DCT

1:18-cv-01071

Genzyme Corp v. Gland Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01071, D. Del., 07/19/2018
  • Venue Allegations: Venue is asserted based on Defendant’s alleged systematic and continuous business contacts within Delaware, including the filing of its Abbreviated New Drug Application (ANDA) which Plaintiffs claim constitutes a tortious injury in the state, where Plaintiff sanofi-aventis U.S. LLC is organized.
  • Core Dispute: Plaintiffs allege that Defendant’s filing of an ANDA to market a generic version of Plaintiffs’ Mozobil® (plerixafor) drug product constitutes infringement of three U.S. patents covering the drug’s composition and its methods of use for stem cell mobilization.
  • Technical Context: The technology relates to mobilizing hematopoietic stem cells from the bone marrow into the bloodstream, a critical procedure for patients undergoing autologous transplantation for cancers such as non-Hodgkin's lymphoma and multiple myeloma.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant’s Paragraph IV certification asserting non-infringement or invalidity of the patents-in-suit. The complaint notes that the validity of U.S. Patent No. 7,897,590 was previously challenged and upheld in a decision affirmed by the U.S. Court of Appeals for the Federal Circuit. It also alleges that the invalidity arguments for both the '590 and '102 patents are substantially similar to those presented in other litigation in the same district.

Case Timeline

Date Event
1992-12-16 U.S. Patent No. RE42,152 Priority Date
2001-07-31 U.S. Patent No. 6,987,102 Priority Date
2001-07-31 U.S. Patent No. 7,897,590 Priority Date
2006-01-17 U.S. Patent No. 6,987,102 Issued
2008-12-15 FDA Approval of Mozobil® New Drug Application
2011-02-15 U.S. Reissue Patent No. RE42,152 Issued
2011-03-01 U.S. Patent No. 7,897,590 Issued
2016-05-11 District Court decision in Genzyme v. Dr. Reddy's
2017-12-18 Federal Circuit affirmance in Genzyme v. Dr. Reddy's
2018-06-06 Gland Pharma sends Paragraph IV Notice Letter
2018-07-19 Complaint Filed

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

U.S. Reissue Patent No. RE42,152 - "Aromatic-Linked Polyamine Macrocyclic Compounds with Anti-HIV Activity"

The Invention Explained

  • Problem Addressed: The patent addresses the need for alternative treatments for Human Immunodeficiency Virus (HIV) infection, noting the high toxicity and potential for resistance associated with existing therapies like AZT (RE42152 Patent, col. 1:23-31).
  • The Patented Solution: The invention provides a class of chemical compounds, specifically polyamine macrocycles linked by an aromatic group, which are disclosed as having anti-HIV activity (’152 Patent, Abstract). These compounds, including the general structure Z-R-A-R'-Y, are presented as a novel basis for pharmaceutical compositions to combat HIV (’152 Patent, col. 2:45-55).
  • Technical Importance: The technology disclosed a new structural class of compounds with a distinct chemical profile for potential use as antiviral agents at a time when diversification of HIV treatment options was a critical medical goal (’152 Patent, col. 1:23-31).

Key Claims at a Glance

  • The complaint asserts infringement of Claim 37, which depends from independent Claim 1 (Compl. ¶40).
  • Independent Claim 1:
    • A pharmaceutical composition active against HIV comprising as an active ingredient a linked cyclic compound of the formula I: Z-R-A-R'-Y
    • wherein Z and Y are identical cyclic polyamine moieties having from 10 to 15 ring members and from 3 to 4 amine nitrogens
    • A is an unsubstituted aromatic or heteroaromatic moiety other than quinoline
    • R and R' are each methylene linked to an amine nitrogen atom in Z and in Y
    • in admixture or association with a pharmaceutically acceptable diluent or carrier.
  • The complaint’s specific focus on Claim 37 narrows the asserted scope to compositions where the Z and Y moieties have 14 ring members and 4 amine nitrogens (’152 Patent, Claim 37).

U.S. Patent No. 7,897,590 - "Methods to Mobilize Progenitor/Stem Cells"

The Invention Explained

  • Problem Addressed: The patent identifies a need for small-molecule drugs capable of mobilizing progenitor and stem cells, citing the disadvantages of then-current treatments that relied on proteins and peptides, such as production challenges (’590 Patent, col. 1:56-64).
  • The Patented Solution: The invention is a method for elevating progenitor and/or stem cell counts by administering compounds that bind to the chemokine receptor CXCR4. This binding inhibits the natural ligand SDF-1, leading to the mobilization of stem cells from the bone marrow into the peripheral blood, where they can be harvested for transplantation (’590 Patent, Abstract; col. 4:51-61).
  • Technical Importance: This patent repurposed a known class of CXCR4-antagonist compounds for a new therapeutic use—stem cell mobilization—providing a small-molecule alternative to biologic-based treatments in oncology and hematology (’590 Patent, col. 4:56-64).

Key Claims at a Glance

  • The complaint asserts infringement of independent claims 8 and 19 (Compl. ¶53).
  • Independent Claim 8:
    • A method to obtain progenitor and/or stem cells from a subject, comprising:
    • (a) administering to the subject the compound 1,1'-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane or a salt thereof;
    • in an amount effective to mobilize said cells into the peripheral blood; followed by
    • (b) harvesting said cells.
  • Independent Claim 19:
    • A method to obtain progenitor and/or stem cells from a subject, comprising:
    • (a) administering G-CSF to the subject;
    • prior to administering the compound 1,1'-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane or a salt thereof.

U.S. Patent No. 6,987,102 - "Methods to Mobilize Progenitor/Stem Cells"

  • Multi-Patent Capsule:
    • Patent Identification: U.S. Patent No. 6,987,102, "Methods to Mobilize Progenitor/Stem Cells", issued January 17, 2006 (Compl. ¶15).
    • Technology Synopsis: As a parent to the ’590 patent, this patent similarly discloses methods of using polyamine compounds that act as antagonists to the CXCR4 receptor to mobilize progenitor and stem cells into the peripheral blood. The mobilized cells can then be harvested for use in transplantation therapies, such as for patients whose bone marrow has been affected by chemotherapy or radiotherapy (’102 Patent, Abstract; col. 4:56-64).
    • Asserted Claims: The complaint asserts infringement of independent Claim 8 (Compl. ¶66).
    • Accused Features: The accused feature is the proposed use of Gland's ANDA product, which contains the active ingredient plerixafor. Plaintiffs allege that the product's prescribing information will instruct medical professionals to administer the drug for the purpose of mobilizing and harvesting stem cells, thereby practicing the claimed method (Compl. ¶66, ¶69).

III. The Accused Instrumentality

Product Identification

  • Defendant's proposed Plerixafor Injection, 24 mg/1.2mL, which is the subject of Abbreviated New Drug Application (ANDA) No. 206644 (Compl. ¶2).

Functionality and Market Context

  • The accused product is a proposed generic version of Genzyme's Mozobil® drug (Compl. ¶2). Its active ingredient is plerixafor, and it is intended to be used for the same FDA-approved indication as Mozobil®: to "mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma," typically in combination with granulocyte-colony stimulating factor (G-CSF) (Compl. ¶12, ¶19, ¶21). The complaint alleges the product is bioequivalent to Mozobil® and will be sold with substantially similar prescribing information (Compl. ¶20, ¶22).

IV. Analysis of Infringement Allegations

RE42,152 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition ... comprising as an active ingredient a linked cyclic compound of the formula I: Z-R-A-R'-Y... The accused ANDA product is a pharmaceutical composition containing the active ingredient plerixafor, which Plaintiffs allege is the specific compound claimed in the patent. ¶19 col. 2:45-55
wherein Z and Y are identical cyclic polyamine moieties having from 10 to 15 ring members and from 3 to 4 amine nitrogens... Plerixafor's chemical structure, 1,1'-[1,4-phenylenebis(methylene)]-bis(1,4,8,11-tetraazacyclotetradecane), is alleged to meet the structural limitations of the claim, including having 14-membered rings with 4 nitrogen atoms as specified in dependent Claim 37. ¶19 col. 2:45-48
in admixture or association with a pharmaceutically acceptable diluent or carrier. The accused product is an injectable solution formulated for medical use, and is therefore alleged to contain the active ingredient with a pharmaceutically acceptable diluent or carrier. ¶2 col. 2:54-55
  • Identified Points of Contention:
    • Scope Questions: A primary question for the ’152 Patent is whether the preamble phrase "active against HIV" is a legally limiting element of Claim 1. Defendant may argue that because its product is indicated for stem cell mobilization, not HIV, this claim limitation is not met. Plaintiffs may counter that the property is inherent to the claimed chemical structure (plerixafor), and thus any composition containing it necessarily meets the limitation regardless of its marketed indication.

7,897,590 Infringement Allegations

Claim Element (from Independent Claim 8) Alleged Infringing Functionality Complaint Citation Patent Citation
A method to obtain progenitor and/or stem cells from a subject which method comprises: (a) administering to said subject the compound 1,1'-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane... The prescribing information for Gland's ANDA product, which contains plerixafor (the claimed compound), will allegedly instruct medical professionals to administer the drug to patients. ¶23 col. 27:48-52
in an amount effective to mobilize said progenitor and/or stem cells into the peripheral blood of said subject; The product's labeled indication is for mobilizing hematopoietic stem cells to the peripheral blood. ¶21, ¶23 col. 4:31-35
followed by (b) harvesting said progenitor and/or stem cells. The labeled indication is for "collection and subsequent autologous transplantation," which necessarily includes the step of harvesting the mobilized cells. ¶12, ¶23 col. 4:65-67
  • Identified Points of Contention:
    • Technical Questions: Since infringement of these method claims is based on inducement, the central question is evidentiary: will the final, FDA-approved label for Gland's product instruct users to perform every step of the asserted claims? For Claim 19, this includes the administration of G-CSF prior to the administration of plerixafor.

V. Key Claim Terms for Construction

  • The Term: "active against HIV" ('152 Patent, Claim 1)
  • Context and Importance: The construction of this preamble phrase may be dispositive for the ’152 patent. Practitioners may focus on this term because Defendant will likely argue it is a necessary limitation that its product does not meet, as its product is not marketed for HIV treatment. The court's decision on whether this phrase limits the claim's scope to an anti-HIV context will determine if there is a fundamental mismatch between the claim and the accused product's use.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Plaintiffs may argue that the body of the claim defines a specific chemical composition. As the patent specification teaches that this composition possesses anti-HIV activity, any formulation containing it would meet the "active against HIV" description, making the property inherent to the claimed subject matter.
    • Evidence for a Narrower Interpretation: Defendant may argue that the patent's title, abstract, and background consistently frame the invention as a treatment for HIV. This context could support an interpretation that the preamble is not merely descriptive but is a statement of intended purpose that limits the scope of the claim, meaning infringement requires that the accused composition be used or intended for use as an anti-HIV agent (’152 Patent, Title; col. 1:12-16).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents-in-suit (Compl. ¶44, ¶46-48, ¶57, ¶59-61, ¶70, ¶72-74). The factual basis for inducement is the allegation that Gland's product, upon approval, will be accompanied by prescribing information that instructs and encourages physicians and other users to perform the patented methods (Compl. ¶22-24). The complaint alleges inducement will occur through Gland's product label, which is expected to be substantially similar to the prescribing information for Mozobil® attached as Exhibit A (Compl. ¶12, ¶22). Contributory infringement is alleged on the basis that the product is especially made for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶30, ¶47, ¶60, ¶73).
  • Willful Infringement: Willfulness is alleged for all asserted patents (Compl. ¶49, ¶62, ¶75). The allegations are based on Gland's alleged knowledge of the patents, as evidenced by its Paragraph IV certification notice (Compl. ¶35). The complaint further supports this claim by asserting Gland's awareness of prior litigation in which the validity of the '590 patent was affirmed by the Federal Circuit and the '102 patent was at issue (Compl. ¶36, ¶62, ¶75).

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

  • A core issue will be one of definitional scope: For the '152 patent, can the preamble term "active against HIV," rooted in the patent's original purpose, be construed to read on a product indicated and marketed exclusively for hematopoietic stem cell mobilization?
  • A key question will be one of validity and preclusion: Given the complaint’s reference to prior successful litigation affirming the validity of the '590 patent, a central issue will be the extent to which Defendant is able to raise the same or similar invalidity arguments, and what preclusive or persuasive effect the prior rulings may have on this case.
  • A third central question will be one of inducement: For the '590 and '102 method patents, the dispute will likely focus on whether the final, FDA-approved prescribing information for Defendant's generic product will contain instructions that direct or encourage users to perform each and every limitation of the asserted method claims.