DCT
1:11-cv-11681
Momenta Pharma Inc v. Amphastar Pharma Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Momenta Pharmaceuticals, Inc. (Delaware) and Sandoz Inc. (Colorado)
- Defendant: Amphastar Pharmaceuticals, Inc. (Delaware), International Medication Systems, Ltd. (Delaware), and Watson Pharmaceuticals, Inc. (Nevada)
- Plaintiff’s Counsel: Choate, Hall & Stewart LLP
- Case Identification: 1:11-cv-11681, D. Mass., 09/21/2011
- Venue Allegations: Venue is alleged to be proper based on Defendants transacting business in Massachusetts, committing acts of infringement in the district, and causing injury within the district.
- Core Dispute: Plaintiffs allege that Defendants' methods for manufacturing and selling a generic enoxaparin drug product infringe two patents related to analytical techniques for characterizing low molecular weight heparins.
- Technical Context: The technology involves methods for analyzing the chemical structure of enoxaparin, a complex biologic anticoagulant, to ensure that generic versions are equivalent to the branded drug, Lovenox®.
- Key Procedural History: The complaint notes that Plaintiff Momenta collaborated with Plaintiff Sandoz to develop a generic enoxaparin product, which received FDA approval on July 23, 2010. The suit was filed two days after Defendant Watson announced on September 19, 2011, that the FDA had approved an ANDA for a generic enoxaparin product manufactured by Defendant Amphastar.
Case Timeline
| Date | Event |
|---|---|
| 2002-03-11 | U.S. Patent No. 7,575,886 Priority Date |
| 2005-08-26 | Momenta and Sandoz enter collaboration agreement |
| 2007-01-26 | U.S. Patent No. 7,790,466 Priority Date |
| 2009-08-18 | U.S. Patent No. 7,575,886 Issues |
| 2010-07-23 | FDA approves Momenta/Sandoz ANDA for enoxaparin |
| 2010-09-07 | U.S. Patent No. 7,790,466 Issues |
| 2011-09-19 | FDA approves Amphastar's ANDA for enoxaparin |
| 2011-09-21 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,575,886 - “Analysis of Sulfated Polysaccharides,” issued August 18, 2009
The Invention Explained
- Problem Addressed: The patent describes that low molecular weight heparins (LMWHs) are structurally complex and heterogeneous, making it difficult to create generic versions with consistent batch-to-batch quality and to correlate their chemical structure with their therapeutic activity (’886 Patent, col. 4:32-49).
- The Patented Solution: The invention provides analytical methods to create a 'structural signature' for a given LMWH preparation. The method involves identifying and quantifying specific chemical markers, including a 'non-naturally occurring sugar' that is created as a byproduct of certain LMWH manufacturing processes ('886 Patent, Abstract; col. 64:1-6). By analyzing for this signature, a manufacturer can ensure consistency and characterize its product.
- Technical Importance: This analytical framework provided a way to meet the high regulatory bar for demonstrating that a generic version of a complex biologic drug is equivalent to the branded version, a key step for market approval (Compl. ¶19).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent; a representative independent claim is Claim 1 (Compl. ¶42).
- The essential elements of Claim 1 include:
- Providing an enoxaparin sample that has been exhaustively digested with heparin degrading enzymes.
- Using a separation method to determine the presence of a structural signature associated with a specific 'non naturally occurring sugar' (identified as associated with peak 9 in the patent's FIG. 1).
- Making a determination about the sample by comparing the detected signature to a reference standard.
- Analyzing a second batch to compare against the first, thereby ensuring consistency.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 7,790,466 - “Evaluating Mixtures of Low Molecular Weight Heparins By Chain Profiles Or Chain Mapping,” issued September 7, 2010
The Invention Explained
- Problem Addressed: As with the '886 patent, the technical challenge is the difficulty in analyzing complex polysaccharide mixtures like enoxaparin to control the manufacturing process and ensure product consistency (’466 Patent, col. 1:11-20).
- The Patented Solution: The invention provides methods for evaluating LMWH preparations using chromatography (HPLC) to generate 'chain profiles.' This involves separating the drug into fractions based on the length of the polysaccharide chains (e.g., tetrasaccharide fraction, hexasaccharide fraction) and analyzing the specific chemical structures within those fractions ('466 Patent, col. 2:27-35).
- Technical Importance: This method allows a generic manufacturer to demonstrate that its product has a distribution of oligosaccharide chain lengths and sequences equivalent to that of the branded drug, which the complaint alleges is an FDA requirement for approval (Compl. ¶24).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent; a representative independent claim is Claim 1 (Compl. ¶46).
- The essential elements of Claim 1 include:
- Providing an isolated tetrasaccharide fraction from a size-fractioned enoxaparin preparation.
- Analyzing that fraction using strong anion exchange HPLC.
- Determining if one or more of fifteen specific tetrasaccharide chain structures, listed in a table within the claim, are present.
- Processing the preparation (e.g., selecting, accepting, or selling it) if the specified chains are found.
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are the methods used by Defendants Amphastar and IMS to manufacture generic enoxaparin sodium for commercial sale, and the subsequent sale of that product by Defendants Amphastar and Watson (Compl. Intro; ¶27).
Functionality and Market Context
- The complaint alleges that in order to obtain FDA approval for a generic enoxaparin product, a manufacturer must perform specific analytical tests on each batch to prove its equivalence to the branded drug, Lovenox® (Compl. ¶¶ 22, 24).
- These allegedly required tests include determining that the product contains defined amounts of a non-naturally occurring sugar with a 1,6-anhydro ring structure, which Plaintiffs allege is the method claimed in the '886 patent (Compl. ¶22).
- The tests also allegedly include determining that the product's tetrasaccharide chains contain particular sequences in particular amounts, which Plaintiffs allege is the method claimed in the '466 patent (Compl. ¶24).
- The complaint references a Watson press release announcing the FDA approval of Amphastar's generic product and its anticipated launch in the fourth quarter of 2011 (Compl. ¶¶ 25-26).
IV. Analysis of Infringement Allegations
The complaint alleges that in order for the FDA to approve the defendants' generic enoxaparin, the defendants must have used manufacturing and quality control processes that infringe the asserted patents (Compl. ¶27). The complaint references Figure 1 from the '886 patent, which is a chromatogram depicting the output of an analytical method for Lovenox®, showing various chemical components as distinct peaks, including the allegedly infringing 'peak 9' (Compl. ¶21; '886 Patent, Fig. 1A).
'886 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for analyzing an enoxaparin sample for the presence or amount of a non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin... | The complaint alleges that Defendants' method for manufacturing generic enoxaparin includes determining that a defined percentage of oligosaccharide chains include a non-naturally occurring sugar with a 1,6-anhydro ring structure, which is the signature associated with peak 9. | ¶27(a) | col. 64:1-6 |
| comprising: providing an enoxaparin sample that has been exhaustively digested with two or more heparin degrading enzymes; | The complaint does not provide specific details on the digestion step but alleges that the overall analytical method is performed. | ¶27(a) | col. 5:1-12 |
| using a separation method to determine... the presence of a structural signature associated with the non naturally occurring sugar... | It is alleged that the FDA requires generic manufacturers to analyze each batch to confirm the presence of oligosaccharides with a 1,6-anhydro ring structure. The complaint asserts that Defendants must perform this analysis to sell their product. | ¶22 | col. 63:50-58 |
| making a determination about the enoxaparin sample based upon a comparison of the determination of the presence of a structural signature... to a reference standard for enoxaparin... | The complaint alleges that generic manufacturers must confirm their product has a structural profile equivalent to that of Lovenox®, which functions as the reference standard. | ¶¶19, 22 | col. 64:1-6 |
'466 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| providing an isolated tetrasaccharide fraction from a size fractioned enoxaparin preparation; | The complaint alleges that to gain FDA approval, Defendants must determine that the tetrasaccharide chains in their product have certain defined sequences, which implies the isolation and analysis of the tetrasaccharide fraction. | ¶27(b) | col. 2:1-14 |
| analyzing the tetrasaccharide fraction using strong anion exchange high performance liquid chromatography (HPLC) to determine if one or more chains shown in the... table is present... | The complaint states that the FDA requires generic manufacturers to confirm that the distribution of chain sequences within the tetrasaccharide subset of their product is equivalent to that of Lovenox®. | ¶24 | col. 27:3-10 |
| if one or more of said chains is present... processing said preparation, wherein processing includes one or more of selecting, accepting, processing into drug product... or selling... | The complaint alleges on information and belief that Defendants have manufactured and/or are in the process of manufacturing commercial quantities of generic enoxaparin sodium for their anticipated launch, which constitutes the 'processing' of the material for commercial sale based on the results of the allegedly infringing analytical methods. | ¶28 | col. 27:4-10 |
Identified Points of Contention
- Scope Questions: The core of the plaintiffs' case appears to be 'infringement by regulatory necessity'—that is, the defendants must infringe the patents to satisfy FDA requirements for generic approval. A primary question for the court will be whether the defendants' actual, specific quality control methods, once revealed, fall within the scope of the claims, or if they achieve the required regulatory equivalence through a different, non-infringing technical process.
- Technical Questions: What evidence demonstrates that the defendants' analytical methods perform the specific steps of the claims? For the '466 patent, does their process involve identifying the discrete molecular chains listed in Claim 1, or does it use a more holistic 'fingerprint' comparison that does not map to that limitation? For the '886 patent, do defendants specifically test for the 'non naturally occurring sugar' defined in the patent, or for a different marker of equivalence?
V. Key Claim Terms for Construction
The Term: "analyzing... to determine if one or more chains shown in the... table is present" ('466 Patent, Claim 1)
- Context and Importance: The construction of this term is central to the infringement analysis for the '466 patent. The dispute will likely focus on whether this requires the discrete identification of one of the 15 specific chemical structures listed in the claim's table, or if it can be satisfied by a less specific method that confirms the overall chromatographic profile matches a reference.
- Evidence for a Broader Interpretation: A party could argue that confirming the overall HPLC profile of a sample matches the profile of a reference standard (which is known to contain those chains) is sufficient to 'determine' that the chains are 'present' in the correct proportions, even without isolating and identifying each one individually.
- Evidence for a Narrower Interpretation: The claim language recites 'determine if one or more chains shown in the... table is present,' which a party could argue requires a specific, positive identification of at least one of the enumerated molecular structures, not just a general pattern match. The patent's detailed description focuses on resolving and identifying individual species (e.g., '466 Patent, col. 2:1-5).
The Term: "non naturally occurring sugar associated with peak 9 of FIG. 1" ('886 Patent, Claim 1)
- Context and Importance: The identity of this structure is the lynchpin of the '886 patent infringement claim. Practitioners may focus on this term because the infringement allegation hinges on whether defendants' process both creates and detects this specific manufacturing artifact.
- Evidence for a Broader Interpretation: A party might argue the term should cover any non-natural species that elutes at the same point as 'peak 9' in a defined separation method when analyzing enoxaparin, treating 'peak 9' as a positional definition.
- Evidence for a Narrower Interpretation: The specification explicitly defines the sugar as having a '1,6-anhydro ring structure' that 'results from a method of making enoxaparin that included β-eliminative cleavage with a benzyl ester and depolymerization' ('886 Patent, col. 64:1-6). This suggests the term is limited to a specific chemical entity created by a specific process.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendants Amphastar and IMS (manufacturers) have induced infringement by Defendant Watson (distributor) and others by, among other things, offering the allegedly infringing product for sale in the United States (Compl. ¶¶ 31, 36).
- Willful Infringement: The complaint alleges that the defendants' infringement is 'willful, deliberate, or objectively reckless' (Compl. ¶¶ 34, 39). The pleading does not state a factual basis for pre-suit knowledge, such as a prior notice letter.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: The complaint's theory of 'infringement by regulatory necessity' is based on information and belief. A key question will be whether discovery reveals that Defendants' actual manufacturing and quality control processes contain the specific, discrete steps recited in the asserted claims, or if they use a technically distinct, non-infringing method to satisfy FDA bioequivalence requirements.
- The outcome may also depend on claim construction: Can the term 'determine if one or more chains... is present' ('466 patent) be satisfied by a holistic comparison of chromatographic fingerprints, or does it require the positive identification of a specific molecular structure? The scope of what constitutes the 'non naturally occurring sugar' ('886 patent) will similarly be a critical point of dispute.