Federal Circuit Upholds Validity of Lysteda Patents

28 August 2014 PharmaPatents Blog

In two decisions issued under the same name (Ferring B.V. v. Watson Laboratories, Inc.), the Federal Circuit upheld the validity of the Orange Book-listed patents for Lysteda®, but found that they were not infringed by either Apotex’s or Watson’s Abbreviated New Drug Applications (ANDAs). In this article, I focus on the decision relating to the validity of the patents. Although Judge Lourie only spends three pages on his obviousness analysis, any Federal Circuit decision that upholds the validity of formulation claims seems to be worth noting! I also find it interesting that the Federal Circuit cited the FDA’s “fast track” review of Lysteda® as evidence of non-obviousness.

The Patents at Issue

The patents at issue were Ferring’s U.S. 7,947,739; U.S. 8,022,106, and U.S. 8,273,795, which are listed in the Orange Book for Lysteda®, Ferring’s tranexamic acid product for the treatment of heavy menstrual bleeding. As summarized by the Federal Circuit, the claims are directed to “oral dosage forms or formulations and methods of treating menorrhagia and require three elements: (1) about 650 mg of tranexamic acid; (2) a so-called modified release material that comprises either about 10% to about 35% or about 5% to about 50% by weight of the formulation; and (3) a specified dissolution release rate of the tranexamic acid in water as measured by a particular United States Pharmacopeia (“USP”) method.”

The Obviousness Arguments

Watson argued that the claims were invalid as obvious based on the prior art disclosures:

  • A “July 27, 2000 report by the European Agency for the Evaluation of Medicinal Products Committee for Proprietary Medicinal Products (“EMA report”) that evaluates the safety and efficacy of a 500 mg tranexamic acid product comprising the excipient hydroxypropylcellulose,”
  • U.S. 5,858,411, which lists “tranexamic acid as one of many medicinal ingredients that could be used with proposed sustained release granular preparations containing binders such as hydroxypropylcellulose and hypromellose.”

In particular, Watson argued that “it would have been obvious to increase the amount of tranexamic acid to 650 mg and to package the drug in a modified oral dosage form.”

Ferring argued against these assertions, and also that “secondary considerations support the district court’s conclusion of nonobviousness.”

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Lourie and joined by Judges Dyk and Reyna.

In affirming the district court’s finding that Watson had failed to establish obviousness by clear and convincing evidence, Judge Lourie noted:

In this case, the cited prior art references neither set forth the limitations required by the asserted claims, nor provided any reason or motivation to combine those teachings to derive the claimed formulations with specific dissolution profiles.

With regard to the recited dose, Judge Lourie found that the prior art did not disclose “higher tablet strengths” above 500 mg, “and particularly not the claimed 650 mg formulation.” Moreover, the cited EMA report stated that increased doses were associated with “a concomitant dose-dependent increase in gastrointestinal side effects.”

Judge Lourie also noted that “the references do not disclose the claimed amounts of modified release polymers, with the EMA report being silent on the amount of inactive ingredients, and the ’411 patent teaching “that binders such as hydroxypropylcellulose and hypromellose may only be added in an amount from 1% to 5% by weight of the preparation.”

With regard to the dissolution profiles, Judge Lourie emphasized that “Watson did not identify any prior art references disclosing the critical dissolution limitations of the patented claims, but merely asserted in a conclusory manner that those limitations would have been obvious or could have been predicted while failing to address why one of ordinary skill in the art would choose the specific release profiles claimed.”

In this regard, Judge Lourie cited with favor Ferring’s “supporting evidence [that] demonstrated that there was a long-felt and unmet need for a treatment for menorrhagia that avoided adverse events.” That evidence was found in the FDA’s decision to grant “fast track” status to the NDA covering Lysteda® under 21 U.S.C. § 356(b)(1) , “which is the undisputed commercial embodiment of Ferring’s asserted claims.”

Fast-Track FDA Review as Evidence of Non-Obviousness

In addition to being interesting for the basic reason that the challenged formulation claims withstood an obviousness challenge, this case also is interesting for the weight the Federal Circuit gave to the fact that the FDA granted “fast track” review to the New Drug Application for Lysteda®.

The governing FFDA statute is 21 USC § 355(b)(1):

(b) Designation of drug as fast track product
(1) In general
The Secretary shall, at the request of the sponsor of a new drug, facilitate the development and expedite the review of such drug if it is intended, whether alone or in combination with one or more other drugs, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition, or if the Secretary designates the drug as a qualified infectious disease product under section 355f(d) of this title. (In this section, such a drug is referred to as a “fast track product”.)

The Federal Circuit also noted:

Lysteda® is the first tranexamic drug approved by the FDA for treating menorrhagia in the United States.

I think it is notable that even though the claims at issue were based on a novel formulation, and even though the use of tranexamic acid to treat menorrhagia was “known” in the literature, the Federal Circuit seemed to give at least some weight to the fact that the patents at issue were directed to the first tranexamic acid product to actually earn FDA approval.

This blog is made available by Foley & Lardner LLP (“Foley” or “the Firm”) for informational purposes only. It is not meant to convey the Firm’s legal position on behalf of any client, nor is it intended to convey specific legal advice. Any opinions expressed in this article do not necessarily reflect the views of Foley & Lardner LLP, its partners, or its clients. Accordingly, do not act upon this information without seeking counsel from a licensed attorney. This blog is not intended to create, and receipt of it does not constitute, an attorney-client relationship. Communicating with Foley through this website by email, blog post, or otherwise, does not create an attorney-client relationship for any legal matter. Therefore, any communication or material you transmit to Foley through this blog, whether by email, blog post or any other manner, will not be treated as confidential or proprietary. The information on this blog is published “AS IS” and is not guaranteed to be complete, accurate, and or up-to-date. Foley makes no representations or warranties of any kind, express or implied, as to the operation or content of the site. Foley expressly disclaims all other guarantees, warranties, conditions and representations of any kind, either express or implied, whether arising under any statute, law, commercial use or otherwise, including implied warranties of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Foley or any of its partners, officers, employees, agents or affiliates be liable, directly or indirectly, under any theory of law (contract, tort, negligence or otherwise), to you or anyone else, for any claims, losses or damages, direct, indirect special, incidental, punitive or consequential, resulting from or occasioned by the creation, use of or reliance on this site (including information and other content) or any third party websites or the information, resources or material accessed through any such websites. In some jurisdictions, the contents of this blog may be considered Attorney Advertising. If applicable, please note that prior results do not guarantee a similar outcome. Photographs are for dramatization purposes only and may include models. Likenesses do not necessarily imply current client, partnership or employee status.

Related Services

Insights

A Review of Recent Whistleblower Developments
19 July 2019
Legal News: Whistleblower Developments
Cloud security inadequate for Cyber threats, are you surprised?
19 July 2019
Internet, IT & e-Discovery Blog
Blockchain: A Tool With a Future in Healthcare
18 July 2019
Health Care Law Today
Do You Know What IMMEX Stands For?
16 July 2019
Dashboard Insights
Review of 2020 Medicare Changes for Telehealth
11 December 2019
Member Call
2019 NDI Executive Exchange
14-15 November 2019
Chicago, IL
MAGI’s Clinical Research Conference
29 October 2019
Las Vegas, NV
Association for Corporate Counsel Annual Meeting 2019
27-30 October 2019
Phoenix, AZ