PTAB

PGR2024-00009

BeiGene USA Inc v. Pharmacyclics LLC

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods of Treating Certain Lymphomas with Bruton's Tyrosine Kinase Inhibitors
  • Brief Description: The ’803 patent relates to methods for treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) by orally administering an irreversible inhibitor of Bruton’s tyrosine kinase (Btk). The claims define the inhibitor by a broad generic chemical structure and several functional requirements.

3. Grounds for Unpatentability

Ground 1: Lack of Written Description and Enablement under 35 U.S.C. §112 - Claims 1-8, 12, and 20

  • Basis of Challenge: The patent specification itself.
  • Core Argument for this Ground: Petitioner argued that the ’803 patent’s specification fails to provide adequate written description and enabling support for the full scope of the challenged claims. The claims encompass a genus of potentially billions of structurally diverse irreversible Btk inhibitors (BTKIs), defined by a generic structure and functional limitations. However, the specification’s disclosure is narrowly focused on a single compound, IMBRUVICA (ibrutinib), and a few structurally similar, adenine-mimetic compounds. Petitioner contended that the Structure-Activity Relationship (SAR) for BTKIs is highly unpredictable, and the specification provides no guidance for a Person of Ordinary Skill in the Art (POSITA) to identify which of the billions of potential compounds would satisfy the claims' functional requirements.
    • Key Assertions (Written Description): The specification allegedly fails to describe common structural features or a representative number of species to demonstrate the inventor's possession of the entire claimed genus. Critically, Petitioner noted the specification is devoid of any non-biaryl heterocyclic cores, such as that of its own product BRUKINSA, which is alleged to fall within the claim scope but is structurally and functionally distinct from IMBRUVICA.
    • Key Assertions (Enablement): A POSITA would require undue experimentation to practice the full scope of the claims. This would involve a massive, unpredictable research program to synthesize and screen countless candidate compounds to determine which ones (1) covalently bind to Btk, (2) safely and effectively treat CLL/SLL, and (3) result in lymphocytosis, as functionally required by the claims.

Ground 2: Anticipation over Byrd - Claims 1-8, 12, and 20

  • Prior Art Relied Upon: Byrd (J.C. Byrd et al., “Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia,” N. Engl. J. Med. 2013).
  • Core Argument for this Ground: Petitioner argued that the challenged claims are not entitled to their asserted 2010/2011 priority dates due to the §112 deficiencies, making the 2013 Byrd publication prior art under 35 U.S.C. §102. Petitioner asserted that the Byrd publication, which details a clinical study of ibrutinib, discloses every limitation of the challenged claims.
    • Prior Art Mapping: Byrd allegedly disclosed a method of treating CLL/SLL by orally administering a therapeutically effective amount of ibrutinib (disclosed as a covalent inhibitor of Btk) on a continuous daily regimen. The structure of ibrutinib meets the structural limitations of the claims. Byrd further disclosed that ibrutinib covalently binds to the cysteine-481 residue of the Btk enzyme. Finally, Byrd taught that treatment-related lymphocytosis occurred and was not considered a sign of progressive disease, satisfying the claim limitation requiring continuation of treatment despite this effect.

Ground 3: Obviousness over Byrd and IMBRUVICA Label - Claim 5

  • Prior Art Relied Upon: Byrd and the IMBRUVICA Prescribing Information Label (revised June 2016).
  • Core Argument for this Ground: Petitioner argued that dependent claim 5, which recites a specific pharmacokinetic parameter (an AUC(0-24) of about >100 ng*h·mL), would have been obvious over the teachings of Byrd in view of the publicly available IMBRUVICA label.
    • Prior Art Mapping: Byrd disclosed all limitations of independent claim 1, including the administration of ibrutinib at a 420 mg daily dose for CLL/SLL. The IMBRUVICA label described the steady-state AUC in patients receiving the same 420 mg dose as 680 ± 517 ng·h/mL, which satisfies the claimed AUC limitation.
    • Motivation to Combine: A POSITA practicing the method taught in the Byrd study would have been motivated to consult the official IMBRUVICA prescribing label for established pharmacokinetic data and to confirm expected outcomes.
    • Expectation of Success: Because both Byrd and the label concern the exact same drug, dose, and indication, a POSITA would have had a very high expectation that combining their teachings would yield the claimed pharmacokinetic result.

4. Key Claim Construction Positions

  • Petitioner argued that the preamble term “method of treating” and the body term “therapeutically effective amount” are limiting and should be construed together. The proposed construction requires that a claimed BTKI must both (1) effectively treat CLL/SLL ("efficacy") and (2) do so without causing undue adverse side effects ("safety"). This construction is central to the §112 arguments, as it broadens the functional requirements that Petitioner claims are unsupported by the specification.

5. Key Technical Contentions (Beyond Claim Construction)

  • Petitioner's central technical contention, underlying its §112 arguments, was the high unpredictability of the Structure-Activity Relationship (SAR) for BTKIs. It argued that minor changes to the claimed fused heterocyclic ring system (the “Z’-structure”) unpredictably affect a compound’s ability to bind Btk, its orientation for covalent bonding, its clinical efficacy, and its safety profile. Therefore, the specification’s limited disclosure of adenine-mimetic structures like IMBRUVICA allegedly provides no predictive value for the vast array of other structurally different compounds covered by the claims.

6. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under §325(d) is inappropriate because the Examiner was not presented with, and did not consider, key evidence and arguments. This included the structure of BRUKINSA (as an example of the claims' breadth), expert declarations on the unpredictability of BTKI SAR, and contradictory statements made by the Patent Owner in other litigation regarding unpredictability. Further, Petitioner argued against denial under Fintiv factors, noting that the parallel district court litigation had been stayed by joint stipulation pending the outcome of the Post-Grant Review (PGR), thus avoiding duplicative efforts.

7. Relief Requested

  • Petitioner requests institution of the PGR and cancellation of claims 1-8, 12, and 20 as unpatentable under 35 U.S.C. §§ 102, 103, and 112.