DCT
3:20-cv-10444
Merck Sharp & Dohme Corp v. Aurobindo Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme Corp. (New Jersey)
- Defendant: Aurobindo Pharma USA Inc., AuroMedics Pharma LLC, and Aurobindo Pharma Ltd. (Delaware and India)
- Plaintiff’s Counsel: McCarter & English, LLP; Gibson, Dunn & Crutcher LLP
- Case Identification: 3:20-cv-10444, D.N.J., 08/13/2020
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendants Aurobindo USA and AuroMedics have regular and established places of business in the district and have committed acts of infringement there, including sending a Notice Letter to Plaintiff Merck in New Jersey. The foreign parent, APL, may be sued in any judicial district.
- Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's NOXAFIL® intravenous solution constitutes an act of infringement of two patents covering the drug's formulation.
- Technical Context: The lawsuit concerns pharmaceutical formulations designed to improve the solubility and stability of posaconazole, a poorly water-soluble antifungal drug, for intravenous administration.
- Key Procedural History: This action was triggered by Defendants' submission of an ANDA with a Paragraph IV certification, a statutory act of infringement under the Hatch-Waxman Act. The complaint notes that Defendants' certification alleges the patents-in-suit are invalid but does not contest that the proposed generic product would infringe the asserted claims if they are found to be valid.
Case Timeline
| Date | Event |
|---|---|
| 2010-06-29 | Priority Date for ’790 and ’297 Patents |
| 2015-05-05 | U.S. Patent No. 9,023,790 Issued |
| 2016-06-07 | U.S. Patent No. 9,358,297 Issued |
| 2020-07-01 | Date of Defendants' Notice Letter to Plaintiff |
| 2020-08-13 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,023,790 - “Posaconazole Intravenous Solution Formulations Stabilized by Substituted β-Cyclodextrin,” Issued May 5, 2015
The Invention Explained
- Problem Addressed: The patent addresses the technical challenge that posaconazole, a potent antifungal agent, is "a weakly basic and poorly-aqueous soluble drug that has poor bioavailability and variable absorption" (’790 Patent, col. 1:57-59). This poor solubility makes it difficult to create a stable and effective intravenous (IV) formulation, which is needed for patients who cannot take oral medicine (’790 Patent, col. 2:2-5).
- The Patented Solution: The invention uses a specific solubilizing agent, sulfobutylether-β-cyclodextrin (SBECD), in an acidified aqueous solution to form a complex with posaconazole, dramatically increasing its solubility (’790 Patent, Abstract; col. 2:16-21). The formulation may also include a chelating agent, such as EDTA, to improve stability and prevent color changes over time (’790 Patent, col. 7:20-31).
- Technical Importance: This formulation technology enables the delivery of posaconazole via an intravenous route, providing a critical therapeutic option for severely immunocompromised patients who cannot rely on oral administration (’790 Patent, col. 1:47-56; col. 2:2-5).
Key Claims at a Glance
- The complaint asserts claims 1-19 (Compl. ¶24). Independent claim 1 is representative.
- Essential elements of independent claim 1 include:
- A pharmaceutical composition for intravenous administration comprising posaconazole.
- A modified β-cyclodextrin which is specifically sulfobutylether-β-cyclodextrin "having a degree of substitution of 6.5 and a molecular weight of 2163 g/mole."
- An aqueous solution wherein the pH is between about 2.0 and about 3.5.
- A posaconazole concentration between about 14 and about 22 mg/mL.
- A modified β-cyclodextrin concentration between about 350 and about 450 mg/mL.
- The complaint reserves the right to assert dependent claims (Compl. ¶24, ¶28-30).
U.S. Patent No. 9,358,297 - “Posaconazole Intravenous Solution Formulations Stabilized by Substituted β-Cyclodextrin,” Issued June 7, 2016
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’790 Patent, this patent addresses the same problem of posaconazole's poor aqueous solubility and the resulting difficulty in creating an IV formulation (’297 Patent, col. 2:2-9).
- The Patented Solution: The invention described is substantively identical to that of the ’790 Patent, employing an acidified solution of sulfobutylether-β-cyclodextrin to solubilize posaconazole for intravenous use (’297 Patent, Abstract; col. 2:21-27). The specification similarly discloses the use of a chelating agent to enhance stability (’297 Patent, col. 7:45-50).
- Technical Importance: The technical contribution is the same as described for the ’790 Patent: enabling a stable, effective IV formulation of a critical but poorly soluble antifungal drug (’297 Patent, col. 1:56-65).
Key Claims at a Glance
- The complaint asserts claims 1-34 (Compl. ¶24). Independent claim 1 is representative.
- Essential elements of independent claim 1 include:
- A pharmaceutical composition for intravenous administration comprising 100 mg to 400 mg of posaconazole.
- A modified β-cyclodextrin which is specifically sulfobutylether-β-cyclodextrin "having a degree of substitution of 6.5 and a molecular weight of 2163 g/mole."
- An aqueous solution wherein the pH is between about 2.0 and about 3.5.
- A posaconazole concentration between about 14 and about 22 mg/mL.
- A modified β-cyclodextrin concentration between about 350 and about 450 mg/mL.
- The complaint reserves the right to assert dependent claims (Compl. ¶24, ¶35-37).
III. The Accused Instrumentality
Product Identification
The "Generic Posaconazole IV Solution Product" described in Aurobindo's Abbreviated New Drug Application (ANDA) No. 214842 (Compl. ¶1).
Functionality and Market Context
The complaint alleges that by filing its ANDA, Aurobindo represented to the FDA that its generic product has the "same active ingredient as NOXAFIL® for Injection, has the same method of administration, dosage form, and strength as NOXAFIL® for Injection and is bioequivalent to NOXAFIL® for Injection" (Compl. ¶25). NOXAFIL® for Injection is approved for the prophylaxis of invasive fungal infections in high-risk patients and is an embodiment of the patents-in-suit (Compl. ¶16-17). The accused product is therefore alleged to be a pharmaceutical formulation designed for intravenous delivery of posaconazole.
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint’s infringement theory is based on 35 U.S.C. § 271(e)(2), where the filing of an ANDA seeking approval to market a drug claimed in a patent is a statutory act of infringement (Compl. ¶27, ¶34). The complaint alleges that Aurobindo does not contest that its product would infringe if the claims are found to be valid (Compl. ¶24). The allegations effectively state that the accused product meets every limitation of the asserted claims.
’790 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| posaconazole, or a pharmaceutically acceptable salt thereof | The accused product contains posaconazole as its active ingredient. | ¶25 | col. 10:19-20 |
| a modified β-cyclodextrin which comprises sulfobutylether-β-cyclodextrin having a degree of substitution of 6.5 and a molecular weight of 2163 g/mole | The accused product is alleged to have the same formulation as NOXAFIL® for Injection, which is an embodiment of the patent. | ¶17, ¶25 | col. 10:31-35 |
| in aqueous solution, wherein the pH of said composition is between about 2.0 and about 3.5 | The accused product is an intravenous solution alleged to be bioequivalent to NOXAFIL®, which has a target pH of 2.6. | ¶17, ¶25 | col. 14:23-25 |
| wherein the concentration of said posaconazole...is between about 14 and about 22 mg/mL | The accused product is alleged to have the same strength as NOXAFIL® for Injection, which is formulated at 18 mg/mL. | ¶1, ¶17, ¶25 | col. 10:44-46 |
| and the concentration of said modified β-cyclodextrin is between about 350 and about 450 mg/mL | The accused product is alleged to have the same formulation as NOXAFIL®, which is formulated with 400 mg/mL of SBECD. | ¶17, ¶25 | col. 10:46-48 |
’297 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| 100 mg to 400 mg of posaconazole, or a pharmaceutically acceptable salt thereof | The accused product is a generic version of a 300 mg posaconazole IV solution. | ¶1 | col. 19:8-10 |
| a modified β-cyclodextrin which comprises sulfobutylether-β-cyclodextrin having a degree of substitution of 6.5 and a molecular weight of 2163 g/mole | The accused product is alleged to have the same formulation as NOXAFIL® for Injection, which is an embodiment of the patent. | ¶17, ¶25 | col. 19:11-15 |
| in aqueous solution, wherein the pH of said composition is between about 2.0 and about 3.5 | The accused product is an intravenous solution alleged to be bioequivalent to NOXAFIL®, which has a target pH of 2.6. | ¶17, ¶25 | col. 14:55-60 |
| wherein the concentration of said posaconazole...is between about 14 and about 22 mg/mL | The accused product is alleged to have the same strength as NOXAFIL® for Injection, which is formulated at 18 mg/mL. | ¶1, ¶17, ¶25 | col. 19:18-20 |
| and the concentration of said modified β-cyclodextrin is between about 350 and about 450 mg/mL | The accused product is alleged to have the same formulation as NOXAFIL®, which is formulated with 400 mg/mL of SBECD. | ¶17, ¶25 | col. 19:20-22 |
Identified Points of Contention
- Validity vs. Infringement: The primary point of contention, as alleged in the complaint, is not infringement but validity. The complaint states that Aurobindo's Paragraph IV certification alleges the patents are invalid (Compl. ¶23). Given Aurobindo's concession on infringement pending a validity determination (Compl. ¶24), the case will likely focus on whether the claimed formulations were obvious or anticipated by the prior art.
- Scope Questions: A latent question of scope may arise regarding the precise definitions in the claims. For example, does Aurobindo's specific SBECD excipient meet the claim requirement of "having a degree of substitution of 6.5 and a molecular weight of 2163 g/mole"? While the complaint alleges bioequivalence, a detailed factual inquiry could reveal subtle differences that might form a basis for a non-infringement argument.
V. Key Claim Terms for Construction
The Term: "a modified β-cyclodextrin which comprises sulfobutylether-β-cyclodextrin having a degree of substitution of 6.5 and a molecular weight of 2163 g/mole" (’790 Patent, claim 1)
- Context and Importance: This term defines the specific excipient required to practice the invention. Its construction is critical because any deviation in the accused product's excipient from this precise definition could support a non-infringement defense. Practitioners may focus on whether this highly specific language can be interpreted to cover any range or average, or if it is limited to the exact values recited.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the open-ended term "comprises" suggests the modified β-cyclodextrin could include other components or forms of SBECD, as long as it contains the specifically defined one.
- Evidence for a Narrower Interpretation: The specification provides a table that explicitly lists "Sulfobutyl ether-β-cyclodextrins, (SBE-β-CD) sodium salt" with a "Molecular weight" of "2163 g/mole" and a "(Degree of substitution = 6.5)" (’790 Patent, Table 1). This specific disclosure could be used to argue that the claim is limited to this exact material, known commercially as Captisol®.
The Term: "about" (e.g., "pH...is between about 2.0 and about 3.5") (’790 Patent, claim 1)
- Context and Importance: The term "about" precedes nearly every numerical value in the independent claims (pH, concentrations). The scope of "about" will define the boundaries of the claimed ranges. A narrow construction would make it easier for a defendant to design around the patent, while a broad construction would capture a wider range of formulations.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses experiments across a range of pH values (e.g., pH 2.0 to 4.5 in Figure 1), which may support a view that the inventors did not intend the values to be exact and absolute.
- Evidence for a Narrower Interpretation: The specification identifies a specific target pH of 2.6 for the final clinical formulation (’790 Patent, col. 10:8). Parties arguing for a narrower scope may point to such specific embodiments as evidence that "about" should not be interpreted to greatly expand the claimed ranges beyond what was specifically tested and proven effective.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon approval of its ANDA, Aurobindo will actively induce infringement by providing prescribing instructions to "health care professionals, resellers, pharmacies, and end users" that will encourage use of the generic product in an infringing manner (Compl. ¶30, ¶37).
- Willful Infringement: The complaint alleges that Aurobindo had "actual and constructive knowledge" of the patents-in-suit prior to filing its ANDA, and was aware that the filing would constitute infringement (Compl. ¶31, ¶38). While the term "willful" is not used in the infringement counts, the prayer for relief requests a declaration that the case is "exceptional" and an award of attorneys' fees, which is consistent with an allegation of willful or egregious conduct (Compl., Prayer for Relief ¶K).
VII. Analyst’s Conclusion: Key Questions for the Case
- The Central Question of Validity: As infringement is reportedly conceded if the claims are valid, the case will pivot on whether Aurobindo can prove by clear and convincing evidence that the asserted claims are invalid. The key question for the court will be whether the combination of posaconazole with a specific SBECD at a specific pH and concentration range was obvious to a person of ordinary skill in the art at the time of the invention.
- The Definitional Question of "About": A secondary but critical issue will be the construction of the term "about." The court's interpretation of how much variability this term allows around the claimed numerical values for pH and concentrations will directly impact the scope of the claims, which in turn could influence both the infringement and validity analyses.
- The Factual Question of Equivalence: Should Aurobindo contest infringement, a key evidentiary question will be whether its "Generic Posaconazole IV Solution Product" is in fact identical to the formulation defined by the claims. This will require a detailed factual comparison of the excipients, concentrations, and properties of the accused product against the highly specific limitations recited in the patent claims.