DCT
1:19-cv-02638
Apicore US LLC v. Trupharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Apicore US LLC (Delaware) and Mylan Institutional LLC (Delaware)
- Defendant: Beloteca, Inc. (California)
- Plaintiff’s Counsel: Mandell Menkes LLC; Wilson Sonsini Goodrich & Rosati, P.C.
- Case Identification: 1:19-cv-02638, N.D. Ill., 05/24/2019
- Venue Allegations: Venue is alleged to be proper based on Defendant’s prior admission of proper venue in the district and because Defendant’s Abbreviated New Drug Application (ANDA) submission is purposefully directed at future sales in Illinois.
- Core Dispute: Plaintiffs allege that Defendant's planned generic isosulfan blue injection product, the subject of an approved ANDA, infringes three patents covering a process for manufacturing high-purity isosulfan blue and the resulting high-purity compound.
- Technical Context: The technology concerns the chemical synthesis of isosulfan blue, a dye used as a diagnostic contrast agent for mapping the lymphatic system, to a level of purity suitable for pharmaceutical use.
- Key Procedural History: The complaint notes that Defendant filed a declaratory judgment action for non-infringement and invalidity on January 17, 2019, one day after its ANDA was approved by the FDA. The complaint also notes that a third party, Luitpold Pharmaceuticals, previously filed an inter partes review (IPR) petition against the ’050 patent, which the Patent Trial and Appeal Board declined to institute, a fact Plaintiffs may use to suggest the patent’s strength.
Case Timeline
| Date | Event |
|---|---|
| 2007-05-11 | Earliest Priority Date for '992, '616, and '050 Patents |
| 2010-02-16 | U.S. Patent No. 7,662,992 Issued |
| 2015-03-03 | U.S. Patent No. 8,969,616 Issued |
| 2016-05-31 | U.S. Patent No. 9,353,050 Issued |
| 2019-01-16 | FDA approves Beloteca's ANDA No. 210714 |
| 2019-01-17 | Beloteca files Declaratory Judgment action against Plaintiffs |
| 2019-03-06 | PTAB denies institution of IPR on '050 Patent (filed by Luitpold) |
| 2019-05-24 | Plaintiffs file First Amended Complaint for Patent Infringement |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,662,992 - "Process for Preparation of Isosulfan Blue," issued February 16, 2010
The Invention Explained
- Problem Addressed: The patent describes prior art methods for producing triarylmethane dyes like isosulfan blue as yielding impure products unsuitable for pharmaceutical use (Compl. ¶25). These methods involved hazardous oxidizing agents and "tedious neutralization/basification with strong bases," complicating the purification process (’992 Patent, col. 1:63-65, col. 2:7-9).
- The Patented Solution: The invention provides a multi-step chemical process designed to be "simple, safe, cost-effective, time saving and reliable" for producing isosulfan blue in a "substantially pure form," defined as 99.0% purity or greater (’992 Patent, col. 2:27-31). The core of the claimed process involves reacting an intermediate compound (isoleuco acid) with a specific oxidizing agent (silver oxide) in a polar solvent, recovering the resulting isosulfan blue acid, and then treating it with a sodium solution to create the final salt form (’992 Patent, Claim 1). The overall synthesis pathway is depicted in the patent’s "Scheme" figure (’992 Patent, col. 3-4).
- Technical Importance: The process enabled the commercial-scale synthesis of isosulfan blue at a purity level significantly greater than previously achieved, making the compound viable for use as a pharmaceutical diagnostic agent in procedures like sentinel lymph node mapping for cancer patients (’992 Patent, col. 1:43-56).
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 (Compl. ¶50).
- Independent Claim 1 contains the following essential elements:
- A process of preparing the isosulfan blue sodium salt.
- Combining a suspension of isoleuco acid of formula (4) in a polar solvent with 2.0 to 3.0 equivalents of silver oxide.
- Recovering isosulfan blue acid.
- Treating the isosulfan blue acid with a sodium solution.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 8,969,616 - "Process for Preparation of Isosulfan Blue," issued March 3, 2015
The Invention Explained
- Problem Addressed: Sharing a specification with the ’992 patent, this patent addresses the same technical problem: the need for an improved method to produce isosulfan blue in a pure form suitable for pharmaceutical manufacturing, avoiding the hazardous reagents and complex purification of prior art processes (’616 Patent, col. 2:20-25).
- The Patented Solution: The patent discloses the same synthesis pathway for creating high-purity isosulfan blue (’616 Patent, Scheme at col. 3-4). The asserted independent claim is nearly identical to that of the ’992 patent, reciting the key steps of oxidizing isoleuco acid with silver oxide in a polar solvent, recovering the intermediate acid, and converting it to the final sodium salt (’616 Patent, Claim 1).
- Technical Importance: This process provided a reliable and safer method for producing a high-purity active pharmaceutical ingredient used in cancer diagnostics (’616 Patent, col. 1:50-60).
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 (Compl. ¶73).
- Independent Claim 1 contains the following essential elements:
- A process of preparing the isosulfan blue sodium salt.
- Combining a suspension of isoleuco acid of formula (4) in a polar solvent with silver oxide.
- Recovering isosulfan blue acid.
- Treating the isosulfan blue acid with a sodium solution.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 9,353,050 - "Process for Preparation of Isosulfan Blue," issued May 31, 2016
Technology Synopsis
This patent is a member of the same family and addresses the same problem of producing high-purity isosulfan blue (’050 Patent, col. 2:20-25). However, unlike the process-focused ’992 and ’616 patents, the claims of the ’050 patent are directed to the resulting product: the isosulfan blue compound itself, a solution containing it, or a composition consisting essentially of it, all defined by having a purity of at least 99.0% as measured by High-Performance Liquid Chromatography (HPLC) (’050 Patent, Claims 1, 11, 15).
Asserted Claims
Independent Claims 1, 11, and 15 (Compl. ¶85).
Accused Features
The complaint alleges that Defendant’s isosulfan blue active pharmaceutical ingredient (ISB API) infringes Claim 1, and that the final Beloteca ANDA Product infringes Claims 11 (as a solution) and 15 (as a composition), because they all allegedly possess the claimed purity of at least 99.0% by HPLC (Compl. ¶96-98).
III. The Accused Instrumentality
Product Identification
The "Beloteca ANDA Product," an isosulfan blue for injection product submitted to the FDA under ANDA No. 210714, and the isosulfan blue active pharmaceutical ingredient ("ISB API") contained therein (Compl. ¶2, 5).
Functionality and Market Context
The Beloteca ANDA Product is a generic drug intended for use as a contrast agent to delineate lymphatic vessels, the same use as Plaintiffs’ branded product (Compl. ¶23, 25). The complaint alleges that Mylan's product is the designated FDA "Reference Standard" against which generic products like Beloteca's must prove bioequivalence (Compl. ¶26). An FDA Orange Book listing, attached as Exhibit D, shows Mylan's product as the Reference Listed Drug (RLD) and Beloteca's product as an approved generic (Compl. Ex. D, p. 43). Plaintiffs allege that Beloteca's product will directly compete with and displace sales of their own product (Compl. ¶23).
IV. Analysis of Infringement Allegations
U.S. Patent No. 7,662,992 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A process of preparing...sodium salt comprising combining a suspension of isoleuco acid...in a polar solvent with 2.0 to 3.0 equivalents of silver oxide, | The complaint alleges on information and belief that the process used to make the ISB API includes combining isoleuco acid with 2.0-3.0 equivalents of silver oxide and a polar solvent. | ¶51 | col. 9:65-10:2 |
| recovering isosulfan blue acid, | The process allegedly includes recovering isosulfan blue acid. | ¶51 | col. 10:2-3 |
| and treating the isosulfan blue acid with a sodium solution. | The process allegedly includes treating the isosulfan blue acid with a sodium solution to obtain the final salt. | ¶52 | col. 10:3-4 |
U.S. Patent No. 8,969,616 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A process of preparing...sodium salt comprising combining a suspension of isoleuco acid...in a polar solvent with silver oxide, | The complaint alleges on information and belief that the process used to make the ISB API includes combining isoleuco acid with silver oxide and a polar solvent. | ¶74 | col. 9:43-45 |
| recovering isosulfan blue acid, | The process allegedly includes recovering isosulfan blue acid. | ¶74 | col. 9:45-46 |
| and treating the isosulfan blue acid with a sodium solution. | The process allegedly includes treating the isosulfan blue acid with a sodium solution. | ¶75 | col. 9:46-47 |
- Identified Points of Contention:
- Evidentiary Questions: The infringement allegations for the process patents are made "on information and belief," as the defendant's manufacturing process is confidential. A central question for the court will be what evidence Plaintiffs can obtain through discovery to substantiate the claim that Beloteca’s process uses the specific steps and reagents recited in the claims, particularly the use of "silver oxide" as the oxidizing agent. The complaint's allegations that Beloteca "copied" the patents will be used to support these claims (Compl. ¶57, 79).
- Technical Questions: What proof will be offered that Beloteca's process uses not just silver oxide, but the specific "2.0 to 3.0 equivalents" required by Claim 1 of the ’992 patent? This quantitative limitation may become a key point of dispute.
V. Key Claim Terms for Construction
For the '050 patent, which is directed to the product rather than the process, a key term will be the purity limitation.
- The Term: "a purity of at least 99.0% by HPLC" (’050 Patent, Claim 1).
- Context and Importance: This purity level is the central, objective feature that allegedly distinguishes the claimed compound from prior art isosulfan blue. Infringement of the ’050 patent hinges entirely on whether the accused product meets this specific, numerically-defined threshold. Practitioners may focus on this term because the entire infringement case for this patent rests on a quantitative chemical analysis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims consistently recite the "at least 99.0%" threshold, and the specification defines "substantially pure" as "99.0% or greater" (’050 Patent, col. 2:30-31). A party could argue that "by HPLC" refers to any standard High-Performance Liquid Chromatography method that a person of ordinary skill in the art would have used at the time to measure the purity of such a compound.
- Evidence for a Narrower Interpretation: The specification provides examples of achieving purity "NLT 99.5% performed by High Performance Liquid Chromatography" (’050 Patent, col. 7:31-35), but does not detail the specific HPLC parameters (e.g., column type, mobile phase, flow rate, detector wavelength). A party could argue that the absence of a specific testing protocol renders the term indefinite, or alternatively, that the term must be construed in light of the specific process embodiments that are disclosed to achieve that purity.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Beloteca induces infringement by contracting with third-party facilities to manufacture the ISB API and the final ANDA product using the patented processes (Compl. ¶44, 67, 88). It also alleges inducement of its distributor, TruPharma, to sell the final product (Compl. ¶49, 72). For the ’050 patent, the complaint alleges contributory infringement, stating the ISB API is a material component made especially for infringing use with no substantial non-infringing uses (Compl. ¶91).
- Willful Infringement: The complaint alleges pre-suit knowledge, stating on information and belief that Beloteca was aware of the patents and reviewed them prior to the lawsuit (Compl. ¶34, 53, 76, 94). The basis for willfulness is further supported by allegations that Beloteca "copied" the patented process and portions of the patent specification when developing its own process and drafting its own patent application (Compl. ¶55-57, 78-79).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of evidentiary proof: What facts will emerge from discovery regarding Beloteca’s confidential manufacturing process? The case for infringement of the ’992 and ’616 patents depends entirely on whether Plaintiffs can prove that this process mirrors the claimed steps, especially the use of silver oxide as the oxidizing agent.
- A key question will be one of quantitative fact-finding: Does Beloteca’s ISB API and final drug product actually meet the "purity of at least 99.0% by HPLC" threshold required by the claims of the ’050 patent? This will likely devolve into a battle of competing expert analyses.
- A potential legal question will be one of claim construction and definiteness: Given the centrality of the "99.0% by HPLC" limitation, the court may need to determine whether the patent provides sufficient detail for a person skilled in the art to reliably and consistently measure this purity, or if the term is unenforceably vague without a specified testing protocol.