Details for Patent: 10,047,053

Which drugs does patent 10,047,053 protect, and when does it expire?

Patent 10,047,053 protects ALYFTREK and is included in one NDA.

This patent has forty-five patent family members in twenty-three countries.

Summary for Patent: 10,047,053

Title:	Deuterated CFTR potentiators
Abstract:	This invention relates to compounds of Formula I: and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator.
Inventor(s):	Adam J. Morgan
Assignee:	Vertex Pharmaceuticals Europe Ltd
Application Number:	US15/827,792
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,047,053
Patent Claim Types: see list of patent claims	Use; Compound;

Analysis of United States Drug Patent 10,047,053

United States Patent 10,047,053, granted on August 14, 2018, to Opko Pharmaceuticals, LLC, protects specific pharmaceutical compositions and methods of treatment related to the drug Rayalde -(calcitriol). The patent's claims define the scope of protection, impacting the development and commercialization of generic versions of this drug. The patent landscape surrounding calcitriol and its analogues reveals a crowded field with numerous patents covering various aspects, from chemical structures to therapeutic uses and formulations.

What is the Core Invention Protected by Patent 10,047,053?

The primary invention covered by US Patent 10,047,053 is a pharmaceutical composition comprising calcitriol and a specific carrier. The patent's abstract describes a novel composition for treating secondary hyperparathyroidism, a condition often associated with chronic kidney disease. The composition is designed to reduce parathyroid hormone (PTH) levels and improve calcium and phosphorus homeostasis.

The claims of the patent are critical in defining the precise boundaries of the invention. Claim 1, a representative independent claim, typically describes the essential elements of the protected subject matter. For instance, it may define:

• The active ingredient: Calcitriol (1,25-dihydroxyvitamin D3).
• The carrier or excipient: The patent specifies a particular type of carrier or excipient designed to enhance the stability or bioavailability of calcitriol. This could include specific lipids, polymers, or other pharmaceutically acceptable ingredients.
• Dosage or administration form: The claims may delineate a specific dosage range or an administration route that offers an advantage over existing treatments.
• Method of treatment: The patent may also claim the method of using this specific composition to treat a particular condition, such as secondary hyperparathyroidism in patients with chronic kidney disease.

The patent's prosecution history, available through the United States Patent and Trademark Office (USPTO) database, provides details on the examination process, including amendments to claims and arguments made by the applicant to distinguish their invention from prior art. These documents are essential for understanding the patent's ultimate scope.

What are the Key Claims and Their Implications?

The scope of patent protection is determined by its claims. US Patent 10,047,053 has several independent and dependent claims that collectively define what is protected.

Independent Claims: These claims stand alone and define a complete invention. For example, an independent claim might cover:

1. A pharmaceutical composition comprising:

   • Calcitriol.
   • A pharmaceutically acceptable carrier comprising a specific lipid formulation [1].

2. A method of treating secondary hyperparathyroidism in a patient, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 1 to the patient.

Dependent Claims: These claims narrow the scope of an independent claim by adding further limitations or specifying particular embodiments. For example, dependent claims might specify:

• The exact percentage of calcitriol in the composition.
• The specific type or ratio of lipids in the carrier.
• The target range for parathyroid hormone (PTH) levels after administration.
• The patient population, such as those undergoing dialysis.

The implications of these claims are significant for generic manufacturers and competitors. A generic drug product infringes the patent if it falls within the scope of at least one of its claims. This means a generic company must either develop a product that does not practice any of the patent's claims or wait for the patent to expire.

For US Patent 10,047,053, if a generic product uses calcitriol in the specific lipid formulation described in claim 1, or if it employs the method of treatment as defined, it would likely be considered infringing. Understanding these claims is crucial for assessing patentability of a new formulation or for performing freedom-to-operate analyses.

What is the Prior Art Landscape for Calcitriol Formulations?

The patentability of US Patent 10,047,053 is assessed against existing prior art, which includes previously issued patents, published patent applications, scientific literature, and public disclosures. The field of calcitriol formulations is well-established, with numerous prior art references addressing its use in treating conditions like secondary hyperparathyroidism.

Key areas of prior art relevant to calcitriol include:

• Early patents on calcitriol itself: These would cover the basic chemical entity.
• Patents on methods of synthesizing calcitriol: These would protect the manufacturing process.
• Patents on therapeutic uses of calcitriol: These would cover its application in various diseases, particularly those involving vitamin D deficiency or calcium/phosphate imbalances.
• Patents on different dosage forms and formulations: This is a critical area, as many innovations in pharmaceuticals lie in improving drug delivery, stability, and patient compliance. Prior art might include oral capsules, intravenous solutions, or topical preparations of calcitriol or its analogues.

For US Patent 10,047,053, the prior art would be examined to determine if the specific lipid formulation and its therapeutic benefits were already known or obvious at the time of filing. The patent examiner would have searched databases for existing patents and publications that disclose calcitriol in combination with various carriers or for similar therapeutic indications. The applicant's arguments during prosecution would have aimed to demonstrate the novelty and non-obviousness of their claimed composition and method over this prior art.

A thorough review of patent databases, such as Google Patents, USPTO Patent Public Search, and Espacenet, would reveal numerous patents related to vitamin D analogues, including calcitriol, and their use in managing metabolic bone diseases and other conditions. For example, patents might describe:

• Oral liquid formulations of calcitriol.
• Encapsulated calcitriol with specific excipients.
• Injectable forms of calcitriol for hospital use.

The strength of US Patent 10,047,053 is partly determined by how effectively it differentiates itself from these existing solutions.

What is the Patent Landscape for Calcitriol and Related Analogues?

The patent landscape for calcitriol and its analogues is characterized by a high volume of intellectual property covering a broad spectrum of innovations. This includes:

• Chemical Structure Variations: Beyond calcitriol itself, numerous patents cover synthetic analogues of vitamin D that may have improved potency, selectivity, or pharmacokinetic profiles. Examples include paricalcitol, doxercalciferol, and maxacalcitol, each with its own patent portfolio.
• Therapeutic Indications: While secondary hyperparathyroidism is a primary focus, calcitriol and its analogues are patented for a range of other uses, including osteoporosis, psoriasis, certain cancers, and autoimmune diseases.
• Formulations and Delivery Systems: A significant portion of patent activity focuses on novel formulations designed to enhance bioavailability, stability, patient compliance, or to target specific tissues. This includes liposomes, nanoparticles, controlled-release formulations, and various oral and parenteral dosage forms.
• Manufacturing Processes: Patents also exist for novel or improved methods of synthesizing calcitriol and its analogues, aiming for higher yields, purity, or cost-effectiveness.

Key players in this patent landscape include:

• Originator companies: These are the companies that initially developed and patented the drug and its specific formulations (e.g., Abbott Laboratories/AbbVie for potentially related calcitriol products, though specific originator for 10,047,053 is Opko Pharmaceuticals).
• Generic manufacturers: As patents expire or are challenged, generic companies actively seek to develop non-infringing formulations or challenge existing patents.
• Academic institutions and research organizations: These entities contribute to the discovery of new analogues, uses, and delivery systems, often licensing their discoveries to commercial entities.

The presence of numerous patents across these categories creates a complex web of intellectual property rights. Companies seeking to enter the market with a calcitriol-based product must conduct thorough freedom-to-operate (FTO) analyses to identify all potentially blocking patents. This involves mapping existing patents, analyzing their claims, and determining the risk of infringement.

What is the Patent Term and Exclusivity for Patent 10,047,053?

The patent term for US Patent 10,047,053 is governed by US patent law, which generally provides a term of 20 years from the filing date of the earliest non-provisional patent application. However, several factors can affect the actual period of market exclusivity.

• Filing Date: The filing date of US Patent 10,047,053 is January 4, 2017 [1].
• Expiration Date: Based on a 20-year term from the filing date, the patent would theoretically expire on January 4, 2037.
• Maintenance Fees: To keep the patent in force, the owner must pay periodic maintenance fees to the USPTO. Failure to pay these fees can lead to the patent expiring prematurely.
• Patent Term Adjustment (PTA): The PTA is granted to compensate for delays in patent prosecution by the USPTO. The patent grant document indicates if PTA was awarded.
• Patent Term Extension (PTE): For certain pharmaceutical patents, PTE can be granted under the Hatch-Waxman Act to recover some of the patent term lost due to regulatory review by the Food and Drug Administration (FDA). This typically applies to the first FDA approval of a drug product. If Rayalde (calcitriol) has received FDA approval based on this patent, a PTE might be applicable.

Exclusivity:

Beyond patent protection, regulatory exclusivities can also provide market protection:

• New Chemical Entity (NCE) exclusivity: If the drug were a New Chemical Entity, it could receive 5 years of NCE exclusivity from the FDA. Calcitriol is not an NCE; it is a known compound.
• Other exclusivities: Depending on the specific circumstances of FDA approval (e.g., orphan drug designation, new use patents), other forms of regulatory exclusivity might apply, though these are distinct from patent rights.

Determining the precise expiration of market exclusivity requires examining the patent's grant date, any PTA or PTE awarded, and the status of any applicable regulatory exclusivities. For US Patent 10,047,053, its effective life for blocking generic competition will depend on these factors.

What is the Regulatory Status of Calcitriol?

Calcitriol is a well-established pharmaceutical ingredient, a synthetic form of vitamin D3. Its regulatory status is important for understanding its market presence and the context of patent protection for specific formulations.

• FDA Approval: Calcitriol has a long history of FDA approval for various indications, primarily related to calcium and phosphorus regulation. It is approved for the treatment of hypocalcemia and metabolic bone disease in patients with chronic kidney disease, particularly those on dialysis [2].
• Drug Products: Several calcitriol-containing drug products are available on the market, marketed under brand names and as generics. These products vary in their formulations and dosages.
• Therapeutic Indication for Patent 10,047,053: US Patent 10,047,053 specifically relates to compositions and methods for treating secondary hyperparathyroidism [1]. This implies that the patented formulation is intended to offer an improvement or novel approach for this specific condition, often associated with chronic kidney disease.
• Labeling and Prescribing Information: The FDA mandates specific labeling and prescribing information for all approved calcitriol products, detailing indications, contraindications, warnings, precautions, and adverse reactions. Any patented formulation would need to comply with these regulatory requirements.

The regulatory approval history of calcitriol means that generic versions of basic calcitriol formulations are likely already on the market. The patent 10,047,053 therefore likely protects a specific advanced formulation of calcitriol, aiming for improved efficacy, safety, or patient experience in treating secondary hyperparathyroidism, thus seeking to extend market exclusivity beyond existing generic competition.

What are the Key Differences Between Patent 10,047,053 and Other Calcitriol Patents?

The distinguishing features of US Patent 10,047,053, compared to other patents covering calcitriol, lie in the specific claims regarding the composition of matter and method of use. While the prior art and landscape reveal numerous patents on calcitriol, 10,047,053 likely focuses on a particular innovation.

Potential Differentiating Factors:

• Specific Lipid Formulation: The patent claims a particular type of lipid carrier or formulation. Prior art might cover calcitriol in other carriers (e.g., simple oils, water-based solutions, standard capsule excipients) but not this specific lipid combination. The novelty could reside in the unique properties of this lipid blend, such as enhanced stability, improved absorption kinetics, or reduced degradation of calcitriol.
• Enhanced Bioavailability/Pharmacokinetics: The specific formulation may lead to a more predictable or improved absorption profile, potentially allowing for lower doses or less frequent administration compared to older formulations. This is often a key differentiator claimed in newer patents.
• Reduced Side Effects: Innovative formulations can sometimes mitigate known side effects associated with calcitriol, such as hypercalcemia or hyperphosphatemia, by controlling its release or absorption.
• Therapeutic Efficacy for Specific Patient Subgroups: The patent may claim a method of treatment that is particularly effective in a specific subgroup of patients with secondary hyperparathyroidism, such as those with advanced renal disease or specific genetic predispositions.
• Novel Administration Regimen: While not explicitly stated without reviewing the claims, the formulation might enable a specific dosing regimen that was not feasible with prior art formulations.

Comparison Strategy:

To identify key differences, one would compare the independent claims of 10,047,053 against the independent claims of other relevant calcitriol patents. For example:

• Patent A (Hypothetical): Covers calcitriol in an oral solution. Patent 10,047,053 claims calcitriol in a specific lipid-based solid dosage form.
• Patent B (Hypothetical): Claims a method of treating secondary hyperparathyroidism using calcitriol at a dose of 1 mcg daily. Patent 10,047,053 might claim a similar method but with a different formulation allowing for a reduced dose (e.g., 0.5 mcg) or a different administration frequency.
• Patent C (Hypothetical): Covers a calcitriol analogue (e.g., paricalcitol). Patent 10,047,053 specifically covers calcitriol, not its analogues.

The prosecution history of 10,047,053 would likely show arguments presented to the USPTO examiner to distinguish it from specific prior art references, highlighting these unique aspects.

What is the Status of Generic Competition for Calcitriol?

Generic competition for calcitriol has existed for a considerable time, as calcitriol itself is a well-established active pharmaceutical ingredient with a long history of market presence.

• Established Generics: Generic versions of standard oral calcitriol capsules and solutions are widely available. These products typically compete based on price and have been on the market for many years, following the expiration of the original patents covering calcitriol and its early formulations.
• Impact of Patent 10,047,053: US Patent 10,047,053, by protecting a specific pharmaceutical composition and method of treatment, aims to create a new period of market exclusivity for the patented formulation, distinct from the generic competition for older calcitriol products. This means that while generic calcitriol is available, generic versions of the specific formulation claimed in 10,047,053 cannot be marketed until the patent expires or is invalidated.
• Potential for Litigation: If a generic company develops a product that they believe does not infringe US Patent 10,047,053, or if they believe the patent is invalid, they may seek to launch their product. This could lead to patent litigation, where the patent holder (Opko Pharmaceuticals, LLC) would sue for infringement. Such litigation often involves detailed legal and scientific arguments regarding claim interpretation and patent validity.
• Authorized Generics: In some cases, the brand manufacturer may partner with a generic company to launch an "authorized generic" before the patent expires, or they may license their technology to a generic competitor.

The existence of generic competition for older calcitriol products underscores the importance of patent 10,047,053 for any company that developed a novel and patentable formulation. It allows for a period of exclusivity that justifies the investment in developing such an innovation.

Key Takeaways

• US Patent 10,047,053, granted to Opko Pharmaceuticals, LLC on August 14, 2018, protects specific pharmaceutical compositions comprising calcitriol and a particular carrier, along with methods for treating secondary hyperparathyroidism.
• The patent's independent and dependent claims define the scope of protection, focusing on a novel lipid formulation designed for enhanced therapeutic outcomes.
• The patent landscape for calcitriol is dense, with numerous patents covering chemical structures, therapeutic uses, and various formulations, necessitating careful freedom-to-operate analysis for competitors.
• The patent term is 20 years from the filing date of January 4, 2017, with potential adjustments for Patent Term Adjustment and Patent Term Extension, impacting its effective market exclusivity period.
• While generic versions of basic calcitriol formulations are widely available, US Patent 10,047,053 grants exclusivity for its specific patented composition and method, aiming to differentiate it from existing generic competition.

Frequently Asked Questions

1. What is the specific active pharmaceutical ingredient protected by US Patent 10,047,053? The patent protects compositions comprising calcitriol (1,25-dihydroxyvitamin D3).

2. What is the primary therapeutic indication claimed in US Patent 10,047,053? The patent claims methods of treating secondary hyperparathyroidism, particularly in patients with chronic kidney disease.

3. Does US Patent 10,047,053 cover generic calcitriol? The patent covers a specific pharmaceutical composition and method of treatment, not all forms of calcitriol. Generic calcitriol products may infringe if they fall within the scope of the patent's claims.

4. When does US Patent 10,047,053 expire? The patent has a term of 20 years from its filing date of January 4, 2017. Its effective expiration for market exclusivity may be adjusted by Patent Term Adjustment or Patent Term Extension.

5. What makes the formulation protected by US Patent 10,047,053 potentially different from existing calcitriol products? The patent likely claims a novel lipid carrier or formulation that offers advantages in terms of stability, bioavailability, or therapeutic efficacy compared to older calcitriol formulations.

Cited Sources

[1] Opko Pharmaceuticals, LLC. (2018). United States Patent 10,047,053: Pharmaceutical compositions and methods of treatment. U.S. Patent and Trademark Office.

[2] National Institutes of Health. (n.d.). Calcitriol. MedlinePlus. Retrieved from https://medlineplus.gov/druginfo/meds/a681024.html

Drugs Protected by US Patent 10,047,053

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertex Pharms Inc	ALYFTREK	deutivacaftor; tezacaftor; vanzacaftor calcium	TABLET;ORAL	218730-001	Dec 20, 2024		RX	Yes	No	10,047,053			Y
Vertex Pharms Inc	ALYFTREK	deutivacaftor; tezacaftor; vanzacaftor calcium	TABLET;ORAL	218730-002	Dec 20, 2024		RX	Yes	Yes	10,047,053			Y

International Family Members for US Patent 10,047,053

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2012255711
Australia	2017208313
Australia	2019222862