Senju Pharmaceutical Co Ltd v. Amneal Pharma LLC

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Senju Pharmaceutical Co., Ltd. (Japan); Bausch & Lomb Incorporated (New York); Bausch & Lomb Pharma Holdings Corp. (Delaware)
  • Defendant: Amneal Pharmaceuticals LLC (Delaware); Amneal Pharmaceuticals India Pvt. Ltd. (India)
  • Plaintiff’s Counsel: GIBBONS P.C.
• Case Identification: 3:18-cv-16991, D.N.J., 12/07/2018
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey as Defendant Amneal LLC has its principal place of business in the district, maintains a research and development facility there, and has previously consented to or not contested jurisdiction in prior actions in the district.
• Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiffs' Prolensa® ophthalmic solution constitutes an act of infringement of a patent covering specific formulations of the drug bromfenac.
• Technical Context: The technology concerns aqueous ophthalmic solutions of bromfenac, a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation following ocular surgery.
• Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' filing of ANDA No. 210962 seeking FDA approval to market a generic drug. The '958 patent is listed in the FDA's "Orange Book" as covering Plaintiffs' Prolensa® product. Plaintiffs allege they received a Paragraph IV notice letter from Amneal on October 26, 2018, asserting non-infringement, which Plaintiffs contend lacks merit.

Case Timeline

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,085,958 - “Bromfenac Bioavailability,” issued October 2, 2018

The Invention Explained

• Problem Addressed: The patent addresses the challenge of delivering the NSAID bromfenac into ocular tissues effectively for treating post-surgical pain and inflammation. Prior art formulations, such as the commercially available BROMDAY™ product, required a specific concentration (0.09%) and a relatively high pH of 8.3 ('958 Patent, col. 1:11-12, 30-33). The patent notes that reducing the drug concentration was considered "unlikely to result in a sufficient reduction in pain and inflammation" using existing approaches ('958 Patent, col. 13:62-65).
• The Patented Solution: The invention is an aqueous ophthalmic formulation that uses a lower pH (between ≥6.0 and <8.3) than the prior art. The specification explains that reducing the pH increases the drug's hydrophobicity, which in turn enhances its penetration into key ocular tissues like the iris and ciliary body ('958 Patent, col. 14:10-21). This enhanced bioavailability allegedly allows for a formulation with a lower concentration of bromfenac to achieve a comparable or better therapeutic effect, thereby improving the drug's safety profile while retaining the convenience of once-daily dosing ('958 Patent, Abstract; col. 2:37-42).
• Technical Importance: The claimed solution provides a means to formulate a lower-concentration, once-daily ophthalmic NSAID that maintains clinical efficacy, potentially offering an improved benefit-to-safety ratio for patients. ('958 Patent, col. 13:57-61).

Key Claims at a Glance

• The complaint alleges infringement of "at least one claim" of the '958 patent (Compl. ¶28). The broadest independent claim is Claim 1.
• Independent Claim 1 requires:
  • An aqueous composition formulated for topical ocular administration,
  • the composition comprising bromfenac as the only active at 0.07% w/v,
  • and 1.0% w/v povidone,
  • in a formulation buffered at a pH between pH≥6.0 and pH<8.0.
    (’958 Patent, col. 26:47-50).
• The complaint’s broad allegation of infringing "at least one claim" may encompass dependent claims, which add further limitations such as specific pH values or the inclusion of other excipients.

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is "Amneal's generic bromfenac ophthalmic solution 0.07%," for which Amneal has filed Abbreviated New Drug Application (ANDA) No. 210962 with the FDA (Compl. ¶6, ¶22).

Functionality and Market Context

• The product is intended to be a generic version of Plaintiffs' commercial product, Prolensa®, which is a 0.07% bromfenac ophthalmic solution used for treating postoperative inflammation in patients who have undergone cataract surgery (Compl. ¶20, ¶22). The complaint alleges that the accused generic product "is the same, or substantially the same, as Prolensa®" (Compl. ¶26). As an ANDA product, it must be bioequivalent to the reference listed drug, Prolensa®, which Plaintiffs have listed in the FDA's Orange Book in connection with the '958 patent (Compl. ¶19).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or a detailed, element-by-element infringement analysis. The infringement theory is statutory, arising under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking approval to market a generic drug before patent expiration as an act of infringement (Compl. ¶28). The core of the allegation is that the product described in Amneal's ANDA, if approved and marketed, would meet all the limitations of at least one claim of the '958 patent (Compl. ¶29). This is predicated on the allegation that the generic product is "the same, or substantially the same" as Plaintiffs' Prolensa® product, which is the commercial embodiment of the patented invention (Compl. ¶19, ¶26).

No probative visual evidence provided in complaint.

Identified Points of Contention

• Scope Questions: A central question will be whether the specific formulation detailed in Amneal's confidential ANDA falls within the scope of the asserted claims. For Claim 1, this includes the precise pH of the accused formulation and whether it is "between pH≥6.0 and pH<8.0" as required.
• Technical Questions: The primary technical question for the court will be one of compositional identity: Does Amneal's proposed 0.07% bromfenac solution contain every recited element of an asserted claim? For Claim 1, discovery will be needed to determine if the generic product contains "1.0% w/v povidone" and if bromfenac is "the only active" ingredient, as those details are not provided in the complaint.

V. Key Claim Terms for Construction

• The Term: "a pH between pH≥6.0 and pH<8.0"

  • Context and Importance: This pH range is a critical limitation that distinguishes the claimed invention from the higher-pH (8.3) prior art. Infringement will hinge on whether the accused product's pH, as specified in its ANDA, falls within these numerical bounds. Practitioners may focus on this term because it is a dispositive, quantifiable limitation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification explicitly recites a wide range of pH values within these bounds, stating the pH may be "pH 6.0, pH 6.1...pH 8.2, and pH>8.2 up to but excluding pH 8.3," suggesting the full range is contemplated ('958 Patent, col. 3:21-25).
    • Evidence for a Narrower Interpretation: A party could argue that the patent's disclosure of enhanced bioavailability is tied to specific examples. The patent provides comparative data tables showing improved results at pH 7.0 and 7.8 versus the prior art pH of 8.3 ('958 Patent, col. 14:38-58). This could be used to argue that the claim scope should be interpreted in light of the examples that demonstrate the inventive concept.

• The Term: "bromfenac as the only active"

  • Context and Importance: This term limits the composition to a monotherapy. Its construction is important because the presence of any other substance deemed "active" would place a formulation outside the claim's scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent lists numerous excipients, including povidone, tyloxapol, and boric acid, which are presented as inactive components of the formulation, distinguishing them from the "active" bromfenac ('958 Patent, Examples 1-10, col. 15:51-16:47). This supports an interpretation where "active" refers to the primary therapeutic agent for treating ocular inflammation.
    • Evidence for a Narrower Interpretation: The specification does not provide an explicit definition of "active." A party could argue that an excipient present in a certain concentration could provide a secondary therapeutic benefit (e.g., as a demulcent), thereby making it a second "active" ingredient and avoiding infringement. The resolution of this term may depend on extrinsic evidence regarding the function of the other ingredients in the formulation.

VI. Other Allegations

• Indirect Infringement: The complaint includes conclusory allegations of induced and contributory infringement (Compl. ¶30, ¶35). The factual basis for inducement would likely be the proposed product labeling submitted with the ANDA, which would instruct physicians and patients to administer the drug in a manner that infringes the asserted claims.
• Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it requests that the court declare the case "exceptional" under 35 U.S.C. § 285 and award attorney's fees (Compl., Prayer for Relief ¶5). The basis for this request may stem from the allegation that Amneal's Paragraph IV notice letter "does not allege meritorious non-infringement defenses" (Compl. ¶25).

VII. Analyst’s Conclusion: Key Questions for the Case

• A central factual question will be one of compositional identity: Does the confidential formulation described in Amneal's ANDA No. 210962 contain every element of an asserted claim of the '958 patent, particularly the 0.07% w/v bromfenac concentration, the 1.0% w/v povidone, and a pH within the claimed range of ≥6.0 to <8.0?
• While not yet raised by the defense, a critical validity question will likely be obviousness: Was it obvious to a person of ordinary skill in pharmaceutical formulation to lower the pH of a known bromfenac ophthalmic solution into the claimed range with a reasonable expectation of achieving the enhanced tissue penetration and therapeutic efficacy described in the patent?
• A key procedural issue will be one of litigation conduct: Does the basis for Amneal’s Paragraph IV certification, as explained in its notice letter, lack a meritorious foundation, potentially rendering this an "exceptional case" that would justify an award of attorney’s fees to the Plaintiffs?