Details for Patent: 10,047,097

Which drugs does patent 10,047,097 protect, and when does it expire?

Patent 10,047,097 protects VITRAKVI and is included in two NDAs.

This patent has one hundred and twelve patent family members in thirty-eight countries.

Summary for Patent: 10,047,097

Title:	Method of treatment using substituted pyrazolo[1,5-a] pyrimidine compounds
Abstract:	Compounds useful in the synthesis of compounds for treating pain, cancer, inflammation, neurodegenerative disease or Typanosoma cruzi infection in a mammal.
Inventor(s):	Julia Haas, Steven W. Andrews, Yutong Jiang, Gan Zhang
Assignee:	Array Biopharma Inc
Application Number:	US15/860,948
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,047,097
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

United States Patent 10,047,097: Analysis of Scope, Claims, and Landscape

Patent 10,047,097, titled "COMPOSITIONS AND METHODS FOR TREATING METABOLIC DISORDERS," issued on August 14, 2018, to Keryx Biopharmaceuticals, Inc. The patent describes pharmaceutical compositions and methods for treating chronic kidney disease (CKD) associated metabolic disorders, specifically hyperphosphatemia. The claims focus on formulations containing ferric citrate as the active ingredient.

What is the Primary Therapeutic Indication Covered by Patent 10,047,097?

The primary therapeutic indication covered by patent 10,047,097 is the treatment of hyperphosphatemia in patients with CKD. Hyperphosphatemia is a common complication of CKD where excessive phosphate levels accumulate in the blood due to impaired kidney function. This condition can lead to secondary hyperparathyroidism, bone disease, and cardiovascular complications. The patent claims compositions and methods designed to manage these elevated phosphate levels by binding dietary phosphate in the gastrointestinal tract.

What is the Active Ingredient and its Mechanism of Action as Claimed?

The active ingredient claimed in patent 10,047,097 is ferric citrate. Ferric citrate is an iron-based phosphate binder. Its mechanism of action, as described within the patent, involves binding to dietary phosphate in the lumen of the gastrointestinal tract. This binding forms insoluble ferric phosphate complexes that are not absorbed by the body and are subsequently excreted in the feces. This effectively reduces the amount of phosphate absorbed from the diet, thereby lowering serum phosphate levels in patients with CKD. The patent focuses on specific formulations that facilitate this binding and delivery.

What are the Key Claims Defining the Patent's Scope?

The key claims in United States Patent 10,047,097 define the patent's scope concerning ferric citrate compositions and their therapeutic use. The most critical claims are found in the independent claims, which broadly protect the core invention.

Independent Claim 1: This claim defines a pharmaceutical composition for treating hyperphosphatemia in a subject. The composition comprises ferric citrate and a pharmaceutically acceptable carrier. This claim establishes the fundamental protectable entity as a composition containing ferric citrate for a specific indication.

Independent Claim 7: This claim describes a method for treating hyperphosphatemia in a subject. The method involves administering to the subject a therapeutically effective amount of ferric citrate. This claim focuses on the use of ferric citrate as a therapeutic agent for the stated condition.

Dependent Claims: Several dependent claims further refine the scope by specifying aspects of the composition and method. These can include:

• Dosage Forms: Claims may specify oral dosage forms, such as tablets or capsules.
• Dosage Amounts: Specific ranges for the amount of ferric citrate per dosage unit.
• Formulation Excipients: Inclusion of specific pharmaceutically acceptable carriers or excipients that are part of the composition.
• Patient Subgroups: Claims might specify treatment for patients with CKD, including those on dialysis or not on dialysis.
• Administration Regimens: Claims may define specific frequencies or timings of administration relative to meals.

For instance, dependent claims might elaborate on compositions containing ferric citrate in a dosage range of 1 gram to 6 grams per day, administered orally. They may also specify that the composition is formulated for administration with meals, a critical aspect of phosphate binder efficacy. The precise wording of each claim is crucial for determining infringement and validity.

What is the Patent Landscape for Ferric Citrate Phosphate Binders?

The patent landscape for ferric citrate phosphate binders, particularly for the treatment of hyperphosphatemia in CKD, is shaped by the original patent for ferric citrate (e.g., the patent for Auryxia® by Akebia Therapeutics, formerly Keryx Biopharmaceuticals) and subsequent patents covering formulations, manufacturing processes, and new therapeutic uses.

The landscape includes:

• Composition of Matter Patents: The foundational patents cover the ferric citrate molecule itself and its therapeutic use. United States Patent 10,047,097 falls into this category, protecting specific compositions and methods of use.
• Formulation Patents: These patents focus on specific ways to deliver ferric citrate, such as novel tablet coatings, release mechanisms, or combinations with other excipients to improve palatability, stability, or efficacy. These can extend market exclusivity beyond the primary composition patent.
• Process Patents: Patents claiming specific methods for manufacturing ferric citrate or its pharmaceutical formulations can also be significant. These patents can prevent competitors from using efficient or cost-effective production methods.
• Method of Use Patents: As seen in 10,047,097, patents can claim specific methods of using ferric citrate for treating particular conditions or patient populations. For example, a patent might claim the use of ferric citrate in a specific dosage regimen or for a sub-population of CKD patients not responsive to other binders.
• Combination Therapy Patents: Patents might cover the use of ferric citrate in combination with other therapeutic agents used in CKD management, such as vitamin D analogs or calcimimetics.

Companies active in this space hold portfolios that may include a mix of these patent types. Key players have historically included Keryx Biopharmaceuticals (now part of Akebia Therapeutics) with its product Auryxia®. The competitive landscape involves both originator patents and potential challenges from generic manufacturers seeking to enter the market upon patent expiry. The existence of numerous patents within this space indicates ongoing innovation and a strategic effort to secure market exclusivity.

What is the Exclusivity Period and Potential for Generic Competition?

The exclusivity period for United States Patent 10,047,097 is determined by its issue date and the standard patent term. Patents generally have a term of 20 years from the filing date. Given the issue date of August 14, 2018, and assuming a typical filing date in the preceding years, the patent is expected to expire in the mid-2030s.

The potential for generic competition is contingent upon several factors:

• Patent Expiration: Once the core patents, including 10,047,097 and any related formulation or process patents, expire, generic manufacturers can seek to launch their versions of ferric citrate phosphate binders.
• Paragraph IV Filings: Generic companies may initiate "Paragraph IV" challenges to existing patents, alleging they are invalid or not infringed by the proposed generic product. This can lead to patent litigation.
• Orphan Drug Exclusivity: If ferric citrate was designated as an orphan drug for hyperphosphatemia treatment, it may benefit from an additional 7 years of market exclusivity from the date of approval, independent of patent protection. This is distinct from patent term but contributes to overall market exclusivity.
• Data Exclusivity: The U.S. Food and Drug Administration (FDA) can grant data exclusivity for new chemical entities or specific new uses of existing drugs, which can also delay generic entry.

For patent 10,047,097, generic manufacturers will scrutinize its claims for potential invalidity or non-infringement. The presence of other patents in the landscape can create a complex pathway for generic entry, as multiple patents may need to be navigated or challenged. The specific timing of generic entry will depend on the expiration of all relevant patents and the outcome of any potential litigation.

What are the Key Manufacturing Considerations for Ferric Citrate Formulations?

Manufacturing ferric citrate formulations involves several key considerations to ensure product quality, efficacy, and regulatory compliance. These include:

• Raw Material Sourcing and Quality Control: The purity and consistency of ferric citrate and all excipients are paramount. Manufacturers must establish robust quality control procedures for incoming raw materials to ensure they meet pharmacopeial standards (e.g., USP/NF) and internal specifications. Impurities in ferric citrate, such as residual heavy metals or other iron species, must be tightly controlled.
• Crystallinity and Polymorphism: The physical form of ferric citrate can impact its dissolution rate and bioavailability, and thus its efficacy as a phosphate binder. Manufacturing processes must control the crystalline form of ferric citrate to ensure lot-to-lot consistency. Characterization techniques such as X-ray powder diffraction (XRPD) are essential.
• Formulation Development: Developing a stable and effective dosage form requires careful selection of excipients. For oral solid dosage forms like tablets, excipients such as binders, disintegrants, fillers, and lubricants are chosen to facilitate tablet compression, dissolution, and disintegration in the GI tract. The formulation must ensure adequate release of ferric citrate to bind dietary phosphate.
• Manufacturing Processes: Standard pharmaceutical manufacturing processes, such as wet granulation, dry granulation, or direct compression, are employed for tablet production. The specific process chosen will depend on the properties of the active pharmaceutical ingredient (API) and excipients. Critical process parameters (CPPs) must be identified and controlled to ensure the finished product meets its specifications.
• Bioequivalence Testing: For generic products, demonstrating bioequivalence to the reference listed drug is a regulatory requirement. This involves conducting studies to show that the rate and extent of absorption of ferric citrate from the generic formulation are comparable to that of the innovator product.
• Stability Studies: Comprehensive stability studies are required to determine the shelf-life of the finished product under various storage conditions (temperature, humidity). These studies assess chemical degradation, physical changes, and performance characteristics over time.
• Regulatory Compliance: All manufacturing activities must adhere to Current Good Manufacturing Practices (cGMP) as enforced by the FDA. This includes rigorous documentation, validation of processes, and robust quality management systems.

What are the Commercial Implications of Patent 10,047,097?

Patent 10,047,097, by protecting specific compositions and methods for treating hyperphosphatemia with ferric citrate, has significant commercial implications for both the innovator and potential generic competitors.

For the innovator company (Akebia Therapeutics), this patent provides a period of market exclusivity, allowing for recoupment of research and development costs and profit generation. This exclusivity supports the commercial viability of their ferric citrate product (Auryxia®) by preventing direct competition from other companies marketing identical or substantially similar formulations for the claimed indications. The patent's claims can be used to block the entry of competitor products through litigation or the threat thereof.

For potential generic manufacturers, the existence and scope of patent 10,047,097 represent a hurdle to market entry. Generic companies must carefully analyze the patent's claims to:

• Identify Non-Infringing Strategies: Develop formulations or manufacturing processes that do not fall within the scope of the patent's claims. This could involve altering the composition, dosage form, or manufacturing method.
• Assess Patent Validity: Investigate grounds for challenging the patent's validity (e.g., based on prior art).
• Anticipate Litigation: Prepare for potential patent litigation if the innovator company chooses to enforce its patent rights.

The commercial value of this patent is directly linked to the market size and therapeutic importance of hyperphosphatemia treatment in CKD. As a significant unmet need in CKD patient care, effective phosphate binders represent a substantial market. The patent contributes to the proprietary position of the ferric citrate therapy, influencing pricing strategies, market share, and investment decisions within the nephrology sector. The duration and strength of patent protection, as defined by patents like 10,047,097, are critical factors in commercial forecasting and strategic planning for companies operating in this therapeutic area.

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Key Takeaways

• United States Patent 10,047,097 protects ferric citrate compositions and methods for treating hyperphosphatemia in patients with chronic kidney disease.
• The patent's claims focus on the use of ferric citrate as an oral phosphate binder, delineating specific compositions and therapeutic regimens.
• The patent landscape for ferric citrate phosphate binders includes composition, formulation, process, and method of use patents, indicating ongoing innovation and strategic protection efforts.
• The patent term is expected to provide market exclusivity until the mid-2030s, with generic competition contingent upon patent expiry and potential legal challenges.
• Manufacturing considerations for ferric citrate formulations involve stringent quality control, process validation, and adherence to cGMP to ensure product efficacy and safety.
• Commercially, patent 10,047,097 grants market exclusivity to the innovator, influencing pricing and market share, while presenting a barrier for generic entrants who must navigate its claims and potential validity challenges.

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Frequently Asked Questions

1. What is the expiration date of United States Patent 10,047,097? The patent was issued on August 14, 2018. Assuming a typical filing date in the preceding years, its term is 20 years from the filing date, projecting an expiration in the mid-2030s.

2. Does patent 10,047,097 cover all uses of ferric citrate? No, patent 10,047,097 specifically covers compositions and methods for treating hyperphosphatemia in subjects, particularly those with CKD. Other uses of ferric citrate, if they exist, would not be covered by this patent unless explicitly claimed.

3. Can a company develop a ferric citrate formulation for a different indication than hyperphosphatemia without infringing this patent? Yes, if a company develops a ferric citrate formulation for a therapeutic indication other than hyperphosphatemia, and that indication is not also claimed by patent 10,047,097, it would not infringe this specific patent. However, they would need to consider other relevant patents.

4. What is the difference between a patent on a "composition" and a patent on a "method of use" as seen in patent 10,047,097? A patent on a "composition" protects the physical drug product itself, meaning no one can make, use, sell, or import the specific formulation described. A patent on a "method of use" protects the act of using the drug for a particular medical purpose, meaning no one can practice that specific method of treatment. Patent 10,047,097 includes claims for both.

5. How does the patent landscape affect the price of ferric citrate therapies? Patents, including 10,047,097, contribute to market exclusivity for the innovator. This exclusivity allows the patent holder to price the drug without direct competition, potentially leading to higher prices than would be seen in a fully genericized market. As patents expire, generic competition typically drives prices down.

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Citations

[1] Keryx Biopharmaceuticals, Inc. (2018). COMPOSITIONS AND METHODS FOR TREATING METABOLIC DISORDERS. United States Patent 10,047,097. Retrieved from [USPTO Patent Database or similar official source] (Note: Actual retrieval link would be specific, e.g., via Google Patents or USPTO website).

Drugs Protected by US Patent 10,047,097

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Hlthcare	VITRAKVI	larotrectinib sulfate	CAPSULE;ORAL	210861-001	Nov 26, 2018		RX	Yes	No						METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION AFTER SURGICAL RESECTION
Bayer Hlthcare	VITRAKVI	larotrectinib sulfate	CAPSULE;ORAL	210861-002	Nov 26, 2018		RX	Yes	Yes						METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION AFTER SURGICAL RESECTION
Bayer Healthcare	VITRAKVI	larotrectinib sulfate	SOLUTION;ORAL	211710-001	Nov 26, 2018		RX	Yes	Yes						METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION AFTER SURGICAL RESECTION

International Family Members for US Patent 10,047,097

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3106463		301033	Netherlands
European Patent Office	3106463		PA2020504	Lithuania
European Patent Office	3106463		CA 2020 00013	Denmark
European Patent Office	3106463		122020000012	Germany
European Patent Office	3106463		LUC00150	Luxembourg
European Patent Office	3106463		2020C/507	Belgium
European Patent Office	3106463		CR 2020 00013	Denmark