United States Patent 8,318,802: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
The United States Patent 8,318,802, hereafter referred to as the '802 patent, is a significant patent in the pharmaceutical industry, particularly in the field of epoprostenol formulations. This patent, owned by Actelion Pharmaceuticals Ltd., addresses the stability of epoprostenol compositions when reconstituted with commercially available intravenous fluids. Here, we delve into the scope, claims, and the broader patent landscape surrounding this invention.
Background and Invention
Epoprostenol is a prostacyclin analogue used primarily for the treatment of pulmonary arterial hypertension (PAH). The '802 patent focuses on improving the stability of epoprostenol formulations, which is crucial for maintaining the drug's efficacy and safety.
Historical Context
The initial application for this patent was part of a larger patent family that included multiple inventions related to epoprostenol. The patent examiner required Actelion to elect a single invention to which the claims must be restricted, leading to the divisional application that resulted in the '802 patent[1].
Claims and Scope
The '802 patent includes several key claims that define the scope of the invention.
Claim 1: Pharmaceutical Composition
Claim 1 is representative of the asserted claims and describes a pharmaceutical composition comprising:
- Epoprostenol or a salt thereof
- An alkalinizing agent
- A pH of the reconstituted solution greater than 11[1][4].
Claim 11: Lyophilisate Formation
Claim 11 details the formation of a lyophilisate from a bulk solution comprising epoprostenol or a salt thereof and an alkalinizing agent, with the pH of the bulk solution adjusted to greater than 13[5].
Key Components and Their Significance
Epoprostenol
Epoprostenol is the active ingredient, a prostacyclin analogue that is sensitive to pH and requires specific conditions to maintain stability.
Alkalinizing Agent
The inclusion of an alkalinizing agent is critical for achieving the required pH level, which ensures the stability of the epoprostenol in the reconstituted solution.
pH Adjustment
The specification and claims emphasize the importance of adjusting the pH of the bulk solution to greater than 13, which is a key factor in maintaining the stability of the epoprostenol composition[1][4].
Claim Construction and Interpretation
The interpretation of the claims, particularly the term "a pH of 13 or higher," has been a subject of dispute.
Federal Circuit Rulings
In the case of Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc., the Federal Circuit addressed the meaning of this term. The court held that the specification and prosecution history did not provide clear guidance on the level of precision intended for this term. The court ultimately relied on the plain and ordinary meaning of the term within the context of the patent[2][5].
Prosecution History
The prosecution history of the '802 patent is significant in understanding the scope and validity of the claims.
Overcoming Obviousness Rejections
Actelion had to overcome obviousness rejections by demonstrating unexpected improved stability between the compositions of the instant invention and those of the prior art. This was achieved through amendments and responses to the examiner's rejections, leveraging the unexpected results doctrine[1].
Patent Landscape and Related Patents
The '802 patent is part of a broader patent landscape that includes other related patents.
United States Patent 8,598,227 ('227 Patent)
This patent, also owned by Actelion, covers methods of making and treating patients with epoprostenol compositions. It was filed as another divisional application from the same initial patent family as the '802 patent[1][2].
Evergreening and Patent Strategies
The strategy of filing multiple divisional applications and maintaining a robust patent portfolio is often seen in the pharmaceutical industry to extend patent protection and prevent generic competition. This practice, known as "evergreening," is a subject of ongoing debate and regulatory scrutiny[3].
Industry Impact and Competitive Landscape
The '802 patent has significant implications for the pharmaceutical industry, particularly in the treatment of PAH.
Market Dominance and Generic Competition
Actelion's successful prosecution and enforcement of the '802 patent have helped maintain market dominance for their epoprostenol formulation, Veletri. This has limited the entry of generic competitors, ensuring continued revenue streams for the company[1][5].
Challenges and Controversies
The patent has faced challenges and controversies, including disputes over claim construction and the impact on generic competition.
Litigation and Appeals
The case against Mylan Pharmaceuticals Inc. highlights the legal battles surrounding the interpretation and enforcement of the '802 patent. The Federal Circuit's decision reinforced Actelion's claims, but the broader implications of such patents on generic competition remain a topic of debate[2][5].
Key Takeaways
- The '802 patent is crucial for the stability of epoprostenol formulations, ensuring efficacy and safety.
- The patent includes key claims related to the composition and pH adjustment of the epoprostenol solution.
- The Federal Circuit's interpretation of the claim terms has been pivotal in defining the scope of the patent.
- The patent is part of a broader strategy to maintain market dominance and prevent generic competition.
- The impact of such patents on the pharmaceutical industry and generic competition is a subject of ongoing debate.
Frequently Asked Questions (FAQs)
What is the primary invention covered by the '802 patent?
The primary invention is a stable epoprostenol composition that can be combined with commercially available intravenous fluids, ensuring the stability of the drug upon reconstitution.
Why is the pH adjustment crucial in the '802 patent?
The pH adjustment to greater than 13 is critical for maintaining the stability of the epoprostenol in the reconstituted solution, which is essential for the drug's efficacy and safety.
How did Actelion overcome obviousness rejections during the prosecution of the '802 patent?
Actelion demonstrated unexpected improved stability between the compositions of the instant invention and those of the prior art, leveraging the unexpected results doctrine.
What is the relationship between the '802 patent and the '227 patent?
Both patents are part of the same initial patent family and cover different aspects of epoprostenol formulations, with the '227 patent focusing on methods of making and treating patients.
How has the '802 patent impacted the pharmaceutical industry?
The patent has helped Actelion maintain market dominance for their epoprostenol formulation, limiting the entry of generic competitors and ensuring continued revenue streams.
Cited Sources:
- Actelion Pharms., Ltd. v. Sun Pharm. Indus., Inc. - Casetext
- Latest Precedential Claim Construction Cases - Maynard Nexsen
- A Call for Relevant Data to Support “Evergreening” Allegations - Fordham Intellectual Property, Media & Entertainment Law Journal
- US8318802B2 - Epoprostenol formulation and method of making thereof - Google Patents
- Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc - Federal Circuit Court of Appeals
