DCT
3:22-cv-06341
Fresenius Kabi USA LLC v. Accord Healthcare Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Fresenius Kabi USA, LLC (Delaware)
- Defendant: Accord Healthcare Inc. (North Carolina)
- Plaintiff’s Counsel: Robinson Miller LLC
- Case Identification: 3:22-cv-06341, D.N.J., 10/28/2022
- Venue Allegations: Plaintiff alleges venue is proper because Defendant, through its counsel, consented to jurisdiction and venue in the District of New Jersey prior to the filing of the complaint.
- Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market generic levothyroxine sodium for injection constitutes an act of infringement of three patents covering stable pharmaceutical formulations.
- Technical Context: The technology concerns lyophilized (freeze-dried) formulations of levothyroxine, a synthetic thyroid hormone, designed to improve chemical stability and extend shelf life compared to previous formulations.
- Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant's filing of ANDA No. 217708, which seeks FDA approval to market a generic version of Plaintiff’s levothyroxine product. Defendant submitted a Paragraph IV certification alleging that Plaintiff's patents are invalid, unenforceable, or will not be infringed. The patents-in-suit are listed in the FDA's "Orange Book" for Plaintiff's New Drug Application (NDA) No. 202231.
Case Timeline
| Date | Event |
|---|---|
| 2011-06-24 | FDA approval of Plaintiff's NDA No. 202231 |
| 2011-08-30 | Earliest Priority Date for ’289, ’238, and ’239 Patents |
| 2015-04-14 | ’289 Patent Issued |
| 2015-10-27 | ’238 Patent Issued |
| 2015-10-27 | ’239 Patent Issued |
| 2022-09-13 | Plaintiff received Defendant’s Paragraph IV Notice Letter |
| 2022-10-28 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,006,289 - "Levothyroxine Formulations," issued April 14, 2015
The Invention Explained
- Problem Addressed: The patent addresses the chemical instability of conventional injectable levothyroxine sodium formulations, which can degrade over time, particularly at or above room temperature (’289 Patent, col. 2:17-23).
- The Patented Solution: The invention is a stable, lyophilized (freeze-dried) solid composition of levothyroxine sodium that uses a lower amount of the excipient mannitol (a bulking agent) than conventional formulations (’289 Patent, col. 6:49-65). The specification asserts that reducing the mass of mannitol and the mass ratio of mannitol to levothyroxine improves the drug's stability and reduces the formation of degradation products (’289 Patent, col. 7:20-29; col. 8:1-17).
- Technical Importance: Developing a more stable injectable formulation of a widely used hormone is significant for ensuring consistent dosage, extending product shelf life, and simplifying storage requirements for a drug often used in urgent clinical settings (’289 Patent, col. 2:1-3).
Key Claims at a Glance
- The complaint asserts independent claim 1 and reserves the right to assert additional claims (Compl. ¶¶ 39-40).
- Independent Claim 1 requires:
- A composition, comprising:
- about 100 or about 200 micrograms of levothyroxine sodium;
- a phosphate buffer; and
- from 2 to 4 milligrams of mannitol,
- where the composition is a lyophilized solid.
U.S. Patent No. 9,168,238 - "Levothyroxine Formulations," issued October 27, 2015
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’289 Patent, this patent addresses the same technical problem of instability in levothyroxine formulations (’238 Patent, col. 2:17-23).
- The Patented Solution: The invention is also a lyophilized solid composition of levothyroxine sodium with a specified, reduced amount of mannitol to enhance stability (’238 Patent, Abstract; col. 6:49-65). The claims of the ’238 patent cover slightly different dosage combinations and properties than the ’289 Patent.
- Technical Importance: The invention provides alternative formulations that achieve the goal of improved stability for injectable levothyroxine, expanding the range of protected compositions (’238 Patent, col. 2:17-23).
Key Claims at a Glance
- The complaint asserts independent claim 1 and notes the patent contains dependent method claims (Compl. ¶¶ 52, 54).
- Independent Claim 1 requires:
- A lyophilized solid composition, comprising:
- about 100 micrograms of levothyroxine sodium;
- a buffer; and
- between 2 to 4 milligrams of mannitol.
U.S. Patent No. 9,168,239 - "Levothyroxine Formulations," issued October 27, 2015
- Patent Identification: U.S. Patent No. 9,168,239, “Levothyroxine Formulations,” issued October 27, 2015 (Compl. ¶21).
- Technology Synopsis: Belonging to the same patent family as the ’289 and ’238 patents, the ’239 patent also describes a solution to the problem of levothyroxine instability in injectable drugs (’239 Patent, col. 2:17-23). The patented solution is a lyophilized solid composition containing a salt of levothyroxine, a buffer, and a specific range of mannitol, which is claimed to provide superior stability compared to conventional formulations (’239 Patent, Abstract; col. 6:49-65).
- Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶66).
- Accused Features: The complaint alleges that Defendant's lyophilized levothyroxine sodium products meet the limitations of claim 1 of the ’239 patent (Compl. ¶67).
III. The Accused Instrumentality
Product Identification
- Defendant's generic "levothyroxine sodium for powder for injection, 100 mcg/vial, 200 mcg/vial, and 500 mcg/vial," which is the subject of ANDA No. 217708 (Compl. ¶¶ 1, 31).
Functionality and Market Context
- The accused product is a lyophilized solid that is reconstituted for injection (Compl. ¶31). It is intended for the treatment of myxedema coma (Compl. ¶28). As a generic drug seeking approval under an ANDA, the product is required by the FDA to have the same active ingredient, strength, and dosage form as, and to be bioequivalent to, Plaintiff's approved NDA product (Compl. ¶29). The complaint indicates the active ingredient is "lyophilized levothyroxine sodium" (Compl. ¶31). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’289 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A composition, comprising: about 100 or about 200 micrograms of levothyroxine sodium; | Defendant's generic products are offered in strengths of 100 mcg/vial and 200 mcg/vial. | ¶31 | col. 11:2-4 |
| a phosphate buffer; | The complaint alleges on information and belief that the accused products contain each element of claim 1. | ¶40 | col. 11:5 |
| and from 2 to 4 milligrams of mannitol, | The complaint alleges on information and belief that the accused products contain each element of claim 1. | ¶40 | col. 11:6-7 |
| where the composition is a lyophilized solid. | The proposed dosage form for Defendant's product is a "lyophilized levothyroxine sodium" for injection. | ¶31 | col. 11:8 |
- Identified Points of Contention:
- Technical Questions: A primary factual dispute will concern the exact composition of Defendant's product. The complaint does not provide specific factual allegations regarding the type of buffer or the precise amount of mannitol in the accused product, relying instead on a general allegation of infringement "upon information and belief" (Compl. ¶40). The case may turn on whether discovery reveals the presence of "a phosphate buffer" and "from 2 to 4 milligrams of mannitol."
- Scope Questions: The construction of "about" will be critical. The court will need to determine the numerical range encompassed by "about 100" and "about 200" micrograms, which will define the scope of literal infringement for the active ingredient.
’238 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A lyophilized solid composition, comprising: about 100 micrograms of levothyroxine sodium; | Defendant's generic product line includes a strength of 100 mcg/vial. | ¶31 | col. 11:2-3 |
| a buffer; | The complaint alleges on information and belief that the accused products contain each element of claim 1. | ¶53 | col. 11:4 |
| and between 2 to 4 milligrams of mannitol. | The complaint alleges on information and belief that the accused products contain each element of claim 1. | ¶53 | col. 11:5-6 |
- Identified Points of Contention:
- Technical Questions: As with the ’289 Patent, a key question is whether Defendant's product contains the claimed "buffer" and the specified amount of mannitol. The ’238 Patent claim is slightly broader in reciting "a buffer" rather than "a phosphate buffer," which may alter the infringement analysis if the accused product contains a non-phosphate buffer.
- Scope Questions: The term "about 100 micrograms" will require construction to determine if the corresponding dosage strength of the accused product falls within the claimed range.
V. Key Claim Terms for Construction
The Term: "about" (as in "about 100 micrograms") (’289 Patent, cl. 1; ’238 Patent, cl. 1)
Context and Importance: This term's construction is central to determining the scope of the claimed dosage amounts. Its interpretation will dictate whether Defendant's product, which is supplied in a 100 mcg/vial strength (Compl. ¶31), literally infringes. Practitioners may focus on this term because even minor deviations in the manufactured amount of the active ingredient could place the accused product inside or outside the claim scope, depending on how much variability "about" permits.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification uses "about" when introducing preferred amounts, such as "about 100 µg, about 200 µg, and about 500 µg," suggesting the numbers are not intended to be rigid, absolute values (’289 Patent, col. 6:21-23).
- Evidence for a Narrower Interpretation: The patent presents stability data in tables where compositions are identified with precise values (e.g., "100 µg"), which a party could argue suggests "about" is intended to cover only minor variations consistent with standard pharmaceutical manufacturing tolerances (’289 Patent, Table 1).
The Term: "a phosphate buffer" (’289 Patent, cl. 1)
Context and Importance: This limitation defines the specific type of stabilizing agent required. Infringement of the ’289 Patent hinges on whether Defendant's product contains this specific class of buffer. The complaint does not identify the buffer in the accused product, making this a critical potential point of non-infringement.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discloses examples like "dibasic sodium phosphate" and "monobasic sodium phosphate" (’289 Patent, col. 6:46-47), but uses the general term "a phosphate buffer," which could be argued to encompass any buffer system based on phosphate chemistry.
- Evidence for a Narrower Interpretation: The specification explicitly notes that the ingredients "preferably do not include tribasic sodium phosphate" (’289 Patent, col. 6:44). A party could argue this disclaimer narrows the scope of "a phosphate buffer" to exclude certain species or to require specific functional characteristics associated with the preferred dibasic and monobasic examples.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant will induce and contribute to infringement of dependent method claims in the ’238 and ’239 patents. This allegation is based on the distribution of Defendant's generic products with a product label that will allegedly instruct or encourage medical professionals to use the product in an infringing manner (Compl. ¶¶ 54, 68).
- Willful Infringement: The complaint alleges that Defendant was aware of the patents-in-suit before it submitted its ANDA (Compl. ¶¶ 43, 57, 71). It further alleges that Defendant has "no reasonable basis" for its certifications of non-infringement and invalidity, which forms the basis for the claims of willful infringement and for seeking a declaration that the case is "exceptional" under 35 U.S.C. § 285 (Compl. ¶¶ 44-45, 58-59, 72-73).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of factual proof: what is the precise chemical composition of Defendant's generic levothyroxine product? The outcome will likely depend on whether discovery reveals that the product contains the specific buffer systems and mannitol quantities recited in the asserted claims.
- A key legal question will be one of claim scope: how will the court construe the term "about" as it applies to the amount of levothyroxine sodium? This determination will be critical in defining the boundaries of infringement for the claimed dosage amounts.
- A third question will relate to indirect infringement: assuming the court finds the asserted composition claims are not directly infringed, will the instructions on Defendant's proposed product label be sufficient to induce infringement of the dependent method claims?