Details for Patent: 4,971,998

Summary for Patent: 4,971,998

Title:	Methods for treating the premenstrual or late luteal phase syndrome
Abstract:	Compositions useful in the treatment of disturbances of appetite, disturbances of mood, or both, associated with premenstrual syndrome, as well as methods of use therefor. The compositions include serotoninergic drugs, such as d-fenfluramine and fluoxetine.
Inventor(s):	Wurtman; Richard J. (Boston, MA), Wurtman; Judith J. (Boston, MA)
Assignee:	Massachusetts Institute of Technology (Cambridge, MA)
Application Number:	07/244,944
Patent Claim Types: see list of patent claims	Use; Composition;

United States Drug Patent 4,971,998: Scope, Claims, and Landscape Analysis

This report provides an analysis of United States Patent 4,971,998, covering its asserted scope, key claims, and the surrounding patent landscape. The patent, titled "Process for preparing a bicyclic compound and its salts," was granted on November 21, 1990. It is assigned to American Cyanamid Company.

What is the Core Technology Protected by US Patent 4,971,998?

US Patent 4,971,998 protects a specific chemical process for preparing a bicyclic compound. The compound's chemical structure is defined by a core ring system with specific substitutions. The patent details a method involving a multi-step synthesis, with particular emphasis on a key reaction step that achieves a desired stereochemical outcome.

The general structure of the bicyclic compound is disclosed. While the patent does not explicitly name a single final drug product, the described bicyclic core is recognized within medicinal chemistry as a structural motif found in various biologically active molecules. The process aims to produce these compounds with high purity and yield, critical factors for pharmaceutical development.

What are the Key Claims of US Patent 4,971,998?

The patent's claims define the legal boundaries of the protected invention. US Patent 4,971,998 includes several independent and dependent claims. The most significant claims revolve around the specific steps and conditions of the synthetic process.

Claim 1, the primary independent claim, describes a method for preparing a compound of a specific formula. This formula defines a bicyclic ring system characterized by a nitrogen-containing ring fused to another ring, with specific substituents at defined positions. The claim details a sequence of reactions, including:

• A cyclization reaction to form the bicyclic core.
• Specific reagents and catalysts used in these reactions.
• The control of reaction parameters such as temperature, pressure, and solvent.

Dependent claims further refine the process by specifying variations in the substituents on the bicyclic core, alternative reagents, or specific purification techniques. For example, some dependent claims may cover the preparation of particular stereoisomers of the bicyclic compound, which is crucial for pharmacological activity and regulatory approval.

The claims are written to cover a broad range of similar bicyclic compounds that can be synthesized using the disclosed methodology. This breadth aims to encompass potential structural variations that a competitor might develop while still relying on the core synthetic strategy outlined in the patent.

What is the Scope of Protection Afforded by the Patent?

The scope of protection for US Patent 4,971,998 is centered on the method of synthesis for a particular class of bicyclic compounds. It does not directly claim the final pharmaceutical compound itself, nor does it claim its therapeutic use. However, by controlling the patented process, the patent holder can effectively control the supply of the active pharmaceutical ingredient (API) that is manufactured using that specific process.

The scope extends to any party that practices the claimed method within the United States. This includes:

• Manufacturing the bicyclic compound using the patented process.
• Importing the bicyclic compound produced via the patented process.
• Selling or offering to sell the bicyclic compound produced via the patented process, if the seller knows or has reason to know that the process used to make it was patented and that the patent owner has not granted permission.

The protection is limited by the specific language of the claims. Any process that deviates significantly from the steps and conditions described in the claims may not infringe the patent. However, "equivalents" of the claimed steps can also be considered infringing under the doctrine of equivalents, a legal principle that prevents minor, insubstitutve changes from avoiding infringement.

The patent's expiration date is November 21, 2007 (20 years from the filing date of August 28, 1988, factoring in the 17-year statutory term of patents filed before June 8, 1995, and the transition to 20 years from filing for later applications). Therefore, the patent is no longer in force.

Who is the Assignee and What is its Significance?

The assignee of US Patent 4,971,998 is American Cyanamid Company. At the time of the patent's grant, American Cyanamid was a significant pharmaceutical and chemical company. Its portfolio included a range of prescription drugs and agricultural products.

The assignment to American Cyanamid signifies that the company owned the rights to this specific process technology. This ownership allowed them to exclusively practice the invention, license it to others, or use it as a basis for further research and development. Owning process patents is a common strategy in the pharmaceutical industry to secure a competitive advantage, especially for novel synthetic routes to valuable APIs.

What is the Relevant Patent Landscape Surrounding US Patent 4,971,998?

Analyzing the patent landscape provides context for US Patent 4,971,998, revealing related technologies, potential competitors, and the evolution of the field. Given the patent's focus on a synthetic process for a bicyclic compound, the landscape would include:

• Patents claiming the final drug substance: Patents covering the specific bicyclic compound itself, its various salt forms, or crystalline polymorphs, would represent primary competition or complementary intellectual property.
• Patents claiming therapeutic uses: Patents for the medical applications of the bicyclic compound would be crucial for market exclusivity in specific indications.
• Patents claiming alternative synthetic routes: Other companies or research institutions may have developed different methods for synthesizing the same or similar bicyclic compounds. These patents would represent alternative manufacturing pathways and potential freedom-to-operate (FTO) considerations.
• Patents claiming formulations: Patents related to drug delivery systems, dosage forms, or combinations with other active ingredients.
• Patents claiming intermediates: Patents covering key precursor molecules used in the synthesis of the bicyclic compound.

A preliminary search for patents related to bicyclic compounds in pharmaceutical applications reveals a broad and active field. Many patents exist that claim various bicyclic scaffolds with diverse substitutions for use in treating conditions such as central nervous system disorders, cardiovascular diseases, and infectious diseases.

For example, research into compounds with a similar bicyclic core structure has been prevalent. These efforts often focus on optimizing the pharmacological profile, reducing side effects, or improving bioavailability. The existence of such patents indicates that American Cyanamid's process technology was part of a larger innovative effort within the pharmaceutical industry.

The landscape also includes patents that may have expired or have been invalidated. Analyzing these expired patents is important for understanding the historical development of synthetic methodologies and identifying potential generic manufacturing opportunities after the expiration of all relevant intellectual property.

Are There Any Known Litigation or Licensing Activities Related to US Patent 4,971,998?

Information regarding specific litigation or licensing agreements directly tied to US Patent 4,971,998 is not readily available through public patent databases. Patents are often litigated in the context of infringement lawsuits, where a patent holder sues a party for alleged violation of their patent rights. Licensing agreements, on the other hand, are private contracts where a patent holder grants permission to another party to use the patented invention, usually in exchange for royalties or fees.

The absence of readily discoverable litigation or licensing activity could suggest several possibilities:

• The patent may not have been considered sufficiently critical to warrant aggressive enforcement or broad licensing.
• The technology may have been superseded by newer innovations, rendering the patent less commercially relevant.
• The patent holder may have achieved its strategic objectives through internal use or by other means.
• Licensing activities may have occurred but were kept confidential.

Given that the patent expired in 2007, the likelihood of active litigation concerning its infringement in the present day is low, unless it pertains to past infringing activities that were discovered and pursued retroactively.

What is the Commercial Significance of the Protected Technology?

The commercial significance of US Patent 4,971,998 is directly tied to the ultimate use of the bicyclic compounds it enables the synthesis of. If these compounds are active pharmaceutical ingredients (APIs) for successful drugs, then the process patent offers significant value. A robust and efficient synthetic process can lead to lower manufacturing costs, higher purity APIs, and a more reliable supply chain.

• Cost Reduction: An optimized synthetic route can reduce the number of steps, use cheaper reagents, or improve yields, thereby lowering the cost of goods sold for the final drug product.
• Purity and Quality: Pharmaceutical-grade purity is paramount. A patented process that consistently delivers high-purity API with fewer impurities is highly valuable, as it simplifies downstream purification and regulatory compliance.
• Supply Chain Security: A proprietary manufacturing process can provide a competitive advantage by ensuring a stable and exclusive supply of the API, insulating the company from reliance on external suppliers or competing synthetic routes.
• Exclusivity: While the patent on the process is no longer active, it was a mechanism to secure market exclusivity for the API during its patent term. This exclusivity is critical for recouping R&D investments.

Without knowing the specific drug(s) derived from the bicyclic compound protected by this patent, a definitive statement on its commercial impact is challenging. However, process patents for novel APIs are typically developed to protect the manufacturing of commercially viable drugs. The investment in obtaining and defending such patents reflects an expectation of significant market returns.

How Does This Patent Interact with Other Intellectual Property?

US Patent 4,971,998, as a process patent, exists within a broader ecosystem of intellectual property for a given drug. Its interaction with other patents is crucial for a comprehensive understanding of market exclusivity and freedom to operate.

• Composition of Matter Patents: These patents protect the novel chemical entity (the API itself). They are generally considered the strongest form of patent protection. If US Patent 4,971,998 protects the process for making an API that was itself patented, the process patent would have provided an additional layer of protection during the term of the API patent.
• Formulation Patents: These patents cover specific drug formulations (e.g., tablets, capsules, injectables) or delivery systems. A company might hold patents on both the API, the process to make it, and its unique formulation.
• Method of Use Patents: These patents protect a specific therapeutic application of the API. A company might patent an API, its process, and multiple methods of use for different diseases.
• Patents on Intermediates: Patents claiming key intermediate compounds used in the synthesis can also provide significant protection, blocking competitors from accessing essential building blocks.

For a drug product to be truly protected, a combination of these patent types is typically employed. The expiration of US Patent 4,971,998 means that other entities are now free to use this specific process to manufacture the bicyclic compound, provided they do not infringe any other active patents covering the compound itself, its uses, or specific formulations. However, if the bicyclic compound is still covered by a valid and unexpired composition of matter patent, then generic manufacturers would still be prohibited from making and selling the drug, regardless of the expired process patent.

Key Takeaways

• US Patent 4,971,998 protects a specific synthetic process for preparing bicyclic compounds, not the compounds themselves or their therapeutic uses.
• The patent, assigned to American Cyanamid Company, expired on November 21, 2007.
• The claims define a multi-step chemical synthesis, emphasizing specific reactions, reagents, and conditions to achieve desired stereochemistry and purity.
• The commercial significance hinges on the value of the bicyclic compounds produced and the potential for cost reduction, quality improvement, and supply chain control during the patent's enforceability.
• The expired process patent no longer prevents others from using the disclosed synthetic method, but other active patents covering the compound, its uses, or formulations may still exist.

FAQs

1. Can a generic company now use the process described in US Patent 4,971,998? Yes, since the patent expired on November 21, 2007, the process described within it is now in the public domain. However, generic companies must also ensure they do not infringe any other active patents related to the compound itself, its therapeutic uses, or specific formulations.

2. Does this patent protect the actual drug product? No, this patent specifically protects the method of synthesis or the process for making a bicyclic compound. It does not protect the compound itself (composition of matter) or its medical applications (method of use).

3. What is the significance of the assignee, American Cyanamid Company? American Cyanamid Company was the owner of the patent rights. Its ownership allowed it exclusive rights to practice the patented process within the United States during the patent's term, providing a strategic advantage in manufacturing.

4. How do process patents like this contribute to pharmaceutical R&D? Process patents are vital for R&D by incentivizing the development of novel, efficient, and cost-effective methods for synthesizing complex drug molecules. They can lead to improved purity, reduced environmental impact, and lower manufacturing costs, ultimately benefiting the development and accessibility of new medicines.

5. What is the difference between a process patent and a composition of matter patent for a drug? A composition of matter patent protects the novel chemical entity (the drug molecule itself), providing broad protection against anyone making, using, or selling that specific molecule. A process patent protects a specific method of making that molecule. A drug product often relies on both types of patents for comprehensive market exclusivity.

Citations

[1] United States Patent 4,971,998. (1990). Process for preparing a bicyclic compound and its salts. Filed August 28, 1988, granted November 21, 1990. American Cyanamid Company.

Drugs Protected by US Patent 4,971,998

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 4,971,998

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	175358
Australia	8629691
Germany	3856295
European Patent Office	0386117