DCT
1:23-cv-01079
Orphalan SA v. Novitium Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Orphalan SA (France)
- Defendant: Novitium Pharma LLC (Delaware)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:23-cv-01079, D. Del., 09/29/2023
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant's Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's CUVRIOR® tablets infringes two patents covering a specific crystalline polymorph of trientine tetrachloride and its method of use for treating Wilson's disease.
- Technical Context: The technology concerns pharmaceutical formulations, specifically a stable crystalline form of a copper-chelating agent used to treat Wilson's disease, a rare genetic disorder that causes copper accumulation in the body.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a notice letter from Defendant. The letter stated that Defendant had filed an ANDA with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2018-05-04 | Priority Date for '436 and '577 Patents |
| 2021-04-27 | U.S. Patent No. 10,988,436 Issues |
| 2021-07-27 | U.S. Patent No. 11,072,577 Issues |
| 2022-04-28 | FDA approves Orphalan's New Drug Application for CUVRIOR® |
| 2023-08-17 | Date of Novitium's Notice Letter to Orphalan |
| 2023-09-29 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,988,436 - “Crystalline form of triethylenetetramine tetrahydrochloride and its pharmaceutical use,” issued April 27, 2021
The Invention Explained
- Problem Addressed: The patent describes that prior art forms of trientine, particularly the dichloride salt, lacked sufficient stability at room temperature and were sensitive to humidity, creating an "onerous requirement" for patients to store the medication under reduced temperature conditions (’436 Patent, col. 1:47-58).
- The Patented Solution: The invention is a new, stable crystalline polymorph of trientine tetrachloride (TETA.4HCl), designated "Form B." This form is produced by carefully controlling manufacturing conditions, such as temperature and the rate of crystallization, to avoid a different, less stable crystalline form known as "Form A" (’436 Patent, Abstract; col. 2:14-29). The complaint provides a diagram of the chemical structure for trientine tetrachloride, the active ingredient's salt form (Compl. ¶15).
- Technical Importance: This new crystalline form is intended to provide a drug product for Wilson's disease that can be delivered orally and remains stable under ambient conditions, improving patient convenience and the reliability of the treatment (’436 Patent, col. 1:64-col. 2:2).
Key Claims at a Glance
- The complaint asserts at least one claim of the patent (Compl. ¶23). Independent claim 1 is representative:
- A crystalline form of triethylenetetramine tetrahydrochloride Form B having specific characteristics defined by an X-ray powder diffraction (XRPD) pattern and/or a Raman spectrum.
- The crystalline form contains no more than 10 wt % of triethylenetetramine tetrahydrochloride Form A, which is itself defined by a different XRPD pattern.
- The XRPD peaks are specified as being measured using a specific wavelength of radiation (1.5418 Å).
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 11,072,577 - “Crystalline form of triethylenetetramine tetrahydrochloride and its pharmaceutical use,” issued July 27, 2021
The Invention Explained
- Problem Addressed: The ’577 patent, a continuation of the application that led to the ’436 patent, addresses the same technical problem of the instability of prior art trientine salts used for treating Wilson's disease (’577 Patent, col. 1:45-58).
- The Patented Solution: Instead of claiming the compound itself, this patent claims a method of treating Wilson's disease by administering an effective amount of the specific "Form B" crystalline polymorph of TETA.4HCl, as defined by its characteristic XRPD/Raman spectra and purity relative to Form A (’577 Patent, Abstract; col. 2:54-65).
- Technical Importance: By claiming the method of use, the patent provides a different scope of protection than the composition-of-matter claims in the parent ’436 patent, covering the therapeutic application of the stable drug form.
Key Claims at a Glance
- The complaint asserts at least one claim of the patent (Compl. ¶38). Independent claim 1 is representative:
- A method of treating or preventing Wilson's disease in a subject.
- The method comprises administering an effective amount of the crystalline Form B of triethylenetetramine tetrahydrochloride.
- The crystalline Form B is defined by the same XRPD/Raman spectra and the same "no more than 10 wt %" purity limitation with respect to Form A as in the ’436 patent.
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
- Product Identification: Defendant’s proposed generic trientine tetrachloride tablets, 300 mg, as described in ANDA No. 218493 ("Novitium's Proposed ANDA Product") (Compl. ¶1, ¶4).
- Functionality and Market Context: The proposed product is a generic version of Plaintiff’s CUVRIOR®, an orphan drug used as a copper chelator for the treatment of adult patients with stable Wilson's disease (Compl. ¶1, ¶14). The complaint alleges, on information and belief, that Novitium's product is manufactured using the patented crystalline Form B and meets the claimed purity limitations (Compl. ¶23, ¶35). It is further alleged that the proposed product labeling will be "substantially identical" to the CUVRIOR® label, instructing its use for the treatment of Wilson's disease (Compl. ¶36).
IV. Analysis of Infringement Allegations
10,988,436 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A crystalline form of triethylenetetramine tetrahydrochloride Form B having at least one of the following characteristics: (i) an XRPD pattern having at least two peaks selected from the peaks at 22.9, 25.4, 25.8, 26.6, 34.6 and 35.3±0.1°20; and/or ... | On information and belief, Novitium's Proposed ANDA Product contains and/or is manufactured using a crystalline form of trientine tetrahydrochloride Form B. | ¶23 | col. 2:23-38 |
| wherein the crystalline form contains no more than 10 wt % of triethylenetetramine tetrahydrochloride Form A having an XRPD pattern having peaks at 25.2 and 35.7±0.1°20... | The complaint alleges that the crystalline form in Novitium's product contains no more than 10 weight % of trientine tetrahydrochloride Form A. | ¶23 | col. 8:60-9:3 |
- Identified Points of Contention:
- Factual Question: The central dispute will be factual: does Novitium’s proposed product actually contain the specific crystalline polymorph "Form B" as defined by the patent's analytical (XRPD and Raman) characteristics?
- Evidentiary Question: What analytical evidence will be produced in discovery to establish the precise polymorphic composition and purity of Novitium's product, and how will it compare to the patent’s definitions of Form A and Form B?
11,072,577 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating or preventing Wilson's disease in a subject, which method comprises the administration to said subject of an effective amount of... | On information and belief, Novitium's proposed product labeling will be substantially identical to the CUVRIOR® label, which instructs and encourages physicians to administer the product to treat Wilson's disease. | ¶36, ¶37 | col. 2:54-58 |
| a crystalline form of triethylenetetramine tetrahydrochloride Form B... and which contains no more than 10 wt % of triethylenetetramine tetrahydrochloride Form A... | On information and belief, Novitium's product contains the specified crystalline Form B and meets the claimed purity limitation of containing no more than 10 weight % of Form A. | ¶35 | col. 2:14-29 |
- Identified Points of Contention:
- Scope Question: Does the act of submitting an ANDA with a proposed label that mirrors the branded drug's indication for Wilson's disease satisfy the requirements for inducing infringement of a method-of-treatment claim, contingent on the product itself meeting the claim's technical limitations?
- Technical Question: This analysis is dependent on the same factual question as the ’436 patent: does the accused product actually contain the claimed crystalline form? If it does not, the method of using it cannot infringe.
V. Key Claim Terms for Construction
The Term: "crystalline form of triethylenetetramine tetrahydrochloride Form B"
Context and Importance: This term defines the core of the invention in both patents. The dispute will center on whether Novitium's product embodies this specific polymorph. The definition is not a plain English one but is explicitly tied to analytical data in the claims themselves. Practitioners may focus on whether the claim language requires meeting the exact peak values or allows for measurement variability inherent in XRPD and Raman spectroscopy.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims use "at least two peaks selected from" a list of six XRPD peaks, suggesting that not all peaks must be present. This language may support an interpretation that a product infringes even if its analytical signature is not a perfect match to all recited characteristics. (’436 Patent, col. 26:11-24).
- Evidence for a Narrower Interpretation: The specification repeatedly distinguishes "Form B" from the prior art "Form A," emphasizing that Form B is only produced under carefully controlled and specific manufacturing conditions (e.g., crystallization below 20° C) (’436 Patent, col. 9:4-25). This could support a narrower construction where Form B is strictly limited to the polymorph produced by such exacting processes.
The Term: "contains no more than 10 wt % of triethylenetetramine tetrachloride Form A"
Context and Importance: This negative limitation is a critical aspect of purity that defines the claimed invention. Infringement requires Novitium's product to be relatively pure of Form A. A central dispute may arise over the analytical methods used to quantify the percentage of Form A versus Form B in the accused product.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail for analysis of this element.
- Evidence for a Narrower Interpretation: The patent defines "Form A" with its own specific XRPD peaks (25.2 and 35.7±0.1°20) and notes that standard crystallization techniques produce it (’436 Patent, col. 8:45-54). The patent's focus on the discovery of a process to avoid Form A suggests that the "no more than 10 wt %" limit is a meaningful and strict boundary for the invention.
VI. Other Allegations
- Indirect Infringement: For the ’577 patent, the complaint alleges both induced and contributory infringement. Inducement is based on the allegation that Novitium's proposed product label will instruct and encourage physicians and patients to perform the claimed method of treating Wilson's disease (Compl. ¶36, ¶39). Contributory infringement is alleged on the basis that Novitium's product is "especially made or especially adapted for use in infringing" the patent and is not a staple commodity with substantial non-infringing uses (Compl. ¶40).
- Willful Infringement: The complaint alleges that Novitium has "actual knowledge" of the patents-in-suit, citing Novitium's reference to them in its Paragraph IV notice letter and their listing in the FDA's Orange Book (Compl. ¶24, ¶39). While the word "willful" is not used in the infringement counts, this allegation of pre-suit knowledge provides a basis for a later claim of willful infringement and supports the request for a finding that the case is "exceptional" (Prayer for Relief ¶G).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of factual proof: Can Plaintiff demonstrate through analytical testing that Defendant’s proposed generic product is, in fact, composed of the specific crystalline polymorph "Form B" and meets the purity requirements as defined by the spectral data in the patent claims? The outcome will likely depend on a battle of experts in pharmaceutical analytical chemistry.
- A key question for the method-of-treatment patent (’577 Patent) will be one of inducement: Assuming the accused product is found to contain the claimed crystalline form, will the contents of Defendant’s proposed product label be deemed sufficient evidence of the specific intent required to encourage or persuade others to directly infringe the claimed method?