DCT

2:24-cv-10567

Genentech Inc v. Natco Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-10567, D.N.J., 11/18/2024
  • Venue Allegations: Venue is alleged to be proper as Defendants Natco and the foreign Zydus entities are foreign corporations subject to personal jurisdiction in the district, and Defendant Zydus Pharmaceuticals (USA) Inc. is incorporated and has an established place of business in New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants’ submissions of Abbreviated New Drug Applications (ANDAs) to the FDA, seeking to market generic versions of the spinal muscular atrophy treatment EVRYSDI® (risdiplam), constitute an act of infringement of five U.S. patents covering the risdiplam compound, methods of its use, specific dosing regimens, and pharmaceutical formulations.
  • Technical Context: The technology relates to small-molecule therapeutics for Spinal Muscular Atrophy (SMA), a rare genetic neurodegenerative disease, which previously had limited treatment options.
  • Key Procedural History: This is a Hatch-Waxman action initiated within the 45-day window following Plaintiffs’ receipt of Defendants' Paragraph IV certification notice letters, which alleged that the asserted patents are invalid, unenforceable, and/or will not be infringed by the proposed generic products.

Case Timeline

Date Event
2012-02-10 ’955 Patent Priority Date
2014-05-15 ’754 and ’646 Patents Priority Date
2015-11-12 ’136 Patent Priority Date
2017-03-07 ’955 Patent Issue Date
2017-10-03 ’444 Patent Priority Date
2018-05-15 ’754 Patent Issue Date
2022-12-27 ’444 Patent Issue Date
2023-11-28 ’646 Patent Issue Date
2024-03-26 ’136 Patent Issue Date
2024-10-10 Natco sends Paragraph IV Notice Letter to Plaintiffs
2024-10-21 Zydus sends Paragraph IV Notice Letter to Plaintiffs
2024-11-18 Complaint Filing Date

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

U.S. Patent No. 9,586,955 - "Compounds for Treating Spinal Muscular Atrophy"

The Invention Explained

  • Problem Addressed: The patent addresses Spinal Muscular Atrophy (SMA), a neurodegenerative disease caused by a deficiency of the Survival of Motor Neuron (SMN) protein, for which there was no known cure at the time of the invention (’955 Patent, col. 1:17-49). While humans have a nearly identical SMN2 gene, it cannot fully compensate because alternative splicing predominantly excludes exon 7, leading to a truncated, unstable protein (’955 Patent, col. 1:50-col. 2:2).
  • The Patented Solution: The invention provides a class of chemical compounds with a pyridopyrimidinone core designed to modulate the splicing of SMN2 pre-mRNA, thereby increasing the inclusion of exon 7 and the production of functional, full-length SMN protein (’955 Patent, Abstract; col. 5:5-15). This approach aims to treat SMA by correcting the underlying protein deficiency.
  • Technical Importance: This technology represents a shift from supportive care to a disease-modifying therapy for SMA by targeting the underlying genetic splicing defect.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶91).
  • Claim 1 recites:
    • A compound of Formula (IIa1), or a form thereof
    • Wherein R1 is heterocyclyl, optionally substituted
    • Wherein R2 is heteroaryl, optionally substituted
    • Wherein Ra, Rb, and Rc are independently selected from specified groups (hydrogen, halogen, C1-8alkyl, etc.)
    • Wherein R3, R4, R5, R6, and R7 define various substituent groups attached to R1 and R2
  • The complaint also asserts dependent claim 11 and states that Natco has not contested infringement of claims 1-8, 10, 11, or 20 (Compl. ¶¶91-92).

U.S. Patent No. 9,969,754 - "Compounds for Treating Spinal Muscular Atrophy"

The Invention Explained

  • Problem Addressed: Similar to the ’955 Patent, the ’754 Patent is directed to treating SMA by modulating SMN2 splicing to produce functional SMN protein (’754 Patent, col. 2:4-10).
  • The Patented Solution: The patent claims a narrower set of compounds than the ’955 Patent, including the specific compound known as risdiplam, and methods of using these compounds to treat SMA (’754 Patent, col. 1:30-36). Claim 36, for example, specifically recites the chemical name for risdiplam.
  • Technical Importance: This patent claims the specific chemical entity that became the active pharmaceutical ingredient in the FDA-approved drug EVRYSDI®, representing the culmination of the discovery effort described more broadly in the parent ’955 Patent.

Key Claims at a Glance

  • The complaint asserts independent claim 28 and dependent claim 36 (Compl. ¶99).
  • Claim 28 is a method claim reciting:
    • A method for the treatment of spinal muscular atrophy in a human
    • Which method comprises administering a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable thereof, to a human in need of such treatment
  • Claim 36 depends from claim 24 (which depends from claim 1) and recites:
    • A compound of claim 24, wherein the compound is 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazine-6-yl)pyrido[1,2-a]pyrimidin-4-one (risdiplam).

U.S. Patent No. 11,534,444 - "Treatment of SMA"

Technology Synopsis

The patent addresses the need for an effective oral treatment for SMA (’444 Patent, col. 2:42-47). It claims a specific, weight-based dosing regimen for administering risdiplam to treat SMA, distinguishing between patients weighing less than 20 kg and those weighing 20 kg or more (’444 Patent, col. 3:1-12; Claim 1).

Asserted Claims

At least claim 1 is asserted (Compl. ¶¶109, 139).

Accused Features

The proposed generic products' labels are accused of infringing by instructing the claimed weight-based dosing regimen, which allegedly copies the label for EVRYSDI® (Compl. ¶¶110, 141).

U.S. Patent No. 11,827,646 - "Compounds for Treating Spinal Muscular Atrophy"

Technology Synopsis

The patent addresses the need for treatments for SMA, a neurodegenerative disorder with no known cure at the time of invention (’646 Patent, col. 2:8-10). The invention claims methods for treating SMA by administering a therapeutically effective amount of the compound risdiplam, which is identified by its chemical structure (’646 Patent, Claim 1).

Asserted Claims

At least claims 1 and 11 are asserted (Compl. ¶119).

Accused Features

The proposed generic products are accused of infringing because they contain risdiplam and their proposed labels will instruct their use for the treatment of SMA (Compl. ¶120).

U.S. Patent No. 11,938,136 - "Compositions for Treating Spinal Muscular Atrophy"

Technology Synopsis

The patent is directed to stable pharmaceutical compositions of risdiplam suitable for oral administration (’136 Patent, col. 1:20-27). The invention claims specific formulations, including a dry granulated powder blend for an oral solution that comprises risdiplam along with a specific stabilizer (disodium ethylenediaminetetraacetate), antioxidant (ascorbic acid), and acidifier (tartaric acid) (’136 Patent, Claim 1).

Asserted Claims

At least claims 1, 35, and 36 are asserted (Compl. ¶¶129, 150).

Accused Features

The formulation of the proposed generic ANDA products is accused of infringing the claimed composition claims (Compl. ¶¶129, 150).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the generic drug products for which Natco Pharma Limited and the Zydus entities have filed ANDAs with the FDA, identified as the "Natco ANDA Product" (ANDA No. 219848) and the "Zydus ANDA Product" (ANDA No. 219902) (Compl. ¶1).

Functionality and Market Context

The proposed generic products contain the active ingredient risdiplam and are intended to be marketed as an oral solution for the treatment of spinal muscular atrophy (SMA) (Compl. ¶¶38, 40, 44, 53). According to the complaint, the branded product EVRYSDI® is the first and only oral therapy for SMA approved by the FDA (Compl. ¶2). The proposed generic products are provided as a powder for constitution into a 0.75 mg/mL solution, with recommended dosages based on patient age and body weight (Compl. ¶¶41-42). The complaint includes a table from the EVRYSDI® label detailing the weight-based dosing recommendations, which Plaintiffs allege the generic labels will copy (Compl. ¶42).

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,586,955 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of Formula (IIa1): [structure] or a form thereof, wherein: R1 is heterocyclyl... R2 is heteroaryl... [and definitions for Ra, Rb, Rc, R3-R7] The active ingredient of the Natco ANDA Product, risdiplam, is alleged to be a compound that falls within the scope of Formula (IIa1) as defined by the claim. ¶91 col. 13:14-col. 14:45

U.S. Patent No. 9,969,754 Infringement Allegations

Claim Element (from Asserted Claims 28 and 36) Alleged Infringing Functionality Complaint Citation Patent Citation
Claim 36: A compound of claim 24, wherein the compound is 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazine-6-yl)pyrido[1,2-a]pyrimidin-4-one. The active ingredient of the Natco ANDA Product is risdiplam, the specific compound recited in the claim. ¶99 col. 61:19-24
Claim 28: A method for the treatment of spinal muscular atrophy in a human, which method comprises administering a therapeutically effective amount of a compound of formula (I)... The proposed label for the Natco ANDA Product allegedly instructs physicians and patients to administer risdiplam for the treatment of SMA, thereby inducing infringement of the claimed method. ¶100 col. 60:49-55

Identified Points of Contention

  • Scope Questions: For the '955 Patent, a potential question for the court may be whether the specific risdiplam molecule is encompassed by the genus of compounds defined by Claim 1. The complaint alleges that Natco has not contested infringement of this claim in its notice letter, which may suggest the dispute will center on validity rather than literal scope (Compl. ¶91).
  • Technical Questions: In this ANDA context, the infringement analysis is primarily statutory rather than a factual dispute over the composition of the accused product, as the generic must be bioequivalent to the branded drug. The central questions will therefore concern the validity of the patents-in-suit and the legal interpretation of claim terms. The complaint notes that the defendants' notice letters challenge validity and/or enforceability of the asserted patents (Compl. ¶¶46, 57).

V. Key Claim Terms for Construction

The Term: "therapeutically effective amount"

(from ’754 Patent, Claim 28)

Context and Importance

This term is central to the asserted method-of-use claims (e.g., ’754 Patent, Claim 28; ’646 Patent, Claim 1). Its construction will determine whether the specific dosages approved by the FDA and included on the generic label fall within the scope of the patent. Practitioners may focus on this term because its breadth could be a point of contention for both infringement and validity (e.g., enablement or indefiniteness).

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification does not appear to provide a specific numerical range for a "therapeutically effective amount," which may support an interpretation that the term should be given its plain and ordinary meaning as understood by a person of ordinary skill in the art.
  • Evidence for a Narrower Interpretation: Defendants may argue that the scope of "therapeutically effective amount" should be limited by the examples and data disclosed in the specification. For instance, the patent describes specific dosages used in mouse models, which could be argued to inform the meaning of the term in the context of the patent (’754 Patent, col. 59:5-20).

The Term: "a dry granulated powder blend"

(from ’136 Patent, Claim 1)

Context and Importance

This term is critical to the asserted formulation claims of the ’136 Patent. The infringement analysis will depend on whether the defendants' proposed generic formulation, which is supplied as a powder for reconstitution (Compl. ¶41), meets the definition of a "dry granulated powder blend."

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification describes the blend as being prepared through dry granulation by roller compaction, but the claim itself is directed to the blend, not the process of making it. Plaintiffs may argue the term should be construed based on the final properties of the composition, not the manufacturing method.
  • Evidence for a Narrower Interpretation: The specification states that the powder blend "is prepared through dry granulation by roller compaction" (’136 Patent, col. 18:40-43). A defendant might argue that this description limits the claim to blends made by this specific process, potentially raising a process-based limitation in a product claim.

VI. Other Allegations

Indirect Infringement

The complaint alleges that by submitting ANDAs with proposed labeling that copies the EVRYSDI® label, Defendants will induce and contribute to infringement of the asserted method-of-use claims (e.g., ’754, ’444, ’646 Patents) once the generic products are marketed (Compl. ¶¶100, 102, 110, 112). The basis for inducement is the allegation that the labels will instruct physicians and patients to administer the drug for the patented indications and at the patented dosages. The complaint also asserts the products have no substantial non-infringing uses (Compl. ¶¶101, 111).

Willful Infringement

While not explicitly using the word "willful," the complaint alleges that both Natco and Zydus were aware of the asserted patents when they submitted their ANDAs and that their statements regarding invalidity and non-infringement are "devoid of a good faith basis in either the facts or the law" (Compl. ¶¶96, 106, 116, 126, 136, 147, 158). These allegations lay the groundwork for a potential claim of willful infringement if infringement is found.

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

  • A core issue will be one of patent validity: The central conflict in this Hatch-Waxman litigation will likely be Defendants' challenges to the validity of the five asserted patents on grounds such as obviousness, lack of written description, or enablement, as foreshadowed by their Paragraph IV certifications. The complaint’s repeated assertion that these challenges lack a "good faith basis" signals that the patentability of the claimed inventions will be a primary focus.
  • A key evidentiary question will be one of claim construction and scope: The case may turn on the interpretation of key claim terms. For the method patents ('754, '444, '646), the definition of "therapeutically effective amount" and the scope of the specific dosage limitations will be critical. For the formulation patent ('136), the meaning of "dry granulated powder blend" will determine whether the generic composition infringes.