DCT
1:19-cv-01067
Silvergate Pharma Inc v. Bionpharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Silvergate Pharmaceuticals, Inc. (Delaware)
- Defendant: Bionpharma Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Wilson Sonsini Goodrich & Rosati
- Case Identification: 1:19-cv-01067, D. Del., 06/07/2019
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, Bionpharma Inc., is a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's Epaned® oral solution constitutes an act of infringement of a patent directed to stable liquid enalapril formulations.
- Technical Context: The technology concerns stable, ready-to-use liquid formulations of enalapril, an ACE inhibitor used to treat hypertension, heart failure, and related conditions, with a focus on solving stability and dosing-accuracy problems for populations like children.
- Key Procedural History: This action was filed under the Hatch-Waxman Act following Defendant’s April 25, 2019 notification to Plaintiff of its ANDA submission. The complaint notes a prior, pending lawsuit between the same parties in the same district (C.A. No. 1:18-cv-01962) concerning different patents from the same family, and states Plaintiff’s intent to seek consolidation of the two cases.
Case Timeline
| Date | Event |
|---|---|
| 2016-03-18 | ’987 Patent Priority Date |
| 2018-12-12 | Prior litigation against Bionpharma filed by Silvergate |
| 2018-12-18 | ’987 Patent Issue Date |
| 2019-04-25 | Bionpharma sends ANDA Notice Letter to Silvergate |
| 2019-06-07 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,154,987 - "Enalapril Formulations"
- Patent Identification: U.S. Patent No. 10,154,987, "Enalapril Formulations," issued December 18, 2018. (’987 Patent).
The Invention Explained
- Problem Addressed: The patent addresses the lack of a stable, ready-to-use liquid formulation of enalapril, an important drug for hypertension. Conventional administration via solid tablets presents challenges for certain patients, such as children and the elderly, while compounding tablets into liquids often leads to inaccurate dosing, rapid degradation of the active ingredient, and potential contamination (’987 Patent, col. 5:24-54).
- The Patented Solution: The invention is a stable oral liquid formulation that solves these problems by combining enalapril with a specific set of excipients: the sweetener sucralose, a citric acid/sodium citrate buffer, and the preservative sodium benzoate. A key aspect of the solution is maintaining the formulation's pH at less than 3.5, which the patent teaches is critical for minimizing the formation of degradants and ensuring stability for at least 12 months under refrigerated conditions (’987 Patent, Abstract; col. 2:21-29).
- Technical Importance: The invention provides a commercially viable, ready-to-use liquid enalapril product with a long shelf life, thereby improving dosing accuracy and patient compliance, particularly in pediatric populations where weight-based dosing is critical (’987 Patent, col. 5:32-38; Compl. ¶7).
Key Claims at a Glance
The complaint does not specify which claims it will assert but alleges that Defendant's product will infringe "one or more claims" of the ’987 Patent (Compl., Prayer for Relief ¶a). Independent claim 1 is representative of the invention's core composition and method.
- Independent Claim 1 (Method of Treating Hypertension):
- Administering a stable oral liquid formulation comprising:
- About 0.6 to 1.2 mg/ml of enalapril (or a salt/solvate thereof);
- A buffer comprising about 0.8 to 3.5 mg/ml of citric acid and about 0.1 to 0.8 mg/ml of sodium citrate;
- About 0.7 to 1.2 mg/ml of sodium benzoate;
- Water;
- Wherein the formulation is stable at about 5±3° C. for at least 12 months; and
- Wherein the formulation has about 95% or greater of the initial enalapril amount and 5% or less total impurities after the storage period.
III. The Accused Instrumentality
Product Identification
- The "Bionpharma ANDA Product," a generic version of Silvergate’s Epaned® oral solution, as described in ANDA No. 212408 filed with the FDA (Compl. ¶13).
Functionality and Market Context
- The accused product is an oral liquid solution of enalapril intended for the treatment of hypertension (Compl. ¶1, ¶7). The complaint alleges that by filing its ANDA, Bionpharma has represented to the FDA that its proposed generic product has the same active ingredient, route of administration, dosage form, and strength as Silvergate’s Epaned® product, and that it is bioequivalent (Compl. ¶14). The infringement action is premised on the technical identity between the proposed generic and the patented formulation. No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a detailed claim chart. The infringement theory is based on the statutory act of filing an ANDA for a product that, if approved and marketed, would infringe the ’987 Patent. The core allegation is that because the Bionpharma ANDA Product is designed to be a bioequivalent copy of Silvergate's Epaned® product, which is covered by the patent, the ANDA product will necessarily meet the limitations of the asserted claims (Compl. ¶¶14, 17).
’987 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating hypertension ... comprising administering ... a stable oral liquid formulation comprising: (i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof | The Bionpharma ANDA Product is an oral liquid formulation alleged to contain the same active ingredient at the same strength as Epaned®, which is covered by the patent. | ¶14 | col. 7:11-14 |
| (ii) a buffer comprising about 0.8 to about 3.5 mg/ml citric acid and about 0.1 to about 0.8 mg/ml sodium citrate | The Bionpharma ANDA Product is alleged to be a bioequivalent formulation, and therefore its buffer system is alleged to meet the claimed component and concentration requirements. | ¶14 | col. 15:35-40 |
| (iii) about 0.7 to about 1.2 mg/ml sodium benzoate | The Bionpharma ANDA Product is alleged to be a bioequivalent formulation, and therefore its preservative system is alleged to meet the claimed component and concentration requirements. | ¶14 | col. 11:7-10 |
| (iv) water | The Bionpharma ANDA product is an oral liquid solution and is therefore alleged to comprise water as a vehicle. | ¶14 | col. 2:27 |
| wherein the formulation is stable at about 5±3° C. for at least 12 months | As a proposed bioequivalent, the Bionpharma ANDA product is alleged to possess the same stability profile as the patented formulation. | ¶14 | col. 2:27-29 |
| wherein the stable oral liquid formulation has about 95% w/w or greater of the initial enalapril amount and about 5% w/w or less total impurity ... | As a proposed bioequivalent, the Bionpharma ANDA product is alleged to meet the same impurity profile as the patented formulation. | ¶14 | col. 18:41-45 |
Identified Points of Contention
- Scope Questions: A primary question for the court will be whether the precise formulation detailed in Bionpharma's ANDA literally falls within the quantitative boundaries of the asserted claims. For example, does the accused product's buffer system contain both citric acid and sodium citrate within the specific concentration ranges recited in claim 1?
- Technical Questions: The functional limitations concerning stability and impurity levels will require factual evidence. A key question will be what data Bionpharma's ANDA contains to support stability, and whether that data demonstrates stability for "at least 12 months" at "about 5±3° C" with the claimed low level of impurities, as required by the claims.
V. Key Claim Terms for Construction
The complaint does not identify any specific claim term disputes. However, based on the technology and claim language, the following terms may become central to the litigation.
The Term: "a buffer comprising about 0.8 to about 3.5 mg/ml citric acid and about 0.1 to about 0.8 mg/ml sodium citrate"
Context and Importance: This limitation defines the chemical environment essential for the claimed stability. Practitioners may focus on this term because infringement will hinge on whether the accused product's buffer literally meets these specific compositional and concentration requirements. Any deviation could be a basis for a non-infringement argument.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of "comprising" is open-ended, which could support an argument that the buffer may contain other, unlisted ingredients so long as it contains citric acid and sodium citrate in the claimed amounts.
- Evidence for a Narrower Interpretation: The claim recites specific concentration ranges for both components, suggesting that both are required and must fall within their respective ranges. The specification provides specific examples with concentrations that fall within these ranges (e.g., Formulation B2 contains 1.65 mg/ml citric acid and 0.38 mg/ml sodium citrate), which could be used to argue that the ranges are strict requirements (’987 Patent, col. 31, Table B-1).
The Term: "stable"
Context and Importance: This is a functional limitation that defines the required performance of the formulation. The term's meaning is partially defined by the subsequent clauses ("at about 5±3° C. for at least 12 months" and the impurity clause), but its full scope may be contested.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent itself defines "stable" as "having about 95% or greater of the initial enalapril amount and about 5% w/w or less total impurities or related substances at the end of a given storage period" (’987 Patent, col. 18:40-45). A plaintiff would argue this explicit definition controls.
- Evidence for a Narrower Interpretation: A defendant might argue that "stable" implies more than just the impurity profile, potentially including physical characteristics like appearance or lack of precipitation. Further, a defendant may challenge whether accelerated stability data, as presented in the patent's examples (e.g., testing at 60°C), is sufficient to prove stability under the claimed refrigerated conditions (’987 Patent, col. 31, Example A).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Bionpharma had "specific intent to infringe" and that its product has "no substantial non-infringing uses," which lays the groundwork for claims of induced and contributory infringement (Compl. ¶18). The basis for inducement would be the proposed product labeling, which will allegedly instruct medical professionals and patients to administer the drug for treating hypertension, thereby performing the steps of the patented method.
- Willful Infringement: Willfulness is alleged based on Bionpharma's "actual knowledge of the '987 Patent prior to filing" its ANDA (Compl. ¶18). The complaint also seeks a finding that the case is "exceptional" under 35 U.S.C. § 285 to recover attorney's fees (Compl., Prayer for Relief ¶e).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of literal infringement: Does the specific formulation disclosed in Bionpharma’s ANDA contain every component within the exact quantitative ranges recited in the asserted claims, and does it demonstrably meet the functional requirements for pH, stability, and purity?
- A second core issue, common in ANDA litigation, will likely be validity: Can Bionpharma prove by clear and convincing evidence that the claimed formulation—a specific combination of known pharmaceutical excipients to achieve stability at a particular pH—would have been obvious to a person of ordinary skill in the art at the time of the invention?
- Finally, a key procedural question is the impact of the related litigation involving the same parties and technology. A primary issue for the court will be whether to grant the plaintiff's anticipated request to consolidate this case with the earlier-filed action to promote judicial efficiency.