DCT

2:22-cv-06886

Nevakar Injectables Inc v. InfoRLife SA

Log In
Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:22-cv-06886, D.N.J., 04/03/2023
  • Venue Allegations: Venue is alleged as proper for WG Critical Care as a New Jersey LLC and for InfoRLife as a foreign corporation subject to personal jurisdiction within the district.
  • Core Dispute: Plaintiff alleges that Defendants’ ready-to-administer norepinephrine bitartrate intravenous solution infringes seven patents related to stable pharmaceutical compositions for treating hypotension.
  • Technical Context: The technology concerns creating stable, ready-to-use injectable norepinephrine solutions that do not require dilution from concentrate and avoid using sulfite-based antioxidants, which can cause allergic reactions.
  • Key Procedural History: This Second Amended Complaint was filed on April 3, 2023. The complaint alleges infringement of provisional rights for U.S. Patent No. 11,602,508, indicating that litigation was underway prior to this patent's issuance and that Defendants allegedly had notice of the corresponding published application.

Case Timeline

Date Event
2017-01-30 Earliest Priority Date for all Patents-in-Suit
2019-03-12 U.S. Patent No. 10,226,436 Issued
2019-09-24 U.S. Patent No. 10,420,735 Issued
2019-11-12 U.S. Patent No. 10,471,026 Issued
2020-02-25 U.S. Patent No. 10,568,850 Issued
2020-05-12 U.S. Patent No. 10,646,458 Issued
2022-08-16 U.S. Patent No. 11,413,259 Issued
2022-09-15 Defendants' Accused Product receives FDA Approval (NDA No. 215700)
2022-10-06 Plaintiff's Product receives FDA Approval (NDA No. 214628)
2022-11-17 U.S. Pub. No. 2022/0362175 (related to '508 Patent) Published
2023-02-10 Defendants allegedly received actual notice of the '175 Publication
2023-03-14 U.S. Patent No. 11,602,508 Issued
2023-04-03 Second Amended Complaint Filed

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

U.S. Patent No. 10,226,436 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: March 12, 2019.

The Invention Explained

  • Problem Addressed: The patent’s background section describes problems with then-current norepinephrine products, which were supplied as concentrates requiring dilution, creating risks of microbial contamination and calculation errors. These products also used sulfite antioxidants (e.g., sodium metabisulphite) that could cause severe allergic reactions and had poor storage stability once diluted (’436 Patent, col. 2:1-14).
  • The Patented Solution: The invention is a stable, ready-to-administer norepinephrine composition that is substantially free of antioxidants (’436 Patent, Abstract). It achieves stability through a specific combination of features: an aqueous solution with a pH between 3.7 and 4.3, a chelating agent to bind metal ions that can catalyze degradation, and a pharmaceutically acceptable salt to adjust tonicity, which collectively prevent both degradation of the norepinephrine and its isomerization from the active R-isomer to the inactive S-isomer (’436 Patent, col. 3:56-65).
  • Technical Importance: This approach provides a ready-to-use critical care drug that enhances patient safety by eliminating the need for bedside dilution and removing potentially allergenic sulfite preservatives (’436 Patent, col. 2:5-14).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶88).
  • Essential elements of Claim 1 include:
    • A ready-to-administer norepinephrine composition.
    • An aqueous acidic solution with a pH between 3.7 and 4.3, further comprising a chelating agent and a pharmaceutically acceptable salt.
    • The chelating agent is present in an amount between 1 µg/ml and 100 µg/ml.
    • The pharmaceutically acceptable salt is present in an amount between 0.6 wt % and 1.2 wt %.
    • The norepinephrine is dissolved at a suitable concentration for administration and is an R-isomer.
    • The composition is substantially free of antioxidants.
    • The composition is formulated such that after at least three months of storage, ≤10% of the R-isomer isomerizes to the S-isomer and ≤5% of total norepinephrine degrades.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 10,420,735 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: September 24, 2019.

The Invention Explained

  • Problem Addressed: The patent addresses the same technical problems as the ’436 Patent: the instability, risk of dilution errors, and potential for allergic reactions associated with existing concentrated norepinephrine formulations (’735 Patent, col. 2:2-15).
  • The Patented Solution: This patent claims a method of treating hypotension by administering a ready-to-administer norepinephrine composition using a specific two-phase dosing regimen (’735 Patent, Abstract). The method comprises administering an initial higher dose followed by a lower maintenance dose, using a stable, antioxidant-free composition with the same key characteristics (pH, chelating agent, tonicity agent) described in the ’436 Patent family to ensure product stability throughout administration (’735 Patent, col. 4:26-38).
  • Technical Importance: The invention provides a standardized, safe method of administration for a ready-to-use norepinephrine solution, potentially improving therapeutic outcomes in acute hypotension cases by using a pre-defined, clinically relevant dosing protocol with a stable formulation (’735 Patent, Table 21, col. 20:45-53).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶120).
  • Essential elements of Claim 1 include:
    • A method of treating hypotension.
    • Administering a ready-to-administer norepinephrine composition at an initial dose per minute.
    • Administering the composition at a maintenance dose per minute, where the initial dose is greater than the maintenance dose.
    • The initial dose is between 8 and 12 µg/min, and the maintenance dose is between 2 and 4 µg/min.
    • The composition comprises norepinephrine or a salt thereof (10-100 µg/ml) in an aqueous acidic solution (pH 3.7-4.3) with a chelating agent (1-100 µg/ml) and a tonicity agent.
    • The composition is substantially free of antioxidants.
    • The composition comprises at least about 90% R-isomer of norepinephrine after at least three months of storage under specified conditions.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 10,471,026 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: November 12, 2019 (Compl. ¶35).
  • Technology Synopsis: This patent is directed to a method of controlling the content of the less active S-isomer in a ready-to-administer norepinephrine composition. The method involves admixing an R-isomer of norepinephrine, a chelating agent, and a tonicity agent into an aqueous solution with a specific pH range (3.7-4.3) and being substantially free of anti-oxidants (Compl. ¶152).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶152).
  • Accused Features: The complaint alleges that Defendants' manufacture of the Accused Product, which contains the claimed components and has the claimed pH, infringes this method claim (Compl. ¶153).

U.S. Patent No. 10,568,850 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: February 25, 2020 (Compl. ¶40).
  • Technology Synopsis: This patent claims a sterile, ready-to-administer, packaged norepinephrine composition. The claims require a primary container filled with the sterile composition, which is itself packaged in a secondary container, and recites specific stability requirements after three months of storage (Compl. ¶184).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶184).
  • Accused Features: The Accused Product is alleged to be a packaged composition, supplied in an intravenous bag within a secondary overwrap, that meets the claimed compositional and stability limitations (Compl. ¶67, ¶185).

U.S. Patent No. 10,646,458 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: May 12, 2020 (Compl. ¶45).
  • Technology Synopsis: This patent is directed to a method of preparing a sterile, ready-to-administer norepinephrine composition. The claimed method comprises the steps of combining the ingredients, adjusting the pH, filling the composition into a container, and heat sterilizing the filled container to achieve sterility (Compl. ¶216).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶216).
  • Accused Features: The complaint alleges on information and belief that the process used to manufacture the Accused Product includes the claimed steps of combining, pH adjustment, filling, and heat sterilizing (Compl. ¶217).

U.S. Patent No. 11,413,259 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: August 16, 2022 (Compl. ¶50).
  • Technology Synopsis: This patent claims a method of preparing a storage-stable, substantially antioxidant-free norepinephrine composition that exhibits specific low levels of isomerization and degradation after three months of storage. The method steps include admixing an R-isomer of norepinephrine bitartrate and adjusting the pH to a range of 3.7-5.0 (Compl. ¶248).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶248).
  • Accused Features: The complaint alleges on information and belief that the manufacturing process for the Accused Product meets the steps of the claimed method and results in a product with the claimed stability characteristics (Compl. ¶249).

U.S. Patent No. 11,602,508 - “Norepinephrine Compositions and Methods Therefor”

  • Issued: March 14, 2023 (Compl. ¶55).
  • Technology Synopsis: This patent claims a ready-to-administer norepinephrine composition where the "chelating agent" is specifically defined as comprising a "tartrate bicarboxylic acid." This claim language appears to directly target the use of norepinephrine bitartrate, where the bitartrate component itself is alleged to serve as the chelating agent (Compl. ¶280).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶280).
  • Accused Features: The complaint alleges that the Accused Product, which is a norepinephrine bitartrate solution, meets the limitations of this claim because its bitartrate component is a tartrate bicarboxylic acid that functions as the claimed chelating agent (Compl. ¶67, ¶281).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' norepinephrine bitartrate in 0.9% sodium chloride injection, approved under NDA No. 215700 (the "Accused Product") (Compl. ¶17, ¶65).

Functionality and Market Context

  • The Accused Product is a sterile, aqueous, ready-to-use solution for intravenous infusion, indicated to raise blood pressure in adult patients with severe, acute hypotension (Compl. ¶67). It is supplied in 250 mL single-dose transparent intravenous bags in three strengths (16, 32, and 64 mcg per mL of norepinephrine base) (Compl. ¶65, ¶67). The product is packaged in an overwrap containing an oxygen scavenger to prevent deterioration (Compl. ¶10-11). The complaint alleges that Defendants' product directly competes with Plaintiff's own FDA-approved norepinephrine solution and was launched to enter the same market (Compl. ¶2, ¶22).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

10,226,436 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
an aqueous acidic solution having a pH range of between 3.7 and 4.3 The Accused Product is an aqueous solution with an alleged pH of 3.4 to 4.0. ¶67 col. 3:59-61
wherein the aqueous acidic solution further comprises a chelating agent and a pharmaceutically acceptable salt The Accused Product contains the bitartrate component of the active ingredient, alleged to be a chelating agent, and sodium chloride (9 mg/mL), a pharmaceutically acceptable salt. ¶67 col. 3:61-63
wherein the chelating agent is present in an amount of between 1 µg/ml and 100 µg/ml The Accused Product contains norepinephrine bitartrate monohydrate at concentrations (e.g., 32, 64, or 128 micrograms per mL) that allegedly result in a bitartrate concentration within the claimed range. ¶67 col. 4:62-65
wherein the ready-to-administer norepinephrine composition is substantially free of antioxidants The FDA-approved label for the Accused Product does not list any antioxidants. ¶67 col. 4:4-6
wherein the ready-to-administer norepinephrine composition is formulated such that after storage over at least three months equal or less than 10% of the R-isomer form will isomerize...and such that equal or less than 5%...will degrade The complaint alleges on information and belief that the Accused Product is formulated to meet these stability requirements. ¶89 col. 4:13-21
  • Identified Points of Contention:
    • Scope Questions: The infringement allegation for the pH element raises the question of whether an accused product with a labeled pH range of 3.4-4.0 meets a claim limitation requiring a range of 3.7-4.3. The analysis may depend on the actual pH of manufactured batches or arguments under the doctrine of equivalents. A further question is whether the bitartrate component of the active ingredient (norepinephrine bitartrate) can be construed as the claimed "chelating agent," which is recited as a distinct component in the claim.
    • Technical Questions: The complaint alleges the Accused Product meets the long-term stability limitations of the claim on "information and belief." What evidence the complaint or subsequent discovery provides to substantiate that the Accused Product exhibits ≤10% isomerization and ≤5% degradation after three months will be a central factual question.

10,420,735 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating hypotension, comprising: administering a ready-to-administer norepinephrine composition at an initial dose per minute; The FDA-approved label for the Accused Product is indicated to treat acute hypotension and allegedly instructs users to administer the product. ¶67 col. 22:36-37
administering the norepinephrine composition at a maintenance dose per minute The FDA-approved label allegedly provides instructions for a maintenance dosage. ¶67 col. 22:41-42
wherein the initial dose per minute is a dose of between 8 and 12 µg/min, and wherein the maintenance dose per minute is a dose of between 2 and 4 µg/min The Accused Product's FDA-approved label allegedly instructs an initial dosage of 8 to 12 mcg per minute and a typical maintenance dosage of 2 to 4 mcg per minute. ¶67 col. 22:46-49
wherein the norepinephrine composition comprises...an aqueous acidic solution having a pH range of between 3.7 and 4.3...a chelating agent...and a tonicity agent The Accused Product is an aqueous solution with a pH of 3.4-4.0, and contains bitartrate (alleged chelating agent) and sodium chloride (tonicity agent). ¶67 col. 22:50-58
wherein the norepinephrine composition is substantially free of antioxidants The Accused Product's label does not list any antioxidants. ¶67 col. 22:59-60
  • Identified Points of Contention:
    • Scope Questions: This analysis raises the same scope questions as for the ’436 Patent regarding the pH range and the interpretation of "chelating agent."
    • Legal Questions: As this is a method claim and Defendants are manufacturers, not practitioners, infringement liability would be indirect. The central legal question will be whether the instructions on the Accused Product's label are sufficiently specific and direct to establish that Defendants actively induced medical professionals to perform each step of the claimed method.

V. Key Claim Terms for Construction

  • The Term: "chelating agent" (’436 Patent, Claim 1; ’735 Patent, Claim 1)

  • Context and Importance: This term is critical because the infringement theory for most of the asserted patents relies on the bitartrate component of the active pharmaceutical ingredient also serving as the claimed "chelating agent." The defense may argue that the claims require a chelating agent to be a separate excipient added to the composition, distinct from the salt form of the active ingredient. The construction of this term may determine whether the Accused Product meets a key limitation of the claims.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification of the ’436 Patent explicitly lists "bicarboxylic acid (e.g., optionally hydroxylated, tartrate)" as a type of chelating agent, which would support Plaintiff's position that the bitartrate in the accused product qualifies (’436 Patent, col. 5:2-4).
    • Evidence for a Narrower Interpretation: The same section of the specification also lists more conventional chelators like "EDTA, EGTA, etc." as examples (’436 Patent, col. 5:3-5). Furthermore, the specification notes that "the bitartrate appeared to act as a weak buffer," which a defendant could argue describes its primary function, distinguishing it from a chelating agent (’436 Patent, col. 6:39-41).

  • The Term: "pH range of between 3.7 and 4.3" (’436 Patent, Claim 1; ’735 Patent, Claim 1)

  • Context and Importance: The Accused Product's label specifies a pH range of 3.4 to 4.0, which only partially overlaps with the claimed range (Compl. ¶67). The dispute will likely center on whether the product is consistently manufactured within the overlapping 3.7-4.0 range (literal infringement) or whether infringement can be established for products in the 3.4-3.69 range under the doctrine of equivalents. The patent emphasizes the criticality of the pH range for stability, making this a potentially dispositive issue.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Practitioners may argue that the patent's stability data shows a trend, and a pH slightly outside the claimed range performs the same function in substantially the same way to achieve the same result. The patent itself tested a pH of 3.4, showing it was more stable than higher pH values, which could support an equivalence argument (’436 Patent, Table 5).
    • Evidence for a Narrower Interpretation: The patent repeatedly and specifically claims the 3.7 to 4.3 range after testing a broader range, suggesting a deliberate selection of these endpoints for optimal stability against both degradation and isomerization (’436 Patent, Claim 1; col. 6:45-50). A defendant could argue this represents a clear demarcation that cannot be expanded.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement for the asserted method claims (e.g., in the '735, '026, '458, and '259 patents). The basis for inducement is Defendants’ FDA-approved product label, which allegedly instructs healthcare professionals to perform the steps of the claimed methods of treatment and preparation (Compl. ¶89, ¶121, ¶153, ¶217, ¶249).
  • Willful Infringement: The complaint alleges willful infringement based on Defendants' alleged pre-suit knowledge of the patents-in-suit. It claims Defendants tracked the patents during their prosecution at the USPTO and were aware of each patent since its issue date, but proceeded with infringing conduct despite this knowledge (Compl. ¶78-79, ¶91).

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

  • A core issue will be one of definitional scope: can the term "chelating agent," recited as a distinct component in the claims, be construed to be satisfied by the bitartrate counterion of the active ingredient, norepinephrine bitartrate? The resolution of this question may vary across the patent family, particularly for the '508 patent, which explicitly claims a "tartrate bicarboxylic acid" as the chelating agent.
  • A key evidentiary question will be one of factual overlap and equivalence: does the Accused Product, with a labeled pH range of 3.4-4.0, infringe claims requiring a pH of 3.7-4.3? This will likely require evidence of the actual pH of manufactured batches and may necessitate a doctrine of equivalents analysis regarding whether the lower, non-overlapping portion of the pH range performs substantially the same function in substantially the same way to achieve the same stability result.
  • A central dispute for the method-of-preparation claims will be one of proof: can the Plaintiff demonstrate, likely through discovery, that Defendants' confidential manufacturing process for the Accused Product practices the claimed steps of combining, pH adjustment, filling, and heat sterilizing as recited, for example, in the ’458 patent?