1:10-cv-00746
Sepracor Inc v. Teva Parenteral Medicines Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Sepracor Inc. (Delaware)
- Defendant: Teva Parenteral Medicines, Inc. (Delaware), Teva Pharmaceuticals USA, Inc. (Delaware), and Teva Pharmaceutical Industries, Ltd. (Israel)
- Plaintiff’s Counsel: Fitzpatrick, Cella, Harper & Scinto
- Case Identification: 1:10-cv-00746, S.D.N.Y., 02/01/2010
- Venue Allegations: Venue is alleged to be proper based on the Defendants' marketing and selling of generic drugs throughout the United States, including continuous and systematic business contacts within the Southern District of New York.
- Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Brovana® (arformoterol tartrate) inhalation solution constitutes an act of patent infringement.
- Technical Context: The technology concerns pharmaceutical chemistry, specifically the isolation of a highly pure and thermodynamically stable crystalline form (polymorph) of arformoterol tartrate, a bronchodilator used to treat Chronic Obstructive Pulmonary Disease (COPD).
- Key Procedural History: The lawsuit was triggered by Defendant Teva Parenteral Medicines' submission of ANDA No. 200293 to the FDA, which included a "Paragraph IV certification" asserting that the patents-in-suit are not infringed by its proposed generic product. The patents are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") for Brovana®.
Case Timeline
| Date | Event |
|---|---|
| 2001-11-09 | Priority Date for '563, '453, and '036 Patents |
| 2002-10-29 | U.S. Patent No. 6,472,563 Issues |
| 2004-04-13 | U.S. Patent No. 6,720,453 Issues |
| 2006-10-06 | FDA Approves Brovana® (arformoterol tartrate) NDA |
| 2006-12-05 | U.S. Patent No. 7,145,036 Issues |
| 2010-02-01 | Complaint for Patent Infringement Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,472,563 - "Formoterol Tartrate Process and Polymorph" (issued Oct. 29, 2002)
The Invention Explained
- Problem Addressed: The patent describes the significant technical challenge of producing the (R,R)-isomer of formoterol L-tartrate with very high chemical purity. It notes that even the most thermodynamically stable polymorph, designated "Polymorph A," is difficult to purify via standard recrystallization because the process itself can cause chemical degradation and introduce new impurities ('563 Patent, col. 7:1-10).
- The Patented Solution: The invention discloses a novel, third polymorphic form of (R,R)-formoterol L-tartrate, designated "Polymorph C." This new polymorph serves as a key intermediate in an improved purification process. The process involves converting a less pure crystalline form (Polymorph B) into the highly pure Polymorph C, which is then isolated and subsequently crystallized to yield the desired, highly pure, and thermodynamically stable Polymorph A ('563 Patent, col. 9:20-34; Scheme II).
- Technical Importance: For pharmaceutical products, achieving a high degree of purity and controlling the specific crystalline form is critical for ensuring drug safety, stability, and consistent bioavailability ('563 Patent, col. 1:48-56).
Key Claims at a Glance
- The complaint does not identify specific asserted claims. Independent claim 8 is a representative composition claim.
- Independent Claim 8:
- (R,R)-formoterol L-tartrate in the form of a crystalline solid
- consisting of greater than 99.5% by weight of formoterol L-tartrate
- at least 95% in the polymorphic form of a thermodynamically stable third polymorph (A)
- wherein said polymorph (A) has a specific X-ray powder diffraction pattern with 23 identified peaks.
- The complaint reserves the right to assert infringement of "one or more claims" of the patent (Compl. ¶25).
U.S. Patent No. 6,720,453 - "Formoterol Tartrate Polymorph" (issued Apr. 13, 2004)
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’563 Patent, this patent addresses the same problem: the difficulty of obtaining (R,R)-formoterol L-tartrate that is both highly pure (i.e., free of chemical impurities) and in its most desirable, stable crystalline state for pharmaceutical use ('453 Patent, col. 5:25-34).
- The Patented Solution: The invention claims the highly pure composition of (R,R)-formoterol L-tartrate itself, defined by specific purity levels, low levels of specific impurities, and its existence as the stable "Polymorph A." The specification describes the process involving the intermediate "Polymorph C" as the method for achieving this level of purity ('453 Patent, col. 10:35-42).
- Technical Importance: The invention claims a specific, highly pure pharmaceutical composition, which is valuable for its improved therapeutic characteristics and regulatory compliance ('453 Patent, col. 2:30-46).
Key Claims at a Glance
- The complaint does not identify specific asserted claims. Independent claim 1 is a representative composition claim.
- Independent Claim 1:
- A crystalline solid consisting of greater than 99.5% by weight of (R,R)-formoterol L-tartrate and less than 0.5% by weight of chemical impurities.
- The chemical impurities include less than 0.2% by weight of a specific impurity (formula 7).
- The (R,R)-formoterol L-tartrate is at least 95% in the polymorphic form of a thermodynamically stable third polymorph (A).
- Polymorph (A) is defined by a specific X-ray powder diffraction pattern.
- The complaint reserves the right to assert infringement of "one or more claims" of the patent (Compl. ¶31).
U.S. Patent No. 7,145,036 - "Formoterol Tartrate Polymorph" (issued Dec. 5, 2006)
- Technology Synopsis: This patent, which is part of the same family as the '563 and '453 patents, is also directed to highly pure compositions of (R,R)-formoterol L-tartrate. It addresses the need to produce the drug in its most thermodynamically stable crystalline form (Polymorph A) while minimizing chemical impurities, which is achieved through a process involving a novel intermediate polymorph ('036 Patent, col. 5:56-62).
- Asserted Claims: The complaint does not specify claims but alleges infringement of "one or more claims" (Compl. ¶37). Independent claim 1 is a product-by-process claim directed to a "highly pure (R,R)-formoterol L-tartrate composition obtained by a process comprising crystallizing a first polymorph (C)."
- Accused Features: The complaint alleges that Teva's generic arformoterol tartrate product, as submitted for approval in its ANDA, will infringe the patent (Compl. ¶¶34, 37).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is the generic arformoterol tartrate inhalation solution (Eq. 0.015 mg base/2 mL) for which Teva Parenteral Medicines, Inc. filed Abbreviated New Drug Application (ANDA) No. 200293 with the FDA (Compl. ¶19).
Functionality and Market Context
The product is a generic equivalent of Sepracor's Brovana®, a long-acting beta-agonist indicated for the long-term treatment of bronchoconstriction in patients with COPD (Compl. ¶14). The filing of the ANDA signifies Teva's intent to engage in the commercial manufacture, use, and sale of this generic drug product in the United States, which would compete directly with Brovana® (Compl. ¶19). The complaint alleges that the parent companies, Teva USA and Teva Israel, encouraged and directed the ANDA submission (Compl. ¶20).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed claim chart or specify which claims are asserted. The infringement allegation is based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2), which states that the submission of an ANDA for a drug claimed in a patent is an act of infringement. The following tables summarize the implied infringement theory for representative composition claims from the lead patents.
'563 Patent Infringement Allegations
| Claim Element (from Independent Claim 8) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (R,R)-formoterol L-tartrate in the form of a crystalline solid | The generic drug product described in ANDA No. 200293 is alleged to be a crystalline solid of (R,R)-formoterol L-tartrate. | ¶25 | col. 17:8-9 |
| consisting of greater than 99.5% by weight of formoterol L-tartrate | The accused generic product is alleged to contain the active ingredient at a purity level of greater than 99.5%. | ¶25 | col. 17:9-10 |
| at least 95% in the polymorphic form of a thermodynamically stable third polymorph (A) of (R,R)-formoterol L-tartrate, | The accused generic product is alleged to be composed of at least 95% of the specific crystalline form designated Polymorph A. | ¶25 | col. 17:11-14 |
| said polymorph (A) having peaks at the diffraction degrees with the intensity shown below in an X-ray powder diffraction pattern... | The crystalline form in the accused generic product is alleged to exhibit the specific X-ray powder diffraction pattern defined in the claim. | ¶25 | col. 17:15-20 |
'453 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A crystalline solid consisting of greater than 99.5% by weight of (R,R)-formoterol L-tartrate and less than 0.5% by weight of chemical impurities | The generic product in ANDA No. 200293 is alleged to be a crystalline solid meeting these specific purity requirements. | ¶31 | col. 11:50-52 |
| said chemical impurities including less than 0.2% by weight (based on total crystalline solid) of a compound of formula 7 | The accused generic product is alleged to contain less than 0.2% of the specified impurity of formula 7. | ¶31 | col. 11:61-65 |
| said (R,R)-formoterol L-tartrate being at least 95% in the polymorphic form of a thermodynamically stable third polymorph (A) | The accused generic product is alleged to be composed of at least 95% of the specific crystalline form designated Polymorph A. | ¶31 | col. 11:66 - col. 12:3 |
Identified Points of Contention
- Factual/Technical Question: The central dispute will be factual and will turn on analytical chemistry. Does the generic product that Teva proposes to market, as described in its ANDA, actually meet the specific quantitative limitations of the claims? This raises the question of what evidence (e.g., X-ray powder diffraction, high-performance liquid chromatography) will show regarding the product's polymorphic form and purity levels.
- Scope Question: A potential dispute may arise over the claim term "consisting of." Does this term, as used in the claims, preclude the presence of any other substances, such as excipients or trace unlisted impurities, within the crystalline solid itself, and would the presence of such substances allow Teva to design around the claims?
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, practitioners may focus on the following terms:
The Term: "a thermodynamically stable third polymorph (A)" ('563 Patent, Claim 8)
Context and Importance: The identity and stability of the polymorphic form are central to the patent's claims. The definition of "Polymorph A" is critical, as infringement hinges on whether Teva's product contains this specific crystalline structure.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes Polymorph A as "the most thermodynamically stable polymorph" ('563 Patent, col. 4:48-49). A party could argue this functional language means the claim covers any polymorph with this stability characteristic, even if its measured diffraction pattern varies slightly from the claimed peaks.
- Evidence for a Narrower Interpretation: The claim explicitly defines Polymorph A as "having peaks at the diffraction degrees with the intensity shown below" followed by a detailed table of 23 peaks ('563 Patent, col. 17:15-20). A party could argue this recitation strictly limits the claim to a polymorph that exhibits this exact XRPD fingerprint, and any significant deviation constitutes non-infringement.
The Term: "consisting of" ('563 Patent, Claim 8; '453 Patent, Claim 1)
Context and Importance: Practitioners may focus on this term because "consisting of" is a term of art in patent law that creates a strong presumption that the claim is closed to unrecited elements. Its interpretation will determine whether the presence of additional impurities or components in Teva's crystalline solid avoids infringement.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that in the context of a pharmaceutical composition, the term applies to the active ingredient and its specified impurities, and does not exclude trace elements or other materials that do not materially alter the basic and novel properties of the claimed pure polymorph.
- Evidence for a Narrower Interpretation: A party will likely argue that "consisting of" means exactly what it says: the crystalline solid must contain only (R,R)-formoterol L-tartrate and the recited impurities. The presence of any other component within the crystal lattice would place the product outside the literal scope of the claim.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendants Teva USA and Teva Israel "caused, actively encouraged, and/or directed Teva Parenteral to submit ANDA No. 200293" (Compl. ¶20). These allegations could form the basis for claims of induced infringement against the parent entities.
- Willful Infringement: The complaint does not explicitly use the word "willful." However, it alleges that Teva filed a Paragraph IV certification with its ANDA, stating its belief that the patents are not infringed (Compl. ¶¶23, 29, 35). This certification establishes that Teva had pre-suit knowledge of the patents-in-suit.
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case will likely depend on the answers to two central questions:
A core issue will be one of analytical characterization: Will the evidence developed during discovery demonstrate that Teva’s proposed generic product, as specified in its ANDA, actually meets the quantitative purity (>99.5%) and polymorphic composition (>95% Polymorph A) thresholds recited in the asserted claims? This is a factual question that will be decided by a battle of expert analytical testing.
A key legal question will be one of definitional precision: How will the court construe the specific numerical limitations and XRPD data in the claims? Can Sepracor prove infringement if Teva's product is substantially similar but not identical to the claimed profile, or will the "consisting of" language and precise peak data be interpreted so narrowly that any measurable deviation allows Teva to avoid infringement?