PTAB

IPR2023-00049

TWi Pharmaceuticals Inc v. Merck Serono SA

Title: Cladribine Regimen for Treating Multiple Sclerosis
Brief Description: The ’947 patent relates to a method for treating multiple sclerosis (MS) through the oral administration of cladribine. The method comprises a specific sequence of treatment phases, including an initial induction period, a drug-free period, a subsequent maintenance period, and another drug-free period.

Prior Art Relied Upon: Bodor (Patent 7,888,328).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Bodor, which teaches an oral cladribine formulation for treating MS, discloses every limitation of independent claim 36 and its dependent claims. Bodor’s regimen specifies administering 10 mg of cladribine for 5-7 days in a first month and again in a second month, which Petitioner asserted constitutes an induction period of "about 2 months." Petitioner contended that Bodor’s disclosed total dosage (100-140 mg) anticipates the claimed total dose of "about 1.7 mg/kg" when applied to a patient of average weight. Crucially, Petitioner argued that Bodor's teaching of this two-month treatment cycle "followed by ten months of no treatment" implies that the cycle repeats, thereby teaching the claimed maintenance period with the same dosage as the induction period.
- Key Aspects: This anticipation argument relied on a POSITA reasonably inferring a repeated treatment cycle from Bodor, a position Petitioner noted was endorsed by the Examiner during prosecution of a related application.

Prior Art Relied Upon: Bodor (Patent 7,888,328) and the common knowledge of a Person of Ordinary Skill in the Art (POSITA).
Core Argument for this Ground:
- Prior Art Mapping: This ground presented an alternative to the anticipation argument. Petitioner asserted that Bodor teaches all elements of the claimed method except for an explicit instruction to repeat the initial treatment cycle after the 10-month drug-free period.
- Motivation to Combine: A POSITA would be motivated to repeat the treatment cycle described in Bodor because it was well-known that immunotherapies for chronic conditions like MS required multiple rounds of administration to be effective. A single round was understood to be unlikely to provide a lasting therapeutic benefit. Repeating the cycle was standard medical practice to manage MS symptoms over time.
- Expectation of Success: A POSITA would have a reasonable expectation of success in repeating Bodor's regimen. The standard of care for similar immunosuppressants involved cyclical administration, and this approach was known to be effective. Therefore, applying this standard practice to Bodor's specific oral cladribine treatment would have been a predictable and straightforward modification.

Prior Art Relied Upon: Bodor (Patent 7,888,328) and Rice (a 2000 Neurology journal article).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Bodor teaches an oral cladribine formulation and an initial treatment cycle, while Rice explicitly teaches retreating MS patients with cladribine after a drug-free period of at least 12 months. Rice demonstrated that retreatment using the same dosage showed a trend toward a beneficial long-term effect.
- Motivation to Combine: A POSITA would combine Bodor’s oral formulation with the cyclical retreatment strategy taught by Rice. Rice’s positive clinical results for a repeated cladribine regimen would motivate a POSITA to apply that successful, evidence-based approach to Bodor's method to ensure long-term efficacy. Bodor itself cited literature that discussed cyclical dosing, suggesting the field was already focused on such methods.
- Expectation of Success: The combination was supported by a strong expectation of success. Rice’s study provided direct evidence that retreatment with cladribine was beneficial. A POSITA would expect that combining Bodor's oral dosage form with Rice’s proven cyclical administration strategy would predictably yield a successful long-term treatment for MS.

Petitioner’s central argument was that independent claim 36 possesses a broader scope than other independent claims in the patent (e.g., claims 1 and 20). Unlike claims that explicitly require the maintenance dose to be lower than the induction dose, Petitioner asserted that claim 36’s language (induction dose of "about 1.7 mg/kg to about 3.5 mg/kg" and maintenance dose of "about 1.7 mg/kg") covers an embodiment where the induction and maintenance doses are equal. Petitioner contended that the Examiner overlooked this critical distinction during prosecution, allowing claim 36 based on arguments that were only applicable to the narrower claims.

§325(d) (Same Art/Arguments): Petitioner argued against discretionary denial, asserting that while Bodor was before the Examiner, the Office committed a material error by misapprehending the scope of claim 36. The Examiner never properly considered the patentability of the "equal dosage" embodiment, which is taught by Bodor and covered by claim 36, but not by other independent claims. Petitioner claimed this error of interpretation meant the core invalidity argument was never substantively reviewed by the Office.
§314(a) (Fintiv Factors): Petitioner argued that discretionary denial based on the parallel district court proceeding (Merck KGaA v. Accord Healthcare, Inc.) was unwarranted. The primary reasons cited were that the parallel litigation was in its earliest preliminary stages with no trial date set, Petitioner is not a party to that litigation, and the IPR proceeding would conclude long before a potential district court trial, thereby promoting efficiency and avoiding duplicative efforts.

Petitioner requests institution of an inter partes review and cancellation of claims 36, 38-39, and 41-48 of Patent 7,713,947 as unpatentable.