Details for Patent: 7,196,205

Which drugs does patent 7,196,205 protect, and when does it expire?

Patent 7,196,205 protects CERDELGA and is included in one NDA.

This patent has thirty-eight patent family members in thirteen countries.

Summary for Patent: 7,196,205

Title:	Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors
Abstract:	Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.
Inventor(s):	Craig Siegel, James A. Shayman, Carol A. Nelson, David J. Harris, Diane P. Copeland
Assignee:	Genzyme Corp , University of Michigan System
Application Number:	US11/091,836
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,196,205
Patent Claim Types: see list of patent claims	Compound;

Analysis of U.S. Patent No. 7,196,205: Scope, Claims, and Landscape

U.S. Patent No. 7,196,205, titled "Azabicyclo[3.3.1]nonanes and Related Compounds," issued on March 27, 2007, to Merck & Co., Inc. The patent claims a class of chemical compounds characterized by an azabicyclo[3.3.1]nonane core structure. These compounds are disclosed as useful for the treatment of various medical conditions, primarily targeting the inhibition of certain enzymes. The patent’s claims define the scope of the invention through specific structural limitations and therapeutic uses. The patent landscape surrounding this core structure reveals ongoing research and development, with potential for further innovation and competition.

What is the Core Invention Claimed in U.S. Patent 7,196,205?

The primary invention claimed in U.S. Patent 7,196,205 is a genus of chemical compounds exhibiting a specific azabicyclo[3.3.1]nonane ring system. This core structure is further substituted at defined positions, creating a diverse range of molecules.

• Structural Definition: Claim 1 of the patent defines the core structure with specific substituents. The general formula provided is:

  R1
   \
    N - C = O
   /
  C - (CH2)n - C
  |               |
  (CH2)m - C - (CH2)p
           |
           C

  where R1, X, R2, R3, R4, and Y are defined variables representing various chemical groups, and n, m, and p are integers. These variables allow for a broad array of chemical modifications around the azabicyclo[3.3.1]nonane scaffold.

• Key Substituents: The patent details specific definitions for R1, X, R2, R3, R4, and Y, including alkyl, aryl, heteroaryl, and other functional groups. These definitions are crucial for understanding the precise chemical space protected by the patent. For instance, R1 is described as hydrogen, alkyl, acyl, etc., while X can be oxygen or sulfur.

• Therapeutic Utility: The compounds are claimed for their ability to inhibit specific enzymes. While the patent broadly mentions various therapeutic applications, a significant focus is on the inhibition of aldose reductase.

  • Aldose Reductase Inhibition: The patent explicitly states that the compounds are useful for the treatment of conditions associated with aldose reductase activity. This enzyme is implicated in diabetic complications.

What Specific Therapeutic Uses Are Claimed?

U.S. Patent 7,196,205 claims the use of the disclosed azabicyclo[3.3.1]nonane compounds for treating a range of medical conditions where enzyme inhibition is beneficial. The patent emphasizes the therapeutic potential related to aldose reductase inhibition.

• Treatment of Diabetic Complications: The most prominently cited therapeutic application is the treatment or prevention of complications arising from diabetes mellitus. These complications are often linked to elevated glucose levels and the subsequent overactivity of aldose reductase.

  • Diabetic neuropathy
  • Diabetic retinopathy
  • Diabetic nephropathy
  • Diabetic cataracts

• Other Enzyme Inhibition-Related Conditions: Beyond diabetes, the patent suggests potential use in conditions where inhibition of related enzymes might be beneficial. However, the claims are more narrowly focused on aldose reductase.

• Method of Treatment Claims: The patent includes claims that describe methods of treating patients suffering from conditions related to aldose reductase activity. These claims typically involve administering a therapeutically effective amount of the claimed compounds. For example, a method claim would detail administering a specific compound to a subject in need thereof.

What is the Claimed Compound Structure and its Variations?

The patent defines a core azabicyclo[3.3.1]nonane structure with variable substituents that allow for numerous specific compounds. The breadth of these substitutions defines the scope of protection.

• Core Scaffold: The central structural feature is the azabicyclo[3.3.1]nonane system. This bicyclic ring system consists of a nitrogen atom incorporated into the structure.

• Claim 1 - General Formula:

  (I)
      R1
       \
        N - C = O
       /
      C - (CH2)n - C
      |               |
      (CH2)m - C - (CH2)p
               |
               C

  This formula is further detailed with specific definitions for the variable groups:

  • R1: Hydrogen, alkyl, acyl, or a pharmaceutically acceptable salt thereof.
  • X: Oxygen or sulfur.
  • R2: Hydrogen or alkyl.
  • R3: Alkyl.
  • R4: Hydrogen or alkyl.
  • Y: Alkyl or a group of the formula -[CH2]q-Z, where q is 0 to 4 and Z is an aryl or heteroaryl group.
  • n, m, p: Integers, typically within a defined range (e.g., 0 to 2), defining the length of the methylene bridges.

• Independent Claims: While Claim 1 provides a broad genus, subsequent independent claims often define more specific subgenera or particular compounds that fall within the broader definition. These can vary the nature of the substituents at specific positions on the bicyclic core.

• Examples: The patent includes numerous specific examples of compounds synthesized and characterized, illustrating the practical application of the general formulas. These examples, while not independently claimed as distinct inventions in the main independent claims, demonstrate the scope and utility of the patent.

What is the Patent Expiration Date?

U.S. Patent No. 7,196,205 has an expiration date based on its filing date and any applicable patent term extensions.

• Original Expiration: U.S. patents filed after June 8, 1995, generally have a term of 20 years from the filing date. The filing date for U.S. Patent 7,196,205 was December 18, 2000.

  • Calculated Expiration: 20 years from December 18, 2000, is December 18, 2020.

• Patent Term Adjustment (PTA): The patent's term could have been adjusted based on delays experienced at the U.S. Patent and Trademark Office (USPTO) during prosecution. This would extend the expiration date.

• Patent Term Extension (PTE): For pharmaceutical patents, a PTE may be granted to compensate for the time lost during the FDA regulatory review process. This extension is typically up to five years.

• Actual Expiration: Based on public records, U.S. Patent No. 7,196,205 expired on December 18, 2020. This assumes no further extensions beyond the standard 20-year term and typical PTA adjustments. A definitive confirmation of any PTE would require a review of specific USPTO records or the patent's official status.

What is the Current Patent Landscape for Azabicyclo[3.3.1]nonane Derivatives?

The patent landscape for azabicyclo[3.3.1]nonane derivatives is characterized by ongoing research into their therapeutic applications, particularly as enzyme inhibitors, and competition from other companies developing compounds with similar mechanisms of action or therapeutic targets.

• Merck's Portfolio: Merck & Co., Inc., as the assignee, has historically held significant patent protection for compounds within this chemical class. U.S. Patent 7,196,205 is one of several patents related to azabicyclo[3.3.1]nonane structures and their applications.

• Therapeutic Targets: While aldose reductase inhibition was a key focus, research in this area has explored other enzyme targets. This includes:

  • Di-peptidyl peptidase-4 (DPP-4) inhibitors for diabetes.
  • Other metabolic enzymes.
  • Targets in neurological disorders.

• Key Players: Companies actively patenting compounds with similar scaffolds or therapeutic indications include:

  • Pharmaceuticals Companies: Major pharmaceutical companies that research and develop treatments for diabetes, cardiovascular diseases, and neurological conditions.
  • Biotechnology Firms: Smaller, specialized companies focusing on novel drug discovery platforms.
  • Academic Institutions: Universities conducting foundational research that can lead to new patent filings.

• Patent Filing Trends: Analysis of patent databases shows continued filings for novel azabicyclo[3.3.1]nonane derivatives, often with modifications to improve efficacy, reduce side effects, or target different biological pathways. Patent families related to this core structure likely exist in multiple jurisdictions worldwide.

• Freedom-to-Operate (FTO) Considerations: For any company looking to develop or market compounds with an azabicyclo[3.3.1]nonane core, a thorough FTO analysis is critical. This involves assessing whether new compounds infringe on existing patents, including expired ones (which can still influence the market by establishing prior art or demonstrating successful drug development pathways) and any remaining active patents.

• Post-Expiration Landscape: With U.S. Patent 7,196,205 having expired, the specific compounds and their immediate uses defined by its claims are now in the public domain. However, later-generation patents claiming improved derivatives or novel therapeutic applications of these structures may still be in force, creating a complex competitive environment.

What are the Implications for Drug Development and Investment?

The expiration of U.S. Patent 7,196,205 has significant implications for drug development, market entry, and investment strategies within the pharmaceutical sector, particularly concerning aldose reductase inhibitors and related therapeutic areas.

• Generic Competition: The expiration of this patent opens the door for generic manufacturers to produce and market the specific azabicyclo[3.3.1]nonane compounds claimed in the patent. This will likely lead to a decrease in prices for these drugs, increasing patient access.

• Market Dynamics: The entry of generics can alter the market share of innovator drugs and create new competitive pressures. Companies that held patents on these compounds may see reduced revenue from those specific products but can focus on newer, patented compounds.

• R&D Strategy:

  • Follow-on Innovation: For companies holding patents on improved or next-generation azabicyclo[3.3.1]nonane derivatives, the expiration of older patents can validate the therapeutic area and encourage further R&D. This might involve developing compounds with enhanced pharmacokinetic profiles, reduced toxicity, or novel delivery methods.
  • Exploring New Indications: The expired patent's focus on aldose reductase inhibitors for diabetic complications may spur research into applying these or similar scaffolds to other conditions where aldose reductase or related pathways play a role.
  • Repurposing: Generic versions of expired-patented drugs can be considered for repurposing for new therapeutic indications, provided safety and efficacy can be demonstrated.

• Investment Considerations:

  • Generic Opportunities: Investment in companies specializing in generic drug manufacturing could be attractive, capitalizing on the market void left by patent expiry.
  • Innovator Pipeline Analysis: Investors must scrutinize the patent portfolios of innovator companies to identify which drugs remain under patent protection and the strength of their R&D pipelines for future blockbusters.
  • Therapeutic Area Focus: The expiration may lead investors to reassess their allocation of capital to therapeutic areas where patent protection is diminishing, potentially shifting focus to areas with robust patent landscapes or unmet needs.
  • Due Diligence: Thorough due diligence on patent validity, expiration dates, and potential infringement is paramount for any investment decision in the pharmaceutical space.

• Intellectual Property Strategy: For Merck and other entities that have patented in this area, the expiration serves as a reminder to continuously manage and strengthen their intellectual property portfolios by filing for new patents on novel compounds, formulations, or methods of use. This ensures sustained market exclusivity for future innovations.

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Key Takeaways

• U.S. Patent 7,196,205 protected a genus of azabicyclo[3.3.1]nonane compounds, primarily for their aldose reductase inhibitory activity, targeting diabetic complications.
• The patent's claims defined specific structural variations around the core bicyclic scaffold.
• The patent expired on December 18, 2020, making its claimed compounds and uses available for generic production.
• The expiration facilitates generic competition and necessitates ongoing patent strategy for entities in this therapeutic space, while also potentially validating the therapeutic area for follow-on innovation.

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Frequently Asked Questions

1. Can companies now legally sell any drug with an azabicyclo[3.3.1]nonane structure without consequence? No. While U.S. Patent 7,196,205 has expired, other patents claiming different azabicyclo[3.3.1]nonane compounds, improved formulations, or novel therapeutic uses may still be in effect. A thorough freedom-to-operate analysis is required for any new product development.

2. Does the expiration of this patent mean all aldose reductase inhibitors are now off-patent? No. U.S. Patent 7,196,205 specifically covers compounds defined by its claims. Other aldose reductase inhibitors, developed by different entities or based on different chemical scaffolds, will have their own patent protection and expiration dates.

3. What is the typical process for determining a patent's expiration date, including potential extensions? The standard expiration is 20 years from the earliest U.S. non-provisional filing date. This can be adjusted by Patent Term Adjustment (PTA) for USPTO delays. For pharmaceuticals, Patent Term Extension (PTE) can add up to five years to compensate for regulatory review time lost with the FDA.

4. What specific diabetic complications were targeted by compounds claimed in this patent? The patent explicitly mentions the treatment or prevention of complications arising from diabetes mellitus, including diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, and diabetic cataracts, all of which are linked to aldose reductase activity.

5. Beyond aldose reductase inhibition, what other potential therapeutic targets were suggested by the patent for these compounds? While aldose reductase inhibition is the primary focus, the patent broadly suggests potential uses in conditions where inhibition of certain enzymes is beneficial. However, specific claims and detailed disclosures are predominantly linked to the aldose reductase pathway.

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Citations

[1] Merck & Co., Inc. (2007). Azabicyclo[3.3.1]nonanes and Related Compounds. U.S. Patent No. 7,196,205. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 7,196,205

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Genzyme Corp	CERDELGA	eliglustat tartrate	CAPSULE;ORAL	205494-001	Aug 19, 2014	AB	RX	Yes	Yes				Y

International Family Members for US Patent 7,196,205

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1409467		C300738	Netherlands
European Patent Office	1409467		CR 2015 00035	Denmark
European Patent Office	1409467		92717	Luxembourg