DCT
2:17-cv-03159
Celgene Corp v. Par Pharmaceutical Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Celgene Corporation (Delaware)
- Defendant: Par Pharmaceutical, Inc. (Delaware); Par Pharmaceutical Companies, Inc. (Delaware); Teva Pharmaceuticals USA, Inc. (Delaware); and Teva Pharmaceutical Industries Limited (Israel)
- Plaintiff’s Counsel: Saul Ewing LLP
- Case Identification: 2:17-cv-03159, D.N.J., 05/04/2017
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendants' systematic and continuous business contacts with the state, including registration to conduct business, and because the district will be a destination for the accused generic drug products.
- Core Dispute: Plaintiff alleges that Defendants’ submission of Abbreviated New Drug Applications (ANDAs) to the U.S. Food and Drug Administration seeking to market generic versions of Plaintiff's POMALYST® (pomalidomide) drug product constitutes an act of patent infringement.
- Technical Context: The patents relate to methods of using and formulating pomalidomide, an immunomodulatory compound, for the treatment of multiple myeloma, a type of blood cancer.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of Paragraph IV Notice Letters from Defendants. In these letters, Defendants certified that their proposed generic products would not infringe the patents-in-suit or that the patents are invalid and/or unenforceable.
Case Timeline
| Date | Event |
|---|---|
| 2002-05-17 | Priority Date for ’262, ’939, and ’428 Patents |
| 2009-05-19 | Priority Date for ’427 Patent |
| 2012-06-12 | U.S. Patent No. 8,198,262 Issues |
| 2014-03-18 | U.S. Patent No. 8,673,939 Issues |
| 2014-05-27 | U.S. Patent No. 8,735,428 Issues |
| 2014-09-09 | U.S. Patent No. 8,828,427 Issues |
| 2017-03-30 | Teva sends Paragraph IV Notice Letter to Celgene (no earlier than) |
| 2017-04-12 | Par sends Paragraph IV Notice Letter to Celgene (no earlier than) |
| 2017-05-04 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,198,262 - "Methods for treating multiple myeloma using 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione," issued June 12, 2012
The Invention Explained
- Problem Addressed: The patent describes a significant need for safe and effective methods of treating cancer, particularly for cancers that are refractory to conventional therapies such as chemotherapy and radiation, while reducing or avoiding the associated toxicities and side effects (’262 Patent, col. 3:9-14).
- The Patented Solution: The invention provides a method for treating multiple myeloma by administering a specific compound, 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione (pomalidomide), often in combination with a second active agent such as dexamethasone, according to a specific cyclic dosing regimen (’262 Patent, Abstract; col. 24:4-13). This immunomodulatory compound is described as being significantly more potent than thalidomide at inhibiting MM cell proliferation, as illustrated in the patent’s clinical study data (’262 Patent, FIG. 1; col. 32:1-17).
- Technical Importance: The invention provided a specific, high-potency compound and dosing protocol for treating multiple myeloma, a cancer for which new therapeutic options were needed, particularly for relapsed or refractory patient populations (’262 Patent, col. 16:36-52).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims of the patent, with independent claims 1 and 20 being representative method claims (Compl. ¶47).
- Essential elements of independent claim 1 include:
- A method of treating multiple myeloma.
- Administering to a patient a compound (pomalidomide) having a specific chemical formula, or its salt, solvate, or stereoisomer.
- The compound is administered at a dose of about 1 mg to about 5 mg per day.
- The administration occurs for 21 consecutive days followed by seven consecutive days of rest in a 28-day cycle.
- The method includes co-administration of 40 mg of dexamethasone.
- The complaint does not explicitly reserve the right to assert dependent claims, but alleges infringement of "one or more claims" (Compl. ¶47).
U.S. Patent No. 8,673,939 - "Methods for treating multiple myeloma with 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione," issued March 18, 2014
The Invention Explained
- Problem Addressed: This patent, related to the ’262 Patent, also addresses the need for effective treatments for multiple myeloma, particularly for patients whose disease is relapsed, refractory, or has progressed after a previous therapy (’939 Patent, col. 3:12-21).
- The Patented Solution: The patent claims a method of treating a specific patient population—those with relapsed or refractory multiple myeloma who have received previous therapy—by administering pomalidomide in a cyclic regimen (’939 Patent, col. 4:50-59). The specification provides detailed results from clinical studies on such patient populations, demonstrating the efficacy of the method (’939 Patent, col. 35:21-54).
- Technical Importance: The invention defined a specific treatment protocol for a challenging patient population (relapsed/refractory multiple myeloma) for whom prior treatments had failed, offering a new therapeutic option (’939 Patent, col. 3:9-11).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims, with independent claims 1 and 26 being representative (Compl. ¶65).
- Essential elements of independent claim 1 include:
- A method of treating multiple myeloma in a patient who has received previous therapy.
- Administering from about 1 mg to about 5 mg per day of pomalidomide.
- The compound is administered in one or more cycles, each comprising a period of administration followed by a period of rest.
- The patient's multiple myeloma is relapsed, refractory, or relapsed and refractory.
- The complaint does not explicitly reserve the right to assert dependent claims, but alleges infringement of "one or more claims" (Compl. ¶65).
U.S. Patent No. 8,735,428 - "Methods for treating multiple myeloma with 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione," issued May 27, 2014
- Technology Synopsis: This patent addresses the treatment of multiple myeloma in patients who have already undergone therapy but whose disease has progressed. The claimed solution is a method of administering pomalidomide according to a specified cyclic regimen to this patient population (’428 Patent, Abstract; col. 4:50-65).
- Asserted Claims: Independent claims 1 and 22 are asserted (Compl. ¶83).
- Accused Features: The accused features are the intended uses of Defendants' proposed generic pomalidomide products for treating multiple myeloma, as will allegedly be instructed on their product labeling (Compl. ¶¶ 16, 86-87).
U.S. Patent No. 8,828,427 - "Formulations of 4-amino-2-(2,6-dioxopiperidine-3-YL)isoindoline-1,3-dione," issued September 9, 2014
- Technology Synopsis: This patent addresses the need for stable, effective oral dosage forms of pomalidomide. The patented solution is a specific pharmaceutical formulation for a capsule containing pomalidomide, pregelatinized starch, sodium stearyl fumarate, and spray dried mannitol, which provides advantageous physical and pharmaceutical properties for manufacturing and administration (’427 Patent, Abstract; col. 1:12-16).
- Asserted Claims: Independent claims 1, 3, 5, 7, 9, and 11 are asserted (Compl. ¶101).
- Accused Features: The accused features are the physical formulations of the generic pomalidomide capsules that Defendants seek to market, which are alleged to contain the same active ingredient and excipients as claimed in the patent (Compl. ¶¶ 38, 42, 103-105).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the generic pomalidomide capsule products ("Par's Proposed Products" and "Teva's Proposed Products") that are the subject of ANDA Nos. 210245 (Par) and 209956 (Teva) (Compl. ¶1). Par's ANDA covers 2 mg, 3 mg, and 4 mg capsules, while Teva's covers 1 mg, 2 mg, 3 mg, and 4 mg capsules (Compl. ¶¶38, 42).
Functionality and Market Context
- The proposed generic products are intended to be bioequivalent to Celgene's POMALYST® drug product, which is an FDA-approved medication for the treatment of multiple myeloma (Compl. ¶13). The complaint alleges that the labeling for these generic products will instruct and encourage physicians and patients to administer them according to the methods claimed in the patents-in-suit (Compl. ¶16). Defendants are major generic pharmaceutical companies, and Teva is described as "the leading generic drug company in the United States" (Compl. ¶32).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed claim chart. The infringement allegations are based on the statutory act of filing an ANDA under 35 U.S.C. § 271(e)(2) and the future infringement that is alleged will occur upon commercialization. The following table summarizes the infringement theory for a representative claim based on the complaint's narrative allegations.
’262 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating multiple myeloma... | The complaint alleges Defendants' proposed products are for the treatment of multiple myeloma. | ¶¶13, 16, 38, 42 | col. 35:35-40 |
| which comprises administering to a patient... from about 1 mg to about 5 mg per day of a compound having the formula... | The complaint states Defendants seek approval to market capsules in dosages of 1, 2, 3, and 4 mg, falling within the claimed range. | ¶¶38, 42 | col. 18:1-4 |
| for 21 consecutive days followed by seven consecutive days of rest from administration of said compound in a 28 day cycle... | The complaint alleges that the labeling for Defendants' products will instruct and encourage administration according to the methods claimed in the patents-in-suit, which includes the specified cycle. | ¶16 | col. 24:4-13 |
| and (b) 40 mg of dexamethasone. | The complaint alleges Defendants' product labels will instruct use according to the patented methods, which includes co-administration with dexamethasone. | ¶16 | col. 54:14-23 |
’939 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating multiple myeloma... wherein the patient has received previous therapy for multiple myeloma... | The complaint alleges the proposed generic products will be marketed for treating multiple myeloma, including in patients who have received prior therapies, consistent with the approved uses for POMALYST®. | ¶¶13, 16 | col. 35:21-25 |
| wherein the multiple myeloma is relapsed, refractory, or relapsed and refractory multiple myeloma. | The proposed products are allegedly intended for patient populations with relapsed or refractory multiple myeloma, as will be described on the product labeling. | ¶16 | col. 35:21-25 |
| from about 1 mg to about 5 mg per day of a compound... administered in one or more cycles, each of which comprises... a period of time followed by a period of rest. | The complaint alleges Defendants seek to market capsules in the claimed dosage strengths and that the labeling will instruct administration in a cyclic manner consistent with the patent claims. | ¶¶16, 38, 42 | col. 33:50-58 |
- Identified Points of Contention:
- Validity and Enforceability: The complaint states that Defendants' Paragraph IV certifications allege the patents-in-suit are "invalid, unenforceable, and/or will not be infringed" (Compl. ¶¶40, 44). This suggests the central legal dispute will be over the patentability of the claimed methods, raising questions such as whether the claimed dosing regimens were obvious in light of prior art related to immunomodulatory drugs and cancer treatment.
- Infringement Scope: While the complaint alleges future infringement, a potential point of contention could be whether the instructions on the Defendants' proposed labels will require administration in a manner that meets every limitation of the asserted claims. For example, a question may arise as to whether the label provides for or allows substantial non-infringing uses, which could impact the claims for induced infringement.
V. Key Claim Terms for Construction
The Term: "treating multiple myeloma"
Context and Importance: This term defines the fundamental purpose and scope of the method claims. The construction of "treating" is critical to determining whether the administration of the accused products for the indications on their proposed labels falls within the claim scope. Practitioners may focus on this term because its breadth could determine whether palliative care, slowing of progression, or only reversal of the disease constitutes "treating."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes methods of "treating, preventing and/or managing" cancer, suggesting "treating" could encompass a range of therapeutic outcomes beyond a cure (e.g., ’262 Patent, col. 3:40-42).
- Evidence for a Narrower Interpretation: The detailed description provides specific clinical trial endpoints and outcomes, such as achieving a certain percentage reduction in M-protein levels, which could be argued to define the scope of what the patent discloses as effective "treating" (’262 Patent, col. 35:21-54).
The Term: "a period of rest"
Context and Importance: This term is a crucial limitation of the claimed cyclic dosing regimen. Its definition will determine what constitutes an infringing cycle of administration. A dispute could arise over whether "rest" requires complete cessation of the drug or allows for a reduced dosage.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail for analysis of broader interpretations.
- Evidence for a Narrower Interpretation: Claim 1 of the ’262 patent specifies "seven consecutive days of rest from administration of said compound in a 28 day cycle," which provides a precise temporal definition. The specification further describes this as "21-day treatment, 7-day rest cycles," reinforcing a specific meaning of cessation for a defined period (’262 Patent, col. 54:37-41).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendants will induce infringement by virtue of their proposed product labeling, which will allegedly instruct and encourage physicians and patients to use the generic products in accordance with the patented methods. Knowledge is alleged based on Defendants' submission of Paragraph IV certifications, which demonstrates awareness of the patents-in-suit (Compl. ¶¶50, 59, 68, 77, 86, 95, 104, 113).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it alleges that each case is an "exceptional one" and requests an award of reasonable attorneys' fees under 35 U.S.C. § 285, which suggests an assertion of litigation misconduct or infringement that is egregious in character (Compl. ¶¶54, 72, 90, 108).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue, triggered by the Defendants' Paragraph IV certifications, will be one of patent validity: will the court find that the claimed methods of using pomalidomide in specific patient populations and dosing regimens are non-obvious and novel over prior art treatments for multiple myeloma?
- A key question for infringement will be one of label-induced infringement: does the language of the Defendants' proposed product labels, which must be consistent with the approved label for POMALYST®, inevitably direct medical professionals to prescribe and patients to use the generic products in a manner that practices all limitations of the asserted method claims?