DCT

1:24-cv-01408

Novartis Pharma Corp v. Umedica Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01408, D. Del., 12/23/2024
  • Venue Allegations: Venue is alleged to be proper because Defendant is a foreign entity, which may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application ("ANDA") to market generic versions of Plaintiff's ENTRESTO® (sacubitril/valsartan) tablets constitutes an act of infringement of eight U.S. patents related to the drug's composition, crystalline and amorphous forms, and methods of use for treating heart failure.
  • Technical Context: The technology concerns pharmaceutical compositions combining an angiotensin receptor blocker (valsartan) and a neprilysin inhibitor (sacubitril) for the treatment of various forms of heart failure.
  • Key Procedural History: The lawsuit was filed under the Hatch-Waxman Act following a notification letter from the Defendant, dated November 12, 2024, which included a Paragraph IV certification against the asserted patents. The complaint notes that claims 1-6 of U.S. Patent No. 9,517,226 were disclaimed on July 30, 2019, which will limit the scope of assertions for that patent.

Case Timeline

Date Event
2002-01-17 Priority Date for U.S. Patent No. 8,101,659
2005-11-09 Priority Date for U.S. Patent Nos. 8,877,938 & 9,388,134
2012-01-24 U.S. Patent No. 8,101,659 Issues
2012-08-24 Priority Date for U.S. Patent Nos. 9,517,226, 9,937,143 & 11,135,192
2014-11-04 U.S. Patent No. 8,877,938 Issues
2015-05-11 Priority Date for U.S. Patent No. 11,058,667
2016-07-12 U.S. Patent No. 9,388,134 Issues
2016-12-13 U.S. Patent No. 9,517,226 Issues
2018-04-10 U.S. Patent No. 9,937,143 Issues
2019-07-30 Claims 1-6 of U.S. Patent No. 9,517,226 are Disclaimed
2021-07-13 U.S. Patent No. 11,058,667 Issues
2021-08-24 U.S. Patent No. 11,096,918 Issues
2021-10-05 U.S. Patent No. 11,135,192 Issues
2024-11-12 Umedica sends Paragraph IV Notice Letter to Novartis
2024-12-23 Complaint Filed

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 Invention Explained

  • Problem Addressed: The patent's background describes the renin-angiotensin system's role in hypertension and congestive heart failure, noting that while inhibitors of this system (like valsartan) are effective, there remains a need for more efficacious therapies (US 8,101,659, col. 1:45-2:50).
  • The Patented Solution: The invention is a pharmaceutical composition that combines an angiotensin receptor blocker (valsartan) with a neutral endopeptidase (NEP) inhibitor (sacubitril) (US 8,101,659, Abstract). The detailed description explains that this dual-action approach provides complementary therapeutic effects for treating cardiovascular conditions like heart failure (US 8,101,659, col. 3:1-15).
  • Technical Importance: This combination therapy represented a novel approach to treating heart failure by simultaneously blocking the harmful effects of angiotensin II and enhancing the beneficial effects of natriuretic peptides degraded by NEP (US 8,101,659, col. 2:51-60).

Key Claims at a Glance

  • The complaint alleges infringement of claims 1-4 (Compl. ¶47). Independent claim 1 is asserted.
  • Essential elements of independent claim 1 include:
    • A pharmaceutical composition comprising (i) valsartan or a pharmaceutically acceptable salt thereof; and (ii) a NEP inhibitor or a pharmaceutically acceptable salt thereof.
    • Wherein (i) and (ii) are administered in combination in about a 1:1 ratio.
  • The complaint does not explicitly reserve the right to assert dependent claims for the ’659 patent.

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 Invention Explained

  • Problem Addressed: The patent's background section notes the difficulty in preparing solid oral dosage forms of combination therapies, particularly in achieving stable, bioavailable crystalline forms (US 8,877,938, col. 1:15-2:45).
  • The Patented Solution: The invention is a specific, stable crystalline solid form of a supramolecular complex containing valsartan, sacubitril, and sodium cations (US 8,877,938, Abstract). This specific complex, trisodium hemipentahydrate, is described as having advantageous properties for pharmaceutical formulation, such as improved stability and handling characteristics compared to a simple physical mixture of the components (US 8,877,938, col. 5:45-6:20).
  • Technical Importance: The creation of a stable, single crystalline complex of two distinct active pharmaceutical ingredients solved significant formulation and manufacturing challenges, enabling the development of a reliable solid oral dosage form (US 8,877,938, col. 17:45-55).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’938 patent (Compl. ¶50). The primary independent claim, claim 1, covers the composition of matter.
  • Essential elements of independent claim 1 include:
    • A compound which is trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3'-methyl-2'-(pentanoyl{2"-(tetrazol-5-ylate)biphenyl-4'-ylmethyl}amino)butyrate] hemipentahydrate.
    • In crystalline form.
  • The complaint does not explicitly reserve the right to assert dependent claims for the '938 Patent.

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

  • Technology Synopsis: This patent is related to the '938 Patent and claims a method of treating heart failure or hypertension. The method comprises administering a therapeutically effective amount of the same sacubitril/valsartan trisodium hemipentahydrate complex claimed in the '938 Patent (Compl. ¶23).
  • Asserted Claims: One or more claims (Compl. ¶54).
  • Accused Features: The proposed product labeling for the Umedica ANDA Products, which will allegedly contain instructions for administering the complex to treat heart failure (Compl. ¶55).

U.S. Patent No. 9,517,226 - Inhibitors for Treating Diseases Characterized by Atrial Enlargement or Remodeling

  • Technology Synopsis: This patent claims a method for treating or delaying the progression of heart failure with preserved ejection fraction (HF-PEF). The method involves administering a NEP inhibitor (like sacubitril) and valsartan, where the treatment is characterized by a reduction in left atrial volume or dimension (Compl. ¶26). Claims 1-6 were disclaimed (Compl. ¶25).
  • Asserted Claims: One or more claims, including claims 7-10 (Compl. ¶¶59, 62).
  • Accused Features: The proposed product labeling, which will allegedly direct physicians and patients to use the generic product for treating HF-PEF, thereby causing a reduction in left atrial volume (Compl. ¶60).

U.S. Patent No. 9,937,143 - Inhibitors for Treating Diseases Characterized by Atrial Enlargement or Remodeling

  • Technology Synopsis: This patent claims a method for treating HF-PEF by administering a therapeutically effective amount of the sacubitril/valsartan complex (LCZ696) in a 1:1 molar ratio (Compl. ¶28). It is related to the ’226 Patent but specifically claims administration of the complex itself.
  • Asserted Claims: One or more claims, including claims 1-8 (Compl. ¶¶66, 69).
  • Accused Features: The proposed product labeling, which will allegedly contain instructions for practicing the method of treating HF-PEF using the complex (Compl. ¶67).

U.S. Patent No. 11,058,667 - Sacubitril-Valsartan Dosage Regimen for Treating Heart Failure

  • Technology Synopsis: This patent claims a specific dosage regimen for treating chronic heart failure with reduced ejection fraction. The regimen involves a titration schedule, starting with a 50 mg twice-daily dose, increasing to 100 mg, and then to a 200 mg target dose, under specific conditions regarding prior ACE inhibitor or ARB use (’667 Patent, Claim 1; Compl. ¶30).
  • Asserted Claims: One or more claims, including claims 1-19 (Compl. ¶¶73, 76).
  • Accused Features: The proposed product labeling, which will allegedly instruct practicing the specific titration regimen for treating chronic heart failure (Compl. ¶74).

U.S. Patent No. 11,096,918 - Amorphous solid form of 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 sodium cations

  • Technology Synopsis: This patent is directed to an amorphous (non-crystalline) solid form of a compound comprising anionic valsartan, anionic sacubitril, and sodium cations in a 1:1:3 molar ratio (Compl. ¶32). This contrasts with the crystalline form claimed in the '938 patent.
  • Asserted Claims: One or more claims (Compl. ¶80).
  • Accused Features: The Umedica ANDA Products, which are alleged to be a pharmaceutical composition comprising the claimed amorphous solid form (Compl. ¶81).

U.S. Patent No. 11,135,192 - Inhibitors for Treating Diseases Characterized by Atrial Enlargement or Remodeling

  • Technology Synopsis: This patent claims methods for treating HF-PEF by administering specific doses (50 mg, 100 mg, or 200 mg) of the sacubitril/valsartan combination twice daily for at least 36 weeks (Compl. ¶34). It focuses on a specific duration of treatment.
  • Asserted Claims: One or more claims, including claims 1-6 (Compl. ¶¶84, 87).
  • Accused Features: The proposed product labeling, which will allegedly instruct practicing the claimed method of treating HF-PEF with the specified dosages and duration (Compl. ¶85).

III. The Accused Instrumentality

Product Identification

The accused products are Umedica's generic sacubitril/valsartan tablets in 24 mg/26 mg, 49 mg/51 mg, and 97 mg/103 mg dosage strengths, for which Umedica has filed ANDA No. 219946 with the FDA (Compl. ¶1, ¶5).

Functionality and Market Context

The Umedica ANDA Products are intended to be generic equivalents to Novartis's ENTRESTO® tablets (Compl. ¶1). As alleged, they are pharmaceutical compositions containing the active ingredients sacubitril and valsartan and are intended for use in treating heart failure (Compl. ¶¶1, 36). The filing of the ANDA itself is the statutory act of infringement, which seeks approval for commercial manufacture, use, and sale in the United States prior to the expiration of the patents-in-suit (Compl. ¶41).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,101,659 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising (i) valsartan...; and (ii) a NEP inhibitor... The complaint alleges that the Umedica ANDA Products, if approved, will be pharmaceutical compositions comprising valsartan (or a salt) and sacubitril (or a salt), which is a NEP inhibitor, and a pharmaceutically acceptable carrier (Compl. ¶45). ¶45 col. 8:5-8
wherein (i) and (ii) are administered in combination in about a 1:1 ratio. The complaint alleges the Umedica ANDA Products will administer valsartan and sacubitril in combination in about a 1:1 ratio (Compl. ¶45). The dosage strengths are specified as 24/26 mg, 49/51 mg, and 97/103 mg (Compl. ¶1). ¶45 col. 8:9-11
  • Identified Points of Contention:
    • Scope Questions: A potential point of contention may be the construction of "administered in combination." While the accused product is a fixed-dose tablet, which appears to fall squarely within the claim, the defendant could argue for a construction that requires a specific type of combination not met by their formulation.
    • Technical Questions: The complaint alleges that the Umedica Notice Letter does not deny that the ANDA products would infringe claims 1-4 (Compl. ¶47). This suggests infringement of this patent may be less contentious, but the primary technical question would be whether the ratio of active ingredients in the proposed generic product falls within the scope of "about a 1:1 ratio" as construed by the court.

U.S. Patent No. 8,877,938 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound which is trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3'-methyl-2'-(pentanoyl{2"-(tetrazol-5-ylate)biphenyl-4'-ylmethyl}amino)butyrate] hemipentahydrate The complaint alleges that the Umedica ANDA Products, if approved, will contain the specifically claimed sacubitril/valsartan trisodium hemipentahydrate complex (Compl. ¶51). ¶51 col. 32:45-56
in crystalline form. The complaint alleges the complex in the Umedica ANDA Products will be in crystalline form (Compl. ¶51). ¶51 col. 32:56
  • Identified Points of Contention:
    • Scope Questions: A central issue will be the definition of "crystalline form." The patent specification provides detailed characterization data, such as X-ray powder diffraction (XRPD) peaks ('938 Patent, col. 17-18). The scope of "crystalline form" will likely be construed to mean the specific polymorph disclosed in the patent, raising the question of whether minor variations in an accused product's crystal structure fall outside the claim.
    • Technical Questions: The key technical question will be whether the active pharmaceutical ingredient in Umedica's proposed product exhibits the same crystalline structure as the one claimed in the '938 patent. This is a factual question that will depend on expert analysis of scientific data (e.g., XRPD, DSC) comparing the proposed generic product to the patented compound.

V. Key Claim Terms for Construction

  • Patent: U.S. Patent No. 8,101,659

    • The Term: "administered in combination"
    • Context and Importance: This term is critical because it defines the relationship between the two active ingredients. Its construction will determine whether infringement requires simultaneous administration from a single dosage form, co-administration of separate tablets, or sequential administration over a period of time.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification states that the term is "meant to encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time" (’659 Patent, col. 8:15-21). This language may support a broad construction covering various administration methods.
      • Evidence for a Narrower Interpretation: The claims themselves recite a "pharmaceutical composition" comprising both agents, which may suggest that the "combination" for the purposes of that claim must be within a single formulation. A defendant may argue that the broader definition in the specification applies to method claims, not the composition claim itself.

  • Patent: U.S. Patent No. 8,877,938

    • The Term: "crystalline form"
    • Context and Importance: In pharmaceutical patenting, "crystalline form" is often linked to a specific polymorph with unique physical properties. The infringement analysis will turn on whether Umedica's product contains the exact crystalline polymorph claimed by Novartis, not just any crystalline version of the complex. Practitioners may focus on this term because polymorphism is a common area of dispute in ANDA litigation.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language itself does not specify a particular polymorph (e.g., "Form I"). A party could argue that "crystalline form" should be given its plain and ordinary meaning, covering any crystalline structure of the claimed compound, unless the specification explicitly disclaims other forms.
      • Evidence for a Narrower Interpretation: The specification provides detailed characterization data, including a table of specific XRPD peaks, that defines a particular crystal structure (’938 Patent, Table 1, col. 18). A party will likely argue that this data implicitly defines the claimed "crystalline form" and limits the claim scope to that specific polymorph, effectively disavowing other potential crystalline forms.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced and contributory infringement of the method-of-use patents (’134, '226, ’143, '667, and ’192 patents). The allegations are based on the assertion that Umedica's proposed product labeling will instruct and encourage physicians and patients to use the generic drug in accordance with the patented methods, and that Umedica knows these acts will constitute infringement (e.g., Compl. ¶¶55-56, 60-61). It is also alleged that the products are especially made or adapted for infringing use and are not suitable for substantial non-infringing use (e.g., Compl. ¶56).
  • Willful Infringement: While not explicitly pleaded as a count, the complaint alleges that Umedica was aware of the patents-in-suit when it filed its ANDA containing Paragraph IV certifications (Compl. ¶42). This allegation of pre-suit knowledge, established through the statutory ANDA process, could form the basis for a subsequent claim of willful infringement.

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

This case presents a multi-faceted challenge to a generic entrant, covering the basic composition, specific physical forms, and various methods of using a blockbuster heart failure drug. The litigation will likely center on the following key questions:

  • A core issue will be one of structural identity: for the patents on specific solid forms ('938 and ’918), does the active pharmaceutical ingredient in the proposed generic product possess the exact crystalline or amorphous structure, respectively, as defined and claimed in the patents? This will be a fact-intensive inquiry driven by competing expert analyses of analytical data.
  • A key evidentiary question will be one of induced infringement: for the multiple method-of-use patents, will the language in the Defendant's proposed product label be found to instruct or encourage medical professionals and patients to perform all the steps of the claimed methods, thereby establishing the requisite intent for inducement?
  • A central question of validity will arise in defense: can the combination of two known classes of drugs (a NEP inhibitor and an ARB) for treating heart failure, or the specific dosage regimens for their use, withstand challenges of obviousness based on the prior art available at the time of the inventions?