DCT

1:19-cv-00201

Novartis Pharma Corp v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00201, N.D.W. Va., 10/30/2019
  • Venue Allegations: Venue is alleged to be proper because Defendant Mylan Pharmaceuticals Inc. is incorporated in West Virginia and therefore resides in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's ENTRESTO® tablets constitutes an act of infringement of four U.S. patents related to pharmaceutical compositions and methods for treating heart failure and hypertension.
  • Technical Context: The technology concerns combination therapies for cardiovascular disease that simultaneously block the angiotensin II receptor (valsartan) and inhibit the neprilysin enzyme (sacubitril) to achieve a dual therapeutic effect.
  • Key Procedural History: The complaint states this action is a "backup suit" to a substantively identical case filed earlier in the District of Delaware, intended to safeguard jurisdictional and venue rights. The current action was triggered by Defendants' submission of ANDA No. 213646, which included a certification under 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (a "Paragraph IV certification") against the patents-in-suit.

Case Timeline

Date Event
2002-01-17 Earliest Priority Date for ’659 and ’331 Patents
2005-11-09 Earliest Priority Date for ’938 and ’134 Patents
2012-01-24 ’659 Patent Issued
2014-08-05 ’331 Patent Issued
2014-11-04 ’938 Patent Issued
2016-07-12 ’134 Patent Issued
2019-09-16 Date of Mylan's ANDA Notice Letter to Novartis
2019-10-30 Complaint Filing Date

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

U.S. Patent No. 8,101,659 - "Methods of treatment and pharmaceutical composition"

  • Patent Identification: U.S. Patent No. 8,101,659, "Methods of treatment and pharmaceutical composition", issued January 24, 2012 (the "’659 Patent").

The Invention Explained

  • Problem Addressed: The patent's background describes the limitations of existing therapies for hypertension and heart failure, which typically target single mechanisms like the renin-angiotensin system (RAS) via ACE inhibitors or Angiotensin II (Ang II) antagonists. The patent notes the need for more efficacious combination therapies that can provide enhanced benefits with potentially fewer side effects than prior approaches (Compl. ¶24; ’659 Patent, col. 3:1-5).
  • The Patented Solution: The invention is a pharmaceutical composition that combines two active agents: valsartan, an Ang II (AT1) receptor antagonist, and a specific neprilysin (NEP) inhibitor, sacubitril. This combination is designed to simultaneously block the detrimental effects of Ang II on the cardiovascular system while enhancing the beneficial vasodilatory and diuretic effects of natriuretic peptides, which are normally degraded by the NEP enzyme (Compl. ¶25; ’659 Patent, Abstract; col. 3:51-65).
  • Technical Importance: This dual-mechanism approach represented a novel strategy for treating cardiovascular diseases by addressing two distinct pathophysiological pathways with a single combination product (’659 Patent, col. 5:41-49).

Key Claims at a Glance

  • The complaint alleges infringement of claims 1-4 (Compl. ¶41). Independent claim 1 is representative.
  • Claim 1 Elements:
    • A pharmaceutical composition comprising:
    • (i) the AT1-antagonist valsartan or a pharmaceutically acceptable salt thereof;
    • (ii) the NEP inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic acid ethyl ester or (2R,4S)-5-biphenyl-4-yl-4(3-carboxy-propionyl amino)-2-methyl-pentanoic acid or a pharmaceutically acceptable salt thereof; and
    • (iii) a pharmaceutically acceptable carrier;
    • wherein (i) and (ii) are administered in combination in about a 1:1 ratio (’659 Patent, col. 16:20-33).

U.S. Patent No. 8,796,331 - "Methods of treatment and pharmaceutical composition"

  • Patent Identification: U.S. Patent No. 8,796,331, "Methods of treatment and pharmaceutical composition", issued August 5, 2014 (the "’331 Patent").

The Invention Explained

  • Problem Addressed: Similar to the ’659 Patent, the background identifies the need for more effective therapies for conditions like hypertension and heart failure than those provided by single-mechanism agents (Compl. ¶26; ’331 Patent, col. 3:1-5).
  • The Patented Solution: The invention is a method for treating hypertension or heart failure by administering a combination of valsartan and the NEP inhibitor sacubitril. The patent specifies that the two components can be administered either together in a single unit dose form or in two separate unit dose forms, providing flexibility in treatment regimens (Compl. ¶27; ’331 Patent, Abstract).
  • Technical Importance: By claiming the method of use, the patent provides coverage for the therapeutic application of the dual-mechanism combination, complementing the composition claims of related patents (’331 Patent, col. 5:41-50).

Key Claims at a Glance

  • The complaint alleges infringement of claims 1, 2, and 5-8 (Compl. ¶41). Independent claim 1 is representative.
  • Claim 1 Elements:
    • A method for the treatment of a condition or disease selected from hypertension and heart failure, comprising:
    • administering to a patient in need thereof a therapeutically effective amount of the combination of:
    • (i) the AT1-antagonist valsartan or a pharmaceutically acceptable salt thereof; and
    • (ii) the NEP inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic acid ethyl ester or... a pharmaceutically acceptable salt thereof;
    • wherein components (i) and (ii) are administered in one unit dose form or in two separate unit dose forms (’331 Patent, col. 16:15-29).

U.S. Patent No. 8,877,938 - "Compounds containing S-N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations"

  • Patent Identification: U.S. Patent No. 8,877,938, "Compounds containing S-N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations", issued November 4, 2014 (the "’938 Patent").

Multi-Patent Capsule

  • Technology Synopsis: This patent addresses the technical challenge of formulating valsartan and sacubitril together. It claims a specific supramolecular complex comprising the anionic forms of both valsartan and sacubitril, along with trisodium cations, in a hydrated, crystalline form. This specific complex, described as "sacubitril/valsartan trisodium hemipentahydrate," may provide benefits in terms of stability, purity, or manufacturing consistency compared to a simple mixture of the two active ingredients (Compl. ¶28-29; ’938 Patent, Abstract, FIG. 1).
  • Asserted Claims: The complaint asserts one or more claims of the ’938 patent (Compl. ¶43).
  • Accused Features: The Mylan ANDA Products are alleged to infringe by containing the claimed crystalline sacubitril/valsartan trisodium hemipentahydrate complex (Compl. ¶29, 43).

U.S. Patent No. 9,388,134 - "Compounds containing S-N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations"

  • Patent Identification: U.S. Patent No. 9,388,134, with the same title as the ’938 Patent, issued July 12, 2016 (the "’134 Patent").

Multi-Patent Capsule

  • Technology Synopsis: This patent is related to the ’938 Patent and claims a method of treatment for heart failure or hypertension that comprises administering a therapeutically effective amount of the specific sacubitril/valsartan trisodium hemipentahydrate complex. It protects the therapeutic use of the novel crystalline form itself (Compl. ¶30-31; ’134 Patent, Abstract).
  • Asserted Claims: The complaint asserts one or more claims of the ’134 patent (Compl. ¶46).
  • Accused Features: The use of the Mylan ANDA Products for treating heart failure or hypertension is alleged to infringe. Infringement would be based on the product label instructing physicians and patients to administer the drug, which allegedly contains the claimed complex, for these indications (Compl. ¶31, 46).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the "Mylan ANDA Products," which are generic sacubitril/valsartan tablets in 24 mg/26 mg, 49 mg/51 mg, and 97 mg/103 mg dosages for which Defendants seek FDA approval via ANDA No. 213646 (Compl. ¶10). The act of infringement under the Hatch-Waxman Act is the filing of the ANDA itself (Compl. ¶11, 38).

Functionality and Market Context

  • The Mylan ANDA Products are intended to be generic versions of Novartis's ENTRESTO® tablets (Compl. ¶1). ENTRESTO® is indicated to reduce the risk of cardiovascular death and hospitalization for patients with chronic heart failure (Compl. ¶32). The complaint alleges that upon approval, the Mylan ANDA Products will be commercially manufactured and sold for the same therapeutic uses (Compl. ¶44-45). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element mapping of the accused products to the asserted claims. Instead, it presents a narrative infringement theory and notes that Defendants' Paragraph IV notice letter "does not deny" infringement of specific claims of the ’659 and ’331 patents (Compl. ¶41).

  • Narrative Summary of Allegations:
    • ’659 Patent: The complaint alleges that the commercial manufacture, use, or sale of the Mylan ANDA Products will directly infringe one or more claims of the ’659 Patent (Compl. ¶42). The implicit theory is that the proposed generic tablets are pharmaceutical compositions containing the combination of valsartan and sacubitril in the claimed ratio.
    • ’331 Patent: The complaint alleges that the Mylan ANDA Products, if approved, will contain instructions for treating heart failure by administering sacubitril/valsartan, and that physicians and patients following these instructions will directly infringe. It further alleges that Defendants will actively encourage this use with knowledge of the ’331 patent, constituting induced infringement (Compl. ¶44), and that the products are especially adapted for this infringing use, constituting contributory infringement (Compl. ¶45).
    • ’938 Patent: The infringement theory is that the Mylan ANDA Products will contain the specific crystalline sacubitril/valsartan trisodium hemipentahydrate complex claimed in the ’938 Patent (Compl. ¶29, 43).
    • ’134 Patent: The theory for the ’134 Patent is one of indirect infringement, parallel to the allegations for the ’331 Patent. It is alleged that Defendants' product labeling will instruct users to administer the Mylan ANDA Products for treating heart failure, thereby inducing infringement of the claimed method of using the specific crystalline complex (Compl. ¶46, 47).
  • Identified Points of Contention:
    • Evidentiary Questions: A central question will be factual and evidentiary: Does the specific drug substance described in Mylan's confidential ANDA filing meet the limitations of the asserted claims? For the ’938 Patent, this raises the question of whether Mylan's active pharmaceutical ingredient is, in fact, the claimed crystalline "sacubitril/valsartan trisodium hemipentahydrate complex."
    • Scope Questions: For the ’659 Patent, a potential point of contention may be whether Mylan's formulation meets the "about a 1:1 ratio" limitation, raising a question of claim scope. For the method patents (’331 and ’134), the analysis will focus on whether the language of Mylan's proposed product label instructs infringing acts and demonstrates the requisite intent for inducement.

V. Key Claim Terms for Construction

  • The Term: "about a 1:1 ratio" (from ’659 Patent, claim 1)
  • Context and Importance: This term is critical for defining the scope of the claimed composition in the ’659 Patent. The definition of "about" will determine how much deviation from a precise 1:1 molar or weight ratio is permissible while still falling within the claim. Practitioners may focus on this term because Mylan's ANDA product, while containing both active ingredients, might be formulated at a ratio that it argues is not "about 1:1."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification does not provide an explicit definition for "about." A party arguing for a broader scope may contend that in the context of pharmaceutical formulation, "about" should be interpreted to cover a range of ratios that achieve the desired combined therapeutic effect.
    • Evidence for a Narrower Interpretation: The patent lacks specific examples of ratios other than 1:1. A party arguing for a narrower scope may point to the consistency of the 1:1 language and the absence of disclosure supporting significant deviation, suggesting "about" should be construed to cover only minor, conventional manufacturing tolerances.
  • The Term: "crystalline form" (from ’938 Patent, claim 1)
  • Context and Importance: The ’938 Patent claims a specific crystalline complex, not just a mixture of the active ingredients. The definition of this term, and the evidence required to prove its presence (e.g., via X-ray powder diffraction), will be central to determining infringement. The dispute will likely involve a comparison of the analytical data for Mylan's drug substance with the characterization data for the claimed crystalline form disclosed in the patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claims themselves recite the chemical name of the complex "in crystalline form." A party might argue that any crystalline form of that specific chemical complex infringes, regardless of minor variations in crystal habit or morphology not specified in the claims.
    • Evidence for a Narrower Interpretation: The ’938 Patent specification provides detailed characterization data, including a figure depicting the unit cell of the supramolecular complex (’938 Patent, FIG. 1, col. 18:40-50). A party could argue that "crystalline form" should be limited to a form exhibiting the specific structural and analytical properties disclosed in the specification, potentially excluding other polymorphs or crystalline structures.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for the method claims of the ’331 and ’134 patents. Inducement is based on the allegation that Defendants' product labeling will instruct and encourage physicians and patients to perform the patented methods of treatment (Compl. ¶44, 46). Contributory infringement is based on the allegation that the Mylan ANDA Products are especially made or adapted for the infringing use of treating heart failure and are not suitable for a substantial non-infringing use (Compl. ¶45, 47).
  • Willful Infringement: The complaint does not contain an explicit count or prayer for relief regarding willful infringement. It does, however, allege that Defendants were aware of the patents-in-suit when they filed their ANDA (Compl. ¶39), which could form a basis for a future willfulness allegation.

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

  1. A core issue will be one of structural identity: Does the active pharmaceutical ingredient detailed in Mylan’s confidential ANDA possess the specific crystalline structure of the "sacubitril/valsartan trisodium hemipentahydrate complex" as claimed and characterized in the ’938 Patent? The case may turn on a battle of analytical chemistry experts comparing the parties' data.
  2. A second key question will be one of induced infringement: Assuming Mylan’s product is found to contain the claimed composition or complex, will the text of its proposed product label be found to actively encourage or instruct medical professionals and patients to administer the drug in a manner that directly infringes the method claims of the ’331 and ’134 patents?
  3. The analysis will also involve a question of definitional scope: How broadly will the court construe the term "about a 1:1 ratio" in the ’659 Patent? The resolution of this claim construction issue may determine whether Mylan's specific formulation, even if not precisely 1:1, falls within the scope of the asserted composition claim.