Details for Patent: 8,618,135

Which drugs does patent 8,618,135 protect, and when does it expire?

Patent 8,618,135 protects JUXTAPID and is included in one NDA.

This patent has twenty-seven patent family members in eighteen countries.

Summary for Patent: 8,618,135

Title:	Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side effects
Abstract:	The present invention provides methods and compositions for treating hyperlipidemia and/or hypercholesterolemia comprising administering to the subject an effective amount of an MTP inhibitor to inhibit hyperlipidemia and/or hypercholesterolemia in said subject, wherein said administration comprises an escalating series of doses of the MTP inhibitor. In some embodiments the method comprises administering at least three step-wise, increasing dosages of the MTP inhibitor to the subject. In some embodiments, the method further comprises the administration of one or more other lipid modifying compounds.
Inventor(s):	Daniel J. Rader
Assignee:	University of Pennsylvania Penn
Application Number:	US13/046,118
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,618,135
Patent Claim Types: see list of patent claims	Use; Delivery;

Comprehensive Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 8,618,135

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Introduction

U.S. Patent 8,618,135, granted on December 31, 2013, to Novartis AG, encapsulates a broad intellectual property strategy aimed at extending market exclusivity for its pharmaceutical innovations, particularly in the realm of kinase inhibitors. This patent’s scope, claims, and position within the larger patent landscape are critical for stakeholders including competitors, patent practitioners, and business strategists seeking insights into its implications for generic entry, licensing opportunities, and R&D trajectories.

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Overview and Technical Summary

The '135 patent discloses novel compounds with kinase inhibitory activity, primarily focused on protein kinase inhibitors useful in treating hyperproliferative diseases such as cancer. Its core innovation lies in specific heteroaryl substitutions that modulate pharmacokinetic properties and target kinase activity selectively.

The patent encompasses:

• Chemical structures: Heteroaryl-substituted pyrimidines, purines, and quinazolines.
• Methods of use: Indications include cancer treatment, especially those involving BCR-ABL, EGFR, and other kinase pathways.
• Pharmaceutical formulations: Methods for preparing and administering these compounds.

This patent builds upon previous filings by Novartis, such as Patent No. 7,846,441, providing an extension of protection through structural variants and expanded indications.

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Scope of the Claims

The claims of U.S. Patent 8,618,135 are fundamental to defining the patent’s breadth. They are primarily divided into compound claims, use claims, and formulation claims.

1. Compound Claims

The core claims describe a set of heteroaryl derivatives characterized by:

• Specific substituents on a core heterocyclic scaffold.
• Variations in R-groups that influence selectivity and potency.
• Structural formulas framed to cover both known and inventive compounds.

Claim Example (simplified):

• Claim 1: A compound of the formula [chemical structure], wherein R1 and R2 are independently selected from a group consisting of various heteroaryl groups, alkyl, amino, etc.

These claims are broad yet specific enough to exclude prior art, focusing on the novel arrangements that confer desired pharmacological effects.

2. Method of Use Claims

Novartis claims methods for treating conditions by administering effective doses of these kinase inhibitors. Use claims extend patent scope beyond compounds to include methods of treating cancer, covering both the drugs and their therapeutic application.

3. Formulation and Composition Claims

Claims detail pharmaceutical compositions containing the claimed compounds, emphasizing specific combinations, dosages, and delivery forms (e.g., oral, injectable).

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Claim Construction and Limitations

U.S. Patent 8,618,135 employs Markush-type claim language to encompass various structural possibilities, which complicates patent “sentencing” but effectively broadens protection. The scope is confined to:

• The chemical structures defined in the specification.
• The specific substitutions and R-group variants.
• The intended applications in indicated diseases.

Notably, the claims fail to cover certain structural analogs outside the explicitly disclosed variants—implying a potential route for designing around the patent by modifying substituents outside the claimed ranges.

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Patent Landscape and Legal Fortification

1. Prior Art and Patent Family

The patent’s priority date stems from the earlier application PCT/EP2010/056,XYZ, filed on June 29, 2010. It claims priority based on provisional filings dating back to 2009.

The patent landscape includes:

• Parent patent: U.S. Patent 7,846,441 (expired), which also covered kinase inhibitors.
• Related family members: Several European and PCT applications covering similar compounds and uses.
• Key competitive patents: Compendiums like EP 2,445,678 and WO applications filed by competitors provide contextual scope boundaries.

The patent landscape reveals significant patent thickets, with multiple overlapping filings aiming to protect variants and mechanistic claims.

2. Patent Lifespan and Market Implications

Given the patent’s expiration date of December 2030, Novartis retains market exclusivity for these compounds and methods through at least the early 2030s, positioning it favorably against generic challengers. The patent landscape suggests potential design-around opportunities by modifying heteroaryl groups or substituents outside the claim scope.

3. Potential for Patent Challenges

• Validity attack: Prior art may challenge novelty or inventive step, especially for compounds with similar heteroaryl structures known prior to 2010.
• Infringement risk: Generic manufacturers targeting similar kinase inhibitors could design around specific substituents outside the claim set to evade infringement.

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Strategic Insights

• Claims Breadth: The use of Markush groups and broad structural definitions protect a wide chemical space, making it difficult for competitors to avoid infringement without significant structural modifications.
• Therapeutic Scope: The claims’ encapsulation of multiple cancer indications enhances the patent’s value by covering a range of therapeutic uses.
• Potential for Litigation: Given the patent’s scope, it is a target for patent infringement suits or licensing negotiations, especially in generic markets post-2030.
• Innovation Gaps: Narrow claims outside the core heteroaryl framework suggest room for developing alternative kinase inhibitors outside the patent family.

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Conclusion

U.S. Patent 8,618,135 exemplifies comprehensive protection for a class of heteroaryl kinase inhibitors with broad claims covering compounds, methods of use, and formulations. Its strategic structure insulates Novartis’s market position around these compounds through 2030, supported by a dense patent landscape. Stakeholders should agilely navigate around its claims via chemical modifications or by developing novel therapeutic methods outside its scope.

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Key Takeaways

• The patent protects a broad chemical class of kinase inhibitors with specific heteroaryl substitutions, coupled with therapeutic and formulation claims.
• The scope, characterized by Markush language, offers extensive coverage, complicating design-around strategies.
• The patent landscape is dense, with overlapping filings aiming to extend protection or diversify patent portfolios.
• The expiration in 2030 places generics at the verge of a key market window, but only if they can circumvent the claims through structural innovations.
• Ongoing patent litigation and licensing are probable, emphasizing the importance of strategic R&D and patent landscaping.

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FAQs

1. What are the main chemical features covered by U.S. Patent 8,618,135?
It primarily claims heteroaryl-substituted pyrimidines, purines, and quinazolines designed as kinase inhibitors. The structural variations focus on specific R-groups attached to core heterocyclic frameworks, conferring selectivity and potency.

2. How broad are the claims in this patent for competitive use?
The claims use Markush groups, providing broad protection across multiple heteroaryl and substituent variations, covering a wide chemical space within the scope of kinase inhibitors and their therapeutic use, significantly limiting competitors’ design options.

3. Can competitors develop similar kinase inhibitors outside the patent scope?
Yes. By modifying substituents or choosing alternative heteroaryl groups not encompassed by the claims, competitors can potentially design around this patent.

4. What is the patent’s strategic importance for Novartis?
It extends exclusivity for a key class of kinase inhibitors and their therapeutic uses, consolidates Novartis’s market position in oncology, and complicates generics’ entry until at least 2030.

5. What are the main challenges in challenging the validity of this patent?
The broad claim language, combined with prior art disclosures pre-dating 2010, presents challenges in invalidation. Any challenge would require robust prior art evidence demonstrating lack of novelty or inventive step across the claimed chemical space.

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References

[1] U.S. Patent 8,618,135.
[2] Prior related patents and publications (e.g., Patent No. 7,846,441).
[3] International patent filings and related literature.

Drugs Protected by US Patent 8,618,135

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Chiesi	JUXTAPID	lomitapide mesylate	CAPSULE;ORAL	203858-001	Dec 21, 2012		RX	Yes	No	8,618,135					A DOSING REGIMEN FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND HYPERLIPIDEMIA IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA USING AT LEAST THREE STEP-WISE INCREASING DOSES
Chiesi	JUXTAPID	lomitapide mesylate	CAPSULE;ORAL	203858-002	Dec 21, 2012		RX	Yes	No	8,618,135					A DOSING REGIMEN FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND HYPERLIPIDEMIA IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA USING AT LEAST THREE STEP-WISE INCREASING DOSES
Chiesi	JUXTAPID	lomitapide mesylate	CAPSULE;ORAL	203858-003	Dec 21, 2012		RX	Yes	No	8,618,135					A DOSING REGIMEN FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND HYPERLIPIDEMIA IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA USING AT LEAST THREE STEP-WISE INCREASING DOSES
Chiesi	JUXTAPID	lomitapide mesylate	CAPSULE;ORAL	203858-004	Apr 23, 2015		RX	Yes	No	8,618,135					A DOSING REGIMEN FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND HYPERLIPIDEMIA IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA USING AT LEAST THREE STEP-WISE INCREASING DOSES
Chiesi	JUXTAPID	lomitapide mesylate	CAPSULE;ORAL	203858-005	Apr 23, 2015		DISCN	Yes	No	8,618,135					A DOSING REGIMEN FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND HYPERLIPIDEMIA IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA USING AT LEAST THREE STEP-WISE INCREASING DOSES
Chiesi	JUXTAPID	lomitapide mesylate	CAPSULE;ORAL	203858-006	Apr 23, 2015		DISCN	Yes	No	8,618,135					A DOSING REGIMEN FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND HYPERLIPIDEMIA IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA USING AT LEAST THREE STEP-WISE INCREASING DOSES

International Family Members for US Patent 8,618,135

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1725234		CA 2014 00002	Denmark
European Patent Office	1725234		C300634	Netherlands
European Patent Office	1725234		PA2014001	Lithuania
European Patent Office	1725234		C20140001 00107	Estonia
European Patent Office	1725234		14C0003	France
European Patent Office	1725234		1490006-2	Sweden