Modified AMH Proteins Delay Ovarian Senescence

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Solution Overview

Problem

Current methods fail to effectively address ovarian senescence and premature menopause, leading to reduced ovarian reserve and associated health issues, particularly in women undergoing gonadotoxic treatments or with genetic predispositions, resulting in unmanageable menopause onset and detrimental symptoms.

Innovation Solution

The use of modified Anti-Müllerian hormone (AMH) proteins, specifically modified to enhance bioactivity and stability, which regulate folliculogenesis by inhibiting follicle maturation and depletion, thereby delaying menopause and alleviating menopausal symptoms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If follicle maturation and depletion are accelerated to achieve reproductive goals, then reproductive potential is realized, but ovarian reserve is depleted and menopause occurs prematurely

Engineering Contradiction:

Improvereproductive potentialVSAvoidovarian reserve

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by administering modified AMH proteins before ovarian senescence occurs to prevent accelerated follicle depletion. The modified AMH proteins are designed to maintain follicular pool integrity and delay menopause onset, allowing women to preserve their ovarian reserve while still achieving reproductive goals when desired.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements preliminary anti-action by using modified AMH proteins that counteract the harmful effects of gonadotoxic treatments and genetic predispositions before they cause irreversible ovarian damage. The modified proteins prevent premature follicle activation and depletion, thereby protecting the ovarian reserve from accelerated loss.

Inventive Principle:

Principle #9Preliminary anti-action

2Reliability

If conventional AMH proteins are used to regulate folliculogenesis, then follicle maturation is inhibited, but the proteins lack sufficient bioactivity and stability for effective treatment

Engineering Contradiction:

Improvefolliculogenesis regulationVSAvoidprotein bioactivity

Core Design Contradiction:

ReliabilityVSStrength

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequence of AMH proteins to enhance their bioactivity and stability. Specific amino acid substitutions are introduced to improve the proteins' half-life, receptor binding affinity, and resistance to proteolytic degradation, thereby achieving reliable folliculogenesis regulation with enhanced therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent implements composite materials by creating modified AMH proteins that combine the natural AMH structure with engineered enhancements. The modified proteins integrate wild-type AMH sequences with mutated regions that confer improved stability and bioactivity, resulting in a composite protein structure that achieves both reliable folliculogenesis regulation and enhanced therapeutic properties.

Inventive Principle:

Principle #40Composite materials

3Object-affected harmful factors

If women undergo gonadotoxic treatments to treat cancer, then cancer is treated, but ovarian reserve is depleted and menopause occurs prematurely

Engineering Contradiction:

Improvecancer treatmentVSAvoidovarian reserve

Core Design Contradiction:

Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent applies beforehand cushioning by administering modified AMH proteins before gonadotoxic treatments to protect the ovarian reserve from treatment-induced damage. The modified proteins create a protective effect that cushions the ovaries against the harmful impacts of chemotherapy and radiation, preserving follicular integrity and delaying menopause onset.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The patent implements blessing in disguise by using modified AMH proteins to convert the harmful effects of gonadotoxic treatments into beneficial outcomes. The modified proteins counteract the treatment-induced follicle depletion and oxidative stress, transforming the potentially devastating impact of cancer treatment into an opportunity to preserve reproductive potential and delay menopause.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20220389069A1Compositions and methods regulating folliculogenesis for the treatment of ovarian senescence

Publication Date: 2022.12.08 GEDEON RICHTER

AI summary

Provided herein are methods and compositions relating to modified proteins of Anti-Müllerian hormone (AMH) for regulating folliculogenesis in a woman, and in particular regulating follicle activation and maturation and immature (primordial) follicle depletion. In certain embodiments, regulating or inhibiting folliculogenesis in a woman treats ovarian senescence, pauses or slows down ovarian aging and/or delays the onset of menopause and/or the symptoms related to menopause, premature ovarian decline induced by gonadotoxic treatment, or diseases or conditions caused by genetic mutations in genes regulating folliculogenesis and ovarian biology.