DCT
1:22-cv-01422
Alcon Inc v. Padagis Israel Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Alcon Inc., Alcon Vision, LLC, and Alcon Laboratories Inc (Switzerland/Delaware/Texas)
- Defendant: Padagis Israel Pharmaceuticals Ltd., Padagis US LLC, and Padagis LLC (Israel/Delaware)
- Plaintiff’s Counsel: Shaw Keller LLP; Allen Overy LLP
- Case Identification: 1:22-cv-01422, D. Del., 10/27/2022
- Venue Allegations: Venue is asserted in the District of Delaware based on Defendant entities Padagis US LLC and Padagis LLC being incorporated in Delaware. Venue over the foreign Defendant Padagis Israel Pharmaceuticals Ltd. is asserted on the basis that it is not a U.S. resident and may be sued in any judicial district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the ophthalmic suspension SIMBRINZA® constitutes an act of patent infringement.
- Technical Context: The technology relates to aqueous ophthalmic compositions, specifically formulations for eye drops used to reduce intraocular pressure in patients with conditions like glaucoma or ocular hypertension.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from Padagis, dated September 14, 2022, informing Alcon of its ANDA filing. The ANDA included a Paragraph IV certification, alleging that the asserted patents are invalid, unenforceable, or will not be infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2009-06-19 | Priority Date for '484 and '265 Patents |
| 2013-01-01 | FDA approves New Drug Application for SIMBRINZA® (approximate date) |
| 2015-06-02 | U.S. Patent No. 9,044,484 Issues |
| 2016-08-23 | U.S. Patent No. 9,421,265 Issues |
| 2022-09-14 | Padagis sends Notice Letter regarding ANDA submission |
| 2022-10-10 | Padagis produces documents from ANDA to Alcon’s counsel |
| 2022-10-27 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,044,484 - "Aqueous Pharmaceutical Compositions Containing Borate-Polyol Complexes," Issued June 2, 2015
The Invention Explained
- Problem Addressed: The patent describes the technical challenge of formulating multi-dose ophthalmic products that are both effectively preserved against microbial contamination and non-toxic to sensitive corneal tissue. Specifically, it notes that common preservatives like benzalkonium chloride (BAC) can be toxic at higher concentrations, but ineffective at lower ones. (’484 Patent, col. 2:9-21).
- The Patented Solution: The invention claims a solution using a unique combination of two different types of polyols (a sugar alcohol like mannitol and a shorter-chain polyol like propylene glycol) in conjunction with borate and a low concentration of BAC. This specific combination is described as enhancing the anti-microbial effect of low levels of BAC, thereby achieving the required preservation without the associated toxicity of higher BAC concentrations. (’484 Patent, col. 3:40-54).
- Technical Importance: This approach sought to create preserved ophthalmic formulations that could be used repeatedly over extended periods with a reduced potential for ocular irritation, a significant consideration for chronic conditions like glaucoma. (’484 Patent, col. 9:16-31).
Key Claims at a Glance
- Independent Claim 1 is asserted in the complaint (Compl. ¶36).
- Essential elements of Claim 1:
- A multi-dose ophthalmic composition, comprising:
- a therapeutically effective amount of brimonidine;
- a first polyol selected from mannitol, sorbitol or a combination thereof at a concentration of at least 0.15 w/v % but less than 0.5 w/v %;
- a second polyol selected from propylene glycol, glycerine or a combination thereof at a concentration of at least 0.3 w/v % but less than 1.2 w/v %;
- borate at a concentration of at least 0.1 w/v % but less than about 0.5 w/v %;
- BAC as an anti-microbial preservative, at a concentration greater than 0.0007 w/v % but less than 0.0035 w/v %;
- water;
- wherein the composition has a pH that is at least 4 but less than 7.0.
- The complaint does not explicitly reserve the right to assert dependent claims, but refers generally to infringement of the patent.
U.S. Patent No. 9,421,265 - "Aqueous Pharmaceutical Compositions Containing Borate-Polyol Complexes," Issued August 23, 2016
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’484 Patent, this patent addresses the same technical problem of balancing preservation efficacy and low toxicity in ophthalmic formulations. (’265 Patent, col. 2:9-21).
- The Patented Solution: The solution is also based on the combination of two different polyols with borate and low-concentration BAC. However, the claims of the ’265 Patent are specifically directed to compositions that are a "suspension" and contain a "carboxyvinyl polymer" as a suspending agent to keep an insoluble therapeutic agent evenly dispersed. (’265 Patent, col. 8:10-14, col. 8:31-37).
- Technical Importance: This invention provided a method for formulating suspensions, which are necessary for water-insoluble drugs, that could meet preservative standards while using low levels of BAC, a formulation challenge noted in the patent. (’265 Patent, col. 8:20-27).
Key Claims at a Glance
- Independent Claim 1 is asserted in the complaint (Compl. ¶50).
- Essential elements of Claim 1:
- A multi-dose ophthalmic composition, comprising:
- a first polyol selected from mannitol, sorbitol or a combination thereof;
- a second polyol selected from propylene glycol, glycerine or a combination thereof;
- an effective amount of borate, being less than about 0.5 w/v %;
- BAC as an anti-microbial preservative, at a concentration greater than 0.00001 w/v % but less than 0.0035 w/v %;
- a therapeutic agent;
- water;
- wherein the composition is a "suspension" with the therapeutic agent and "carboxyvinyl polymer" as a suspending agent.
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
- Product Identification: The "Padagis ANDA Product," identified as ANDA No. 212137, which is a proposed generic version of SIMBRINZA® (brinzolamide/brimonidine tartrate ophthalmic suspension) (Compl. ¶¶1, 25).
- Functionality and Market Context:
- The complaint alleges that the Padagis ANDA Product has the same active ingredients (brinzolamide and brimonidine tartrate), dosage form (ophthalmic suspension), and strength as SIMBRINZA®, and is bioequivalent to it (Compl. ¶30).
- The product is intended for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension (Compl. ¶25). The filing of the ANDA itself indicates a commercial intent to enter the market for this treatment upon receiving FDA approval (Compl. ¶10).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that documents produced by Padagis from its confidential ANDA submission indicate that the proposed generic product meets every limitation of the asserted claims (Compl. ¶¶38, 52).
’484 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A multi-dose ophthalmic composition, comprising: a therapeutically effective amount of brimonidine | The complaint alleges the Padagis ANDA Product contains brimonidine as a therapeutic agent. | ¶¶30, 36, 38 | col. 7:19-22 |
| a first polyol, the first polyol being selected from mannitol, sorbitol or a combination thereof wherein the concentration...is at least 0.15 w/v % but is less than 0.5 w/v % | The complaint alleges, based on confidential ANDA documents, that the accused product contains a first polyol meeting this definition and concentration range. | ¶¶36, 38 | col. 5:19-27 |
| a second polyol, the second polyol being selected from propylene glycol, glycerine or a combination thereof wherein the concentration...is at least 0.3 w/v % but less than 1.2 w/v % | The complaint alleges, based on confidential ANDA documents, that the accused product contains a second polyol meeting this definition and concentration range. | ¶¶36, 38 | col. 5:44-50 |
| borate in the composition at a concentration that is at least 0.1 w/v % but less than about 0.5 w/v % | The complaint alleges, based on confidential ANDA documents, that the accused product contains borate within the specified concentration range. | ¶¶36, 38 | col. 5:59-63 |
| BAC as an anti-microbial preservative, the concentration of BAC...being greater than 0.0007 w/v % but less than 0.0035 w/v % | The complaint alleges, based on confidential ANDA documents, that the accused product contains BAC as a preservative within the specified concentration range. | ¶¶36, 38 | col. 4:46-54 |
| water; wherein the composition has a pH that is at least 4 but less than 7.0 | The complaint alleges the Padagis ANDA Product is an aqueous composition and, based on confidential ANDA documents, has a pH within the specified range. | ¶¶36, 38 | col. 8:1-2 |
- Identified Points of Contention:
- Quantitative Questions: The core of the infringement analysis will be a factual, quantitative comparison. A primary question is whether the precise w/v % concentrations of mannitol/sorbitol, propylene glycol/glycerine, borate, and BAC in Padagis's formulation, as disclosed in its ANDA, fall squarely within the ranges recited in Claim 1.
- Scope Questions: The term "about 0.5 w/v %" for borate introduces a potential scope question. If Padagis's formulation contains a concentration at or slightly above 0.5 w/v %, the parties may dispute whether it is still "about" 0.5 w/v % and thus infringing.
’265 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a first polyol, the first polyol being selected from mannitol, sorbitol or a combination thereof | The complaint alleges, based on confidential ANDA documents, that the accused product contains a first polyol as defined. | ¶¶50, 52 | col. 5:19-21 |
| a second polyol, the second polyol being selected from propylene glycol, glycerine or a combination thereof | The complaint alleges, based on confidential ANDA documents, that the accused product contains a second polyol as defined. | ¶¶50, 52 | col. 5:36-42 |
| an effective amount of borate, the effective amount being less than about 0.5 w/v % of the overall composition | The complaint alleges, based on confidential ANDA documents, that the accused product contains an effective amount of borate within the specified concentration limit. | ¶¶50, 52 | col. 5:59-63 |
| BAC as an anti-microbial preservative, the concentration...being greater than 0.00001 w/v % but less than 0.0035 w/v % | The complaint alleges, based on confidential ANDA documents, that the accused product contains BAC within the specified concentration range. | ¶¶50, 52 | col. 4:46-54 |
| a therapeutic agent; and water | The complaint alleges the Padagis ANDA Product is an aqueous composition containing therapeutic agents (brinzolamide/brimonidine). | ¶¶25, 30, 50, 52 | col. 7:10-13 |
| wherein the composition is a suspension with the therapeutic agent and carboxyvinyl polymer as a suspending agent | The complaint alleges the Padagis ANDA Product is an ophthalmic suspension and, based on confidential ANDA documents, contains a carboxyvinyl polymer. | ¶¶25, 50, 52 | col. 8:10-14, 31-37 |
- Identified Points of Contention:
- Technical Questions: A key question will be whether the polymer used in the Padagis ANDA Product qualifies as a "carboxyvinyl polymer" as that term is understood in the patent. The analysis will focus on the chemical structure of the polymer used by Padagis.
- Functional Questions: The claim requires the composition to be a "suspension". While SIMBRINZA® is a suspension, the properties of the Padagis product will be scrutinized to confirm it meets the technical definition of a suspension where the therapeutic agent is suspended by the carboxyvinyl polymer.
V. Key Claim Terms for Construction
The Term: "carboxyvinyl polymer" ('265 Patent, Claim 1)
Context and Importance: This term is critical to the infringement analysis of the ’265 Patent, as it defines the required suspending agent. The dispute will center on whether the specific excipient used by Padagis in its generic formulation falls within the scope of this term.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not provide a formal definition, which may support an argument for the term’s plain and ordinary meaning to one of skill in the art, potentially covering a wide range of polymers with carboxylic acid functional groups.
- Evidence for a Narrower Interpretation: The specification explicitly identifies preferred polymers as "water-soluble and water-swellable carbomers, available under the trade name CARBOPOL from the B.F. Goodrich Company," and lists "Carbopol 934 P, 940 and 974 P" as "highly preferred" (’265 Patent, col. 8:31-37). A defendant could argue this language limits the scope of "carboxyvinyl polymer" to these specific types of carbomers.
The Term: "about 0.5 w/v %" (’484 Patent, Claim 1; ’265 Patent, Claim 1)
Context and Importance: This term appears in the concentration limitation for borate. Its interpretation is crucial because if Padagis’s formulation is at or near the 0.5 w/v % boundary, the case may turn on how much variance "about" permits. Practitioners may focus on this term as a potential route to design around the claim.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of "about" itself implies the patentee did not intend the 0.5 w/v % value to be a strict, absolute limit. A plaintiff may argue it covers concentrations that achieve the same result in substantially the same way, consistent with the function of the invention.
- Evidence for a Narrower Interpretation: The patent provides numerous examples with specific concentration values, such as 0.3 w/v % and 0.6 w/v % for boric acid (e.g., ’484 Patent, Table C). A defendant may argue that these specific examples inform the meaning of "about" and suggest that it does not extend to encompass values that would be functionally different or were not contemplated by the inventors.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon approval of its ANDA, Padagis will actively induce infringement by "marketing the Padagis ANDA Product along with instructions directing users to infringe" the asserted patents (Compl. ¶¶42, 56). It also alleges contributory infringement, stating the product is "especially made or adapted for use in infringing" the patents and is "not suitable for substantial noninfringing use" (Compl. ¶¶43, 57).
- Willful Infringement: Willfulness is alleged based on Padagis's knowledge of the Asserted Patents at the time it submitted its ANDA (Compl. ¶32) and its subsequent actions "without a reasonable basis for believing that it would not be liable for directly and indirectly infringing" the patents (Compl. ¶¶47, 61). The complaint further requests a declaration that the case is "exceptional," which would be a basis for seeking attorneys' fees (Compl. ¶69).
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this ANDA litigation will likely depend on the answers to three central questions:
- A central evidentiary question will be one of "compositional identity": Does the precise formulation disclosed in Padagis’s confidential ANDA contain each chemical component within the exact quantitative ranges specified by the asserted claims, particularly the narrow w/v % windows for the two polyols, borate, and BAC?
- A key legal question will be one of "definitional scope": How broadly will the court construe terms like "about" and "carboxyvinyl polymer"? The outcome of the infringement analysis for the ’265 Patent, for instance, may turn entirely on whether the specific suspending agent used by Padagis is determined to be a "carboxyvinyl polymer" as defined by the patent.
- A determinative issue, raised by the defendant's Paragraph IV certification but not detailed in the complaint, will be "patent validity": Can Padagis prove by clear and convincing evidence that the claims are invalid, for example, by arguing that the claimed combination of well-known ophthalmic excipients would have been obvious to a person of ordinary skill in the art at the time of the invention?