Details for Patent: 5,688,792

Summary for Patent: 5,688,792

Title:	Substituted oxazine and thiazine oxazolidinone antimicrobials
Abstract:	A compound of structural Formula I: ##STR1## or pharmaceutically acceptable salts thereof wherein: X is O, S, SO, SO.sub.2, SNR.sup.10 or S(O)NR.sup.10 ; R is (a) hydrogen, (b) C.sub.1 -C.sub.8 alkyl optionally substituted with one or more of the following: F, Cl, hydroxy, C.sub.1 -C.sub.8 alkoxy, C.sub.1 -C.sub.8 acyloxy or --O--CH.sub.2 --Ph, (c) C.sub.3 -C.sub.6 cycloalkyl, (d) amino, (e) C.sub.1 -C.sub.8 alkylamino, (f) C.sub.1 -C.sub.8 dialkylamino or (g) C.sub.1 -C.sub.8 alkoxy; R.sup.1 is H, except when X is O then R.sup.1 can be H, CH.sub.3, CN, CO.sub.2 H, CO.sub.2 R or (CH.sub.2).sub.m R.sup.11 (m is 1 or 2); R.sup.2 is independently H, F or Cl; R.sup.3 is H except when X is O and R.sup.1 is CH.sub.3 then R.sup.3 can be H or CH.sub.3 ; R.sup.10 is independently H, C.sub.1 -C.sub.4 alkyl (optionally substituted with chloro, fluoro, hydroxy, C.sub.1 -C.sub.8 alkoxy, amino, C.sub.1 -C.sub.8 alkylamino, or C.sub.1 -C.sub.8 dialkylamino) or p-toluenesulfonyl; R.sup.11 is hydrogen, OH, OR, OCOR, NH.sub.2, NHCOR or N(R.sup.10).sub.2 ; and n is 0, 1 or 2. The oxazine and thiazine oxazolidinone derivatives are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply-resistant staphylococci, streptococci and enterococci as well as anaerobic organisms such as Bacteroides spp. and Clostridia spp. species, and acid-fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.
Inventor(s):	Barbachyn; Michael R. (Kalamazoo, MI), Brickner; Steven J. (Portage, MI), Hutchinson; Douglas K. (Kalamazoo, MI)
Assignee:	Pharmacia & Upjohn Company (Kalamazoo, MI)
Application Number:	08/617,877
Patent Claim Types: see list of patent claims	Compound; Use; Composition; Delivery;

United States Patent 5,688,792: A Detailed Analysis of Scope, Claims, and Patent Landscape

Introduction

United States Patent 5,688,792, granted to Pharmacia & Upjohn, is a pivotal patent in the pharmaceutical industry, particularly for the antibacterial agent Linezolid. This patent, which expired on May 18, 2015, including its pediatric extension, played a significant role in the treatment of infections caused by multi-resistant bacteria.

Linezolid: The Antibacterial Agent

Linezolid is a synthetic antibacterial agent belonging to the oxazolidinone class. It is used to treat infections caused by bacteria that are resistant to other antibiotics, making it a crucial drug in the fight against antibiotic-resistant infections[1].

Chemical Structure and Synonyms

The chemical formula for Linezolid is C16H20FN3O4, with the exact mass being 337.14400. It is also known by its chemical name, N-[[(5S)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide[1].

Patent Overview

Grant and Expiration

The patent was granted on November 18, 1997, and initially set to expire on November 14, 2014. However, due to a pediatric extension, the effective expiration date was extended to May 18, 2015[4].

Patent Claims

The patent claims cover the compound Linezolid itself, as well as processes for its preparation. The claims are specific to the chemical structure and the methods used to synthesize the drug. The patent also includes claims related to the use of Linezolid for treating bacterial infections[2].

Scope of the Patent

Claim Language and Scope

The scope of the patent is defined by its claim language, which outlines what is protected under the patent. For US Patent 5,688,792, the claims are focused on the specific chemical structure of Linezolid and its synthesis methods. This narrow scope ensures that the patent protection is clear and well-defined, avoiding overly broad claims that could lead to disputes over patent validity and infringement[3].

Impact on Innovation

The patent scope and claim clarity are crucial for innovation. Narrow and clear claims, as seen in this patent, can facilitate innovation by providing a clear understanding of what is protected and what is not. This clarity can reduce licensing and litigation costs, encouraging further research and development in related areas[3].

Patent Landscape

Related Patents

In addition to US Patent 5,688,792, there are other patents related to Linezolid that extend the protection period and cover different aspects of the drug. For example, US Patent 6,559,305, which expired on January 29, 2021, and its pediatric extension, which expired on July 29, 2021, also protected Linezolid[4].

Generic Entry and Litigation

The expiration of the patent allowed for generic entry into the market. Companies like Hospira submitted Paragraph III and Paragraph IV certifications, indicating their intention to market a generic version of Linezolid after the patent expiration and challenging the validity of other related patents. This process ensured that the generic versions could enter the market without litigation from the original patent holders[4].

Regulatory Issues

FDA Approvals and Certifications

The FDA approval process for generic versions of Linezolid involved certifications regarding the expiration of the original patent. Hospira, for instance, submitted certifications stating that they would not market their Linezolid injection until after the expiration of US Patent 5,688,792, including any pediatric extension[4].

Pediatric Research and Equity Act (PREA)

The application for Linezolid injection was exempt from the requirements of the Pediatric Research and Equity Act (PREA), as it did not involve new active ingredients, indications, dosage forms, dosing regimens, or routes of administration that would necessitate an assessment of safety and effectiveness in pediatric patients[4].

Industry Impact

Market Competition

The expiration of US Patent 5,688,792 and related patents opened the market to generic competition, which can lead to lower prices and increased accessibility of the drug. This competition can drive innovation as companies seek to differentiate their products and improve upon existing treatments[4].

Research and Development

The clear and well-defined scope of the patent allowed for focused research and development in the area of antibacterial agents. The expiration of the patent has encouraged further innovation, as companies are now free to develop and market their own versions of Linezolid and related compounds[3].

Key Takeaways

• Patent Scope and Claims: The patent's scope is narrowly defined, focusing on the chemical structure and synthesis methods of Linezolid.
• Expiration and Generic Entry: The patent expired on May 18, 2015, allowing for generic entry into the market.
• Regulatory Compliance: Generic manufacturers had to comply with FDA regulations, including certifications regarding patent expiration.
• Industry Impact: The patent's expiration has increased market competition and encouraged further innovation in antibacterial agents.

FAQs

What is Linezolid used for?

Linezolid is used for the treatment of infections caused by multi-resistant bacteria.

When did the patent for Linezolid expire?

The patent for Linezolid (US Patent 5,688,792) expired on May 18, 2015, including its pediatric extension.

What are the implications of the patent expiration for generic manufacturers?

The expiration of the patent allowed generic manufacturers to enter the market, increasing competition and potentially lowering the price of the drug.

How does the patent scope affect innovation?

A narrow and clear patent scope, as seen in US Patent 5,688,792, can facilitate innovation by providing clarity on what is protected, reducing licensing and litigation costs.

What regulatory certifications were required for generic versions of Linezolid?

Generic manufacturers had to submit Paragraph III and Paragraph IV certifications to the FDA, indicating their compliance with patent expiration dates and challenging the validity of other related patents if necessary.

Sources

1. New Drug Approvals: Linezolid.
2. Drug Patent Watch: Patent 5,688,792.
3. Hoover Institution: Patent Claims and Patent Scope.
4. FDA: NDA 206473, Linezolid Injection Summary Review.

Drugs Protected by US Patent 5,688,792

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: 5,688,792

PCT Information
PCT Filed	August 16, 1994	PCT Application Number:	PCT/US94/08904
PCT Publication Date:	March 16, 1995	PCT Publication Number:	WO95/07271

International Family Members for US Patent 5,688,792

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0717738		CA 2002 00004	Denmark
European Patent Office	0717738		C00717738/01	Switzerland
European Patent Office	0717738		SPC001/2002	Ireland
European Patent Office	0717738		PA2004004	Lithuania
European Patent Office	0717738		SPC/GB01/025	United Kingdom
European Patent Office	0717738		PA2004004,C0717738	Lithuania