DCT
1:24-cv-01331
Amicus Therap US LLC v. Aurobindo Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Amicus Therapeutics US, LLC and Amicus Therapeutics, Inc. (Delaware)
- Defendant: Aurobindo Pharma Ltd. (India) and Aurobindo Pharma USA, Inc. (Delaware)
- Plaintiff’s Counsel: Barnes & Thornburg LLP
- Case Identification: 1:24-cv-01331, D. Del., 12/06/2024
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Aurobindo Pharma USA is incorporated in Delaware, and because Defendant Aurobindo Pharma Ltd., as a foreign corporation, may be sued in any judicial district. The complaint also asserts that both entities are submitters of the underlying drug application central to the suit.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of GALAFOLD (migalastat) constitutes an act of infringement of three patents related to methods of treating Fabry disease in patients with renal impairment.
- Technical Context: The technology concerns a specific dosing regimen for migalastat, an oral small-molecule drug used as a pharmacological chaperone to treat Fabry disease, a rare genetic lysosomal storage disorder.
- Key Procedural History: The complaint notes prior, consolidated patent infringement litigation between Amicus and Aurobindo involving other patents covering GALAFOLD (Case No. 22-1461). The parties had reportedly agreed that Amicus would assert newly issued patents, such as those in the present suit, in additional actions that would be consolidated with the original case.
Case Timeline
| Date | Event |
|---|---|
| 2017-05-30 | Priority Date for ’489, ’490, and ’205 Patents |
| 2018-08-10 | FDA Approval of GALAFOLD (NDA No. 208623) |
| 2022-02-25 | Aurobindo submitted Drug Master File for migalastat hydrochloride |
| 2022-10-06 | First Aurobindo ANDA Notice Letter sent to Amicus |
| 2024-07-23 | U.S. Patent No. 12,042,489 Issued |
| 2024-07-23 | U.S. Patent No. 12,042,490 Issued |
| 2024-10-08 | U.S. Patent No. 12,109,205 Issued |
| 2024-12-06 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 12,042,489 - "Methods of Treating Fabry Patients Having Renal Impairment"
- Patent Identification: U.S. Patent No. 12,042,489, "Methods of Treating Fabry Patients Having Renal Impairment", issued July 23, 2024 (the "’489 Patent").
The Invention Explained
- Problem Addressed: The patent addresses the treatment of Fabry disease, a lysosomal storage disorder that frequently leads to renal impairment (Compl. ¶4). Existing enzyme replacement therapies (ERT) have drawbacks, including poor penetration into key organs like the kidneys and the potential for rapid degradation, which complicates treatment, particularly in patients with compromised renal function (’489 Patent, col. 2:59-67).
- The Patented Solution: The invention is a method of treatment using migalastat, a small-molecule pharmacological chaperone that binds to and stabilizes a patient's own deficient α-galactosidase A (α-Gal A) enzyme. This stabilization allows the enzyme to be properly trafficked to the lysosome to perform its function. The method is specifically directed to patients with "amenable" genetic mutations who may also have renal impairment (’489 Patent, Abstract; col. 2:52-58).
- Technical Importance: The invention provides an oral therapeutic alternative to intravenous ERT that functions by enhancing a patient's endogenous, albeit mutated, enzyme activity (Compl. ¶4).
Key Claims at a Glance
- The complaint asserts dependent claims 17 and 23 (Compl. ¶88). These claims depend on independent claim 1.
- The essential elements of independent claim 1 are:
- A method of treating Fabry disease,
- comprising administering migalastat to a patient in need thereof,
- wherein the patient has an α-galactosidase A protein comprising a HEK assay amenable mutation selected from a specific list of mutations.
- Asserted claim 17 adds the limitations that the patient has mild renal impairment and is male. Asserted claim 23 adds the limitations that the patient has mild renal impairment and is female (’489 Patent, col. 51-52).
U.S. Patent No. 12,042,490 - "Methods of Treating Fabry Patients Having Renal Impairment"
- Patent Identification: U.S. Patent No. 12,042,490, "Methods of Treating Fabry Patients Having Renal Impairment", issued July 23, 2024 (the "’490 Patent").
The Invention Explained
- Problem Addressed: As with the related ’489 Patent, this invention is directed to the challenge of treating Fabry disease, particularly in patients who exhibit renal impairment, for whom traditional ERT may be suboptimal (’490 Patent, col. 2:59-67).
- The Patented Solution: The patent claims a method of treating Fabry disease by administering a specific dose of migalastat hydrochloride (about 150 mg) at a specific frequency (once every other day) to patients having particular amenable mutations in the α-Gal A enzyme (’490 Patent, Abstract; col. 31-32).
- Technical Importance: This patent claims a specific dosing regimen for the oral pharmacological chaperone, providing a defined therapeutic protocol for a difficult-to-treat patient population (Compl. ¶40).
Key Claims at a Glance
- The complaint asserts independent claim 9 (Compl. ¶123).
- The essential elements of independent claim 9 are:
- A method of treating Fabry disease,
- comprising administering about 150 mg of migalastat hydrochloride to a patient in need thereof,
- at a frequency of once every other day,
- wherein the patient has an α-galactosidase A protein comprising a HEK assay amenable mutation selected from a specific list of mutations.
U.S. Patent No. 12,109,205 - "Methods of Treating Fabry Patients Having Renal Impairment"
- Patent Identification: U.S. Patent No. 12,109,205, "Methods of Treating Fabry Patients Having Renal Impairment", issued October 8, 2024 (the "’205 Patent").
- Technology Synopsis: This patent is part of the same family as the ’489 and ’490 patents and is directed to similar subject matter. It addresses the technical problem of treating Fabry disease patients with renal impairment using an oral pharmacological chaperone (’205 Patent, col. 2:59-67). The patented solution is a method of administering migalastat to patients with specific, amenable genetic mutations to stabilize their endogenous enzyme and treat the disease (’205 Patent, Abstract).
- Asserted Claims: The complaint asserts claims 59, 73, 86, and 89 (Compl. ¶158). Claim 59 is independent; the others are dependent upon it.
- Accused Features: The accused features are the methods of use that will allegedly be described in the product labeling for Aurobindo’s proposed generic migalastat product, which are expected to instruct administration for treating Fabry disease in patients with amenable mutations (Compl. ¶68, 162).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Aurobindo’s generic version of GALAFOLD, identified as "Aurobindo's ANDA Product," for which Aurobindo submitted Abbreviated New Drug Application No. 217786 to the FDA (Compl. ¶1, 63).
Functionality and Market Context
- The product is described as a capsule containing 123 mg of migalastat free base, which is intended to be bioequivalent to Amicus's GALAFOLD Capsules (Compl. ¶63, 90). GALAFOLD is an oral medication administered every other day for the treatment of adults with Fabry disease who have an amenable genetic variant (Compl. ¶40). The act of infringement alleged under the Hatch-Waxman Act is Aurobindo's filing of the ANDA seeking FDA approval to market this generic product for the patented methods of use prior to the expiration of the Patents-in-Suit (Compl. ¶1, 88). The complaint alleges that Aurobindo will provide its product with a label that is "identical in all relevant respects to the labeling of GALAFOLD," thereby instructing physicians and patients to use the drug in a manner that infringes the asserted patents (Compl. ¶68).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’489 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating Fabry disease... | Aurobindo's ANDA seeks approval to market its product for the treatment of Fabry disease, as instructed by its proposed label. | ¶1, ¶68 | col. 2:11-13 |
| ...comprising administering migalastat to a patient in need thereof... | Aurobindo's ANDA Product contains migalastat, and its proposed label will instruct administration to patients with Fabry disease. | ¶63, ¶72 | col. 3:25-32 |
| ...wherein the patient has an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of... | The proposed product label will allegedly instruct use in patients with an amenable mutation, mirroring the approved use of GALAFOLD. | ¶40, ¶68 | col. 17:30-36 |
’490 Patent Infringement Allegations
| Claim Element (from Independent Claim 9) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating Fabry disease... | Aurobindo's ANDA seeks approval to market its product for the treatment of Fabry disease, as instructed by its proposed label. | ¶1, ¶68 | col. 2:11-13 |
| ...comprising administering about 150 mg of migalastat hydrochloride to a patient in need thereof at a frequency of once every other day... | Aurobindo’s product is a 123 mg free base capsule, which is the approved dosage equivalent of 150 mg migalastat HCl, and its label will instruct administration every other day. | ¶40, ¶63, ¶68 | col. 29:40-47 |
| ...wherein the patient has an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of... | The proposed product label will allegedly instruct use in patients with an amenable mutation, mirroring the approved use of GALAFOLD. | ¶40, ¶68 | col. 17:30-36 |
- Identified Points of Contention:
- Scope Questions: A central question will be whether Aurobindo's proposed product label will necessarily instruct users to perform every step of the claimed methods. For the ’489 Patent, this raises the question of whether the label will specifically direct use in patients with "mild renal impairment," as required by asserted claims 17 and 23.
- Technical Questions: In an ANDA case based on induced infringement, a key question for the court is whether the proposed generic product has a substantial non-infringing use. The complaint alleges that the product is not a staple article of commerce and is especially adapted for the infringing use, which suggests the possibility that this will be a point of contention (Compl. ¶81).
V. Key Claim Terms for Construction
The Term: "mild renal impairment"
- Context and Importance: This term appears in the asserted claims of the ’489 Patent (claims 17 and 23). Its construction is critical because it defines the specific patient subpopulation covered by those claims, and thus will be dispositive for the infringement analysis of that patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification provides several definitions for degrees of renal impairment based on estimated glomerular filtration rate (eGFR). It defines "mild" renal impairment as corresponding to Stage 2 kidney disease, with a GFR of 60 to 89 mL/min/1.73 m² (’489 Patent, col. 14:1-2). Parties may argue this explicit definition should control.
- Evidence for a Narrower Interpretation: The specification discusses clinical trials that enrolled patients with specific GFR cutoffs, such as "≥30 mL/min/1.73 m²" (’489 Patent, col. 29:51-52). A party could argue that the term's meaning should be narrowed by the context of these disclosed embodiments, potentially limiting its scope to patient profiles matching those in the trials.
The Term: "HEK assay amenable mutation"
- Context and Importance: This term appears in the independent claims of all asserted patents and defines the genetic profile of the eligible patient population. Its scope is fundamental to the infringement case, as the accused product's label must be found to instruct use in patients with such mutations.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition, stating that an amenable mutation is one that shows "a relative increase (+10 µM migalastat) of ≥1.20-fold and an absolute increase... of ≥3.0% wild-type" in a specific in-vitro assay (’489 Patent, col. 17:30-36). This functional language could be argued to cover any mutation that meets the test, whether explicitly listed or not.
- Evidence for a Narrower Interpretation: The patents provide an extensive, multi-page table (Table 1) explicitly listing hundreds of mutations identified as "amenable" (’489 Patent, col. 19-28). A party might argue that the claim term should be limited to the mutations explicitly recited in this list, treating it as a closed set that defines the invention's scope.
VI. Other Allegations
- Indirect Infringement: The complaint centers on allegations of indirect infringement. It alleges inducement on the basis that Aurobindo's proposed product label will actively encourage and instruct physicians and patients to perform the patented methods (Compl. ¶79, 94, 129). It also alleges contributory infringement, stating that Aurobindo's product is not a staple article of commerce suitable for substantial non-infringing use and is especially made for an infringing purpose (Compl. ¶81).
- Willful Infringement: The complaint does not include an explicit allegation of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement: does Aurobindo's proposed product label, by allegedly being identical to the GALAFOLD label, necessarily instruct physicians to prescribe and patients to use the generic drug in a manner that meets every limitation of the asserted method claims, particularly the limitation requiring a specific "HEK assay amenable mutation"?
- A key question will be one of claim scope: how will the court construe the term "mild renal impairment" in the ’489 Patent? The outcome will determine whether the infringement analysis for that patent can proceed and will define the precise patient population at issue.
- An underlying evidentiary question will be whether there are substantial non-infringing uses for Aurobindo's generic migalastat product. The court’s finding on this issue will be critical to resolving the claims for both induced and contributory infringement.