Details for Patent: 5,362,718

Summary for Patent: 5,362,718

Title:	Rapamycin hydroxyesters
Abstract:	A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3 R.sup.4).sub.b (CR.sup.5 R.sup.6).sub.d CR.sup.7 R.sup.8 R.sup.9 ; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3 R.sup.4).sub.f OR.sup.10, --CF.sub.3, --F, or --CO.sub.2 R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with --(CR.sup.3 R.sup.4).sub.f 0R.sup.10 ; R.sup.7 is hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3 R.sup.4).sub.f OR.sup.10, --CF.sub.3, --F, or --CO.sub.2 R.sup.11 ; R.sup.8 and R.sup.9 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3 R.sup.4).sub.f OR.sup.10, --CF.sub.3, --F, or --CO.sub.2 R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with --(CR.sup.3 R.sup.4).sub.f OR.sup.10 ; R.sup.10 is hydrogen, alkyl, alkenyl, alkynyl, tri-(alkyl)silyl, tri-(alkyl)silylethyl, triphenylmethyl, benzyl, alkoxymethyl, tri-(alkyl)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl, alkenyl, alkynyl, or phenylalkyl; X is 5-(2,2-dialkyl)[1,3]dioxanyl, 5-(2,2-dicycloalkyl)[1,3]dioxanyl, 4-(2,2-dialkyl)[1,3]dioxanyl, 4-(2,2-dicycloalkyl)[1,3]dioxanyl, 4-(2,2dialkyl)[1,3]dioxalanyl, or 4-(2,2-dicycloalkyl)[1,3]dioxalanyl; b=0-6; d=0-6; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3 R.sup.4).sub.f OR.sup.10, X, or --(CR.sup.3 R.sup.4).sub.f OR.sup.10 substituted cycloalkyl group, or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.
Inventor(s):	Skotnicki; Jerauld S. (Allentown, NJ), Leone; Christina L. (Princeton, NJ), Schiehser; Guy A. (Yardley, PA)
Assignee:	American Home Products Corporation (Madison, NJ)
Application Number:	08/229,261
Patent Claim Types: see list of patent claims	Compound; Use; Composition;

United States Patent 5,362,718: A Detailed Analysis of Scope, Claims, and Patent Landscape

Introduction

The United States Patent 5,362,718, titled "Rapamycin hydroxyesters," is a significant patent in the field of pharmaceuticals, particularly in the synthesis and application of rapamycin derivatives. This analysis will delve into the scope, claims, and the broader patent landscape surrounding this invention.

Background of Rapamycin

Rapamycin, also known as sirolimus, is a macrolide compound that has been widely used in medical applications, including as an immunosuppressant and in the treatment of certain cancers. The patent in question focuses on the synthesis of specific rapamycin derivatives, which are crucial for expanding the therapeutic uses of rapamycin.

Scope of the Patent

The patent US 5,362,718 describes a method for preparing 31-ester-42-hydroxy compounds of rapamycin. This involves protecting the 42-alcohol of rapamycin with a protecting group, such as a tert-butyl group, and then esterifying the 31-hydroxyl group. This process allows for the creation of rapamycin derivatives with enhanced stability and bioavailability[4].

Key Components of the Invention

• Protection of the 42-Alcohol: The method involves protecting the 42-alcohol group of rapamycin to prevent unwanted reactions during the esterification process.
• Esterification of the 31-Hydroxyl Group: The 31-hydroxyl group is esterified with various esterifying agents to produce the desired derivatives.
• Removal of Protecting Group: After esterification, the protecting group is removed to yield the final 31-ester-42-hydroxy compounds.

Claims of the Patent

The patent includes several claims that define the scope of the invention:

Independent Claims

• Claim 1: A method for preparing a 31-ester-42-hydroxy compound of rapamycin, involving the protection of the 42-alcohol group and esterification of the 31-hydroxyl group.
• Claim 2: The compound produced by the method described in Claim 1.

Dependent Claims

• Claims 3-10: Various specific embodiments of the method and compounds, including different protecting groups and esterifying agents.

Patent Landscape

Related Patents

The patent landscape around US 5,362,718 includes other patents related to rapamycin and its derivatives. For example:

• US 6,277,983 B1: This patent describes a regioselective process for preparing 42-ester or ether derivatives of rapamycin, which complements the method described in US 5,362,718[2].

Global Patent Family

The patent is part of a global patent family, with corresponding patents filed in other countries. This is evident from the use of services like the Global Dossier, which provides access to the file histories of related applications from participating IP Offices[1].

Competitors and Licensing

Companies involved in the development and commercialization of rapamycin derivatives, such as pharmaceutical companies, may hold related patents or have licensing agreements. For instance, Sandoz's involvement in producing temsirolimus, a related compound, highlights the competitive landscape in this field[5].

Patent Analytics and Claim Coverage

To fully understand the protection and gaps in the patent landscape, patent analytics tools can be employed. These tools help in categorizing patents by claims and scope concepts, making it easier to identify which patents and claims are actively protecting the intellectual property.

Claim Coverage Matrix

A Claim Coverage Matrix can show which patents and claims are protecting the technology intended by the inventors. This matrix helps in identifying gaps or opportunities in the current patent portfolio[3].

Interactive Claim Charts

Interactive claim charts generated by tools like ClaimScape® can be reviewed by technical experts to determine the applicability of specific scope concepts to target products or methods. This helps in spotting areas where claim coverage is lacking and highlights future design opportunities[3].

Legal Status and Expiration

The legal status of US 5,362,718 indicates that it has ceased or expired due to fee-related issues. This means that the patent is no longer in force, and the inventions described are now in the public domain. However, related patents or continuations may still be active[4].

Impact on Industry

The expiration of this patent allows other companies to develop and commercialize similar rapamycin derivatives without infringing on the original patent. This can lead to increased competition and innovation in the field of immunosuppressants and cancer treatments.

Key Takeaways

• Method of Synthesis: The patent describes a specific method for synthesizing 31-ester-42-hydroxy compounds of rapamycin.
• Claims and Scope: The claims define the method and compounds produced, with dependent claims specifying various embodiments.
• Patent Landscape: The patent is part of a broader landscape including related patents and global patent families.
• Patent Analytics: Tools like Claim Coverage Matrix and interactive claim charts are essential for understanding the patent portfolio.
• Legal Status: The patent has expired, making the inventions public domain.

FAQs

What is the main invention described in US 5,362,718?

The main invention is a method for preparing 31-ester-42-hydroxy compounds of rapamycin by protecting the 42-alcohol group and esterifying the 31-hydroxyl group.

What is the significance of protecting the 42-alcohol group in the synthesis process?

Protecting the 42-alcohol group prevents unwanted reactions during the esterification process, ensuring the production of the desired rapamycin derivatives.

How does the patent landscape around US 5,362,718 look?

The patent is part of a global patent family with related patents filed in other countries and is connected to other patents describing similar methods for synthesizing rapamycin derivatives.

What tools can be used to analyze the claim coverage of this patent?

Tools like Claim Coverage Matrix and interactive claim charts generated by software such as ClaimScape® can be used to analyze the claim coverage and identify gaps or opportunities.

What is the current legal status of US 5,362,718?

The patent has ceased or expired due to fee-related issues, making the inventions described in the patent public domain.

How does the expiration of this patent impact the industry?

The expiration allows other companies to develop and commercialize similar rapamycin derivatives, leading to increased competition and innovation in the field.

Drugs Protected by US Patent 5,362,718

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 5,362,718

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0763039		CA 2008 00028	Denmark
European Patent Office	0763039		91438	Luxembourg
European Patent Office	0763039		PA2008009	Lithuania
European Patent Office	0763039		300348	Netherlands
European Patent Office	0763039		PA2008009,C0763039	Lithuania
European Patent Office	0763039		SPC017/2008	Ireland
European Patent Office	0763039		08C0018	France