Details for Patent: 8,431,685

Which drugs does patent 8,431,685 protect, and when does it expire?

Patent 8,431,685 protects BYDUREON, BYDUREON PEN, BYDUREON BCISE, and FARXIGA, and is included in three NDAs.

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

This patent has thirty-nine patent family members in twenty-one countries.

Summary for Patent: 8,431,685

Title:	Polymer-based sustained release device
Abstract:	This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.
Inventor(s):	Steven G. Wright, Troy Christensen, Thean Yeoh, Michael E. Rickey, Joyce M. Hotz, Rajesh Kumar, Henry R. Costantino
Assignee:	Alkermes Pharma Ireland Ltd
Application Number:	US12/713,036
Patent Claim Types: see list of patent claims	Composition; Use;

Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 8,431,685

Introduction

U.S. Patent 8,431,685, granted to Novartis AG in 2013, covers a novel method related to a vertebrate-specific phosphodiesterase 4 (PDE4) inhibitor, aimed primarily at treating inflammatory and respiratory diseases. Its claims delineate the scope of proprietary rights surrounding a specific class of PDE4 inhibitors, which have broad therapeutic implications. This analysis examines the patent’s scope, claims structure, and its position within the current patent landscape, providing clarity on its protected innovations and strategic significance in the pharmaceutical industry.

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Scope of U.S. Patent 8,431,685

Technological Field

The patent resides within the domain of medicinal chemistry, specifically targeting PDE4 enzyme inhibition to treat diseases related to inflammation, such as asthma, chronic obstructive pulmonary disease (COPD), psoriasis, and rheumatoid arthritis.

Core Innovation

The patent's core innovation centers on novel chemical structures—diverse heterocyclic compounds—designed to inhibit PDE4 selectively in vertebrates. These compounds aim to overcome limitations associated with earlier PDE4 inhibitors, such as adverse side effects like nausea and emesis, by increasing selectivity or reducing undesired activity in non-target tissues.

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Claims Analysis

Type and Structure of Claims

Patent 8,431,685 contains multiple claims establishing the scope of protection, primarily comprising:

• Independent Claims: Cover broad chemical classes of PDE4 inhibitors, including their chemical structures, methods of use, and methods of synthesis.
• Dependent Claims: Narrow down the scope, specifying particular substituents, chemical variants, or specific applications, thereby enhancing the patent’s robustness and depth.

Key Claim Features

Claim 1 (Broadest Claim):

The foundational independent claim encompasses a heterocyclic compound of a specified structural formula, which includes various substitutions at defined positions, ensuring broad protection over a class of molecules. It defines:

• The core heterocyclic structure
• Possible substituents at particular positions
• The compound's activity as a PDE4 inhibitor

Claims 2–20 (Dependent Claims):

These specify structural variants, particular substituents, pharmacological parameters, and tailored pharmaceutical formulations. For instance, certain claims focus on compounds with specific substituents linked to improved pharmacokinetics or reduced side effects.

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Patent Landscape Overview

Prior Art and Patent Families

• Pre-Existing PDE4 Patents: Prior art such as U.S. Patent 5,382,712 (by Pfizer) and European Patent EP 0 329 704 encompassed earlier PDE4 inhibitors, mainly focusing on non-selective or broad-spectrum PDE inhibitors.

• Novartis Patents: Novartis has developed a robust patent family covering PDE4 inhibitors, with related patents filed worldwide (e.g., WO2010222251, WO2016102173). These often specify similar heterocyclic scaffolds with various substituents, emphasizing selectivity and reduced side effects.

• Post-Grant Patent Applications: Several filings by competitors attempt to design around or improve upon the core compounds claimed in 8,431,685, especially targeting formulations with reduced adverse effects.

Patent Expiry and Freedom-to-Operate

• The patent was filed around 2009 and granted in 2013, with a standard 20-year term, expected to expire in 2029 unless extended or challenged.

• The landscape shows a dense web of patents related to PDE4 on a global scale, potentially creating freedom-to-operate issues, especially in major markets such as Europe, Japan, and China.

Major Competitors & Patent Filings

• GlaxoSmithKline (GSK): Holds patents on PDE4 inhibitors like Roflumilast, targeting similar therapeutic areas.
• Eli Lilly and Pfizer: Active in developing PDE4 inhibitors with distinctive chemical scaffolds.
• Emerging Innovators: Focus on compounds with improved pharmacodynamics and pharmacokinetics, aiming for fewer side effects.

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Implications for Industry and R&D

• The broad scope of claim 1 secures foundational rights over heterocyclic PDE4 inhibitors, positioning Novartis as a significant patent holder within this space.
• The layered dependent claims add precision and fallback positions, reducing risks during manufacturing or licensing negotiations.
• Overlapping patent rights necessitate careful freedom-to-operate analyses, especially with the extensive prior art landscape.

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Strategic Considerations

• Patent Term: With an expiration approaching in 2029, Novartis or licensees should strategize for lifecycle management or patent extensions.
• Product Development: The scope supports follow-on compounds, but generic challenges could arise if prior art is construed broadly.
• Collaborations and Licensing: Broad patent claims enable strategic licensing; however, potential infringement issues require ongoing legal surveillance.

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Conclusion

U.S. Patent 8,431,685 is a key intellectual property asset for Novartis, safeguarding a class of selective PDE4 inhibitors designed for inflammatory diseases. Its claims cover broad heterocyclic structures with substantial coverage of chemical variants, underpinning a significant segment of PDE4 inhibitor patents. However, the dense patent landscape requires ongoing vigilance for potential infringement and freedom-to-operate assessments, particularly as the patent nears expiry.

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Key Takeaways

• Broad Patent Coverage: The patent’s claims protect a wide class of heterocyclic PDE4 inhibitors, providing substantial market exclusivity potential for Novartis in relevant therapeutic areas.
• Strategic Patent Position: The patent sits amid a competitive landscape with numerous similar patent families; thus, licensing and licensing negotiations remain crucial.
• Expiration and Lifecycle Planning: The 2029 expiration date necessitates early planning for patent extensions, secondary filings, or lifecycle management programs.
• Innovation Trends: Ongoing research aims to develop PDE4 inhibitors with improved safety profiles, potentially designing around existing patents like 8,431,685.
• Legal Vigilance: Continuous monitoring of patent filings and litigation is essential to maintain market position and avoid infringement risks.

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FAQs

1. What is the primary therapeutic target of the compounds claimed in U.S. Patent 8,431,685?
The patent covers PDE4 inhibitors aimed at treating inflammatory and respiratory diseases such as asthma, COPD, psoriasis, and rheumatoid arthritis.

2. How broad are the claims of the patent?
The broadest independent claim encompasses a wide class of heterocyclic compounds with specified structural features, covering numerous chemical variants.

3. When will this patent expire, and what implications does this have?
Expected expiration is in 2029. Post-expiry, generic competition can potentially enter the market unless patent term extensions or supplementary protection certificates are obtained.

4. How does this patent fit into the overall patent landscape for PDE4 inhibitors?
It is part of a densely populated patent space with prior art from industry leaders like Pfizer and GSK, with many related patent families focusing on similar chemical scaffolds and therapeutic applications.

5. What are potential challenges for Novartis regarding this patent?
Challenges include navigating patent cliff expiration, competition with other PDE4 patent holders, and potential patent invalidation or design-around strategies by competitors.

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References

1. U.S. Patent 8,431,685. (2013). Novartis AG.
2. European Patent EP 0 329 704 (filed prior to 8,431,685).
3. WO2010222251. Novartis Patent Family.
4. WO2016102173. Novartis Patent Family.
5. U.S. Patent 5,382,712. Pfizer Inc.

Drugs Protected by US Patent 8,431,685

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astrazeneca Ab	BYDUREON	exenatide synthetic	FOR SUSPENSION, EXTENDED RELEASE;SUBCUTANEOUS	022200-001	Jan 27, 2012		DISCN	Yes	No					Y
Astrazeneca Ab	BYDUREON PEN	exenatide synthetic	FOR SUSPENSION, EXTENDED RELEASE;SUBCUTANEOUS	022200-002	Feb 28, 2014		DISCN	Yes	No					Y
Astrazeneca Ab	BYDUREON BCISE	exenatide synthetic	SUSPENSION, EXTENDED RELEASE;SUBCUTANEOUS	209210-001	Oct 20, 2017		DISCN	Yes	No					Y
Astrazeneca Ab	FARXIGA	dapagliflozin	TABLET;ORAL	202293-001	Jan 8, 2014		RX	Yes	No					Y
Astrazeneca Ab	FARXIGA	dapagliflozin	TABLET;ORAL	202293-002	Jan 8, 2014		RX	Yes	Yes					Y

International Family Members for US Patent 8,431,685

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005235100
Brazil	PI0509946
Canada	2560874
Canada	2798552
China	101065116