DCT

1:19-cv-03112

Otsuka Pharmaceutical Co Ltd v. Sandoz Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-03112, D. Colo., 11/01/2019
  • Venue Allegations: Venue is alleged to be proper in the District of Colorado because Defendant Sandoz Inc. is incorporated in Colorado, and Defendant Sandoz GmbH is a foreign corporation that may be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) seeking to market generic versions of Plaintiffs' REXULTI® (brexpiprazole) tablets constitutes an act of infringement of five U.S. patents covering the compound, its formulation, and its methods of use.
  • Technical Context: The technology relates to pharmaceutical compounds and formulations used for the treatment of mental disorders, specifically schizophrenia and major depressive disorder.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Paragraph IV Notice Letter from Sandoz, which asserted that the patents-in-suit are invalid, unenforceable, or would not be infringed by Sandoz's proposed generic product. Several of the asserted patents are subject to terminal disclaimers, fixing their expiration dates to that of an earlier-expiring patent in the family. Plaintiffs have also filed for a Patent Term Extension for the earliest-issued patent, which, if granted, could extend its term.

Case Timeline

Date Event
2005-04-14 Priority Date for ’362, ’840, ’109, ’637 Patents
2011-02-15 U.S. Patent No. 7,888,362 Issues
2011-10-14 Priority Date for ’419 Patent
2013-01-08 U.S. Patent No. 8,349,840 Issues
2013-12-31 U.S. Patent No. 8,618,109 Issues
2015-07-10 FDA Approves REXULTI® (brexpiprazole) NDA
2017-12-12 U.S. Patent No. 9,839,637 Issues
2019-06-04 U.S. Patent No. 10,307,419 Issues
2019-09-18 Plaintiffs Receive Sandoz's Notice Letter
2019-11-01 Complaint Filed

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

U.S. Patent No. 7,888,362 - "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders"

  • Patent Identification: U.S. Patent No. 7,888,362, "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders," issued February 15, 2011 (Compl. ¶18).

The Invention Explained

  • Problem Addressed: The patent's background notes that because the causal factors of mental disorders like schizophrenia are heterogeneous, it is desirable for a drug to have multiple pharmacological effects to achieve a wide treatment spectrum ('362 Patent, col. 3:11-14).
  • The Patented Solution: The invention discloses novel heterocyclic compounds that exhibit a combination of pharmacological activities, including dopamine D2 receptor partial agonism, serotonin 5-HT2A receptor antagonism, and adrenalin α1 receptor antagonist activity, along with serotonin reuptake inhibition ('362 Patent, col. 3:15-22). This multi-receptor profile is intended to create a "dopamine system stabilizer" capable of treating both positive and negative symptoms of schizophrenia with improved tolerability and safety compared to existing antipsychotic drugs ('362 Patent, col. 17:31-34, col. 3:8-11). The patent specifically describes the synthesis of the compound that would become known as brexpiprazole ('362 Patent, col. 29:30-56, Example 1).
  • Technical Importance: This "polypharmacology" approach represented an effort to develop treatments for complex neurological disorders that could offer a broader therapeutic window and a more favorable side-effect profile than earlier generations of antipsychotics ('362 Patent, col. 17:31-40).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the '362 patent (Compl. ¶48). The patent contains one independent claim.
  • Independent Claim 1:
    • A specific chemical compound: 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, or a salt thereof.

U.S. Patent No. 8,349,840 - "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders"

  • Patent Identification: U.S. Patent No. 8,349,840, "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders," issued January 8, 2013 (Compl. ¶23).

The Invention Explained

  • Problem Addressed: The patent addresses the need for improved treatments for schizophrenia and other central nervous system disorders where existing therapies may have limited efficacy or undesirable side effects ('840 Patent, col. 1:12-15).
  • The Patented Solution: The patent claims methods of treating schizophrenia by administering the specific heterocyclic compound disclosed in the '362 Patent ('840 Patent, col. 47:46-52). The specification explains that this compound's unique combination of receptor activities allows it to function as a dopamine system stabilizer, improving symptoms without causing the side effects associated with simple dopamine receptor antagonists ('840 Patent, col. 17:28-40).
  • Technical Importance: The invention extends protection for the core compound from the composition of matter to specific therapeutic applications, a common strategy in pharmaceutical patenting to cover the commercial use of a drug for its approved indications.

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’840 Patent (Compl. ¶59). The patent contains one independent claim.
  • Independent Claim 1:
    • A method for treating schizophrenia
    • comprising administering a heterocyclic compound
    • wherein the heterocyclic compound is 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, or a salt thereof
    • to a human or animal.

U.S. Patent No. 8,618,109 - "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders"

  • Patent Identification: U.S. Patent No. 8,618,109, "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders," issued December 31, 2013 (Compl. ¶27).
  • Technology Synopsis: This patent, from the same family as the ’362 and ’840 patents, claims methods of using the same active compound, brexpiprazole, for treating depression. The patent leverages the compound's serotonin-related activities, in addition to its dopamine stabilization effects, to provide a therapeutic benefit for depressive disorders ('109 Patent, col. 47:48-52).
  • Asserted Claims: "one or more claims" (Compl. ¶73). Independent claim 1 covers a method for treating depression.
  • Accused Features: The complaint alleges that Sandoz will induce infringement by marketing its generic product with a package insert that instructs or encourages its use for treating depression (Compl. ¶¶ 75-77).

U.S. Patent No. 9,839,637 - "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders"

  • Patent Identification: U.S. Patent No. 9,839,637, "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders," issued December 12, 2017 (Compl. ¶31).
  • Technology Synopsis: This patent is also from the same family and claims methods of using brexpiprazole. The claims are directed to a method of treating schizophrenia by administering a pharmaceutical composition that contains the active ingredient.
  • Asserted Claims: "one or more claims" (Compl. ¶87). Independent claim 1 covers a method for treating schizophrenia by administering a pharmaceutical composition containing the compound and a carrier.
  • Accused Features: The complaint alleges inducement of infringement through Sandoz's proposed product labeling, which will instruct on the use of its generic brexpiprazole composition for treating schizophrenia (Compl. ¶¶ 89-91).

U.S. Patent No. 10,307,419 - "Tablet Comprising 7-[4-(4-benzo[b]thiopen-4-yl-piperazine-1-yl)butoxy]-1H-quinolin-2-one or a Salt Thereof"

  • Patent Identification: U.S. Patent No. 10,307,419, "Tablet Comprising 7-[4-(4-benzo[b]thiopen-4-yl-piperazine-1-yl)butoxy]-1H-quinolin-2-one or a Salt Thereof," issued June 4, 2019 (Compl. ¶35).
  • Technology Synopsis: This patent addresses the technical challenge of creating a stable and effective oral dosage form of brexpiprazole ('419 Patent, col. 2:43-47). The invention is a specific tablet formulation comprising the active ingredient along with a defined set of excipients, binders, disintegrants, and a coating layer, which together are purported to provide excellent disintegration ability, storage stability, and photostability ('419 Patent, col. 2:50-63).
  • Asserted Claims: "one or more claims" (Compl. ¶101). Independent claim 1 covers a coated tablet with specific components in defined weight-percentage ranges.
  • Accused Features: The composition of Sandoz's proposed generic brexpiprazole tablets, which the complaint alleges are "pharmaceutically and therapeutically equivalent" to Plaintiffs' REXULTI® tablets and therefore will meet the compositional requirements of the claims (Compl. ¶99).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Sandoz's proposed generic brexpiprazole tablets in 0.25, 0.5, 1, 2, 3, and 4 mg dosage forms (Compl. ¶39). The filing of Abbreviated New Drug Application (ANDA) No. 213570 with the U.S. Food and Drug Administration (FDA) to obtain approval for these products is the statutory act of infringement alleged in the complaint (Compl. ¶¶ 39, 48).
  • Functionality and Market Context: The Sandoz products are intended to be generic versions of Plaintiffs’ REXULTI® tablets (Compl. ¶39). REXULTI® is a prescription drug approved for the adjunctive treatment of major depressive disorder and the treatment of schizophrenia, with brexpiprazole as its active ingredient (Compl. ¶17). The complaint alleges that Sandoz's ANDA represents to the FDA that its generic products are "pharmaceutically and therapeutically equivalent" to REXULTI® (Compl. ¶46).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’362 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, or a salt thereof. Sandoz's ANDA No. 213570 seeks approval to manufacture and sell tablets in which the active ingredient is brexpiprazole, which is the chemical compound identified in the claim. ¶39 col. 29:30-56

’840 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating schizophrenia, Sandoz's proposed package insert for its generic products will allegedly recommend, suggest, or instruct healthcare professionals and patients to use the products to treat schizophrenia. ¶63 col. 47:46-52
comprising administering a heterocyclic compound ... wherein the heterocyclic compound is 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, or a salt thereof, The active ingredient in Sandoz's generic product is brexpiprazole, which is the compound recited in the claim. ¶39 col. 47:46-52
to a human or animal. The administration will be to human patients as directed by the proposed product labeling. ¶63 col. 47:46-52
  • Identified Points of Contention:
    • Scope Questions: In Hatch-Waxman litigation concerning method-of-use patents, a central question often involves the scope of the proposed product label. This raises the question of whether Sandoz's final, FDA-approved label will instruct users to perform all the steps of the claimed methods for treating schizophrenia and depression, or if Sandoz might pursue a "skinny label" omitting patented indications.
    • Technical Questions: For the '419 formulation patent, a key technical question will be one of compositional equivalence: what evidence does the complaint provide that Sandoz's proposed tablet formulation contains the specific combination of excipients, binders, disintegrants, lubricants, and coating agents required by the asserted claims? The allegation of pharmaceutical equivalence (Compl. ¶99) suggests this will be a point of discovery and contention.

V. Key Claim Terms for Construction

  • The Term: "a tablet ... wherein said coating substantially does not contain polyethylene glycol" (from claim 1 of the '419 Patent).
  • Context and Importance: This negative limitation is central to defining the scope of the '419 patent's formulation claims. The definition of "substantially does not contain" will determine the threshold, if any, for the amount of polyethylene glycol (PEG) that can be present in an accused generic tablet without infringing. Practitioners may focus on this term because the presence of even trace amounts of PEG in Sandoz's product could become a dispositive issue of non-infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation (i.e., allowing for trace amounts): The use of the word "substantially" itself suggests that an absolutely zero, analytically undetectable amount is not required. Parties arguing for this interpretation may assert that the term is intended to exclude functionally significant amounts of PEG that would impact stability, not incidental impurities.
    • Evidence for a Narrower Interpretation (i.e., requiring near-zero amounts): The patent specification explicitly states that when PEG "exists in the coating layer, the obtained tablet tends to have reduced photostability and storage stability," and therefore "it is more preferable if [PEG] is substantially not contained" ('419 Patent, col. 6:47-51). This stated technical reason for excluding PEG could support a construction that prohibits any amount that could plausibly affect stability, which may be a very low threshold.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for the method-of-use patents ('840, '109, '637). The basis for these allegations is that Sandoz knows of the patents and, through its proposed package insert, "will recommend, suggest, encourage and/or instruct" healthcare professionals and patients to use the generic products in a manner that directly infringes the claimed methods of treating schizophrenia and depression (Compl. ¶¶ 63, 77, 91).
  • Willful Infringement: The complaint does not use the word "willful." However, it alleges that Sandoz has "actual knowledge" of each asserted patent, as evidenced by its Paragraph IV Notice Letter (Compl. ¶¶ 47, 58, 72, 86, 100). The prayer for relief also requests a declaration that this is an "exceptional case" and an award of attorney fees, which is a remedy often associated with findings of willful infringement or litigation misconduct (Request for Relief ¶F).

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

  • A central issue in this Hatch-Waxman litigation will be one of patent validity: did Sandoz, in its Paragraph IV certification, correctly assert that the claims of the five patents-in-suit are invalid as, for example, anticipated by or obvious over the prior art? The litigation was triggered by this assertion, and its resolution will be foundational to the case.
  • A key infringement question will be one of compositional identity with respect to the '419 formulation patent: does Sandoz's generic tablet formulation, which is intended to be bioequivalent, also contain the specific combination of excipients and coating agents, and lack others (such as PEG), as required to fall within the literal scope of the asserted formulation claims?
  • Finally, the case may turn on a question of induced infringement scope for the method-of-use patents: will the final, FDA-approved labeling for Sandoz's product contain explicit instructions for the treatment of schizophrenia and/or depression, thereby directly encouraging the infringing acts claimed in the '840, '109, and '637 patents?