Oral GnRH Antagonist Combination for Heavy Menstrual Bleeding

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Solution Overview

Problem

Current treatments for conditions like endometriosis, uterine fibroids, and adenomyosis, particularly heavy menstrual bleeding, are inconvenient due to the need for daily injections and lack of orally available nonpeptide GnRH antagonists, and there is a need for effective management of associated pain and symptoms.

Innovation Solution

Administration of 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid (Compound A) or its pharmaceutically acceptable salt, combined with estrogens and progestogens, in various dosages and durations, to treat endometriosis and reduce heavy menstrual bleeding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptide GnRH antagonists are used to treat heavy menstrual bleeding, then the treatment effectiveness is improved, but the ease of operation deteriorates due to requiring daily subcutaneous injections or long-acting depot formulations

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidease of operation

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the peptide-based GnRH antagonist (which requires injection) with a nonpeptide small molecule oral antagonist. This substitution changes the administration route from mechanical injection to oral ingestion, resolving the contradiction between treatment effectiveness and ease of operation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If GnRH agonists are used to suppress pituitary-gonadal axis activity, then the treatment effectiveness is improved, but object-generated harmful factors worsen due to initial stimulation of gonadotropic and gonadal hormones

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidinitial hormone stimulation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent inverts the mechanism from GnRH agonist (which stimulates receptors initially) to GnRH antagonist (which blocks receptors from the start). This inversion eliminates the harmful initial stimulation effect while maintaining the desired suppression of gonadotropic hormones.

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If hormone-blocking strategies are used to treat uterine fibroids, then the treatment effectiveness is improved, but object-generated harmful factors worsen due to bone mineral density loss

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidbone mineral density loss

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the pharmacological parameter from traditional hormone-blocking agents (which cause significant bone density loss) to a selective nonpeptide GnRH antagonist with a more favorable side effect profile. This parameter change maintains treatment effectiveness while reducing harmful effects on bone mineral density.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260091041A1Methods of Treating Heavy Menstrual Bleeding

Publication Date: 2026.04.02 ABBVIE INC

AI summary

The present invention relates to the method of treating heavy menstrual bleeding in a subject with or without uterine fibroids and in need of treatment by administering an effective amount of 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid or a pharmaceutically acceptable salt thereof, in combination with estrogens and progestogens.