DCT
2:18-cv-13628
Symed Labs Ltd v. Amneal Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Symed Labs Limited (India) and Hetero USA, Inc. (Delaware)
- Defendant: Amneal Pharmaceuticals LLC (Delaware) and Raks Pharma Private Limited (India)
- Plaintiff’s Counsel: Tarter Krinsky & Drogin LLP
- Case Identification: 2:18-cv-13628, D.N.J., 09/06/2018
- Venue Allegations: Venue is alleged to be proper for Amneal because it maintains a regular and established place of business in New Jersey and has committed acts of infringement in the state. Venue for Raks, a foreign entity, is alleged based on its being subject to personal jurisdiction.
- Core Dispute: Plaintiffs allege that Defendants' manufacture and sale of generic linezolid tablets infringe patents claiming novel chemical intermediates used in the synthesis of the linezolid active pharmaceutical ingredient (API).
- Technical Context: The technology concerns chemical process innovations for manufacturing the antibiotic linezolid, a drug used to combat serious, drug-resistant bacterial infections and included on the World Health Organization's List of Essential Medicines.
- Key Procedural History: Plaintiffs allege they provided Defendants with actual notice of the patents-in-suit in 2015, more than three years before filing the complaint. The complaint also notes other ongoing litigation between the parties regarding a different patent related to a specific crystalline form of linezolid. Defendants' generic linezolid product was approved by the FDA on December 21, 2015, via ANDA No. 204536, which references a Drug Master File from Defendant Raks Pharma.
Case Timeline
| Date | Event |
|---|---|
| 2004-04-19 | '824 Patent Priority Date |
| 2004-07-20 | '661 Patent Priority Date |
| 2008-04-01 | '824 Patent Issue Date |
| 2008-09-30 | '661 Patent Issue Date |
| 2015-01-30 | Alleged written notice of patents to Defendant Raks |
| 2015-06-02 | Alleged written notice of patents to Defendant Amneal |
| 2015-12-21 | FDA approval of Defendants' ANDA No. 204536 for linezolid tablets |
| 2018-09-06 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,351,824, "Process for the Preparation of Linezolid and Related Compounds," issued April 1, 2008
The Invention Explained
- Problem Addressed: The patent describes prior art processes for preparing linezolid as having significant drawbacks, including the use of hazardous, expensive, and "difficult to handle" reagents such as butyl lithium at extremely low temperatures and phosgene gas, which are not ideal for commercial-scale operations ('824 Patent, col. 2:55-62; Compl. ¶25).
- The Patented Solution: The invention provides a novel process and novel chemical intermediates to create a safer, simpler, and more economical synthesis of linezolid. A key aspect of this process is the creation of a novel chlorohydrin compound (Formula IV) by reacting a specific phenyl amine compound with R-epichlorohydrin, thereby avoiding the problematic reagents of the prior art ('824 Patent, col. 3:5-12, 30-40).
- Technical Importance: The patented process provides an industrially advantageous and commercially viable method for producing intermediates essential for synthesizing an important antibiotic (Compl. ¶25).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2 and 3 (Compl. ¶40).
- Independent Claim 1 recites:
- A compound of formula IV, a chemical structure containing a chlorohydrin group attached to a phenyl-morpholine core.
- The formula includes several variable "R" groups and a variable "X" atom, which are defined by a Markush group (e.g., "X is O, S, SO or SO2").
- The complaint alleges infringement of "one or more claims" of the '824 patent, reserving the right to assert others (Compl. ¶38).
U.S. Patent No. 7,429,661, "Intermediates for Linezolid and Related Compounds," issued September 30, 2008
The Invention Explained
- Problem Addressed: Like the '824 patent, the '661 patent addresses the drawbacks of prior art linezolid synthesis, such as the use of dangerous reagents that are difficult to handle in large-scale production ('661 Patent, col. 2:40-48; Compl. ¶25).
- The Patented Solution: This invention discloses a different novel intermediate useful for synthesizing linezolid. The patent claims a compound of Formula IV, which is a novel N-phthalimido derivative. This compound is produced by reacting a chlorohydrin compound (like the one claimed in the '824 patent) with potassium phthalimide, representing a different step in a novel, commercially viable synthesis pathway ('661 Patent, col. 3:45-56).
- Technical Importance: The invention provides novel, high-yield intermediates that can be converted to linezolid using common, easy-to-handle reagents, thus improving the safety and efficiency of manufacturing ('661 Patent, col. 2:49-54).
Key Claims at a Glance
- The complaint asserts independent claim 64 and dependent claims 65 and 66 (Compl. ¶47).
- Independent Claim 64 recites:
- A compound of formula IV, a chemical structure containing an N-phthalimido group attached to a phenyl-morpholine core.
- Like the '824 patent, the formula is defined by a Markush group of variables for "R" groups and the "X" atom.
- The complaint alleges infringement of "one or more claims" of the '661 Patent, reserving the right to assert others (Compl. ¶45).
III. The Accused Instrumentality
Product Identification
Defendants' "linezolid 600 mg. tablets" and the linezolid active pharmaceutical ingredient (API) used therein (Compl. ¶¶ 1, 12).
Functionality and Market Context
The accused products are generic versions of the antibiotic linezolid, used to treat serious bacterial infections, including those resistant to other antibiotics (Compl. ¶21). The infringement allegations center on the chemical process used to manufacture the linezolid API. The complaint alleges that this process, described in Raks' Drug Master File (DMF) No. 26042 and referenced in Amneal's approved Abbreviated New Drug Application (ANDA) No. 204536, uses patented chemical intermediates (Compl. ¶¶ 10-11, 38, 45). The complaint further alleges, based on an "analysis of Defendants' linezolid tablets," that these intermediates are present in the final sold product (Compl. ¶¶ 39, 46). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'824 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound of formula IV [a chlorohydrin compound] | Defendants are alleged to make, use, sell, or import linezolid tablets containing the specific intermediate N-[3-Chloro-2-(R)-hydroxypropyl]-3-fluoro-4-morpholinyl aniline ("CHFA"), which is alleged to be an embodiment of the claimed formula and to be present in the final tablets. | ¶36, ¶38-40 | col. 9:22-41 |
'661 Patent Infringement Allegations
| Claim Element (from Independent Claim 64) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound of formula IV [an N-phthalimido compound] | Defendants are alleged to make, use, sell, or import linezolid tablets and API containing the specific intermediate N-[3-Phthalimido-2-(R)-hydroxypropyl]-3-flouro-4-morpholinyl aniline ("PHPFMA"), which is alleged to be an embodiment of the claimed formula and to be present in the final tablets. | ¶36, ¶45-47 | col. 15:1-16 |
- Identified Points of Contention:
- Technical Question: The complaint's assertion that infringement is based on an "analysis of Defendants' linezolid tablets" raises the evidentiary question of whether the claimed intermediates (CHFA and PHPFMA) can be detected in the final, formulated drug product. A key point of contention may be whether discovery, including analysis of the confidential manufacturing process described in Raks' DMF, will confirm the use or presence of these specific compounds.
- Scope Questions: The patents claim chemical intermediates, while the accused act is the sale of a final drug product. This raises the question of whether the sale of a product that either contains trace amounts of a patented intermediate or was produced using that intermediate constitutes direct infringement of a patent claiming the intermediate itself.
V. Key Claim Terms for Construction
The patents-in-suit claim chemical compounds via Markush groups, which may limit the scope for claim construction disputes compared to other technology areas. However, the interpretation of the claimed genus remains central.
- The Term: "A compound of formula IV" (as defined in claim 1 of the '824 Patent and claim 64 of the '661 Patent).
- Context and Importance: The entirety of the direct infringement case rests on whether the intermediates allegedly used by Defendants fall within the structural definitions of "formula IV" in each patent. Practitioners may focus on this term because, while seemingly straightforward, any ambiguity in the scope of the Markush variables (e.g., R₁, X) could create non-infringement arguments.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims themselves define the scope by listing the members of the Markush group (e.g., "X is O, S, SO or SO2") ('824 Patent, col. 9:28; '661 Patent, col. 15:7). This language may support an interpretation that includes any compound meeting the structural formula where the variables are chosen from the specified lists.
- Evidence for a Narrower Interpretation: The patents provide specific examples of preferred embodiments, including the very compounds (CHFA and PHPFMA) that Plaintiffs accuse Defendants of using ('824 Patent, Example 1, col. 7:53-59; '661 Patent, Example 2, col. 8:62-67). A party could argue that the scope should be understood in light of these specific, disclosed examples, although separating claim scope from preferred embodiments is a standard tenet of claim construction.
VI. Other Allegations
- Willful Infringement: The complaint alleges that Defendants' infringement has been and continues to be willful and deliberate (Compl. ¶¶ 41, 48). This allegation is based on claims of pre-suit actual notice, specifically that Plaintiffs advised Amneal in written correspondence on June 2, 2015, and Raks on January 30, 2015, of Plaintiffs' patent rights relating to the linezolid intermediates (Compl. ¶¶ 33-34).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: Can Plaintiffs demonstrate, through discovery of Defendants' confidential manufacturing processes (via the DMF) or through forensic analysis of the final drug product, that the specific chemical intermediates claimed in the '824 and '661 patents are actually used or created during the synthesis of Defendants' linezolid API?
- The case may turn on a legal theory of infringement: If the patented intermediates are consumed during the manufacturing process and are not detectably present in the final imported and sold tablets, a key question will be whether the sale of that final product constitutes direct infringement under 35 U.S.C. § 271(a) of the patents on the intermediates.
- A significant damages question will be one of willfulness: Given the explicit allegations of pre-suit written notice to both defendants in 2015, the court will need to determine whether any infringement was "willful and deliberate," which could expose Defendants to a potential award of enhanced damages.