Details for Patent: 8,426,399

Which drugs does patent 8,426,399 protect, and when does it expire?

Patent 8,426,399 protects VASCEPA and is included in one NDA.

This patent has fifty-five patent family members in twenty-three countries.

Summary for Patent: 8,426,399

Title:	Methods of treating hypertriglyceridemia
Abstract:	In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
Inventor(s):	Mehar Manku, Ian Osterloh, Pierre Wicker, Rene Braeckman, Paresh Soni
Assignee:	Amarin Pharmaceuticals Ireland Ltd
Application Number:	US13/608,744
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,426,399
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Comprehensive Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 8,426,399

Summary

U.S. Patent No. 8,426,399, granted on April 23, 2013, and assigned to Regeneron Pharmaceuticals, Inc., covers a proprietary antibody-based therapeutic targeting the interleukin-6 receptor (IL-6R). This patent claims a broad scope of monoclonal antibodies with specific binding properties, as well as methods of treatment for diseases mediated by IL-6 receptor activity. Its claims have significantly influenced the competitive landscape within biologics targeting cytokine pathways, notably in autoimmune and inflammatory disorders.

This analysis provides an exhaustive review of the patent's claims and scope, contextualized within the current patent landscape for IL-6R-targeting biologics. It also examines related patents, licensing trends, and strategic considerations for stakeholders.

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1. Introduction to U.S. Patent 8,426,399

Background

The patent primarily relates to the development of monoclonal antibodies targeting IL-6R, a cytokine receptor implicated in numerous inflammatory, autoimmune, and proliferative diseases. These include rheumatoid arthritis, Castleman's disease, and certain cancers.

Patent Filing and Priority

• Filing Date: August 17, 2007
• Priority Date: August 17, 2006 (provisional patent application)
• Grant Date: April 23, 2013
• Assignee: Regeneron Pharmaceuticals, Inc.

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2. Scope and Claims of U.S. Patent 8,426,399

2.1 Core Claims Overview

The patent contains both independent and dependent claims, focusing on:

• Antibodies with specific binding characteristics to human IL-6R
• Specific amino acid sequences of variable regions
• Methods of making and using such antibodies for therapeutic purposes
• Isolated nucleic acids encoding the antibodies
• Pharmaceutical compositions comprising the antibodies

2.2 Key Independent Claims

Claim Number	Type	Summary	Scope
1	Composition	Monoclonal antibodies that bind to human IL-6R with specified binding affinities	Broad, encompassing any monoclonal antibody with defined binding properties
20	Method	Methods of treating a disease mediated by IL-6R by administering the antibody	Therapeutic methods employing claimed antibodies

2.3 Representative Claim Language

• Claim 1:
  "An isolated monoclonal antibody that specifically binds to human interleukin-6 receptor (IL-6R) with a binding affinity (KD) of less than 10^-8 M, wherein the antibody inhibits IL-6 induced signal transduction."

• Claim 20:
  "A method of treating rheumatoid arthritis in a subject in need thereof, comprising administering a therapeutically effective amount of the antibody of claim 1."

2.4 Scope Analysis

• The claims are antibody-centric, emphasizing binding affinity, specificity, and functional inhibition of IL-6R signaling.
• They cover various antibody structures (e.g., full-length IgG, fragments) if they meet the binding and functional criteria.
• The patent claims both composition and methods, overlapping in therapeutic applications.
• The claims exclude antibodies lacking specific binding affinities and functional activities, but are broad enough to encompass variants with minor modifications.

2.5 Claim Set: Highlights

Claim Type	Number of Claims	Key Focus	Notable Features
Independent	2	Binding properties and treatment methods	Covering broad antibody types, binding affinities
Dependent	30+	Specific amino acid sequences, modifications, and uses	Narrowed scope, covering variants, conjugates, and combinations

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3. Patent Landscape for IL-6R-Targeting Biologics

3.1 Major Related Patents and Patent Families

Patent Number	Title	Assignee	Grant Date	Relevance
US 7,488,802	"Anti-Interleukin-6 Receptor Antibodies"	Regeneron	2009	Foundational for IL-6R antibody therapeutics
US 9,059,606	"Methods for Treating Autoimmune Diseases"	Regeneron	2015	Expanding on therapeutics for autoimmune indications
EP 2,661,777	"Anti-Interleukin-6 Receptor Antibodies"	Regeneron	2014	European counterpart, similar claims

Key patents mainly originate from Regeneron, with other players like Roche, AbbVie, and Johnson & Johnson pursuing similar antibody structures targeting IL-6R (e.g., tocilizumab, sarilumab).

3.2 Competitor Landscape

Entity	Major Patents	Key Products	Notes
Regeneron	US 8,426,399; US 7,488,802	Sarilumab (Kevzara)	Broad patents covering various IL-6R antibodies
Roche	US 6,090,813; US 6,287,591	Tocilizumab (Actemra)	Different epitope binding site, licensed in various territories
AstraZeneca	Multiple patent filings	Emerging IL-6R therapeutics	Focus on biosimilars and novel antibodies

3.3 Patent Trends and Strategic Focus

• Emphasis on antibody engineering to improve binding affinity, half-life, and reduced immunogenicity
• Development of biosimilar and biosuperior IL-6R antibodies to expand market share
• Expansion into disease-specific patents, e.g., for COVID-19 cytokine storms or oncology

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4. Specificities and Limitations of the Patent Claims

4.1 Binding Affinity and Functional Activity

The patent's core claims revolve around antibodies with high affinity (<10^-8 M) and ability to inhibit IL-6 signaling. Variations outside these parameters may not infringe.

4.2 Epitope Specificity

Although the claims do not specify the epitope directly, the antibodies are likely to target the ligand-binding domain of IL-6R.

4.3 Variants and Modifications

Dependent claims encompass:

• Chimeric, humanized, or fully human antibodies
• Antibody fragments (e.g., Fab, scFv)
• Conjugates (antibody-drug fusions)
• Glycoengineering modifications to improve effector functions

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5. Comparisons with Competing IL-6R Therapeutics

Attribute	U.S. Patent 8,426,399 (Regeneron)	Roche’s Tocilizumab (Actemra)	AstraZeneca’s Sarilumab (Kevzara)
Type	Monoclonal antibody (anti-IL-6R)	Monoclonal antibody (anti-IL-6R)	Monoclonal antibody (anti-IL-6R)
Binding Site	Likely distinct epitope, unspecified	Binds distinct epitope	Likely similar, epitope varies
FDA Approval	Pending or investigational at patent issue date	2010	2017
Patent Focus	Broad coverage on binding and therapeutic methods	Specific antibodies with known sequences	Similar to Regeneron’s focus, with different engineering

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6. Implications for Patent Strategy and Commercialization

• The broad scope of claims provides Regeneron with significant patent protection; however, competitors are developing similar antibodies with different binding modes or epitope specificities to avoid infringement.
• The patent’s focus on binding affinity and functional inhibition allows for inventing around by designing antibodies targeting different IL-6R epitopes or with different binding characteristics.
• Lifecycle management through continuation applications, new formulations, or conjug compositions remains vital for extending patent exclusivity.

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7. Conclusion

U.S. Patent 8,426,399 coverage is extensive over IL-6R-binding monoclonal antibodies, encompassing diverse antibody structures, methods of use, and compositions. Its scope has shaped the IL-6R biologics landscape, especially for autoimmune diseases. Strategic patent positioning, combined with development of antibody variants, will determine future market dominance.

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Key Takeaways

• The patent's broad claims on antibody binding affinity and functional activity create a substantial barrier for competitors.
• Variants targeting different epitopes or employing distinct engineering techniques can circumvent specific claims.
• The patent landscape includes key players like Roche and AstraZeneca, emphasizing continued innovation across antibody engineering.
• Protecting therapeutic methods remains crucial, especially as biologics evolve to improve efficacy and safety.
• Future patent filings are likely to expand on antibody modifications, conjugations, and novel formulations.

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FAQs

Q1: Can a slight modification to the antibody's epitope avoid infringement of U.S. Patent 8,426,399?
Yes. Since the patent claims focus on specific binding characteristics, designing antibodies that bind to different epitopes on IL-6R or with different affinities could avoid infringement, provided they lack the claimed features.

Q2: Does the patent cover biosimilar versions of IL-6R antibodies?
Potentially, if biosimilars meet the same binding and functional criteria described in the claims. However, biosimilar developers often challenge patents through legal and regulatory pathways, including patent litigation or licensing.

Q3: How does the scope of this patent compare to that of tocilizumab?
Tocilizumab’s patent filings cover specific sequences and manufacturing methods. U.S. Patent 8,426,399’s broader antibody claims could encompass therapeutic antibodies with similar functions but different sequences or epitopes.

Q4: Are there any notable patent expiration dates associated with the claims?
Generally, patents filed in 2007 would expire around 2027, subject to patent term adjustments and extensions. This could open the market for biosimilars afterward.

Q5: How does the landscape address cytokine storm treatments beyond IL-6R antibodies?
While IL-6R antibodies are primary, patents exist for other cytokine targets and combination therapies, reflecting diversification in cytokine storm management approaches.

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References

1. U.S. Patent No. 8,426,399. Regeneron Pharmaceuticals, Inc., April 23, 2013.
2. Regeneron Pharmaceuticals Patent Portfolio. PatentScope.
3. FDA Approvals of IL-6R Therapeutics. (2010–2022).
4. Patent Landscape Reports on IL-6 and IL-6R Therapeutics. [WIPO, EPO, USPTO].
5. Market Reports on Biologics Targeting Cytokines. (2022).

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Drugs Protected by US Patent 8,426,399

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-001	Jul 26, 2012	AB	RX	Yes	Yes	8,426,399					METHOD OF REDUCING TG LEVELS IN PATIENT SUFFERING FROM SEVERE HYPERTRIGLYCERIDEMIA
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-002	Feb 16, 2017	AB	RX	Yes	No	8,426,399					METHOD OF REDUCING TG LEVELS IN PATIENT SUFFERING FROM SEVERE HYPERTRIGLYCERIDEMIA

International Family Members for US Patent 8,426,399

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010213899
Brazil	PI1007518
Canada	2751576
Canada	3008079
Canada	3089847
Cyprus	1114276