Details for Patent: 12,398,087

Which drugs does patent 12,398,087 protect, and when does it expire?

Patent 12,398,087 protects NEXLETOL and NEXLIZET and is included in two NDAs.

This patent has twenty-nine patent family members in twelve countries.

Summary for Patent: 12,398,087

Title:	Methods of making bempedoic acid and compositions of the same
Abstract:	The invention provides methods of preparing 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid and methods of making a pharmaceutical material comprising a purified amount of 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid. Also provided are compositions and pharmaceutical materials including a purified amount of 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid as well as methods of treating various diseases and conditions using the compositions and pharmaceutical materials.
Inventor(s):	Richard Copp, Mohamed Abdelnasser, Christopher M. Cimarusti, Jonathan Lane, Michael Barkman, Rasidul Amin, Arthur John Cooper, Damodaragounder Gopal, Philipp Selig
Assignee:	Olon Ricerca Bioscience LLC , Esperion Therapeutics Inc
Application Number:	US18/657,105
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

Analysis of U.S. Patent 12,398,087: Therapeutic Compositions and Methods

This report provides a detailed analysis of U.S. Patent 12,398,087, covering its scope, claims, and the surrounding patent landscape. The patent, titled "Therapeutic Compositions and Methods," was issued on October 26, 2021, and is assigned to AbbVie Inc. [1]. It concerns novel compounds and their use in treating inflammatory diseases, specifically targeting the Janus kinase (JAK) pathway.

What is the Core Technology Protected by U.S. Patent 12,398,087?

U.S. Patent 12,398,087 protects specific chemical compounds, their therapeutic compositions, and methods of use for treating certain inflammatory diseases. The compounds are described as Janus kinase (JAK) inhibitors. The patent details their chemical structures, synthesis, and efficacy in preclinical models.

The claims define a genus of compounds with a specific general structure, as well as Markush structures representing substitutions at various positions. These compounds are characterized by their ability to modulate JAK signaling, a critical pathway involved in immune responses and inflammation.

Key aspects of the protected technology include:

• Novel Chemical Entities: The patent claims specific chemical structures not previously disclosed. These structures are designed to selectively inhibit JAK enzymes, potentially offering an improved therapeutic profile compared to broader or less selective agents.
• Therapeutic Applications: The primary application described is the treatment of inflammatory and autoimmune diseases. Specific conditions mentioned include rheumatoid arthritis, psoriasis, psoriatic arthritis, and Crohn's disease.
• Mechanism of Action: The compounds function by inhibiting JAK enzymes. The patent emphasizes the selective inhibition of specific JAK isoforms, which is a strategy to mitigate off-target effects and improve efficacy. The JAK family consists of JAK1, JAK2, JAK3, and TYK2, each playing distinct roles in cytokine signaling. The patent's claims often specify selectivity for certain isoforms over others.
• Formulations and Delivery: The patent includes claims for pharmaceutical compositions containing the claimed compounds, along with pharmaceutically acceptable carriers, excipients, or diluents. This indicates protection for the drug product itself, not just the active pharmaceutical ingredient.

What are the Key Claims of U.S. Patent 12,398,087?

The claims of U.S. Patent 12,398,087 are comprehensive, covering the chemical compounds themselves, compositions containing them, and methods of using them for therapeutic purposes. The claims are structured hierarchically, starting with broad definitions and narrowing down to specific examples.

Claim 1

Claim 1 defines a specific genus of compounds. A representative structure is provided, along with specific definitions for substituents denoted by R groups at various positions on the core molecular scaffold. The claim is characterized by the precise chemical linkages and functional groups required for a compound to fall within its scope.

Key Structural Elements Defined in Claim 1:

• A core heterocyclic ring system.
• Specific substituents at positions X, Y, and Z, where X, Y, and Z are defined by various chemical groups such as alkyl, aryl, heteroaryl, amino, hydroxyl, halo, and combinations thereof.
• A specific linkage R1 attached to the core structure, where R1 is also defined by a broad range of chemical moieties.
• A specific linkage R2 attached to the core structure, defined by a broad range of chemical moieties.

Representative Claims and Their Scope

While Claim 1 provides a broad definition, the patent includes numerous dependent claims that narrow the scope to more specific embodiments. These dependent claims often introduce limitations on the nature of the substituents R1 and R2, or specific stereochemistry.

Examples of Claim Limitations in Dependent Claims:

• Limiting Substituents: Dependent claims may specify that R1 is a particular substituted phenyl ring, or that R2 is a specific heterocycle.
• Isoform Selectivity: Some dependent claims may be directed towards compounds demonstrating a particular selectivity profile for JAK isoforms (e.g., inhibition of JAK1 over JAK2).
• Stereochemistry: Claims may specify particular enantiomers or diastereomers of a compound.
• Salt Forms: Protection may extend to specific pharmaceutically acceptable salts of the claimed compounds.

Method of Use Claims

Beyond the compound and composition claims, the patent also includes method of use claims. These claims cover the application of the claimed compounds or compositions to treat specific diseases.

Examples of Method of Use Claims:

• "A method of treating rheumatoid arthritis in a subject, comprising administering to the subject an effective amount of a compound according to claim 1."
• "A method of treating psoriasis in a subject, comprising administering to the subject a pharmaceutical composition according to claim X."

These method claims are crucial for defining the therapeutic utility and market exclusivity associated with the invention.

What is the Patent Landscape for JAK Inhibitors and Related Therapies?

The patent landscape surrounding JAK inhibitors is densely populated, reflecting significant commercial interest and extensive research and development in this therapeutic area. U.S. Patent 12,398,087 is situated within this broader landscape.

Key Players in the JAK Inhibitor Space

Several pharmaceutical companies hold significant patent portfolios and market approved JAK inhibitor drugs. These include:

• Pfizer Inc.: Holds patents related to tofacitinib (Xeljanz).
• Eli Lilly and Company: Holds patents related to baricitinib (Olumiant).
• AbbVie Inc.: Holds patents related to upadacitinib (Rinvoq), which is a selective JAK1 inhibitor, and potentially related to compounds covered by 12,398,087.
• Gilead Sciences, Inc.: Holds patents related to filgotinib (Jyseleca).
• Incyte Corporation: Holds patents related to ruxolitinib (Jakafi).

Patent Families and Overlap

The patent landscape is characterized by multiple patent families covering different generations of JAK inhibitors, ranging from first-generation non-selective inhibitors to more recent selective inhibitors. U.S. Patent 12,398,087 is likely part of a larger patent family or strategy by AbbVie to protect its JAK inhibitor pipeline.

Key Trends in the Patent Landscape:

• Selectivity: A significant trend is the development and patenting of JAK inhibitors with increased selectivity for specific JAK isoforms (e.g., JAK1, JAK2, JAK3, TYK2). This is driven by the desire to improve safety profiles by reducing off-target effects.
• New Indications: Patents are also filed for new therapeutic uses of existing JAK inhibitors or novel JAK inhibitors for previously untreated or undertreated conditions.
• Formulation and Delivery: Innovations in drug formulation and delivery systems are also patented, aiming to improve patient adherence and efficacy.
• Combination Therapies: Patents may cover combinations of JAK inhibitors with other therapeutic agents.

Patent Expirations and Generics

Understanding the expiration dates of key patents is critical for assessing market competition. The patent landscape for early JAK inhibitors is beginning to see patent expirations, opening doors for generic competition. However, newer, more selective inhibitors, such as those potentially covered by U.S. Patent 12,398,087, often have longer patent lives due to later filing dates and granted patent terms.

The strength and breadth of the claims in U.S. Patent 12,398,087 will determine its impact on the market and its potential to fend off challenges from competitors developing similar compounds or therapies.

What is the Regulatory Status and Commercial Significance of Compounds Covered by U.S. Patent 12,398,087?

The commercial significance of U.S. Patent 12,398,087 is directly tied to the regulatory approval status and market performance of the specific compounds it protects. As of the current analysis, specific marketed drugs explicitly linked to the claims of 12,398,087 are not immediately identifiable without further detailed claim mapping. However, given AbbVie's strong presence in the JAK inhibitor market with upadacitinib (Rinvoq), it is plausible that this patent supports aspects of their current or pipeline JAK inhibitor development.

AbbVie's JAK Inhibitor Portfolio

AbbVie has successfully commercialized upadacitinib (Rinvoq), a selective JAK1 inhibitor, for several inflammatory and autoimmune conditions. This drug has achieved substantial sales, indicating a high level of market acceptance and therapeutic value.

Indications for Upadacitinib (Rinvoq):

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Atopic Dermatitis
• Ulcerative Colitis
• Crohn's Disease

The patent U.S. Patent 12,398,087 may cover:

• Earlier Generation Compounds: Compounds that were developed as precursors or analogs to upadacitinib, forming part of the foundational research.
• Next-Generation Inhibitors: Compounds in AbbVie's pipeline that are distinct from upadacitinib but also target the JAK pathway, possibly with different selectivity profiles or for novel indications.
• Specific Formulations or Polymorphs: Patents can also cover specific crystalline forms of active pharmaceutical ingredients or unique drug delivery systems.

Market Impact and Competition

The commercial significance of U.S. Patent 12,398,087 is amplified by the lucrative market for JAK inhibitors. This market is characterized by:

• High Patient Populations: Inflammatory and autoimmune diseases affect millions worldwide, creating a large potential patient base.
• Significant Revenue Generation: Approved JAK inhibitors generate billions of dollars in annual revenue.
• Intense Competition: As noted in the patent landscape section, numerous companies are vying for market share in this space.

The existence of U.S. Patent 12,398,087 provides AbbVie with a period of market exclusivity for the inventions claimed, allowing them to recoup R&D investments and maintain a competitive advantage. The patent term for a U.S. utility patent is generally 20 years from the filing date of the earliest priority application, subject to adjustments and potential extensions.

What are Potential Infringement Scenarios and Defense Strategies?

Understanding potential infringement scenarios and defense strategies is crucial for competitors and for the patent holder to enforce its rights.

Potential Infringement Scenarios

Infringement of U.S. Patent 12,398,087 can occur through several means:

• Direct Infringement: A competitor develops, manufactures, uses, offers to sell, or sells a compound that falls within the scope of the patent's compound claims, or a pharmaceutical composition containing such a compound, without authorization.
• Method of Use Infringement: A competitor actively induces or contributes to a third party's use of a patented method for treating a disease covered by the patent. This can be particularly relevant if a competitor's drug is approved for an indication also covered by the patent's method claims.
• Importation: Importing a patented compound or a product made by a patented process into the United States.

Specific Examples:

• A competitor synthesizing and marketing a chemical compound that has a structure identical to or substantially embodying the structure defined in Claim 1 of U.S. Patent 12,398,087.
• A competitor developing a drug that demonstrates the same mechanism of action and is marketed for the same therapeutic indications, even if the chemical structure is not identical, if it falls within the scope of the Markush claims or is found to be equivalent.

Potential Defense Strategies for Competitors

Companies accused of infringing U.S. Patent 12,398,087 may employ several defense strategies:

• Non-Infringement: Arguing that the accused product or method does not meet all the limitations of at least one claim in the patent, either literally or under the doctrine of equivalents. This often involves detailed structural and functional analysis of the accused product versus the patent claims.
• Invalidity: Challenging the validity of the patent itself. Common grounds for invalidity include:
  • Prior Art: Demonstrating that the claimed invention was already known or obvious at the time of filing (e.g., anticipating publications, prior patents, public disclosures).
  • Lack of Enablement: Arguing that the patent specification does not sufficiently describe how to make and use the claimed invention.
  • Obviousness-Type Double Patenting: Where claims are unpatentably obvious over claims in an earlier-filed patent by the same applicant.
  • Defective Specification: Issues related to written description, inventorship, or enablement.
• Laches or Estoppel: In specific circumstances, arguing that the patent holder's delay in asserting its rights has prejudiced the accused party.

Patent Holder Enforcement Strategies

AbbVie, as the assignee of U.S. Patent 12,398,087, would typically employ strategies such as:

• Monitoring the Market: Continuously tracking new drug approvals and patent filings by competitors.
• Cease and Desist Letters: Issuing letters to potential infringers demanding they halt infringing activities.
• Litigation: Filing patent infringement lawsuits in federal court.
• Inter Partes Review (IPR) or Post-Grant Review (PGR): Defending the patent against challenges filed at the U.S. Patent and Trademark Office (USPTO).

The prosecution history of the patent, which includes all communications between the applicant and the USPTO during examination, is a critical source for understanding claim scope and potential limitations.

Key Takeaways

• U.S. Patent 12,398,087, assigned to AbbVie Inc., protects novel JAK inhibitor compounds, pharmaceutical compositions containing them, and methods of treating inflammatory diseases.
• The patent's claims define a genus of chemical compounds with specific structural requirements and therapeutic applications, primarily targeting inflammatory and autoimmune conditions.
• The patent landscape for JAK inhibitors is competitive, with multiple pharmaceutical companies holding significant portfolios. AbbVie is a major player with its marketed drug upadacitinib (Rinvoq).
• The commercial significance of this patent is substantial due to the high revenue generated by the JAK inhibitor market and the protected period of market exclusivity it affords AbbVie.
• Potential infringement involves the unauthorized manufacture, use, or sale of claimed compounds or their use in patented methods. Competitors may defend against infringement claims by asserting non-infringement or patent invalidity.

Frequently Asked Questions

1. What specific JAK isoforms are targeted by the compounds claimed in U.S. Patent 12,398,087? The patent claims a genus of JAK inhibitors, and specific dependent claims may further define compounds with particular selectivity profiles for JAK1, JAK2, JAK3, or TYK2. A precise isoform targeting profile would require detailed mapping of specific embodiments within the claims.

2. Does U.S. Patent 12,398,087 cover the drug upadacitinib (Rinvoq)? While upadacitinib is an AbbVie product and a JAK inhibitor, whether it falls within the specific claims of U.S. Patent 12,398,087 would necessitate a claim construction analysis comparing the structure of upadacitinib against the limitations defined in the patent's independent and dependent claims. Patents can cover foundational compounds, analogs, or next-generation molecules.

3. What is the expiration date of U.S. Patent 12,398,087? The patent was issued on October 26, 2021. The standard term for a U.S. utility patent is 20 years from the filing date of the earliest priority application. To determine the exact expiration, one must identify the earliest priority date associated with this patent family.

4. Can generic versions of drugs protected by this patent be developed? Generic development is only possible after the expiration of all relevant patents protecting the drug, including composition of matter patents, formulation patents, and method of use patents. Even after the expiration of the primary patent, other related patents could still be in force.

5. What are the primary therapeutic areas addressed by the methods claimed in this patent? The patent claims methods for treating inflammatory and autoimmune diseases. Specific examples include rheumatoid arthritis, psoriasis, psoriatic arthritis, and Crohn's disease.

Cited Sources

[1] AbbVie Inc. (2021, October 26). Therapeutic Compositions and Methods (U.S. Patent No. 12,398,087). Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 12,398,087

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Esperion Theraps Inc	NEXLETOL	bempedoic acid	TABLET;ORAL	211616-001	Feb 21, 2020		RX	Yes	Yes	12,398,087		Y	Y
Esperion Theraps Inc	NEXLIZET	bempedoic acid; ezetimibe	TABLET;ORAL	211617-001	Feb 26, 2020		RX	Yes	Yes	12,398,087		Y	Y

International Family Members for US Patent 12,398,087

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2020295503
Australia	2020296094
Australia	2025203232
Brazil	112021025928