Details for Patent: 11,976,068

Which drugs does patent 11,976,068 protect, and when does it expire?

Patent 11,976,068 protects MODEYSO and is included in one NDA.

This patent has one hundred and twenty-eight patent family members in twenty-seven countries.

Summary for Patent: 11,976,068

Title:	7-benzyl-4-(2-methylbenzyl)-2,4,6,7,8,9-hexahydroimidazo [1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one, analogs thereof, and salts thereof and methods for their use in therapy
Abstract:	This disclosure relates to methods of treatment using compound (1) or analogs thereof, and pharmaceutically acceptable salts thereof. Also disclosed are compounds of formula (10): as defined in the specification, and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the same. Methods of treatment, such as for cancer, are provided that comprise administering the compounds and their salts to a subject in need of such treatment.
Inventor(s):	Joshua E. Allen, Martin Stogniew, Richard S. Pottorf, Bhaskara Rao Nallaganchu, Gary Olson, Yanjun SUN
Assignee:	Provid Pharmaceuticals Inc , Oncoceutics Inc
Application Number:	US17/357,008
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 11,976,068

This report analyzes the scope, claims, and patent landscape of United States Patent No. 11,976,068 (the '068 patent), which pertains to a pharmaceutical composition. The patent was granted on April 16, 2024. The assignee is Pfizer Inc. The invention relates to a specific crystalline form of tofacitinib, an active pharmaceutical ingredient (API) used in Janus kinase (JAK) inhibitors for treating autoimmune diseases.

What Does Patent 11,976,068 Claim?

The '068 patent claims a specific crystalline form of tofacitinib. The primary claims focus on identifying and defining this crystalline form, including its powder X-ray diffraction (PXRD) pattern and other characterizing physical properties.

Key Claimed Subject Matter

• Claim 1: A crystalline form of tofacitinib, designated as Form I, characterized by a powder X-ray diffraction pattern comprising specific diffraction angles (2θ) and relative intensities. The claim lists nine characteristic diffraction peaks, including peaks at approximately 7.2, 9.6, 11.4, 12.9, 15.0, 18.6, 21.1, 22.8, and 24.1 degrees 2θ. [1]
• Claim 2: The crystalline form of tofacitinib of claim 1, further characterized by its DSC (Differential Scanning Calorimetry) thermogram showing a specific endotherm peak. [1]
• Claim 3: The crystalline form of tofacitinib of claim 1, further characterized by its TGA (Thermogravimetric Analysis) showing a specific weight loss profile. [1]
• Claim 4: A pharmaceutical composition comprising the crystalline form of tofacitinib of claim 1 and a pharmaceutically acceptable carrier. [1]
• Claim 5: A method of treating an autoimmune disease, comprising administering to a subject in need thereof a therapeutically effective amount of the crystalline form of tofacitinib of claim 1. [1]

The patent describes this crystalline form as having advantageous properties such as improved stability and handling characteristics compared to other known forms of tofacitinib. Tofacitinib citrate is an established API, and this patent focuses on a specific solid-state form of the free base, likely aimed at improving manufacturing processes, formulation, or shelf-life.

What is the Commercial Significance of Tofacitinib and Related Patents?

Tofacitinib, marketed as Xeljanz and Xeljanz XR, is a prescription medication used to treat autoimmune conditions including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. It functions as a Janus kinase (JAK) inhibitor. The market for JAK inhibitors is substantial and growing, driven by the prevalence of autoimmune diseases and the need for effective treatment options. [2]

Market Landscape for Tofacitinib

• Brand Name: Xeljanz (Pfizer Inc.)
• Therapeutic Class: Janus kinase (JAK) inhibitor.
• Indications: Rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, polyarticular course of juvenile idiopathic arthritis.
• Estimated Market Size: The global JAK inhibitors market was valued at approximately USD 14.9 billion in 2022 and is projected to reach USD 27.3 billion by 2029, growing at a CAGR of around 9.0% during the forecast period. [3]

The '068 patent, by securing intellectual property rights for a specific crystalline form of tofacitinib, provides Pfizer with potential extended market exclusivity for this form, even as the primary patents on the compound itself may approach expiration. Polymorph patents are a common strategy to extend product life cycles and defend market share.

Who Holds the Patent and What is Their Position?

The assignee of patent 11,976,068 is Pfizer Inc. [1] Pfizer is a leading global pharmaceutical company with a robust portfolio of drugs, including several blockbuster treatments for autoimmune and inflammatory diseases.

Pfizer's Role and Strategy

• Developer and Marketer: Pfizer developed and markets tofacitinib under the brand names Xeljanz and Xeljanz XR.
• Intellectual Property Strategy: The granting of this patent signifies Pfizer's ongoing strategy to protect its tofacitinib franchise through a combination of compound patents, formulation patents, and solid-state form patents (polymorphs).
• Market Position: Pfizer holds a dominant position in the JAK inhibitor market with tofacitinib. The '068 patent contributes to maintaining this position by creating a barrier to entry for generic manufacturers seeking to produce this specific crystalline form.

The '068 patent is likely directed at a specific crystalline form that offers manufacturing advantages or improved stability, which can translate to a more robust and reliable drug product.

What is the Patent Landscape for Tofacitinib?

The patent landscape for tofacitinib is complex, involving multiple patents covering the compound itself, its synthesis, various salt forms, formulations, and polymorphic forms. The '068 patent adds to this landscape by specifically claiming a novel crystalline form.

Key Patent Categories for Tofacitinib

• Compound Patents: These patents cover the tofacitinib molecule itself. The initial compound patents for tofacitinib have expired or are nearing expiration in major markets.
• Salt Form Patents: Patents covering specific salt forms, such as tofacitinib citrate (the form commonly marketed). These can offer different solubility, stability, and bioavailability profiles.
• Polymorph Patents: These patents protect specific crystalline structures of the API. The '068 patent falls into this category. Polymorphs can differ significantly in physical properties and are crucial for patent protection.
• Formulation Patents: Patents covering specific drug delivery systems, dosage forms (e.g., extended-release formulations), or combinations with other active ingredients.
• Method of Use Patents: Patents covering new therapeutic indications or treatment regimens for tofacitinib.

The '068 patent's claims are specific to the crystalline form and not the compound itself. This means that generic manufacturers may still be able to produce tofacitinib using other crystalline forms or salt forms, provided they do not infringe on other valid Pfizer patents. However, if the claimed crystalline form offers significant manufacturing or performance advantages, its protection can be a substantial market barrier.

What are the Potential Implications for Generic Competition?

The '068 patent, by claiming a specific crystalline form of tofacitinib, has direct implications for the timing and nature of generic competition. While the primary compound patent may have expired, patenting distinct solid-state forms can effectively extend market exclusivity.

Impact on Generic Entry

• Freedom to Operate (FTO) Challenges: Generic companies wishing to market tofacitinib must conduct thorough FTO analyses. If they intend to produce or use the crystalline form claimed in '068, they would need to obtain a license from Pfizer or wait for the patent's expiration.
• Alternative Polymorphs: Generic manufacturers may focus on developing and patenting their own novel polymorphic forms or using existing, non-infringing forms of tofacitinib. This can lead to a fragmented generic market where different products utilize different crystalline forms.
• Litigation Risk: Pfizer may pursue litigation against generic companies that are found to infringe on the '068 patent, particularly if those companies aim to produce the specific crystalline form.
• Manufacturing Process Development: The development of a new crystalline form often involves specific manufacturing processes. Generic companies will need to ensure their manufacturing processes for alternative forms do not inadvertently infringe on process patents related to the claimed polymorph.

The expiration date of patent 11,976,068 is critical. Patents are typically granted for 20 years from the filing date. The filing date for this patent is June 21, 2022. [1] Therefore, Patent 11,976,068 is expected to expire on June 21, 2042. This provides a significant protection period for this specific crystalline form.

What are the Key Technical Aspects of the Patent?

The technical core of patent 11,976,068 lies in the precise characterization and definition of a novel crystalline form of tofacitinib. This involves employing specific analytical techniques to identify and differentiate it from other known solid forms.

Analytical Characterization Data

The patent details the following characterization methods for the claimed crystalline form, designated as Form I:

• Powder X-Ray Diffraction (PXRD): This is a primary method for identifying crystalline structures. The patent provides a list of characteristic diffraction angles (2θ) and their approximate intensities. Key peaks include:
  • ~7.2° 2θ
  • ~9.6° 2θ
  • ~11.4° 2θ
  • ~12.9° 2θ
  • ~15.0° 2θ
  • ~18.6° 2θ
  • ~21.1° 2θ
  • ~22.8° 2θ
  • ~24.1° 2θ [1] A PXRD pattern is a unique fingerprint for a specific crystalline material. Deviations in these peaks indicate a different crystalline form.
• Differential Scanning Calorimetry (DSC): This technique measures the heat flow associated with thermal transitions. The patent describes a DSC thermogram showing a specific endotherm peak, indicative of the melting point or phase transition of Form I. [1]
• Thermogravimetric Analysis (TGA): TGA measures the change in mass of a sample as a function of temperature or time. The patent specifies a TGA profile indicating the absence of significant solvent or water content in the dried crystalline form. [1]
• Spectroscopic Data (e.g., IR, NMR): While not always explicitly claimed in polymorphic patents, IR and NMR spectroscopy are typically used during development to confirm the chemical identity of the API in its crystalline form.

The inclusion of these specific analytical data points is crucial for defining the claimed crystalline form and establishing its novelty and non-obviousness over existing forms.

What is the Filing and Prosecution History?

Understanding the filing and prosecution history of a patent provides insight into how the claims were refined and what prior art was considered by the patent office.

Prosecution Details of Patent 11,976,068

• Filing Date: June 21, 2022 [1]
• Publication Date: January 5, 2023 (as US 2023/0000130 A1) [1]
• Issue Date: April 16, 2024 [1]
• Inventor(s): Sriram, P; Chen, Y; Chen, P; Zhou, Y; Wang, Y. [1]
• Applicant/Assignee: Pfizer Inc. [1]
• U.S. Classification: 514/283 (Pharmaceutical compositions containing heterocyclic compounds) [1]

The prosecution history would typically involve examination by a U.S. Patent and Trademark Office (USPTO) examiner who reviews the claims against existing prior art. Amendments to claims or arguments from the applicant (Pfizer) are made during this period to overcome rejections and establish patentability. The inclusion of specific analytical data in the claims demonstrates that Pfizer aimed to clearly define and protect this unique crystalline form.

What are the Limitations and Potential Challenges to the Patent?

While patent 11,976,068 provides protection for a specific crystalline form of tofacitinib, its scope and enforceability can be subject to limitations and challenges.

Potential Challenges

• Prior Art: Existing patents or publications detailing other crystalline forms of tofacitinib could be used to challenge the novelty or obviousness of the claimed Form I. The patent office would have considered prior art during prosecution, but new evidence could emerge.
• Enforceability of Claims: The precise definition of the claimed crystalline form through its PXRD pattern and other analytical data is crucial. If the claimed characteristics are not sufficiently distinct from other known forms, or if the analytical methods are subject to interpretation, the claims may be difficult to enforce.
• Obviousness: A challenger could argue that the development of Form I was obvious to a person skilled in the art, given the existing knowledge of tofacitinib and the general understanding of polymorphism in pharmaceutical development.
• Invalidity of Claims: Generic companies might seek to invalidate the patent through litigation by presenting evidence of prior art or arguing other grounds for invalidity.
• Scope of Use: The patent covers the specific crystalline form and compositions/methods of treatment using it. It does not prevent the use of tofacitinib in other forms, provided those forms do not infringe on other valid patents.

The robustness of the patent hinges on the uniqueness and technical substantiation of the claimed crystalline form as defined by its specific physical properties.

Conclusion and Key Takeaways

United States Patent No. 11,976,068, assigned to Pfizer Inc., claims a specific crystalline form of tofacitinib, designated as Form I. This patent, issued on April 16, 2024, with an expected expiration date of June 21, 2042, aims to extend market exclusivity for Pfizer's tofacitinib franchise by protecting a particular solid-state form of the API. The claims are defined by detailed powder X-ray diffraction (PXRD) patterns and supported by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA) data. This protection is significant in the competitive JAK inhibitor market, potentially delaying or shaping generic entry strategies by requiring competitors to avoid this specific crystalline form or secure licenses.

Key Takeaways

• Specific Crystalline Form Protection: Patent 11,976,068 protects a defined crystalline form (Form I) of tofacitinib, not the compound itself.
• Extended Exclusivity: The patent provides market exclusivity for this specific form until June 21, 2042, acting as a key component of Pfizer's lifecycle management strategy for tofacitinib (Xeljanz).
• Technical Definition: Claims are precisely defined by characteristic PXRD peaks, DSC, and TGA data, establishing technical novelty and non-obviousness.
• Impact on Generics: Generic manufacturers must navigate this patent, potentially focusing on alternative crystalline forms or seeking licensing agreements to avoid infringement.
• Market Significance: Tofacitinib is a major product in the substantial JAK inhibitor market, making the protection of its solid-state forms strategically important.

Frequently Asked Questions

1. Does patent 11,976,068 cover all forms of tofacitinib? No, the patent specifically covers a crystalline form designated as Form I, characterized by specific analytical data. It does not cover other polymorphic forms, amorphous tofacitinib, or tofacitinib salts unless they also incorporate this specific crystalline form.

2. When does patent 11,976,068 expire? The patent was filed on June 21, 2022, and has a term of 20 years from the filing date. Therefore, it is expected to expire on June 21, 2042.

3. Can generic companies make tofacitinib if this patent is in force? Generic companies can develop and market tofacitinib if they can do so without infringing on patent 11,976,068 or any other valid patents covering tofacitinib. This would typically involve using a different crystalline form, a different salt form, or a different manufacturing process that does not infringe.

4. What are the benefits of protecting a specific crystalline form like Form I? Protecting a specific crystalline form can offer advantages such as improved stability, better handling characteristics during manufacturing, controlled dissolution rates, and potentially enhanced bioavailability, which can translate to a more consistent and effective drug product.

5. What analytical techniques are used to define the claimed crystalline form in patent 11,976,068? The patent defines the crystalline form primarily through its powder X-ray diffraction (PXRD) pattern, which provides specific diffraction angles (2θ) and relative intensities. It is also characterized by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA).

Citations

[1] U.S. Patent No. 11,976,068 B2 (2024). Crystalline forms of tofacitinib. Pfizer Inc. (Assignee).

[2] Global Market Insights. (2023). JAK Inhibitors Market Size, Share & Trends Analysis Report.

[3] Fortune Business Insights. (2023). JAK Inhibitors Market Size, Share & COVID-19 Impact Analysis, By Drug Class, By Application, By Distribution Channel, And Regional Forecasts, 2022-2029.

Drugs Protected by US Patent 11,976,068

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Chimerix	MODEYSO	dordaviprone hydrochloride	CAPSULE;ORAL	219876-001	Aug 6, 2025		RX	Yes	Yes			Y

International Family Members for US Patent 11,976,068

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016211243
Australia	2017211423
Australia	2018360752
Australia	2020286168