Brazil mailbox litigation update: Good news to start the year for the pharmaceutical industry

On January 22, 2015, another mailbox case was favorably decided for a pharmaceutical company.  This latest case was decided by Judge Ana Amelia Antoun of the 9th Federal District Court.  Judge Antoun is the fourth Judge to decide a mailbox case and the third Judge to issue a favorable decision for a pharmaceutical company.

The Judge rejected the Brazilian Patent Office’s (INPI) request to reduce the term of the patent.  Instead, the Judge maintained the term of the patent for a period of ten years from grant. According to the Judge, INPI’s delay in examining the application required the application of the constitutional principles of trust and good faith that govern the relationship with public administration. The Judge followed the reasoning of the previous two judges who favorably decided for pharmaceutical companies.

Judge Antoun is handling nine mailbox cases.  We expect that she will issue similar decisions in the remaining cases relatively soon. Additionally, it is expected that the appeals pending before the Federal Court of Appeals will be decided in March 2015.

Please watch the BRIC Wall Blog for further updates on mailbox litigation.

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

 

The Copaxone Story in the U.S. and India: U.S. Supreme Court Decision

As an update to our earlier 2014 postings, The Copaxone Story in the U.S. and India, The Copaxone Story in the U.S. and India: An Update, The Copaxone Story in the U.S. and India: A Further Update and The Copaxone Story in the U.S. and India: To Stay or Not to Stay is the Question, the U.S. Supreme Court (Supreme Court), on January 20, 2015, held 6-2 that questions of fact resolved by a district court prior to claim construction must be given deference by the Court of Appeals of the Federal Circuit (Federal Circuit) and can only be reversed if clearly erroneous.

Background

On December 27, 2007, Sandoz, Inc. (Sandoz) filed the first abbreviated new drug application (ANDA) with the U.S. Food and Drug Administration (FDA) seeking approval to manufacture and sell its proposed generic version of Copaxone®, before the expiration of the Orange Book patents. On June 29, 2009, Mylan filed its own ANDA. In view of the ANDA submissions, Teva Pharmaceutical Industries Ltd.’s (and Yeda Research and Development Co., Ltd.) (Teva) separately sued Sandoz (in August 2008) and Mylan and Natco (in October 2009) in the U.S. District Court, Southern District of New York (District Court) for infringement of the Orange Book patents as well as U.S. Patent Numbers 5,800,808 (‘808 patent) and 6,048,898 (‘898 patent). The District Court issued an injunction barring Sandoz and Mylan from marketing their generic versions of Copaxone® until September 1, 2015 (the expiration date of the ‘808 patent).

The lawsuits were consolidated and on June 29, 2012, the Judge found all nine patents valid, enforceable and infringed. Specifically, the Judge found Mylan had infringed seven of the patents and Sandoz infringed four patents. On July 26, 2013, the Federal Circuit ruled that four of the patents were valid but found five invalid for indefiniteness. Specifically, the Federal Circuit ruled that the claims of the five patents were indefinite because a person skilled in the art could not discern the boundaries of the claims. The patents declared invalid were U.S. Patent Numbers 5,800,808, 5,981,589, 6,048,898, 6,620,847 and 6,939,539. The patents held valid were U.S. Patent Numbers 6,054,430, 6,342,476, 6,362,161 and 7,199,098. The invalidation of the ‘808 patent was significant because of all the Orange Book listed patents, it had the longest expiration date (namely, September 1, 2015 (all of the remaining patents expire on the same date – May 24, 2014)). The Federal Circuit remanded the case to the District Court to determine whether to modify its injunction.

On November 13, 2013, the Supreme Court denied Teva’s request to stay the Federal Circuit’s decision during appeal. As a result of this denial, the District Court was compelled to follow the Federal Circuit’s mandate and modified its injunction. As a result, Sandoz and Mylan are permitted launch their respective generic versions of Copaxone® beginning May 24, 2014 (rather than September 1, 2015).

On March 31, 2014, the Supreme Court granted Teva’s writ of certiorari to review the Federal Circuit’s decision. Specifically, Teva petitioned for writ of certiorari to clarify the correct standard of review used by Federal appellate courts when reviewing factual findings made by a district court.

U.S. Supreme Court Decision

The Supreme Court reversed the Federal Circuit and established a new split standard of review of district courts’ claim construction rulings. Since Markman v. Westview Instruments, Inc., 517 U.S. 370 (1996) (Markman), the Federal Circuit has applied a de novo standard of review to all portions of district courts’ claim construction rulings, meaning the Federal Circuit reviewed “anew” the district court’s entire ruling, including the lower courts’ factual findings. The Supreme Court ruled that the de novo standard alone is improper and instead, the Federal Circuit must apply a “clear error” standard of review on “subsidiary factual disputes” resolved by district courts in construing a patent’s claims.

The Supreme Court agreed with Teva that the Federal Circuit applied the wrong standard of review in not giving deference to the District Court’s factual determinations. Specifically, the Supreme Court concluded that while Markman determined that the issue of claim construction is a question of law, Markman also recognized that “subsidiary factfinding is sometimes necessary” during this construction. Id. at 6, 574 U.S. ____. Federal Rule of Civil Procedure 52(a)(6) (Rule 52) required that courts of appeal not set aside a district court’s findings of fact unless “clearly erroneous.” Based upon Rule 52, as well as additional precedent, the clearly erroneous standard applied to district courts’ factual findings used in the proper construction of a patent claim. The Supreme Court also relied on the fact that “practical considerations favor clear error review.” In particular, patent law frequently requires knowledge of specific scientific problems and principles that are “not usually contained in the general storehouse of knowledge and experience.” Id. at 7, 574 U.S. ____, (citing Graver Tank & Mfg. Co. v. Linde Air Products Co., 339 U.S. 605, 610 (1950)). The Court noted that a district court judge who has presided over a proceeding has a “comparatively greater opportunity to gain” more familiarity with the specific scientific problems and principles than an appeals court judge.

Additionally, the Supreme Court held that while the ultimate issue of the proper construction of a claim remains a question of law that the Federal Circuit reviews de novo, any subsidiary factual disputes resolved by a district court, including those that may be dispositive to the proper construction of a claim, must be reviewed under Rule 52’s “clearly erroneous” standard.

The Supreme Court also provided an explanation to ensure that the federal courts properly applied this change in the standard of review. The Court explained that when a district court’s claim construction required it to review only evidence intrinsic to a patent, that is, only the patent claims and the specification, along with the prosecution history, the district court’s determination would be solely a question of law, and thus, subject to de novo review. Conversely, where a district court is forced to look beyond the patent’s intrinsic evidence and consider extrinsic evidence in constructing a patent’s claims the clear error standard must apply. Thus, for example, where a district court considers opposing testimony of experts and makes a factual finding, that determination is subject to clear error review, but the ultimate construction based upon that factual underpinning remains subject to de novo review.

Application of the new split standard to the facts required reversal of the Federal Circuit’s determination. The Supreme Court found that the Federal Circuit erred in not accepting the District Court’s determination that Teva’s expert’s explanation was correct in analyzing how to determine molecular weight. The Supreme Court reversed and remanded to the Federal Circuit to consider the appeal in light of the new standard.

Finally, Justices Thomas and Alito dissented from the majority decision. Writing for the dissent, Justice Thomas argued that the District Court’s “subsidiary findings” made in the course of constructing the patent’s claims were not “factual findings” that fall within the purview of Rule 52. Instead, according to the dissent, the subsidiary findings associated with construing claim language is more closely related to the findings associated with construing a statute and thus, according to the dissent, de novo review should be applied.

This post was written by John C. Scheller, Albert Bianchi, Jr. and Lisa Mueller.

5 Lessons From FDA’s First Biosimilar Review

Lisa Mueller, partner in Michael Best’s Intellectual Property and Chair of the Life Sciences and Chemical Practice Groups and Laura Opperman, Ph.D., a Patent Scientist in the Intellectual Property Practice group, gave input for a Law360 article titled, “5 Lessons From FDA’s First Biosimilar Review – Law360,” on January 8, 2015. To view the full article, click here.

Inching Closer to the First Biosimilar Approval in the U.S.

Last week we saw some significant biosimilar activity in the U.S. Specifically, on January 7, 2015, a U.S. Food and Drug Administration (FDA) Advisory Committee (Advisory Committee) voted 14-0 to approve Sandoz Inc.’s (Sandoz) filgrastim biosimilar (referred to as “EP2006”) for all five indications of Neupogen® (the reference product manufactured by Amgen Inc. (Amgen)).  Specifically, the Advisory Committee found EP2006 to be “highly similar” to filgrastim, “notwithstanding minor differences in clinically inactive components,” and that “there are no clinically meaningful differences between EP2006 and filgrastim in terms of [purity], safety, and effectiveness.”  Typically, the FDA follows an Advisory Committee’s recommendation, although it is not required to do so.  Assuming the FDA follows the Advisory Committee’s recommendation, EP2006 would be the first biosimilar approved under the FDA’s 351(k) biosimilar pathway.  Sandoz manufactures a biosimilar version of filgrastim under the brand name Zarzio® in more than 40 countries. For example, Zarzio® was first approved in the European Union in 2009.

As mentioned above, EP2006 received a recommendation for approval in five indications (all of which are somewhat related):  (1) cancer patients receiving myelosuppressive chemotherapy; (2) patients with acute myeloid leukemia receiving induction or consolidation chemotherapy; (3) cancer patients receiving bone marrow transplant; (4) patients undergoing peripheral blood progenitor cell collection and therapy; and (5) patients with severe chronic neutropenia.  Interestingly, because Sandoz provided Phase III data for only one of the five indications, the remaining four indications were awarded by extrapolation.

Extrapolation is highly controversial but viewed as crucial in keeping the research and development costs down for biosimilars.  It will be interesting to see how the FDA handles extrapolation with more complex molecules (such as antibodies), which have been approved for very distinct applications (such as, for example, infliximab and adalimumab, which are approved for such distinct indications such as rheumatoid arthritis, ulcerative colitis and Crohn’s disease).  For example, in Europe, Celltrion Inc. (Celltrion) was able to fully extrapolate to six indications (including psoriasis and digestive disorders) for its biosimilar version of infliximab.  However,  extrapolation was not permitted in Canada where regulators found that differences between Celltrion’s biosimilar and the reference product raised questions about whether the biosimilar infliximab would be suitable for every condition.

Sandoz’ requested approval for EP2006 as a biosimilar to Neupogen® and not as an interchangeable product.  However, switching studies are in process that could support a future interchangeability application.  Publication of the FDA’s guidance document on interchangeability is expected in 2015.

One significant issue not discussed by the Advisory Committee or in its briefing document released prior the meeting was naming.  Will Sandoz’ product have the generic name filgrastim or some variant?  Novartis proposed the brand name, Zarxio for EP2006.  However, this brand name has not yet been approved by the FDA.  Industry is still waiting publication of the FDA’s guidance document on naming.

Despite the good news, significant challenges still remain for Sandoz and its biosimilar product.  On January 6, 2015, the day before the Advisory Board’s vote, Amgen filed a motion for partial summary judgment in its lawsuit filed against Sandoz on October 24, 2014.  Specifically, Amgen urged a California federal judge to find that pursuant to the Biologics Price Competition and Innovation Act (BPCIA) Sandoz was required to provide Amgen with a copy of its 351(k) application for its biosimilar product as well as its manufacturing information no later than 20 days after the FDA notified Sandoz of acceptance of its 351(k) application.  Additionally, Amgen requested that the judge find that Sandoz could not have provided notice of commercial marketing as required under the BPCIA because the FDA had not yet approved Sandoz’ 351(k) application.  Thus, according to Amgen, Sandoz’s conduct violated the BPCIA and this violation represented unfair competition under California law.  Unfortunately, this litigation will likely need to be resolved before EP2006 can enter the marketplace.  Resolution could be years away thus  further delaying entry of the first biosimilar product into the U.S. marketplace.

This post was written by Lisa Mueller.

Be Mindful of Your Claims in Divisional Applications and Patents in South Africa

 

In September 2014, the Supreme Court of Appeal of South Africa (Supreme Court) issued a decision in Pharma Dynamics (Proprietary) Limited (Pharma) versus Bayer Pharma AG (formerly Bayer Schering Pharma AG) and Bayer (Proprietary) Limited (Bayer Pharma AG and Bayer Limited will be collectively referred to as “Bayer”) relating to Bayer’s South African Patent No. 2004/4083 entitled “Pharmaceutical combination of ethinylestradiol (EE) and drospirenone (DSP)” (the 2004 patent).  A copy of the decision is provided here: DECISION.  The decision is important because the Court held that while it is possible to obtain parent and divisional patents in South Africa having overlapping claims of varying scope, coterminous claims (meaning claims of identical scope) are not permitted.

The claims of the 2004 patent relate to a female contraceptive sold by Bayer under the brand name Yasmin® which is a combination of the DSP and EE.  The 2004 patent is a divisional patent of South African Patent No. 2002/1668 (the 2002 patent).  Claim 1 of the 2004 patent recites:

1.  A pharmaceutical composition comprising:

as a first active agent drospirenone in an amount corresponding to a daily dosage, on administration of the composition, of  from about 2 mg to 4 mg, and

as a second active agent ethinylestradiol in an amount corresponding to a daily dosage of from about 0.01 mg to 0.05 mg,

together with one or more pharmaceutically acceptable carriers or excipients,

wherein at least 70% of said drospirenone is dissolved from said composition within 30 minutes, as determined by USP XXIII Paddle Method II using water at 37ºC as the dissolution media and 50 rpm as the stirring rate.

In contrast, claim 1 of the 2002 patent recites that the drospirenone is in micronized form.

In March 2011, Pharma obtained approval from the Medical Control Council in South Africa to import and sell “Ruby”, a generic version of Yasmin®.  Bayer alleged infringement of claim 1 of the 2004 patent by Pharma and sought judicial relief in the form of an interdict and ancillary relief.  Pharma denied infringement and counterclaimed for revocation of the 2004 patent alleging invalidity.  The lower court, a quo, held that the 2004 patent was valid and infringed by Pharma.  The relief requested by Bayer was granted and Pharma’s counterclaim dismissed.  Pharma appealed.  On appeal, regarding invalidity, Pharma argued that the 2004 patent lacked inventive step and was not a “true” divisional of the 2002 patent and thus lacked novelty in view of the disclosure in the 2002 patent.

In South Africa, divisional patent applications are governed by Section 37 of the Patents Act (Section 37) which provides:

1.  Where at any time after an application has been lodged at the patent office and before it is accepted, a fresh application is made in the prescribed manner by the same applicant in respect of part of the matter disclosed in the first-mentioned application, the registrar may, on application made to him in the prescribed manner before that application is accepted, direct that such fresh application be antedated to a date not earlier than the date on which the first-mentioned application was so lodged.

2.  A patent granted on such fresh application shall not be revoked or invalidated on the ground only that the invention claimed in such fresh application is not new having regard to the matter disclosed in the first-mentioned application.

Pharma made several arguments as to why it believed the 2004 patent was not a “true” divisional.  Specifically, Pharma argued that the “body”and the claims of the 2002 and 2004 patents were the same,  and that Section 37 did not allow for a divisional claim to be broader than the claim of its parent.

The Supreme Court rejected all of Pharma’s arguments. First, the Court noted that the very idea of a divisional patent is that it contains the same text as its parent.  From a practical standpoint, this made sense since the invention disclosed in a divisional and parent was the same and the difference between the two resided in their respective claims.  Next, the Court stated that the claims of the 2002 and 2004 patents were not coterminus (namely, the claims of each did not have identical scope).  Specifically, claim 1 of the 2002 patent was expressly limited to DSP in micronized form.  Claim 1 of the 2004 patent did not recite that DSP was limited to any specific form.  Thus, claim 1 of the 2004 patent was broader than claim 1 of the 2002 patent. Finally, the Court examined previous case law and found that there was nothing that prohibited the claims of a divisional application from being broader than the claims of its parent.  Instead, the Court noted that previous case law stood for the proposition that the claims of a divisional application could not be broader than the invention disclosed in the “body” of its parent.

Under South African patent law, a single invalid claim in a patent renders the entire patent invalid and unenforceable until such invalidity has been cured via an amendment.  Therefore, in view of this recent decision and the fact that patent applications are not formally examined in South Africa, applicants should carefully review the claims of any of their divisional patent applications and patents to make sure that none of the claims is identical in scope (coterminus) with one or more parent applications or patents.

This post was written by Lisa Mueller.

Happy New Year!

Happy New Year from the BRIC Wall Blog!  We would like to take this opportunity to thank our readers for for their interest and support during 2014!!!  We have been taking a short break for the Christmas holidays but will be resuming with a new post starting on January 5, 2015!  Our goal for 2015 is to have more frequent and regular posts.  We would love to receive your comments and suggestions on topics you would like to read about in the new year!