Details for Patent: 6,172,233

Summary for Patent: 6,172,233

Title:	Process for making paroxetine
Abstract:	Compounds of structure (2) are prepared by reaction of an arecoline analogue of structure(4) with an organometallic compound containing an X-substituted phenyl group, such as a compound of structure (3). ##STR1## Suitably the compound of structure (3) is a Grignard reagent, where M is magnesium and Y is a halogen atom, or M may be a Group II metal and Y is a halogen atom or a second X-substituted phenyl group. When structure (3) is a Grignard reagent, the reaction is carried out either in a suitable non-ether solvent, typically a hydrocarbon or a non-reactive chlorinated hydrocarbon, or in a mixture of such a solvent with diethyl ether. Compounds of structure (2) are important intermediates in the preparation of inter alia paroxetine.
Inventor(s):	Ward; Neal (Tonbridge, GB)
Assignee:	SmithKline Beecham plc (Brentford, GB)
Application Number:	09/007,475
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,172,233
Patent Claim Types: see list of patent claims	Compound; Process;

Analyzing the Scope and Claims of United States Patent 6,172,233

Introduction

United States Patent 6,172,233, titled "Process for making paroxetine," is a significant patent in the pharmaceutical industry, particularly for the manufacture of the antidepressant paroxetine. This patent, granted on January 9, 2001, outlines a new process for preparing pharmaceutically active compounds and intermediates, addressing several shortcomings in existing methods.

Background and Purpose

The patent aims to improve the synthesis of paroxetine, a widely used selective serotonin reuptake inhibitor (SSRI). The existing processes had several disadvantages, including inefficiencies and the need for better chemical intermediates. This invention provides alternative processes to overcome these issues, focusing on the preparation of valuable chemical intermediates such as 4-(4′-fluorophenyl)-3-hydroxymethyl-1-methyl piperidine[1].

Key Chemical Intermediates

The patent revolves around the synthesis of specific chemical intermediates crucial for the manufacture of paroxetine. Here are some key intermediates and their preparation methods:

Structure (1) and Structure (2)

Compounds of structure (1) and (2) are central to this patent. Structure (1) involves the preparation of 4-(4′-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine, which is then converted into structure (2) by reaction with formaldehyde to form 4-(4′-fluorophenyl)-3-hydroxymethyl-1-methyl-1,2,3,6-tetrahydropyridine. This compound is further reduced to obtain the desired intermediate[1].

Use of Grignard Reagents

The patent also describes the use of Grignard reagents, where a compound of structure (3) acts as a Grignard reagent. Here, M is typically magnesium, and Y is a halogen atom. This step is crucial for introducing the necessary functional groups into the molecule[1].

Claims and Their Significance

The patent includes several claims that define the scope and protection of the invention.

Independent and Dependent Claims

The patent has multiple claims, including independent and dependent claims. For instance:

• Claim 1 specifies the solvent used in the process, which can be a hydrocarbon or a non-reactive chlorinated hydrocarbon.
• Claim 4 details the use of magnesium (Mg) and a halogen (Cl or Br) in the Grignard reagent.
• Claim 8 and 9 focus on obtaining paroxetine as the hydrochloride salt, particularly as the hemihydrate of that salt[1].

Strategic Claim Management

The strategic management of these claims is crucial for maximizing the patent's value. As highlighted in other contexts, ensuring that each patent utilizes its full complement of claims can enhance its defensive capabilities and value in licensing discussions or infringement disputes[2].

Patent Scope and Breadth

The scope of the patent is defined by the claims, which cover various aspects of the process, including the synthesis of intermediates and the final product.

Metrics for Measuring Patent Scope

Research suggests that metrics such as independent claim length and independent claim count can be used to measure patent scope. Narrower claims at publication are associated with a higher probability of grant and a shorter examination process, indicating the importance of well-crafted claims in this patent[3].

Industrial Scale Manufacture

The patent is not only theoretically significant but also practically applicable. It describes processes suitable for industrial-scale manufacture, ensuring that the methods are scalable and efficient.

Example Processes

For instance, the process involves the addition of 4-fluorophenylmagnesium halide, which is a critical step in the industrial-scale manufacture of the necessary intermediates. This step is detailed in other related patents as well, highlighting the broader applicability of these methods[4].

Legal and Regulatory Aspects

The patent landscape around this invention is subject to various legal and regulatory considerations.

Expiration and Fee-Related Status

The patent has expired due to fee-related issues, which is a common fate for many patents if maintenance fees are not paid. This expiration affects the legal status and enforceability of the patent[1].

False Patent Marking

While not directly related to this specific patent, the concept of false patent marking is relevant in the broader patent landscape. Recent legal developments, such as the Federal Circuit's decision in Crocs, Inc. v. Effervescent, Inc., have revived private actors' rights to bring claims for false marking under the Lanham Act, which could impact how expired patents are marked and used[5].

Conclusion

United States Patent 6,172,233 is a comprehensive patent that addresses critical aspects of paroxetine synthesis. The patent's claims are meticulously crafted to cover various steps and intermediates in the process, ensuring robust protection for the invention. Understanding the strategic management of these claims and the broader patent landscape is essential for maximizing the value and impact of such intellectual property.

Key Takeaways

• The patent provides a new process for preparing paroxetine and its intermediates.
• Key intermediates include 4-(4′-fluorophenyl)-3-hydroxymethyl-1-methyl piperidine.
• Grignard reagents play a crucial role in the synthesis.
• Strategic claim management is vital for maximizing patent value.
• The patent has expired due to fee-related issues.
• Legal considerations such as false patent marking are relevant in the broader context.

FAQs

Q1: What is the main focus of United States Patent 6,172,233? A1: The main focus is on a new process for preparing paroxetine and its chemical intermediates.

Q2: What are the key chemical intermediates described in the patent? A2: The key intermediates include 4-(4′-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine and 4-(4′-fluorophenyl)-3-hydroxymethyl-1-methyl-1,2,3,6-tetrahydropyridine.

Q3: How do Grignard reagents contribute to the synthesis process? A3: Grignard reagents, typically involving magnesium and a halogen, are used to introduce necessary functional groups into the molecule.

Q4: Why is strategic claim management important for this patent? A4: Strategic claim management ensures that the patent utilizes its full entitlement of claims, enhancing its defensive capabilities and value.

Q5: What is the current legal status of the patent? A5: The patent has expired due to fee-related issues.

Sources

1. US6172233B1 - Process for making paroxetine - Google Patents
2. Maximizing Patent Value: A Strategic Approach to Claim Management - Harrity LLP
3. Patent Claims and Patent Scope - SSRN
4. WO2003097599A1 - Preparation of 4-(4-fluorophenyl)-N-alkylnipecotinate esters - Google Patents
5. The Federal Circuit Breathes New Life into False Patent Marking Claims via Section 43(a) of the Lanham Act - Spencer Fane

Drugs Protected by US Patent 6,172,233

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

Foreign Priority and PCT Information for Patent: 6,172,233

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9700690	Jan 15, 1997

International Family Members for US Patent 6,172,233

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
United Kingdom	9700690