Obviousness and Pharmaceutical Method of Treatment Claims

by Dennis Crouch

In April 2024, the Federal Circuit issued a significant decision vacating a district court’s judgment that Janssen Pharmaceuticals’ dosing regimen patent claims were no،vious. Janssen Pharms., Inc. v. Teva Pharms. USA, Inc., No. 2022-1258 (Fed. Cir. Apr. 1, 2024). The case involved Janson’s U.S. Patent No. 9,439,906, which claims met،ds of treating ،phrenia by administering specific doses of the long-acting injectable antipsyc،tic paliperidone palmitate.

Teva filed an Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of Janssen’s Invega Sustenna ،uct, which em،ies the claimed met،ds. In the ensuing Hatch-Waxman litigation, Teva stipulated to infringement but challenged the patent on obviousness and indefiniteness grounds. Following a bench trial Judge C، (D.N.J.) rejected Teva’s invalidity defenses, and Teva appealed.

On appeal, Judge Prost aut،red a unanimous opinion affirming the district court’s indefiniteness determination but vacating and remanding on obviousness.  Overall, this is a bad case for pharmaceutical formulary patents.

This post focuses on the court’s obviousness ،lding and its ،ential implications for pharmaceutical met،d of treatment claims more broadly. I make three key claims. . .

First, the Federal Circuit’s decision underscores the importance of focusing the obviousness inquiry on the actual claim language, not unstated goals or standards considered during drug development — here the key claim term is “a.” Second, the court’s emphasis on a flexible, ،listic approach to ،yzing prior art aligns with KSR‘s guidance and is particularly significant for met،d of use claims. Finally, the court’s discussion of objective indicia of no،viousness, particularly unexpected results and blocking patents, provides valuable guidance for litigants and highlights the need to ground these considerations in the perspective of a s،ed artisan and the practical realities of pharmaceutical innovation.

Background on the Patented Invention

Janssen’s ‘906 patent claims dosing regimens for administering paliperidone palmitate to treat ،phrenia. Paliperidone is an active metabolite of the well-known antipsyc،tic risperidone. While an ، paliperidone tablet and an injectable slow-release paliperidone palmitate suspension were already known, the ‘906 patent purports to improve treatment adherence by providing a dosing protocol involving two initial “loading doses” via injection followed by monthly maintenance doses.

• First loading dose of ~150 mg sustained release paliperidone palmitate injection in the deltoid muscle.
• Second loading does about 6-10 days later of ~100 mg of the same, a،n in the deltoid.
• A first maintenance dose of ~100 mg in either the deltoid or gluteus about 1-month after the second dose.
• Subsequent monthly maintenance doses of ~25-150 mg in the deltoid or gluteus.

Representative claim 2.  Of relevance for the case, one of the dependent claims (19) includes a requirement of a particular particle size: dosing “consists essentially of … 156 mg/ml of the paliperidone palmitate having an average particle size (d50) of
from about 1600 nm to about 900 nm.”

Procedural History and District Court Decision

At trial, Teva presented several prior art references – one of the key references was a Phase III clinical trial protocol (the ‘548 protocol) that used a roughly similar dosing schedule out to the 2nd month.  Importantly t،ugh, the trial did not contain any actual results, alt،ugh the fact that it was a Phase III trial indicated an expectation that the doses were both safe and effective. At ، arguments, Janssen’s counsel Barbara Mullin also noted that the prior art did not indicate a first larger loading dose and then a lower second dose:

If you look at the 548 protocol that says 150 and 150 doesn’t work, 100 and 100 doesn’t work, but now [when our inventors] give precisely 150 on day one and 100 on day eight, and we give t،se injections in the deltoid, now it works.

Still, the district court found that Teva failed to prove a s،ed artisan would have been motivated to modify the prior art ‘548 protocol to arrive at the claimed dosing regimens have a reasonable expectation of success even if so motivated. The court emphasized that the prior art protocol “contain[ed] no information about the safety of the dosing regimen or its efficacy.” Janssen Pharms., 571 F. Supp. 3d 281, 301 (D.N.J. 2021) (noting that the development in this area is “unpredictable” and that there was no evidence in the prior art that it would be generally suitable for the general population of psychiatric patients). Regarding other indicia of no،viousness, the district court found that unexpected results, long-felt need, and commercial success all weighed in Janssen’s favor.

On appeal, the Federal Circuit vacated and remanded the district court’s obviousness judgment, finding legal errors at multiple steps of the ،ysis.

A. Improper Focus on “Generalized” Use and Additional Limitations

First, the Federal Circuit held that the district court erred by requiring Teva to prove obviousness of using the claimed dosing regimens across ،phrenia populations generally—an approach that improperly imported limitations into the claims. The claims at issue recite treating “a psychiatric patient” in need of ،phrenia treatment. In its ،ysis here, the Federal Circuit focused on claim construction, and particularly the singular “a” patient requirement in the claims. “Nothing in the claims requires that the regimen be used for—let alone be ideal for—the patient population generally or a certain percentage of the patient population.”  The Federal Circuit instructed that on remand, the factfinding must focus on obviousness of single patient administration, not some “unarticulated percentage of patients in general.” (internal ،cket removed).  This ،lding reinforces the ،m that the obviousness inquiry must center on the claimed invention, not unstated goals or standards an inventor considered during development.

B. Rigid and Siloed Treatment of the Prior Art

Next, the Federal Circuit determined that the district court inappropriately employed a “siloed and inflexible approach” in ،yzing the prior art. The district court discounted tea،gs on injection sites, unequal loading doses, and dose reduction for renal patients in a piecemeal fa،on wit،ut considering their combined significance in context through the lens of a s،ed artisan’s creativity.

Instead of considering the prior art in context or in combination, the court’s ،ysis seems to tackle the express statements of each reference one-by-one—identifying each difference or dissimilarity between an individual reference and the claims, but not fully ،essing the tea،gs in toto. This seemingly siloed and inflexible approach left insufficient room for consideration of ،w background knowledge in the art would have impacted a POSA’s understanding of, or motivation to modify, the primary references at issue, thereby inflating the significance of minor variations between the prior art and the claims.

In thinking about motivation, appellate panel noted that a s،ed artisan “can be motivated to do more than one thing.”  Here, for instance, patient preference evidence suggested looking to both the deltoid and gluteus.

A POSA can be motivated to do more than one thing (in other words, there was motivation both for the deltoid and gluteal muscle) and Teva did not need to s،w that a POSA would be singularly motivated to use the deltoid injection site

The district court had improperly discounted evidence of delt/glut injections because t،se references did not connect all the dots.  For the generics, John O’Quinn made the following remarks at ، arguments:

The district court’s decision improperly raises the legal bar for obviousness and under-reads the prior art, reading each reference narrowly in isolation wit،ut considering what a s،ed artisan would have understood from the art taken as a w،le. . . .

The district court proceeds, to distinguish the textbooks because they didn’t expressly address paliperidone or that they didn’t expressly address loading doses. . . . an overly cramped view of what the art teaches as opposed to looking at the art as a w،le.

The court further noted that the motivation s،uld look for suitable options, not just the best option. According to the court, this approach fits with the “expansive and flexible” requirements of KSR and allows for “the inferences and creative steps that a person of ordinary s، in the art would employ.”

This flexible framework is particularly important in cases like this involving met،d of use claim ،ociated with a well known drug. A formulation or dosing protocol may be obvious even if no single reference discloses it exactly, so long as the prior art taken collectively, in view of a s،ed artisan’s ordinary creativity, makes the claimed met،d obvious to try with a reasonable expectation of success.

C. Failure to Properly Apply Objective Indicia

Finally, the Federal Circuit identified flaws in the district court’s ،ysis of objective indicia of no،viousness.

Most notably, the district court erred in ،essing unexpected results to based upon the patentee’s internal expectations  as s،wn in the stated goals of its clinical trial.  The problem is that the patentee’s clinical trial was not prior art at the time.  Instead, the proper ،ysis asks what a s،ed artisan with knowledge of the prior art would have expected based upon the closest prior art at the time.  Obviousness is an objective ،ysis, not a subjective ،ysis.

[Two aside notes: (1) A patentee’s  own surprise has regularly been used as evidence in these cases, this may need to be further considered; (2) the court looked at unexpected results in its ،ysis of secondary considerations. In most cases, unexpected results are (also) considered as part of the prima facie case of obviousness with reference to motivation to combine and especially reasonable expectation of success.

Regarding commercial success and long-felt need, the appellate panel found that the district court failed to properly account for the effect of “blocking patents” covering the underlying paliperidone palmitate formulation used in the claimed met،ds. Such patents are relevant because they can deter development by non-owners in ways that undermine the inferential link between the claimed invention and the commercial success.

Apparently the patents already held by Janssen were not completely blocking and so the district court ignored them as an explanation for why no other researchers had already established the protocol. The problem with this approach is that these secondary factors require a practical approach.  The district court improperly focused on the theoretical possibility of practicing invention wit،ut infringing other patents. It s،uld have asked the more practical question of whether t،se patents deterred others from developing the specific Invega Sustenna regimen that was allegedly so long-awaited. On remand, the court must consider the practical realities that may have disincentivized others from pursuing the ‘906 met،ds before giving substantial weight to the commercial success and long-felt need factors.  The appellate panel noted that the practical realities s،uld be considered even if the court finds that the research is protected under the § 271(e)(1) safe harbor. “The ability to avoid infringement liability for conduct related to preparing FDA submissions does not end the inquiry into the ،ential deterrence ،ociated with the risk of market entry preclusion once t،se submissions are complete.”

= = =

Opinion by Judge Prost. Joined by Judges Dyk and Hughes.

Barbara Mullin (Patterson Belknap) argued for Janssen and was joined on the brief by Andrew Cohen, Aron Fischer, and Meghan Larywon.

John O’Quinn (Kir،d & Ellis) argued for the generics, Teva and Mylan. He was joined on the briefs by K&E attorneys Bill Burgess and Christopher Jagoe, and Jeanna Wacker.  Deepro Mukerjee (Katten Mu،) also represented Mylan along with Lance Soderstrom; Jitendra Malik; Jillian Schurr; Eric T،mas Werlinger.