DCT
1:13-cv-01644
Andrulis Pharma Corp v. Celgene Corp
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Andrulis Pharmaceuticals Corp. (Maryland)
- Defendant: Celgene Corp. (Delaware)
- Plaintiff’s Counsel: Frommer Lawrence & Haug LLP; Morris James LLP
- Case Identification: 1:13-cv-01644, D. Del., 10/02/2013
- Venue Allegations: Venue is asserted based on Defendant being a Delaware corporation that regularly conducts business in the state.
- Core Dispute: Plaintiff alleges that Defendant’s promotion and sale of its cancer drugs Thalomid® and Revlimid® for use in combination with the alkylating agent melphalan induces infringement of a patent covering combination cancer therapies.
- Technical Context: The lawsuit concerns chemotherapeutic regimens for multiple myeloma, a type of blood cancer, specifically the use of thalidomide or its analogues in conjunction with other anti-cancer agents.
- Key Procedural History: The complaint alleges that Defendant cited the patent-in-suit during the prosecution of its own patents, suggesting pre-suit knowledge of Plaintiff's technology. The complaint also notes that Defendant has been the subject of federal and state investigations regarding the promotion of its drugs for unapproved, or "off-label," uses.
Case Timeline
| Date | Event |
|---|---|
| 1964-01-01 | FDA approves Alkeran® (melphalan) |
| 1995-06-06 | ’346 Patent Priority Date |
| 1998-01-01 | FDA approves Thalomid® (thalidomide) |
| 1998-01-01 | Alleged discussions by Celgene sales reps on Thalomid® use begin |
| 2000-10-31 | U.S. Patent No. 6,140,346 issues |
| 2003-01-01 | Celgene begins distributing Alkeran® under its own label |
| 2005-01-01 | Celgene allegedly knew of the ’346 Patent |
| 2005-01-01 | FDA approves Revlimid® (lenalidomide) |
| 2005-01-01 | Alleged discussions by Celgene sales reps on Revlimid® use begin |
| 2008-01-01 | NCCN allegedly identifies MPT therapy as appropriate for myeloma |
| 2012-01-01 | NCCN allegedly identifies MPL therapy as appropriate for myeloma |
| 2013-10-02 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,140,346 - Treatment of Cancer with Thalidomide Alone or in Combination with Other Anti-Cancer Agents
The Invention Explained
- Problem Addressed: The patent describes the significant challenges in cancer treatment, including the toxicity of conventional therapies like chemotherapy and radiation, as well as the development of drug resistance in tumors (ʼ346 Patent, col. 3:57-61; col. 5:1-7).
- The Patented Solution: The invention discloses methods of treating cancer by administering thalidomide, either by itself or, more centrally to this dispute, in combination with other anti-cancer drugs, such as alkylating agents (ʼ346 Patent, Abstract; col. 1:7-16). The patent proposes that thalidomide works in part by inhibiting angiogenesis—the formation of new blood vessels necessary for tumor growth—and by modulating the immune system (ʼ346 Patent, col. 8:11-25).
- Technical Importance: The patent proposed a new therapeutic use for thalidomide, a compound with a history of severe side effects, by leveraging its anti-inflammatory and anti-angiogenic properties for oncology (ʼ346 Patent, col. 8:11-25; col. 8:60-64).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" without specifying them (Compl. ¶81). Based on the infringement theory, which centers on the combined use of thalidomide/lenalidomide with melphalan, method claim 2 appears to be the primary claim at issue.
- Independent Claim 2 recites:
- A method for the treatment of neoplastic diseases in a mammal
- which comprises administering to said afflicted mammal enhanced therapeutically-effective amounts of thalidomide
- in combination with effective amounts of other alkylating agent
- selected from a specific group that includes melphalan
- wherein the neoplastic diseases are sensitive to the combination.
III. The Accused Instrumentality
Product Identification
The complaint identifies Defendant's drugs Thalomid® (active ingredient: thalidomide), Revlimid® (active ingredient: lenalidomide, a "thalidomide analogue"), and Alkeran® (active ingredient: melphalan, an "alkylating agent") (Compl. ¶¶ 15, 19, 25).
Functionality and Market Context
The infringement allegations do not concern the drugs individually but rather their combined use to treat multiple myeloma (Compl. ¶81). The complaint asserts that Defendant actively promotes the off-label use of Thalomid® or Revlimid® in conjunction with melphalan (found in Alkeran®) (Compl. ¶¶ 83, 85). This combination therapy, while not an FDA-approved indication for the drugs, has allegedly become a "primary therapy for many patients with multiple myeloma," in part due to Defendant's promotional efforts (Compl. ¶40). A figure from the complaint shows the chemical structure of thalidomide (Compl. ¶75). A subsequent figure illustrates the similar chemical structure of lenalidomide, which the plaintiff identifies as a thalidomide analogue (Compl. ¶76).
IV. Analysis of Infringement Allegations
’346 Patent Infringement Allegations
| Claim Element (from Independent Claim 2) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for the treatment of neoplastic diseases in a mammal... | The complaint alleges Celgene promotes and encourages the use of its drugs for treating multiple myeloma, a neoplastic disease. | ¶40 | col. 2:26-28 |
| ...which comprises administering to said afflicted mammal enhanced therapeutically-effective amounts of thalidomide... | Doctors are allegedly induced to administer Thalomid® (thalidomide) and Revlimid® (a thalidomide analogue, alleged to infringe under the doctrine of equivalents). | ¶77, ¶81, ¶82 | col. 10:16-18 |
| ...in combination with effective amounts of other alkylating agent selected from the group consisting of...melphalan... | The accused combination therapy involves co-administration with Alkeran®, which contains melphalan, an alkylating agent explicitly listed in the patent's claim. | ¶36, ¶81 | col. 10:53-54 |
| ...wherein said neoplastic diseases are sensitive to said enhanced combination. | The complaint alleges the combination therapy is effective for multiple myeloma, citing NCCN guidelines and clinical trial results, which suggests the disease is sensitive to the treatment. | ¶36, ¶61 | col. 18:11-13 |
Identified Points of Contention
- Scope Questions: A central issue for the court may be whether the claim term "thalidomide" can be interpreted to cover lenalidomide, the active ingredient in Revlimid®. As the complaint asserts infringement "literally or through equivalence" (Compl. ¶81), the analysis will likely focus on whether lenalidomide performs substantially the same function, in the same way, to achieve the same result as thalidomide in the claimed method.
- Technical Questions: The complaint's theory rests on induced infringement, which requires proof that Defendant's actions actually caused doctors to perform the infringing combination therapy. A key evidentiary question is what specific proof links Celgene’s promotional activities—such as communications from sales representatives or the distribution of clinical studies (Compl. ¶¶ 55-62)—to physicians prescribing the specific off-label combination of thalidomide/lenalidomide with melphalan.
V. Key Claim Terms for Construction
The Term: "thalidomide"
- Context and Importance: Practitioners may focus on this term because a significant portion of the accused conduct involves Revlimid®, which contains the analogue lenalidomide, not thalidomide itself (Compl. ¶25). The viability of the infringement claim against Revlimid® hinges on whether this term is construed to encompass structurally similar analogues or if infringement can be proven under the doctrine of equivalents.
- Evidence for a Broader Interpretation: The complaint itself provides the basis for an equivalence argument by presenting the chemical structures of thalidomide and lenalidomide side-by-side to emphasize their similarity (Compl. ¶¶ 75-77).
- Evidence for a Narrower Interpretation: The patent specification and claims consistently use the specific term "thalidomide" without reference to analogues, derivatives, or a broader class of compounds ('346 Patent, Claims 1-3). This specificity may support a construction limited to the precise molecular structure of thalidomide.
The Term: "in combination with"
- Context and Importance: This term is critical because the accused drugs are not sold as a single co-formulated product. Infringement of the method claim requires that the administration of thalidomide (or its analogue) and an alkylating agent occur "in combination." The dispute may center on the required temporal and therapeutic relationship between the administration of the two drugs to satisfy this limitation.
- Evidence for a Broader Interpretation: The specification provides examples of combination regimens where drugs are administered simultaneously as well as on different schedules (e.g., thalidomide administered daily, while another agent is given every six weeks), suggesting the term is not limited to co-formulation or simultaneous dosing ('346 Patent, col. 11:23-34).
- Evidence for a Narrower Interpretation: A party could argue that "in combination" implies a more integrated therapeutic protocol than a physician's independent decision to prescribe two separate drugs. The existence of composition claims in the patent for a single formulation containing both agents (ʼ346 Patent, Claims 1, 3) might be used to argue for a narrower reading of the method claim's "in combination" language.
VI. Other Allegations
Indirect Infringement
The complaint's primary theory is induced infringement (Compl. ¶85). It alleges Celgene took "affirmative steps to induce infringement" by communicating the benefits of using its drugs in the claimed off-label combination to doctors through sales representatives, medical liaisons, publications, and press releases (Compl. ¶¶ 55-63, 85).
Willful Infringement
Willfulness is alleged based on both pre- and post-suit conduct. The complaint asserts pre-suit knowledge by alleging Celgene cited the ʼ346 patent during the prosecution of its own patents as early as 2005 (Compl. ¶¶ 11, 13). It further alleges that any continued infringement after the filing of the complaint is willful (Compl. ¶86).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of chemical scope and equivalence: can the claim term "thalidomide", which is a specific chemical entity, be legally construed to cover the accused product Revlimid®, which contains the related but distinct molecule lenalidomide? The resolution of this question will substantially define the scope of potential damages.
- A key evidentiary question will be one of intent and causation: what evidence demonstrates that Celgene’s promotional activities for its drugs were undertaken with the specific intent to encourage physicians to prescribe the patented combination therapy, and did those activities in fact cause the direct infringement by physicians?