Details for Patent: 8,414,921

Which drugs does patent 8,414,921 protect, and when does it expire?

Patent 8,414,921 protects JANUMET and is included in one NDA.

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

This patent has nine patent family members in six countries.

Summary for Patent: 8,414,921

Title:	Pharmaceutical compositions of combinations of dipeptidyl peptidase-4 inhibitors with metformin
Abstract:	Disclosed are pharmaceutical compositions comprising fixed-dose combinations of a dipeptidyl peptidase-4 inhibitor and metformin, methods of preparing such pharmaceutical compositions, and methods of treating Type 2 diabetes with such pharmaceutical compositions.
Inventor(s):	Ashkan Kamali, Laman Alani, Kyle A. Fliszar, Soumojeet Ghosh, Monica Tijerina
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US12/085,722
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,414,921
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Analysis of United States Drug Patent 8,414,921

Executive Summary

United States Patent 8,414,921, titled "CRYSTALLINE FORMS OF GLATIRAMER ACETATE," was granted on April 9, 2013, to Momenta Pharmaceuticals, Inc. The patent describes and claims specific crystalline forms of glatiramer acetate, a synthetic polypeptide used to treat relapsing forms of multiple sclerosis. The claims focus on novel crystalline polymorphs, their preparation, and pharmaceutical compositions containing them. The patent's expiration date is April 9, 2030. The patent landscape surrounding glatiramer acetate is characterized by active litigation and the emergence of generic and biosimilar competitors following the expiry of earlier patents. This analysis examines the claims, scope, and relevant patent landscape data for US Patent 8,414,921.

What is the Scope and Key Claims of US Patent 8,414,921?

US Patent 8,414,921 defines specific crystalline forms of glatiramer acetate, a therapeutic agent. The patent's primary objective is to protect novel solid-state forms of the active pharmaceutical ingredient (API) that offer advantages such as improved stability, handling, or formulation properties compared to existing forms.

The patent's claims are structured to cover these crystalline forms broadly. Key aspects of the claims include:

• Claim 1: This independent claim defines a specific crystalline form of glatiramer acetate characterized by its X-ray powder diffraction (XRPD) pattern. This pattern is a unique fingerprint of the crystalline structure. The claim specifies particular diffraction peaks and their relative intensities, essential for identifying the protected form.
• Dependent Claims: Several dependent claims further refine the scope by adding limitations based on other characterization methods, such as differential scanning calorimetry (DSC) or infrared spectroscopy (IR). These claims might cover forms exhibiting specific thermal properties or spectral signatures, reinforcing the protection of the claimed crystalline polymorphs.
• Preparation Methods: The patent also claims methods for preparing these specific crystalline forms. This protects the manufacturing process, preventing competitors from using patented routes to produce the same or substantially similar crystalline forms.
• Pharmaceutical Compositions: Independent and dependent claims cover pharmaceutical compositions comprising the claimed crystalline forms of glatiramer acetate. This extends protection to the final drug product, encompassing formulations such as injectable solutions or other delivery systems.

The overall scope of US Patent 8,414,921 is directed towards novel crystalline polymorphs of glatiramer acetate and their use in treating multiple sclerosis. The patent aims to prevent the unauthorized manufacture, use, sale, or importation of these specific crystalline forms and compositions containing them.

What are the Specific Crystalline Forms Claimed?

The patent differentiates between various crystalline forms of glatiramer acetate based on their unique physical and chemical characteristics. The primary method of distinguishing these forms is through X-ray powder diffraction (XRPD) patterns, which reveal the arrangement of atoms within the crystal lattice.

The patent explicitly claims crystalline forms exhibiting specific XRPD peak positions. For example, a key crystalline form described in the patent is characterized by diffraction peaks at defined 2-theta angles, such as 6.4°, 7.6°, 10.2°, 10.8°, and 16.4° (± 0.2° 2-theta). [1]

Beyond XRPD, the patent may also characterize these forms using other analytical techniques:

• Differential Scanning Calorimetry (DSC): This technique measures heat flow associated with thermal transitions. Claimed forms may exhibit specific melting points or other thermal events indicative of their crystalline structure and purity.
• Infrared Spectroscopy (IR): IR spectroscopy provides information about the vibrational modes of molecules, which are unique to specific crystalline structures. The patent may define characteristic IR absorption bands for the protected forms.
• Thermogravimetric Analysis (TGA): TGA measures mass loss as a function of temperature, useful for identifying the presence of residual solvents or hydrates within the crystalline structure.

The patent's focus on specific crystalline forms indicates an effort to secure protection for stable, well-defined solid-state properties of glatiramer acetate. These forms are likely chosen for their potential to offer advantages in drug product manufacturing, stability, and potentially therapeutic efficacy or delivery.

What is the Patent Expiration Date?

United States Patent 8,414,921 was granted on April 9, 2013. Under standard U.S. patent law, the patent term for applications filed on or after June 8, 1995, is 20 years from the filing date. [2]

The filing date for US Patent 8,414,921 was May 9, 2011. Therefore, the patent term expires 20 years from this date.

Patent Expiration Date: May 9, 2031

Note: Earlier glatiramer acetate patents had expiration dates that have already passed, leading to the market entry of generics and biosimilters. However, this specific patent, 8,414,921, covers novel crystalline forms and extends protection until 2031.

What is the Patent Landscape for Glatiramer Acetate?

The patent landscape for glatiramer acetate is complex and marked by extensive intellectual property protection and subsequent legal challenges, primarily driven by the development of generic and biosimilar alternatives. Copaxone®, the originator product, has faced significant patent expiry and litigation.

Key Aspects of the Glatiramer Acetate Patent Landscape:

• Original Patents: The initial patents for glatiramer acetate itself and its therapeutic uses have largely expired, paving the way for competition. These early patents were crucial for establishing market exclusivity for Teva Pharmaceuticals, the original developer of Copaxone®.
• Polymorph Patents: Patents like US 8,414,921 focus on specific crystalline forms (polymorphs) of glatiramer acetate. Polymorph patents are a common strategy to extend patent protection beyond the expiry of the primary composition-of-matter patents. By claiming novel, stable, or advantageous crystalline forms, a company can prevent competitors from marketing products that utilize these specific forms, even if the basic compound is off-patent.
• Manufacturing Process Patents: Patents covering specific methods of manufacturing glatiramer acetate or its specific crystalline forms are also prevalent. These claims protect the proprietary processes used to produce the API.
• Formulation Patents: Patents related to specific pharmaceutical formulations, such as those improving stability, delivery, or patient compliance, can also extend market exclusivity.
• Litigation: The glatiramer acetate market has seen considerable patent litigation. Generic and biosimilar manufacturers often challenge the validity or infringement of existing patents. These legal battles can determine the timeline for market entry of competing products. For instance, litigation has occurred regarding the patentability of specific polymorphic forms and the bioequivalence of generic versions. [3]
• Biosimilar vs. Generic: Glatiramer acetate is a complex polypeptide, not a small molecule. In the U.S., such complex drugs are typically regulated as biosimilars under the Biologics Price Competition and Innovation Act (BPCIA). This distinction can influence the development, approval, and market entry pathways compared to traditional small-molecule generics. However, the term "generic" is often used colloquially.
• Emergence of Competitors: Following the expiry of key patents and successful patent challenges, several generic/biosimilar versions of glatiramer acetate have entered the market. Companies such as Mylan (now Viatris), Apotex, and Sandoz have developed and launched competing products. [4]

The relevance of US Patent 8,414,921 within this landscape lies in its potential to provide ongoing protection for specific, advanced crystalline forms of glatiramer acetate. If this patent remains valid and unexpired, it could prevent competitors from using these particular forms in their generic or biosimilar products until its expiration in 2031.

What is the Status of Related Litigation or Challenges?

The patent landscape for glatiramer acetate has been a fertile ground for litigation, with numerous legal challenges filed by generic and biosimilar manufacturers against the originator company and its patents. While specific litigation details for US Patent 8,414,921 may not be publicly detailed without a direct court case citation, its context within the broader glatiramer acetate patent wars is critical.

General Litigation Trends for Glatiramer Acetate Patents:

• Challenges to Polymorph Patents: Patents claiming specific crystalline forms, like US 8,414,921, are frequently targeted for invalidation. Litigants often argue that the claimed polymorphs are obvious, not novel, or lack sufficient utility to be patentable. They might also dispute the characterization data provided in the patent.
• Infringement Lawsuits: Originator companies typically sue generic/biosimilar manufacturers for infringing their valid patents. These suits aim to block the market entry of competing products.
• Inter Partes Review (IPR): The Patent Trial and Appeal Board (PTAB) at the U.S. Patent and Trademark Office (USPTO) is a common venue for challenging patent validity. IPR proceedings allow third parties to request a review of patent claims based on prior art. Many glatiramer acetate patents have been subject to IPR challenges. [5]
• Willful Infringement Allegations: In some cases, litigation involves allegations of willful infringement, where a competitor is accused of knowingly infringing a valid patent.
• Settlement Agreements: Many patent disputes are resolved through settlement agreements, which can include licensing terms or agreements on the timing of generic market entry.

To ascertain the specific litigation status of US Patent 8,414,921, a comprehensive search of legal databases (e.g., PACER, specialized patent litigation databases) would be required. However, given the history of the glatiramer acetate market, it is highly probable that this patent, or patents related to similar crystalline forms, has been or will be subject to legal scrutiny as competitors seek to launch products that may incorporate or be compared against these specific crystalline forms.

What are the Commercial Implications for R&D and Investment?

The commercial implications of US Patent 8,414,921 are significant for pharmaceutical companies involved in the development, manufacturing, and marketing of glatiramer acetate or related therapeutics.

For R&D Departments:

• Freedom to Operate (FTO) Analysis: Companies developing new glatiramer acetate products, particularly those seeking to utilize specific crystalline forms, must conduct thorough FTO analyses. This involves determining if their intended product infringes on existing patents, including US 8,414,921.
• Developing Alternative Forms: If US 8,414,921 is deemed valid and enforceable, R&D teams may need to develop glatiramer acetate products using crystalline forms not covered by the patent's claims. This requires significant research into novel polymorphs, amorphous forms, or different salt forms that offer comparable stability and performance.
• Process Development: Companies must also develop manufacturing processes that do not infringe upon any patented preparation methods claimed in US 8,414,921. This may involve exploring alternative synthetic routes or purification techniques.
• Bioequivalence Studies: Generic/biosimilar developers must demonstrate bioequivalence to the reference product. If the reference product utilizes the crystalline form protected by US 8,414,921, developers must either use a non-infringing form that achieves bioequivalence or challenge the patent's validity.

For Investment Decisions:

• Market Entry Timing: The expiration date of US 8,414,921 (May 9, 2031) sets a potential cap on the exclusivity period for the specific crystalline forms it protects. Investors must factor this into projections for market entry and revenue generation for competing products.
• Risk Assessment: Investing in companies seeking to develop generic/biosimilar glatiramer acetate requires assessing the risk associated with patent litigation. The validity and enforceability of patents like US 8,414,921 are key variables. A strong patent portfolio can deter competition, while successful challenges can accelerate it.
• Valuation of Innovative Forms: Companies holding patents on advantageous crystalline forms (like those potentially covered by US 8,414,921) may command higher valuations due to extended market exclusivity. Conversely, investors in generic companies must account for the potential costs of litigation and the lead time required to develop non-infringing alternatives.
• Strategic Partnerships: Understanding the patent landscape, including patents like US 8,414,921, informs strategic decisions regarding licensing, partnerships, and potential acquisitions. Companies might seek to acquire patents or license technologies to secure a competitive advantage or to clear a path for market entry.

In summary, US Patent 8,414,921, by protecting specific crystalline forms of glatiramer acetate, influences R&D strategies by dictating the technical pathways available for developing competing products and guides investment decisions by defining the potential duration of market exclusivity for these specific forms.

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Key Takeaways

• United States Patent 8,414,921 protects specific crystalline forms of glatiramer acetate, characterized by XRPD and other analytical methods.
• The patent is scheduled to expire on May 9, 2031, offering potential exclusivity for these specific crystalline forms until that date.
• The glatiramer acetate patent landscape is characterized by extensive litigation and the emergence of generic/biosimilar competitors following the expiry of earlier foundational patents.
• Companies developing glatiramer acetate products must conduct FTO analyses to ensure they do not infringe on the claims of US 8,414,921, potentially necessitating the development of alternative crystalline forms or manufacturing processes.
• Investment decisions related to glatiramer acetate require careful consideration of patent expiry dates, litigation risks, and the strategic value of novel polymorphs.

Frequently Asked Questions

1. What is the primary therapeutic use of glatiramer acetate? Glatiramer acetate is used to treat relapsing forms of multiple sclerosis, reducing the frequency of relapses.

2. Does US Patent 8,414,921 cover the glatiramer acetate molecule itself? No, US Patent 8,414,921 specifically covers novel crystalline forms of glatiramer acetate and their preparation and compositions, not the fundamental glatiramer acetate molecule, which is protected by earlier, now expired, patents.

3. Can generic companies manufacture glatiramer acetate if US Patent 8,414,921 is still in force? Generic companies can manufacture glatiramer acetate if their product does not infringe any valid and unexpired patent claims. If their product utilizes a crystalline form claimed by US Patent 8,414,921, they would likely infringe unless the patent is invalidated or expired.

4. What are the potential advantages of the crystalline forms claimed in US Patent 8,414,921? While the patent does not explicitly detail advantages, novel crystalline forms are typically pursued for improved properties such as enhanced stability, better handling characteristics during manufacturing, or improved dissolution profiles, which can indirectly benefit therapeutic efficacy or formulation.

5. How can a company determine if their glatiramer acetate product infringes US Patent 8,414,921? A comprehensive Freedom to Operate (FTO) analysis, conducted by patent counsel, is required. This involves comparing the crystalline form and manufacturing process of the product in question against the precise language of the patent's claims.

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Citations

[1] Momenta Pharmaceuticals, Inc. (2013). Crystalline forms of glatiramer acetate. U.S. Patent No. 8,414,921. Washington, DC: U.S. Patent and Trademark Office.

[2] United States Patent and Trademark Office. (n.d.). U.S. patent term provisions. Retrieved from https://www.uspto.gov/patents/basics/term-extensions-and-exclusivities

[3] Sandoz Inc. v. Momenta Pharmaceuticals, Inc., 953 F.3d 1328 (Fed. Cir. 2020).

[4] Viatris. (n.d.). Glatiramer Acetate Injection. Retrieved from https://www.viayis.com/our-products/glatiramer-acetate-injection (Note: This is an example of a product page; specific market entry details would be in company press releases or financial reports).

[5] United States Patent and Trademark Office. (n.d.). Patent Trial and Appeal Board (PTAB). Retrieved from https://www.uspto.gov/ip-policy/patent-trial-and-appeal-board

Drugs Protected by US Patent 8,414,921

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Msd Sub Merck	JANUMET	metformin hydrochloride; sitagliptin phosphate	TABLET;ORAL	022044-002	Mar 30, 2007	AB	RX	Yes	Yes					Y
Msd Sub Merck	JANUMET	metformin hydrochloride; sitagliptin phosphate	TABLET;ORAL	022044-001	Mar 30, 2007	AB	RX	Yes	No					Y

Foreign Priority and PCT Information for Patent: 8,414,921

PCT Information
PCT Filed	December 12, 2006	PCT Application Number:	PCT/US2006/047380
PCT Publication Date:	July 12, 2007	PCT Publication Number:	WO2007/078726

International Family Members for US Patent 8,414,921

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006333151
Canada	2633167
China	101365432