DCT
3:18-cv-11216
Amgen Inc v. Prinston Pharmaceutical Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Celgene Corporation (Delaware)
- Defendant: Prinston Pharmaceutical Inc. (Delaware)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP; Covington & Burling LLP
- Case Identification: 3:18-cv-11216, D.N.J., 06/28/2018
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey as Defendant maintains its principal place of business in the state and has allegedly committed acts of infringement there.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for generic versions of Plaintiff's OTEZLA® drug constitutes an act of infringement of a patent covering the drug's active ingredient, apremilast.
- Technical Context: The technology concerns a specific, stereomerically pure enantiomer of a chemical compound that functions as a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory conditions such as psoriatic arthritis and psoriasis.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 211614 with a Paragraph IV certification, asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed. The complaint was filed within the 45-day statutory window, triggering an automatic 30-month stay on the FDA’s approval of Defendant's ANDA.
Case Timeline
| Date | Event |
|---|---|
| 2002-03-20 | ’638 Patent Priority Date |
| 2008-09-23 | ’638 Patent Issue Date |
| 2014-03-21 | FDA Approval of OTEZLA® (apremilast) |
| 2018-05-25 | Plaintiff received Defendant's Paragraph IV Notice Letter |
| 2018-06-28 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,427,638 - "(+)-2-[1-(3-Ethoxy-4-Methoxyphenyl)-2-Methylsulfonylethyl]-4-Acetylaminoisoindoline-1,3-Dione, and Methods of Synthesis and Compositions Thereof"
- Patent Identification: U.S. Patent No. 7,427,638, "(+)-2-[1-(3-Ethoxy-4-Methoxyphenyl)-2-Methylsulfonylethyl]-4-Acetylaminoisoindoline-1,3-Dione, and Methods of Synthesis and Compositions Thereof," issued September 23, 2008.
The Invention Explained
- Problem Addressed: The patent describes a need for treatments for diseases associated with unregulated production of Tumor Necrosis Factor alpha (TNF-α) and for conditions that benefit from the elevation of cyclic adenosine monophosphate (cAMP) ('638 Patent, col. 1:21-29, col. 2:46-51). Existing inhibitors of phosphodiesterase type IV (PDE4), an enzyme that degrades cAMP, are noted as lacking the necessary selective action at acceptable therapeutic doses ('638 Patent, col. 2:65-67).
- The Patented Solution: The invention is directed to a stereomerically pure form of a specific compound, the (+) enantiomer of 2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, known as apremilast ('638 Patent, Abstract). This specific enantiomer is asserted to have increased potency and other benefits compared to the previously known racemic mixture, providing a more effective way to inhibit TNF-α and PDE4 for treating inflammatory diseases ('638 Patent, col. 3:22-29, col. 3:45-54). A chemical synthesis pathway for the compound is illustrated in the patent's figures ('638 Patent, Fig. 1).
- Technical Importance: The invention provided a specific, purified enantiomer as a therapeutic agent, which was believed to offer a more potent and potentially safer treatment for inflammatory diseases compared to the racemic mixture from which it was derived ('638 Patent, col. 3:22-29).
Key Claims at a Glance
- The complaint’s allegations implicate independent claims directed to the compound itself, pharmaceutical compositions, and single unit dosage forms (Compl. ¶37, ¶49). The primary asserted independent claims appear to be 1, 7, and 13.
- Independent Claim 13 (Compound):
- Stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione
- substantially free of its (-) isomer
- Independent Claim 1 (Composition):
- A pharmaceutical composition comprising the stereomerically pure (+) compound
- and a pharmaceutically acceptable carrier, excipient or diluent
- Independent Claim 7 (Dosage Form):
- A single unit dosage form
- comprising about 1 mg to 1000 mg of the stereomerically pure (+) compound
- and a pharmaceutically acceptable carrier, excipient or diluent
III. The Accused Instrumentality
Product Identification
- The complaint identifies "Prinston's Infringing ANDA Products" as generic versions of OTEZLA® (apremilast) in 10 mg, 20 mg, and 30 mg tablets (Compl. ¶1).
Functionality and Market Context
- The accused products are tablets that contain apremilast as the active pharmaceutical ingredient, specifically the (+) enantiomer of 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione (Compl. ¶25, ¶38).
- These products are intended to be generic equivalents to Celgene’s OTEZLA®, a commercially successful drug indicated for the treatment of active psoriatic arthritis and moderate to severe plaque psoriasis (Compl. ¶1, ¶17). The complaint references the prescribing information for OTEZLA®, attached as Exhibit A, which details its clinical use and dosage (Compl. ¶17; Compl. Ex. A).
IV. Analysis of Infringement Allegations
'638 Patent Infringement Allegations
| Claim Element (from Independent Claim 13) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, | The complaint alleges that Prinston's Infringing ANDA Products contain "(+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione." | ¶38 | col. 5:12-23 |
| substantially free of its (-) isomer | The allegation that the accused product contains the specific "(+)-..." enantiomer necessarily implies that it is substantially free of the (-) isomer, as required for a product to be considered a stereomerically pure enantiomer. | ¶38 | col. 6:12-32 |
- Identified Points of Contention:
- Validity Questions: As this is an ANDA case, the central dispute will almost certainly concern the validity of the ’638 Patent's claims, which Defendant must have challenged in its Paragraph IV certification (Compl. ¶28). The specific grounds for the invalidity challenge (e.g., obviousness over the prior art racemate, lack of written description) are not detailed in the complaint but will be a primary focus of the litigation.
- Scope Questions: A potential point of contention in infringement may arise from the construction of the terms "stereomerically pure" and "substantially free of its (-) isomer." The parties may dispute the specific level of enantiomeric purity required to fall within the scope of the claims, raising the question of whether Defendant's product meets that threshold.
V. Key Claim Terms for Construction
- The Term: "stereomerically pure"
- Context and Importance: The patent is directed to a specific (+) enantiomer, distinguishing it from the racemic mixture. The precise definition of "stereomerically pure," particularly the required percentage of the (+) enantiomer, is critical for determining infringement. Practitioners may focus on this term because the outcome of its construction will establish the evidentiary threshold for proving that the accused product meets this limitation.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification provides a definition: "a composition that comprises one stereoisomer of a compound and is substantially free of other stereoisomers of that compound" and further specifies that a "typical stereomerically pure compound comprises greater than about 80% by weight of one stereoisomer" ('638 Patent, col. 6:12-22).
- Evidence for a Narrower Interpretation: The same passage offers more restrictive preferred embodiments, such as "more preferably greater than about 95% by weight" or "most preferably greater than about 97% by weight" of the stereoisomer ('638 Patent, col. 6:26-32). A party could also point to the working examples, which describe achieving a product with "98% ee," corresponding to 99% purity of the desired enantiomer, as evidence of the level of purity contemplated by the inventors ('638 Patent, col. 22:20).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Prinston will induce infringement by marketing its generic product with a product label and insert that will include instructions for use substantially similar to those for OTEZLA®. It is alleged that Prinston knows that following these instructions will cause physicians and patients to directly infringe claims of the '638 Patent (Compl. ¶41, ¶53).
- Willful Infringement: The complaint alleges that Prinston had actual and constructive notice of the '638 Patent prior to filing its ANDA, in part due to the patent's listing in the FDA's Orange Book (Compl. ¶21, ¶42). The pleading further asserts that Prinston's filing was made "without adequate justification," rendering the case "exceptional" under 35 U.S.C. § 285 and supporting a claim for enhanced damages and attorneys' fees (Compl. ¶45).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue for the court will be one of patent validity: can the Defendant prove by clear and convincing evidence that the asserted claims, which cover a stereomerically pure enantiomer, are invalid, likely on grounds of obviousness in view of the previously known racemic mixture?
- A key question of claim construction will be the required level of purity: how will the court define "stereomerically pure" and "substantially free of its (-) isomer"? The patent provides a range of definitions, and the specific threshold chosen will directly impact the infringement analysis.
- An underlying procedural question will be one of remedy and deterrence: will the facts surrounding Defendant’s ANDA filing and its litigation positions support Plaintiff's allegation that this is an "exceptional" case, warranting an award of attorneys' fees?