DCT
1:10-cv-00032
Daiichi Sankyo Inc. v. Impax Laboratories Inc.
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Daiichi Sankyo, Inc. (Delaware) and Genzyme Corporation (Massachusetts)
- Defendant: Impax Laboratories, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:10-cv-00032, D. Del., 01/14/2010
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant, Impax Laboratories, is a Delaware corporation and markets and sells pharmaceutical products in the district.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs’ cholesterol-lowering drug, Welchol®, constitutes an act of infringement of two patents related to polymer-based bile acid sequestrants.
- Technical Context: The technology concerns specialized polymer compositions designed to bind to bile acids in the digestive tract, thereby preventing their reabsorption and prompting the body to use cholesterol to produce more bile acids, which lowers blood cholesterol levels.
- Key Procedural History: This lawsuit was filed under the Hatch-Waxman Act, triggered by a notice letter from Impax dated December 8, 2009. The letter informed Plaintiffs that Impax had filed ANDA No. 91-600 with the FDA, including a "Paragraph IV" certification asserting that its proposed generic product would not infringe the patents-in-suit or that the patents are invalid. The patents are listed in the FDA's "Orange Book" as covering the branded drug Welchol®.
Case Timeline
| Date | Event |
|---|---|
| 1994-06-10 | Priority Date for ’669 and ’675 Patents |
| 1997-03-04 | U.S. Patent No. 5,607,669 Issued |
| 1997-12-02 | U.S. Patent No. 5,693,675 Issued |
| 2000-05-26 | FDA approves NDA for Welchol® (colesevelam hydrochloride) |
| 2009-12-08 | Impax sends ANDA Notice Letter to Plaintiffs |
| 2010-01-14 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,607,669 - "Amine Polymer Sequestrant and Method of Cholesterol Depletion" (Issued Mar. 4, 1997)
The Invention Explained
- Problem Addressed: The patent describes that prior bile acid sequestrants, while effective at reducing cholesterol, do not bind certain types of bile acids (conjugated primary bile acids) strongly enough to prevent them from being reabsorbed by the body, thus limiting their overall therapeutic effect (ʼ669 Patent, col. 1:29-36).
- The Patented Solution: The invention is a method of lowering cholesterol by administering a novel amine polymer. This polymer is chemically modified to include two distinct types of substituents: one containing a "hydrophobic moiety" (e.g., a long alkyl chain) and another containing a "quaternary amine-containing moiety" (a permanently positively charged group) ('669 Patent, Abstract; col. 1:43-55). This dual-functionality design is intended to improve the polymer's ability to irreversibly bind a wider range of bile acids in the intestine, leading to their excretion and a greater reduction in blood cholesterol ('669 Patent, col. 1:56-67).
- Technical Importance: The claimed method represents an attempt to create a second-generation bile acid sequestrant with superior binding affinity and efficacy compared to then-existing standards like cholestyramine.
Key Claims at a Glance
- The complaint alleges infringement of one or more unspecified claims (Compl. ¶16). Independent claim 1 is representative of the invention's core method.
- Independent Claim 1: A method for binding bile salts in a mammal, comprising the step of orally administering a therapeutic amount of an amine polymer having:
- a first substituent, bound to a first amine of the amine polymer, that includes a hydrophobic aliphatic moiety, and
- a second substituent, bound to a second amine of the amine polymer, that includes an aliphatic quaternary amine-containing moiety.
U.S. Patent No. 5,693,675 - "Alkylated Amine Polymers" (Issued Dec. 2, 1997)
The Invention Explained
- Problem Addressed: The patent notes that existing bile salt-removing resins like cholestyramine, while functional, suffer from poor patient compliance due to being "unpalatable, gritty and constipating" ('675 Patent, col. 1:48-53).
- The Patented Solution: The invention discloses a new class of cross-linked amine polymer compositions. The polymer is alkylated with at least one agent, but the reaction is controlled such that: (i) at least some of the polymer's nitrogen atoms remain unreacted, and (ii) "less than 10 mol %" of the nitrogen atoms that do react form quaternary ammonium units (a permanent positive charge) ('675 Patent, Abstract; col. 2:20-27). This specific chemical structure is intended to improve bile salt sequestration while avoiding the negative physical properties of prior resins.
- Technical Importance: This technology aimed to create a more palatable and better-tolerated ion-exchange resin, thereby improving patient compliance and the overall effectiveness of cholesterol treatment.
Key Claims at a Glance
- The complaint alleges infringement of one or more unspecified claims (Compl. ¶16). Independent claim 1 is representative of the core composition.
- Independent Claim 1: An alkylated crosslinked polymer comprising the reaction product of:
- one or more crosslinked polymers, salts or copolymers thereof characterized by a specified repeat unit (e.g., polyallylamine), and
- at least one aliphatic alkylating agent,
- wherein the reaction product is characterized in that at least some of the nitrogen atoms are unreacted, and
- less than 10 mol % of the nitrogen atoms form quaternary ammonium units.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is the "625 mg colesevelam hydrochloride tablets" that Defendant Impax Laboratories, Inc. seeks to manufacture, use, and sell, as described in its Abbreviated New Drug Application (ANDA) No. 91-600 (Compl. ¶11).
- Functionality and Market Context: The product is a proposed generic version of the branded drug Welchol® (Compl. ¶¶8, 10). As an ANDA product, it is intended to have the same active ingredient (colesevelam hydrochloride), dosage form, strength, and indications as Welchol®, which is used to treat primary hyperlipidemia and type 2 diabetes by acting as a bile acid sequestrant (Compl. ¶8). The filing of the ANDA signifies Impax's intent to compete with Plaintiffs' branded product upon receiving FDA approval (Compl. ¶11).
IV. Analysis of Infringement Allegations
The complaint alleges that the filing of ANDA No. 91-600 is an act of infringement under 35 U.S.C. § 271(e)(2) and that future commercialization would constitute direct and induced infringement (Compl. ¶¶15-17). The complaint does not contain a detailed element-by-element infringement analysis. The allegations are summarized below against the representative independent claims.
No probative visual evidence provided in complaint.
’669 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for binding bile salts in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of an amine polymer | The complaint alleges that Impax seeks approval to market colesevelam hydrochloride tablets, a polymer intended for oral administration to bind bile salts. | ¶¶8, 11, 15 | col. 1:37-41 |
| having a first substituent, bound to a first amine of the amine polymer, that includes a hydrophobic aliphatic moiety, | The complaint alleges that the product described in ANDA No. 91-600, if approved, would infringe the patent, which implies the polymer contains the claimed substituents. | ¶16 | col. 1:43-47 |
| and a second substituent, bound to a second amine of the amine polymer, that includes an aliphatic quaternary amine-containing moiety. | The complaint alleges that the product described in ANDA No. 91-600, if approved, would infringe the patent, which implies the polymer contains the claimed substituents. | ¶16 | col. 1:47-50 |
’675 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An alkylated crosslinked polymer comprising the reaction product of: a) one or more crosslinked polymers... | The complaint alleges Impax's proposed product is a 625 mg colesevelam hydrochloride tablet, which is a formulation of a crosslinked polymer. | ¶¶8, 11, 15 | col. 5:29-39 |
| and b) at least one aliphatic alkylating agent, | The complaint alleges the ANDA product will infringe, which implies it is the result of a reaction with an alkylating agent. | ¶16 | col. 3:11-14 |
| said reaction product characterized in that: (i) at least some of the nitrogen atoms in said repeat units are unreacted with said alkylating agent; and | The complaint's general allegation of infringement suggests the ANDA product possesses this claimed characteristic. | ¶16 | col. 2:21-23 |
| (ii) less than 10 mol % of the nitrogen atoms in said repeat units that react with said alkylating agent form quaternary ammonium units. | The complaint's general allegation of infringement suggests the ANDA product meets this negative limitation. | ¶16 | col. 2:23-27 |
- Identified Points of Contention:
- Factual Question: The central dispute will be factual: does the specific colesevelam hydrochloride polymer described in Impax's confidential ANDA filing meet all the structural and method limitations of the asserted claims? The complaint provides no specific technical evidence, making this a primary subject for discovery.
- Scope Questions: The case may raise questions about the scope of the claims. For the ’675 Patent, a key issue will be whether Impax's polymer, as manufactured, in fact has "less than 10 mol %" of its reacted nitrogen atoms forming quaternary ammonium units. For the ’669 Patent, a question may arise as to whether the substituents on Impax's polymer meet the definitions of a "hydrophobic aliphatic moiety" and an "aliphatic quaternary amine-containing moiety."
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of specific disputed terms. However, based on the technology and claim language, certain terms are likely to be central to the dispute.
Term from ’675 Patent, Claim 1: "less than 10 mol % of the nitrogen atoms... form quaternary ammonium units"
- Context and Importance: This negative limitation is a critical differentiator of the claimed invention. Its interpretation is vital because if Impax's product has 10% or more such units, it would not infringe. Practitioners may focus on this term because the method of measuring and calculating this percentage in a final polymer product could be a point of significant technical and legal dispute.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims and specification repeatedly emphasize the desirability of avoiding a high degree of quaternization, but do not provide a specific analytical method for its calculation. A party might argue that any scientifically reasonable method of measurement should apply.
- Evidence for a Narrower Interpretation: The specification distinguishes the invention from prior art resins, which may have had higher degrees of such charged groups ('675 Patent, col. 1:48-53). A party could argue the term must be interpreted in a way that preserves this distinction and is tied to the synthesis methods described in the patent's examples.
Term from ’669 Patent, Claim 1: "hydrophobic aliphatic moiety"
- Context and Importance: The presence of this specific type of substituent is a required element of the claimed method. The definition of "hydrophobic" and the required length and structure of the "aliphatic moiety" will determine the breadth of the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification lists broad categories of suitable groups, such as alkyl groups of "at least six carbons" ('669 Patent, col. 3:25-26), suggesting the term is not narrowly limited.
- Evidence for a Narrower Interpretation: The specific examples provided in the patent, such as the use of 1-bromodecane to create a decyl moiety ('669 Patent, col. 7:55-56), could be used to argue that the term should be construed more narrowly to encompass only structures similar to those explicitly disclosed.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if the FDA approves Impax's ANDA, Impax's subsequent offer to sell and sale of its colesevelam tablets would induce infringement of the method claims of the patents-in-suit (Compl. ¶17). This allegation is predicated on the assumption that Impax's product labeling will instruct physicians and patients to administer the drug in a manner that practices the claimed methods.
VII. Analyst’s Conclusion: Key Questions for the Case
- A Core Factual Question: Does the chemical product defined in Impax’s confidential ANDA No. 91-600 possess the specific structural characteristics required by the asserted patents? In particular for the ’675 patent, does the polymer have "less than 10 mol %" of its reacted nitrogens in a quaternary ammonium state? This will be a fact-intensive inquiry dependent on discovery into Impax’s manufacturing process and product specifications.
- A Question of Claim Scope: How will the court construe the key limitations of the claims? The definition of terms like "hydrophobic aliphatic moiety" (’669 patent) and the precise analytical meaning of the "less than 10 mol %" limitation (’675 patent) will be critical in determining the boundary between infringing and non-infringing products.
- A Question of Validity: Although not detailed in the complaint, Impax's Paragraph IV certification necessarily asserts that the patents are invalid or not infringed. The litigation will likely involve a challenge by Impax to the validity of the patents-in-suit on grounds such as anticipation or obviousness in view of prior art polymer sequestrants.