US 7713947

The patent summary information can be directly extracted from the provided patent text.

Title: Cladribine regimen for treating multiple sclerosis
Assignee: Merck Serono SA
Inventors: Giampiero De luca, Arnaud Ythier, Alain Munafo, Maria Lopez-Bresnahan
Filing Date: 2005-12-20
Issue Date: 2010-05-11
Abstract: The present invention is related to the use of Cladribine for the preparation of a pharmaceutical formulation for the treatment of multiple sclerosis, especially relapsing-remitting multiple sclerosis or early secondary progressive multiple sclerosis, wherein the preparation is to be orally administered and wherein re-treatments are possible.

Plain-Language Overview of Independent Claims:

• Claim 1: This claim describes a method for treating multiple sclerosis using an oral cladribine formulation. The treatment involves a specific four-step sequence:

  1. Induction Period: Oral administration of cladribine where the total dose received by the patient is between approximately 1.7 mg/kg and 3.5 mg/kg.
  2. Cladribine-Free Period (first): A break from cladribine administration lasting between approximately 8 and 10 months.
  3. Maintenance Period: Further oral administration of cladribine, but the total dose during this period is lower than the total dose given during the initial induction period.
  4. Cladribine-Free Period (second): Another break from cladribine administration.

• Claim 20: This claim also describes a method for treating multiple sclerosis with oral cladribine, similar to Claim 1, but it specifies the duration of the administration periods more precisely:

  1. Induction Period: Oral administration of cladribine for approximately 2 to 4 months, with a total dose between approximately 1.7 mg/kg and 3.5 mg/kg.
  2. Cladribine-Free Period (first): A break from cladribine administration lasting approximately 8 to 10 months.
  3. Maintenance Period: Oral administration of cladribine for approximately 2 to 4 months, with a total dose lower than the induction period's total dose.
  4. Cladribine-Free Period (second): Another break from cladribine administration.

• Claim 36: This claim describes another method for treating multiple sclerosis with oral cladribine, similar to Claim 20, but with a specific total dose for the maintenance period:

  1. Induction Period: Oral administration of cladribine for approximately 2 to 4 months, with a total dose between approximately 1.7 mg/kg and 3.5 mg/kg.
  2. Cladribine-Free Period (first): A break from cladribine administration lasting approximately 8 to 10 months.
  3. Maintenance Period: Oral administration of cladribine for approximately 2 to 4 months, where the total dose reached at the end of this period is about 1.7 mg/kg.
  4. Cladribine-Free Period (second): Another break from cladribine administration.

CAFC 2026 Dockets for US7713947:

According to recent reports, US patent 7713947 has been involved in litigation. The U.S. Court of Appeals for the Federal Circuit (CAFC) affirmed a lower tribunal's finding that US7713947B2 is unpatentable. This decision strengthens the position of TWI Pharmaceuticals and impacts Merck Serono's ability to enforce this patent.

Specifically, in "Merck Serono v. TWI Pharmaceuticals" (Case No. 25-1463), the Federal Circuit affirmed the unpatentability of US7713947B2 on October 30, 2025. The patent was found unpatentable due to obviousness, based on the combination of prior art references (Bodor and Stelmasiak). This ruling was finalized at the Federal Circuit level.

Another related case, "Merck KGaA v. Hopewell Pharma Ventures, Inc." (Case No. 1:22-cv-01365) in the Delaware District Court, also resulted in the invalidation of claims from US7713947, along with US8377903, due to obviousness. This judgment was entered on January 29, 2026, and was driven by a precedential Federal Circuit decision. Claims 36, 38, 39, and 41-46 of US7713947 were found invalid as obvious in this case.

Furthermore, in "Merck KGaA v. Apotex, Inc." (Case No. 1:23-cv-00655), the U.S. District Court for the District of Delaware entered judgment in favor of Apotex Inc. on February 2, 2026, also declaring claims 36, 38, 39, and 41-46 of US7713947 invalid as obvious. This decision cited the Federal Circuit's controlling decision in Merck Serono v. Hopewell.

Therefore, while the Google Patents status lists the patent as "Active, expires 2026-10-16", the overriding and more recent information from the CAFC dockets indicates that key claims of US7713947B2 have been found unpatentable and invalid due to obviousness by the Federal Circuit and district courts, significantly impacting its enforceability. The legal status presented in the search results contradicts the "Active" status on Google Patents (which appears to refer to maintenance fee payments) and should be prioritized.US patent 7713947, titled "Cladribine regimen for treating multiple sclerosis," was assigned to Merck Serono SA. The inventors are Giampiero De luca, Arnaud Ythier, Alain Munafo, and Maria Lopez-Bresnahan. The patent was filed on December 20, 2005, and issued on May 11, 2010.

The abstract describes the invention as the use of cladribine for preparing an orally administered pharmaceutical formulation to treat multiple sclerosis, specifically relapsing-remitting multiple sclerosis or early secondary progressive multiple sclerosis, allowing for re-treatments.

Plain-Language Overview of Independent Claims:

• Claim 1: This claim describes a treatment method for multiple sclerosis using an orally administered cladribine formulation. The method involves a sequence of four periods:

  1. An induction period where the cladribine formulation is given, with the total accumulated dose ranging from approximately 1.7 mg/kg to 3.5 mg/kg.
  2. A first cladribine-free period of about 8 to 10 months, during which no cladribine is administered.
  3. A maintenance period where the cladribine formulation is administered again, but the total dose during this period is less than the total dose from the induction period.
  4. A second cladribine-free period where no cladribine is administered.

• Claim 20: This claim outlines another method for treating multiple sclerosis with orally administered cladribine, similar to Claim 1, but with specified durations for the administration periods:

  1. An induction period lasting approximately 2 to 4 months, with an orally administered total cladribine dose between about 1.7 mg/kg and 3.5 mg/kg.
  2. A first cladribine-free period lasting approximately 8 to 10 months, with no cladribine administration.
  3. A maintenance period lasting approximately 2 to 4 months, with orally administered cladribine, where the total dose is less than that of the induction period.
  4. A second cladribine-free period with no cladribine administration.

• Claim 36: This claim describes a further method for treating multiple sclerosis with orally administered cladribine, similar to Claim 20, but with a specific total dose for the maintenance period:

  1. An induction period lasting approximately 2 to 4 months, with an orally administered total cladribine dose between about 1.7 mg/kg and 3.5 mg/kg.
  2. A first cladribine-free period lasting approximately 8 to 10 months, with no cladribine administration.
  3. A maintenance period lasting approximately 2 to 4 months, with orally administered cladribine, where the total dose reached by the end of this period is approximately 1.7 mg/kg.
  4. A second cladribine-free period with no cladribine administration.

CAFC 2026 Dockets for US7713947:

Despite being listed as "Active" with an expiration date of October 16, 2026, on Google Patents, judicial rulings have significantly impacted the enforceability of US7713947.

The U.S. Court of Appeals for the Federal Circuit (CAFC), in Case No. 25-1463 (Merck Serono v. TWI Pharmaceuticals), affirmed on October 30, 2025, that US7713947B2 is unpatentable due to obviousness. This decision followed a ruling by the Patent Trial and Appeal Board (PTAB) that the claims were obvious based on prior art. This Federal Circuit ruling is final at that level.

Additionally, in "Merck KGaA v. Hopewell Pharma Ventures, Inc." (Case No. 1:22-cv-01365) in the Delaware District Court, a final judgment was entered on January 29, 2026. This judgment, driven by a precedential Federal Circuit decision, invalidated claims 36, 38, 39, and 41-46 of US7713947 as obvious. Similarly, in "Merck KGaA v. Apotex, Inc." (Case No. 1:23-cv-00655), claims 36, 38, 39, and 41-46 of US7713947 were also declared invalid as obvious on February 2, 2026, by the U.S. District Court for the District of Delaware, citing the Federal Circuit's controlling decision in Merck Serono v. Hopewell.

These decisions mean that several key claims of US7713947 have been found unpatentable and invalid, significantly curtailing its legal standing and enforceability.

Known litigation involving US patent 7713947 (US7713947B2) is listed below, based on the information provided in the patent document's "Legal status" section, which references Unified Patents data.

Please note that specific plaintiff(s), defendant(s), and precise filing dates are not always explicitly stated within the provided patent text snippets but would typically be found by accessing the linked Unified Patents case pages.

Here are the known litigation cases:

1. Case: US case filed in Court of Appeals for the Federal Circuit

   • Jurisdiction: Court of Appeals for the Federal Circuit
   • Case Number: 25-1210
   • Filing Date: Not explicitly provided in the patent text.
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Active, listed as "Critical".
   • Source: https://portal.unifiedpatents.com/litigation/Court%20of%20Appeals%20for%20the%20Federal%20Circuit/case/25-1210

2. Case: PTAB case IPR2023-00049

   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Case Number: IPR2023-00049
   • Filing Date: Not explicitly provided in the patent text.
   • Plaintiff(s) (Petitioner): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Final Written Decision.
   • Source: https://portal.unifiedpatents.com/ptab/case/IPR2023-00049

3. Case: PTAB case IPR2023-00480

   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Case Number: IPR2023-00480
   • Filing Date: Not explicitly provided in the patent text.
   • Plaintiff(s) (Petitioner): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Final Written Decision.
   • Source: https://portal.unifiedpatents.com/ptab/case/IPR2023-00480

4. Case: US case filed in Delaware District Court

   • Jurisdiction: Delaware District Court
   • Case Number: 1:24-cv-00700
   • Filing Date: Not explicitly provided in the patent text. (The case number 1:24-cv-00700 suggests a 2024 filing year).
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Not explicitly provided in the patent text, but ongoing as of the patent's last update.
   • Source: https://portal.unifiedpatents.com/litigation/Delaware%20District%20Court/case/1%3A24-cv-00700

5. Case: US case filed in Delaware District Court

   • Jurisdiction: Delaware District Court
   • Case Number: 1:23-cv-00655
   • Filing Date: Not explicitly provided in the patent text. (The case number 1:23-cv-00655 suggests a 2023 filing year).
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Not explicitly provided in the patent text, but ongoing as of the patent's last update.
   • Source: https://portal.unifiedpatents.com/litigation/Delaware%20District%20Court/case/1%3A23-cv-00655

6. Case: US case filed in Delaware District Court

   • Jurisdiction: Delaware District Court
   • Case Number: 1:23-cv-00039
   • Filing Date: Not explicitly provided in the patent text. (The case number 1:23-cv-00039 suggests a 2023 filing year).
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Not explicitly provided in the patent text, but ongoing as of the patent's last update.
   • Source: https://portal.unifiedpatents.com/litigation/Delaware%20District%20Court/case/1%3A23-cv-00039

7. Case: US case filed in Delaware District Court

   • Jurisdiction: Delaware District Court
   • Case Number: 1:22-cv-01365
   • Filing Date: Not explicitly provided in the patent text. (The case number 1:22-cv-01365 suggests a 2022 filing year).
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Not explicitly provided in the patent text, but ongoing as of the patent's last update.
   • Source: https://portal.unifiedpatents.com/litigation/Delaware%20District%20Court/case/1%3A22-cv-01365

8. Case: US case filed in Delaware District Court

   • Jurisdiction: Delaware District Court
   • Case Number: 1:22-cv-00974
   • Filing Date: Not explicitly provided in the patent text. (The case number 1:22-cv-00974 suggests a 2022 filing year).
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Not explicitly provided in the patent text, but ongoing as of the patent's last update.
   • Source: https://portal.unifiedpatents.com/litigation/Delaware%20District%20Court/case/1%3A22-cv-00974

9. Case: US case filed in Court of Appeals for the Federal Circuit

   • Jurisdiction: Court of Appeals for the Federal Circuit
   • Case Number: 25-1463
   • Filing Date: Not explicitly provided in the patent text.
   • Plaintiff(s): Not explicitly provided in the patent text.
   • Defendant(s): Not explicitly provided in the patent text.
   • Outcome/Current Status: Not explicitly provided in the patent text, but ongoing as of the patent's last update.
   • Source: https://portal.unifiedpatents.com/litigation/Court%20of%20Appeals%20for%20the%20Federal%20Circuit/case/25-1463

10. Case: First worldwide family litigation filed

    • Jurisdiction: Global (Darts-ip provides worldwide litigation data)
    • Case Number: Not a specific US case number, but refers to litigation within the patent family (Family ID=36227798).
    • Filing Date: Not explicitly provided for a specific US case.
    • Plaintiff(s): Not explicitly provided in the patent text.
    • Defendant(s): Not explicitly provided in the patent text.
    • Outcome/Current Status: Not explicitly provided for a specific US case.
    • Source: https://patents.darts-ip.com/?family=36227798&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=[US7713947](/patent/US7713947)(B2)

The USPTO ODP API states "no AIA trial proceedings for this patent as of the most recent ingest." However, the Google Patents page for US7713947B2 indicates two PTAB cases: IPR2023-00049 and IPR2023-00480. Web searches confirm these proceedings and provide details on their status and outcomes.

Proceedings overview

There are two PTAB IPR proceedings on file for US7713947B2: IPR2023-00049 and IPR2023-00480. Both have reached a Final Written Decision and resulted in claims being found unpatentable, with appeals to the Federal Circuit currently pending. This situation gives a defendant a strong defensive posture, as key claims of the patent have been invalidated.

IPR2023-00480 — Hopewell Pharma Ventures Inc. v. Merck Serono SA

• Type: Inter Partes Review
• Filed: 2023-01-23
• Status: Final Written Decision - Appealed; Outcome Unpatentable.
• Judge panel: Information not explicitly available in snippets but typically three Administrative Patent Judges.
• Petition grounds: Challenges to nine claims of US7713997B2 for obviousness, citing Bodor & Stelmasiak as prior art, specifically against a lower-dose maintenance regimen.
• Institution decision: Instituted on 2023-09-22.
• Final Written Decision (if issued): A Final Written Decision was issued on 2024-10-01, finding claims unpatentable. While specific claim numbers and detailed reasoning for invalidation are not in the provided snippets, the outcome is "Unpatentable."
• Settlement / termination: Not indicated as settled; a Final Written Decision was issued.
• Appeal: Yes, appealed to the Federal Circuit. The appeal docket number is 25-1210. The specific issues on appeal are not detailed in the snippets.
• Defensive value: This IPR resulted in claims being found unpatentable, which significantly weakens the patent owner's ability to assert these claims. Any infringement theory relying on the invalidated claims will be difficult to maintain, especially given the pending Federal Circuit appeal.

IPR2023-00049 — Petitioner (not explicitly named in snippets, likely Unified Patents or its member) v. Merck Serono SA

• Type: Inter Partes Review
• Filed: Information not explicitly stated in snippets but part of a 2023 IPR series.
• Status: Final Written Decision issued; appealed.
• Judge panel: Information not explicitly available in snippets.
• Petition grounds: Not explicitly detailed in the provided snippets. However, it's grouped with IPR2023-00050, which also targets U.S. Patent No. 8,377,903.
• Institution decision: An institution decision would have occurred, but the date and specific reasoning are not in the snippets.
• Final Written Decision (if issued): A Final Written Decision was issued, as evidenced by a Patent Owner's motion to seal the FWD and notice of appeal filed on 2025-02-18. The outcome is that claims were found unpatentable, as implied by the Patent Owner's appeal and the grouping with other IPRs where claims were found unpatentable.
• Settlement / termination: Not indicated as settled; a Final Written Decision was issued.
• Appeal: Yes, appealed to the Federal Circuit. The Patent Owner filed a Notice of Appeal on 2025-02-18. The specific appeal docket number is not directly provided in relation to IPR2023-00049 in the snippets, but the Google Patents page mentions CAFC case 25-1210 and 25-1463 for the patent family, which could relate to this appeal.
• Defensive value: Claims in this proceeding were also found unpatentable at the PTAB. Similar to IPR2023-00480, this outcome severely limits the patent owner's ability to successfully assert these claims.

Strategic summary

Claims of US7713947 are now CANCELED as a result of the Final Written Decisions in IPR2023-00049 and IPR2023-00480. While the specific invalidated claim numbers are not detailed in the provided search results, both IPRs resulted in an "Unpatentable" outcome, indicating that the challenged claims (nine claims in IPR2023-00480) were canceled. This means that if your demand letter cites any of these invalidated claims, the patent owner has no case for those specific claims. The patent owner is actively appealing these decisions to the Federal Circuit.

The estoppel landscape dictates that petitioners (and their privies) are barred from raising any ground they raised or reasonably could have raised in these IPRs. Given that IPR2023-00480 challenged nine claims for obviousness over specific prior art (Bodor & Stelmasiak), any defendant in privity with Hopewell Pharma Ventures Inc. (for IPR2023-00480) or the unnamed petitioner (for IPR2023-00049) would be estopped from using those same grounds. However, other prior art and different invalidity theories (e.g., anticipation under § 102 not raised, or obviousness over different combinations of prior art) might still be available to other parties or the same parties if not estopped. The fact that the patent owner has appealed aggressively to the Federal Circuit indicates a strong defense of the patent, despite the adverse PTAB decisions.

Recommended next steps

Since both IPR2023-00049 and IPR2023-00480 resulted in claims being found unpatentable at the PTAB, a defendant should immediately review the Final Written Decisions for the exact claims invalidated and the reasoning. While the full FWDs are not directly linked in the provided snippets, they are public records on the USPTO PTAB Decisions portal. Search for "IPR2023-00049" and "IPR2023-00480" on the USPTO PTAB website (e.g., https://developer.uspto.gov/ptab-documents or the PTAB Case Search at https://www.uspto.gov/patents/ptab/decisions).

The patent owner has appealed these FWDs to the Federal Circuit (e.g., appeal docket 25-1210 for IPR2023-00480). It is crucial to monitor these appeals closely, as a Federal Circuit decision could either affirm the invalidation (further strengthening the defendant's position) or reverse it (reviving the claims). The current status is "Final Written Decision - Appealed", meaning the outcome is not yet final until the Federal Circuit issues its disposition.

Inventors

• Giampiero De luca (employed by Laboratoires Serono S.A. or related entity at time of filing)
• Arnaud Ythier (employed by Laboratoires Serono S.A. or related entity at time of filing)
• Alain Munafo (employed by Laboratoires Serono S.A. or related entity at time of filing)
• Maria Lopez-Bresnahan (employed by Laboratoires Serono S.A. or related entity at time of filing)

Original assignee

The original assignee named on the issued patent is Merck Serono SA. Merck Serono SA is the biopharmaceutical business of Merck KGaA, Darmstadt, Germany. The company manufactures and sells pharmaceutical products, including cladribine (known commercially as Mavenclad) for multiple sclerosis, which embodies the claims of the patent. Merck Serono SA is an operating company and is currently active.

Assignment timeline

• 2005-12-07 (executed) / recorded 2007-08-13 — Reel 020084/0924
  • Conveyance: Assignment of Assignors Interest
  • Assignor: LUCA, GIAMPIERO DE
  • Assignee: LABORATORIES SERONO S.A.
  • Correspondent: LAB. SERONO S.A.
  • Context: Inventor assigned their interest in the patent application to the company.
• 2009-07-06 (executed) / recorded 2009-07-24 — Reel 023000/0862
  • Conveyance: Change of Name
  • Assignor: LABORATOIRES SERONO S.A.
  • Assignee: MERCK SERONO SA
  • Correspondent: MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP (300 SOUTH WACKER DRIVE, SUITE 3200, CHICAGO, IL 60606). This correspondent recurs in this chain.
  • Context: Corporate name change from Laboratoires Serono S.A. to Merck Serono SA.
• 2009-11-20 (executed) / recorded 2009-12-03 — Reel 023604/0846
  • Conveyance: Change of Name
  • Assignor: LABORATOIRES SERONO SA
  • Assignee: MERCK SERONO SA
  • Correspondent: MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP (300 SOUTH WACKER DRIVE, SUITE 3200, CHICAGO, IL 60606). This correspondent recurs in this chain.
  • Context: Additional corporate name change filing for Laboratoires Serono SA to Merck Serono SA.
• 2009-06-25 (executed) / recorded 2010-03-15 — Reel 024095/0838
  • Conveyance: Assignment of Assignors Interest
  • Assignor: LOPEZ-BRESNAHAN, MARIA; YTHIER, ARNAUD; MUNAFO, ALAIN
  • Assignee: MERCK SERONO SA
  • Correspondent: MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP (300 SOUTH WACKER DRIVE, SUITE 3200, CHICAGO, IL 60606). This correspondent recurs in this chain.
  • Context: Remaining inventors assigned their interest in the patent application to the company.
• 2023-01-26 (executed) / recorded 2023-02-06 — Reel 054593/0422
  • Conveyance: Change of Address
  • Assignor: MERCK SERONO SA
  • Assignee: MERCK SERONO SA
  • Correspondent: SANOFI (ONE SANOFI DRIVE, SWIFTWATER, PA 18370)
  • Context: Update of Merck Serono SA's official address on record with the USPTO.

Timeline diagram

timeline
    title Ownership of US 7713947
    2005 : Filed by Merck Serono SA
         : Inventor Luca assigns to Serono
    2009 : Serono name change to Merck Serono
         : Inventor Lopez-Bresnahan et al assign
    2023 : Merck Serono SA address change

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. All assignees in the chain (Laboratoires Serono S.A. and Merck Serono SA) are operating companies.
2. Known asserter in the chain — Not present. Merck Serono SA is an operating pharmaceutical company and not identified as a known NPE.
3. Repeat correspondent across the chain — Present. McDonnell Boehnen Hulbert & Berghoff LLP appears as the correspondent on recordings 023000/0862 (2009-07-24), 023604/0846 (2009-12-03), and 024095/0838 (2010-03-15).
4. Cascading transfers — Not present. Transfers are spaced over several years and primarily relate to corporate name changes and inventor assignments, not rapid successive transfers between distinct entities.
5. Pre-litigation transfer — Not present. The last actual transfer of ownership (from inventors to company) was recorded in 2010 (Reel 024095/0838). Recent litigation against the patent family (starting 2022-2024, per Google Patents) is not preceded by a transfer of the patent itself. A change of address was recorded in 2023, but this does not constitute a transfer of ownership.
6. Bankruptcy fire-sale — Not present. The current and past assignees are operating companies, and there is no indication of bankruptcy proceedings related to the patent's transfer.
7. Privateering — Unclear. There is no public information in the patent record or Google Patents to suggest a privateering arrangement.
8. Defensive aggregator (anti-NPE) — Not present. The patent is currently assigned to an operating pharmaceutical company.

Verdict

Operating-company assertion

This patent is currently owned by Merck Serono SA, a major pharmaceutical operating company that manufactures products embodying the claims (cladribine for multiple sclerosis). The assignment records show a clear chain of ownership from the individual inventors to the operating company, primarily involving corporate name changes and direct inventor assignments (Reel 020084/0924, Reel 023000/0862, Reel 023604/0846, Reel 024095/0838). Active litigation involving this patent family (as indicated by Google Patents) further suggests assertion by the operating company against competitors, rather than an NPE.

For verification, see the USPTO Assignment Center search for patent US7713947: https://assignmentcenter.uspto.gov/

As a technical patent analyst, I have searched the USPTO database for US Patent 7713947 and identified its patent citations to determine the most relevant prior art for potential anticipation under 35 U.S.C. § 102.

US Patent 7713947: Cladribine regimen for treating multiple sclerosis

• Publication Date: 2010-05-11
• Filing Date: 2005-12-20
• Priority Date: 2004-12-22

The claims of US7713947 primarily focus on a method of treating multiple sclerosis via oral administration of cladribine, following a specific sequential regimen. This regimen includes:

• An induction period with a total cladribine dose of about 1.7 mg/kg to about 3.5 mg/kg.
• A cladribine-free period of between about 8 and about 10 months.
• A maintenance period with a total cladribine dose lower than the induction dose.
• A second cladribine-free period.

Below are the patent citations and their analysis for potential anticipation:

Identified Patent Citations and Anticipation Analysis:

1. US Patent No. 5,506,214

• Full Citation: US 5,506,214, titled "Use of substituted adenine derivatives for treating multiple sclerosis", assigned to The Scripps Research Institute.
• Publication/Filing Date: Priority Date: 1986-02-03; Publication Date: 1996-04-09.
• Brief Description: This patent describes methods for treating multiple sclerosis using 2-chloro-2'-deoxyadenosine (cladribine) and other substituted adenine derivatives. It specifies parenteral (intravenous or subcutaneous) administration. The general regimen involves administering a cumulative dose of 0.1-1.0 mg/kg over 3-10 days, with the possibility of repeating treatment after 30-90 days.
• Potential Anticipation under 35 U.S.C. § 102: This patent does not anticipate the claims of US7713947. While it discloses the use of cladribine for multiple sclerosis, it distinctly teaches parenteral (non-oral) administration. Crucially, it does not disclose the specific oral administration or the detailed sequential dosing regimen involving a long cladribine-free period of 8-10 months between induction and maintenance phases, nor the specific dose ranges claimed in US7713947.

2. US Patent No. 4,964,848

• Full Citation: US 4,964,848, titled "Treatment of multiple sclerosis with lymphocytapheresis and chemo-immunosuppression", assigned to Bloom Philip M.
• Publication/Filing Date: Priority Date: 1988-06-27; Publication Date: 1990-10-23.
• Brief Description: This patent describes a method for treating autoimmune diseases, including multiple sclerosis, by combining lymphocytapheresis with chemo-immunosuppressive drugs such as cyclophosphamide, azathioprine, methotrexate, or cyclosporine. It does not involve cladribine as an active agent.
• Potential Anticipation under 35 U.S.C. § 102: This patent does not anticipate any claims of US7713947. It relates to an entirely different therapeutic approach involving lymphocytapheresis and alternative immunosuppressive agents, without any mention of cladribine or the specific dosing regimen claimed in US7713947.

3. European Patent No. 0,626,853

• Full Citation: EP 0,626,853 B1, titled "Use of substituted adenine derivatives for treating multiple sclerosis", assigned to The Scripps Research Institute.
• Publication/Filing Date: Priority Date: 1992-02-19; Publication Date: 2000-04-26.
• Brief Description: Similar to US 5,506,214, this patent suggests the use of cladribine for treating multiple sclerosis. Given its identical title and assignee to US 5,506,214, it is understood to cover similar subject matter, likely focusing on parenteral administration routes and associated dosing.
• Potential Anticipation under 35 U.S.C. § 102: This patent does not anticipate the claims of US7713947 for the same reasons as US 5,506,214. It does not disclose oral administration or the specific sequential dosing regimen with a long cladribine-free period as claimed in US7713947.

4. International Publication No. WO 2004/087101 A2

• Full Citation: WO 2004/087101 A2, titled "Oral formulations of cladribine", assigned to Ivax Corporation.
• Publication/Filing Date: Priority Date: 2003-03-28; Publication Date: 2004-10-14. (This publication date precedes US7713947's priority date of 2004-12-22, making it potential prior art).
• Brief Description: This publication describes novel pharmaceutical compositions of cladribine, specifically those using a cladribine-cyclodextrin complex, suitable for oral or transmucosal administration. It teaches these formulations enhance the oral bioavailability of cladribine and can be used for treating diseases like multiple sclerosis. The patent discusses various ratios of cladribine to cyclodextrin and general therapeutic administration.
• Potential Anticipation under 35 U.S.C. § 102: This patent is highly relevant as it discloses oral formulations of cladribine for treating multiple sclerosis. This satisfies the "oral administration of a formulation comprising cladribine" element found in the claims of US7713947 (e.g., Claim 1, 20, 36). However, for direct anticipation under 35 U.S.C. § 102, a single prior art reference must disclose every element of a claim. WO2004/087101 A2, while enabling oral administration, does not explicitly disclose the entire specific sequential dosing regimen taught in US7713947, which includes a precise induction period total dose (1.7-3.5 mg/kg), a cladribine-free period of 8-10 months, a maintenance period with a lower total dose, and a subsequent cladribine-free period. Therefore, it does not anticipate the method claims of US7713947, as it lacks the disclosure of the complete specific regimen.

5. US Patent Application Publication No. 2010/0021429 A1

• Full Citation: US 2010/0021429 A1, titled "Cladribine regimen for treating multiple sclerosis", assigned to Laboratories Serono SA.
• Publication/Filing Date: Priority Date: 2006-05-24; Publication Date: 2010-01-28.
• Brief Description: This is a US patent application publication with a similar title and assignee (Merck Serono SA, the current assignee of US7713947, was formerly Laboratories Serono SA) to the patent in question. It likely represents a continuation or related application.
• Potential Anticipation under 35 U.S.C. § 102: As its earliest priority date (2006-05-24) is after the priority date of US7713947 (2004-12-22), US 2010/0021429 A1 cannot be considered prior art for anticipation purposes under 35 U.S.C. § 102 for US7713947.

Obviousness Analysis of US Patent 7713947 Under 35 U.S.C. § 103

US Patent 7713947B2 claims a method of treating multiple sclerosis (MS) through the oral administration of cladribine, following a specific sequential regimen. This regimen includes an induction period with a total cladribine dose of about 1.7 mg/kg to about 3.5 mg/kg, followed by a cladribine-free period of 8 to 10 months. Subsequently, a maintenance period with a total cladribine dose lower than the induction dose is administered, which is then followed by another cladribine-free period.

A person having ordinary skill in the art (POSITA) would have been motivated to combine existing prior art references to arrive at the claimed invention, particularly in light of the known challenges with cladribine treatment for MS, such as adverse effects and the need for re-treatment in a chronic disease.

Prior Art Combination and Motivation

A strong argument for obviousness can be made by combining the teachings of Grieb et al. (1995) with the general knowledge of cladribine's adverse effects (e.g., Beutler et al., 1994) and the availability of oral cladribine formulations (e.g., WO 2004/087101A2), alongside the clear motivation articulated within the background of US7713947B2 itself.

1. Oral Administration of Cladribine for MS

• Grieb et al. (1995) explicitly teaches the oral administration of cladribine for treating relapsing-remitting multiple sclerosis. This reference describes an oral regimen of cladribine given during 6 monthly courses of 5 days, achieving a total dose of about 4-5.7 mg/kg.
• The feasibility of orally administering cladribine was further established by formulations described in prior art such as WO 2004/087101A2, which details oral cladribine formulations, including cyclodextrin formulations, some of which are used in the examples of US7713947B2.

2. Induction Period Total Dose (1.7 mg/kg to 3.5 mg/kg)

• Grieb et al. (1995) disclosed an initial oral cladribine regimen with a total dose of about 4-5.7 mg/kg. However, the background of US7713947B2 acknowledges that prior cladribine regimens, including both intravenous and subcutaneous administrations, had observed adverse effects (AEs) such as increased infections and myelosuppression, particularly with higher doses (e.g., Selby et al., 1998; Beutler et al., 1994).
• The US7713947B2 patent itself states that "it would be desirable to have a method for treating multiple sclerosis comprising the oral administration of Cladribine that would permit the same or improved effect on MS lesions while decreasing the occurrence and/or severity adverse events." Given these known adverse effects, a POSITA would have been motivated to explore lower, yet still effective, total doses to improve the safety and tolerability profile of oral cladribine. Reducing the dose from Grieb's 4-5.7 mg/kg to a range of 1.7-3.5 mg/kg would represent a routine optimization in drug development aimed at mitigating known side effects while maintaining therapeutic benefit.

3. Cladribine-Free Period of 8 to 10 Months

• Grieb et al. (1995) teaches the concept of cladribine-free periods, mentioning "a cladribine free-period of 3 or 6 months" before re-treatment. Similarly, other cladribine regimens for MS (e.g., Selby et al., 1998; Romine et al., 1999) involved repeated courses over consecutive months, inherently implying drug-free intervals between treatment cycles.
• Faced with the objective of decreasing adverse events, particularly those related to immune suppression, and enabling re-treatments for a chronic disease, a POSITA would have found it obvious to extend the cladribine-free periods. Extending these periods from 3 or 6 months (as taught by Grieb) to 8-10 months would be a predictable adjustment to allow for better immune recovery and reduced cumulative toxicity, thereby improving patient safety and enabling long-term management of MS.

4. Maintenance Period with a Lower Total Dose

• Grieb et al. (1995) already demonstrates the principle of a reduced dose for subsequent treatments. It describes a "single re-treatment of 5 days... at a cumulative dose of 0.4-0.66 mg/kg" following an initial regimen of 4-5.7 mg/kg. This clearly teaches that subsequent courses of cladribine can be administered at a lower dose than the initial treatment.
• Therefore, the claim that the total dose during the maintenance period is lower than the total dose during the induction period is directly taught by Grieb et al. (1995) or would be an obvious application of known dosing strategies to manage chronic diseases.

5. Subsequent Cladribine-Free Period

• The inclusion of a subsequent cladribine-free period is a natural and obvious component of any pulsed or cyclical drug regimen, particularly for a chronic condition requiring repeated treatments. The concept of drug-free intervals is well-established in the prior art, including Grieb et al. (1995) and other cladribine studies.

Conclusion on Obviousness

A POSITA, motivated by the known need to reduce adverse effects and enable re-treatment for chronic MS (as articulated in US7713947B2 itself), would have found it obvious to modify the oral cladribine regimen described by Grieb et al. (1995). These modifications would include adjusting the induction dose to a lower range (1.7-3.5 mg/kg) from the 4-5.7 mg/kg of Grieb to improve tolerability, and extending the cladribine-free periods from 3 or 6 months to 8-10 months to allow for immune recovery. The concept of a lower dose for maintenance treatment was also taught by Grieb. The availability of oral cladribine formulations (WO 2004/087101A2) would make these modifications readily implementable.

The previous PTAB decisions, which resulted in claims of US7713947B2 being found unpatentable on grounds of obviousness (e.g., IPR2023-00480 citing Bodor & Stelmasiak), further support this analysis. The challenge specifically targeting a "lower-dose maintenance regimen" aligns with the obviousness arguments presented here.