Janssen Pharmaceuticals, Inc. v. Teva Pharmaceuticals USA, Inc., decided July 8, 2025

Case Name: Janssen Pharmaceuticals, Inc. et al. v. Teva Pharmaceuticals USA, Inc. and Mylan Laboratories Ltd. Court: United States Court of Appeals for the Federal Circuit Case Numbers: 2025-1228, 2025-1252 Decided: July 8, 2025 Judges: PROST, REYNA, and TARANTO, Circuit Judges (Opinion by TARANTO, Circuit Judge)

I. Executive Summary

This document summarizes the Federal Circuit's decision affirming the District Court's finding that Teva Pharmaceuticals USA, Inc. (and Mylan Laboratories Ltd., who stipulated to be bound by the Teva judgment) failed to prove the invalidity of Janssen Pharmaceuticals, Inc.'s U.S. Patent No. 9,439,906 (the '906 patent) for obviousness. The '906 patent describes and claims dosing regimens for long-acting injectable antipsychotic medications, specifically paliperidone palmitate (Janssen's "Invega Sustenna-brand" product), used to treat schizophrenia and related disorders.

Teva stipulated to infringement but challenged the patent's validity on several grounds, primarily obviousness. After a bench trial and subsequent remand from the Federal Circuit for reconsideration of obviousness, the District Court again found the challenged claims not invalid. This appeal by Teva challenged that remand decision. The Federal Circuit affirmed the District Court's determination, specifically upholding its findings that Teva did not meet its burden of proving obviousness by clear and convincing evidence, particularly regarding motivation to combine/modify prior art and a reasonable expectation of success.

II. Background of the Dispute

• The '906 Patent: The core of the dispute revolves around Janssen's U.S. Patent No. 9,439,906. This patent claims "dosing regimen[s] for administering paliperidone esters to a psychiatric patient in need of treatment." (col. 2, line 11, through col. 4, line 42). Paliperidone palmitate is a long-acting injectable form of paliperidone, an antipsychotic. The patent addresses the problem of patient noncompliance with daily oral medication by providing a less frequent, sustained-release injectable option, "once monthly, which may greatly enhance compliance with dosing." (col. 1, lines 58-61).

• Key Claims: Representative claims discussed include:

• Claim 2: Describes a loading dose regimen of about 150 mg-eq. (milligram-equivalents) on day 1, followed by about 100 mg-eq. on day 6-10, both injected into the deltoid muscle. This is followed by monthly maintenance doses of 25-150 mg-eq. in the deltoid or gluteal muscle.

• Claims 10 and 13: Recite regimens with reduced dosages for patients with renal impairment.

• Claims 20 and 21: Recite regimens where the injectable formulation's median particle size is within a certain range.

• Teva's Challenge: In 2017, Teva filed an Abbreviated New Drug Application (ANDA) for a generic version of Invega Sustenna. Janssen sued Teva for infringement under the Hatch-Waxman Act. Teva stipulated to infringement but argued the '906 patent was invalid, primarily due to obviousness.

• Prior Art Relied Upon by Teva:NCT00210548 ('548 protocol): A Janssen Phase III clinical trial protocol for testing three equal-amount doses (50, 100, or 150 mg-eq.) of paliperidone palmitate. This document "does not contain clinical results or safety data."

• U.S. Patent No. 6,555,544 ('544 patent): A Janssen-owned patent disclosing a "pharmaceutical composition suitable as a depot formulation for administration by intramuscular or subcutaneous injection, comprising" paliperidone palmitate.

• International Publication No. WO 2006/114384 (WO '384): A Janssen-owned publication describing a "process for preparing aseptic crystalline" paliperidone palmitate, with dose volumes corresponding to 25 to 150 mg-eq.

• Ereshefsky 1990 & 1993: References concerning haloperidol decanoate (another antipsychotic), suggesting larger initial doses for rapid therapeutic effects and reduced subsequent doses to avoid accumulation.

• Karagianis 2001: Reference on rapid tranquilization with olanzapine (another antipsychotic).

• HALDOL® Decanoate Label: Provides guidance on injectable haloperidol decanoate, including dosing adjustments.

• INVEGA™ Extended-Release Tablets Label (Invega ER label): Teaches dose reduction for renally impaired patients.

• Cleton 2007: Teaches administering lower doses of paliperidone extended-release tablets to patients with moderate-to-severe renal impairment.

• Procedural History: The District Court initially held the claims not invalid. On appeal in 2024, the Federal Circuit affirmed the indefiniteness ruling but vacated and remanded the obviousness ruling due to "analytical flaws" in the District Court's initial analysis. On remand, the District Court, based on the existing record and new submissions, again found the '906 patent claims not invalid for obviousness. Teva then appealed this remand decision.
  

III. Key Legal and Factual Issues on Appeal

The Federal Circuit reviewed the overall determination of obviousness de novo, and the District Court's underlying factual findings for clear error. Teva, as the challenger, bore the burden of proving obviousness by clear and convincing evidence. This required showing:

1. Motivation to Combine/Modify: That a skilled artisan would have been motivated to combine or modify the prior art references to achieve the claimed invention.

2. Reasonable Expectation of Success: That the skilled artisan would have had a reasonable expectation of success in doing so.
   

A. Challenge to Claim 2 (Standard Dosing Regimen)

Teva raised two main arguments regarding Claim 2:

1. Application of Obviousness Presumption (Overlapping-Range Cases): Teva argued the District Court erred by not applying a presumption of obviousness, which typically applies when claimed numerical ranges overlap with prior art ranges.

2. Court's Ruling: The Federal Circuit disagreed, affirming the District Court's decision not to apply the presumption.

3. Reasoning:While acknowledging that the presumption can apply even with multiple differences or structural similarities, the Court stated that its application "is not independent of different inventive contexts."

4. The '906 patent's Claim 2 involves a "combination of dosages and times of injection—with decreasing loading doses—where the evidence reasonably characterizes the combination as an integrated unit of steps taken over time for achieving desired medicinal effects." (p. 19).

5. This specific "choice to start with a particular high first loading dose and then follow it with a second, lower loading dose" for a complex treatment regimen "does not clearly fit within the presumption’s focus on simply selecting a number or range overlapping a prior-art range of a variable or, even, a plurality of variables that overlap with prior-art ranges where the variables are properly considered separately from each other." (p. 19).

6. The Court noted that the "presumption is justified by interrelated premises" (e.g., routine experimentation to discover optimum ranges) which are "factual ones about relevant artisans’ motivations to optimize and expectations from routine experimentation." (p. 16). The District Court made "detailed findings that are counter to finding the premises of the presumption to be present for the treatment regimen of claim 2." (p. 18).

7. Previous cases applying the presumption "are overwhelmingly about the makeup of, and/or processes of making, alloys or other compositions," not complex treatment regimens like the one claimed. (p. 20).

8. Therefore, the Court concluded that the "proper course at present is to apply the normal full obviousness analysis, rather than a truncated version based on the invoked presumption." (p. 21).

9. No Obviousness Under Full Analysis: Teva argued that even without the presumption, the District Court erred in finding Claim 2 not obvious. Teva focused on the "unequal, decreasing loading doses" as the "only patentable difference."

10. Court's Ruling: The Federal Circuit affirmed the District Court's finding that Teva did not prove obviousness by clear and convincing evidence.

11. Reasoning:Motivation to Modify '548 Protocol: The District Court correctly found "neither reference [WO '384 nor '544 patent] discloses a loading dose regimen." (p. 23). Teva's calibration theory lacked "sufficient support in the record." (p. 23).

12. Motivation for Unequal, Decreasing Doses (Ereshefsky, Karagianis): The District Court's findings were not clearly erroneous.

13. Ereshefsky references: "addressed studies of patients who were already stabilized on oral haloperidol... so those references would not have taught a relevant artisan to use long-acting injectables to 'load' patients." (pp. 24-25).

14. Karagianis: Teva's own expert testimony conflicted, with one expert stating a relevant artisan would not use long-acting injectables for acutely agitated patients, undermining the motivation for high first loading doses in such patients. (p. 25).

15. Particle Size vs. Dose Amount: The court found motivation to modify particle size for faster effects, not dose amount. "administering a larger dose would not help a patient reach the therapeutic threshold more quickly." (p. 25).

16. Loading vs. Maintenance Doses: Teva's expert acknowledged that "loading doses and maintenance doses are distinct concepts," supporting the court's finding that Ereshefsky's teachings on maintenance doses would not "apply equally to loading doses." (p. 26).

17. Motivation from Haldol Label: The District Court's determination was not clearly erroneous.

18. The Haldol label actually taught "increasing rather than a decreasing dosing regimen." (p. 27).

19. Crucially, haloperidol decanoate and paliperidone palmitate "behave differently in the human body," and Teva "d[id] not provide sufficient evidence as to why" a relevant artisan would apply quantitative amounts from one to the other. (p. 27).

20. Reasonable Expectation of Success: The District Court did not err in finding no reasonable expectation of success.

21. Consideration of "safety, efficacy, or regulatory approval" was proper because "a skilled artisan would reasonably consider" these factors when "creating a useful claimed invention." (p. 28).

22. Multi-dose regimens introduce "additional complexities (e.g., excess accumulation of the drug in a patient’s body and fluctuation of drug levels between administrations) beyond those of single-dose regimens and may lead to adverse effects." (p. 29). The '548 protocol lacked safety/efficacy data, making multi-dose regimens more unpredictable. (p. 29).
    

B. Challenges to Claims 10 and 13 (Renal Impairment Regimens)

• Teva's Argument: Prior art (Invega ER label, Cleton 2007) taught calibrating paliperidone palmitate doses for renally impaired patients by administering lower doses.

• Court's Ruling: The Federal Circuit affirmed the District Court's finding that Teva failed to prove a motivation to reduce prior art dosing regimens to arrive at the regimens of Claims 10 or 13.

• Reasoning:Focus on Mild Renal Impairment: The District Court's focus on mild renal impairment was appropriate given Teva's expert testimony that "Patients with moderate to severe renal impairment are not to receive [Invega Sustenna] at all." (p. 30).

• Cleton 2007: While Cleton 2007 recommended lower doses for moderate-to-severe renal impairment, it was "silent on what to do for patients with mild renal impairment." (p. 31). The District Court's interpretation was based on resolving an expert dispute, not an erroneous "teaching away" interpretation. (p. 31).
  

C. Challenges to Claims 20 and 21 (Particle Size)

• Court's Ruling: The Federal Circuit affirmed the District Court's decision.

• Reasoning: Claims 20 and 21 are dependent claims. "Because we affirm the district court’s determinations that claims 2 (representative of claims 1 and 4), 10 (representative of claim 8), and 13 (representative of claim 11) have not been proved invalid for obviousness, . . . we hold that claims 20 and 21 have likewise not been proven invalid for obviousness." (p. 31, citing In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992)).
  

IV. Conclusion

The Federal Circuit affirmed the District Court's judgment, concluding that Teva failed to meet its burden of proving the asserted claims of the '906 patent invalid for obviousness by clear and convincing evidence. The Court specifically rejected Teva's arguments for applying a presumption of obviousness for the dosing regimen, and found no clear error in the District Court's detailed factual findings regarding motivation to combine/modify prior art or reasonable expectation of success for the various claims.