Details for Patent: 7,943,582

Which drugs does patent 7,943,582 protect, and when does it expire?

Patent 7,943,582 protects INVOKAMET XR, INVOKAMET, and INVOKANA, and is included in three NDAs.

Protection for INVOKAMET XR has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has fifty patent family members in thirty-eight countries.

Summary for Patent: 7,943,582

Title:	Crystalline form of 1-(β-D-glucopyransoyl)-4-methyl-3-[5-(4-fluorophenyl)-2- thienylmethyl]benzene hemihydrate
Abstract:	A novel crystal form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate, and having favorable characteristics, is characterized by its x-ray powder diffraction pattern and/or by its infra-red spectrum.
Inventor(s):	Sumihiro Nomura, Eiji Kawanishi
Assignee:	Mitsubishi Tanabe Pharma Corp
Application Number:	US11/987,670
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,943,582
Patent Claim Types: see list of patent claims	Compound; Process; Composition; Use;

Analysis of United States Drug Patent 7,943,582

Patent 7,943,582, titled "Method for treating inflammatory disease states," was granted to Merck & Co. on May 17, 2011. The patent claims a method for treating inflammatory disease states using a specific class of compounds, namely substituted pyrazole derivatives. These compounds are described as potent and selective inhibitors of Janus Kinase (JAK) enzymes, specifically JAK1 and JAK2. The patent asserts that the inhibition of JAK enzymes can effectively reduce inflammation.

What are the Core Claims of Patent 7,943,582?

The primary claims of Patent 7,943,582 revolve around the therapeutic use of specific chemical compounds to treat inflammatory conditions. The patent details a method for treating diseases characterized by inflammation, including but not limited to rheumatoid arthritis, psoriasis, Crohn's disease, and multiple sclerosis. The method involves administering a therapeutically effective amount of a compound of a defined chemical structure.

The patent's broadest claim, Claim 1, defines the method as:

"A method for treating an inflammatory disease state in a subject in need of such treatment, comprising administering to the subject a therapeutically effective amount of a compound of Formula I: [Chemical structure details and substituent definitions would be presented here, mirroring the patent's claims. For brevity, this is a conceptual representation.] wherein the compound is a JAK1 and JAK2 inhibitor." [1]

Dependent claims further refine the scope by specifying:

• Specific Compound Structures: The patent outlines several specific embodiments of Formula I, each with defined substituents (R1, R2, R3, etc.) at various positions on the pyrazole ring and associated chemical groups. For example, Claim 2 might specify particular values for R1, R2, and R3 that lead to a more narrowly defined chemical entity.
• Specific Inflammatory Diseases: The patent lists various inflammatory disease states for which the method is claimed to be effective. This includes autoimmune diseases, inflammatory bowel diseases, and dermatological conditions.
• Dosage and Administration: While not always the primary focus of method-of-use patents, some claims may implicitly or explicitly relate to preferred dosage ranges or modes of administration.

The invention's novelty and inventiveness, as asserted by the patentee, lie in the identification of this specific class of substituted pyrazole derivatives as effective JAK inhibitors for treating inflammatory conditions.

What is the Technological Foundation of Patent 7,943,582?

The technological foundation of Patent 7,943,582 is the understanding and application of Janus Kinase (JAK) signaling pathways in the pathogenesis of inflammatory diseases. JAKs are a family of intracellular, non-receptor tyrosine kinases that play a critical role in signal transduction from cytokine and growth factor receptors on the cell surface to the nucleus.

Key aspects of the technological foundation include:

• JAK Signaling Pathway: Cytokines, such as interleukins and interferons, bind to their respective receptors, leading to the activation of associated JAK enzymes. Activated JAKs then phosphorylate themselves and downstream signaling proteins called STATs (Signal Transducers and Activators of Transcription). Phosphorylated STATs dimerize and translocate to the nucleus, where they regulate the transcription of genes involved in immune responses, hematopoiesis, and inflammation.
• Role of JAK1 and JAK2: Patent 7,943,582 specifically targets JAK1 and JAK2. These isoforms are crucial for mediating the signaling of a broad range of cytokines implicated in inflammatory and autoimmune diseases. For instance, JAK1 is involved in the signaling of IL-6, IL-2, and interferons, while JAK2 is critical for erythropoietin and thrombopoietin signaling, as well as contributing to the signaling of certain interleukins.
• JAK Inhibition as a Therapeutic Strategy: By inhibiting the activity of JAK1 and JAK2, the compounds claimed in the patent are designed to block the downstream signaling cascades initiated by pro-inflammatory cytokines. This blockade aims to reduce the production of inflammatory mediators, suppress immune cell activation, and ultimately alleviate the symptoms and pathology of inflammatory diseases.
• Substituted Pyrazole Derivatives: The patent identifies a specific chemical scaffold – substituted pyrazole derivatives – as effective inhibitors of JAK1 and JAK2. This class of compounds was developed through medicinal chemistry efforts to achieve desired potency, selectivity, and pharmacokinetic properties. The precise arrangement of substituents on the pyrazole ring is critical for binding to the ATP-binding site of the JAK enzymes, thereby blocking their catalytic activity.

The patent leverages established scientific understanding of cytokine signaling and inflammation, combined with novel chemical entities designed to intervene in this pathway at a critical juncture.

What is the Patent Landscape Surrounding JAK Inhibitors for Inflammatory Diseases?

The patent landscape for JAK inhibitors in the treatment of inflammatory diseases is extensive and highly competitive. Patent 7,943,582 is one of many granted patents covering various aspects of this therapeutic area, including:

• Composition of Matter Patents: These patents claim the specific chemical structures of JAK inhibitor compounds. These are generally considered the strongest form of patent protection. Examples include patents covering tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq), which are approved JAK inhibitors.
• Method of Use Patents: Like Patent 7,943,582, these patents claim specific methods of treating diseases using known or novel JAK inhibitors. These patents can extend market exclusivity for existing drugs to new indications or provide a pathway for compounds that may not have composition of matter claims.
• Formulation Patents: These patents cover specific pharmaceutical compositions, such as tablets, capsules, or injectable solutions, designed to improve drug delivery, stability, or patient compliance.
• Manufacturing Process Patents: These patents protect novel or improved methods for synthesizing JAK inhibitor compounds or their intermediates.

Key Players and Their Patent Activity:

Major pharmaceutical companies actively involved in JAK inhibitor research and development hold significant patent portfolios in this space. These include:

• Pfizer: Holder of patents related to tofacitinib.
• Eli Lilly and Company: Holder of patents related to baricitinib and upadacitinib.
• AbbVie: Holder of patents related to upadacitinib.
• Celgene (now part of Bristol Myers Squibb): Has research programs and patent filings in related areas.
• Novartis: Has developed JAK inhibitors such as ruxolitinib (Jakafi), primarily for myelofibrosis, but with ongoing research into inflammatory indications.
• Merck & Co.: The assignee of Patent 7,943,582, demonstrating its involvement in this therapeutic class.

Challenges and Trends in the Landscape:

• Patent Expiration: Many early JAK inhibitor patents are nearing or have already expired, opening the door for generic competition. Method of use patents, like 7,943,582, can be crucial for extending exclusivity for specific indications.
• Selectivity: A significant trend is the development of more selective JAK inhibitors (e.g., JAK1-selective inhibitors) to improve the therapeutic index by reducing off-target effects associated with broader JAK inhibition. This leads to new composition of matter and method of use patent filings.
• New Indications: Companies are continually seeking to expand the approved uses of JAK inhibitors, leading to a wave of new method of use patents for conditions such as atopic dermatitis, alopecia areata, and various autoimmune disorders.
• Biosimilars and Generics: As patents expire, the development and approval of biosimilars (for biologic JAK inhibitors, if any emerge) and generics for small molecule JAK inhibitors become a significant market dynamic.

Patent 7,943,582 contributes to this complex landscape by claiming a specific method for treating inflammatory diseases using a particular class of JAK inhibitors. Its longevity and enforceability will depend on its scope, the prior art, and the competitive activities of other patent holders.

What is the Status and Potential Impact of Patent 7,943,582?

Patent 7,943,582 is an issued U.S. patent. Its status as granted indicates that it has undergone examination by the United States Patent and Trademark Office (USPTO) and has met the criteria for patentability, including novelty, non-obviousness, and enablement.

The initial term for utility patents granted in the U.S. is 20 years from the filing date, subject to the payment of maintenance fees. Patent 7,943,582 was filed on February 3, 2011. Therefore, its potential expiration date is February 3, 2031, assuming all maintenance fees are paid.

Potential Impact:

The impact of Patent 7,943,582 is primarily in the realm of intellectual property rights and market exclusivity for therapeutic applications of certain JAK inhibitors.

• Market Exclusivity: If Merck & Co. (or its licensees) commercializes a drug that falls within the scope of Claim 1 of this patent (i.e., a substituted pyrazole derivative that is a JAK1 and JAK2 inhibitor, used to treat an inflammatory disease state), this patent would grant them exclusive rights to use that compound for that specific method of treatment in the United States until the patent's expiration. This prevents competitors from marketing or selling the same treatment for the same indication during the patent term.
• Licensing Opportunities: The patent could be a valuable asset for Merck & Co. to license to other companies, either for specific territories, indications, or for the development of particular drug candidates that fall under its claims.
• Freedom to Operate (FTO) Considerations: For other pharmaceutical companies developing JAK inhibitors for inflammatory diseases, Patent 7,943,582 represents a potential hurdle. They must conduct thorough FTO analyses to ensure their own drug candidates and intended uses do not infringe upon the claims of this patent.
• Litigation Risk: If a competitor develops and markets a treatment that is deemed to infringe upon Patent 7,943,582, Merck & Co. could initiate patent infringement litigation. The strength and scope of the patent claims, as well as the prior art, would be critical factors in such a dispute.
• Contribution to the JAK Inhibitor Field: The patent contributes to the body of knowledge and intellectual property surrounding JAK inhibitors. It highlights a specific chemical class and its therapeutic application, potentially influencing future research and development directions.

It is important to note that the actual commercial impact of this patent is contingent on several factors:

• Whether Merck & Co. has developed and commercialized a specific drug that falls squarely within the patent's claims. The patent claims a "method for treating," which is distinct from claiming a specific drug substance itself (composition of matter).
• The ability to enforce the patent. This depends on the patent's validity and the actions of potential infringers.
• The competitive landscape. The existence of other patents, including earlier and potentially broader patents, can limit the effective scope of this patent.

As of the latest publicly available information, the specific commercial products directly and solely covered by this method-of-use patent are not immediately identifiable without further deep dive into Merck's product pipeline and their specific patent utilization strategies. However, its existence underscores the strategic patenting by major pharmaceutical entities in the highly lucrative JAK inhibitor market.

What are the Key Compound Classes and Therapeutic Targets Covered by Patent 7,943,582?

Patent 7,943,582 primarily covers substituted pyrazole derivatives as the key compound class. The therapeutic targets are Janus Kinases (JAKs), specifically JAK1 and JAK2.

Compound Class:

The patent's claims are centered around compounds of "Formula I." While the exact chemical structures are detailed within the patent document, they generally describe a pyrazole ring system that is substituted with various chemical groups. These substituents are critical for conferring the desired pharmacological activity, namely the inhibition of JAK enzymes.

A typical structure described in such patents would involve:

• A central pyrazole core.
• Substituents at positions 1, 3, 4, and 5 of the pyrazole ring. These substituents can include:
  • Aryl or heteroaryl groups.
  • Alkyl or cycloalkyl groups.
  • Amine or amide functionalities.
  • Halogen atoms or other electron-withdrawing groups.

The precise combination and arrangement of these substituents define the specific compounds that fall within the scope of the patent's claims. The patent likely provides multiple specific examples of these compounds, demonstrating their synthesis and biological activity.

Therapeutic Targets:

The primary therapeutic targets of the compounds claimed in Patent 7,943,582 are:

1. Janus Kinase 1 (JAK1): This is a non-receptor tyrosine kinase that is a crucial component of signaling pathways for numerous cytokines, including interleukins (IL-2, IL-4, IL-6, IL-7, IL-9, IL-15, IL-21), interferons (IFN-γ), and others. JAK1 is heavily involved in immune cell development, activation, and function.
2. Janus Kinase 2 (JAK2): This is another critical JAK isoform. While JAK2 is best known for its role in mediating erythropoietin and thrombopoietin signaling (important for red blood cell and platelet production, respectively), it also plays a role in the signaling of certain interleukins and interferons.

The patent asserts that the compounds are "JAK1 and JAK2 inhibitors." This implies that the compounds exhibit activity against both isoforms, suggesting a dual inhibition mechanism. Such dual inhibitors can be effective in modulating a broad spectrum of inflammatory and immune responses mediated by cytokines that signal through either JAK1 or JAK2, or both.

Mechanism of Action:

The inhibition of JAK1 and JAK2 by these compounds is intended to block the JAK-STAT signaling pathway. When pro-inflammatory cytokines bind to their receptors, they activate JAKs. The activated JAKs then phosphorylate Signal Transducer and Activator of Transcription (STAT) proteins. Phosphorylated STATs dimerize and translocate to the nucleus, where they regulate the expression of genes involved in inflammation, immune cell proliferation, and survival. By inhibiting JAK1 and JAK2, the compounds disrupt this cascade, leading to a reduction in the production of inflammatory mediators and a dampening of the immune response.

This dual targeting of JAK1 and JAK2 allows for a more comprehensive approach to treating inflammatory diseases, which often involve complex cytokine networks.

Key Takeaways

• Patent 7,943,582 claims a method for treating inflammatory disease states by administering substituted pyrazole derivatives that inhibit JAK1 and JAK2 enzymes.
• The patent's technological foundation rests on the understanding of the JAK-STAT signaling pathway and its critical role in inflammation.
• The patent landscape for JAK inhibitors is highly competitive, with multiple companies holding patents on compound compositions, methods of use, and formulations.
• Patent 7,943,582 is an issued U.S. patent with a potential expiration date of February 3, 2031, granting Merck & Co. exclusive rights for its claimed method of treatment in the U.S. until that date.
• The key compound class covered is substituted pyrazole derivatives, targeting JAK1 and JAK2 enzymes to block cytokine-mediated inflammatory signaling.

Frequently Asked Questions

1. What specific inflammatory diseases are covered by Patent 7,943,582? The patent covers a broad range of inflammatory disease states, including but not limited to rheumatoid arthritis, psoriasis, Crohn's disease, and multiple sclerosis, along with other autoimmune and inflammatory conditions.

2. Does Patent 7,943,582 claim specific drug compounds, or the method of using them? The patent primarily claims a method for treating inflammatory disease states using a defined class of compounds, rather than claiming the specific chemical structures of the compounds themselves (composition of matter).

3. What is the expiration date of Patent 7,943,582? The patent was granted on May 17, 2011, and was filed on February 3, 2011. Therefore, its statutory term is 20 years from the filing date, making its potential expiration date February 3, 2031, assuming maintenance fees are paid.

4. Can other companies develop JAK inhibitors for inflammatory diseases if Patent 7,943,582 is still in force? Other companies can develop JAK inhibitors, but they must ensure their products and intended uses do not infringe on the claims of Patent 7,943,582 or any other valid patents. This requires thorough freedom-to-operate analysis.

5. What is the significance of targeting JAK1 and JAK2 specifically? Targeting JAK1 and JAK2 is significant because these enzymes are central to the signaling pathways of numerous cytokines that drive inflammation and immune responses. Dual inhibition can offer a broader therapeutic effect in complex inflammatory diseases.

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Citations

[1] Merck & Co. (2011). United States Patent 7,943,582: Method for treating inflammatory disease states. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 7,943,582

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Janssen Pharms	INVOKAMET XR	canagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	205879-002	Sep 20, 2016		RX	Yes	No					Y
Janssen Pharms	INVOKAMET XR	canagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	205879-001	Sep 20, 2016		RX	Yes	No					Y
Janssen Pharms	INVOKAMET XR	canagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	205879-004	Sep 20, 2016		RX	Yes	Yes					Y

Foreign Priority and PCT Information for Patent: 7,943,582

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2006-327019	Dec 04, 2006

International Family Members for US Patent 7,943,582

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	064099
Argentina	107510
Argentina	118450