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.