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 nonobvious. 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 methods of treating schizophrenia by administering specific doses of the long-acting injectable antipsychotic paliperidone palmitate.
Teva filed an Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of Janssen’s Invega Sustenna product, which embodies the claimed methods. In the ensuing Hatch-Waxman litigation, Teva stipulated to infringement but challenged the patent on obviousness and indefiniteness grounds. Following a bench trial Judge Cecchi (D.N.J.) rejected Teva’s invalidity defenses, and Teva appealed.
On appeal, Judge Prost authored 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 holding and its potential implications for pharmaceutical method 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, holistic approach to analyzing prior art aligns with KSR‘s guidance and is particularly significant for method of use claims. Finally, the court’s discussion of objective indicia of nonobviousness, particularly unexpected results and blocking patents, provides valuable guidance for litigants and highlights the need to ground these considerations in the perspective of a skilled 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 schizophrenia. Paliperidone is an active metabolite of the well-known antipsychotic risperidone. While an oral 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, again 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 though, the trial did not contain any actual results, although the fact that it was a Phase III trial indicated an expectation that the doses were both safe and effective. At oral 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 those injections in the deltoid, now it works.
Still, the district court found that Teva failed to prove a skilled 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 nonobviousness, 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 analysis.
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 schizophrenia populations generally—an approach that improperly imported limitations into the claims. The claims at issue recite treating “a psychiatric patient” in need of schizophrenia treatment. In its analysis 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 bracket removed). This holding reinforces the maxim 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 analyzing the prior art. The district court discounted teachings on injection sites, unequal loading doses, and dose reduction for renal patients in a piecemeal fashion without considering their combined significance in context through the lens of a skilled artisan’s creativity.
Instead of considering the prior art in context or in combination, the court’s analysis 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 assessing the teachings in toto. This seemingly siloed and inflexible approach left insufficient room for consideration of how 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 skilled 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 show 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 those references did not connect all the dots. For the generics, John O’Quinn made the following remarks at oral 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 without considering what a skilled artisan would have understood from the art taken as a whole. . . .
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 whole.
The court further noted that the motivation should 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 skill in the art would employ.”
This flexible framework is particularly important in cases like this involving method of use claim associated 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 skilled artisan’s ordinary creativity, makes the claimed method 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 analysis of objective indicia of nonobviousness.
Most notably, the district court erred in assessing unexpected results to based upon the patentee’s internal expectations as shown 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 analysis asks what a skilled artisan with knowledge of the prior art would have expected based upon the closest prior art at the time. Obviousness is an objective analysis, not a subjective analysis.
[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 analysis 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 methods. 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 without infringing other patents. It should have asked the more practical question of whether those 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 methods before giving substantial weight to the commercial success and long-felt need factors. The appellate panel noted that the practical realities should 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 potential deterrence associated with the risk of market entry preclusion once those 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 (Kirkland & 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 Muchin) also represented Mylan along with Lance Soderstrom; Jitendra Malik; Jillian Schurr; Eric Thomas Werlinger.
Surgical method patents are not enforceable against infringers, and surgery is a treatment. Someday, these petty diffrences in the amount of injeciton of a drug and timing regimens will be seen as what they are… akin to a surgery , the nexus being the treatment of the body, generally, and, these squabblings over obviousness will be irrelevant as all the time anon ppl spend dribbling on such nonsense. 🙂
There is one question with regard to the reasonable expectation of success that I have never seen addressed in the context of pharmaceutical patents – would a company initiate a Phase II or Phase III clinical trial using a dosing regimen if they did not have a reasonable expectation of success? The simple fact that the company is willing to spend the money on the trials suggests they have an expectation of success. Would they spend the money for the trials if they did not expect them to succeed?
The patentee’s own “reasonable expectations” are not at issue.
Wouldn’t this mean that there’s a reasonable expectation of success for any invention? After all, the patentee must have a seen a reasonable chance of succeeding, or else why do it? I don’t think that can be right. It swallows the obviousness inquiry.
+1
DVan’s proposed approach looks like a reformulation of the old Cuno Engineering “flash of genius” test.
Putting aside the Sprint Left claptrap, and on the actual topic, Greg appears to be correct in the view that this appears to be a revival of the Flash of Genius standard (something Congress explicitly rejected).
I would be amiss to not draw the parallel to Random Examiner’s mantra that also sound in the same canard (his tendency of “predictable arts” dismissal, as well as his tendency to view 103 art as nothing more than piecemeal 102 art).
This is more of the same from former Chief Judge Prost, the author of the opinion. Eleven years ago in Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731 (Fed. Cir. 2013), Prost authored a strikingly similar decision (with Judge Newman dissenting) that also reversed a nonobviousness judgment in a drug patent case and also complained that the district court too readily accepted objective indicia of unexpected results and commercial success — and her complaint about the commercial success was more or less exactly the same as here, namely, that “[w]here market entry by others was precluded due to blocking patents, the inference of non-obviousness of the asserted claims, from evidence of commercial success, is weak” (Galderma). The parties’ counsel knew (or, at least, should’ve) how this decision was going to come out as soon as they saw the presiding judge at oral argument.
It’s so funny, and so typical on the Federal Circuit, that although the opinion cites Galderma it never cites it for the secondary considerations issues, the issues for which it is actually the most (or almost the most) on-point case, but only cites the case for side notes on other points. Because we don’t want to make this that obvious, do we?
“Likewise, while assessing whether a POSA would be motivated to use unequal loading doses (even where the loading dosage amounts were undisputedly disclosed in the prior art, both as a particular dose and as a point within a
disclosed range), the district court dismissed Teva’s reliance on references related to administering unequal loading doses because they “t[aught] individualized, rather than generalized, dosing.” Id. at 306.
Additionally, although the court’s analysis of reasonable expectation of success has minimal explanation, there too it seemed to require an expectation of success not for administering paliperidone palmitate to a patient according to the dosing regimen claimed, but rather success in achieving the goals a POSA would have across an (undefined) average population of patients, such that a POSA
would expect to use the regimen as a “generalized multidose regimen.” Id. at 310. The court also appeared to conflate the invention or the claims with Janssen’s approval process when it referred to the difficulties encountered with the PSY-3003 clinical trial as an indication of unpredictability in the “invention process.” Id. at 311. ”
Here is the claim language in question:
“A dosing regimen for administering paliperidone palmitate to a psychiatric patient in need of treatment for schizophrenia, schizoaffective disorder, or schizophreniform disorder comprising…”
I think the court is unnecessarily narrowing the claim to the extreme. One only doses one patient at a time. One does not dose multiple patients.
If the claim recited “patients” instead of “a patient,” the argument could then be that more than one patient has to be dosed.
Nor should one have to recite that the treatment is meant for patients in general. The Federal Circuit latched onto that argument because the references that disclose unequal load dosing as claimed taught individualized dosing, not general. The claim does not recite tailoring the doses to the individuals.
+1
The sustained indefiniteness decision did not apply to all of the claims, hence this remand to re-decide validity on other claims with different standards.
As to “a” versus a larger context, I am reminded of the curing of rubber items.
To note: in the prior art, a singular ‘perfect cure’ was NOT novel.