render the claim patent eligible.  And given the sweeping language of Mayo, particularly as interpreted by the Federal Circuit in Ariosa, it is not hard to see how the magistrate judge came to this conclusion.

It is important to note that the Endo claim is not a straightforward method of treatment claim, i.e., “a method of treating disease X by administering drug Y,” and does not necessarily indicate that the magistrate judge would have ruled such a claim patent ineligible.  The decision does explicitly note that “oxymorphone is ‘widely used’ for acute and chronic pain relief, the showing that the utilization of oxymorphone is not the invention.”  Thus, the magistrate judge seemed to imply that in a case where the “invention” is the discovery of a new pharmaceutical agent for the treatment of some medical condition a method of treatment claim could still be patent eligible under Mayo. 

It seems inevitable that before long we will be seeing a decision involving an allegation that a more conventional method of treatment claim is patent ineligible.  It will be interesting to see how the courts handle that case, and also how the district court judge in Endo v. Actavis (and perhaps the Federal Circuit eventually) responds to the magistrate judge’s recommendation.

Tuesday, September 22, 2015

Amgen Sues Hospira, Claims That Biosimilar Version of Epogen Infringes

In Amgen v. Sandoz, a fractured panel of the Federal Circuit held that an applicant seeking approval of a biosimilar under the abbreviated BPCIA pathway is not required to participate in the so-called “patent dance,” and that if a biosimilar applicant fails to provide the reference product sponsor with its application and the other patent dance information, then the reference product sponsor’s only recourse is to bring a declaratory judgment action for patent infringement.
On September 18, Amgen did just that, filing a lawsuit against Hospira alleging that Hospira’s planned marketing of a biosimilar version of Amgen’s biologic Epogen (epoiten alfa) infringes Amgen patents.   The complaint is available here. 

Amgen states that this “is one of the first actions for patent infringement under 35 USC 271(e)(2)(C), which was enacted in 2010 as part of the” BPCIA.
According to the complaint, Hospira submitted its Biologic License Application (BLA) under the expedited subsection (k) pathway, relying on Amgen’s demonstration of the safety and efficacy of Epogen, but has failed to comply with the patent provisions of the BPCIA.  For example, Hospira has not provided Amgen with manufacturing information that “would have given Amgen the opportunity to evaluate the manufacturing processes used by Hospira to determine whether those processes would infringe any patents held by Amgen.”  This is essentially the same complaint Amgen had with respect to Sandoz's application for expedited approval of a biosimilar filigrastim based on Amgen’s Neupogen product.
Amgen is also seeking a declaratory judgment that Hospira is required to provide Amgen with legally effective notice of commercial marketing of its biosimilar product, and information describing the processes or products used to manufacture the biosimilar product.  In Amgen v. Sandoz, the Federal Circuit held that a biosimilar applicant must provide notice to the reference sponsor on or after the date that the FDA approves its biosimilar application, but according to the complaint Hospira has refused to do so.


Tuesday, September 1, 2015

Rapid Litigation Management (Celsis) v. Cellzdirect: BIO Files Amicus Brief in Another Patent Eligibility Case before the Federal Circuit

On August 28, 2015, the Biotechnology Industry Organization (BIO) filed an amicus brief in another important patent eligibility case currently before the Federal Circuit, Rapid Litigation Management (formerly Celsis In Vitro) v. Cellzdirect.  The claims at issue are directed towards a "method for freezing hepatocytes multiple times without further significant loss of cell health and viability."  The method has three steps: (1) previously frozen cells are thawed, (2) nonviable cells are separated from viable ones using a “density gradient fractionation,” and then (3) viable cells are cryopreserved for later use.  In the decision below, the District Court invalidated the claims, finding them to be directed towards patent ineligible subject matter.
In applying the first step of the Mayo two-step test for patent eligibility, the District Court found that the “patent is directed to an ineligible law of nature: the discovery that hepatocytes are capable of surviving multiple freeze-thaw cycles.”  In the second step, the court found the claimed method to lack sufficient “inventive concept,” because claimed elements such as freezing cells and the use of density gradient fractionation were found to be “well understood.”

In its brief, BIO urges the Federal Circuit to clarify the boundaries regarding the scope of the term “law of nature,” and argues that hepatocytes are not subject to repeated freezing in nature under the conditions of the claimed methods, and thus that the claim does not implicate a law of nature.  The brief also argues that the district court’s approach, which essentially “requires an undefined ‘something else,’ that cannot be satisfied by the application of known techniques and reagents to a newly recognized natural phenomenon, threatens the availability of patent protection for a host of important innovations spanning the length and breadth of biotechnology.”

BIO also argues that “[b]ecause of its well-developed record on the non-obviousness of the claimed invention, this case may present a good opportunity for this court to clarify the interplay between Section 103 and Step II of the Mayo/Alice framework."

Friday, August 28, 2015

Here Are All the Amicus Briefs That Have Been Filed Seeking En Banc Rehearing of Ariosa v. Sequenom

Yesterday I posted the amici brief I filed on behalf of BIO and PhRMA seeking en banc rehearing of Ariosa v. Sequenom.  Here are links to all twelve amicus briefs that were filed, in one place for your convenience.  Enjoy.  I have not read most of them, but I am glad to see people have taken notice and agree that there is a need for action.




Thursday, August 27, 2015

BIO and PhRMA File Amici Brief Urging En Banc Reconsideration of Ariosa v. Sequenom

The Biotechnology Industry Organization (BIO) and the Pharmaceutical Research and Manufacturers of America (PhRMA) have jointly filed an amici brief curiae brief urging the Federal Circuit to grant en banc rehearing of Ariosa v. Sequenom.  The brief is available here.  I am the counsel of record.

BIO and PhRMA are concerned that the development and commercialization of a range of biotechnology and pharmaceutical innovations will be impeded if the Federal Circuit does not address the mounting uncertainty currently afflicting patentable subject matter jurisprudence.  The brief points out the critical importance of effective patent protection for biotechnology and pharmaceutical innovators, and the current unprecedented level of uncertainty with respect to the scope of patent eligible subject matter.  This uncertainty is affecting both the patent user community and the PTO, which has responded with an ongoing stream of revised and re-revised non-final and interim guidance documents.  With each new PTO Guidance, BIO members have observed an increasing rate of claim rejections, affecting a diverse range of biotechnology, including novel antibiotic molecules, industrial enzymes, diagnostic processes, and crop production products.

The unsettled state of the law has also created doubt as to whether issued patents will be able to withstand challenge. The brief points out that the vast majority of judicial decisions addressing patent eligibility under the recently articulated standards have resulted in a determination of ineligibility.  For example, Appendix 3 of the recent PTO “July 2015 Update: Subject Matter Eligibility,” identifies 24 post-Mayo  subject matter eligibility cases decided by the Federal Circuit, of which 22 held all of the challenged claims to be patent ineligible.

The brief urges the court to clarify the contours of both Step I and Step II of the Mayo two-step test for patent eligibility.  It posits that the Supreme Court would not have articulated a two-step test if it did not intend the first step to serve some meaningful gatekeeping function, but that under the standard applied by the panel it is difficult to see how any analytical or detection method would ever not satisfy Step I, so long as that method is designed to detect something that occurs naturally.  With regard to Step II, the brief asks for clarification with regard to the proper application of the “inventive concept” and “preemption” standards of patent eligibility.  As an example, the brief discusses the practical challenges facing the inventor of a new diagnostic test under the new patent eligibility jurisprudence.

In its recent decisions the Supreme Court apparently assumed the existence of limiting principles that would maintain patent eligibility for truly meritorious inventions (this was Judge Linn’s characterization of Sequenom’s claimed invention in his concurring opinion), even if that invention can be deconstructed into a combination of natural phenomena and conventional technology. The brief argues that en banc reconsideration would allow the Federal Circuit to address the nature of these limiting principles suggested in Mayo.  Alternatively, if the court finds that Supreme Court precedent does not provide for limiting principles that provide a meaningful opportunity for patenting important biotechnology innovations, that would suggest a need for the Supreme Court to readdress the contours of patent eligibility in the context of biotechnology. Ariosa v. Sequenom would be an appropriate vehicle for alerting the Supreme Court to the urgent need for this clarification.

Law Professors File Amicus Brief Supporting En Banc Rehearing of Ariosa v. Sequenom

A group of 23 law professors, myself included, have filed an amicus brief in support of en banc rehearing of Ariosa v. Sequenom.

The brief is available here.

Adam Mossoff, a professor at George Mason University School of Law and a Director at the Center for the Protection of Intellectual Property (CPIP), and Kevin Noonan, a partner at MBHB, took the lead in drafting the brief.

Eli Lilly v. Teva: District Court Applies the Federal Circuit's Recent Akamai Decision to Drug Method-of-Treatment Claim

In 2014 I published an article entitled “Caught between a Rock and a Hard Place: How Limelight Compounds the Challenges Facing Biotechnology Innovators after Mayo and Myriad” (available here), which explained how Supreme Court’s decision in Limelight Networks v. Akamai Technologies limiting the ability of patentees to establish liability in cases of divided infringement had undermined the value of method claims, particularly with respect to diagnostics and drugs.  In that article, I noted that in Limelight the Court had explicitly pointed out that its decision did not necessarily preclude the Federal Circuit from revisiting that court's decision in Muniauction, and to reinterpret 271(a) in a manner that would allow a patent owner to hold at least certain parties liable for active participation in a concerted act of divided infringement.  I also predicted that that the Federal Circuit would likely revisit the issue and expand 271(a) in a manner that would hold at least some divided infringer’s liable.

On Aug. 13, 2015, the Federal Circuit did just that when it issued an en banc opinion unanimously setting forth the law of divided infringement under 35 U.S.C. § 271(a) and vacating the earlier panel decision. Akamai Technologies, Inc. v. Limelight Networks, Inc., 2015 WL 4760450 (Fed. Cir.).  Akamai explicitly overruled prior case law regarding divided infringement, “[t]o the extent [those] prior cases formed the predicate for the vacated panel decision,” and no longer limited § 271(a) to principal-agent relationships, contractual arrangements, and joint enterprises.

Under 35 U.S.C. § 271(a), direct patent infringement occurs where all steps of a claimed method are performed by or attributable to a single entity. In Akamai, the court held that “[w]here more than one actor is involved in practicing the steps, a court must determine whether the acts of one are attributable to the other such that a single entity is responsible for the infringement.” On a claim for direct infringement of a method patent, the court will hold an entity responsible for anothers’ performance of method steps under two circumstances: (1) where that entity directs or controls others’ performance, and (2) where the actors form a joint enterprise. With respect to the former requirement, Akamai concluded that “liability under § 271(a) can also be found when an alleged infringer conditions participation in an activity or receipt of a benefit upon performance of a step or steps of a patented method and establishes the manner or timing of that performance.” In those instances, the third party’s actions are attributed to the alleged infringer “such that the alleged infringer becomes the single actor chargeable with direct infringement.”
In Limelight, Eli Lilly filed an amicus brief with the Supreme Court explaining the critical role of method-of-treatment claims in pharmaceutical innovation, and noting that such claims ‘‘routinely and sometimes necessarily present divided infringement issues.’’ According to Lilly, ‘‘[i]t has been increasingly common for patent challengers to argue that the relationship between these various actors does not meet the current standard articulated by the Federal Circuit necessary to find liability for direct infringement under 35 USC 271(a).’’

On August 25, 2015, Eli Lilly’s concerns were presumably at least partially abated by the district court's decision  in Eli Lilly v. Teva (available here).  The  Eli Lilly court applied the new Akamai standard and held that doctors directly infringed an Eli Lilly method-of-treatment claim, even though the claim explicitly recites the step of administering folic acid to a patient prior to administration of the drug, and it is the patient that takes the folic acid, i.e., the doctor does not administer the folic acid to the patient.  As a consequence, a generic company would be liable for inducing the doctor’s infringement based on drug labeling that instructs doctors to have their patients take folic acid prior to the doctor administering the drug to the patient.  It is significant that the generic drug company is required by law to use essentially the same label as the branded drug, and is thus required to “induce” doctors to instruct patients to take their folic acid.

In particular, the district court found that “the instant case involves the administration of a medical treatment, the factual circumstances are sufficiently analogous to those in Akamai to support a finding of direct infringement by physicians under § 271(a), and thus inducement of infringement by Defendants under § 271(b), under the legal standard recently set forth by the Federal Circuit.”  The generic company defendants argued unsuccessfully that the "actions of the patient in taking folic acid prior to [administration of the drug] cannot be attributed to the physician because the physician does not physically place the folic acid into the patients’ mouth, and because patients are instructed to obtain folic acid, either by prescription or over the counter, and take it on their own.”  But the district court found this argument to be premised on “now overruled case law on divided infringement,” and found the following language of the label to be unambiguous on this point:
The prescribing information requires physicians to “[i]nstruct patients to initiate folic acid 400 mcg to 1000 mcg orally once daily beginning 7 days before the first dose of ALITMA®.” Additionally, the patient information states “[i]t is very important to take folic acid . . . during your treatment with ALITMA to lower your chances of harmful side effects. You must start taking 400-1000 micrograms of folic acid every day for at least 5 days out of the 7 days before your first dose of ALITMA.” TX. 3017 at 2 (emphasis in original). It is clear from the patent, the prescribing information, and the patient information that taking folic acid in the manner specified is a condition of the patient’s participation in pemetrexed treatment as described by the patent, and is necessary in order to receive the benefit of such treatment. If the patient fails to carry out this step, he or she would not receive the benefit of the patented method, i.e. a reduction of potentially life-threatening toxicities caused by pemetrexed. The physician, based upon the patented method, directs the manner and timing of the patient’s ingestion of folic acid—400 to 1000 μg of folic acid for at least five days out of the seven days prior to and during pemetrexed administration—and the patient is required to do so to receive the full benefit of the treatment.

Wednesday, August 26, 2015

WARF Files Amicus Brief in Support of En Banc Rehearing of Ariosa v. Sequenom

The Federal Circuit’s discouraging opinion in Ariosa v. Sequenom has been discussed in previous posts.  Sequenom has petitioned for en banc rehearing, its brief is available here, Amicus briefs are due tomorrow, Aug 27, but WARF got its in a bit early, and it is available here.

Here is a summary of WARF’s argument, i.e., their argument as set forth in the Table of Contents:

  • The goal of the two-step Mayo/Alice framework is to ensure that patentees cannot effectively monopolize natural phenomena, laws of nature, and abstract ideas—no more and no less
  •  Where an inventor claims only an application that makes practical use of a natural phenomenon, the claims do not monopolize the natural phenomenon itself and are patent-eligible under Section 101
  • The panel’s analysis of Mayo/Alice Step Two was mistaken because isolation, amplification, and analysis of cffDNA in maternal fluids were not conventional

      More briefs will be posted shortly, including one I am helping to prepare for Biotechnology Industry Organization

Tuesday, July 21, 2015

Former Grad Student Fails in Bid for “Constructive Trust” in Professor’s Patent

On July 16, 2015, in Genspera v. Mahka, the Federal Circuit affirmed without discussion (i.e., under Rule 36) a district court decision denying a former doctoral student’s claim to a constructive trust in a patent issued to her former thesis advisor, a professor at Johns Hopkins University. The affirmed district court decision also denied her conversion claim against the professor.

The professor, along with another professor at Johns Hopkins, are named inventors on patents claiming a cancer prodrug. The graduate student, Mahka, claims that she came up with the idea for the only specific chemical compound claimed in the patents, a compound that is currently undergoing clinical testing. Genspera is a company started by the professors to develop and commercialize the prodrug.

Mahka initially sought to be added as an inventor to the patents, but the district court granted Genspera summary judgment because “a finding that Mhaka added an invention to the Application after the disclosure was filed would invalidate the Patents, and a district court cannot apply § 256 to require the Patent Office to add an inventor to an issued patent when doing so would invalidate the patent.”  The problem was that the prodrug allegedly invented by Mahka was not created until after the filing date of the patents.

Mahka then turned to state law causes of action. She claimed conversion of her invention by the professors, but the district court rejected this claim. The court found that under Maryland law the tort of conversion does not extend to completely intangible rights, and that Mahka’s asserted rights in the “invention” claimed in the patents was completely intangible.

Mahka also sought a constructive trust, a form of equitable relief which would have required the professors to share some of the benefits they derived from the patents, specifically stock in Genspera.  A constructive trust remedy is applied when “property has been acquired by fraud, misrepresentation, or other improper method, or where the circumstances render it inequitable for the party holding the title to retain it.” Its purpose is “to prevent the unjust enrichment of the holder of the property.”

The district court denied this claim, finding that it was barred by laches, i.e., Mahka waited too long to file her lawsuit.  The district court held that she needed to file her claim within three years of learning of the alleged failure to name her on the patent, and that she had waited more than four years.  After leaving Johns Hopkins, Mahka worked at a venture capital firm doing intellectual property research, which is where she allegedly learned of the patents.  She learned about them, and her omission as an inventor, in 2008, and contacted John Hopkins at that time, who advised her to hire her own lawyer. She waited until 2012 to file a lawsuit, at which point her cause of action was time-barred.