DCT

1:08-cv-00050

Alpharma Inc v. Purdue Pharma LP

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:08-cv-50, W.D. Va., 12/07/2009
  • Venue Allegations: Venue is alleged to be proper because Defendant Purdue conducts business in the Western District of Virginia and is subject to personal jurisdiction there.
  • Core Dispute: Plaintiffs seek a declaratory judgment that their abuse-deterrent opioid analgesic, EMBEDA®, does not infringe, and that the claims of nine of Defendant’s patents are invalid.
  • Technical Context: The technology concerns pharmaceutical formulations of opioid analgesics designed to deter abuse by incorporating an opioid antagonist.
  • Key Procedural History: The complaint alleges that a direct and immediate controversy exists based on pre-suit communications in which Defendant’s representative allegedly stated its patents were broad enough to encompass Plaintiffs’ technology and that it would be “necessary to let the lawyers work [the dispute] out,” which Plaintiffs construed as a threat of litigation.

Case Timeline

Date Event
1997-12-22 Priority Date for ’384, ’957, and ’863 Patents
2001-05-08 U.S. Patent No. 6,228,863 Issued
2001-08-21 U.S. Patent No. 6,277,384 Issued
2002-04-23 U.S. Patent No. 6,375,957 Issued
2002-11-05 U.S. Patent No. 6,475,494 Issued
2003-09-30 U.S. Patent No. 6,627,635 Issued
2004-02-24 U.S. Patent No. 6,696,066 Issued
2004-02-24 U.S. Patent No. 6,696,088 Issued
2006-Fall Alpharma becomes aware of Purdue's patents
2007-02-06 U.S. Patent No. 7,172,767 Issued
2007-09-14 Meeting where Purdue allegedly threatened litigation
2008-06-30 Alpharma re-submits New Drug Application for EMBEDA
2008-09-02 U.S. Patent No. 7,419,686 Issued
2009-08-15 FDA approves EMBEDA
2009-09-01 King begins marketing EMBEDA
2009-12-07 Complaint Filed

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

U.S. Patent No. 6,277,384 - Opioid Agonist/Antagonist Combinations

  • Patent Identification: U.S. Patent No. US6277384A, “Opioid Agonist/Antagonist Combinations,” issued August 21, 2001.

The Invention Explained

  • Problem Addressed: The patent addresses the widespread abuse of opioid analgesics, noting that abuse occurs not only via parenteral injection of extracted opioids but also via oral ingestion of higher-than-prescribed doses to achieve euphoria (’384 Patent, col. 3:45-4:43). Prior art solutions focused primarily on deterring parenteral abuse, leaving a need for a formulation that also deters oral abuse (’384 Patent, col. 4:30-43).
  • The Patented Solution: The invention is an oral dosage form that combines an opioid agonist (the painkiller) with an opioid antagonist (a blocker). The two are combined in a specific ratio such that when taken as a normal therapeutic dose, the patient receives pain relief. However, if an abuser takes a higher oral dose (e.g., 2-3 times the prescribed amount), the increased amount of the antagonist is intended to cause an "aversive" experience, such as precipitating withdrawal symptoms in a physically dependent person, thereby deterring oral abuse (’384 Patent, col. 5:5-18; col. 6:35-44). The antagonist also deters parenteral abuse if extracted.
  • Technical Importance: The invention describes a method to deter both oral and parenteral opioid abuse within a single dosage form, addressing a key challenge in pain management.

Key Claims at a Glance

  • The complaint seeks a declaratory judgment of non-infringement as to all claims but does not single out any specific claims (Compl. ¶ 52). Independent claim 1 is representative of the core invention.
  • Essential elements of Independent Claim 1 include:
    • An oral dosage form comprising an orally therapeutically effective dose of an opioid agonist and an opioid antagonist.
    • The ratio of antagonist to agonist provides a product that is analgesically effective when administered orally.
    • The product is "aversive in physically dependent human subjects" when administered at the same or a higher dose.
    • The product "maintains an analgesic effect but does not increase analgesic efficacy" compared to the agonist alone.
  • The complaint denies infringement of all claims, including any dependent claims (Compl. ¶ 52).

U.S. Patent No. 6,375,957 - Opioid Agonist/Opioid Antagonist/Acetaminophen Combinations

  • Patent Identification: U.S. Patent No. US6375957B1, “Opioid Agonist/Opioid Antagonist/Acetaminophen Combinations,” issued April 23, 2002.

The Invention Explained

  • Problem Addressed: This patent addresses the same opioid abuse problem as the ’384 Patent but incorporates an additional therapeutic agent (’957 Patent, col. 3:45-4:43).
  • The Patented Solution: The solution is similar to that of the ’384 Patent—an agonist/antagonist ratio designed to be therapeutic at normal doses and aversive at abuse-level oral doses—but adds acetaminophen to the formulation (’957 Patent, Abstract). The addition of acetaminophen is intended to provide augmented pain relief, potentially through a synergistic effect with the opioid agonist (’957 Patent, col. 13:50-61).
  • Technical Importance: This patent extends the abuse-deterrent ratio concept to combination drug products that include a non-opioid analgesic like acetaminophen, which are common in pain management.

Key Claims at a Glance

  • The complaint seeks a declaratory judgment of non-infringement as to all claims (Compl. ¶ 60). Independent claim 1 is representative.
  • Essential elements of Independent Claim 1 include:
    • An oral dosage form comprising an opioid agonist, acetaminophen, and an opioid antagonist.
    • The ratio of the three components provides a product that is analgesically effective when administered orally.
    • The product is "aversive in physically dependent human subjects" when administered at the same or a higher dose.
    • The product "maintains an analgesic effect but does not increase analgesic efficacy" compared to the agonist/acetaminophen combination alone.
  • The complaint denies infringement of all claims, including any dependent claims (Compl. ¶ 60).

Multi-Patent Capsules

  • Patent Identification: U.S. Patent No. US6475494B2, “Opioid Agonist/Antagonist Combinations,” issued November 5, 2002.

    • Technology Synopsis: The patent describes oral dosage forms containing a combination of an opioid agonist and an opioid antagonist in a specific ratio intended to provide analgesia at prescribed doses while creating an aversive experience at supra-therapeutic doses to deter oral abuse (Compl. ¶ 10). This technology appears closely related to the ’384 Patent.
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 68).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

  • Patent Identification: U.S. Patent No. US6696066B2, “Opioid Agonist/Antagonist Combinations,” issued February 24, 2004.

    • Technology Synopsis: The patent describes oral dosage forms containing a combination of an opioid agonist and an opioid antagonist in a specific ratio intended to provide analgesia at prescribed doses while creating an aversive experience at supra-therapeutic doses to deter oral abuse (Compl. ¶ 11). This technology appears closely related to the ’384 Patent.
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 76).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

  • Patent Identification: U.S. Patent No. US7172767B2, “Opioid Agonist/Antagonist Combinations,” issued February 6, 2007.

    • Technology Synopsis: The patent describes oral dosage forms containing a combination of an opioid agonist and an opioid antagonist in a specific ratio intended to provide analgesia at prescribed doses while creating an aversive experience at supra-therapeutic doses to deter oral abuse (Compl. ¶ 12). This technology appears closely related to the ’384 Patent.
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 84).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

  • Patent Identification: U.S. Patent No. US7419686B2, “Opioid Agonist/Antagonist Combinations,” issued September 2, 2008.

    • Technology Synopsis: The patent describes oral dosage forms containing a combination of an opioid agonist and an opioid antagonist in a specific ratio intended to provide analgesia at prescribed doses while creating an aversive experience at supra-therapeutic doses to deter oral abuse (Compl. ¶ 13). This technology appears closely related to the ’384 Patent.
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 92).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

  • Patent Identification: U.S. Patent No. US6228863A, “Method of Preventing Abuse of Opioid Dosage Forms,” issued May 8, 2001.

    • Technology Synopsis: This patent addresses the parenteral abuse of oral opioid medications by describing a dosage form combining an opioid agonist and antagonist that requires at least a two-step chemical extraction process to separate the two components (’863 Patent, Abstract). The formulation is designed such that the antagonist is sufficient to counteract the opioid's effects if they are extracted and administered together parenterally (’863 Patent, col. 4:55-60).
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 100).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

  • Patent Identification: U.S. Patent No. US6627635B2, “Method of Preventing Abuse of Opioid Dosage Forms,” issued September 30, 2003.

    • Technology Synopsis: The patent describes methods for preventing abuse of opioid dosage forms, likely related to the technology of the ’863 Patent that focuses on formulations resistant to extraction for parenteral abuse (Compl. ¶ 15).
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 108).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

  • Patent Identification: U.S. Patent No. US6696088B2, “Tamper Resistant Oral Opioid Agonist Formulations,” issued February 24, 2004.

    • Technology Synopsis: The patent is directed to tamper-resistant oral opioid formulations, suggesting a focus on physical or chemical properties that deter common methods of abuse, such as crushing or dissolving the dosage form (Compl. ¶ 17).
    • Asserted Claims: All claims are implicated in the request for declaratory judgment of non-infringement (Compl. ¶ 116).
    • Accused Features: The EMBEDA® product is the subject of the non-infringement claim (Compl. ¶ 43).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Plaintiffs’ drug product EMBEDA® (Compl. ¶ 28).
  • Functionality and Market Context: EMBEDA® is described as an extended-release oral formulation of morphine for managing moderate to severe pain (Compl. ¶ 28). To deter abuse, it contains a "sequestered" opioid antagonist, naltrexone. According to the complaint, when the drug is taken as directed, the naltrexone is not released and the patient receives pain relief. However, if the drug is abused by crushing or chewing, the sequestered naltrexone is immediately released, which allegedly mitigates the euphoric effects of the morphine (Compl. ¶ 28). The complaint positions EMBEDA® as a novel opioid analgesic with the potential to reduce the risk of substance abuse, developed in response to a public health crisis (Compl. ¶¶ 26-28).
    No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

As this is a complaint for declaratory judgment of non-infringement, Plaintiffs do not allege that their product meets the claim limitations. Instead, they deny infringement and seek a court order to that effect (Compl. ¶¶ 50, 52). The complaint does not contain a claim chart or a narrative infringement theory. The analysis, therefore, must focus on the likely points of contention that would arise in a dispute over these patents.

  • Identified Points of Contention:
    • Scope Questions: A central dispute may arise over the scope of the term "aversive." The ’384 and ’957 Patents appear to teach an aversive effect achieved through a specific pharmacological ratio of agonist and antagonist that becomes active at higher oral doses of an intact pill. The question for the court may be whether this claim language reads on EMBEDA®'s mechanism, which relies on the physical "sequestering" of the antagonist that is only released upon physical tampering (crushing/chewing) of the dosage form.
    • Technical Questions: A key technical question may be whether EMBEDA®'s functionality meets the specific limitations of the asserted claims. For the ’384 family of patents, this may involve evidence of whether ingesting multiple intact EMBEDA® capsules creates the claimed "aversive" experience in physically dependent subjects, or whether the aversive effect only manifests after the physical integrity of the dosage form is compromised, potentially creating a mismatch with the claim language. For the ’863 family, the question may be whether EMBEDA®'s sequestering technology constitutes the claimed "two-step extraction process" required to separate the agonist from the antagonist.

V. Key Claim Terms for Construction

  • The Term: "aversive in a physically dependent human subject" (from claim 1 of the ’384 and ’957 Patents)

    • Context and Importance: This term is the central functional limitation defining the abuse-deterrent property of the claimed invention. The outcome of the non-infringement analysis for the ’384 family of patents may depend entirely on whether EMBEDA®'s mechanism of action is found to be "aversive" in the manner claimed.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The plain language of the term itself does not specify the mechanism (pharmacological ratio vs. physical sequestering) by which the aversive state is achieved, which may support a broader construction covering any mechanism that causes an aversive experience at higher doses.
      • Evidence for a Narrower Interpretation: The patent specification describes the aversive experience in the context of "precipitated abstinence syndrome" (’384 Patent, col. 16:65) and provides clinical data from oral administration of intact dosage forms (’384 Patent, Figs. 1-11). This may support a narrower construction requiring the aversive effect to be generated pharmacologically from an intact pill at higher doses, not from a physical release mechanism triggered by tampering.

  • The Term: "maintains an analgesic effect but does not increase analgesic efficacy" (from claim 1 of the ’384 and ’957 Patents)

    • Context and Importance: This limitation defines the performance of the formulation at the prescribed therapeutic dose. Practitioners may focus on this term because Plaintiffs could argue that EMBEDA®'s sequestered naltrexone has no pharmacological effect when taken as directed, thereby "maintaining" the morphine's full effect, while Defendant may argue the claims require a more nuanced interaction.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The language could be interpreted to mean simply that the antagonist does not interfere with analgesia at normal doses, a condition EMBEDA®'s sequestering mechanism is designed to satisfy (Compl. ¶ 28).
      • Evidence for a Narrower Interpretation: The phrase "does not increase" could imply that the antagonist has some baseline interaction or presence, even at therapeutic doses, which is balanced to avoid reducing efficacy. The specification's focus on specific agonist-to-antagonist ratios could be cited to support an interpretation that the invention requires a specific pharmacological balancing act rather than simple inert sequestration (’384 Patent, Tables 1-3).

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

  • A core issue will be one of technical mechanism: can the functional claim limitation of an "aversive" effect, which in the patents appears to arise from a pharmacological ratio in an intact dosage form, be construed to cover the distinct mechanism of EMBEDA®, which relies on the physical release of a "sequestered" antagonist only upon tampering?
  • A key question of claim scope will be the definition of "aversive." The case may turn on whether this term requires the specific induction of clinical withdrawal symptoms from oral ingestion of multiple intact doses, or if it can be interpreted more broadly to include the mitigation of euphoria following physical destruction of the dosage form.
  • A threshold procedural question will be one of justiciability: did the alleged pre-suit statement about letting "the lawyers work it out," in the full context of the parties' interactions, create a sufficiently real and immediate controversy to give the court declaratory judgment jurisdiction?