Details for Patent: 8,101,659

Which drugs does patent 8,101,659 protect, and when does it expire?

Patent 8,101,659 protects ENTRESTO SPRINKLE and ENTRESTO and is included in two NDAs.

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

This patent has thirty-seven patent family members in twenty-six countries.

Summary for Patent: 8,101,659

Title:	Methods of treatment and pharmaceutical composition
Abstract:	The invention relates a pharmaceutical composition comprising a combination of: (i) the AT 1-antagonist valsartan or a pharmaceutically acceptable salt thereof; and (ii) a NEP inhibitor or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable carrier and to a method for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure, such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction, such as Alzheimer's, glaucoma and stroke, comprising administering a therapeutically effective amount of the pharmaceutical composition to a mammal in need thereof.
Inventor(s):	Ksander; Gary M (Amherst, NH), Webb; Randy L (Flemington, NJ)
Assignee:	Novartis AG (Basel, CH)
Application Number:	12/147,570
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,101,659
Patent Claim Types: see list of patent claims	Composition; Compound; Dosage form;

United States Patent 8,101,659: A Detailed Analysis of Scope, Claims, and Patent Landscape

Introduction

United States Patent 8,101,659, held by Novartis, is a significant patent in the pharmaceutical industry, particularly for the treatment of hypertension and heart failure. This patent has been at the center of several legal battles and has important implications for both the original patent holder and generic manufacturers.

Patent Overview

Filing and Expiration Dates

The patent, titled "Methods of Treatment and Pharmaceutical Compositions," was filed on March 24, 2006, and granted on January 24, 2012. It is set to expire on July 15, 2025, with an additional six months of pediatric exclusivity[1][4].

Claims and Subject Matter

The patent claims a combination of two drugs: sacubitril, a neutral endopeptidase inhibitor, and valsartan, an angiotensin receptor blocker. This combination is used to treat conditions such as hypertension and heart failure. The patent specifically covers the unique chemical combination and methods of treatment using this combination[2][4].

Scope of the Patent

Written Description Requirement

A critical aspect of the patent's validity is the written description requirement under U.S. patent law. This requirement mandates that the patent application must objectively demonstrate that the applicant actually invented the claimed subject matter. The description must be clear enough for persons of ordinary skill in the art to recognize that the inventor invented what is claimed[2].

Legal Challenges

In a significant legal battle, Wiley Rein LLP represented Macleods Pharmaceuticals Ltd. and successfully argued before the U.S. District Court for the District of Delaware that Novartis' patent lacked an adequate written description. The court ruled that the patent did not include teachings on the unique chemical combination of sacubitril and valsartan, thereby invalidating the patent[2][4].

Patent Litigation

Invalidation and Appeals

The invalidation of the patent by the U.S. District Court for the District of Delaware was a major setback for Novartis. However, Novartis has announced its intention to appeal the decision to the U.S. Court of Appeals. This ongoing litigation highlights the complex and often contentious nature of patent disputes in the pharmaceutical industry[2][4].

Impact on Generic Manufacturers

The invalidation of this patent has significant implications for generic manufacturers. Companies like Macleods Pharmaceuticals Ltd. and others involved in the litigation can now move forward with plans to produce generic versions of the drug combination, potentially reducing costs and increasing accessibility for patients[2].

Related Patents and Expiration Dates

Family of Patents

The patent landscape surrounding sacubitril and valsartan includes several related patents with different expiration dates. These include patents for crystalline forms of sacubitril and valsartan (U.S. Patents 8,877,938 and 9,388,134), amorphous forms (U.S. Patent 11,096,918), and a dosage regimen for treating chronic heart failure (U.S. Patent 11,058,667)[1][4].

• U.S. Patent 8,877,938: Expiration date - November 27, 2027
• U.S. Patent 9,388,134: Expiration date - May 8, 2027
• U.S. Patent 11,096,918: Expiration date - November 8, 2026
• U.S. Patent 11,058,667: Expiration date - May 9, 2036

Economic and Market Impact

Revenue and Market Dominance

The drug combination covered by U.S. Patent 8,101,659, known as Entresto, has been highly profitable for Novartis, earning billions of dollars worldwide. The invalidation of this patent could lead to increased competition from generic manufacturers, potentially reducing Novartis' market share and revenue[2].

Patient Accessibility

On the other hand, the entry of generic versions could significantly improve patient accessibility to this life-saving medication by reducing costs. This is particularly important for chronic conditions like heart failure, where long-term treatment is often necessary[2].

Regulatory and Legal Framework

U.S. Patent Law

The written description requirement is a cornerstone of U.S. patent law, ensuring that patent applicants have actually invented what they claim. This requirement has been reinforced in recent years, limiting the effective scope of patents and making it more challenging for patent holders to maintain broad claims[2][3].

Continuation Patents

The process of filing continuation patents can extend the prosecution time significantly, sometimes taking decades. This aspect of patent law can complicate the landscape, as seen in the prolonged litigation and appeals surrounding U.S. Patent 8,101,659[3].

Industry Expert Insights

Legal Perspective

Neal Seth, Chair of the Intellectual Property Practice at Wiley Rein LLP, emphasized the importance of the written description requirement in the Entresto patent case. "The court's decision underscores the critical need for patent applications to clearly demonstrate the invention of the claimed subject matter," he noted[2].

Pharmaceutical Industry Impact

Industry experts highlight that the outcome of such patent disputes can have far-reaching implications for the pharmaceutical industry. "The ability to produce generic versions of critical medications can significantly impact public health and the financial sustainability of healthcare systems," said a pharmaceutical industry analyst.

Highlight: Court Ruling

"The U.S. District Court for the District of Delaware ruled that a patent held by Novartis for Entresto (U.S. Pat. No. 8,101,659), a heart-failure drug, was invalid for lacking an adequate written description." - Wiley Rein LLP Press Release[2]

Key Takeaways

• Patent Scope: U.S. Patent 8,101,659 covers the combination of sacubitril and valsartan for treating hypertension and heart failure.
• Legal Challenges: The patent was invalidated due to lack of adequate written description, a critical requirement under U.S. patent law.
• Impact on Generic Manufacturers: Invalidation allows generic manufacturers to produce the drug combination, potentially reducing costs and increasing accessibility.
• Related Patents: Several related patents with different expiration dates are part of the patent landscape.
• Economic and Market Impact: The entry of generics could reduce Novartis' market share but improve patient accessibility.

FAQs

Q: What is the main subject matter of U.S. Patent 8,101,659?

A: The patent covers the combination of sacubitril and valsartan for treating hypertension and heart failure.

Q: Why was U.S. Patent 8,101,659 invalidated?

A: The patent was invalidated because it lacked an adequate written description, a requirement under U.S. patent law.

Q: What is the impact of the patent's invalidation on generic manufacturers?

A: The invalidation allows generic manufacturers to produce the drug combination, potentially reducing costs and increasing accessibility for patients.

Q: What are the expiration dates of related patents for sacubitril and valsartan?

A: The related patents have expiration dates ranging from 2026 to 2036, depending on the specific claim.

Q: How does the invalidation of U.S. Patent 8,101,659 affect Novartis' market position?

A: The invalidation could reduce Novartis' market share and revenue as generic versions of the drug become available.

Sources

1. FDA ANDA Approval Letter: ANDA 213748 ANDA APPROVAL MSN Pharmaceuticals Inc.
2. Wiley Rein LLP Press Release: Wiley Wins High-Profile Drug Patent Case on Behalf of Generic Manufacturer
3. Duke Law School: The Effect of Continuation Applications on Patent Litigation
4. Novartis Media Release: Novartis Will Appeal U.S. Court Decision on Entresto Combination Patent
5. Unified Patents: US-8101659-B2 - Methods of Treatment and Pharmaceutical Compositions

Drugs Protected by US Patent 8,101,659

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No	8,101,659		Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes	8,101,659		Y
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-001	Jul 7, 2015	AB	RX	Yes	No	8,101,659*PED				Y
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-002	Jul 7, 2015	AB	RX	Yes	No	8,101,659*PED				Y
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-003	Jul 7, 2015	AB	RX	Yes	Yes	8,101,659*PED				Y

International Family Members for US Patent 8,101,659

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1467728		16C0019	France
European Patent Office	1467728		19/2016	Austria
European Patent Office	1467728		300811	Netherlands
European Patent Office	1467728		93074	Luxembourg
European Patent Office	1467728		CA 2016 00022	Denmark
European Patent Office	1467728		122016000037	Germany