PTH Polypeptide Derivatives for Bone Mass Anabolism

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Solution Overview

Problem

Current treatments for osteoporosis lack effective therapies to promote fracture repair and prevent fractures, with existing agents like estrogen, calcitonin, and bisphosphonates showing varying success in decreasing bone resorption but no definitive cure.

Innovation Solution

Development of novel parathyroid hormone (PTH) polypeptide derivatives with amino acid substitutions at specific positions, which are biologically active and can be used to treat bone-related defects, including osteoporosis, by administering them to increase bone mass and prevent fractures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing agents like estrogen, calcitonin, and bisphosphonates are used to treat osteoporosis, then bone resorption is decreased, but there is no definitive cure and fracture prevention is insufficient

Engineering Contradiction:

Improveeffectiveness of osteoporosis treatmentVSAvoidfracture repair promotion capability

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent modifies the amino acid sequence of PTH by substituting specific residues (e.g., position 8, 18, 20, 21, 23, 24, 25, 26, 27, 28, 31) to create derivatives with enhanced bone-forming activity. This parameter change in molecular structure results in improved anabolic effects on bone mass while maintaining receptor compatibility, directly addressing the insufficiency of existing treatments in promoting fracture repair

Inventive Principle:

Principle #35Parameter changes

2Strength

If PTH is administered intermittently to promote bone formation, then anabolic effects on bone mass are achieved, but the complexity of administration increases

Engineering Contradiction:

Improvebone massVSAvoidadministration regimen complexity

Core Design Contradiction:

StrengthVSDevice complexity

Solution Approach 1:

The patent creates PTH derivatives with modified amino acid sequences that possess enhanced stability and prolonged half-life characteristics. These parameter changes in molecular properties allow for more convenient administration regimens while maintaining or enhancing the bone-building effects, thereby reducing the practical complexity of treatment protocols

Inventive Principle:

Principle #35Parameter changes

3Strength

If PTH derivatives with amino acid substitutions are developed, then bone-forming effects are enhanced, but the manufacturing precision requirements increase

Engineering Contradiction:

Improvebone-forming activityVSAvoidamino acid substitution accuracy

Core Design Contradiction:

StrengthVSManufacturing precision

Solution Approach 1:

The patent systematically identifies and modifies specific amino acid positions in the PTH molecule independently. By segmenting the modification process into discrete position-specific substitutions (e.g., position 8, 18, 20, etc.), the manufacturing process can be optimized for each position separately, reducing overall complexity while maintaining high precision where critical for biological activity

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS8143374B2Polypeptide derivatives of parathyroid hormone (PTH)

Publication Date: 2012.03.27 THE GENERAL HOSPITAL CORP

AI summary

The present invention is related to novel parathyroid hormone polypeptide derivatives, and to pharmaceutical composition containing the polypeptides, as well as synthetic and recombinant methods for producing the polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing the polypeptides of the present invention. The present invention further provides diagnostic and therapeutic methods using the polypeptide derivatives.