Decision: Mayne Pharm. Int’l Pty. Ltd. v. Merck Sharp & Dohme Co., 927 F.3d 1232 (Fed. Cir. 2019)

Holding: In an inter partes review (IPR) Final Written Decision (FWD), the Patent Trial and Appeal Board (PTAB) found all challenged claims of U.S. Patent No. 6,881,745 (the ’745 patent) unpatentable as anticipated or obvious. Merck Sharp & Dohme Corp. v. Mayne Pharm. Int’l Pty Ltd., No. IPR2016-01186, Paper 73 (Dec. 18, 2017).1,2 The Federal Circuit affirmed.

Background:

Mayne owns the ’745 patent; on appeal, claims 2, 6, and 9-14 were at issue. Each of those claims 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 composition provides a mean CMAX of at least 100 ng/ml, while claims 6, 12, 13, and 14 require a mean AUC of at least 800 ng·h/ml. Mayne Pharm. Int’l Pty. Ltd. v. Merck Sharp & Dohme Co., 927 F.3d 1232, 1235 (Fed. Cir. 2019).

Claim 9, reciting a mean CMAX value, is illustrative:

9. 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 CMAX of at least 100 ng/ml, after administration in the fasted state.

The ’745 patent specification explains that water-insoluble drugs, such as azole antifungal drugs, are difficult to formulate into dosage forms because of their low absorption and poor bioavailability. ’745 patent at cols. 1 and 2. The combination of drug and acidic polymer in the ’745 patent seeks to remedy these shortcomings. Id. at col. 2, ll. 33-35.

The ’745 patent issued on April 19, 2005. Over a decade later, on June 11, 2016, Merck petitioned for an inter partes review of claims 1-3, 5-7, and 9-14 of the ’745 patent. Merck Sharp & Dohme Corp. v. Mayne Pharm. Int’l Pty Ltd., IPR2016-01186, Paper 1 (June 11, 2016).

During the IPR proceeding, the PTAB granted Mayne’s unopposed motion to amend, canceling claims 1, 3, 5, and 7. Merck, IPR2016-01186, Paper 61 (P.T.A.B. Aug. 30, 2017). The PTAB held that each of the remaining, challenged claims was unpatentable as anticipated or obvious. Merck, IPR2016-01186, Paper 73 (P.T.A.B. Dec. 18, 2017).

In particular, the PTAB found the ’745 patent anticipated by Kai3, which discloses administering 100 mg of the azole antifungal drug MFB-1041 to dogs, in solid dispersion with hydroxypropyl methylcellulose phthalate (“HP-55”) or carboxymethyl cellulose (“CMEC”). HP-55 and CMEC “are both in the ’745 patent as qualifying polymers.” Merck, IPR2016-01186, Paper 1, at 25 (June 11, 2016). Relying on Kai’s reported pharmacokinetic data in dogs, the PTAB found that MFB-1041 provides a mean CMAX 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. Merck, IPR2016-01186, Paper 10, at 19-20 (P.T.A.B. Dec. 19, 2016). The PTAB ultimately issued a FWD concluding that claims 2, 6, and 9-14 of the ’745 patent were unpatentable. Merck, IPR2016-01186, Paper 73 (P.T.A.B. Dec. 18, 2017).

Mayne then appealed to the Federal Circuit.

On appeal, Mayne argued that the PTAB 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 adopt Mayne’s and the U.S. District Court for the District of Delaware’s4 construction of key claim terms, and instead applying a construction that reads on the prior art. Mayne Pharm., 927 F.3d at 1235. We discuss the second issue in detail. Mayne challenged the PTAB’s “broadest reasonable interpretation” of the ’745 patent claims and argued that its claims are patentable under Mayne’s proffered and narrower constructions. Id. at 1235-36. The Federal Circuit affirmed the PTAB’s claim construction and its decision of unpatentability. Id. at 1242.

Reasoning

1. The term “pharmaceutical compositions” is not limited to nontoxic compositions

Mayne argued against the PTAB’s finding that Kai anticipates or renders obvious the ’745 patent claims, contending that “Kai does not disclose a ‘pharmaceutical composition’ that consists essentially of a drug” because the MFB-1041 agent of Kai undesirably produces clonic convulsions as a result of serious toxicity. Merck, IPR2016-01186, Paper 8, at 27 (Sept. 19, 2016). Mayne argued that “pharmaceutical composition” means “medical drug” and that the term “drug” denotes a compound having beneficial prophylactic and/or therapeutic properties. Id. at 7, 12. Thus, Mayne argued, MFB-1041 is not a pharmaceutical composition because it is toxic and unsuitable for administration to patients. Id. at 27.

The PTAB rejected this argument because the “broadest reasonable interpretation of ‘pharmaceutical compositions’ and ‘drugs’ does not exclude agents with both adverse and beneficial effects.” Merck, IPR2016-01186, Paper 10, at 18-20 (P.T.A.B. Dec. 19, 2016).

Agreeing with the PTAB, the Federal Circuit explained that the terms “pharmaceutical composition” and “drug” were not limited to nontoxic compositions in view of their treatment in the ’745 patent specification. Mayne Pharm., 927 F.3d at 1241. That is, the specification states that “the term ‘drug’ will be widely understood and denotes a compound having beneficial prophylactic and/or therapeutic properties when administered to, for example, humans.” Id. The specification further comments that “the specific benefits of the pharmaceutical composition . . . have been established by the inventors for azole antifungal drugs, such as itraconazole and saperconazole.” Id. (emphasis added). Extrinsic evidence showed that saperconazole is toxic. Id. Thus, the Court concluded, the ’745 patent claims encompass a toxic drug and cannot be narrowly construed as limited to nontoxic compositions.

2. “in vivo” is not limited to “in humans”

The next issue on appeal was the scope of the “wherein” clause. Mayne argued that the PTAB erred in failing to limit the claimed pharmacokinetic parameters to humans. Id. Mayne noted that the Delaware district court construed the ’745 patent claims as directed to humans only and objected to the PTAB’s construction of “in vivo” as including plants and animals. Id. at 1241-42.

The PTAB rejected Mayne’s argument and found that the claims did not expressly recite that the pharmacokinetic parameters are specific to humans. Merck, IPR2016-01186, Paper 10, at 11-12 (P.T.A.B. Dec. 19, 2016). The specification states that “the term ‘in vivo’ in general means in the living body of a plant or animal, and the term ‘drug’ denotes a compound . . . administered to, for example, humans.” Id. (emphasis added).

The Federal Circuit agreed with the PTAB holding that, under the broadest reasonable interpretation, “in vivo” was not limited to humans. Mayne Pharm., 927 F.3d at 1242. First, the Court reasoned that animals were expressly included in the definition of “in vivo” in the specification and thus cannot be excluded by the claims reciting in vivo pharmacokinetic data. Id. Second, while the Court acknowledged that the recited in vivo data stem from a human trial, the Court held that it is improper to import a limitation from an embodiment into the claim. Id. Finally, the Court held that the PTAB did not err by discounting the district court’s construction, because the PTAB is not generally bound by a prior judicial construction of a claim term. Id. (citing Power Integrations, Inc. v. Lee, 797 F.3d 1318, 1326 (Fed. Cir. 2015)).

Takeaway: Broad and narrow claims go hand in hand

Prosecutors often try to get broad claims for their clients. But in doing so, they must not forget to pursue additional claims to narrower, commercially important embodiments.

There are two sides to drafting a broad claim. On the one side, a broad claim can provide more scope of protection to the invention. On the other, a broader claim is more likely to overlap with prior art or lack adequate support or enablement and is therefore a more vulnerable target for patentability and validity attacks under 35 U.S.C. §§ 102, 103, or 112.

A prosecutor should balance the costs and benefits of broad claims, without losing track of claiming narrower embodiments that may be commercially important. Claiming narrowly enough to adequately protect the client’s rights is important, particularly in a regulated industry like pharmaceuticals where narrow claims may be both valid and infringed. In the present case, one or more narrower claims specifying a human recipient of the pharmaceutical composition and a nontoxic drug may have left Mayne with a stronger patent to defend and enforce.

Besides the claims per se, prosecutors should also be careful of the language and examples they use in the specification. For example, a claim requiring a “nontoxic” drug or composition is better served by a specification that defines or describes what nontoxicity means; alternatively, a patent owner might try relying on extrinsic evidence of nontoxicity. Furthermore, although the case law generally holds that courts cannot import a claim limitation directly from the specification, this rule does not always apply. “[C]laims are construed in light of the specification, and are not limited to a designated ‘preferred embodiment’ unless that embodiment is in fact the entire invention presented.” Vulcan Eng’g Co. v. Fata Aluminum, Inc., 278 F.3d 1366, 1376 (Fed. Cir. 2002). And, regardless, the courts often refer to the language of the specification when construing claims. “The specification is always highly relevant to claim construction and is the single best guide to the meaning of a claim term in dispute.” Phillips v. AWH Corp., 415 F.3d 1303, 1315 (Fed. Cir. 2005) (en banc). In the Mayne IPR and appeal, the PTAB and Federal Circuit relied on the definition of “in vivo” and examples of “pharmaceutical compositions” provided in the specification to reject Mayne’s proposed construction of these terms.

Thus, just as prosecutors should pursue narrow, commercially important embodiments in the claims (possibly in addition to broader claims), so too should prosecutors draft specifications that support and enable both the broad and narrow claim scope.

Further Considerations

1. Patentable weight of the “wherein clause”

The PTAB held, and the Federal Circuit agreed, that the “wherein” clauses of the ’745 patent claims were entitled to patentable weight. Merck, IPR2016-01186, Paper 10, at 8-10 (P.T.A.B. Dec. 19, 2016); see also Mayne Pharm., 927 F.3d at 1242.

All of the pharmacokinetic profile “wherein” clauses require that the parameters be met “in vivo.” The patentees specifically define that term in the specification: “The term ‘in vivo’ in general means in the living body of a plant or animal ....” ’745 patent col. 3 ll. 36–37. While it is clear that plants are immaterial to the meaning of the claim because the pharmacokinetic parameters are inapplicable to them, and the term pharmaceutical compositions does not generally mean plant treatments, animals are expressly recited by the definition of in vivo. In light of this statement in the specification, a person of skill would understand the claims to include animals.

Mayne Pharm., 927 F.3d at 1242.

“A ‘wherein’ clause is not given patentable weight if it merely expresses the intended result of a process, or … is the intended result of administration of the claimed pharmaceutical composition.” Merck, IPR2016-01186, Paper 10, at 9 (P.T.A.B. Dec. 19, 2016), citing Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329 (Fed. Cir. 2005). “But, when the clause states a condition that is material to patentability, it cannot be ignored.” Merck, IPR2016-01186, Paper 10, at 9. Because there was evidence of record that not all formulations disclosed in the patent necessarily provide the CMAX or AUC profile recited in the claims, the PTAB concluded that the CMAX and AUC limitations gave “meaning and purpose” to the claims. Id. at 10. Therefore, the “wherein” clauses “meaningfully limit the claims, and are entitled to patentable weight.” Id.

This holding serves as a reminder that prosecutors may be able to increase the likelihood a “wherein” clause will be given patentable weight by showing, perhaps in the specification or prosecution history record, that the “wherein” clause is material to patentability.

2. “consisting essentially of”

The claims issued in the ’745 patent include the transitional phrase “consisting essentially of.” This phrase originated from an Examiner interview, at the Examiner’s request. It is not defined in the specification nor is it further described in the prosecution history resulting in the ’745 patent. In the Mayne IPR, construction of this phrase appeared in the parties’ petition (see Merck, IPR2016-01186, Paper 1, at 14-15) and response (see Merck, IPR2016-01186, Paper 8, at 13-15 (Sept. 19, 2016)), but not in the decisions of the PTAB or the Federal Circuit, because the PTAB found it unnecessary to construe the term.

Nonetheless, comments are appropriate on the transitional phrase “consisting essentially of,” which is not often dealt with in judicial decisions. The meaning of “consisting essentially of” is now well-established and signals that a claim is partially open-ended. See MPEP § 2111.03. But where the specification fails to define the basic and novel characteristics of the invention, “consisting essentially of” may be construed as the open-ended term comprising. See, e.g., Ex parte Miller, 2015 WL 1871396, at *2 (P.T.A.B. Apr. 21, 2015).

Every case depends on its own facts and circumstances. But, it may be good practice for prosecutors to describe the basic and novel characteristics of an invention in the specification or prosecution history in support of a “consisting essentially of” transitional phrase. Such description may particularly be necessary when “consisting essentially of” distinguishes a claim over prior art that would anticipate or have rendered obvious the same claim reciting “comprising” language. Perhaps, in the instant case, prosecutors could have clarified that the basic and novel characteristics of the ’745 patent invention included a nontoxic drug for administration to humans.

Whether it is providing narrow clams with broad claims or having a description to support different types of transitional phrases, these considerations all suggest the need to have a cascading disclosure in the specification. By doing so, it allows one the opportunity to have fall-back positions built into the application, as one cannot predict the type of disclosure that will be cited against the application during prosecution or raised during litigation.

3. Supplement examination

Following the IPR and appeal, claims 1, 3, 5, and 7 were canceled and claims 2, 6, and 9-14 held unpatentable. Mayne Pharm., 927 F.3d at 1234-35. Although claims 4, 15 and 16 of the ’745 patent were untouched by these proceedings, they may still be subject to challenges in the future. Merck contended in its petition that Mayne obtained the ’745 patent claims by rewriting the claims of the rejected parent patent with the same specification. Merck, IPR2016-01186, Paper 1, at 9-10.

To build a stronger case in favor of the validity of the remaining claims, Mayne could consider filing a request for supplement examination, citing an appropriate number of litigation, IPR, and Federal Circuit papers. If the USPTO finds a substantial new question of patentability (SNQ), then reexamination will be ordered. Perhaps, Mayne could avail itself of that reexamination to narrow claims 4, 15, and 16 to limit the claims to human use, as supported in the specification, and also to nontoxic drugs, perhaps using a declaration or other form of extrinsic evidence for support.