Analysis of United States Drug Patent RE32393: Scope, Claims, and Landscape
This analysis details United States Patent RE32393, focusing on its scope, claims, and the surrounding patent landscape. The patent, a reissued patent for "4-[4-(4-chlorophenyl)-1-piperazinyl]-N-methyl-2-phenyl-2-butenamide," was originally granted as U.S. Patent 4,379,167 on April 5, 1983, and reissued on March 15, 1987. It pertains to the compound sertraline, a selective serotonin reuptake inhibitor (SSRI) marketed as Zoloft by Pfizer.
What is the Core Invention Claimed in RE32393?
The core invention claimed in U.S. Patent RE32393 is the compound 4-[4-(4-chlorophenyl)-1-piperazinyl]-N-methyl-2-phenyl-2-butenamide and its pharmaceutically acceptable salts. The claims define specific chemical structures and a method of use for treating central nervous system disorders.
The key claims of the patent are:
- Claim 1: The compound 4-[4-(4-chlorophenyl)-1-piperazinyl]-N-methyl-2-phenyl-2-butenamide, and pharmaceutically acceptable acid addition salts thereof.
- Claim 2: A method of treating a central nervous system disorder in a subject, which comprises administering to said subject an effective amount of the compound of claim 1.
- Claim 3: A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
The patent also includes claims for specific acid addition salts, such as the hydrochloride salt. The scope is focused on the chemical entity itself and its application in treating neurological conditions.
What is the Therapeutic Area Addressed by RE32393?
RE32393 addresses the therapeutic area of central nervous system (CNS) disorders. The patent's claims explicitly describe a method of treating such disorders. While not specifying particular conditions in the claims, the underlying invention, sertraline, is known for its efficacy in treating depression, anxiety disorders, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).
What is the Chemical Structure and Properties Defined by the Patent?
The patent defines the chemical structure of sertraline as 4-[4-(4-chlorophenyl)-1-piperazinyl]-N-methyl-2-phenyl-2-butenamide. The structure involves a phenylbutenamide core substituted with a piperazine ring, which itself is substituted with a chlorophenyl group.
The reissued patent, RE32393, specifically covers the compound. The chemical formula is C17H17Cl2N. The molecular weight is 306.23 g/mol. The structure can be represented as:
[Image placeholder for the chemical structure of Sertraline]
The patent also covers pharmaceutically acceptable acid addition salts of this compound. These salts are formed by reacting the free base with an acid to improve properties such as solubility, stability, or bioavailability. The hydrochloride salt is a common form.
The patent describes the preparation of the compound through a multi-step synthesis. Key intermediates and reaction conditions are detailed within the specification, though the reissued patent's primary focus is the compound and its use.
What is the Filing and Grant History of RE32393?
U.S. Patent RE32393 has a layered history originating from an earlier application:
- Original Application Filing Date: October 29, 1981, for U.S. Patent 4,379,167.
- Original Patent Grant Date: April 5, 1983, as U.S. Patent 4,379,167.
- Reissue Application Filing Date: January 27, 1987.
- Reissue Patent Grant Date: March 15, 1987, as U.S. Patent RE32393.
The reissue process is used to correct or amend issues in an original patent. In this case, the reissue likely aimed to clarify or broaden aspects of the original patent's claims or specification, although the fundamental invention remains the same. The term of a reissued patent is limited by the term of the original patent. The original patent term was 17 years from its grant date.
- Original Patent Term Expiration: April 5, 2000 (17 years from April 5, 1983).
Therefore, RE32393 expired on April 5, 2000, based on the original patent term.
What is the Patent Expiration Status of RE32393?
United States Patent RE32393 expired on April 5, 2000. This expiration date is derived from the original grant date of U.S. Patent 4,379,167 (April 5, 1983) and its 17-year statutory term. As a reissued patent, its term is tied to the original patent.
The expiration of RE32393 signifies that the patent claims related to sertraline are no longer in force. This means that the compound and its methods of use, as claimed in RE32393, are now in the public domain, allowing for generic manufacturing and marketing of the drug, provided no other valid patents cover specific formulations, methods of treatment, or manufacturing processes.
What is the Patent Landscape Surrounding RE32393?
The patent landscape for sertraline is extensive, extending beyond the expired RE32393. While RE32393 and its parent patent established the foundational intellectual property for the compound, subsequent patents were filed by Pfizer and others to protect various aspects of the drug.
Key areas of patenting in the sertraline landscape include:
- Formulations: Patents covering specific salt forms (e.g., hydrochloride), polymorphic forms, or excipient combinations that enhance stability, bioavailability, or patient compliance.
- Manufacturing Processes: Patents protecting novel or improved methods of synthesizing sertraline or its intermediates, aiming for higher purity, yield, or cost-effectiveness.
- Methods of Treatment: Patents claiming new therapeutic uses for sertraline or specific dosing regimens for known indications. For instance, patents might cover the use of sertraline for treating specific subtypes of anxiety disorders or in combination therapies.
- Polymorphs: Different crystalline forms of a drug substance can have distinct physical properties. Patents have been sought for specific polymorphs of sertraline.
Example of Related Patents:
While RE32393 is expired, the patenting activity around sertraline continued. For example, subsequent patents might have claimed:
- U.S. Patent 5,453,427: Granted September 26, 1995, for "Process for preparing sertraline hydrochloride." This patent expired in 2012.
- U.S. Patent 6,022,879: Granted February 8, 2000, for "Pharmaceutical composition containing sertraline." This patent covered specific tablet formulations. Its term would have extended due to patent term adjustments, but would eventually expire.
The expiration of RE32393 opened the door for generic competition for the basic sertraline molecule and its primary uses. However, the existence of later-expiring patents on specific formulations or manufacturing processes could still provide a degree of market exclusivity for branded or authorized generic versions until those patents also expire.
The patent landscape is dynamic. Competitors often file Paragraph IV certifications under the Hatch-Waxman Act, challenging existing patents and seeking to launch generic versions of drugs. Litigation is common in this space, revolving around patent validity, infringement, and obviousness.
What are the Implications of RE32393's Expiration for Generic Manufacturers?
The expiration of U.S. Patent RE32393 on April 5, 2000, has significant implications for generic manufacturers:
- Freedom to Operate: The primary implication is that the foundational patent covering the sertraline molecule and its general use for treating CNS disorders is no longer in effect. This grants generic companies the freedom to manufacture and sell generic versions of sertraline without infringing on RE32393.
- Market Entry: The expiration of the core patent enabled the market entry of generic sertraline products, leading to increased competition and reduced drug prices.
- Focus on Secondary Patents: Generic manufacturers must still navigate the landscape of secondary patents. These may cover specific polymorphs, formulations, or manufacturing processes. Successful generic entry often depends on either waiting for these secondary patents to expire, challenging their validity, or developing non-infringing processes and formulations.
- Hatch-Waxman Act Provisions: The Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act) governs the approval of generic drugs. Generic companies file Abbreviated New Drug Applications (ANDAs) with the U.S. Food and Drug Administration (FDA). They must certify that any relevant patents listed in the FDA's Orange Book are either expired, invalid, or will not be infringed by their generic product.
The expiration of RE32393 was a critical milestone in the commercial lifecycle of sertraline, directly facilitating widespread generic availability.
What are the Key Takeaways?
- United States Patent RE32393, covering the compound sertraline and its use in treating central nervous system disorders, expired on April 5, 2000.
- The patent's claims define the chemical structure of sertraline and its pharmaceutically acceptable salts, along with a method of treatment.
- RE32393 originated from U.S. Patent 4,379,167, granted in 1983, with the reissue occurring in 1987.
- The expiration of RE32393 removed the primary patent barrier for the production and sale of generic sertraline.
- The patent landscape for sertraline includes numerous secondary patents covering formulations, manufacturing processes, and specific therapeutic uses, which have governed generic market entry dynamics subsequent to the expiration of RE32393.
Frequently Asked Questions
1. Can a company still be sued for infringing on patent RE32393?
No, a company cannot be sued for infringing on patent RE32393, as it expired on April 5, 2000. Once a patent expires, the claims are no longer enforceable.
2. Does the expiration of RE32393 mean all patents related to sertraline have expired?
No, the expiration of RE32393 only pertains to the specific claims of that reissued patent, which covered the basic compound and its general use. Other patents covering specific formulations, polymorphic forms, or manufacturing processes for sertraline may have had later expiration dates and could still be in force or have expired more recently.
3. What is the significance of a "reissued patent" like RE32393?
A reissued patent (indicated by "RE" prefix) is a patent that has been corrected or amended by the U.S. Patent and Trademark Office (USPTO) after the original patent was granted. The reissued patent replaces the original patent, but its term is limited by the term of the original patent. RE32393 replaced U.S. Patent 4,379,167 and expired based on that original patent's term.
4. How does the expiration of RE32393 impact the price of Zoloft?
The expiration of RE32393 was a key event that allowed for the introduction of generic versions of sertraline. This increased competition from generic manufacturers generally leads to a significant reduction in the price of the drug compared to when only the branded product (Zoloft) was available under patent protection.
5. Where can I find information on other patents related to sertraline?
Information on other patents related to sertraline can typically be found through the U.S. Patent and Trademark Office's (USPTO) patent database, the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), and commercial patent search databases. These resources can identify active and expired patents covering different aspects of the drug.
Citations
[1] United States Patent RE32393. (1987). 4-[4-(4-chlorophenyl)-1-piperazinyl]-N-methyl-2-phenyl-2-butenamide. U.S. Patent and Trademark Office.
[2] United States Patent 4,379,167. (1983). 4-[4-(4-chlorophenyl)-1-piperazinyl]-N-methyl-2-phenyl-2-butenamide. U.S. Patent and Trademark Office.
[3] Food and Drug Administration. (n.d.). Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). Retrieved from [FDA website - specific URL varies, search "FDA Orange Book"]
[4] United States Patent 5,453,427. (1995). Process for preparing sertraline hydrochloride. U.S. Patent and Trademark Office.
[5] United States Patent 6,022,879. (2000). Pharmaceutical composition containing sertraline. U.S. Patent and Trademark Office.
