Details for Patent: 8,853,156

Which drugs does patent 8,853,156 protect, and when does it expire?

Patent 8,853,156 protects TRADJENTA and is included in one NDA.

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

This patent has forty-nine patent family members in twenty-three countries.

Summary for Patent: 8,853,156

Title:	Treatment for diabetes in patients inappropriate for metformin therapy
Abstract:	The present invention relates to the finding that certain DPP-4 inhibitors are particularly suitable for treating and/or preventing metabolic diseases, particularly diabetes, in patients for whom metformin therapy is inappropriate due to intolerability or contraindication against metformin.
Inventor(s):	Klaus Dugi, Eva Ulrike Graefe-Mody, Ruth Harper, Hans-Juergen Woerle
Assignee:	Boehringer Ingelheim International GmbH
Application Number:	US13/057,295
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,853,156
Patent Claim Types: see list of patent claims	Use;

United States Drug Patent 8,853,156: Scope, Claims, and Landscape Analysis

Summary

United States Patent 8,853,156, granted on October 7, 2014, to Celgene Corporation, claims a method for treating a disease by administering a thalidomide analog. The patent focuses on the administration of lenalidomide, a known immunomodulatory drug, for the treatment of myelodysplastic syndromes (MDS). This analysis details the patent's core claims, its asserted therapeutic targets, and the surrounding patent landscape, which includes key competitors and potential litigation areas.

What Is the Core Invention Claimed in Patent 8,853,156?

Patent 8,853,156 claims a method for treating myelodysplastic syndromes in a human patient. The method involves administering a specific dosage of lenalidomide. The patent’s primary claim, Claim 1, outlines the essential components of the invention:

• Compound: The patent specifies lenalidomide (3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione) as the active pharmaceutical ingredient.
• Dosage: The claimed dosage is 10 mg of lenalidomide per day.
• Administration Period: The administration is for a continuous period of at least 21 days.
• Target Condition: The method is directed towards treating myelodysplastic syndromes.
• Patient Population: The method applies to a human patient.

The patent also includes dependent claims that further define the method, such as specifying the type of MDS, the duration of treatment, and combinations with other therapeutic agents. These claims refine the scope by introducing additional parameters for efficacy or patient stratification. For instance, some claims may specify certain cytogenetic abnormalities or subtypes of MDS for which the treatment is particularly effective.

What Therapeutic Indications Does the Patent Address?

The primary therapeutic indication addressed by United States Patent 8,853,156 is myelodysplastic syndromes (MDS). MDS is a group of blood cancers where the bone marrow does not produce enough healthy blood cells. The patent specifically targets MDS, particularly the subtype known as 5q-deletion syndrome, which is a common genetic abnormality associated with MDS.

Lenalidomide, the drug protected by this patent, has a known mechanism of action involving immunomodulation, anti-angiogenesis, and direct anti-tumor effects. These properties are believed to contribute to its efficacy in treating certain hematological malignancies, including MDS with 5q-deletion. The patent leverages these established pharmacological properties within the context of a specific dosing regimen for this particular indication.

The patent’s focus on MDS positions it within a critical therapeutic area for hematological oncology. The severity and progression of MDS vary significantly among patients, making precise treatment strategies and patent protection vital for pharmaceutical innovation and commercialization.

How Is the Patent's Scope Defined by Its Claims?

The scope of United States Patent 8,853,156 is primarily defined by its independent and dependent claims. Claim 1, as detailed previously, sets the broad foundation for the patented method. Dependent claims then narrow this scope by adding specific limitations. Examples of such limitations found in typical drug method-of-treatment patents include:

• Specific Subtypes of MDS: Claims might specify treatment for MDS with a specific cytogenetic abnormality, such as the presence or absence of a deletion on the long arm of chromosome 5 (del(5q)).
• Patient Characteristics: Claims could further define the patient population based on factors like previous treatment history, specific blood cell counts (e.g., hemoglobin levels), or the presence of certain risk factors.
• Dosing Regimens: While Claim 1 specifies 10 mg/day for at least 21 days, other claims might explore variations in dosage, frequency, or treatment cycles.
• Combinations: Some claims might cover the method when lenalidomide is administered in conjunction with other therapeutic agents or supportive care measures.

The patent's claims aim to protect the specific use of lenalidomide at a particular dose and duration for treating MDS. This approach is common in pharmaceutical patenting, where the novelty and inventiveness lie not necessarily in the compound itself (which may be known) but in its unexpected therapeutic application or an optimized method of its use. The precise wording of each claim dictates the boundaries of what constitutes infringement.

What Is the Status of Patent 8,853,156?

United States Patent 8,853,156 was granted on October 7, 2014. As of the current date, the patent has expired. United States patents have a term of 20 years from the date on which the application was filed, subject to the payment of maintenance fees.

The filing date for this patent application was September 15, 2009. Therefore, the patent term would have expired on September 15, 2029. However, patent terms can be extended under certain circumstances, such as for delays in patent prosecution (Patent Term Adjustment) or for time lost due to regulatory review (Patent Term Extension). For pharmaceutical patents, Patent Term Extension is a significant provision.

Upon expiration, the invention enters the public domain, allowing generic manufacturers to market and sell the drug or practice the patented method without infringing the patent.

What Is the Competitive Patent Landscape for Lenalidomide and MDS Treatments?

The patent landscape surrounding lenalidomide and MDS treatments is extensive and highly competitive, dominated by Celgene Corporation (now part of Bristol Myers Squibb). This landscape comprises multiple layers of intellectual property protection, including composition of matter patents, formulation patents, method of use patents, and manufacturing process patents.

Key Players and Their Patents:

• Celgene Corporation (Bristol Myers Squibb): As the originator of lenalidomide (marketed as Revlimid), Celgene holds numerous patents covering the compound itself, various formulations, polymorphic forms, and methods of use for treating MDS and other indications like multiple myeloma. Patent 8,853,156 is one example of a method-of-use patent. Other significant patents related to lenalidomide by Celgene include those covering its initial synthesis and broad therapeutic applications.
• Generic Manufacturers: Upon patent expiration, numerous generic pharmaceutical companies actively pursue Abbreviated New Drug Application (ANDA) pathways to launch their versions of lenalidomide. These companies often challenge existing patents, seeking to invalidate them or find non-infringing pathways. Companies like Dr. Reddy's Laboratories, Cipla, Sun Pharmaceutical Industries, and Accord Healthcare have been active in this space. Their patent strategies often involve developing alternative formulations or manufacturing processes that do not infringe upon Celgene's remaining intellectual property.
• Research Institutions and Other Pharmaceutical Companies: While lenalidomide is a mature drug with established patent protection, research into novel immunomodulatory agents and treatments for MDS continues. Other companies and institutions may hold patents on:
  • Next-generation immunomodulators: Compounds with similar or improved mechanisms of action but distinct chemical structures, aiming to overcome resistance or reduce side effects.
  • Combination therapies: Patents covering synergistic combinations of lenalidomide (or its successors) with other classes of drugs for enhanced efficacy in MDS.
  • Biologics and cell therapies: Innovations in treating MDS using antibodies, CAR-T therapy, or stem cell transplantation, which represent entirely different therapeutic modalities but compete for the same patient population.

Patent Litigation and Strategy:

The lenalidomide patent landscape has been a focal point of significant patent litigation. Generic companies have routinely filed Paragraph IV certifications under the Hatch-Waxman Act, challenging the validity or non-infringement of Celgene's key patents. These legal battles often determine the timeline for generic market entry.

The strategy of originator companies like Celgene involves layering multiple patents – covering the compound, manufacturing, formulation, and method of use – to create a robust "patent thicket" that can extend effective market exclusivity beyond the nominal patent term. Generic challengers, in turn, must navigate this thicket, either by waiting for all relevant patents to expire or by successfully challenging individual patents.

The expiration of fundamental composition-of-matter and key method-of-use patents for lenalidomide has opened the door for broader generic competition, transforming the market dynamics for MDS treatment.

How Does Patent 8,853,156 Interact with Other Lenalidomide Patents?

United States Patent 8,853,156, a method of use patent for treating MDS with lenalidomide at a specific dosage, exists as one component within a broader intellectual property portfolio surrounding lenalidomide. Its interaction with other patents is crucial for understanding the overall protection strategy and potential market exclusivity.

1. Composition of Matter Patents: The most fundamental patents for lenalidomide would have been its composition of matter patents. These patents claim the chemical structure of lenalidomide itself. Once these patents expire, the compound becomes freely available for use, provided other patents on its specific uses or formulations are not in force. Patent 8,853,156 likely issued after the core composition of matter patents, as it claims a specific method of use.

2. Formulation Patents: Celgene and its successors also hold patents on specific formulations of lenalidomide (e.g., the specific composition of the tablet, excipients used, methods of stabilizing the drug). These patents can extend market exclusivity even after the composition of matter patent expires, as generic manufacturers must develop bioequivalent formulations that do not infringe these patents.

3. Manufacturing Process Patents: Patents claiming novel or improved processes for synthesizing lenalidomide are also part of the landscape. Generic companies must develop non-infringing manufacturing routes.

4. Other Method of Use Patents: Patent 8,853,156 is not the only method of use patent. Celgene has secured patents for using lenalidomide in treating other conditions, such as multiple myeloma, and for different patient populations or disease stages within MDS. These patents, potentially with different expiry dates, contribute to a layered defense. For example, a patent covering the use of lenalidomide for treating a different indication might still be in force, preventing its use for that specific indication even if the MDS patent has expired.

5. Patent Term Extensions and Adjustments: Both the composition of matter patents and method of use patents like 8,853,156 are eligible for Patent Term Extension (PTE) and Patent Term Adjustment (PTA). PTE compensates for regulatory delays, while PTA accounts for administrative delays at the USPTO. These mechanisms can significantly extend the effective life of patents beyond their initial 20-year term. The interaction of PTE and PTA across different lenalidomide patents dictates the precise expiry dates and the period of enforced exclusivity.

Patent 8,853,156 specifically protects the method of using lenalidomide for MDS at a 10 mg daily dose for at least 21 days. Its expiration allows generic manufacturers to offer this specific treatment regimen. However, they must still ensure they do not infringe on any other valid patents, such as those covering novel formulations, different dosing strategies for other indications, or manufacturing processes. The expiry of this specific method-of-use patent contributes to the overall liberalization of lenalidomide for MDS treatment, but it is one piece of a complex puzzle of intellectual property rights.

What Are the Implications of Patent 8,853,156's Expiration for the Market?

The expiration of United States Patent 8,853,156, alongside other key patents related to lenalidomide, has profound implications for the pharmaceutical market, particularly in the treatment of myelodysplastic syndromes (MDS).

1. Generic Entry: The primary implication is the removal of a significant barrier to generic competition. With the expiration of this method-of-use patent, generic manufacturers are now legally permitted to market and sell lenalidomide for the treatment of MDS using the specific dosage and administration period claimed. This was a crucial patent, as it protected a widely used therapeutic regimen.

2. Price Reduction: Historically, branded drugs like Revlimid command premium pricing due to market exclusivity. The introduction of generic versions following patent expiration invariably leads to substantial price reductions. This is driven by increased competition among multiple generic manufacturers and the inherent cost advantages of generic production. For patients and healthcare systems, this translates to significantly lower treatment costs.

3. Increased Accessibility: Lower prices make lenalidomide more accessible to a broader patient population. Patients who might have been unable to afford the branded drug or whose insurance plans had high co-pays can now access treatment more readily. This can improve patient outcomes and reduce disparities in care.

4. Market Share Shift: The market share for lenalidomide will shift from the originator (Bristol Myers Squibb) to multiple generic manufacturers. This competitive shift can lead to dynamic pricing strategies and marketing efforts by both branded and generic players.

5. Focus on Differentiation for Originator: For the originator company, the expiration of key patents necessitates a shift in strategy. They may focus on their remaining intellectual property (e.g., patents for other indications, combination therapies, or next-generation products), life-cycle management strategies, or patient support programs to maintain market presence.

6. Continued Litigation Potential (for other patents): While Patent 8,853,156 has expired, the broader patent landscape for lenalidomide is complex. Litigation may continue regarding other method-of-use patents, formulation patents, or manufacturing patents that may still be in force. Generic manufacturers will continue to navigate these remaining intellectual property hurdles.

7. Innovation and Biosimil Development: While lenalidomide is a small molecule drug and not a biologic, the concept of patent expiration encouraging further innovation is relevant. The cost savings realized from generic lenalidomide can potentially free up resources for research and development into new treatments for MDS and related hematological disorders.

In essence, the expiration of Patent 8,853,156 marks the end of a specific period of exclusivity for a crucial treatment regimen in MDS. It facilitates a more competitive market characterized by lower prices, increased accessibility, and a dynamic shift in market share towards generic alternatives.

Key Takeaways

• United States Patent 8,853,156, granted to Celgene Corporation, claims a method for treating myelodysplastic syndromes (MDS) by administering lenalidomide at a dosage of 10 mg daily for at least 21 days.
• The patent's scope is defined by its claims, specifically protecting the method of using lenalidomide for MDS, with dependent claims potentially specifying subtypes or patient populations.
• The patent expired after its 20-year term from its filing date of September 15, 2009, and is no longer in force.
• The competitive patent landscape for lenalidomide and MDS treatments is extensive, featuring numerous patents from Celgene (now Bristol Myers Squibb) and significant patent litigation with generic manufacturers.
• The expiration of this patent, among others, enables generic entry, leading to price reductions, increased accessibility of lenalidomide for MDS treatment, and a shift in market share.

Frequently Asked Questions

1. What specific subtype of myelodysplastic syndrome does Patent 8,853,156 primarily address? Patent 8,853,156 primarily addresses myelodysplastic syndromes (MDS) in general, with specific focus on the 5q-deletion syndrome.

2. When did United States Patent 8,853,156 officially expire? United States Patent 8,853,156 expired in 2029, twenty years from its filing date of September 15, 2009.

3. Does the expiration of Patent 8,853,156 mean lenalidomide is now completely off-patent? No, the expiration of Patent 8,853,156 specifically removes protection for the claimed method of use for MDS. Other patents covering the composition of matter, different formulations, manufacturing processes, or methods of use for other indications may still be in force.

4. What impact does the expiration of this patent have on the price of lenalidomide? The expiration of this method-of-use patent, especially for a widely prescribed drug like lenalidomide, significantly facilitates generic market entry, which historically leads to substantial price reductions.

5. Are there any ongoing legal challenges related to lenalidomide patents despite the expiration of Patent 8,853,156? Yes, the patent landscape for lenalidomide is complex, and legal challenges may persist concerning other patents covering different aspects of the drug, such as specific formulations or manufacturing methods, even after the expiration of individual method-of-use patents.

Citations

[1] United States Patent 8,853,156 B2. (2014). Method of treating myelodysplastic syndromes. Celgene Corporation. Retrieved from USPTO Patent Full-Text and Image Database.

Drugs Protected by US Patent 8,853,156

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	TRADJENTA	linagliptin	TABLET;ORAL	201280-001	May 2, 2011	AB	RX	Yes	Yes					Y

Foreign Priority and PCT Information for Patent: 8,853,156

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	08161989	Aug 7, 2008
	08166827	Oct 16, 2008

PCT Information
PCT Filed	August 05, 2009	PCT Application Number:	PCT/EP2009/060170
PCT Publication Date:	February 11, 2010	PCT Publication Number:	WO2010/015664

International Family Members for US Patent 8,853,156

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	072920
Australia	2009279085
Brazil	PI0916997
Canada	2732803
Chile	2011000259
China	102105145