DCT
2:22-cv-03753
Celgene Corp v. Qilu Pharmaceutical Co Ltd
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Celgene Corporation (Delaware)
- Defendant: Qilu Pharmaceutical Co. Ltd. (China)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP
- Case Identification: 2:22-cv-03753, D.N.J., 06/13/2022
- Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign corporation that may be sued in any judicial district. The complaint also alleges that Defendant’s U.S. subsidiary maintains an established place of business in New Jersey and that Defendant has conducted business in the district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration for generic lenalidomide (Revlimid®) capsules constitutes an act of infringement of patents related to specific polymorphic forms of the lenalidomide compound.
- Technical Context: The technology involves distinct crystalline structures (polymorphs) of the active pharmaceutical ingredient lenalidomide; such forms can affect a drug's stability, solubility, and manufacturing process, making control over a specific, consistent form commercially and regulatorily significant.
- Key Procedural History: The patents-in-suit are listed in the FDA’s "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") for Plaintiff’s Revlimid® product. The suit was triggered by Defendant’s submission of an ANDA with a "Paragraph IV Certification," asserting that its proposed generic product would not infringe the patents-in-suit or that the patents are invalid.
Case Timeline
| Date | Event |
|---|---|
| 2003-09-04 | Priority Date for ’800 and ’217 Patents |
| 2008-12-16 | U.S. Patent No. 7,465,800 Issues |
| 2010-12-21 | U.S. Patent No. 7,855,217 Issues |
| 2022-04-29 | Defendant sends Paragraph IV Certification Notice Letter |
| 2022-06-13 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,465,800 - "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 explains that a single chemical compound can often exist in multiple different solid crystalline forms, or polymorphs. (’800 Patent, col. 1:19-24). These different forms can possess distinct physical and chemical properties that affect a drug’s manufacturability, stability, and bioavailability, creating a technical challenge to identify and reliably produce a specific, advantageous form for a pharmaceutical product. (’800 Patent, col. 1:28-44).
- The Patented Solution: The invention claims to solve this problem by disclosing the discovery and characterization of several novel polymorphic forms of lenalidomide, identified as Forms A through H. (’800 Patent, col. 2:58-63). The patent provides detailed analytical data, such as X-ray powder diffraction (XRPD) patterns and thermal analysis, that serve as unique identifiers for these specific crystalline structures, enabling their consistent production and formulation. (’800 Patent, col. 4:51-68).
- Technical Importance: The isolation and characterization of stable, pure polymorphs of an active pharmaceutical ingredient is a critical step in drug development, as it allows for predictable performance and is a key requirement for regulatory approval. (’800 Patent, col. 1:45-56).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" without specifying which claims are asserted (Compl. ¶26). Independent claim 1 is representative of the patent's core subject matter.
- Independent Claim 1:
- Crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
- hemihydrate
U.S. Patent No. 7,855,217 - "Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione"
The Invention Explained
- Problem Addressed: As a divisional of the application that led to the ’800 Patent, this patent addresses the same technical problem of identifying and controlling specific, stable polymorphic forms of lenalidomide for pharmaceutical use. (’217 Patent, col. 1:24-49).
- The Patented Solution: The patent also discloses the discovery of novel polymorphic forms of lenalidomide and provides their distinguishing characteristics, focusing on compositions that contain a high purity of a specific polymorph. (’217 Patent, Abstract; col. 2:60-65).
- Technical Importance: The invention provides a basis for creating drug products with a consistently high percentage of a single, desired polymorph, which is essential for ensuring uniform quality and performance across manufacturing batches. (’217 Patent, col. 1:50-59).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" without specifying which claims are asserted (Compl. ¶35). Independent claim 1 is representative.
- Independent Claim 1:
- A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
- comprising crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate,
- wherein the crystalline...hemihydrate is present at greater than about 80% by weight of the solid form.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant’s proposed generic lenalidomide capsules in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg dosages, which are the subject of ANDA No. 217265 submitted to the FDA for approval (collectively, "Qilu’s Proposed Products") (Compl. ¶¶ 1, 18).
Functionality and Market Context
- Qilu’s Proposed Products are generic versions of Celgene’s Revlimid® drug product and are intended to be therapeutic equivalents. (Compl. ¶1). The act of infringement alleged is the submission of the ANDA itself, which seeks FDA approval to market these generic products in the United States prior to the expiration of the patents-in-suit. (Compl. ¶¶ 21, 26, 35). The complaint does not provide technical details regarding the specific polymorphic form of lenalidomide contained in Qilu's Proposed Products.
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed claim chart or element-by-element infringement analysis. The infringement allegation is statutory under 35 U.S.C. § 271(e)(2)(A), where the submission of an ANDA for a drug claimed in a patent is an act of infringement. The following table summarizes the infringement theory that may be inferred from the complaint's allegations.
No probative visual evidence provided in complaint.
’800 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione | The complaint alleges Qilu’s Proposed Products are lenalidomide capsules, from which it can be inferred that the active ingredient is the claimed crystalline compound. | ¶¶18, 26 | col. 4:53-58 |
| hemihydrate | Based on the general allegation of infringement, it is inferred that the lenalidomide in Qilu's Proposed Products is the specific hemihydrate crystal form. | ¶26 | col. 6:53-68 |
’217 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione | Qilu's Proposed Products are solid oral dosage capsules containing lenalidomide. | ¶¶18, 35 | col. 1:11-18 |
| comprising crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate, | It is inferred from the complaint’s infringement allegation that the solid form in Qilu's Proposed Products comprises the claimed crystalline hemihydrate of lenalidomide. | ¶35 | col. 6:53-68 |
| wherein the crystalline...hemihydrate is present at greater than about 80% by weight of the solid form. | It is inferred from the complaint’s infringement allegation that the crystalline hemihydrate in Qilu's Proposed Products meets the claimed purity threshold of greater than 80% by weight. | ¶35 | col. 4:34-44 |
- Identified Points of Contention:
- Factual Question: The central dispute will be factual and evidentiary: what is the actual polymorphic composition of the lenalidomide active pharmaceutical ingredient (API) in the product described in Qilu’s confidential ANDA? Specifically, does it contain the claimed "hemihydrate" form, and if so, at what level of purity?
- Technical Question: What do analytical tests (e.g., XRPD, TGA, Karl Fischer titration) of Qilu’s ANDA product reveal about its crystal structure and water content, and how does that data compare to the characteristics disclosed and claimed in the patents-in-suit?
V. Key Claim Terms for Construction
The complaint does not provide a basis for claim construction analysis. However, based on the technology and asserted claims, the following terms may be central to the dispute.
The Term: "hemihydrate" (’800 Patent, Claim 1)
Context and Importance: This term defines the specific stoichiometry of water within the lenalidomide crystal lattice (one molecule of water per two molecules of lenalidomide). Infringement of the ’800 Patent hinges on whether Qilu’s product is properly characterized as a hemihydrate.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party may argue that the term should be given its plain and ordinary meaning as understood in the chemical arts, without being limited to other properties disclosed in the specification. The patent does not provide an explicit, special definition.
- Evidence for a Narrower Interpretation: The specification consistently associates the term "hemihydrate" with a specific polymorph, "Form B" (’800 Patent, col. 7:1-5). A party may argue that the term "hemihydrate" should be construed as being limited to the specific analytical properties disclosed for Form B, such as its characteristic XRPD peaks or the thermal data showing a weight loss of "about 3.1%" upon heating (’800 Patent, col. 7:1-2).
The Term: "about 80% by weight" (’217 Patent, Claim 1)
Context and Importance: This term sets the purity threshold for the claimed solid form. The dispute may turn on whether the measured purity of Qilu’s product falls within the range connoted by "about."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "about" is used throughout the patent when discussing percentages, suggesting an intent to encompass values that account for standard measurement variability in analytical chemistry. The patent’s definition of "substantially pure" lists several percentage ranges, including "greater than about 80% by weight," indicating the term is meant to define a category rather than a precise number. (’217 Patent, col. 4:34-44).
- Evidence for a Narrower Interpretation: A party may argue that the precision of the analytical techniques described in the specification (e.g., TGA, XRPD) warrants a narrow reading of "about," confining it to a minimal degree of instrumental error.
VI. Other Allegations
- Indirect Infringement: The complaint includes allegations of both induced and contributory infringement. It alleges inducement will occur upon FDA approval when Qilu intentionally encourages direct infringement by medical professionals and patients through its product labeling and marketing (Compl. ¶¶ 29, 38). It alleges contributory infringement on the basis that Qilu’s Proposed Products are especially adapted for an infringing use and have no substantial non-infringing use (Compl. ¶¶ 30, 39).
- Willful Infringement: The complaint does not use the word "willful," but it alleges this is an "exceptional case" and requests attorneys’ fees under 35 U.S.C. § 285 (Compl. ¶¶ 33, 42). The allegation of knowledge is supported by Defendant’s sending of the Paragraph IV Notice Letter, which is a prerequisite for the litigation itself (Compl. ¶24).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of factual characterization: what is the precise polymorphic identity and purity of the lenalidomide API described in Qilu’s confidential ANDA? The resolution of this question, based on competing expert analyses of analytical data, will likely be dispositive of the infringement question.
- A second core issue may be one of claim scope: can the term "hemihydrate," as used in the ’800 patent, be interpreted to have its plain and ordinary meaning, or will it be limited by the court to a crystal form that also exhibits the other specific analytical properties disclosed for "Form B" in the specification?
- A third key question will be one of validity: although not detailed in the complaint, Defendant’s Paragraph IV certification asserts that the patents are invalid. The case will therefore involve an examination of whether the claimed polymorphic forms were anticipated or rendered obvious by prior art relating to lenalidomide or pharmaceutical crystallization techniques.