Details for Patent: 6,967,208

Which drugs does patent 6,967,208 protect, and when does it expire?

Patent 6,967,208 protects ELIQUIS and is included in one NDA.

This patent has seventy-four patent family members in thirty-six countries.

Summary for Patent: 6,967,208

Title:	Lactam-containing compounds and derivatives thereof as factor Xa inhibitors
Abstract:	The present application describes lactam-containing compounds and derivatives thereof of Formula I: ##STR1## or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.
Inventor(s):	Pinto; Donald J. P. (Churchville, PA), Quan; Mimi L. (Yardley, PA), Orwat; Michael J. (New Hope, PA), Li; Yun-Long (Wilmington, DE), Han; Wei (Yardley, PA), Qiao; Jennifer X. (Princeton, NJ), Lam; Patrick Y. S. (Chadds Ford, PA), Koch; Stephanie L. (Newark, DE)
Assignee:	Bristol-Myers Squibb Pharma Company (Princeton, NJ)
Application Number:	10/245,122
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,967,208
Patent Claim Types: see list of patent claims	Compound; Composition; Use;

United States Patent 6,967,208: A Detailed Analysis of Scope, Claims, and Patent Landscape

Introduction

The United States Patent 6,967,208, hereafter referred to as the '208 patent, is a crucial intellectual property asset owned by Bristol-Myers Squibb Co. (BMS) and Pfizer Inc. This patent is central to the protection of apixaban, the active ingredient in the commercially successful drug Eliquis®, which is used to treat and reduce the risk of certain cardiovascular conditions.

Background of the Invention

The '208 patent relates to lactam-containing compounds and their derivatives, specifically those that inhibit trypsin-like serine protease enzymes, particularly Factor Xa. These compounds are used as anticoagulant agents for the treatment of thromboembolic disorders[1].

Claims of the '208 Patent

The '208 patent includes several key claims that define the scope of the invention. Here are some of the critical claims:

• Claim 13: This claim specifies the compound apixaban, which is the active ingredient in Eliquis®. It describes the chemical structure and composition of apixaban in detail[2][5].
• Claim 104: This claim is also directed towards apixaban and its use as an anticoagulant. It encompasses the compound and its pharmaceutical applications[2][5].

Scope of the Patent

The scope of the '208 patent is defined by its claims, which are narrowly tailored to cover the specific compound apixaban and its use. Here are some key aspects of the patent's scope:

• Chemical Structure: The patent claims are specific to the chemical structure of apixaban, ensuring that any infringement would involve the exact or very similar compounds[1][5].
• Therapeutic Use: The patent covers the use of apixaban as an anticoagulant, which is its primary therapeutic application. This includes its use in treating and reducing the risk of thromboembolic disorders[1].

Patent Landscape

The '208 patent operates within a complex patent landscape, particularly in the pharmaceutical sector.

• Related Patents: The '208 patent is part of a broader portfolio that includes other patents related to apixaban formulations, such as the '945 patent. These patents collectively protect various aspects of the drug, including its composition and use[2][5].
• Generic Challenges: The '208 patent has been subject to challenges from generic manufacturers seeking to bring bioequivalent versions of Eliquis® to market. These challenges often involve disputes over patent infringement and validity[2][5].

Litigation and Enforcement

The '208 patent has been at the center of significant litigation, particularly under the Hatch-Waxman Act.

• BMS v. Sigmapharm Labs. LLC.: In this case, BMS and Pfizer sued several generic manufacturers, including Sigmapharm and Unichem, for infringement of the '208 and '945 patents. The district court and subsequently the Federal Circuit affirmed that the defendants' proposed drug products infringed the asserted claims of the '208 patent and that these claims were not invalid[2][5].

Claim Construction and Infringement

The construction of claims in the '208 patent has been a critical aspect of the litigation.

• Key Limitations: The Federal Circuit's affirmation of the district court's claim construction, particularly regarding the terms "apixaban particles have a D90 equal to or less than about 89 microns" and "crystalline apixaban particles," was pivotal in determining infringement. These limitations are specific to the physical characteristics of apixaban particles, which are essential for the drug's efficacy and stability[5].

Impact on Generic Competition

The '208 patent, along with other related patents, plays a significant role in delaying the entry of generic versions of Eliquis® into the market.

• Exclusivity and Follow-On Patents: The patent landscape for Eliquis® includes follow-on patents that cover various aspects of the drug, such as new dosage forms or methods of use. These patents can extend the market exclusivity period, making it challenging for generic manufacturers to launch competing products until all relevant patents expire[4].

Conclusion

The United States Patent 6,967,208 is a cornerstone of BMS and Pfizer's intellectual property strategy for protecting Eliquis®. The patent's specific claims, particularly those related to the compound apixaban, have been upheld in significant litigation, ensuring that the drug remains protected against generic competition. Understanding the scope, claims, and the broader patent landscape of the '208 patent is crucial for navigating the complex world of pharmaceutical intellectual property.

Key Takeaways

• The '208 patent specifically claims the compound apixaban and its use as an anticoagulant.
• The patent has been upheld in litigation against generic manufacturers.
• The claim construction, particularly regarding particle size and crystalline form, is critical for determining infringement.
• The patent is part of a broader strategy that includes follow-on patents to extend market exclusivity.
• The '208 patent has significant implications for generic competition in the pharmaceutical market.

FAQs

What is the main subject of the '208 patent?

The main subject of the '208 patent is the compound apixaban, which is the active ingredient in the drug Eliquis®, and its use as an anticoagulant.

Which companies own the '208 patent?

The '208 patent is jointly owned by Bristol-Myers Squibb Co. (BMS) and Pfizer Inc.

What are the key claims of the '208 patent?

The key claims include Claim 13 and Claim 104, which specify the chemical structure and composition of apixaban and its use as an anticoagulant.

How has the '208 patent been enforced in litigation?

The '208 patent has been enforced through litigation under the Hatch-Waxman Act, with BMS and Pfizer successfully defending against generic manufacturers who sought to bring bioequivalent versions of Eliquis® to market.

What is the impact of the '208 patent on generic competition?

The '208 patent, along with related follow-on patents, delays the entry of generic versions of Eliquis® into the market by extending the period of market exclusivity.

How does the claim construction affect infringement determinations?

The claim construction, particularly regarding the physical characteristics of apixaban particles (e.g., particle size and crystalline form), is crucial for determining whether a generic product infringes the '208 patent.

Sources

1. United States Patent and Trademark Office, "United States Patent 6,967,208" [PDF].
2. Casetext, "Bristol-Myers Squibb Co. v. Aurobindo Pharma U.S. Inc."
3. Hoover Institution, "Patent Claims and Patent Scope" [PDF].
4. USPTO, "USPTO-FDA Report on Drug Patent and Exclusivity" [PDF].
5. Finnegan, "Federal Circuit Crystallizes BMS' Apixaban District Court Win".

Drugs Protected by US Patent 6,967,208

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bristol Myers Squibb	ELIQUIS	apixaban	TABLET;ORAL	202155-001	Dec 28, 2012	AB	RX	Yes	No			Y	Y		PROPHYLAXIS OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
Bristol Myers Squibb	ELIQUIS	apixaban	TABLET;ORAL	202155-001	Dec 28, 2012	AB	RX	Yes	No			Y	Y		REDUCING THE RISK OF STROKE AND SYSTEMIC EMBOLISM
Bristol Myers Squibb	ELIQUIS	apixaban	TABLET;ORAL	202155-001	Dec 28, 2012	AB	RX	Yes	No			Y	Y		TREATMENT OF PULMONARY EMBOLISM (PE)

International Family Members for US Patent 6,967,208

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1427415		C300500	Netherlands
European Patent Office	1427415		C20110017 00045	Estonia
European Patent Office	1427415		CA 2011 00028	Denmark