DCT
1:10-cv-00112
Genzyme Corp v. Cobrek Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Genzyme Corporation (Massachusetts)
- Defendant: Cobrek Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Goldberg Kohn, Ltd.
- Case Identification: 1:10-cv-00112, N.D. Ill., 01/07/2010
- Venue Allegations: Venue is alleged to be proper in the Northern District of Illinois because Defendant has a principal place of business in the district and has previously availed itself of the court by filing counterclaims in unrelated litigation.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's Hectorol® (doxercalciferol) injectable product constitutes an act of infringement of two patents covering the drug's method of use and formulation.
- Technical Context: The technology relates to vitamin D analog-based treatments for secondary hyperparathyroidism, a common and serious complication of end-stage renal disease.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a November 2009 notification letter from Cobrek regarding its ANDA filing, which included a Paragraph IV certification asserting that Plaintiff's patents are invalid and/or not infringed. The complaint notes a related, prior action against Pentech Pharmaceuticals, which reportedly transferred its interest in the ANDA to Cobrek. Subsequent to the filing of this complaint, the provided documents show that all claims of the '211 patent were cancelled in an inter partes reexamination, which would be expected to terminate the controversy regarding that patent.
Case Timeline
| Date | Event |
|---|---|
| 1988-08-02 | ’116 Patent Priority Date |
| 1997-02-11 | ’116 Patent Issue Date |
| 2000-04-06 | FDA Approval of Hectorol® Injectable |
| 2002-09-18 | ’211 Patent Priority Date |
| 2006-12-12 | ’211 Patent Issue Date |
| 2008-01-08 | Pentech sends ANDA notification letter to Genzyme |
| 2008-02-21 | Genzyme files suit against Pentech |
| 2008-04-01 | Genzyme lists ’116 and ’211 patents with FDA for Hectorol® (approx. date) |
| 2009-11-24 | Cobrek sends ANDA notification letter to Genzyme |
| 2010-01-07 | Complaint Filing Date |
| 2012-08-28 | Inter Partes Reexamination Certificate issues, cancelling all claims of the '211 patent |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,602,116 - "Method For Treating And Preventing Secondary Hyperparathyroidism," issued February 11, 1997
The Invention Explained
- Problem Addressed: The patent describes the problem of secondary hyperparathyroidism in patients with end-stage renal disease, where the body cannot produce enough active vitamin D, leading to bone loss (renal osteodystrophy) ('116 Patent, col. 2:21-30). Conventional treatments using active vitamin D3 analogs were associated with significant toxicity, such as hypercalcemia, at the doses required for efficacy ('116 Patent, col. 2:5-14).
- The Patented Solution: The invention is a method for treating this condition by administering a vitamin D2 analog, specifically 1α-hydroxyvitamin D2 (doxercalciferol). The patent asserts that vitamin D2 analogs provide the necessary therapeutic effect of lowering parathyroid hormone (PTH) levels but with significantly lower toxicity compared to their vitamin D3 counterparts, offering an improved therapeutic window ('116 Patent, col. 4:11-34).
- Technical Importance: The invention proposed a therapeutic alternative with a potentially superior safety profile for managing a chronic and debilitating condition affecting the large population of patients on dialysis ('116 Patent, col. 3:36-41).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent (Compl. ¶19). Independent claim 1 is representative.
- Independent Claim 1 requires:
- A method for lowering or maintaining lowered serum parathyroid hormone
- in human patients suffering from hyperparathyroidism secondary to end stage renal disease
- comprising administering an effective amount of a vitamin D analog of a specific chemical structure (formula I)
- The general allegation in the complaint implicitly reserves the right to assert other independent and dependent claims.
U.S. Patent No. 7,148,211 - "Formulation For Lipophilic Agents," issued December 12, 2006
The Invention Explained
- Problem Addressed: The patent addresses the difficulty of creating stable, injectable (parenteral) formulations for lipophilic (fat-soluble) drugs like doxercalciferol ('211 Patent, col. 3:11-18). Prior art solutions often involved high concentrations of organic solvents, which can cause pain on injection, or used buffering and chelating agents that could introduce contaminants like aluminum, a concern for dialysis patients ('211 Patent, col. 3:19-29).
- The Patented Solution: The invention discloses a pharmaceutical formulation that solubilizes a lipophilic agent in a largely aqueous vehicle. This is achieved by using a specific combination of a non-ionic solubilizer (polysorbate 20) and a lipophilic antioxidant (butylated hydroxytoluene, or BHT), with an optional agent like ethanol. This combination creates a stable formulation suitable for injection without requiring problematic excipients ('211 Patent, Abstract; col. 4:30-45).
- Technical Importance: This technology provided a method for creating a commercially viable, stable, and safe injectable product for lipophilic drugs, which is particularly important for administering medications to patients during dialysis sessions ('211 Patent, col. 3:15-18).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent (Compl. ¶28). Independent claim 1 is representative.
- Independent Claim 1 requires:
- A parenteral formulation
- comprising doxercalciferol (a lipophilic drug)
- comprising polysorbate 20 (a non-ionic solubilizer) at "about 0.05% to about 5% w/w"
- comprising butylated hydroxytoluene (a lipophilic antioxidant) at "about 20 to about 2000 ppm"
- comprising an optional agent of ethanol at "0 to 30% w/w"
- and an aqueous vehicle
- As with the '116 patent, the general allegation implicitly covers all claims.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Cobrek's Proposed Generic Product," which is a generic version of doxercalciferol injectable (2 µg/mL) described in ANDA No. 90-040 (Compl. ¶14).
Functionality and Market Context
- The product is intended to be a generic substitute for Genzyme's Hectorol® injectable, which is used to treat secondary hyperparathyroidism in patients with chronic kidney disease on dialysis (Compl. ¶9, ¶14). The legal act of infringement alleged in the complaint is the submission of the ANDA itself, which seeks FDA approval to market the generic product for this patented use prior to the expiration of the patents-in-suit (Compl. ¶19, ¶28).
IV. Analysis of Infringement Allegations
The complaint does not contain claim charts or detailed, element-by-element infringement allegations. The infringement theory is based on the statutory act of infringement under 35 U.S.C. § 271(e)(2), where filing an ANDA for a drug claimed in a patent is sufficient to create a case or controversy.
No probative visual evidence provided in complaint.
’116 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for lowering or maintaining lowered serum parathyroid hormone in human patients suffering from hyperparathyroidism secondary to end stage renal disease... | Cobrek's ANDA seeks approval for a product indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. | ¶9, ¶14 | col. 2:21-30 |
| ...comprising: administering to said patients an effective amount of a vitamin D analog...said analog comprising formula (I) | The active ingredient in Cobrek's Proposed Generic Product is doxercalciferol, which is a vitamin D analog of formula (I). The product label will instruct administration of an effective amount for the indicated condition. | ¶14, ¶16 | col. 5:39-44 |
- Identified Points of Contention:
- Scope Questions: The primary dispute will likely concern inducement of infringement. A key question is whether the instructions for use in Cobrek's proposed product label will direct physicians and patients to perform all the steps of the claimed method.
- Technical Questions: The case may raise questions about whether the administration of Cobrek's product necessarily results in "lowering or maintaining lowered serum parathyroid hormone" levels as required by the claim, although this is the intended therapeutic outcome.
’211 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A parenteral formulation, comprising a lipophilic drug which is doxercalciferol... | Cobrek's ANDA product is an injectable (parenteral) formulation containing the active ingredient doxercalciferol. | ¶14, ¶25 | col. 15:1-2 |
| ...a non-ionic solubilizer which is polysorbate 20...a lipophilic antioxidant which is butylated hydroxytoluene...an optional agent which is ethanol...and an aqueous vehicle. | The complaint alleges on information and belief that Cobrek's ANDA describes a formulation that contains these specific excipients. | ¶25, ¶30 | col. 9:32-42 |
- Identified Points of Contention:
- Scope Questions: A central dispute would have been whether the concentrations of polysorbate 20 and BHT in Cobrek's formulation fall within the ranges claimed with the term "about."
- Technical Questions: The core issue is factual: does the formulation described in Cobrek's confidential ANDA actually contain all the claimed ingredients? The complaint alleges this on "information and belief," making discovery into the ANDA's contents critical. However, the subsequent cancellation of all claims of the '211 Patent renders these questions largely moot.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for a definitive analysis of claim construction disputes. However, based on the technology and claim language, certain terms are likely to be focal points.
Term: "effective amount" ('116 Patent, Claim 1)
Context and Importance: This term's construction is crucial for defining the scope of the method claim. The parties may dispute what degree of PTH reduction is required for an amount to be "effective," which could impact both infringement and validity analyses.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification suggests a wide dosage range of "about 1 to about 100 µg/week," which may support a broad definition of what constitutes an effective amount ('116 Patent, col. 3:65-66).
- Evidence for a Narrower Interpretation: The patent's detailed clinical examples link specific dosages to specific clinical outcomes, which could be used to argue that "effective amount" should be construed more narrowly in light of these demonstrated results ('116 Patent, Examples 3-5, col. 10:50-col. 12:68).
Term: "about" ('211 Patent, Claim 1)
Context and Importance: Practitioners may focus on this term because its breadth determines whether formulations with excipient concentrations near the endpoints of the claimed ranges literally infringe. This is a classic point of contention in formulation patent cases.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patentee may argue that "about" is used to signal that the invention is not limited to the exact numerical values but extends to values that are functionally equivalent. The general description uses the term to frame the ranges ('211 Patent, col. 15:4-6).
- Evidence for a Narrower Interpretation: A defendant could argue that the specific formulations prepared in the examples, which use precise amounts, limit the scope of "about" to a narrow range of equivalents consistent with the disclosed embodiments ('211 Patent, Table 1, col. 11).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Cobrek's future commercial activity will induce and contribute to infringement of the '116 patent (Compl. ¶21). The factual basis for this is the allegation that Cobrek's product will be sold with a label and instructions that direct users to perform the patented method of treatment.
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it pleads facts that may support such a claim for any future commercial infringement by stating that Cobrek had "notice" of both the '116 and '211 patents before filing its ANDA (Compl. ¶22, ¶31).
VII. Analyst’s Conclusion: Key Questions for the Case
Given the subsequent cancellation of all claims of the '211 patent, the dispute will center exclusively on the '116 patent. The key questions are:
A central issue will be induced infringement: Will Cobrek's proposed product label, as submitted in its ANDA, direct medical professionals and patients to administer doxercalciferol in a manner that satisfies every limitation of the asserted method claims in the '116 patent?
The case will also turn on a question of validity: Can Cobrek demonstrate by clear and convincing evidence that the asserted claims of the '116 patent are invalid as obvious or anticipated by the prior art that existed before the patent's August 1988 priority date, as it certified to the FDA?