DCT
1:17-cv-01086
Horatio Washington Depot Tech LLC v. Tolmar Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Horatio Washington Depot Technologies LLC (Delaware)
- Defendant: Tolmar, Inc., Tolmar Pharmaceuticals, Inc., and Tolmar Therapeutics, Inc. (Delaware)
- Plaintiff’s Counsel: Richards, Layton & Finger, P.A.; Wiley Rein LLP (Of Counsel)
- Case Identification: 1:17-cv-01086, D. Del., 08/03/2017
- Venue Allegations: Venue is alleged to be proper based on Defendants' incorporation in Delaware and their commercial activities within the state, including the marketing, distribution, and sale of the accused product.
- Core Dispute: Plaintiff alleges that Defendant’s Eligard product, a treatment for advanced prostate cancer, infringes three patents related to stable, non-aqueous formulations for peptide drugs.
- Technical Context: The technology concerns pharmaceutical formulations that improve the stability of peptide-based drugs, enabling their use in high-concentration, long-term, sustained-release delivery systems.
- Key Procedural History: The complaint alleges that Defendants had pre-suit knowledge of the patents-in-suit since at least May 2010, based on their submission of an Information Disclosure Statement (IDS) to the USPTO during prosecution of their own patent. That IDS allegedly referenced an FDA Orange Book edition which listed the asserted patents in connection with the active ingredient used in the accused product.
Case Timeline
| Date | Event |
|---|---|
| 1996-07-03 | Priority Date for ’547, ’261, and ’712 Patents |
| 1999-08-03 | U.S. Patent No. 5,932,547 Issues |
| 2000-09-26 | U.S. Patent No. 6,124,261 Issues |
| 2001-05-22 | U.S. Patent No. 6,235,712 Issues |
| 2002-01-23 | First FDA Approval for Accused Eligard Product |
| 2002-10-29 | Certificate of Correction for ’712 Patent Issues |
| 2010-05-20 | Alleged Date of Defendants’ Knowledge of Asserted Patents |
| 2017-08-03 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,932,547 - "Non-Aqueous Polar Aprotic Peptide Formulations"
- Patent Identification: U.S. Patent No. 5,932,547, "Non-Aqueous Polar Aprotic Peptide Formulations," issued August 3, 1999.
The Invention Explained
- Problem Addressed: The patent describes the problem that aqueous formulations of peptide drugs, such as Luteinizing Hormone-Releasing Hormone (LHRH) analogs, suffer from significant chemical and physical instability, particularly at higher concentrations or when stored at room temperature, which limits their suitability for long-term parenteral delivery systems (Compl., Ex. A, ’547 Patent, col. 2:5-12).
- The Patented Solution: The invention solves this by dissolving the peptide compound in a non-aqueous, polar aprotic solvent, such as dimethylsulfoxide (DMSO). This approach creates a high-concentration formulation that is significantly more stable over long periods and at elevated temperatures, making it suitable for use in implantable drug delivery devices (’547 Patent, col. 3:18-29, col. 4:14-25).
- Technical Importance: This formulation strategy enabled the development of long-term (e.g., 1-12 month) implantable delivery systems for chronic conditions, which had previously been hindered by the poor stability of aqueous peptide solutions (’547 Patent, col. 3:25-29).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2, 4, and 6 (Compl. ¶30).
- Independent Claim 1 requires:
- A stable non-aqueous formulation of a peptide compound
- comprising: a) at least one peptide compound; and
- b) at least one polar aprotic solvent
- wherein said peptide compound is an LHRH-related compound
- The complaint does not explicitly reserve the right to assert other claims.
U.S. Patent No. 6,124,261 - "Non-Aqueous Polar Aprotic Peptide Formulations"
- Patent Identification: U.S. Patent No. 6,124,261, "Non-Aqueous Polar Aprotic Peptide Formulations," issued September 26, 2000.
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’547 Patent, this patent addresses the same core problem of instability in aqueous peptide formulations, which limits their use in long-term delivery applications (’261 Patent, col. 2:5-12).
- The Patented Solution: The invention provides a solution using non-aqueous, polar aprotic solvents to create stable, high-concentration peptide formulations. This patent further claims formulations that are stable after sterilizing irradiation or that exhibit inherent bacteriostatic properties without conventional agents, expanding the utility for medical devices (’261 Patent, col. 14:4-10, 14:59-63).
- Technical Importance: By claiming formulations that are stable to irradiation and inherently bacteriostatic, the invention provides solutions particularly well-suited for sterile, long-term implantable medical products.
Key Claims at a Glance
- The complaint asserts independent claims 3 and 4, and dependent claims 23, 26, 32, 33, and 36 (Compl. ¶57).
- Independent Claim 3 requires:
- A stable non-aqueous formulation of a peptide compound
- comprising: a) at least one peptide compound; and
- b) at least one polar aprotic solvent
- which is stable after irradiation
- The complaint does not explicitly reserve the right to assert other claims.
U.S. Patent No. 6,235,712 - "Non-Aqueous Polar Aprotic Peptide Formulations"
- Patent Identification: U.S. Patent No. 6,235,712, "Non-Aqueous Polar Aprotic Peptide Formulations," issued May 22, 2001.
- Technology Synopsis: As a divisional and continuation of the applications for the other asserted patents, the ’712 Patent covers related subject matter. It claims methods of preparing and using stable, non-aqueous formulations of LHRH-related peptide compounds dissolved in polar aprotic solvents for long-term, continuous administration, such as for treating prostate cancer (’712 Patent, Abstract; col. 14:5-10).
- Asserted Claims: Independent claim 1 and dependent claims 2, 4, 8, 9, 10, and 12-16 (Compl. ¶84).
- Accused Features: The complaint alleges that Defendants' activities, including the development and testing of Eligard by dissolving leuprolide acetate in the polar aprotic solvent N-methyl-2-pyrrolidone, infringe the patented methods (Compl. ¶84-85).
III. The Accused Instrumentality
Product Identification
- The accused products are Defendants' Eligard® drug products in 7.5 mg, 22.5 mg, 30 mg, and 45 mg/vial dosages (Compl. ¶23).
Functionality and Market Context
- Eligard is an injectable suspension indicated for the palliative treatment of advanced prostate cancer. It contains leuprolide acetate, an LHRH-related peptide, as its active pharmaceutical ingredient (Compl. ¶23).
- The formulation allegedly contains a polymer and a polar aprotic solvent. Upon subcutaneous administration, it forms a solid drug delivery depot that provides continuous release of leuprolide acetate for up to six months (Compl. ¶25). The complaint alleges, upon information and belief, that the formulation is prepared by dissolving leuprolide acetate in the solvent N-methyl-2-pyrrolidone (NMP) (Compl. ¶24).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
5,932,547 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A stable non-aqueous formulation of a peptide compound | Eligard is alleged to be a stable, non-aqueous formulation. | ¶24 | col. 3:18-22 |
| comprising: a) at least one peptide compound; | The Eligard product contains the peptide compound leuprolide acetate. | ¶23 | col. 6:1-4 |
| and b) at least one polar aprotic solvent | The Eligard formulation is allegedly prepared by dissolving the peptide in the polar aprotic solvent N-methyl-2-pyrrolidone. | ¶24 | col. 5:42-48 |
| wherein said peptide compound is an LHRH-related compound. | Leuprolide acetate is identified as a luteinizing hormone-release hormone (LH-RH) related compound. | ¶23 | col. 5:22-24 |
6,124,261 Infringement Allegations
| Claim Element (from Independent Claim 3) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A stable non-aqueous formulation of a peptide compound | Eligard is alleged to be a stable, non-aqueous formulation. | ¶24 | col. 3:23-28 |
| comprising: a) at least one peptide compound; | The Eligard product contains the peptide compound leuprolide acetate. | ¶23 | col. 6:2-5 |
| and b) at least one polar aprotic solvent | The Eligard formulation is allegedly prepared by dissolving the peptide in the polar aprotic solvent N-methyl-2-pyrrolidone. | ¶24 | col. 5:50-55 |
| which is stable after irradiation. | The complaint does not provide sufficient detail for analysis of this specific element. | N/A | col. 5:10-12 |
- Identified Points of Contention:
- Scope Questions: The patents define "stable formulation" with a specific quantitative threshold (e.g., "at least about 65% chemically and physically stable peptide compound remains after two months at 37° C.") (’547 Patent, col. 5:4-8). A central question will be whether the accused Eligard product meets this definition, an issue on which the complaint offers allegation but no factual evidence.
- Technical Questions: The infringement theory rests on the allegation that Eligard is made by dissolving leuprolide acetate in N-methyl-2-pyrrolidone (NMP) (Compl. ¶24). The patents explicitly list "n-methyl pyrrolidone" as a suitable polar aprotic solvent (’547 Patent, col. 5:47-48). A potential dispute may arise over whether the final Eligard product, which is administered as a suspension also containing a polymer, constitutes a "formulation... comprising... at least one polar aprotic solvent" in the manner claimed.
V. Key Claim Terms for Construction
The Term: "stable formulation"
Context and Importance: This term appears in the preamble of the asserted independent claims and is central to the invention. Infringement requires the accused product to be "stable." Practitioners may focus on this term because the patent specification provides an explicit and quantitative definition, which will likely be a focal point for both infringement and validity arguments.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term itself is general. A party might argue for a more qualitative or comparative meaning of stability relative to prior art aqueous solutions.
- Evidence for a Narrower Interpretation: The specification explicitly defines the term: "The term 'stable formulation' means that at least about 65% chemically and physically stable peptide compound remains after two months at 37° C." (’547 Patent, col. 5:4-8). The patent further provides a "particularly preferred" stability of "at least about 80%" (’547 Patent, col. 5:8-10). A court may find this explicit definition controlling.
The Term: "polar aprotic solvent"
Context and Importance: The use of this type of solvent is the core technical mechanism of the invention. The complaint’s infringement theory identifies N-methyl-2-pyrrolidone (NMP) as this solvent in the accused product (Compl. ¶24).
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition ("a polar solvent which does not contain acidic hydrogen and does not act as a hydrogen bond donor") and a non-exhaustive list of examples, including DMSO and DMF (’547 Patent, col. 5:42-46).
- Evidence for a Narrower Interpretation: The specification explicitly includes "n-methyl pyrrolidone" in the list of exemplary polar aprotic solvents (’547 Patent, col. 5:47-48). This strongly supports its inclusion within the claim scope. A dispute is less likely on the definition of the term itself and more likely on whether NMP as used in the final multi-component Eligard suspension functions as the claimed "polar aprotic solvent."
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement, stating that Defendants' prescribing information for Eligard actively instructs and encourages medical professionals to use the product in a manner that directly infringes the asserted claims (Compl. ¶32, ¶59, ¶86).
- Willful Infringement: Willfulness is alleged based on Defendants having knowledge of the asserted patents "at least as early as May 20, 2010" (Compl. ¶34, ¶61, ¶88). This allegation is specifically grounded in Defendants' submission of an IDS to the USPTO during the prosecution of its own patent, which cited an FDA Orange Book that listed the asserted patents in connection with leuprolide acetate (Compl. ¶26).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary question will be one of meeting a quantitative threshold: Can the Plaintiff demonstrate, through testing and discovery, that the accused Eligard product meets the specific, quantitative definition of a "stable formulation" as explicitly defined in the patents' specifications? The complaint alleges stability but provides no supporting data.
- A key legal and factual question will be one of willfulness and pre-suit knowledge: Does a defendant’s citation to the FDA Orange Book in an Information Disclosure Statement, where that Orange Book lists the patents-in-suit, suffice to establish knowledge of those patents and the objective recklessness required for a finding of willful infringement?
- A core issue of infringement will be one of compositional identity: Does the final, marketed Eligard product—an injectable suspension containing a polymer in addition to leuprolide acetate and a solvent—constitute the claimed "non-aqueous formulation... comprising... at least one polar aprotic solvent," or is there a technical mismatch between the claimed composition and the accused product as a whole?