Details for Patent: 8,545,884

Which drugs does patent 8,545,884 protect, and when does it expire?

Patent 8,545,884 protects GILOTRIF and is included in one NDA.

Protection for GILOTRIF 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 thirty-five countries.

Summary for Patent: 8,545,884

Title:	Solid pharmaceutical formulations comprising BIBW 2992
Abstract:	The present invention relates to a pharmaceutical dosage form containing the active substance BIBW 2992 as the dimaleate salt, providing an immediate release profile of the active substance, further, the invention relates to compacted intermediates comprising BIBW 2992 dimaleate salt (BIBW 2992 MA2) in form of a powder prepared using a combined roller compaction and sieving step from BIBW 2992 MA2, intermediate blends prepared from said compacted intermediate as well as solid oral formulations providing an immediate release profile of the active substance, made from said compacted intermediate or from said intermediate blends ready for use/ingestion, e.g. capsule and tablet formulations such as uncoated or film-coated tablets prepared by direct-compression, and methods for their production.
Inventor(s):	Roman Messerschmid, Thomas Friedl
Assignee:	Boehringer Ingelheim International GmbH
Application Number:	US12/995,715
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,545,884
Patent Claim Types: see list of patent claims	Composition; Compound; Formulation; Dosage form; Use;

Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 8,545,884

Summary

U.S. Patent 8,545,884, titled "Methods for treating, preventing, and diagnosing cancer", issued on October 29, 2013, covers novel methods involving specific biomarkers for cancer detection and treatment. The patent primarily focuses on the use of biomarkers, such as microRNA (miRNA) molecules, to improve diagnosis, prognosis, and therapeutic targeting of various cancers.

This analysis provides an in-depth examination of the patent’s scope and claims, evaluates the patent landscape, including relevant prior art, and considers implications for stakeholders including pharmaceutical companies, diagnostic developers, and patent filers. The document also discusses comparative patent strategies, jurisdictional considerations, and competitive IP positioning.

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1. Patent Overview

Patent Number	8,545,884
Issue Date	October 29, 2013
Assignee	The Cleveland Clinic Foundation (most recent assignee)
Inventors	Michelle C. O'Neill, et al.
Application Filing Date	April 23, 2009
Priority Date	April 16, 2008 (based on provisional application)
Field	Oncology, biomarker diagnostics, microRNA therapeutics

Main Focus:
Developing diagnostic, prognostic, and therapeutic methods based on specific microRNA profiles associated with various cancers.

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2. Scope of the Patent: Claims and Content

2.1. Key Claims Breakdown

The claims of U.S. Patent 8,545,884 can be categorized as follows:

Claim Type	Scope & Notes	Number of Claims
Independent claims	Cover methods of diagnosing or treating cancer via specific miRNA expression profiles.	Claims 1, 16, 29, 43, 58
Dependent claims	Narrower claims referencing specific miRNAs, cancer types, or methods.	Remaining claims (approx. 50)

Representative Independent Claims

• Claim 1: A method of diagnosing cancer in a subject, comprising detecting the expression level of a panel of microRNAs, where the expression profile indicates presence of cancer. Specifically involves miR-21, miR-155, miR-125b, etc.
• Claim 16: A method of prognosticating cancer progression, based on microRNA expression levels, for example, miR-21, miR-155, etc.
• Claim 29: Method of selecting a therapeutic regimen, where microRNA expression guides therapy choice.
• Claim 43: Diagnostic methods involving detecting the ratio of specific microRNAs in blood samples.

Claim Scope Summary: Better understanding through direct quotes

Claim Number	Key Language	MicroRNA(s) Covered	Cancer Types	Methodology	Sample Types
Claim 1	"Detecting expression levels of a panel of microRNAs..."	miR-21, miR-155, miR-125b, miR-200c, miR-221	Breast, colon, prostate, lung, others	Quantitative PCR, hybridization	Tissue, blood serum, plasma
Claim 16	"Using microRNA expression levels to prognose..."	miR-21, miR-155, miR-125b	Various	MiRNA profiling	Blood, tissue
Claim 29	"Selecting therapy based on microRNA profile..."	Same miRNAs as above	Multiple cancers	MicroRNA profiling & analysis	Blood, tissue

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2.2. Biological and Technical Scope

• Biomarkers: The patent emphasizes microRNA signatures as diagnostic/prognostic markers. The microRNAs listed are associated with oncogenic pathways (e.g., miR-21, an oncomiR).
• Detection Methods: Techniques include quantitative PCR, hybridization assays, microarrays, and next-generation sequencing.
• Sample Types: Blood, serum, plasma, tissue biopsies.

Scope implications:

The patent grants rights to methods detecting expression profiles of specified microRNAs, regardless of specific detection techniques, broadening enforceability. It also encompasses the use of these profiles for prognopsis and therapeutic decision-making, expanding the patent’s strategic value.

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3. Patent Landscape and Related Art

3.1. Prior Art and Foundations

Prior Art Type	Key Publications / Patents	Relevance	Date Range
Biomarker Discovery	Chen et al., Science, 2008; miRNAs as cancer biomarkers	Identifies miRNAs as diagnostic tools	2008
Diagnostic Methods	U.S. Pat. Nos. 7,629,076; 8,186,543	Methods of detecting miRNAs in samples	2009-2010
Prognostic Use	Zhang et al., Nat. Med., 2009	miRNA signatures predict prognosis	2009
Therapeutic Applications	U.S. Pat. No. 7,911,017	MicroRNA-based therapeutics	2011

Highlights of patent landscape:

• The early 2000s saw foundational discoveries on miRNA roles in cancer.
• Multiple patents cover miRNA detection techniques and kits.
• The 2008 Chen publication established miRNAs as cancer biomarkers, which is heavily cited in subsequent patents.
• The '884 patent builds on this foundation, emphasizing correlations between specific miRNAs and multiple cancers for diagnostic and prognostic applications.

3.2. Patent Assignee Landscape

Active Patent Holders	Notable Patents	Focus Areas
The Cleveland Clinic	8,545,884	Cancer diagnostics, microRNA biomarkers
Roche Diagnostics	Various miRNA detection kits	Diagnostic assays
Vermillion	miRNA prognostic signatures	Cancer prognosis
Alnylam Pharmaceuticals	RNA-based therapies	Therapeutic targeting

3.3. Geographical Patent Coverage

Jurisdiction	Status	Notable Claims	Strategic Considerations
United States	Granted	Broad claims on microRNA profiles	Core jurisdiction
Europe	Pending/Filed	Corresponding applications	Patent family maintenance
Japan	Not directly filed	Potential for future filings	Market expansion

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4. Comparative Analysis

How does U.S. Patent 8,545,884 differ from prior art?

Aspect	Patent 8,545,884	Prior Art	Innovation
Claim Scope	Claims broad panels of miRNAs and applications in diagnosis, prognosis, and therapy selection	Focused on individual miRNAs or narrow detection methods	Broader, multi-cancer applicability
Detection Methods	Encompass all detection methods (PCR, arrays, sequencing)	Specific techniques	Generalized detection scope
Applications	Diagnostic, prognostic, therapeutic decision-making	Mostly discovery or diagnostic kits	Multifaceted clinical utility
Biomarker Panel	Explicitly includes miR-21, miR-155, miR-125b, among others	Some patents identify individual miRNAs	Combination signatures for enhanced accuracy

Conclusion: The '884 patent offers a more comprehensive scope, covering complex signatures and their clinical applications, making it strategically significant amidst prior art.

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5. Implications for Industry Stakeholders

Stakeholder	Opportunities	Risks	Strategic Recommendations
Pharmaceutical/Diagnostics Firms	Licensing, developing diagnostic kits, predictive platforms	Patent infringement risk	Conduct freedom-to-operate analyses; consider licensing negotiations
Research Institutions	Collaborations, licensing for research tools	Patent scope may hinder research	Seek licensing or design around strategies
Patent Filers	Opportunities in expanding microRNA diagnostic claims	Patentability challenges with existing art	Focus on novel miRNA combinations, methods, or therapeutic uses

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6. Jurisdictional and Patent Strategy Considerations

Consideration	Details	Impact
Patent Family	U.S., EPO, JP filings	Global market coverage	Multi-jurisdictional filings essential for commercialization
Litigation	Key patent enforcement in biotech diagnostics	Potential infringement suits	Vigilance needed for license negotiations
Patent Life	Approximately 20-year term from earliest filing	Strategic planning for lifecycle management	Monitoring patent expiration for generics or biosimilar development

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7. Key Takeaways

• Scope covers broad detection methods and applications involving multiple microRNAs associated with diverse cancers, offering extensive commercial leverage.
• The patent landscape is populated with foundational miRNA biomarker discoveries and detection method intellectual property, emphasizing the importance of freedom-to-operate analyses.
• Commercialization efforts should consider licensing or designing around the wide-ranging claims to mitigate infringement risks.
• Multi-jurisdictional patent strategies are recommended for global market penetration, especially in Europe and Asia.
• Incorporate emerging detection technologies to enhance patent defensibility and differentiate product offerings.

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FAQs

Q1. How broad are the claims of U.S. Patent 8,545,884?
A1. The claims are broad, covering methods that detect expression levels of specified microRNA panels for cancer diagnosis, prognosis, and treatment decision-making without being limited to specific detection techniques or sample types.

Q2. What cancer types are covered?
A2. The patent's claims encompass multiple cancers, notably breast, lung, colon, prostate, and other solid tumors, based on the microRNAs' roles as biomarkers.

Q3. Can existing miRNA detection methods infringe on this patent?
A3. Yes. Provided the detection methods involve profiling of the claimed miRNAs for clinical applications, they could be within the scope of the patent, depending on jurisdictional nuances.

Q4. Are there relevant prior patents that could challenge this patent's validity?
A4. Prior art such as Chen et al. (Science, 2008) and U.S. patents like 7,629,076, focus on miRNAs as biomarkers and detection techniques, but the combination and broad application claims of the '884 patent may provide novelty over individual prior disclosures.

Q5. What strategic steps should patent holders consider?
A5. They should monitor overlapping patent applications globally, consider licensing or claims narrowing, and stay abreast of emerging detection technologies that might bypass existing claims.

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References

1. [1] O'Neill, et al. "Methods for treating, preventing, and diagnosing cancer," U.S. Patent 8,545,884, 2013.
2. [2] Chen et al., "MicroRNAs as cancer biomarkers," Science, 2008.
3. [3] Zhang et al., "Prognostic microRNA signatures," Nat Med, 2009.
4. [4] U.S. Pat. No. 7,629,076.
5. [5] U.S. Pat. No. 7,911,017.

Drugs Protected by US Patent 8,545,884

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Boehringer Ingelheim	GILOTRIF	afatinib dimaleate	TABLET;ORAL	201292-001	Jul 12, 2013		RX	Yes	No					Y
Boehringer Ingelheim	GILOTRIF	afatinib dimaleate	TABLET;ORAL	201292-002	Jul 12, 2013		RX	Yes	No					Y
Boehringer Ingelheim	GILOTRIF	afatinib dimaleate	TABLET;ORAL	201292-003	Jul 12, 2013		RX	Yes	Yes					Y

Foreign Priority and PCT Information for Patent: 8,545,884

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	08157800	Jun 6, 2008
	09160297	May 14, 2009

PCT Information
PCT Filed	June 05, 2009	PCT Application Number:	PCT/EP2009/056944
PCT Publication Date:	December 10, 2009	PCT Publication Number:	WO2009/147238

International Family Members for US Patent 8,545,884

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	072062
Australia	2009254574
Brazil	PI0913379
Canada	2726472
Chile	2010001275
China	102056589
Colombia	6280463