Lower Strength Imiquimod Formulations for Actinic Keratosis

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Solution Overview

Problem

The current FDA-approved topical treatment regimen for actinic keratosis using Aldara® 5% imiquimod cream is lengthy, complex, and associated with high incidence of application site reactions, limiting patient compliance and therapeutic effectiveness.

Innovation Solution

Development of lower dosage strength imiquimod formulations with simplified dosing regimens for daily application over shorter durations, allowing treatment of larger areas with fewer application site reactions, using vehicles like isostearic acid to maintain stability and efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If 5% imiquimod cream is applied twice weekly for 16 weeks, then actinic keratosis treatment efficacy is achieved, but treatment duration is lengthy and patient compliance is reduced

Engineering Contradiction:

Improvetreatment efficacyVSAvoidtreatment duration

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the concentration parameter of imiquimod from 5% to lower strengths (1%, 2%, 2.5%, 3%, 3.75%, 4%, or 4.25%), which enables shorter treatment durations of 2, 3, or 4 weeks while maintaining treatment efficacy for actinic keratosis

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs periodic dosing regimens where imiquimod is applied at specific intervals (e.g., once daily, twice weekly, or three times weekly) over shortened treatment periods of 2-4 weeks, achieving therapeutic effects without requiring continuous 16-week application

Inventive Principle:

Principle #19Periodic action

2Reliability

If 5% imiquimod cream is applied twice weekly for 16 weeks, then actinic keratosis treatment efficacy is achieved, but dosing regimen complexity increases

Engineering Contradiction:

Improvetreatment efficacyVSAvoiddosing regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent simplifies the dosing regimen by reducing application frequency from twice weekly to once daily or three times weekly over shortened treatment periods, and by using lower imiquimod concentrations that require less complex application schedules

Inventive Principle:

Principle #35Parameter changes

3Reliability

If 5% imiquimod cream is applied twice weekly for 16 weeks, then actinic keratosis treatment efficacy is achieved, but application site reactions increase

Engineering Contradiction:

Improvetreatment efficacyVSAvoidapplication site reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent reduces the imiquimod concentration parameter from 5% to lower strengths (1%-4.25%), which decreases the incidence and severity of application site reactions while maintaining treatment efficacy through optimized dosing regimens and shorter treatment durations

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses periodic dosing schedules with shorter treatment periods (2-4 weeks) followed by treatment-free intervals, allowing skin recovery and reducing cumulative irritation and application site reactions associated with continuous 16-week treatment

Inventive Principle:

Principle #19Periodic action

4Object-affected harmful factors

If lower dosage strength imiquimod formulations are used, then application site reactions are reduced, but treatment duration may increase

Engineering Contradiction:

Improveapplication site reactionsVSAvoidtreatment duration

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of moving object

Solution Approach 1:

The patent employs periodic dosing regimens with concentrated application periods (once daily or three times weekly for 2-4 weeks) followed by treatment-free intervals, which maintains efficacy with lower concentrations while preventing treatment duration extension through structured scheduling

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent optimizes the combination of imiquimod concentration parameters (1%-4.25%) with treatment duration parameters (2-4 weeks) and dosing frequency parameters (once daily to three times weekly) to achieve reduced application site reactions without unnecessarily extending treatment duration

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11318130B22x2x2 week dosing regimen for treating actinic keratosis with pharmaceutical compositions formulated with 3.75% imiquimod

Publication Date: 2022.05.03 MEDICIS PHARMACEUTICAL CORP

AI summary

Pharmaceutical formulations and methods for the topical or transdermal delivery of 1-isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine or 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, i.e., imiquimod, to treat actinic keratosis with short durations of therapy, than currently prescribed for the commercially available Aldara® 5% imiquimod cream, as now approved by the U.S. Food & Drug Administration (“FDA”), are disclosed and described. More specifically, lower dosage strength imiquimod formulations to deliver an efficacious dose of imiquimod for treating actinic keratosis with an acceptable safety profile and dosing regimens that are short and more convenient for patient use than the dosing regimen currently approved by the U.S. Food & Drug Administration (“FDA”) for Aldara® 5% imiquimod cream to treat actinic keratosis are also disclosed and described.