DCT
2:18-cv-08964
Celgene Corp v. Cipla Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Celgene Corporation (Delaware)
- Defendant: Cipla Limited (India)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP
- Case Identification: 2:18-cv-08964, D.N.J., 05/08/2018
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendant’s systematic and continuous business contacts with the state, including the marketing and sale of pharmaceutical products. The complaint further alleges that the filing of the Abbreviated New Drug Application (ANDA) constitutes an act of infringement and that notice of this filing was sent to Plaintiff’s headquarters in New Jersey.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an ANDA to market generic versions of Plaintiff's REVLIMID® (lenalidomide) drug product constitutes an act of infringement of three U.S. patents covering specific crystalline forms (polymorphs) of lenalidomide and pharmaceutical compositions containing them.
- Technical Context: The technology relates to pharmaceutical polymorphism, which is the ability of a solid chemical compound to exist in multiple crystalline forms, each possessing distinct physicochemical properties such as solubility and stability that are critical for drug formulation and bioavailability.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 210435 to the FDA. The complaint states that Defendant provided a Paragraph IV Certification notice, alleging that the asserted patents are invalid, unenforceable, and/or will not be infringed by its proposed generic products.
Case Timeline
| Date | Event |
|---|---|
| 2003-09-04 | Priority Date for ’357, ’219, and ’598 Patents |
| 2011-07-12 | U.S. Patent No. 7,977,357 Issues |
| 2012-06-05 | U.S. Patent No. 8,193,219 Issues |
| 2013-04-30 | U.S. Patent No. 8,431,598 Issues |
| 2017-06-30 | Earliest Date Defendant Sent Paragraph IV Notice Letter |
| 2018-05-08 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,977,357 - "Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione"
The Invention Explained
- Problem Addressed: The patent's background section notes that a single chemical compound can exist in different solid crystalline forms, or polymorphs, which can exhibit different physical properties ('357 Patent, col. 2:23-28). These differences in properties like solubility and stability can significantly impact the safety, efficacy, and manufacturability of a drug product ('357 Patent, col. 2:42-48).
- The Patented Solution: The invention claims to have discovered and characterized several distinct polymorphic forms of the compound 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione (lenalidomide), designated as Forms A through H ('357 Patent, col. 2:60-65). The patent provides detailed methods for preparing these forms and characterizes them using analytical techniques such as X-ray powder diffraction (XRPD), as illustrated for Form A in FIG. 1, and differential scanning calorimetry (DSC) ('357 Patent, col. 6:15-28).
- Technical Importance: Identifying and isolating specific, stable polymorphic forms of an active pharmaceutical ingredient is a critical step in developing a consistent, safe, and effective solid oral dosage form. ('357 Patent, col. 2:38-48).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶23). Independent claim 1 is representative:
- The unsolvated crystalline Form A of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione,
- which has a differential scanning calorimetry thermogram having an endotherm at approximately 270° C.
- The complaint reserves the right to assert infringement of other claims (Compl. ¶23).
U.S. Patent No. 8,193,219 - "Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione"
The Invention Explained
- Problem Addressed: Similar to the ’357 Patent, this patent addresses the need for well-characterized, stable solid forms of lenalidomide suitable for use in pharmaceutical products ('219 Patent, col. 2:26-49).
- The Patented Solution: The invention claims pharmaceutical compositions, such as tablets or capsules for oral administration, that contain a specific polymorphic form of lenalidomide ('219 Patent, Abstract). The claims are directed to compositions comprising "unsolvated crystalline Form A," which is defined by a characteristic XRPD pattern with specific peaks, combined with a pharmaceutically acceptable carrier or diluent ('219 Patent, col. 21:49-67).
- Technical Importance: By claiming the final drug formulation containing a specific polymorph, the patent aims to protect the commercial drug product itself, not just the active pharmaceutical ingredient, providing a distinct layer of intellectual property protection. ('219 Patent, col. 11:1-19).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" (Compl. ¶34). Independent claim 1 is representative:
- A pharmaceutical composition for oral administration
- comprising between 5 mg and 25 mg of an unsolvated crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
- having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 20,
- and a pharmaceutically acceptable excipient, diluent, or carrier,
- wherein the composition is a solid dosage form.
- The complaint reserves the right to assert infringement of other claims (Compl. ¶34).
U.S. Patent No. 8,431,598 - "Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione"
- Technology Synopsis: This patent claims solid forms of lenalidomide that are "substantially pure," comprising a high percentage (e.g., greater than 80%) of the unsolvated crystalline Form A ('598 Patent, col. 4:35-51). The invention addresses the need to ensure that the active ingredient in a pharmaceutical product consists predominantly of the single, desired polymorphic form to guarantee consistent performance and quality ('598 Patent, col. 2:20-56).
- Asserted Claims: The complaint asserts "one or more claims" without specification (Compl. ¶45). The patent's independent claims are 1, 5, 10, 14, 15, and 17.
- Accused Features: The accused features are Defendant’s proposed generic lenalidomide capsules (Compl. ¶16).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant Cipla's proposed generic lenalidomide capsules in 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg dosage strengths, for which Cipla filed ANDA No. 210435 seeking FDA approval (Compl. ¶¶1, 16).
Functionality and Market Context
- The proposed products are intended to be generic versions of Celgene’s REVLIMID®, an FDA-approved oral medication for treating certain cancers, including multiple myeloma (Compl. ¶7). The act of infringement alleged in the complaint is the statutory act of filing an ANDA seeking approval to market these generic products before the expiration of the patents-in-suit (Compl. ¶23). The complaint does not provide specific technical details regarding the composition of Cipla's proposed products, as such information is contained within the confidential ANDA submission.
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA for a drug claimed in a patent as a technical act of infringement (Compl. ¶23). The complaint does not contain a claim chart or specific factual allegations mapping the features of Cipla's proposed product to the elements of any asserted claim. The infringement theory appears to be based on the premise that for Cipla to obtain FDA approval for a generic version of REVLIMID®, its product must necessarily practice the inventions claimed in the patents-in-suit.
U.S. Patent No. 7,977,357 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| The unsolvated crystalline Form A of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione, | The complaint alleges that Cipla’s proposed products are generic lenalidomide capsules that will infringe one or more claims of the ’357 patent. | ¶23, ¶25 | col. 6:15-54 |
| which has a differential scanning calorimetry thermogram having an endotherm at approximately 270° C. | The complaint does not specify the characteristics of the accused product but alleges infringement based on the filing of the ANDA. | ¶23, ¶25 | col. 6:46-50; FIG. 4 |
U.S. Patent No. 8,193,219 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition for oral administration | The complaint alleges Cipla’s proposed generic lenalidomide capsules will infringe one or more claims of the ’219 patent. | ¶34, ¶36 | col. 11:1-19 |
| comprising between 5 mg and 25 mg of an unsolvated crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione | The accused products are identified as capsules in 5, 10, 15, 20, and 25 mg dosages. | ¶16 | col. 22:2-20 |
| having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 20, | The complaint does not provide specific details on the polymorph in the accused product but alleges infringement based on the ANDA filing. | ¶34, ¶36 | col. 6:20-24; FIG. 1 |
| and a pharmaceutically acceptable excipient, diluent, or carrier, wherein the composition is a solid dosage form. | The accused products are identified as lenalidomide capsules. | ¶16 | col. 22:2-20 |
Identified Points of Contention
- Factual Questions: A central issue will be the actual polymorphic composition of the lenalidomide active ingredient in Cipla's ANDA product. Discovery into the confidential ANDA submission will be required to determine if it contains the claimed "unsolvated crystalline Form A."
- Scope Questions: The dispute may turn on the interpretation of "approximately" as it modifies the XRPD peak locations and DSC endotherm temperatures. The breadth of this term will be a likely subject of claim construction.
- Technical Questions: A key question is whether Cipla's product meets the "unsolvated" limitation of the asserted claims, or if it contains other polymorphs, solvates, or hydrates of lenalidomide that would place it outside the scope of the claims.
V. Key Claim Terms for Construction
The Term: "approximately"
- Context and Importance: This term appears in the independent claims of both the ’357 and ’219 patents to qualify the numerical values of DSC endotherms and XRPD peaks. Its construction is critical because it defines the permissible range of deviation from the recited values, which will directly impact the scope of the claims and the infringement analysis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The repeated use of "about" and "approximately" throughout the specification when discussing analytical data suggests the patentees understood these measurements to have some inherent variability and did not intend to be limited to the exact numerical values disclosed ('357 Patent, col. 6:22, col. 6:49).
- Evidence for a Narrower Interpretation: The patents distinguish between multiple different polymorphs (A, B, C, etc.), each defined by its own set of distinct numerical peaks and thermal events ('357 Patent, col. 6:15-col. 10:48). An argument may be made that "approximately" must be construed narrowly enough to maintain this distinction between the different claimed and unclaimed forms.
The Term: "unsolvated crystalline Form A"
- Context and Importance: This term defines the specific polymorph at the heart of the asserted claims. Whether Cipla’s generic product infringes will depend on whether its active ingredient meets this definition. Practitioners may focus on this term because Cipla’s non-infringement defense will likely argue its product contains a different form.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patents define "Form A" through a collection of analytical properties, including XRPD, DSC, IR, and Raman data ('357 Patent, col. 6:15-54). A broad interpretation could suggest that a crystal form meeting the essential structural characteristics of Form A, even with minor deviations in some analytical data, would fall within the definition.
- Evidence for a Narrower Interpretation: The specification explicitly distinguishes "unsolvated" Form A from hydrated forms like Form B (hemihydrate) and Form E (dihydrate) ('357 Patent, col. 5:34-42). This suggests "unsolvated" is a material limitation intended to exclude forms containing bound water or solvent molecules. The claims themselves tie Form A to specific XRPD peaks and a DSC endotherm, suggesting these are required definitional elements.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Cipla will induce infringement by "intentionally encourag[ing] acts of direct infringement" and contribute to infringement because its proposed products are "especially adapted for a use that infringes... and that there is no substantial non-infringing use" (Compl. ¶¶ 26-27, 37-38, 48-49). These allegations are based on Cipla’s knowledge of the patents, evidenced by its Paragraph IV notice letter (Compl. ¶19).
- Willful Infringement: The complaint does not explicitly allege willful infringement but does state that the case is "an exceptional one" and requests an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. ¶¶ 30, 41, 52).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of factual characterization: what is the precise polymorphic form, or mixture of forms, of the lenalidomide active pharmaceutical ingredient contained in Cipla’s ANDA product? The outcome of the infringement analysis depends entirely on the answer, which will emerge from discovery of Cipla's confidential regulatory filings.
- A key legal question will be one of definitional scope: how will the court construe the term "approximately" in the context of the claimed analytical data? The degree of latitude afforded by this term will determine whether minor variations in Cipla’s product can successfully avoid a finding of literal infringement.
- The case will also present a central question of validity and enforceability: although not detailed in the complaint, Cipla’s Paragraph IV certification necessarily asserts that the patents-in-suit are invalid or unenforceable. The litigation will likely focus heavily on Cipla’s ability to prove these defenses, for example, by arguing that the claimed polymorphs were not new or were obvious over the prior art.