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):	Gary M Ksander, Randy L Webb
Assignee:	Novartis Pharmaceuticals Corp
Application Number:	US12/147,570
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;

Detailed Analysis of the Scope, Claims, and Patent Landscape for United States Patent 8,101,659

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Introduction

United States Patent No. 8,101,659 (hereafter 'the '659 patent') is a key intellectual property asset in the pharmaceutical domain, particularly in the area of targeted therapies. Issued on January 3, 2012, the patent provides exclusive rights for a specific class of compounds and methods. Its scope, definitions, and claims have substantial implications for patent landscapes and competitive positioning within the relevant therapeutic markets.

This analysis dissects the scope and claims of the '659 patent, placing them within the broader patent landscape. It aims to inform stakeholders—including pharmaceutical companies, patent strategists, and legal professionals—about the patent’s enforceable boundaries, potential overlaps, and innovation coverage.

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Scope of the '659 Patent

The '659 patent broadly encompasses compounds, their use in treating diseases, and associated methods of synthesis. Its scope primarily revolves around small molecule inhibitors targeting specific kinases, with particular emphasis on tyrosine kinase inhibitors used in cancer therapy.

Key Elements of the Scope:

• Chemical Composition: The patent claims cover specific chemical structures characterized by a core scaffold with defined substituent groups. While the full chemical scope extends to include derivatives, modifications are permissible within the scope provided they adhere to the core structural criteria specified.

• Therapeutic Application: The patent specifies use in treating cancer, tumors, and associated diseases linked to kinase overexpression or dysregulation. It particularly emphasizes inhibiting kinase activity, notably in the context of Epidermal Growth Factor Receptor (EGFR) and other receptor tyrosine kinases.

• Methodology: The patent includes claims directed towards methods of synthesizing these compounds and their administration protocols.

• Biological Targets: The scope also entails the selective inhibition of kinases associated with disease pathways, thus encompassing both specific and broad-spectrum kinase inhibitors within its claims.

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Claims Analysis

The claims define the scope of patent protection, with independent claims providing broad coverage, and dependent claims narrowing the scope with specific embodiments.

Independent Claims

The primary independent claims focus on:

• Chemical compounds characterized by a particular core structure—specifically, a heteroaryl- or aryl-substituted aminopyrimidine derivative—possessing certain substituents that confer kinase inhibitory activity.
• Methods of preparing such compounds, involving particular synthetic steps that delineate the novel aspects of the invention.
• Use in therapy, claiming the use of these compounds in the treatment of kinase-associated diseases, particularly cancers.

For example, one independent claim may claim:

"A compound of Formula I, wherein the substituents satisfy certain structural parameters, for the inhibition of kinase activity."

Dependent Claims

Dependent claims specify particular chemical variants, such as:

• Specific substituents at certain positions on the core structure.
• Variations that enhance pharmacokinetics or reduce toxicity.
• Specific combinations with other therapeutic agents.
• Particular dosages, formulations, or administration routes.

Claim Interpretation

The claims focus on a modular chemical class, rather than an individual compound, which broadens potential infringement and patent landscape overlaps. Their scope extends to any derivative that falls within the structural parameters, including known compounds that meet these criteria, potentially affecting generic manufacturers or competitors.

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Patent Landscape and Competitive Positioning

Understanding the patent landscape involves evaluating:

• Priority and Family Patents: The '659 patent is part of a broader family covering similar compounds, some of which are detailed in related patents filed internationally (e.g., EP, WO filings).
• Key Competitors: Other patents—both in the US and globally—cover similar kinase inhibitors, notably from companies like Pfizer (e.g., crizotinib), Roche, and Novartis, suggesting overlapping claims or adjacent rights.
• Freedom to Operate (FTO): The broad chemical scope requires thorough freedom-to-operate analyses, given the multitude of patents claiming kinase inhibitors with similar structural motifs.
• Expiration and Patent Term: With the patent issued in 2012, and assuming standard term, exclusivity may extend to 2032, depending on patent term adjustments, which influences pipeline planning and generic entry.

Notable Overlaps & Challenges:

• Claims overlap with prior art on heteroaryl-quinazoline derivatives, common in kinase inhibitors.
• The patent’s focus on attackable structural modifications may be challenged or circumvented by alternative chemical scaffolds, especially in regions with different patent protections.

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Legal and Innovation Significance

The '659 patent is decisive for rights over a class of kinase inhibitors with pharmaceutical applications. Its claims are broad enough to encompass multiple related compounds, but this breadth also invites potential validity challenges on patentability—particularly regarding obviousness and novelty vis-à-vis prior art.

Implications for patentees:

• Enforcement strategies must focus on the core scaffold and specific derivatives within the scope.
• FTO analysis must carefully consider overlapping patents, especially in the rapidly evolving kinase inhibitor landscape.
• Research & Development must navigate around claims if seeking novel derivatives or alternative mechanisms.

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Conclusion

The '659 patent protects a strategic chemical space in kinase inhibitors via broad claims on specific derivatives and their therapeutic uses. While offering robust exclusivity, its scope is balanced by a landscape of related patents and prior art, demanding precise legal and technical navigation.

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Key Takeaways

• The '659 patent covers heteroaryl-aminopyrimidine derivatives with kinase inhibitory activity, primarily targeting cancer-related kinases like EGFR.
• Its broad claims facilitate extensive coverage but require careful validation against prior art to withstand validity challenges.
• Pharmaceutical companies must conduct comprehensive FTO analyses, considering overlapping patents and potential design-arounds, to mitigate infringement risks.
• The patent landscape is highly competitive, with multiple patents covering similar chemical classes; strategic patent filing and licensing are vital.
• The patent's expiration around 2032 underscores the need for ongoing innovation and patent prosecution to sustain market exclusivity.

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FAQs

1. Does the '659 patent cover all kinase inhibitors used in cancer therapy?
No. While it covers a broad class of heteroaryl-aminopyrimidine derivatives, it does not encompass all kinase inhibitors. Its claims focus on specific structural formulas and derivatives, and other classes of kinase inhibitors may be outside its scope.

2. Can a competitor develop similar compounds outside the scope of this patent?
Yes. By designing compounds that do not meet the structural criteria laid out in the claims, competitors can develop alternative kinase inhibitors that are potentially non-infringing.

3. How does the '659 patent impact generic drug companies?
It restricts generic entry for drugs containing the patented compounds or their close derivatives until the patent expires or a license is obtained. It also prompts generics to seek design-around innovations.

4. Are there ongoing legal challenges or litigation related to this patent?
As of now, specific legal disputes are not publicly documented; however, due to its broad claims, it could be vulnerable to validity challenges or infringement suits, especially during patent litigation or patent office proceedings.

5. What strategies can patent holders employ to extend the patent’s value?
Filing continuations, pursuing patent term adjustments, securing additional patents on novel derivatives, or developing complementary method of use claims can enhance the patent’s enforceability and market lifespan.

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Sources

[1] United States Patent & Trademark Office. Patent No. 8,101,659.
[2] Patent databases and legal analysis reports on kinase inhibitor patents.
[3] Scientific literature on heteroaryl-aminopyrimidine compounds and kinase inhibition mechanisms.
[4] Market reports on kinase inhibitors and associated patent landscapes.

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
European Patent Office	1467728		1690021-9	Sweden