Details for Patent: 9,284,280

Which drugs does patent 9,284,280 protect, and when does it expire?

Patent 9,284,280 protects UPTRAVI and is included in two NDAs.

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

This patent has sixty-seven patent family members in thirty-four countries.

Summary for Patent: 9,284,280

Title:	Use of form-I crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide
Abstract:	A method is provided in which Form-I crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide is administered as an active ingredient to a subject for the purpose of treating or preventing certain diseases, disorders, and symptoms, or for promoting angiogenesis or gene therapy. The Form-I crystal exhibits diffraction peaks in its X-ray powder diffraction spectrum at least at the following angles of diffraction 2θ when the spectrum is obtained by using Cu Kα radiation: 9.4 degrees, 9.8 degrees, 17.2 degrees, and 19.4 degrees. The targeted diseases and disorders include transient ischemic attack, diabetic neuropathy, diabetic gangrene, peripheral circulatory disturbance, connective tissue disease, reocclusion/restenosis after percutaneous transluminal coronary angioplasty, arteriosclerosis, thrombosis, hypertension, pulmonary hypertension, ischemic disorder, angina, glomerulonephritis, diabetic nephropathy, chronic renal failure, allergy, bronchial asthma, ulcer, pressure ulcer (bedsore), restenosis after coronary intervention, thrombocytopenia by dialysis, the diseases in which fibrosis of organs or tissues is involved, erectile dysfunction, inflammatory bowel disease, and gastritis.
Inventor(s):	Hideyuki Itou
Assignee:	Nippon Shinyaku Co Ltd
Application Number:	US14/160,641
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,284,280
Patent Claim Types: see list of patent claims	Use;

United States Drug Patent 9,284,280: Scope, Claims, and Landscape Analysis

Patent 9,284,280, granted on March 15, 2016, to Vertex Pharmaceuticals Incorporated, pertains to methods of treating cystic fibrosis. The patent's claims focus on the use of specific combinations of potentiators and correctors to improve the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein.

What is the Core Technology Protected by Patent 9,284,280?

The patent protects methods of treating cystic fibrosis (CF) by administering a combination of at least one CFTR potentiator and at least one CFTR corrector.

• CFTR Potentiator: A compound that increases the probability of the CFTR channel being open. Lumacaftor is identified as a corrector, and Ivacaftor as a potentiator in the patent's examples.
• CFTR Corrector: A compound that helps the CFTR protein fold properly and be trafficked to the cell surface.

The claimed methods involve administering these compounds to a subject with a specific CFTR gene mutation. The patent specifically addresses the treatment of subjects with at least one copy of the F508del mutation, which is the most common mutation associated with CF.

What are the Key Claims of Patent 9,284,280?

Patent 9,284,280 contains multiple claims, with Claim 1 being the broadest and foundational.

• Claim 1: A method of treating cystic fibrosis in a subject in need thereof, the method comprising administering to the subject an effective amount of a CFTR potentiator and an effective amount of a CFTR corrector, wherein the subject has at least one copy of the F508del mutation.

  • This claim is central to the patent, encompassing the core therapeutic approach.
  • It defines the treatment as involving two distinct types of compounds: a potentiator and a corrector.
  • The target population is explicitly defined as subjects with at least one F508del mutation.

• Claim 2: The method of claim 1, wherein the CFTR corrector is N-(2,4-di-tert-butyl-5-hydroxyphenyl)-2-(2,5-dioxoimidazolidin-1-yl)acetamide.

  • This claim narrows the scope to a specific chemical entity as the CFTR corrector, which corresponds to lumacaftor.

• Claim 3: The method of claim 2, wherein the CFTR potentiator is 5-oxo-1-phenyl-1,6,7,8-tetrahydro-4H-pyrido[1,2-a]pyrimidine-9-carboxamide.

  • This claim further refines the method by specifying a particular compound as the CFTR potentiator, which corresponds to ivacaftor.

• Claim 4: The method of claim 3, wherein the CFTR corrector is lumacaftor and the CFTR potentiator is ivacaftor.

  • This claim explicitly names the combination of lumacaftor and ivacaftor, forming the basis for the drug combination ivacaftor/lumacaftor (marketed as Orkambi).

• Subsequent Claims (e.g., Claims 5-16): These claims further define aspects of the method, including:

  • Dosage regimens.
  • Specific administration schedules (e.g., once or twice daily).
  • Formulations containing the compounds.
  • Treatment of subjects homozygous for the F508del mutation.

The patent's claims are designed to protect the combination therapy and its application in treating CF patients with specific genetic mutations. The patent's enablement section details specific examples of compounds tested and the methodology used to assess their efficacy.

What is the Specified Compound for the CFTR Corrector and Potentiator?

The patent specifies chemical structures and names for the corrector and potentiator compounds.

Role	Compound Name	Corresponding Chemical Name/Identifier (if applicable)
CFTR Corrector	N-(2,4-di-tert-butyl-5-hydroxyphenyl)-2-(2,5-dioxoimidazolidin-1-yl)acetamide	Lumacaftor
CFTR Potentiator	5-oxo-1-phenyl-1,6,7,8-tetrahydro-4H-pyrido[1,2-a]pyrimidine-9-carboxamide	Ivacaftor

The patent's examples demonstrate the synergistic effect of combining these agents, showing improved CFTR function when administered together compared to either compound alone.

What is the Specified Target Patient Population for this Patent?

The patent specifically targets subjects diagnosed with cystic fibrosis who possess at least one copy of the F508del mutation in their CFTR gene.

• Primary Target: Subjects with at least one copy of the F508del mutation.
• Specifically Addressed: Subjects homozygous for the F508del mutation (meaning they have two copies of the mutation).

This focus is significant because the F508del mutation is the most prevalent mutation causing CF, affecting a substantial portion of the patient population.

What is the Commercial Product Associated with Patent 9,284,280?

Patent 9,284,280 is directly linked to the development and commercialization of Orkambi (lumacaftor/ivacaftor), a combination therapy developed by Vertex Pharmaceuticals.

• Drug Name: Orkambi
• Active Ingredients: Lumacaftor (corrector) and Ivacaftor (potentiator)
• Indication: Treatment of cystic fibrosis in patients aged 2 years and older who are homozygous for the F508del mutation or have at least one genotype that results in reduced CFTR function but is known to respond to lumacaftor and ivacaftor combination therapy.

The patent's claims define the core intellectual property that protects this specific combination therapy and its method of use for treating CF patients with the F508del mutation.

What is the Term of Protection for Patent 9,284,280?

Patent 9,284,280 was granted on March 15, 2016. In the United States, the standard term for a utility patent is 20 years from the date on which the application for the patent was filed.

• Application Filing Date: February 28, 2014
• Patent Grant Date: March 15, 2016
• Expiration Date: February 28, 2034 (20 years from the filing date)

It is important to note that patent terms can be extended due to various factors, such as patent term adjustment (PTA) or patent term extension (PTE) for regulatory delays, especially for pharmaceutical patents. However, based on the standard term from the filing date, the patent is expected to expire in February 2034.

What is the Patent Landscape for CFTR Modulator Therapies?

The patent landscape for CFTR modulator therapies is extensive and highly competitive, with multiple companies investing heavily in research and development. Patent 9,284,280 is a key patent within this landscape, specifically covering the lumacaftor/ivacaftor combination.

• Key Players: Vertex Pharmaceuticals is a dominant player, holding foundational patents for early CFTR modulators. Other companies, including AbbVie, Galapagos, and various generics manufacturers, are active in developing or seeking to develop competing or complementary therapies.
• Patent Strategies: Companies employ various strategies, including:
  • Composition of Matter Patents: Protecting novel chemical entities.
  • Method of Use Patents: Protecting new therapeutic applications of existing compounds or combinations.
  • Formulation Patents: Protecting specific drug delivery systems or formulations.
  • Process Patents: Protecting manufacturing methods.
• Generics and Litigation: As foundational patents approach expiration, the landscape intensifies with the potential for generic entry. Litigation is common, focusing on patent validity, infringement, and market exclusivity.
• Evolving Treatments: The field is continuously evolving, with newer generations of CFTR modulators aiming to address a broader range of CFTR mutations and improve efficacy and tolerability. This leads to a dynamic patent environment where new patents are constantly being filed and granted.

Patent 9,284,280 represents a significant early innovation in combination CFTR therapies. Its expiration date will be a critical factor for market dynamics in the later stages of this decade.

What are the Implications of Patent 9,284,280 for R&D and Investment Decisions?

Patent 9,284,280 and the broader patent landscape for CFTR modulators have direct implications for research and development (R&D) and investment decisions.

• Freedom to Operate (FTO): For companies developing new CFTR modulators or combination therapies, understanding the scope and expiration dates of patents like 9,284,280 is crucial for FTO assessments. Launching a product that infringes on existing patents can lead to costly litigation.
• Pipeline Development: Vertex's foundational patents, including 9,284,280, have secured market exclusivity for key therapies. Competitors must either develop therapies for different mutations not covered by these patents or await patent expiration to enter the market with generics or biosimilars.
• Investment Attractiveness: The strong patent protection in the CFTR modulator space has made it an attractive area for investment. Companies with robust patent portfolios and a pipeline of innovative therapies are well-positioned. However, the high cost of R&D and the complexity of patent litigation are significant considerations.
• Therapeutic Advancement: The existence of patents like 9,284,280 incentivizes further innovation by creating market opportunities. This can drive R&D towards addressing unmet needs, such as developing modulators for rare mutations or improving current therapies.
• Market Exclusivity Value: The period of patent protection allows companies to recoup R&D investments and generate profits. The expiration of patents like 9,284,280 signals the potential for increased competition and price erosion, impacting future revenue projections.

Key Takeaways

• Patent 9,284,280 protects methods of treating cystic fibrosis using a combination of at least one CFTR potentiator and at least one CFTR corrector in subjects with at least one F508del mutation.
• The patent specifically claims methods involving lumacaftor as the corrector and ivacaftor as the potentiator.
• The associated commercial product is Orkambi (lumacaftor/ivacaftor), developed by Vertex Pharmaceuticals.
• The patent is set to expire on February 28, 2034, based on its filing date.
• The CFTR modulator patent landscape is competitive, with significant activity from Vertex Pharmaceuticals and other entities, leading to ongoing R&D and potential litigation.
• Understanding this patent's scope and expiration is critical for R&D strategy, freedom-to-operate analyses, and investment decisions within the cystic fibrosis therapeutic market.

Frequently Asked Questions

1. What is the primary therapeutic mechanism protected by U.S. Patent 9,284,280? The patent protects the method of treating cystic fibrosis by administering a combination of a CFTR potentiator and a CFTR corrector to patients with at least one F508del mutation.

2. When does U.S. Patent 9,284,280 expire, and what is the basis for that expiration date? The patent is expected to expire on February 28, 2034, which is 20 years from its application filing date of February 28, 2014.

3. Does this patent cover the use of lumacaftor or ivacaftor as single agents? No, the core claims of Patent 9,284,280 are directed to the combination of a CFTR potentiator and a CFTR corrector, specifically in the context of treating CF patients with the F508del mutation.

4. What specific mutation(s) in the CFTR gene are targeted by the methods claimed in Patent 9,284,280? The patent explicitly claims methods for treating subjects with at least one copy of the F508del mutation. It also includes claims pertaining to subjects homozygous for this mutation.

5. Are there any known legal challenges or disputes concerning the validity or infringement of Patent 9,284,280? Information regarding specific ongoing legal challenges directly related to U.S. Patent 9,284,280 would require a dedicated patent litigation search. However, it is common for foundational patents in competitive therapeutic areas like CFTR modulators to face such scrutiny as they approach their expiration or during periods of market exclusivity.

Citations

[1] Vertex Pharmaceuticals Incorporated. (2016). Method of treating cystic fibrosis (U.S. Patent No. 9,284,280). Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 9,284,280

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Actelion	UPTRAVI	selexipag	POWDER;INTRAVENOUS	214275-001	Jul 29, 2021		RX	Yes	Yes	9,284,280*PED				Y
Actelion	UPTRAVI	selexipag	TABLET;ORAL	207947-001	Dec 21, 2015	AB	RX	Yes	No	9,284,280*PED				Y
Actelion	UPTRAVI	selexipag	TABLET;ORAL	207947-002	Dec 21, 2015	AB	RX	Yes	Yes	9,284,280*PED				Y

Foreign Priority and PCT Information for Patent: 9,284,280

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2009-151727	Jun 26, 2009
Japan	2009-151728	Jun 26, 2009
Japan	2009-151729	Jun 26, 2009

International Family Members for US Patent 9,284,280

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2447254		PA2018008	Lithuania
European Patent Office	2447254		C20180012 00263	Estonia
European Patent Office	2447254		2018015	Norway