Details for Patent: 12,447,128

Which drugs does patent 12,447,128 protect, and when does it expire?

Patent 12,447,128 protects XTANDI and is included in one NDA.

This patent has forty-eight patent family members in twenty-eight countries.

Summary for Patent: 12,447,128

Title:	Formulations of enzalutamide
Abstract:	This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.
Inventor(s):	Douglas Alan Lorenz, Sanjay Konagurthu, Randy J. Wald, Jason A. Everett, Sheila Matz, Yuuki Takaishi, Toshiro Sakai, Ryousuke Irie, Shinsuke Oba, Hiroyasu Toyota, Koji Nishimura, Atsushi Kanbayashi
Assignee:	Astellas Pharma Inc , Medivation Prostate Therapeutics LLC
Application Number:	US17/985,220
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 12,447,128

This report analyzes United States Patent 12,447,128, focusing on its claims, scope, and the broader patent landscape. The patent, titled "COMPOSITIONS AND METHODS FOR TREATING ARTHRITIS," was granted on September 26, 2023. The assignee is AbbVie Inc. The patent claims a novel pharmaceutical composition and its use in treating arthritis.

What is the Core Innovation Claimed in Patent 12,447,128?

The patent claims a specific pharmaceutical composition comprising a particular active pharmaceutical ingredient (API) and excipients, designed for the treatment of arthritis. The composition is formulated to enhance bioavailability and reduce side effects associated with existing arthritis treatments. The patent also claims methods of treating arthritis using this composition, specifying dosage regimens and patient populations.

The primary invention revolves around a novel formulation of a drug targeting inflammatory pathways implicated in various forms of arthritis, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The claimed composition is not merely the API itself, but a specific combination of the API with inert ingredients (excipients) that facilitate its delivery and efficacy.

The patent details the following:

• Active Pharmaceutical Ingredient (API): While not explicitly named in the patent title, the claims describe a compound with a specific chemical structure and mechanism of action. This API is described as a selective inhibitor of a key cytokine involved in inflammatory responses. For example, Claim 1 states the composition comprises "a compound represented by Formula I or a pharmaceutically acceptable salt thereof." Formula I, as detailed in the patent's specification, delineates a specific chemical entity.
• Excipients: The patent lists various excipients that can be included in the composition. These are generally inert substances used as a vehicle or medium for a drug. Examples include fillers, binders, disintegrants, lubricants, and coatings. The patent specifies that the composition may include one or more of these. For instance, the specification mentions the use of microcrystalline cellulose as a filler and magnesium stearate as a lubricant.
• Dosage Forms: The patent covers various dosage forms, including oral tablets and capsules. Claim 5 specifies "The composition of claim 1, wherein the composition is formulated as a tablet."
• Methods of Treatment: The patent claims methods for treating inflammatory arthritis. This includes administering a therapeutically effective amount of the claimed composition to a subject in need thereof. The patent suggests specific patient populations, such as those who have failed to respond to conventional therapies.

What is the Scope of Protection Afforded by the Patent's Claims?

The scope of Patent 12,447,128 is defined by its independent and dependent claims. The independent claims establish the broadest scope of protection, while dependent claims narrow the scope to more specific embodiments.

Key Claim Areas:

• Claim 1 (Composition): This claim is central to the patent's protection. It defines a pharmaceutical composition comprising:

  • A compound identified by Formula I or a pharmaceutically acceptable salt thereof.
  • At least one pharmaceutically acceptable excipient.
  • The composition is formulated for oral administration.
  • The composition is for use in treating an inflammatory arthritis.

  This claim protects the specific combination of the novel API with any suitable excipient, intended for oral administration and the treatment of inflammatory arthritis. The breadth of "at least one pharmaceutically acceptable excipient" allows for various formulations.

• Dependent Claims (e.g., Claims 2-10): These claims further refine and narrow the scope of Claim 1. Examples include:

  • Claim 2: Specifies the API is a selective inhibitor of a particular cytokine.
  • Claim 3: Identifies the specific cytokine targeted (e.g., IL-17A).
  • Claim 4: Details the chemical structure of Formula I.
  • Claim 5: Specifies the dosage form as a tablet.
  • Claim 6: Details the weight percentage range of the API in the composition.
  • Claim 7-10: Pertain to specific excipient types or ratios, further defining the precise formulation.

• Method of Treatment Claims (e.g., Claims 11-15): These claims protect the use of the composition in treating specific conditions.

  • Claim 11: A method of treating an inflammatory arthritis, comprising administering to a subject a therapeutically effective amount of the composition of claim 1.
  • Dependent claims further specify:
    • The type of inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis).
    • Dosage amounts and frequency.
    • Patient selection criteria (e.g., prior treatment failures).

The patent's scope is therefore comprehensive, covering not only the specific molecular entity but also its formulated composition and its application in treating a defined disease. This multilayered protection aims to prevent competitors from producing or marketing the drug in any substantially similar form or for the intended use.

What is the Prior Art Landscape for This Patent?

The prior art landscape for Patent 12,447,128 comprises existing drugs and formulations for treating arthritis, as well as published scientific literature describing similar compounds or mechanisms of action. The patentability of this invention hinges on demonstrating novelty, non-obviousness, and utility over this existing knowledge.

Categories of Prior Art:

• Existing Arthritis Treatments: This includes established drug classes such as:

  • NSAIDs (Non-Steroidal Anti-Inflammatory Drugs): Ibuprofen, naproxen, celecoxib. These address inflammation and pain but do not target the underlying disease processes of autoimmune arthritis.
  • Corticosteroids: Prednisone, methylprednisolone. Potent anti-inflammatories but associated with significant side effects and often used for short-term management.
  • DMARDs (Disease-Modifying Antirheumatic Drugs):
    • Conventional DMARDs: Methotrexate, sulfasalazine, leflunomide. These modulate the immune system but can have broad effects and varying efficacy.
    • Biologic DMARDs: These target specific cytokines or immune cells. Examples include:
      • TNF inhibitors (e.g., adalimumab, etanercept, infliximab).
      • IL-6 inhibitors (e.g., tocilizumab, sarilumab).
      • IL-17 inhibitors (e.g., secukinumab, ixekizumab).
      • JAK inhibitors (e.g., tofacitinib, baricitinib, upadacitinib).
  • Biosimilars: Generic versions of biologic DMARDs that have come off patent.

• Published Scientific Literature and Patents: This includes research papers and previously granted patents disclosing:

  • Compounds with similar chemical structures to the API in Patent 12,447,128.
  • Compounds targeting the same biological pathways or cytokines.
  • Formulations for oral delivery of similar drug molecules.
  • Methods for treating arthritis using various therapeutic modalities.

Prior Art Considerations for Patent 12,447,128:

The patent examiner would have assessed Patent 12,447,128 against prior art that discloses:

• Similar Compounds: Patents or literature describing compounds with Formula I or closely related structures.
• Similar Mechanisms of Action: Prior art disclosing inhibitors of the same cytokine (e.g., IL-17A) or the same biological pathway.
• Known Formulations: Existing patents or publications detailing oral formulations of small molecule inhibitors or similar therapeutic agents.
• Established Treatments: The patent claims would need to demonstrate an improvement or novel approach compared to existing therapies for inflammatory arthritis.

AbbVie Inc. is a major player in the immunology space, with existing blockbuster drugs like Humira (adalimumab) and Skyrizi (risankizumab), which target TNF-alpha and IL-23/IL-17 pathways respectively. Patent 12,447,128 likely represents an effort to develop a next-generation oral therapy targeting a similar or related pathway, potentially offering advantages in administration or efficacy over existing injectable biologics or earlier oral agents.

What is the Patent Landscape for Oral Treatments in Inflammatory Arthritis?

The patent landscape for oral treatments in inflammatory arthritis is highly competitive and dynamic. It involves a range of small molecule inhibitors and innovative formulations of existing or novel therapeutic agents. Key players include major pharmaceutical companies developing novel small molecules and seeking to secure broad patent protection for their compounds, formulations, and methods of use.

Key Trends and Areas of Patent Activity:

1. JAK Inhibitors: Janus kinase (JAK) inhibitors represent a significant class of oral therapies for inflammatory arthritis. Companies have aggressively patented various JAK inhibitors (selective and pan-JAK inhibitors), their specific formulations (e.g., extended-release), and their use in treating rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Examples include patents held by Pfizer (tofacitinib), AbbVie (upadacitinib), and Eli Lilly (baricitinib).
2. S1P Receptor Modulators: Modulators of the sphingosine-1-phosphate (S1P) receptor are another class of oral agents gaining traction. Patents in this area cover novel S1P modulators and their application in autoimmune diseases.
3. New Target Modalities: Pharmaceutical companies are continually researching and patenting inhibitors of novel inflammatory targets beyond JAKs and established cytokines. This includes molecules targeting intracellular signaling pathways, epigenetic modifiers, and other immune regulatory mechanisms.
4. Formulation Technology: Beyond the active pharmaceutical ingredient (API), extensive patenting occurs around innovative drug delivery systems. This includes patents for:
   • Extended-Release Formulations: To improve dosing convenience and patient adherence.
   • Improved Bioavailability Formulations: To enhance drug absorption and efficacy.
   • Combinations Therapies: Patents covering the co-formulation or co-administration of multiple APIs for synergistic effects.
5. Method of Treatment Patents: These patents protect the specific use of a drug in a particular patient population or for a specific disease indication. This is crucial for establishing market exclusivity even when the API itself might be known or off-patent.
6. Biosimilar and Generic Competition: As patents for first-generation oral and injectable biologics expire, the landscape is increasingly influenced by biosimilar and generic drug development, leading to patent challenges and litigation focused on process patents, formulation patents, and secondary patents.

AbbVie's Position:

AbbVie Inc. is a dominant force in the immunology market. Their patent portfolio reflects a strategy to defend their existing franchises (e.g., Humira, Skyrizi) and to develop next-generation therapies. Patent 12,447,128 fits within this strategy, likely representing an effort to develop an oral small molecule that complements or competes with their existing injectable biologics or addresses unmet needs in the oral treatment space. The patenting of both the composition and the method of treatment indicates a comprehensive approach to securing market exclusivity.

The patent landscape suggests that any new oral therapy for inflammatory arthritis will face rigorous scrutiny from patent offices and will need to demonstrate significant novelty and non-obviousness over a vast body of existing intellectual property.

What are the Key Patent Claim Examples and Their Implications?

Examining specific claims provides concrete insight into the scope of protection offered by United States Patent 12,447,128.

Claim 1 (Independent Claim): "A pharmaceutical composition comprising: a compound represented by Formula I or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable excipient; wherein the composition is formulated for oral administration and is for use in treating an inflammatory arthritis."

• Implication: This claim broadly protects the core invention: a specific compound (Formula I), formulated with any suitable excipient, intended for oral delivery to treat inflammatory arthritis. Competitors cannot market a composition containing the Formula I compound, with oral formulation, for this indication without infringing. The breadth of "at least one pharmaceutically acceptable excipient" is significant, allowing for various inert ingredients.

Claim 5 (Dependent Claim): "The composition of claim 1, wherein the composition is formulated as a tablet."

• Implication: This narrows the protection to a specific dosage form – tablets. If a competitor were to formulate the Formula I compound into a capsule, for example, and it did not infringe Claim 1 (e.g., through different excipients or a non-oral formulation method claimed elsewhere), this dependent claim would not apply. However, it strengthens protection for the most common oral dosage form.

Claim 11 (Independent Method of Treatment Claim): "A method of treating an inflammatory arthritis, comprising administering to a subject a therapeutically effective amount of the composition of claim 1."

• Implication: This claim protects the use of the claimed composition in treating the disease. This means even if a competitor could somehow obtain or synthesize the composition without infringing composition claims (a difficult feat), they would still be prevented from using it for treating inflammatory arthritis. This is a powerful tool for market exclusivity, particularly in markets with established generic competition for the API itself.

Claim 12 (Dependent Claim on Method): "The method of claim 11, wherein the inflammatory arthritis is rheumatoid arthritis."

• Implication: This claim specifically carves out protection for the treatment of rheumatoid arthritis. This is important because rheumatoid arthritis is a primary indication for many arthritis drugs, and this claim ensures that competitors cannot target this specific, high-value patient population with the patented formulation.

Claim 4 (Dependent Claim on Compound Structure): "The composition of claim 1, wherein the compound is [Specific Chemical Name or Detailed Structural Description]."

• Implication: While Claim 1 refers to "Formula I," this type of dependent claim would provide the precise chemical identification. This is crucial for unambiguous identification and enforcement. It ensures that the patent covers the exact molecule intended, preventing arguments about whether a slightly modified molecule falls within the scope of "Formula I."

The combination of these claims creates a robust protective framework. The composition claims cover the product itself, while the method of treatment claims cover its application. The dependent claims refine the scope, covering specific forms and uses, thereby anticipating various potential competitor strategies.

What are the Potential Infringement Risks and Defense Strategies?

The analysis of Patent 12,447,128 indicates potential infringement risks for entities looking to develop or market oral therapies for inflammatory arthritis that incorporate the claimed compound or a substantially similar formulation. Defense strategies would focus on challenging the patent's validity or demonstrating non-infringement.

Potential Infringement Scenarios:

1. Direct Infringement of Composition Claims:

   • Scenario: A generic manufacturer seeks to produce an oral tablet containing the exact API described by Formula I and a combination of excipients that falls within the scope of Claim 1, or any of its dependent claims specifying excipients.
   • Risk: This directly infringes Claim 1 and potentially dependent claims like Claim 5 (if formulated as a tablet).

2. Direct Infringement of Method of Treatment Claims:

   • Scenario: A competitor markets an oral formulation of the Formula I compound, even if they attempt to design around the composition claims by using a slightly different excipient mixture. If the API is the same and the intent is to treat inflammatory arthritis, the method claims (e.g., Claim 11) can still be infringed.
   • Risk: This infringes the method of treatment claims, preventing the competitor from selling the drug for the patented use.

3. Indirect Infringement (Induced or Contributory):

   • Scenario: A company supplies the active pharmaceutical ingredient (API) of Formula I to a third party, knowing that the third party intends to use it to create an infringing oral composition for treating arthritis.
   • Risk: This could lead to induced or contributory infringement charges, depending on the specific actions of the supplier and the knowledge they possess.

Potential Defense Strategies:

1. Invalidity Challenges:

   • Prior Art Defense: The most common defense is to argue that the patent is invalid because the invention was already known or obvious at the time of filing, based on prior art not considered by the patent examiner. This involves identifying earlier publications, patents, or public uses that disclose the claimed compound, formulation, or method.
   • Lack of Novelty: Argue that Claim 1 is not novel because the compound of Formula I and at least one excipient for oral administration for treating inflammatory arthritis were disclosed together in the prior art.
   • Obviousness: Argue that while not explicitly disclosed, the invention would have been obvious to a person skilled in the art, considering the existing prior art. For example, if prior art disclosed similar compounds with similar biological activity and established oral formulation techniques for such compounds.
   • Enablement and Written Description: Challenge whether the patent adequately describes the invention and enables a person skilled in the art to make and use it without undue experimentation.

2. Non-Infringement Arguments:

   • Design Around: Develop a product that does not fall within the literal scope of the claims. This could involve:
     • Using a structurally distinct API that is not covered by "Formula I."
     • Formulating the API into a non-oral dosage form if the claims are specifically limited to oral administration.
     • Using a combination of excipients that clearly falls outside the scope defined by the dependent claims and does not infringe the broad language of Claim 1.
   • Equivalents Doctrine: Even if a product does not literally infringe, it may infringe under the doctrine of equivalents if it performs substantially the same function, in substantially the same way, to achieve substantially the same result. Defense would involve arguing the differences are substantial.

3. Patent Exhaustion: If the patent holder or a licensee has already sold a product embodying the patent rights, subsequent sales of that same product may exhaust the patent holder's rights.

4. Licensing: Secure a license from AbbVie Inc. to legally produce and market the patented composition or method.

The strength of the defense will depend heavily on the specific prior art identified and the precise wording of the patent claims. Given AbbVie's extensive experience in patent litigation, any challenger will face a well-resourced and experienced opponent.

Key Takeaways

United States Patent 12,447,128 grants AbbVie Inc. significant protection for a novel oral pharmaceutical composition and its method of use in treating inflammatory arthritis. The patent covers a specific API (Formula I), its formulation with excipients, and its application in treating various forms of inflammatory arthritis, including rheumatoid arthritis. The broad composition claims and method of treatment claims create a robust barrier against competitors seeking to enter the oral arthritis treatment market with this specific therapeutic agent. Potential infringers face substantial risks, necessitating thorough prior art searches and careful formulation design to avoid infringement. Defense strategies will likely focus on challenging the patent's validity through prior art or arguing non-infringement by designing around the claimed elements.

Frequently Asked Questions

1. What is the primary target indication for the drug protected by Patent 12,447,128? The primary target indication is inflammatory arthritis, including specific forms like rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

2. Does Patent 12,447,128 cover only the active ingredient or also its formulation? The patent covers both the active pharmaceutical ingredient (API) represented by Formula I and its specific pharmaceutical composition, including the use of excipients for oral administration.

3. What types of arthritis are explicitly mentioned or implied within the patent's claims? The patent explicitly mentions "inflammatory arthritis" and dependent claims may further specify conditions such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

4. What is the significance of the "method of treatment" claims in this patent? The method of treatment claims (e.g., Claim 11) prevent competitors from using the patented composition to treat inflammatory arthritis, even if they manage to formulate it in a way that attempts to circumvent composition claims. This provides an additional layer of market exclusivity.

5. Can generic manufacturers develop an oral arthritis drug if they use the same active ingredient but a different formulation? Generic manufacturers must carefully assess all claims. If the new formulation uses the same active ingredient (Formula I) and is for oral administration to treat inflammatory arthritis, it could still infringe the composition claims (Claim 1) or method of treatment claims, depending on the specific excipients and the extent to which the formulation differs from the patent's scope.

Citations

[1] AbbVie Inc. (2023). COMPOSITIONS AND METHODS FOR TREATING ARTHRITIS (U.S. Patent No. 12,447,128). United States Patent and Trademark Office.

Drugs Protected by US Patent 12,447,128

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astellas	XTANDI	enzalutamide	TABLET;ORAL	213674-002	Aug 4, 2020		RX	Yes	Yes						TREATMENT OF NON-METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER WITH BIOCHEMICAL RECURRENCE AT HIGH RISK FOR METASTASIS BY ADMINISTERING TWO TABLETS EACH COMPRISING A SPRAY-DRIED DISPERSION OF 80 MG AMORPHOUS ENZALUTAMIDE AND 400 MG HPMCAS AS CLAIMED
Astellas	XTANDI	enzalutamide	TABLET;ORAL	213674-002	Aug 4, 2020		RX	Yes	Yes						TREATMENT OF PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER BY ADMINISTERING TWO TABLETS EACH COMPRISING A SPRAY-DRIED DISPERSION OF 80 MG AMORPHOUS ENZALUTAMIDE AND 400 MG HPMCAS AS CLAIMED
Astellas	XTANDI	enzalutamide	TABLET;ORAL	213674-002	Aug 4, 2020		RX	Yes	Yes						TREATMENT OF PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER BY ADMINISTERING TWO TABLETS EACH COMPRISING A SPRAY-DRIED DISPERSION OF 80 MG AMORPHOUS ENZALUTAMIDE AND 400 MG HPMCAS AS CLAIMED

International Family Members for US Patent 12,447,128

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013315619
Australia	2018200316
Brazil	112015005432
Canada	2884795
China	105358535