AstraZeneca’s Crestor® Patent is Invalidated by the Brazilian Federal Courts

On June 5, 2015, the 13th Federal District Court of Rio de Janeiro invalidated Astrazeneca’s patent BR PI0003364-2 covering Crestor® (rosuvastatin). The Judge, the Honorable Marcia Nunes Barros, agreed with the arguments submitted by the Brazilian Patent Office and National Sanitary Vigilance Agency (ANVISA) that the patent was obvious over the prior art. The Honorable Barros is the same Judge that recently issued a decision holding that ANVISA was allowed to examine patentability requirements during prior approval/consent analysis under Article 229-C of the Patent Statute.

According to the decision, the use of the tribasic calcium phosphate to stabilize statins was expressly recommended in the prior art document PT 547 000E. Even though the use of the term “potentially” in the prior art did not denote certainty regarding stabilization, according to the Court, this meant that tribasic calcium phosphate was “probably useful for stabilizing statins”.

Additionally, although the prior art document recited a pH value of at least 8, preferably 9, for the stabilization of statins, the Court held that this pH value related to the stabilization of fluvastatin and not rosuvastatin. The Court referred to the Handbook of Pharmaceutical Excipients, which stated that tribasic calcium phosphate had a pH value of 6.8 at 20% solubility.

The Court held that a person of ordinary skill in the art (POSITA) would have known from PT 547 000E that tribasic calcium phosphate could be used to stabilize statins. Therefore, because the pH of a stabilizing agent varies based on concentration, a POSITA would have been motivated to investigate using tribasic calcium phosphate to stabilize a statin (in other words, it was “obvious to try”). The Court found this to be true because the pH value of 8 recited in PT 547 000E referred to the stabilization of a different statin (fluvastatin) and not rosuvastatin. Other prior art, such as WO 97/23200, described using a pH value of between 7.0 to 8.0 to stabilize the HMG-CoA inhibitor, E)-3,5-dihydroxy-7-[4′-4″-fluorophenyl-2′-cyclopropyl-quinolin-3′-yl]-6-heptenoic acid.

Therefore, according to the Court, a PHOSITA at the time of the invention would have understood that different statins required different pH values for stabilization. Even though tribasic calcium phosphate only had a pH value of 6.8 based on its solubility data, the Court held that a PHOSITA would have been motivated to test tribasic calcium phosphate as a stabilizing agent for rosuvastatin.

Interestingly, despite the fact that the court-appointed expert issued a report concluding that the patent was valid, the Judge mentioned international standards for assessing inventive step, including the U.S. Supreme Court’s decision in KSR Int’l Co. v. Teleflex, Inc., in concluding that the technical solution presented in the patent was obvious to try and that there was a reasonable expectation of success.

This post was written by Lisa Mueller and Roberto Rodrigues and Luiza Cotia of Licks Attorneys.

13th Federal District Court of Rio de Janeiro Holds that ANVISA Can Examine Patentability Requirements of Patent Applications Claiming Pharmaceutical Inventions

One of the most contentious issues in the Brazilian pharmaceutical landscape is role of National Sanitary Vigilance Agency (ANVISA) during the prior approval/consent analysis of patent applications claiming pharmaceutical inventions. Article 229-C of Brazil’s Patent Statute (Statute) provides that ANVISA shall have the right to provide approval of patent applications claiming pharmaceutical inventions (often referred to as “prior approval” or “prior consent”). Specifically, Article 229-C provides that: “The grant of patents for pharmaceutical products and processes shall depend upon the prior approval from the National Sanitary Vigilance Agency.”

During the past few years, the courts in Brazil have issued decisions holding that Article 229-C did not grant ANVISA the power to examine patent applications for compliance with the patentability requirements under the Statute. Moreover, these cases held that ANVISA was solely limited to determining whether or not a patent application was against public health according to Article 18, I of the Statute and nothing more.

The most favorable decisions for patent owners were issued by District Courts sitting in Brasilia. Specifically, several Courts issued preliminary injunctions ordering ANVISA to grant prior approval of patent applications claiming pharmaceutical inventions holding that the examination of patentability requirements by ANVISA was illegal (for example, in May 2015, the 15th Federal District Court granted a preliminary injunction requested by Novartis on a writ of mandamus filed against ANVISA).

However, on June 11, 2015, the Honorable Marcia Nunes de Barros of the 13th Federal District Court sitting in Rio de Janeiro denied a preliminary injunction and held that ANVISA was permitted to examine a patent application claiming pharmaceutical inventions for compliance with the patentability requirements. The case was filed by Abbvie, Inc. and related to two patent applications involving Kaletra® (lopinavir/ritonavir).

In a 30-page decision, the Judge described the importance of Article 229-C and ANVISA’s ability to examination patent applications for compliance with the patentability requirements under the Statute in order to avoid the patenting of inventions to merely “incremental innovations”. Specifically, the Judge stated that: “…taking into consideration the systematic element, it seems clear, as already exposed, that the goal of the rule that included ANVISA in the proceeding of deciding about pharmaceutical patents, was clearly to include a vision over public health during examination, in a way to avoid the granting of undue patents, with highlights to the incremental ones”.

Unfortunately, but not surprisingly, this unfavorable decision will be used by ANVISA with respect to currently pending and future filed patent applications. However, it is too soon to assess how this decision will impact the current framework relating to Article 229-C and ANVISA with respect to patent prosecution. This decision should be carefully analyzed and rebutted by patent owners in order to avoid what could be a potential game changer in the pharmaceutical sector that might negatively impact innovator companies in Brazil.

Patent owners should keep in mind that the Federal Courts sitting in Brasilia have traditionally been more inclined to hold that ANVISA cannot examine patent applications for compliance with patentability requirements. Hopefully, this decision will not impact Judges sitting in Brasilia.

This post was written by Lisa Mueller and Roberto Rodrigues of Licks Attorneys.

Presentations from 6/14 BRIC Panel at BIO Now Available

Did you miss the BRIC panel “Strategies for Successfully Mastering the Different Challenges of the IP Systems in the BRIC Countries and U.S. in the Pharmaceutical and Life Sciences Sectors,” presented in conjunction with the 2015 BIO International Convention?

The panelist presentations are now available on the Michael Best website. Click here to view them.

Ariosa Diagnostics, Inc. v. Sequenom, Inc. – Another Diagnostic Patent Meets its End

On Friday, June 12, 2015, the Federal Circuit issued its decision in Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015) finding that the claims of U.S. Patent No. 6,258,540 (the ‘540 patent) did not meet the patent-eligibility requirements of 35 U.S.C. §101.

The ‘540 patent

The ‘540 patent claims certain methods of using cell-free fetal DNA (cffDNA). In 1996, the inventors, Doctors Dennis Lo and James Wainscoat, discovered cffDNA in material plasma and serum. Traditionally, this portion of maternal blood samples was discarded by researchers as medical waste. As a result, the inventors developed a method for detecting a small fraction of paternally inherited cffDNA in maternal plasma or serum to determine certain fetal characteristics, such as gender. The method was commercialized by Sequenom as the MaterniT21 test. An advantage provided by the test is that it created an alternative for prenatal diagnosis of fetal DNA that avoided the risks of widely-used techniques that took samples from the fetus or placenta.

In addition to claiming methods of using cffDNA, the ‘540 patent also provides for making a diagnosis of certain fetal characteristics based on the detection of paternally inherited cffDNA. According to the specification, a pregnant woman carrying a fetus with certain genetic defects has more cffDNA in her blood than a woman with a normal fetus.

Claims 1, 24 and 25 of the ‘540 patent recite:

1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises:

amplifying a paternally inherited nucleic acid from the serum or plasma sample, and

detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

24. A method for detecting a paternally inherited nucleic acid on a maternal blood sample, which method comprises:

removing all or substantially all nucleated and a nucleated cell populationS from the blood sample,

amplifying a paternally inherited nucleic acid from the remaining fluid and subjecting the amplified nucleic acid to a test for the paternally inherited fetal nucleic acid.

25. A method for performing a prenatal diagnosis on a maternal blood sample, which method comprises:

obtaining a non-cellular fraction of the blood sample,

amplifying a paternally inherited nucleic acid from the non-cellular fraction,

and performing nucleic acid analysis on the amplified nucleic acid to detect paternally inherited fetal nucleic acid.

The remaining claims describe how the method of detection occurs or how it can be used. For example, claim 2, which depends from claim 1, recites amplification by polymerase chain reaction (PCR). Claim 4, which also depends from claim 1, recites detection by a sequence specific probe.

District Court Proceedings

Ariosa Diagnostics, Inc. (Ariosa) and Natera, Inc. (Natera) make and sell alternative non-invasive tests that compete with Sequenom’s MaterniT21 test. Specifically, Ariosa sells the Harmony Test, a non-invasive test used for prenatal diagnosis of certain fetal characteristics, and Natera sells the Non-Invasive Paternity Test, which is used to confirm the paternity or non-paternity of a gestating fetus from genetic information in fetal DNA available in the blood of a pregnant female.

In response to letters threatening claims of infringement, from December 2011 through early 2012, Ariosa and Natera each filed separate declaratory judgment actions against Sequenom alleging non-infringement of the ‘540 patent. Sequenom counterclaimed alleging infringement. Sequenom filed a motion seeking an preliminary injunction to enjoin Ariosa from selling the Harmony Prenatal test. In July 2012, the district court denied the motion finding that there was a substantial question over whether the subject matter of the asserted claims was directed to eligible subject matter. Sequenom appealed to the Federal Circuit.

In August 2013, the Federal Circuit vacated and remanded the case, holding that the district court erred in certain respects not relevant to this appeal. Additionally, the Court did not offer any opinion regarding the subject matter eligibility of the asserted claims.

After remand, the parties filed cross motions for summary judgment regarding invalidity under 35 U.S.C. §101. The district court found that the ‘540 patent was directed to the natural phenomenon of paternally inherited cffDNA and that the claims did not add enough to the natural phenomenon to make the claims patent eligible under §101. According to the district court, at the time of the filing of the ‘540 patent in 1997, the steps of amplifying and detecting were well-understood, routine, or conventional. Thus, the district court concluded that the ‘540 patent was not directed to patentable subject matter finding that the only “inventive concept of the processes of the ‘540 patent is to apply those well-understood, routine processes to paternally inherited cffDNA, a natural phenomenon”. Additionally, the district court also found that the claimed processes posed a risk of preempting a natural phenomenon. Sequenom appealed.

Federal Circuit Decision

The Federal Circuit began its decision by setting forth the two-prong patent-eligibility test (citing Mayo Collaborative Services v. Prometheus Laboratories, Inc. (March 2012)). The first prong is to determine whether the claims at issue are directed to a patent-ineligible concept. If answered in the affirmative, the second prong is to determine whether the elements of each claim, both individually and as an ordered combination, recite additional elements that transform the nature of the claim into a patent-eligible invention that amounts to significantly more than the ineligible concept itself.

Regarding the first prong, the Federal Circuit noted that the claims of the ‘540 patent were method claims, which generally constitute eligible subject matter. However, upon further inspection, the Court further noted that the claims were directed to a multistep method that began with cffDNA taken from a maternal plasma or serum sample. cffDNA was naturally occurring and circulated freely in the blood stream of a pregnant woman. As a result, the existence of cffDNA in maternal blood was a natural phenomena. The Court further noted that the method ended with paternally inherited cffDNA, which was also a natural phenomena. Therefore, because the method began and ended with a natural phenomenon, the Federal Circuit held that the claims were directed to naturally occurring matter. The Court stated that the specification supported its conclusion. For example, column 1, lines 50-51 states: “[i]t has now been discovered that foetal DNA is detectable in maternal serum or plasma samples”, column 13, line 11-13 states: “[t]hese observations indicate that maternal plasma/serum DNA may be a useful source of material for the non-invasive prenatal diagnosis of certain genetic disorders,” and column 16, lines 12-14 states: “[t]he most important observation in this study is the very high concentration of foetal DNA in maternal plasma and serum”.

Regarding the second prong, the Federal Circuit concluded that the practice of the method claims did not result in an inventive concept that transformed the natural phenomena of cffDNA into a patentable invention. Specifically, the Court stated that for process claims that encompass natural phenomenon, the process steps must recite additional features that are new and useful. According to the Court:

“The method at issue here amounts to a general instruction to doctors to apply routine, conventional techniques when seeking to detect cffDNA. Because the method steps were well-understood, conventional and routine, the method of detecting paternally inherited cffDNA is not new and useful. The only subject matter new and useful as of the date of the application was the discovery of the presence of cffDNA in maternal plasma or serum.”

With respect to the preparation and amplification steps, the Court noted that the specification confirmed that in 1997 that these steps were well-understood, routine, conventional activities performed by doctors. Additionally, Sequenom’s expert testified that PCR and other methodologies for amplifying DNA were well known in 1997. The Court further found that the detecting steps were also similarly well-understood, routine and conventional.

Regarding the dependent claims, the Court found that these claims were broad examples of how to detect cffDNA in maternal plasma. The Court noted that these claims were focused on the use of the natural phenomenon in combination with well-understood, routine and conventional activity.

The Court concluded stating

“Thus in 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.”

Regarding preemption, Sequenom argued that there were numerous other uses of cffDNA aside from those claimed in the ‘540 patent and as a result, the ‘540 patent did not preempt all uses of cffDNA. The Federal Circuit disagreed. The Court noted that while preemption might signal patent ineligible subject matter, the absence of complete preemption did not demonstrate patent eligibility. Specifically, in this case, the Court noted that Sequenom’s attempts to limit the breadth of the breadth of the claims by showing alternative uses of cffDNA outside the scope of the claims did not change the conclusion that the claims were directed to patent ineligible subject matter.

At the end of the opinion, the Court addressed Sequenom’s arguments that before the ‘540 patent that “no one” was using plasma or serum of pregnant mothers to amplify and detect paternally-inherited cffDNA. Moreover, Sequenom noted that the 1997 Lancet publication of the inventors had been cited over a thousand times and that the claimed method utilized the man-made tools of biotechnology in a new way that revolutionized prenatal care. The Court agreed but noted, citing to Ass’n for Molecular Pathology v. Myriad Genetics, Inc. (June 2013), that just because a discovery is groundbreaking, innovative or brilliant does not by itself satisfy §101. The Court stated:

“While Drs. Lo and Wainscoat’s discovery regarding cffDNA may have been a significant contribution to the medical field, that alone does not make it patentable. We do not disagree that detecting cffDNA in maternal plasma or serum that before was discarded as waste material is a positive and valuable contribution to science. But even such valuable and contributions can fall short of statutory patentable subject matter, as it does here”.

This post was written by Lisa Mueller.

BRIC Panel at 2015 BIO International Convention – Sunday, June 14

In conjunction with the 2015 BIO International Convention, Michael Best & Friedrich LLP is excited to be sponsoring a panel discussion this Sunday, June 14, 2015 on “Strategies for Successfully Mastering the Different Challenges of the IP Systems in the BRIC Countries and U.S. in the Pharmaceutical and Life Sciences Sectors.” Lisa Mueller will be presenting with four attorneys from around the globe, for a discussion including informative insight and advice for successfully navigating through some of the challenges associated with the intellectual property systems in these countries and useful strategies for maximizing intellectual property protection. For more information and to register, click the invitation below.

Federal Circuit Hears Oral Arguments in Litigation Involving the First U.S. Biosimilar Product

On June 3, 2015, a three-judge Federal Circuit panel comprising Judges Alan D. Lourie, Raymond T. Chen and Pauline Newman, struggled to understand the patent dispute resolution provisions of the Biologics Price Competition and Innovation Act (BPCIA) during oral arguments in Amgen, Inc. v. Sandoz, Inc., Fed. Cir. No. 15-01499.

Background

On July 24, 2014, Sandoz became the first company to announce acceptance by the U.S. Food and Drug Administration (FDA) of a biologics license application under the abbreviated pathway of the BPCIA at 42 U.S.C. §262(k). The application was for approval to market Zarxio™, a biosimilar of Amgen’s Neupogen® (filigrastim) product.

According to the patent dispute resolution provisions of the BPCIA (also known affectionately as the “patent dance”), once notified by FDA of acceptance of its application for review, Sandoz had 20 days to provide Amgen with a copy of its application and other manufacturing information. After this initial disclosure, certain other exchanges and disclosures of information were to occur between the parties based on a tight time schedule. However, Sandoz refused to provide this initial or other information alleging that participation in the patent dance was not mandatory. As a result, because Sandoz failed to:  (1) provide Amgen with a copy of its application and manufacturing information within the 20 day period, (2) follow any of the other patent dispute resolution procedures of the statute (such as develop a list of patents to enable Amgen to know which, if any, of its patents Zarxio™ might infringe) and (3) provide Amgen with notice 180 days before the first commercial marketing of Zarxio™, Amgen sued Sandoz in the U.S. District Court in the Northern District of California on October 24, 2014. In its complaint, Amgen alleged various state law claims (unfair competition (under Cal. Bus. & Prof. Code Section 17200 et seq.) and conversion) and infringement of U.S. Patent No. 6,162,427. Amgen also requested a preliminary injunction to prevent Sandoz from marketing Zarxio™.

On March 6, 2015, the FDA approved Zarxio™ for the same five indications approved for Neupogen®.

On March 19, 2015, the District Court denied Amgen’s request for a preliminary injunction agreeing with Sandoz’s interpretation that the BPCIA’s patent dance provisions were optional. Final judgement was entered by the District Court on March 25, 2015 and Amgen appealed to the Federal Circuit on the same day.  On March 27, 2015, Amgen sought another preliminary injunction from the District Court pending appeal, or alternatively, an injunction lasting until the Federal Circuit could rule on the appeal. On April 15, 2015, the District Court denied the motion on both grounds.

On April 17, 2015, Amgen filed an emergency motion for an injunction pending appeal with the Federal Circuit pursuant to Fed. R. App. P. 8(a). In its motion, Amgen argued that it would likely succeed on the merits because the District Court erred in its interpretation of the BPCIA. According to Amgen, the District Court, by converting the provisions of the BPCIA from mandatory to optional, “toppled the statutory balance in favour of the Applicant and allowed Applicants to game the system”. Sandoz filed its opposition to the motion on April 24, 2015.  On May 5, 2015, the Federal Circuit granted Amgen’s emergency motion, stalling at least temporarily, Sandoz’s commercial launch of Zarxio™. The Federal Circuit expedited Amgen’s appeal and docketed June 3, 2015 for the oral hearing.

The Oral Arguments

Nick Groombridge of Paul Weiss, representing Amgen, began by addressing whether the disclosure of a biologics license application and certain manufacturing information by a Section 351(k) applicant (K applicant) to the reference product sponsor was mandatory or optional. In response, Judge Lourie quickly commented:

What you are going to tell us Mr. Groombridge is that ‘shall’ means ‘shall’ and in fact, it means ‘must’ and usually that is true, and, this is a statute that is a multifaceted statute and I’m thinking that perhaps it is entitled to a Pulitzer Price for complexity or unclarity or something.”

Mr. Groombridge noted that the BPCIA was “not the most plainly worded statute” and argued that the filing of a §351(k) application was an act of infringement and that such infringement occurs before the reference product sponsor knows which patents are going to be infringed. Judge Chen noted that he had never seen a statute written in such a way to which Mr. Groombridge stated that in his opinion, the BPCIA was “purposefully” written to “deal with the complexities of the patenting around biologics”.

Deanne Maynard of Morrison & Foerster, representing Sandoz, began her argument stating that the “BPCIA procedures on which Sandoz relies creates multiple ways to the same substantive end”. Judge Lourie quickly interjected stating, “It’s awfully detailed concerning the exchange of information – why would that have been for not if you could just skip it?” As Ms. Maynard continued, the Justices appeared sceptical of Sandoz’s interpretations of the patent dance provisions. For example, at one point, Judge Newman stated:

How is the sponsor supposed to know if anything is going on without notice? How can you file suit if no one tells you ‘I’m getting ready to infringe your patent?’  … It’s hard to make sense of the extensive legislative debate about those provisions based on the way you are interpreting it – so help us.

Judge Chen added:

…[Y]ou seem to be reading (l)(2)-(l)(6) as an option and then if the Applicant doesn’t choose that option than there is the (l)(9) option. I just don’t see either through the language or structure of (l) where there is a hint that it is a ‘choose your own adventure’ situation for the K applicant.  It seems much more like that (l)(2)-(l)(6) keeps saying over and over and over again ‘shall’ do this ‘shall’ do that and (l)(9) finally gets to well, if the K applicant fails to provide the application in a timely way then the patent owner can bring a DJ action at that point. So, in that sense, it does feel like it’s mandatory and if you fail to meet you requirements, your obligations under the statute, you deal with the consequences in (l)(9)(c).

Judge Chen asked the question of what would happen if (l)(9) did not exist. Ms. Maynard responded that it would be a “harder issue for us” but acknowledged that “(l)(9) does exist”.

Near the end of the Mr. Groombridge’s rebuttal, Judge Lourie brought the court to laughter when he said, “If the purpose of the statute is to avoid litigation, it’s already failed. It doesn’t show promise of success”.

Please continue to watch the BRIC Wall Blog for updates on Amgen v. Sandoz.