Mayne Pharma Int'l Pty. Ltd. v. Merck Sharp & Dohme Corp.

• Decision Date: 21 June 2019
• Docket Number: 2018-1593
• Citation: 927 F.3d 1232
• Parties: MAYNE PHARMA INTERNATIONAL PTY. LTD., Appellant v. MERCK SHARP & DOHME CORP., Appellee Andrei Iancu, Under Secretary of Commerce for Intellectual Property and Director of the United States Patent and Trademark Office Intervenor
• Court: U.S. Court of Appeals — Federal Circuit

927 F.3d 1232

MAYNE PHARMA INTERNATIONAL PTY. LTD., Appellant

v.MERCK SHARP & DOHME CORP., Appellee

Andrei Iancu, Under Secretary of Commerce for Intellectual Property and Director of the United States Patent and Trademark Office Intervenor

2018-1593

United States Court of Appeals, Federal Circuit.

Decided: June 21, 2019

Jacques Semmelman, Curtis, Mallet-Prevost, Colt & Mosle LLP, New York, NY, argued for appellant. Also represented by Eliot Lauer, Nicole Maria Mazanitis; Thomas K. Hedemann, Axinn Veltrop Harkrider, LLP, Hartford, CT; Jason Murata, Axinn, Veltrop & Harkrider LLP, San Francisco, CA; Teresa Stanek Rea, Crowell & Moring, LLP, Washington, DC.

Jennifer Loraine Swize, Jones Day, Washington, DC, argued for appellee. Also represented by Jane M. Love, Robert Trenchard, Gibson, Dunn & Crutcher LLP, New York, NY.

Molly R. Silfen, Office of the Solicitor, United States Patent and Trademark Office, Alexandria, VA, argued for intervenor. Also represented by Thomas W. Krause, Kakoli Caprihan, Frances Lynch, Joseph Matal.

Before Lourie, Dyk, and O’Malley, Circuit Judges.

Lourie, Circuit Judge,

Mayne Pharma International Pty. Ltd. ("Mayne") appeals from the final written decision of the U.S. Patent and Trademark Office Patent Trial and Appeal Board ("the Board") in an inter partes review, concluding that claims 2, 6, and 9–14 of U.S. Patent 6,881,745 ("the ’745 patent") are unpatentable as anticipated or obvious. See Merck Sharp & Dohme Corp. v. Mayne Pharma Int’l Pty. Ltd., No. IPR 2016-01186, at 2 (P.T.A.B. Dec. 18, 2017), J.A. 76–111 ("Decision "). For the reasons detailed below, we affirm.

BACKGROUND

Mayne owns the ’745 patent, which discloses and claims pharmaceutical compositions of azole antifungal drugs that are practically insoluble in aqueous media. The patent explains that insoluble drugs are difficult to formulate into dosage forms because of their low absorption and poor bioavailability. It thus purports to provide a pharmaceutical composition addressing these shortcomings. At issue here are claims 2, 6, and 9–14. Claim 9 is illustrative:

A pharmaceutical composition, consisting essentially of:

about 100 mg of an azole antifungal drug; and

one or more polymer[s] having acidic functional groups; and

optionally one or more additional ingredients selected from the group consisting of a disintegrant, a diluent, a filler, an inert solid carrier, an inert solid matrix, a lubricant, a glidant, a colouring agent, a pigment, a flavour, water, ammonia, an alkaline agent, and methylene chloride

,

wherein in vivo the composition provides a mean C_MAX of at least 100 ng/ml , after administration in the fasted state. ’745 patent col. 11 ll. 15–28 (emphasis added).

Each claim at issue requires a pharmaceutical composition consisting essentially of about 100 mg of an azole antifungal drug and at least one polymer having acidic functional groups, wherein the composition exhibits certain pharmacokinetic properties in vivo. Specifically, claims 2, 9, 10, and 11 require that the in vivo composition provides a mean C_MAX of at least 100 ng/ml, while claims 6, 12, 13, and 14 require a mean AUC of at least 800 ng.h/ml.

Merck Sharp & Dohme Corp. ("MSD") petitioned for inter partes review of claims 1–3, 5–7, and 9–14 of the ’745 patent. The Board instituted review on three grounds,¹ but, because Mayne cancelled claims 1, 3, 5, and 7 during the proceedings, the Board only considered two grounds in its final written decision: anticipation of claims 2, 6, 9, 11, 12, and 14 by Kai² and obviousness of claims 2, 6, and 9–14 over Kai, Sangekar,³ and Babcock.⁴ The Board held each of the challenged claims unpatentable.

On appeal Mayne argues that the Board erred in two respects: (1) by instituting review when the petition should have been found time-barred under 35 U.S.C. § 315(b) and (2) by declining to limit the claims to nontoxic compositions that produce the claimed pharmacokinetic profile in humans.

We begin by reviewing Mayne’s time-bar arguments, which pervade the proceedings below. Mayne first raised its argument at institution, urging the Board to reject the petition because Merck & Co., Inc. ("MCI") should have been identified as a real party in interest. Based on the record at the time, however, the Board was not persuaded that MCI was a real party in interest and denied Mayne’s request. Mayne then requested rehearing of the institution decision, arguing that the Board abused its discretion by failing to find the petition incomplete and time-barred, but the Board again rejected Mayne’s challenge.

Mayne then raised the real-party-in-interest issue during the review proceedings. On a more developed record, the Board determined that "permitting Petitioner to update its mandatory notice to include MSD’s parent company, Merck & Co., Inc., as a real party in interest in this matter—without affecting the Petition’s filing date—[would] promote[ ] the core functions described in the Trial Practice Guide with respect to [real parties in interest], and serve[ ] the interests of justice." Merck Sharp & Dohme Corp. v. Mayne Pharma Int’l Pty Ltd. , No. IPR2016-01186, 2017 WL 6398319, at *2 (P.T.A.B. Dec. 13, 2017). Accordingly, the Board ordered Petitioner to amend its mandatory notice to name MCI. Because the Board ordered MCI’s addition to the petition without altering the filing date, it rejected Mayne’s continued argument concerning the time bar as moot in its final written decision. J.A. 108.

On the merits, Mayne argued to the Board that it should construe the claims as limited to nontoxic compositions that produce the claimed pharmacokinetic profile in humans. It argued for this narrow claim scope based on the terms "azole antifungal drug" and "pharmaceutical composition," and the "wherein" clauses that detail pharmacokinetic parameters for the apparent purpose of excluding the Kai prior art.

The Board disagreed and found that the claims were not limited to therapeutically beneficial nontoxic drugs in construing the claim terms "azole antifungal drug," and "pharmaceutical composition." The Board pointed to the specification, which discusses both itraconazole

and saperconazole as "azole antifungal drugs" suitable for "pharmaceutical composition," without commenting on their adverse effects, potential or otherwise. J.A. 99–100.

As for the "wherein" clauses, the Board found the claims encompassed compositions meeting the claimed parameters in both humans and animals. Each wherein clause recites that the parameters are achieved "in vivo." For the definition of "in vivo," the Board turned to the specification, which states that "[t]he term ‘in vivo’ in general means in the living body of a plant or animal ...." J.A. 92 (quoting ’745 patent col. 3 ll. 37–39). The Board was persuaded that this definition in the specification was "consistent with the plain meaning of the term ‘in vivo’ as it would have been understood one of ordinary skill in the art at the time of the invention ...." Id. Although the specification disclosed results of a specific clinical trial involving administration of a particular azole, itraconazole, to a particular animal, humans, the Board declined to import limitations from the specification into the claim language.

Following these constructions, the Board considered whether Kai anticipated the claims. Kai discloses a solid dispersion technique for improving the bioavailability of a triazole

antifungal agent, MFB-1041.⁵ First, MFB-1041 is dissolved in a mixed solvent of dichloromethane and ethanol. A polymer is then added to the solution at a drug-to-polymer ratio of from 1:1 to 1:5. Several polymers are disclosed, including hydroxypropylmethylcellulose phthalate (HP-55), the preferred polymer of the ’745 patent. The solution is spray-dried, yielding a powder that was administered to beagle dogs under fasted conditions. Table 1, reproduced below, discloses the pharmacokinetic profile of MFB-1041 upon administration:

  Table 1. Pharmacokinetic Parameters of MFB-1041 after Oral Administration
                  to Beagle Dogs
                       Dosage forms                   Cmax     Tmax(h)    AUC
                                                    (µg/ml)             (µg/mlh)
                  Crystal (MC suspension)             __       0.5         1.0
                  Mctolose solid dispersion (1:5)    0.95      4           6.0
                  CMEC solid dispersion (1:5)        1.73      3          11.8
                  HP-55 solid dispersion (1:3)       1.90      2          11.8
                  HP-55 solid dispersion (1:5)       2.59      4          16.9
                

J.A. 2446.

Based on the above data, the Board found that Kai discloses a composition consisting essentially of 100 mg of an azole and a polymer with acidic functional groups, which provides a mean C_MAX of at least 100 ng/ml and a mean AUC of at least 100 ng.h/ml in vivo after administration in the fasted state. Over Mayne’s objection, the Board also found MFB-1041 to be a drug, and a composition containing the MFB-1041 to be a pharmaceutical composition. Accordingly, the Board found that all of the limitations of claims 2, 6, 9, 11, 12, and 14 were met and hence they are anticipated by Kai.

Regarding the second prior art ground, additionally involving claims 10 and 13, in addition to the arguments the Board had already rejected regarding anticipation by Kai, Mayne argued only that the petition did not articulate a motivation to combine Kai, Sangekar, and Babcock. The Board disagreed, finding that a person of skill would have had a reason to place Kai’s solid dispersion powder into a capsule with a reasonable expectation of successfully doing so, because Sangekar teaches that a comparable composition comprising a solid solution of "tetrahydrofuran [sic] azole antifungal" in a polymer matrix can be manufactured in tablet or capsule form. J.A. 104. The Board also considered objective evidence of failure of others, copying, praise, and commercial success, but found that the evidence was not attributable to anything novel in the claims. Accordingly, the Board found that claims 2, 6, and 9–14 would...