DCT

3:25-cv-17982

Acrotech Biopharma Inc v. Gland Pharma Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:25-cv-17982, D.N.J., 11/26/2025
  • Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign company not residing in any U.S. judicial district and may therefore be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendant's submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of the cancer drug EVOMELA®, constitutes an act of infringement of three U.S. patents related to injectable melphalan formulations.
  • Technical Context: The technology concerns pharmaceutical formulations of melphalan, a chemotherapy agent, using a cyclodextrin derivative to improve the drug's solubility and stability for intravenous administration.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a Notice Letter dated October 14, 2025, in which Defendant Gland Pharma notified Plaintiffs of its ANDA filing containing a Paragraph IV Certification. The complaint notes that in its letter, Gland Pharma did not assert non-infringement defenses against numerous asserted claims of the patents-in-suit.

Case Timeline

Date Event
2009-05-29 Earliest Priority Date for all Patents-in-Suit
2020-12-15 U.S. Patent No. 10,864,183 Issues
2021-03-09 U.S. Patent No. 10,940,128 Issues
2021-06-01 U.S. Patent No. 11,020,363 Issues
2025-10-14 Defendant sends Notice Letter regarding ANDA filing
2025-11-26 Complaint Filing Date

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

U.S. Patent No. 10,864,183 - "Injectable Nitrogen Mustard Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same"

  • Patent Identification: U.S. Patent No. 10,864,183, "Injectable Nitrogen Mustard Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same," issued December 15, 2020.

The Invention Explained

  • Problem Addressed: The patent's background describes the challenges with existing intravenous formulations of the chemotherapy drug melphalan. Melphalan is known to undergo rapid chemical hydrolysis in aqueous solutions, and prior commercial formulations could not be refrigerated due to drug precipitation and could form undesirable derivatives upon reconstitution (’183 Patent, col. 2:20-29).
  • The Patented Solution: The invention is a pharmaceutical composition that uses a specific class of cyclodextrin derivative—a sulfoalkyl ether β-cyclodextrin—as a solubilizing and stabilizing agent for melphalan (’183 Patent, col. 2:32-40). This combination creates a stable formulation, suitable for intravenous use, that avoids the need for organic co-solvents like propylene glycol and ethanol, and which demonstrates improved stability, thereby allowing for longer infusion durations (’183 Patent, col. 2:40-52). The manufacturing process involves carefully controlling pH at various stages to dissolve the components and achieve the final formulation (’183 Patent, FIG. 3).
  • Technical Importance: This technology provided a melphalan formulation with enhanced stability, which could simplify hospital pharmacy preparation and enable different administration protocols, such as longer-duration infusions, that were not feasible with previous formulations (’183 Patent, col. 2:45-52).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2-6 and 8-10 (Compl. ¶28).
  • The essential elements of independent claim 1 include:
    • A solid pharmaceutical composition comprising about 50 mg of melphalan as a hydrochloride salt.
    • An amount of an acid, a base, or a combination thereof sufficient to provide a pH of about 4 to 6 upon dilution.
    • A specific sulfoalkyl ether β-cyclodextrin derivative (defined by formula II) where the degree of substitution is between 6.0 and 7.1.
    • A stability requirement wherein the melphalan degrades by 2% or less within 5 hours at 25° C. after dilution.
    • A requirement that the cyclodextrin derivative is present in a ratio of about 55:1 (w/w) relative to the melphalan.
  • The complaint reserves the right to assert additional claims (’183 Patent, col. 18:38-62; Compl. ¶28).

U.S. Patent No. 10,940,128 - "Injectable Melphalan Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same"

  • Patent Identification: U.S. Patent No. 10,940,128, "Injectable Melphalan Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same," issued March 9, 2021.

The Invention Explained

  • Problem Addressed: The patent addresses the same technical problem as the ’183 Patent: the poor aqueous stability of melphalan and the formulation challenges of prior intravenous products, including precipitation and the formation of derivatives (’128 Patent, col. 2:11-23).
  • The Patented Solution: The invention claims a specific method of using a cyclodextrin-based melphalan formulation for conditioning a patient for stem cell transplantation. The claimed method involves specific steps of reconstituting a lyophilized solid and administering it via "limb perfusion" at a specified dose, pH, and cyclodextrin concentration (’128 Patent, col. 35:60-col. 36:8). The solution provides a specific pharmacokinetic profile (an AUC at least 20% greater than a formulation lacking the cyclodextrin), suggesting improved drug delivery or bioavailability (’128 Patent, col. 36:1-8).
  • Technical Importance: This patent claims a specific therapeutic application and administration protocol for the stabilized melphalan formulation, linking the formulation technology to a clinical outcome in the context of stem cell transplantation, a high-dose chemotherapy regimen (’128 Patent, col. 30:7-12).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2-14 (Compl. ¶28).
  • The essential elements of independent claim 1 include:
    • A method for conditioning a subject for a stem cell transplant.
    • Reconstituting a lyophilized solid of melphalan hydrochloride and a cyclodextrin derivative in an aqueous sodium chloride diluent.
    • The cyclodextrin derivative must be present in a 54:1 (w/w) ratio to melphalan.
    • Administering the reconstituted solid at a dose of 50 mg/m² to 300 mg/m² per day.
    • The cyclodextrin derivative has a specific structure (formula I) with an average degree of substitution of about 6.5.
    • The reconstituted composition has an initial pH of 5 and a cyclodextrin concentration of about 0.125 M.
    • The administration is performed via "limb perfusion."
    • The administration provides a melphalan AUC (Area Under the Curve) that is at least 20% greater than that provided by a formulation lacking the cyclodextrin derivative.
  • The complaint reserves the right to assert additional claims (’128 Patent, col. 35:60-col. 36:8; Compl. ¶28).

U.S. Patent No. 11,020,363 - "Injectable Nitrogen Mustard Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same"

  • Patent Identification: U.S. Patent No. 11,020,363, "Injectable Nitrogen Mustard Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same," issued June 1, 2021.
  • Technology Synopsis: The patent addresses the chemical instability of nitrogen mustard compounds, such as melphalan, when formulated in aqueous solutions for injection (’363 Patent, col. 2:17-29). The patented solution is a pharmaceutical composition that complexes melphalan with a sulfoalkyl ether cyclodextrin derivative, which improves the drug's stability and solubility without requiring organic co-solvents, thereby creating a more stable product suitable for intravenous administration (’363 Patent, col. 2:32-52).
  • Asserted Claims: Claims 1-7 are asserted, with claim 1 being the sole independent claim (Compl. ¶28).
  • Accused Features: The complaint alleges that Defendant's proposed generic product, being a version of EVOMELA®, is a pharmaceutical composition containing melphalan hydrochloride and a cyclodextrin derivative that infringes the patent (Compl. ¶¶ 29-30, 58-63).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Gland Pharma ANDA Product," a generic drug product for which Defendant Gland Pharma has filed ANDA No. 220632 with the FDA (Compl. ¶1). The product is a proposed generic version of Plaintiffs' EVOMELA® (Melphalan Hydrochloride, EQ 50 mg Base/Vial) (Compl. ¶1, ¶29).

Functionality and Market Context

  • The complaint alleges that the Gland Pharma ANDA Product is a generic version of EVOMELA® that contains the "same or equivalent ingredients in the same or equivalent amounts" and will feature the "same or equivalent chemical and therapeutic properties" (Compl. ¶¶ 29-30). The ANDA filing is alleged to rely on the safety and efficacy data of the EVOMELA® New Drug Application and to contain data demonstrating bioequivalence (Compl. ¶33, ¶46, ¶59). The filing of the ANDA itself, which seeks approval for commercial manufacture and sale in the U.S. prior to the expiration of the patents-in-suit, is the statutory act of infringement alleged under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶34, ¶47, ¶60).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed claim chart or specific factual allegations mapping elements of the accused product to the patent claims. The infringement theory is predicated on the allegation that the Gland Pharma ANDA Product is a generic equivalent of EVOMELA® and therefore necessarily practices the patented invention.

’183 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising about 50 mg of melphalan as a hydrochloride salt, The Gland Pharma ANDA Product is alleged to be a solid composition containing melphalan hydrochloride in an equivalent amount to EVOMELA®. ¶¶ 29, 36 col. 18:38-44
an amount sufficient of an acid, a base, or a combination thereof to provide a pH of about 4 to about 6 upon dilution with a saline solution to a volume of about 10 mL, The Gland Pharma ANDA Product is alleged to be formulated to achieve a pH within the claimed range upon reconstitution, equivalent to EVOMELA®. ¶¶ 29-30, 36 col. 18:40-42
and a cyclodextrin derivative of formula II...wherein 21-x of the R groups are H and x of the R groups are —(CH2)4—SO3−Na+, and x=6.0-7.1, The Gland Pharma ANDA Product is alleged to contain a cyclodextrin derivative with the same chemical structure as that used in EVOMELA®. ¶¶ 29-30, 36 col. 17:1-3
wherein dilution of the solid pharmaceutical composition...provides a melphalan solution in which the melphalan degrades by 2% or less at about 25° C. within 5 hours, or by 4% or less at about 25° C. within 10 hours after the diluting, The Gland Pharma ANDA Product is alleged to have a stability profile equivalent to EVOMELA® that meets this degradation limitation. ¶¶ 29-30, 36 col. 24:25-30
and wherein the cyclodextrin derivative is present in a ratio of about 55:1 (w/w) relative to the melphalan. The Gland Pharma ANDA Product is alleged to contain a ratio of cyclodextrin to melphalan equivalent to EVOMELA® that meets this limitation. ¶¶ 29-30, 36 col. 18:29-32
  • Identified Points of Contention:
    • Scope Questions: The analysis may focus on the scope of the term "about 55:1." A central question could be whether the precise weight-to-weight ratio of cyclodextrin to melphalan in Defendant’s product falls within the range connoted by "about," or if it is sufficiently different to be non-infringing.
    • Technical Questions: A key factual question will be whether Defendant's product, upon reconstitution, exhibits the specific degradation profile recited in the claim (e.g., "degrades by 2% or less... within 5 hours"). Evidence from stability studies of the ANDA product will be central to this inquiry.

’128 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for conditioning a subject for whom a stem cell transplantation has been indicated... Infringement is alleged based on the proposed labeling for the Gland Pharma ANDA Product, which is expected to instruct its use for conditioning prior to stem cell transplant. ¶¶ 50, 53-54 col. 30:7-12
reconstituting a lyophilized solid consisting of melphalan hydrochloride and a cyclodextrin derivative... The proposed label is alleged to instruct users to reconstitute the lyophilized ANDA product. ¶¶ 50, 53-54 col. 27:7-11
wherein the cyclodextrin derivative is present in a ratio of 54:1 (w/w) relative to the melphalan... The ANDA product is alleged to contain this specific ratio of cyclodextrin to melphalan. ¶¶ 29-30, 49 col. 66:1-3
administering the reconstituted lyophilized solid at a melphalan dose of 50 mg/m² to 300 mg/m² per day... The proposed label is alleged to instruct administration at a dose falling within this range. ¶¶ 50, 53-54 col. 30:45-61
wherein the initial pH of the composition is 5; and wherein the cyclodextrin concentration is about 0.125 M... The ANDA product and its instructions for reconstitution are alleged to result in a composition with these specific properties. ¶¶ 29-30, 49 col. 66:54
wherein the administration is performed via a limb perfusion... The proposed label is alleged to instruct or recommend administration via limb perfusion. ¶¶ 50, 53-54 col. 27:42-45
and further wherein the administering provides a melphalan AUCo-t...at least 20% greater than a melphalan AUCo-t provided by a melphalan formulation...lacking the cyclodextrin derivative. The ANDA product, alleged to be bioequivalent to EVOMELA®, is expected to produce the claimed pharmacokinetic result when administered as instructed. ¶¶ 30, 46, 49 col. 32:20-43
  • Identified Points of Contention:
    • Scope Questions: A primary dispute may concern the "limb perfusion" limitation. The analysis will raise the question of whether Defendant's proposed product label specifically instructs or encourages this particular method of administration, or if it provides more general instructions that do not meet this specific claim element.
    • Technical Questions: The functional limitation requiring a specific pharmacokinetic result ("provides a melphalan AUCo-t... at least 20% greater") will be a point of focus. This raises the evidentiary question of whether Defendant can demonstrate that its bioequivalent product, when used according to its label, fails to achieve this claimed pharmacokinetic advantage.

V. Key Claim Terms for Construction

  • The Term: "about 55:1 (w/w)" (from ’183 Patent, claim 1)

  • Context and Importance: This term defines the quantitative relationship between the active ingredient and the key excipient. Its construction will be critical because even a small deviation in the accused product's formulation from the "55:1" ratio could form the basis of a non-infringement argument, making the scope of "about" a central issue.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides several ranges for the ratio, such as "50:1 to 100:1" and "55:1 to 60:1," suggesting that the inventors did not intend the claim to be limited to the exact 55:1 ratio (’183 Patent, col. 16:1-3).
    • Evidence for a Narrower Interpretation: The patent's examples detail compositions with specific concentrations, which could be used to argue for a more constrained interpretation of "about" based on the results disclosed at those concentrations (’183 Patent, col. 47-48). The choice to claim "about 55:1" rather than a broader range could also be argued to imply a narrower scope.

  • The Term: "limb perfusion" (from ’128 Patent, claim 1)

  • Context and Importance: This term recites a specific, and relatively specialized, method of drug administration. Practitioners may focus on this term because infringement of this method claim will likely depend on whether Defendant's product label is found to induce physicians to perform this exact procedure, as opposed to more common forms of intravenous administration.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification lists "limb perfusion" as one of several types of "intravenous administration," alongside "bolus injection" and "intravenous infusion," which might support an argument that the term should be viewed within the broader context of parenteral delivery (’128 Patent, col. 27:42-45).
    • Evidence for a Narrower Interpretation: The term "limb perfusion" has a well-understood clinical meaning involving the isolation of a limb's circulatory system for regional drug delivery. The patent does not appear to provide a special definition that deviates from this plain and ordinary meaning, which could support a narrow construction limited to that specific procedure.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents. The inducement allegations are based on the assertion that Defendant’s promotional materials and package inserts for its ANDA product will instruct or encourage medical professionals and patients to use the product in an infringing manner (Compl. ¶¶ 41, 54, 67). Contributory infringement is alleged on the basis that Defendant’s product is not a staple article of commerce and is especially made for use in an infringing manner (Compl. ¶¶ 38-39, 51-52, 64-65).
  • Willful Infringement: The complaint alleges that Defendant had knowledge of the patents-in-suit, at least as of the date of its October 14, 2025 Notice Letter (Compl. ¶¶ 40, 53, 66). While the term "willful" is not used, Plaintiffs request a finding that the case is "exceptional" under 35 U.S.C. § 285, which warrants an award of attorneys' fees (Compl. ¶¶ 43, 56, 69).

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

  • A core issue will be one of infringement by equivalence: given that the infringement allegations are based on the Defendant's product being a generic copy, a key question will be whether the specific formulation details and manufacturing processes of the ANDA product fall within the literal scope of the patent claims. The analysis will likely focus on quantitative limitations, such as the "about 55:1" ratio in the ’183 Patent, and whether minor differences are sufficient to avoid infringement.
  • A second central question will be one of induced infringement of method claims: for the ’128 Patent, which claims a specific method of administration, the dispute may turn on the language in the Defendant's proposed product label. A key legal and factual question for the court will be whether the instructions on that label direct, recommend, or merely allow for an administration protocol that meets all steps of the asserted method claims, including the "limb perfusion" requirement.
  • Finally, as Defendant's ANDA filing included a Paragraph IV certification asserting invalidity (Compl. ¶27), a critical element of the case will be the validity challenge. The court will likely need to determine whether the combination of a known drug (melphalan) with a known class of excipients (cyclodextrins) to achieve improved stability would have been obvious to a person of ordinary skill in the art at the time of the invention.