PTAB

IPR2023-00049

TWi PharmaceuTicals Inc v. Merck Serono SA

Title: Cladribine Regimen for Treating Multiple Sclerosis
Brief Description: The ’947 Patent discloses a method for treating multiple sclerosis (MS) through the oral administration of cladribine. The method involves a specific dosing regimen with sequential induction, drug-free, and maintenance periods.

Prior Art Relied Upon: Bodor (Patent 7,888,328)
Core Argument for this Ground:
- Prior Art Mapping: Petitioner asserted that Bodor discloses every limitation of independent claim 36. Bodor teaches treating MS with oral cladribine, including a two-month induction period (5-7 days of dosing in month 1 and month 2) followed by a ten-month cladribine-free period. Petitioner argued that the claimed total dose of "about 1.7 mg/kg" is disclosed by Bodor's teaching of 10 mg daily doses when calculated for an average-weight patient. Crucially, Petitioner contended that a person of ordinary skill in the art (POSITA) would infer from Bodor's finite "ten months of no treatment" language that the treatment cycle repeats, thereby teaching the claimed maintenance period with the same dosage as the induction period. The dependent claims were asserted to be taught by Bodor’s disclosure of specific time periods (e.g., 2-month induction), dosages, and co-administration with interferon-beta.

Prior Art Relied Upon: Bodor (Patent 7,888,328) and the common knowledge of a POSITA.
Core Argument for this Ground:
- Prior Art Mapping: To the extent Bodor is found not to inherently teach a repeating treatment cycle, Petitioner argued this modification would have been obvious. Bodor discloses all elements of a single treatment cycle.
- Motivation to Combine: A POSITA would be motivated to repeat the treatment cycle taught by Bodor because it was well-known that chronic conditions like MS require long-term management and that single courses of immunotherapy were unlikely to be curative. It was standard practice to repeat immunotherapy phases to manage symptoms over time.
- Expectation of Success: A POSITA would have a reasonable expectation of success in repeating the regimen. The known cyclical nature of other successful immunotherapies for MS (like mitoxantrone) and the promising results from cladribine studies would suggest that repeating the treatment would effectively manage MS symptoms long-term.

Prior Art Relied Upon: Bodor (Patent 7,888,328) and Rice (a 2000 Neurology article).
Core Argument for this Ground:
- Prior Art Mapping: This combination strengthens the argument for repeating the treatment cycle and arriving at the claimed dosage. Bodor teaches the oral formulation and initial cycle, while Rice provides explicit evidence of successful retreatment with cladribine.
- Motivation to Combine: A POSITA would combine Bodor's oral regimen with Rice's teachings on retreatment. Rice demonstrated that a second cladribine administration round a year after the first showed a beneficial effect. This would motivate a POSITA to apply this successful retreatment strategy to Bodor's regimen. Further, Rice’s disclosure of a 0.7 mg/kg subcutaneous dose, when adjusted for the ~42% oral bioavailability taught by Bodor, results in a dose of ~1.67 mg/kg, directly suggesting the claimed "about 1.7 mg/kg" dose.
- Expectation of Success: Rice’s positive results from retreatment, showing a trend toward beneficial effects, would provide a strong expectation of success in repeating Bodor's treatment cycle to achieve long-term efficacy.

Petitioner’s challenge centered on the scope of independent claim 36. It argued that, based on its plain and ordinary meaning, claim 36 permits the total cladribine dose in the maintenance period to be equal to the dose in the induction period (both "about 1.7 mg/kg").
This interpretation was contrasted with other patent claims not challenged in this petition (e.g., claims 1 and 20), which explicitly require the maintenance dose to be lower than the induction dose. Petitioner asserted the Examiner overlooked this distinction during prosecution, which is a central pillar of its unpatentability arguments.

§325(d) - Same Art or Arguments: Petitioner argued that discretionary denial under §325(d) was inappropriate despite the Examiner having previously considered Bodor. The core of this argument was that the Examiner committed a material error by misapprehending the scope of claim 36, analyzing it as if it required a lower maintenance dose. Therefore, the Examiner never actually considered the patentability of the claim’s true scope—which allows for equal dosage periods—in light of Bodor. Petitioner contended this error of law and claim construction warrants a new review on the merits.
§314(a) - Fintiv Factors: Petitioner argued against discretionary denial based on a parallel district court litigation (Merck KGaA v. Accord Healthcare). It asserted that the Fintiv factors weighed against denial because: (1) the litigation was in its earliest stages, with no stay requested and no trial date set; (2) Petitioner is not a party to the parallel case; (3) investment by the court and parties was minimal; and (4) the strong merits of the petition, based on the alleged clear Examiner error, favored institution to correct the record and promote an efficient resolution.

Petitioner requested the institution of an inter partes review and a final written decision canceling claims 36, 38-39, and 41-48 of the ’947 patent as unpatentable under 35 U.S.C. §102 and/or §103.