3:23-cv-03794
Alkermes Pharma Ireland Ltd v. Slayback Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Alkermes Pharma Ireland Limited (Ireland)
- Defendant: Slayback Pharma LLC (Delaware) and Slayback Pharma India LLP (India)
- Plaintiff’s Counsel: Steptoe & Johnson LLP
- Case Identification: 3:23-cv-03794, D.N.J., 07/14/2023
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Slayback Pharma LLC maintains its principal place of business in Princeton, New Jersey, and is registered to conduct business in the state.
- Core Dispute: Plaintiff alleges that Defendants' filing of a New Drug Application to market a generic version of the injectable pain medication ANJESO® constitutes an act of infringement of five U.S. patents related to nanoparticulate meloxicam formulations and associated methods of treatment.
- Technical Context: The technology concerns formulations of meloxicam, a non-steroidal anti-inflammatory drug (NSAID), into nanoparticles to overcome poor water solubility, thereby enabling a fast-acting intravenous product for managing moderate-to-severe pain.
- Key Procedural History: This patent infringement action was initiated under the Hatch-Waxman Act following Defendants' submission of New Drug Application No. 218395, which included a Paragraph IV certification against the five patents-in-suit listed in the FDA's Orange Book for ANJESO®. The complaint notes that Defendants' certification letter did not set forth any grounds for invalidity or unenforceability for the asserted patents.
Case Timeline
| Date | Event |
|---|---|
| 2003-03-03 | Priority Date for '673, '067, '713 Patents |
| 2018-03-08 | Priority Date for '663, '145 Patents |
| 2019-11-05 | U.S. Patent No. 10,463,673 Issued |
| 2019-11-12 | U.S. Patent No. 10,471,067 Issued |
| 2020-02-20 | ANJESO® Reference Listed Drug NDA Approved |
| 2020-07-14 | U.S. Patent No. 10,709,713 Issued |
| 2021-01-05 | U.S. Patent No. 10,881,663 Issued |
| 2022-10-04 | U.S. Patent No. 11,458,145 Issued |
| 2023-06-01 | Slayback sends Paragraph IV Notice Letter |
| 2023-07-14 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,463,673 - "Nanoparticulate meloxicam formulations"
- Issued: November 5, 2019.
The Invention Explained
- Problem Addressed: The patent’s background section states that meloxicam, a non-steroidal anti-inflammatory drug (NSAID), is "practically insoluble in water" ('673 Patent, col. 5:46-48). This poor solubility leads to a slow onset of action for conventional oral formulations, making them "frequently inappropriate for management of acute pain" ('673 Patent, col. 5:44-45).
- The Patented Solution: The invention creates a composition of meloxicam particles with an "effective average particle size of less than about 2000 nm" ('673 Patent, Abstract). By reducing the drug to a nanoparticulate size and using surface stabilizers, the formulation can be administered intravenously, allowing for faster dissolution and absorption to achieve a rapid onset of pain relief ('673 Patent, col. 7:27-33).
- Technical Importance: This nanoparticulate approach enables the development of a fast-acting injectable formulation of meloxicam, seeking to combine the rapid pain relief of traditional narcotics with the longer duration and non-addictive properties of an NSAID ('673 Patent, col. 7:54-63).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims without specifying them (Compl. ¶56); independent claim 1 is representative of the patented composition.
- Essential Elements of Claim 1:
- An injectable pharmaceutical dosage form
- consisting of: 30 mg of meloxicam, or a salt thereof
- wherein the meloxicam is in the form of particles having an effective average particle size of less than about 200 nm
- polyvinylpyrrolidone
- sodium deoxycholate
- sucrose
- and water
- The complaint reserves the right to assert additional claims (Compl. ¶56).
U.S. Patent No. 10,471,067 - "Nanoparticulate meloxicam formulations"
- Issued: November 12, 2019.
The Invention Explained
- Problem Addressed: The patent addresses the same technical challenge as the ’673 patent: meloxicam's poor water solubility, which hinders its use in fast-acting injectable formulations for acute pain ('067 Patent, col. 5:46-48). It also notes the criticality of controlling particle size in injectable formulations to prevent potential embolism ('067 Patent, col. 7:23-27).
- The Patented Solution: The invention is an injectable pharmaceutical dosage form containing nanoparticulate meloxicam. The claims describe a composition "comprising" a specific set of components, including meloxicam particles with an effective average particle size of less than about 2000 nm, and includes a negative limitation excluding vasomodulators ('067 Patent, col. 28:1-15). This formulation is designed to provide rapid and long-lasting pain relief ('067 Patent, col. 7:54-63).
- Technical Importance: The invention provides a stable, injectable nanoparticulate meloxicam formulation that can be used for acute pain management, offering a non-narcotic alternative with a rapid onset of action.
Key Claims at a Glance
- The complaint asserts infringement of one or more claims without specifying them (Compl. ¶69); independent claim 1 is representative.
- Essential Elements of Claim 1:
- An injectable pharmaceutical dosage form
- comprising: 30 mg of meloxicam, or a salt thereof
- wherein the meloxicam is in the form of particles having an effective average particle size of less than or about 2000 nm
- polyvinylpyrrolidone
- sodium deoxycholate
- sucrose
- and water
- wherein the dosage form does not comprise a combination of meloxicam and a vasomodulator
- The complaint reserves the right to assert additional claims (Compl. ¶69).
U.S. Patent No. 10,709,713 - "Nanoparticulate meloxicam formulations"
- Issued: July 14, 2020.
Technology Synopsis
This patent addresses meloxicam's poor solubility by claiming a method of treating moderate to severe pain ('713 Patent, col. 5:21-24). The claimed method involves administering an intravenous bolus injection of a nanoparticulate meloxicam formulation to a human to achieve a specific pharmacokinetic profile, defined by its Area Under the Curve (AUCinf) ('713 Patent, col. 29:9-15).
Asserted Claims
The complaint does not specify claims; independent claims 1 and 6 are directed to the method of treatment.
Accused Features
Defendants are accused of infringement by filing an NDA for a drug product whose administration, as directed by its proposed label, would perform the claimed method of treating pain and achieve the claimed pharmacokinetic results (Compl. ¶¶ 82-83).
U.S. Patent No. 10,881,663 - "Method of treating pain in elderly patients with mild renal impairment"
- Issued: January 5, 2021.
Technology Synopsis
This patent addresses the specific clinical need for safe and effective NSAID-based pain management in elderly patients with mild renal impairment, a population vulnerable to complications ('663 Patent, col. 2:1-9). The invention is a method of treating pain in patients at least 65 years old with mild renal impairment by administering a 30 mg intravenous dose of meloxicam, which the patent asserts is safe and effective without requiring dose adjustment relative to patients with normal renal function ('663 Patent, Abstract; col. 20:1-17).
Asserted Claims
The complaint does not specify claims; independent claim 1 is directed to the method of treatment for this specific patient population.
Accused Features
The accused act is filing an NDA for a product whose proposed label would instruct or encourage its administration to the claimed patient population, thereby infringing the method claims (Compl. ¶¶ 95-96).
U.S. Patent No. 11,458,145 - "Methods of administering intravenous meloxicam in a bolus dose"
- Issued: October 4, 2022.
Technology Synopsis
The patent addresses the need for a pain medication with a rapid onset of action, which is often lacking in conventional NSAIDs ('145 Patent, col. 1:41-48). The invention is a method of administering a nanoparticulate meloxicam formulation as a rapid intravenous bolus dose over a period of about 1 to 60 seconds. This method is disclosed as providing fast pain relief without causing the significant injection site pain that can accompany rapid infusions of other drugs ('145 Patent, col. 4:1-10).
Asserted Claims
The complaint does not specify claims; independent claim 1 is directed to the bolus dose administration method.
Accused Features
Defendants are accused of infringement for seeking approval of a drug product whose label will instruct administration via the claimed rapid bolus dose method (Compl. ¶¶ 108-109).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendants’ "Proposed Drug Product," identified as "meloxicam injection, 30 mg/mL" intended for administration at a 30 mg dose (Compl. ¶¶ 1, 42).
Functionality and Market Context
The product is an injectable formulation of the NSAID meloxicam, intended as a generic equivalent to Plaintiff's ANJESO® product for the management of moderate-to-severe pain (Compl. ¶¶ 1, 31). The complaint arises from Defendants' filing of New Drug Application No. 218395 with the FDA, which contained a Paragraph IV certification stating that the patents-in-suit are invalid, unenforceable, or will not be infringed by the marketing of the Proposed Drug Product (Compl. ¶¶ 1, 38). This act of filing constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
The complaint alleges that Defendants' Proposed Drug Product will infringe claims of the patents-in-suit, based on a review of confidential information from the NDA filing (Compl. ¶51). The infringement theory is that the product for which Defendants seek approval has the same formulation and will be used in the same manner as Plaintiff's patented ANJESO® product.
10,463,673 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An injectable pharmaceutical dosage form | Defendants' Proposed Drug Product is an injectable formulation. | ¶42 | col. 21:5-7 |
| consisting of: 30 mg of meloxicam, or a salt thereof | The Proposed Drug Product contains meloxicam at a concentration of 30 mg/mL and is intended for a 30 mg dose. | ¶¶1, 42 | col. 27:36 |
| wherein the meloxicam is in the form of particles having an effective average particle size of less than about 200 nm | On information and belief, the meloxicam particles in the Proposed Drug Product meet this size limitation. | ¶56 | col. 20:11-12 |
| polyvinylpyrrolidone | On information and belief, the Proposed Drug Product contains this excipient. | ¶56 | col. 13:10-11 |
| sodium deoxycholate | On information and belief, the Proposed Drug Product contains this excipient. | ¶56 | col. 13:15-16 |
| sucrose | On information and belief, the Proposed Drug Product contains this excipient. | ¶56 | col. 21:65-67 |
| and water | The Proposed Drug Product is an aqueous injection. | ¶42 | col. 21:15-16 |
- Identified Points of Contention:
- Scope Questions: A primary legal question may arise from the term "consisting of." This is a closed transition phrase that presumptively excludes any unlisted elements. The dispute may focus on whether Defendants' formulation contains any additional excipients and, if so, whether those components materially alter the basic and novel properties of the claimed invention.
- Technical Questions: A central factual question will be whether the meloxicam particles in the accused product actually have an "effective average particle size of less than about 200 nm." The analysis will depend on evidence from Defendants' confidential NDA regarding its manufacturing process, particle size distribution, and quality control specifications.
10,471,067 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An injectable pharmaceutical dosage form | Defendants' Proposed Drug Product is an injectable formulation. | ¶42 | col. 21:5-7 |
| comprising: 30 mg of meloxicam, or a salt thereof | The Proposed Drug Product contains meloxicam at a concentration of 30 mg/mL and is intended for a 30 mg dose. | ¶¶1, 42 | col. 28:2-3 |
| ...particles having an effective average particle size of less than or about 2000 nm | On information and belief, the meloxicam particles in the Proposed Drug Product meet this size limitation. | ¶69 | col. 20:6-8 |
| polyvinylpyrrolidone; sodium deoxycholate; sucrose; and water | On information and belief, the Proposed Drug Product contains these excipients. | ¶69 | col. 13:10-16; col. 21:65-67 |
| wherein the dosage form does not comprise a combination of meloxicam and a vasomodulator | On information and belief, the Proposed Drug Product does not contain a vasomodulator. | ¶69 | col. 13:15-17 |
- Identified Points of Contention:
- Scope Questions: The use of the open-ended term "comprising" suggests the claim scope is broader than that of the ’673 patent, as it allows for the presence of additional, unrecited ingredients. A potential dispute could involve the negative limitation, raising the question of whether any component in the accused product could be characterized as a "vasomodulator."
- Technical Questions: The particle size limitation ("less than or about 2000 nm") is significantly broader than the corresponding limitation in the ’673 patent. While this may make proving infringement of this element more straightforward, the overall infringement analysis will still depend on the full composition and method of use.
V. Key Claim Terms for Construction
The Term: "consisting of" ('673 Patent, Claim 1)
Context and Importance: This term is critical because it defines the composition claim as closed, meaning it is limited to the enumerated ingredients. Practitioners may focus on this term because if Defendants' product contains any additional, materially significant excipient, it could support a non-infringement defense. The interpretation of this term will be central to determining the scope of the ’673 patent's composition claim.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that the term permits unlisted components that are merely impurities or do not materially affect the invention's properties, a standard exception in patent law. The patent does not provide specific language to broaden the term's standard meaning.
- Evidence for a Narrower Interpretation: The claim language itself and the general principles of claim construction support a narrow, exclusionary reading. The patent consistently describes the formulation in terms of its core components, suggesting an intent to claim only that specific combination ('673 Patent, Abstract; col. 27:35-43).
The Term: "comprising" ('067 Patent, Claim 1)
Context and Importance: This term is central to the scope of the ’067 patent, as it creates an open-ended claim that allows for additional, unrecited components. Its construction is important because it provides a lower bar for proving literal infringement compared to the "consisting of" language in the ’673 patent, potentially covering a wider range of formulations.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain and ordinary meaning of "comprising" in patent law is "including but not limited to." The specification's reference to "at least one surface stabilizer" ('067 Patent, col. 13:50-51) supports the notion that the recited list of components is not exhaustive.
- Evidence for a Narrower Interpretation: A defendant might argue that while the term is open, it does not permit additional elements that would alter the fundamental character of the invention (e.g., an ingredient that destabilizes the nanoparticle suspension). The inclusion of a specific negative limitation ("does not comprise a... vasomodulator") suggests the patentee considered and deliberately excluded certain components, arguably leaving the door open for other, non-excluded additions ('067 Patent, col. 28:13-15).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement of all asserted patents (Compl. ¶¶ 60, 73, 86, 99, 112). This allegation is based on the premise that Defendants’ product labeling and marketing materials will instruct or encourage healthcare professionals to administer the drug in a manner that directly infringes the method claims of the ’713, ’663, and ’145 patents.
- Willful Infringement: The complaint does not use the term "willful," but for each patent it alleges that the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶ 65, 78, 91, 104, 117). The basis for this allegation appears to be pre-suit knowledge of the patents, evidenced by the Paragraph IV certification, and the allegation that Defendants' notice letter failed to provide a factual or legal basis for contesting the patents' validity as required by regulation (Compl. ¶¶ 64, 77, 90, 103, 116).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope: can the narrow "consisting of" language in the '673 patent be used to establish non-infringement if the accused product contains additional excipients, and how will that analysis contrast with the more permissive "comprising" language of the '067 patent?
- A second central question will be one of induced infringement: what evidence does the proposed product label for the accused generic provide to demonstrate that it will inevitably instruct medical professionals to administer the drug to the specific patient populations and using the precise administration protocols (e.g., rapid bolus dose) required by the asserted method patents?
- A key factual question will be one of physicochemical equivalence: does the accused generic product, as manufactured at commercial scale, consistently meet the specific "effective average particle size" limitations recited in the composition claims, an issue that will be resolved through expert analysis of Defendants' confidential manufacturing data.