DCT

1:23-cv-00788

Teva Pharma Intl GmbH v. Bendarx USA Corp

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00788, E.D. Va., 06/16/2023
  • Venue Allegations: Venue is alleged to be proper as Defendant is a Virginia corporation and therefore resides in the district.
  • Core Dispute: Plaintiffs allege that Defendant's submission of a New Drug Application for a generic version of the cancer drug bendamustine hydrochloride infringes eleven patents related to specific pharmaceutical compositions and solid forms of the drug.
  • Technical Context: The technology concerns formulations of bendamustine, an alkylating agent used to treat cancers like leukemia and lymphoma, focusing on improving its stability and defining its crystalline structure.
  • Key Procedural History: This is a Hatch-Waxman Act lawsuit triggered by Defendant’s New Drug Application (NDA) and Paragraph IV certification. The complaint notes that Defendant initially identified a Canadian entity as the NDA submitter in a March 2023 notice letter, later correcting it to the Virginia-based Defendant in a May 2023 letter, after Plaintiffs had already filed suit against the Canadian entity in Delaware. The complaint also alleges that Defendant has not provided sufficient information for Plaintiffs to independently confirm the composition of the accused product.

Case Timeline

Date Event
2005-01-14 Earliest Priority Date for ’190, ’863, ’270, ’756, ’350 Patents
2008-03-26 Earliest Priority Date for ’524, ’279, ’836, ’955 Patents
2009-01-15 Earliest Priority Date for ’366 Patent
2011-12-13 ’366 Patent Issued
2012-03-20 Earliest Priority Date for ’887 Patent
2013-05-07 ’190 Patent Issued
2013-05-21 ’524 Patent Issued
2013-06-11 ’350 Patent Issued
2013-12-17 ’863 Patent Issued
2014-03-11 ’279 Patent Issued
2014-07-29 ’270 Patent Issued
2014-11-11 ’836 Patent Issued
2014-11-25 ’756 Patent Issued
2017-01-03 ’955 Patent Issued
2017-02-21 ’887 Patent Issued
2023-03-23 Defendant sends First Notice Letter
2023-05-04 Plaintiffs file suit against BendaRx Canada in Delaware
2023-05-05 Defendant sends Second (revised) Notice Letter
2023-06-16 Complaint Filed

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

U.S. Patent No. 8,436,190 - “Bendamustine Pharmaceutical Compositions”

The Invention Explained

  • Problem Addressed: The patent’s background section describes that nitrogen mustards like bendamustine are highly reactive and unstable in aqueous solutions, making them difficult to formulate as pharmaceutical products. It also notes that reconstitution of existing lyophilized (freeze-dried) powders can be difficult and time-consuming, which increases the risk of drug degradation prior to administration (’190 Patent, col. 1:25-2:37).
  • The Patented Solution: The invention is a stable, lyophilized pharmaceutical composition of bendamustine that includes mannitol as a bulking agent and a stabilizing amount of an organic solvent, preferably tertiary-butyl alcohol (TBA). This composition is designed to be easier to reconstitute and to have a better impurity profile, particularly reducing the formation of hydrolysis byproducts like HP1 (’190 Patent, col. 2:65-3:4, col. 9:1-12).
  • Technical Importance: The formulation sought to improve the stability, shelf-life, and ease of clinical administration for an important but chemically unstable oncology drug (’190 Patent, col. 2:29-37).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specifying them (Compl. ¶ 71). Independent claim 1 is representative.
  • Claim 1 Elements:
    • A pharmaceutical composition comprising bendamustine or bendamustine hydrochloride,
    • mannitol,
    • tertiary-butyl alcohol and
    • water.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,445,524 - “Solid Forms of Bendamustine Hydrochloride”

The Invention Explained

  • Problem Addressed: The patent explains that active pharmaceutical ingredients (APIs) can exist in different solid-state forms, such as crystalline polymorphs, which can have different physical properties like solubility and stability. For consistent manufacturing and therapeutic effect, it is important to identify and characterize stable, reproducible solid forms of a drug (’524 Patent, col. 1:21-41).
  • The Patented Solution: The invention discloses several novel, stable, crystalline forms (polymorphs) of bendamustine hydrochloride, designated Form 1, Form 2, Form 3, and Form 4. Each form is distinguished by a unique "fingerprint" defined by its X-ray powder diffraction (XRPD) pattern, which is a set of characteristic peaks (’524 Patent, col. 2:40-48; FIG. 2).
  • Technical Importance: The identification of distinct and stable polymorphic forms of bendamustine hydrochloride allows for more reliable and consistent pharmaceutical manufacturing and product performance (’524 Patent, col. 1:33-41).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" (Compl. ¶ 93). Independent claim 2, directed to Form 1, is representative of the allegations.
  • Claim 2 Elements:
    • A crystalline form of bendamustine hydrochloride that is bendamustine hydrochloride Form 1,
    • that produces an X-ray powder diffraction pattern comprising one or more of the following reflections: 8.3, 16.8, 18.5, 22.0, and 24.9±0.2 degrees 2θ.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,609,863 - “Bendamustine Pharmaceutical Compositions”

  • Technology Synopsis: This patent relates to lyophilized bendamustine compositions containing mannitol. It claims specific weight ratios of bendamustine hydrochloride to mannitol and concentrations of the reconstituted solution, aiming to provide a stable and easily administered formulation (’863 Patent, Abstract).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 115). Independent claims 1 and 4 are representative.
  • Accused Features: The accused product is alleged to be a lyophilized preparation with a weight ratio of bendamustine hydrochloride to mannitol of 15:25.5 and to be reconstituted to a concentration of 100 mg per 20 mL (Compl. ¶ 44, ¶ 53).

U.S. Patent No. 8,669,279 - “Solid Forms of Bendamustine Hydrochloride”

  • Technology Synopsis: This patent, related to the ’524 patent, claims additional solid forms of bendamustine hydrochloride. The invention is directed to a crystalline form designated as Form 3, which is characterized by its unique X-ray powder diffraction (XRPD) pattern (’279 Patent, Abstract, col. 2:49-51).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 137). Independent claims 1 and 19 are representative.
  • Accused Features: The accused product is alleged to comprise bendamustine hydrochloride Form 3, producing an XRPD pattern with reflections at 7.9, 15.5, and 26.1±0.2 degrees 2θ (Compl. ¶ 46, ¶ 51).

U.S. Patent No. 8,791,270 - “Bendamustine Pharmaceutical Compositions”

  • Technology Synopsis: This patent, related to the ’190 and ’863 patents, claims pharmaceutical compositions of bendamustine hydrochloride characterized by a low level of total degradants. The invention aims to improve the purity and stability of the final drug product (’270 Patent, Abstract, col. 2:65-3:4).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 159). Independent claim 7 is representative.
  • Accused Features: The accused product is alleged to be a pharmaceutical composition containing less than or equal to 4.0% of bendamustine degradants (Compl. ¶ 49).

U.S. Patent No. 8,883,836 - “Solid Forms of Bendamustine Hydrochloride”

  • Technology Synopsis: This patent, related to the ’524 and ’279 patents, claims methods of treating cancer by administering a solution prepared from a lyophilized composition containing bendamustine hydrochloride Form 3. The claims focus on the method of use for this specific crystalline form (’836 Patent, Abstract, col. 28:1-12).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 181). Independent claims 1 and 13 are representative.
  • Accused Features: The proposed labeling for the accused product is alleged to promote a method of treating leukemia or lymphoma by administering a solution prepared from a composition comprising bendamustine hydrochloride Form 3 (Compl. ¶ 51, ¶ 55).

U.S. Patent No. 8,895,756 - “Bendamustine Pharmaceutical Compositions”

  • Technology Synopsis: This patent, related to the ’190 family, claims reconstituted pharmaceutical compositions of bendamustine containing very low levels of a specific hydrolysis degradant known as HP1. The invention is directed to improving the purity of the drug at the point of administration (’756 Patent, Abstract).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 203). Independent claims 1 and 9 are representative.
  • Accused Features: The proposed labeling for the accused product is alleged to promote the use of a reconstituted composition containing not more than about 0.9% of HP1 (Compl. ¶ 48).

U.S. Patent No. 9,533,955 - “Solid Forms of Bendamustine Hydrochloride”

  • Technology Synopsis: This patent, related to the ’524 family, claims compositions comprising specific crystalline forms of bendamustine hydrochloride, including Form 1 and Form 3. The claims cover compositions containing these specific polymorphs along with a pharmaceutically acceptable excipient (’955 Patent, Abstract).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 225). Independent claims 1, 3, 10, and 12 are representative.
  • Accused Features: The accused product is alleged to be a composition containing bendamustine hydrochloride Form 1 (Compl. ¶ 42) and/or Form 3 (Compl. ¶ 46, ¶ 51).

U.S. Patent No. 9,572,887 - “Formulations of Bendamustine”

  • Technology Synopsis: This patent claims non-aqueous liquid compositions of bendamustine with specified concentrations and long-term stability (e.g., less than 5% total impurities after 15 months). This formulation approach avoids issues associated with aqueous instability and reconstitution of lyophilized powders (’887 Patent, Abstract).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 247). Independent claim 1 is representative.
  • Accused Features: The proposed labeling for the accused product is alleged to promote providing a non-aqueous liquid composition of bendamustine with specific concentrations and stability characteristics for subsequent dilution and administration (Compl. ¶ 58, ¶ 59).

U.S. Patent No. 8,076,366 - “Forms of Bendamustine Free Base”

  • Technology Synopsis: This patent claims novel polymorphic forms of bendamustine free base, as opposed to the hydrochloride salt claimed in other patents-in-suit. The invention describes and characterizes fifteen different crystalline forms of the free base molecule (’366 Patent, Abstract).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 269). Independent claim 1 is representative.
  • Accused Features: The accused product is alleged to be a pharmaceutical composition comprising one or more of fifteen specified forms of bendamustine free base (Compl. ¶ 64).

U.S. Patent No. 8,461,350 - “Bendamustine Pharmaceutical Compositions”

  • Technology Synopsis: This patent, related to the ’190 family, claims pharmaceutical compositions of bendamustine that include specific organic solvents other than or in addition to tertiary-butyl alcohol. The invention covers a range of solvents intended to create stable formulations (’350 Patent, Abstract).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶ 291). Independent claim 1 is representative.
  • Accused Features: The accused product is alleged to be a composition comprising bendamustine, mannitol, water, and a solvent selected from a specified list including ethanol, n-propanol, and isopropanol (Compl. ¶ 65).

III. The Accused Instrumentality

Product Identification

  • The accused product is identified as "BendaRx's NDA Product," for which Defendant submitted New Drug Application No. 215291 to the FDA (Compl. ¶ 1).

Functionality and Market Context

  • The complaint alleges, on information and belief, that the accused product is a generic version of the bendamustine hydrochloride drugs marketed by Plaintiffs as Treanda® and Bendeka® (Compl. ¶ 16-19, ¶ 67). The product is intended for treating chronic lymphocytic leukemia and non-Hodgkin's lymphoma (Compl. ¶ 51, ¶ 57). The complaint alleges the product is a lyophilized preparation that, upon reconstitution and dilution as directed by its proposed labeling, will possess the chemical compositions, specific crystalline forms, and impurity profiles claimed by the patents-in-suit (Compl. ¶¶ 40, 42, 44, 46, 48-49, 51, 53, 55, 58-59, 64-65).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’190 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising bendamustine or bendamustine hydrochloride... The BendaRx NDA Product is alleged to be a pharmaceutical composition containing bendamustine or bendamustine hydrochloride. ¶40 col. 9:1-12
...mannitol... The BendaRx NDA Product is alleged to contain mannitol. ¶40 col. 9:1-12
...tertiary-butyl alcohol and... The BendaRx NDA Product is alleged to contain tertiary-butyl alcohol. ¶40 col. 9:1-12
...water. The BendaRx NDA Product is alleged to contain water. ¶40 col. 9:1-12

Identified Points of Contention

  • Technical Question: A primary point of contention will be factual: does the BendaRx NDA Product contain mannitol and tertiary-butyl alcohol? The complaint alleges their presence on "information and belief" while simultaneously noting that Defendant’s notice letters denied their inclusion (Compl. ¶ 40, ¶ 41). This suggests the case may turn on evidence of the product's actual composition obtained during discovery.
  • Scope Questions: The complaint’s allegation that the product contains the claimed components "or equivalent ingredients" (Compl. ¶ 40) raises the question of whether infringement will be argued under the doctrine of equivalents if the product is found to use different but functionally similar excipients.

’524 Patent Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of bendamustine hydrochloride that is bendamustine hydrochloride Form 1... The BendaRx NDA Product is alleged to comprise bendamustine hydrochloride Form 1. ¶42 col. 3:9-20
...that produces an X-ray powder diffraction pattern comprising one or more of the following reflections: 8.3, 16.8, 18.5, 22.0, and 24.9±0.2 degrees 2θ. The BendaRx NDA Product is alleged to produce an X-ray powder diffraction pattern comprising reflections at 8.3, 16.8, and 18.5±0.2 degrees 2θ. ¶42 col. 6:1-10

Identified Points of Contention

  • Technical Question: A central factual dispute will be whether the crystalline structure of the bendamustine hydrochloride in the accused product is Form 1, as defined by the claimed XRPD peaks. The complaint acknowledges that Defendant denied its product produces the specified reflections (Compl. ¶ 43), positioning this as a key issue to be resolved through expert analysis of the product.
  • Scope Questions: The claim requires "one or more" of the listed peaks. The complaint pleads infringement based on three of the five peaks listed in the claim. This raises the question of how the presence or absence of specific peaks will affect the infringement analysis and whether the overall pattern of the accused product will be deemed to match that of Form 1.

V. Key Claim Terms for Construction

The Term: "tertiary-butyl alcohol" (’190 Patent, claim 1)

  • Context and Importance: This term is critical because it identifies a key stabilizing solvent in the patented formulation. Defendant has expressly denied that its product contains tertiary-butyl alcohol (Compl. ¶ 41). The definition of this term will be central to determining literal infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes the problem as instability in "aqueous solutions" and the solution as using an "organic solvent" to create a more stable pre-lyophilization mixture (’190 Patent, col. 2:29-64). This framing may support an argument under the doctrine of equivalents that other stabilizing organic alcohols could be functional equivalents.
    • Evidence for a Narrower Interpretation: Claim 1 specifically recites "tertiary-butyl alcohol," while other claims and sections of the specification list other alcohols, suggesting the patentee deliberately chose this specific solvent for this claim (’190 Patent, col. 5:12-16). This may support a narrower construction limited to TBA itself.

The Term: "produces an X-ray powder diffraction pattern comprising one or more of the following reflections" (’524 Patent, claim 2)

  • Context and Importance: This phrase defines the patented crystalline structure. Infringement will depend on whether the accused product's physical form meets this structural definition. Practitioners may focus on this term because the parties dispute whether the accused product exhibits the required pattern (Compl. ¶ 43).
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language "one or more" suggests that the presence of any single listed peak is sufficient for literal infringement. This provides a potentially broad basis for an infringement read.
    • Evidence for a Narrower Interpretation: The specification refers to the XRPD spectrum as a "fingerprint" of the crystalline form (’524 Patent, col. 4:1-5). This characterization may support an argument that the overall pattern, not just isolated peaks, is what defines the invention, potentially requiring a substantial match between the accused product's pattern and the pattern of Form 1.

VI. Other Allegations

  • Indirect Infringement: For each asserted patent, the complaint alleges induced infringement. The basis for this allegation is that Defendant’s proposed product labeling will encourage, recommend, and instruct healthcare providers and patients to use the accused product in a manner that directly infringes the claims (e.g., Compl. ¶ 73-74, ¶ 95-96). Contributory infringement is also alleged on the basis that the accused product is especially made or adapted for an infringing use and is not suitable for a substantial non-infringing use (e.g., Compl. ¶ 75, ¶ 97).
  • Willful Infringement: For each asserted patent, the complaint alleges that Defendant acted with full knowledge of the patent and without a reasonable basis for believing it would not be liable for infringement (e.g., Compl. ¶ 77, ¶ 99). This alleged knowledge appears to be based on Defendant's Paragraph IV certification, which requires identifying patents that cover the innovator drug.

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

  • A core issue will be one of factual determination: does the BendaRx NDA Product actually contain the compositions (e.g., tertiary-butyl alcohol, mannitol) and possess the specific crystalline structures (e.g., Form 1, Form 3) alleged by Plaintiffs on "information and belief," particularly in light of Defendant’s express denials outlined in the complaint?
  • A key procedural question will be the adequacy of disclosure: did Defendant’s notice letters and "Offer of Confidential Access" provide sufficient data for Plaintiffs to assess infringement, as required under the Hatch-Waxman Act, and what are the legal consequences if they did not?
  • The case may also present a question of definitional scope for multiple patents: if the accused product does not literally match the claimed chemical or physical structures, can Plaintiffs prove that any alternative components or crystalline forms are functionally equivalent to those claimed in the patents-in-suit?