Hopewell Pharma Ventures Inc v. Merck Serono SA

1. Case Identification

• Case #: IPR2023-00480
• Patent #: 7,713,947
• Filed: January 23, 2023
• Petitioner(s): Hopewell Pharma Ventures, Inc.
• Patent Owner(s): Merck Serono S.A.
• Challenged Claims: 36, 38-39, and 41-46

2. Patent Overview

• Title: Cladribine Regimen for Treating Multiple Sclerosis
• Brief Description: The ’947 patent discloses methods for treating multiple sclerosis (MS) using a specific oral dosing regimen of cladribine. The regimen involves sequential steps of an induction period, a cladribine-free period, a maintenance period with a lower total dose than the induction period, and another cladribine-free period.

3. Grounds for Unpatentability

Ground 1: Obviousness over Bodor and Stelmasiak - Claims 36, 38-39, and 41-46 are obvious over Bodor in view of Stelmasiak.

• Prior Art Relied Upon: Bodor (WO 2004/087101) and Stelmasiak (“A pilot trial of cladribine (2-chlorodeoxyadenosine) in remitting-relapsing multiple sclerosis,” Medical Science Monitor (1998)).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the combination of Bodor and Stelmasiak taught every limitation of the challenged claims. Bodor disclosed an oral cladribine regimen for MS comprising a two-month induction period (e.g., 10 mg/day for 5-7 days each month) followed by a ten-month cladribine-free period. This established the foundational structure of the claimed method. Stelmasiak taught a cyclical oral cladribine treatment for MS that explicitly included a lower-dose maintenance period following a higher-dose induction period (300 mg total induction vs. 50 mg total maintenance). Stelmasiak demonstrated this lower dose was sufficient to maintain lymphocyte suppression. Petitioner contended that applying Stelmasiak's lower-dose maintenance strategy to Bodor's regimen constituted the claimed invention. The claimed total induction dose of "about 1.7 mg/kg to about 3.5 mg/kg" was argued to be prima facie obvious as it overlapped with Bodor's disclosed dose of about 1.4 mg/kg to 2 mg/kg. The remaining limitations, such as the specific durations and doses in the maintenance period, were asserted to be result-effective variables that a POSA would optimize through routine experimentation.
  • Motivation to Combine: A POSA would begin with Bodor’s regimen due to its teaching of an oral cladribine formulation with improved absorption and bioavailability. Given that MS is a chronic and progressive disease requiring ongoing care, a POSA would have understood that patients completing Bodor's initial induction and ten-month drug-free cycle would require retreatment. Stelmasiak’s successful trial provided the rationale for how to conduct that retreatment: using a lower maintenance dose to maintain the therapeutic effect (immunosuppression) achieved during induction while minimizing toxicity. Therefore, a POSA would combine Bodor's initial cycle with Stelmasiak's proven lower-dose maintenance strategy for subsequent treatment cycles.
  • Expectation of Success: A POSA would have had a reasonable expectation of success. Both references involved oral cladribine for treating MS via immunosuppression. Stelmasiak’s clinical data showed that a lower dose effectively maintained reduced lymphocyte counts achieved during the induction phase. Applying this known, successful technique to Bodor's similar regimen to achieve the same therapeutic goal would have been a predictable and straightforward modification.

4. Key Claim Construction Positions

• Petitioner argued for constructions based on the patent specification and prosecution history, focusing on the relationship between "induction" and "maintenance" periods.
• "a maintenance period": Petitioner asserted this term should be construed as "a retreatment period...during which the total dose of cladribine is lower than the total dose in the induction period." This construction was argued to be supported by explicit definitions in the specification and by the Patent Owner's own arguments during prosecution of the ’947 patent and a related patent, where it distinguished prior art by arguing the art failed to teach a lower dose in the maintenance phase. This construction is central to Petitioner's obviousness argument, as Stelmasiak explicitly teaches this "lower dose" feature.

5. Key Technical Contentions (Beyond Claim Construction)

• Examiner's Conflation of Monocytes and Lymphocytes: Petitioner argued that a material error occurred during the original prosecution of the ’947 patent. The Examiner and Patent Owner repeatedly conflated two distinct cell types: monocytes and lymphocytes. Petitioner contended that the Patent Owner leveraged this confusion to argue against a reasonable expectation of success for a lower-dose maintenance therapy. It was argued that while monocyte levels rebound quickly after cladribine treatment, lymphocyte levels (the target of the therapy) remain suppressed for over a year. This fundamental biological distinction was allegedly overlooked, leading to an erroneous allowance of the claims.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under § 325(d) or Fintiv would be inappropriate.
• § 325(d): Denial was argued to be improper because the Examiner made two material errors during prosecution. First was the technical error of conflating monocytes and lymphocytes, which led to an incorrect assessment of the prior art. Second, the Examiner allegedly failed to properly consider Stelmasiak, which was cited in an Information Disclosure Statement (IDS) but not applied in a rejection, despite teaching the key missing limitation (a lower maintenance dose).
• Fintiv Factors: Petitioner argued the Fintiv factors weighed in favor of institution. It asserted it had filed its petition diligently and early in the parallel district court litigation, well before any trial date was set. Furthermore, Petitioner stated it would stipulate not to pursue the same grounds or any grounds that could have reasonably been raised in the IPR in the district court action, a factor that weighs heavily against discretionary denial.

7. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 36, 38-39, and 41-46 of Patent 7,713,947 as unpatentable under 35 U.S.C. § 103.