DCT

1:23-cv-00964

Amicus Therap US LLC v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00964, D. Del., 09/01/2023
  • Venue Allegations: Venue is alleged to be proper for Lupin Pharmaceuticals, Inc. as it is a Delaware corporation. Venue for Lupin Ltd. is alleged based on its submission of an Abbreviated New Drug Application (ANDA) and its status as a foreign corporation that may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants’ submission of an ANDA to the FDA seeking to market a generic version of Plaintiff’s GALAFOLD® (migalastat) product infringes seven U.S. patents related to methods of treating Fabry disease.
  • Technical Context: The technology concerns the use of migalastat, a pharmacological chaperone, for the oral treatment of Fabry disease, a rare X-linked lysosomal storage disorder caused by deficient α-galactosidase A enzyme activity.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 217793 and a corresponding Paragraph IV certification notice. The notice letter asserted that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2006-05-16 Earliest Priority Date for ’011, ’263, ’864, ’143 Patents
2007-04-26 Earliest Priority Date for ’866 Patent
2008-02-12 Earliest Priority Date for ’921 Patent
2008-11-11 Earliest Priority Date for RE48,608 Patent
2015-04-07 U.S. Patent No. 9,000,011 Issued
2018-06-05 U.S. Patent No. 9,987,263 Issued
2018-08-10 FDA Approved GALAFOLD New Drug Application
2019-08-20 U.S. Patent No. 10,383,864 Issued
2019-09-10 U.S. Patent No. 10,406,143 Issued
2020-10-27 U.S. Patent No. 10,813,921 Issued
2021-02-23 U.S. Patent No. 10,925,866 Issued
2021-06-29 U.S. Patent No. RE48,608 Issued
2022-03-31 Lupin Submitted Drug Master File for migalastat hydrochloride
2023-08-09 Lupin's Notice Letter Dated
2023-08-10 Amicus Received Lupin's Notice Letter
2023-09-01 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,000,011 - "Methods for Treatment of Fabry Disease," Issued April 7, 2015

The Invention Explained

  • Problem Addressed: Fabry disease is an inherited disorder caused by a deficiency of the enzyme α-galactosidase A (α-GAL). This deficiency leads to the harmful accumulation of a lipid substance (globotriaosylceramide, or GL-3) in cells throughout the body, resulting in severe symptoms including kidney failure, heart complications, and stroke. Certain genetic mutations result in an unstable α-GAL enzyme that is prematurely degraded by the cell’s quality control mechanisms before it can reach the lysosome to break down GL-3 (’011 Patent, col. 1:40-2:2).
  • The Patented Solution: The invention provides a method of treatment using a "specific pharmacological chaperone" (SPC), identified as 1-deoxygalactonojirimycin (migalastat). This small molecule binds to the unstable α-GAL enzyme in the endoplasmic reticulum, stabilizing its structure. This stabilization allows the enzyme to pass the cell's quality control checks, traffic to the lysosome, and carry out its function of hydrolyzing GL-3, thereby treating the underlying cause of the disease (’011 Patent, col. 3:45-4:12; col. 7:21-30).
  • Technical Importance: This oral small-molecule therapy offers an alternative to intravenous enzyme replacement therapy, with the potential to treat certain patient populations and address pathologies that replacement enzymes may not sufficiently penetrate (’011 Patent, col. 3:50-4:12).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim, including independent claim 1 (Compl. ¶96).
  • Essential elements of independent claim 1 include:
    • A method for enhancing α-galactosidase A (α-GAL) activity in a patient diagnosed with or suspected of having Fabry disease
    • comprising administering to the patient a therapeutically effective dose
    • of 150 mg 1-deoxygalactonojirimycin or a salt thereof
    • every other day.
  • The complaint does not explicitly reserve the right to assert dependent claims, but alleges infringement of "one or more claims" (Compl. ¶99).

U.S. Patent No. 9,987,263 - "Methods for Treatment of Fabry Disease," Issued June 5, 2018

The Invention Explained

  • Problem Addressed: As described for the ’011 Patent, the core problem is the instability of the α-GAL enzyme caused by certain genetic mutations, leading to Fabry disease. The patent notes that it is difficult to predict which specific mutations result in an unstable enzyme that can be "rescued" by a pharmacological chaperone (’263 Patent, col. 3:9-14).
  • The Patented Solution: This patent claims methods of treating Fabry disease by administering a pharmacological chaperone to patients who have specific, enumerated missense mutations in their α-GAL gene. The invention is based on the discovery that patients with these particular mutations produce an enzyme that is responsive to stabilization by the chaperone, allowing for effective treatment (’263 Patent, col. 3:45-4:12, Abstract).
  • Technical Importance: The invention provides a method for treating specific, identified subpopulations of Fabry disease patients for whom the pharmacological chaperone therapy is expected to be effective, enabling a more targeted therapeutic approach (’263 Patent, col. 1:1-2:2).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim, including independent claim 1 (Compl. ¶111).
  • Essential elements of independent claim 1 include:
    • A method for treatment of Fabry disease in a human patient in need thereof
    • the method comprising administering to the patient a therapeutically effective dose of 1-deoxygalactonojirimycin or a salt thereof,
    • wherein the patient has an α-galactosidase A mutation selected from a large, specified group of mutations (e.g., A143T, A97V, M51K, L300P, G328A, P205T, N215S, etc.).
  • The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶114).

U.S. Patent No. 10,383,864 - "Methods for Treatment of Fabry Disease," Issued August 20, 2019

  • Technology Synopsis: This patent addresses the same technical problem as its parent patents. The claimed solution is a method for treating Fabry disease by administering a specific dosage range (50 to 250 mg) of migalastat or its salt every other day (’864 Patent, Claim 1).
  • Asserted Claims: The complaint asserts at least one claim, including independent claim 1 (Compl. ¶126).
  • Accused Features: The accused features are the composition, dosage, and proposed administration schedule of Lupin's ANDA Product, which are alleged to be the same as GALAFOLD (Compl. ¶124).

U.S. Patent No. 10,406,143 - "Methods for Treatment of Fabry Disease," Issued September 10, 2019

  • Technology Synopsis: This patent, part of the same family, claims a method of treating Fabry disease by administering migalastat (or a salt thereof) every other day. The claims are directed to patients having one of a specific list of amenable α-galactosidase A mutations (’143 Patent, Claim 1).
  • Asserted Claims: The complaint asserts at least one claim, including independent claim 1 (Compl. ¶141).
  • Accused Features: The accused features are the composition and proposed method of administration of Lupin's ANDA Product, which is intended for the same patient population as GALAFOLD (Compl. ¶139).

U.S. Patent No. 10,925,866 - "Dosing Regimens for the Treatment of Lysosomal Storage Diseases Using Pharmacological Chaperones," Issued February 23, 2021

  • Technology Synopsis: This patent describes specific dosing regimens for pharmacological chaperones. The claims cover administering migalastat at a dose of 150 mg every other day, with specific pharmacokinetic parameters defined, such as mean maximum plasma concentration (Cmax) and time to Cmax (Tmax) (’866 Patent, Claim 1).
  • Asserted Claims: The complaint asserts at least one claim, including independent claim 1 (Compl. ¶156).
  • Accused Features: Lupin's ANDA Product is accused of infringing because it is bioequivalent to GALAFOLD and will thus exhibit the claimed pharmacokinetic profile when administered as instructed (Compl. ¶154, ¶158).

U.S. Patent No. 10,813,921 - "Method to Predict Response to Pharmacological Chaperone Treatment of Diseases," Issued October 27, 2020

  • Technology Synopsis: This patent relates to methods of treating Fabry disease patients who have been identified as responsive to migalastat therapy. The claims are directed to treating patients with specific mutations that have been determined to produce an enzyme that is stabilized by the chaperone (’921 Patent, Claim 1).
  • Asserted Claims: The complaint asserts at least one claim, including independent claim 1 (Compl. ¶171).
  • Accused Features: Lupin’s ANDA Product is accused because its label will allegedly instruct use in the same patient population as GALAFOLD, which includes patients with the claimed amenable mutations (Compl. ¶169).

U.S. Patent No. RE48,608 - "Method to Predict Response to Pharmacological Chaperone Treatment of Diseases," Issued June 29, 2021

  • Technology Synopsis: This patent is a reissue of U.S. Patent No. 8,592,362 and is directed to similar subject matter as the ’921 patent. It claims methods of treating Fabry disease by administering migalastat to patients with specific, identified amenable mutations in the α-GAL gene (RE48,608 Patent, Claim 1).
  • Asserted Claims: The complaint asserts at least one claim, including independent claim 1 (Compl. ¶186).
  • Accused Features: The features of Lupin's ANDA product are accused of infringement because its proposed use, as defined by its ANDA and label, will be for the same patient population as GALAFOLD, which includes patients having the claimed responsive mutations (Compl. ¶184).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Lupin's ANDA Product," identified as "migalastat hydrochloride capsules, eq 123 mg base" (Compl. ¶6). This is a proposed generic version of Amicus' GALAFOLD® Capsules (Compl. ¶71).

Functionality and Market Context

  • The complaint alleges that Lupin's ANDA Product, by law, must have the same active ingredient (migalastat), dosage form (capsule), dosage amount (equivalent to 123 mg free base), and method of administration as GALAFOLD (Compl. ¶94). It is alleged to be pharmaceutically and therapeutically equivalent to GALAFOLD (Compl. ¶94). The infringement action is based on Lupin’s submission of ANDA No. 217793, which is a statutory act of infringement seeking FDA approval to market this generic drug prior to the expiration of the patents-in-suit (Compl. ¶1, ¶96). The complaint alleges that upon approval, Lupin will provide the ANDA Product with a label that substantially copies the instructions for GALAFOLD, thereby directing its use in an infringing manner (Compl. ¶75).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

U.S. Patent No. 9,000,011 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for enhancing α-galactosidase A (α-GAL) activity in a patient diagnosed with or suspected of having Fabry disease Lupin's proposed product label will instruct physicians and patients to use the drug to treat Fabry disease, which will result in the enhancement of α-GAL activity. ¶75, ¶78, ¶86 col. 5:8-14
comprising administering to the patient a therapeutically effective dose Lupin’s ANDA seeks approval for a product represented to be therapeutically equivalent to GALAFOLD Capsules and administered according to a label that will substantially copy the GALAFOLD label. ¶75, ¶94 col. 7:52-56
of 150 mg 1-deoxygalactonojirimycin or a salt thereof Lupin's ANDA Product is "migalastat hydrochloride capsules, eq 123 mg base." Migalastat is 1-deoxygalactonojirimycin, and 150 mg of the hydrochloride salt is equivalent to 123 mg of the free base. ¶6, ¶98 col. 7:5-8
every other day. The instructions for use on Lupin's proposed label will substantially copy the instructions for GALAFOLD, which is administered every other day. ¶29, ¶75, ¶78 col. 12:45-58

Identified Points of Contention

  • Scope Questions: The primary question for the court will be whether the acts of making and selling Lupin's ANDA Product, with its proposed label, will induce infringement of the claimed method by physicians and patients. This will involve analyzing whether the label encourages, recommends, or promotes the specific administration schedule and dosage to the specified patient population as required by the claim.
  • Technical Questions: In an ANDA case, the defendant often challenges the validity of the patent. A question for the court will be whether claim 1 of the ’011 Patent is valid in light of prior art. Another potential point of contention may be the definition of "therapeutically effective dose," and whether the 150 mg specified in the claim is merely an example or a required limitation.

U.S. Patent No. 9,987,263 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treatment of Fabry disease in a human patient in need thereof... Lupin's ANDA seeks approval for a product to treat Fabry disease, and its label will instruct physicians and patients to use the drug for this purpose. ¶71, ¶75 col. 1:40-44
the method comprising administering to the patient a therapeutically effective dose of 1-deoxygalactonojirimycin or a salt thereof, Lupin’s ANDA Product contains migalastat hydrochloride at a dosage amount equivalent to GALAFOLD and is alleged to be therapeutically equivalent. ¶94, ¶113 col. 12:50-58
wherein the patient has an α-galactosidase A mutation selected from the group consisting of [A143T, A97V, M51K, L300P, G328A, P205T, N215S, etc.]. The GALAFOLD label, which Lupin's label will allegedly copy, instructs use in patients with amenable mutations, which include the specific mutations listed in the claim. ¶29, ¶75 col. 7:6-50

Identified Points of Contention

  • Scope Questions: A central issue will be whether Lupin’s proposed label will specifically induce use in patients having the mutations recited in the claim. The analysis may focus on whether the label must explicitly list the mutations or if a general instruction to use the drug for Fabry disease in patients with "amenable" mutations is sufficient for a finding of inducement.
  • Technical Questions: Lupin's Paragraph IV letter asserts invalidity (Compl. ¶108). A key question will be whether the claimed method, limited to patients with specific mutations, was obvious over prior art that may have disclosed treating Fabry disease generally with migalastat.

V. Key Claim Terms for Construction

The Term: "therapeutically effective dose" (’011 Patent, Claim 1)

  • Context and Importance: This term defines the quantity of the drug to be administered. Its construction is central to the infringement analysis, as Lupin's ANDA product must be administered at a dose that falls within the claim's scope. Practitioners may focus on this term to argue for indefiniteness if its boundaries are not clear from the patent, or to argue that a specific dosage falls outside its scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification defines the term as the dose that achieves one or more of a list of clinical outcomes, such as improvements in renal function or prevention of stroke, rather than a specific numerical amount (’011 Patent, col. 9:10-12). This supports a functional definition based on patient response.
    • Evidence for a Narrower Interpretation: The claim itself recites "150 mg." The specification also provides specific examples of dosages, such as "about 150 mg/day" (’011 Patent, col. 12:40-42). This could support an argument that the term is limited to the specific amounts disclosed.

The Term: "patient has an α-galactosidase A mutation selected from the group consisting of..." (’263 Patent, Claim 1)

  • Context and Importance: This limitation defines the specific patient population covered by the method claim. For induced infringement, Amicus must show that Lupin's label will encourage or instruct physicians to prescribe the drug to patients with these specific mutations. The construction of this term will determine the level of specificity required in the accused product's labeling.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent explains that these listed mutations are ones that result in an unstable enzyme that can be "rescued" (’263 Patent, col. 3:9-14). A party could argue that any label instructing use for Fabry disease patients with amenable mutations implicitly targets this group, even without listing every mutation.
    • Evidence for a Narrower Interpretation: The claim uses the specific transitional phrase "consisting of," which is typically limiting. A party may argue that for infringement to be induced, the proposed label must specifically identify this closed group of mutations as being suitable for treatment.

VI. Other Allegations

Indirect Infringement

  • The complaint's core theory is indirect infringement. It alleges that Lupin will induce infringement by physicians and patients, and contribute to their infringement, by marketing its ANDA Product with a label that "will knowingly... substantially copy the instructions in the label for GALAFOLD Capsules" (Compl. ¶75, ¶88, ¶90). This act is alleged to be intentional and with knowledge of the patents-in-suit (Compl. ¶84, ¶87).

Willful Infringement

  • The complaint does not contain a separate count for willful infringement. However, it alleges that Lupin has "actual knowledge" of each patent-in-suit, as evidenced by its Paragraph IV Notice Letter (e.g., Compl. ¶95, ¶110). These allegations could form the basis for a future claim of willful infringement if Lupin were to launch its product "at risk" after litigation has commenced, potentially leading to a request for enhanced damages. The prayer for relief requests damages under 35 U.S.C. § 285, which pertains to exceptional cases (Compl. Request for Relief ¶R).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A central issue will be one of claim validity: Lupin has certified that the patents-in-suit are invalid. A key question for the court will be whether the asserted method claims, which cover specific dosing regimens and patient populations for the known compound migalastat, are non-obvious and adequately described and enabled by the patent specifications.
  • A second core issue will be induced infringement: Can Amicus prove that Lupin's proposed product label will directly lead physicians and patients to perform the patented methods? This will turn on whether the label's instructions for dosage, frequency, and patient selection are found to map onto the specific limitations of the asserted claims.
  • The case will also involve a significant question of claim scope: How will the court construe key limitations such as "therapeutically effective dose" and the lists of specific genetic mutations? The outcome of claim construction will likely determine whether Lupin's proposed generic product, which is designed to be a mirror image of the branded drug, falls within the scope of the asserted patent claims.