Fucosylated Recombinant AAT Composition for Stronger Immunomodulation

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing recombinant human AAT compositions lack enhanced immunomodulatory effects and are inefficient compared to plasma-derived AAT, with significant production costs and side effects.

Innovation Solution

Development of recombinant human AAT (rAAT) with high fucosylation levels, produced in CHO cells, exhibiting over 75% fucosylated N-linked glycans, which demonstrates superior immunomodulatory activity, including reduced inflammation and increased anti-inflammatory cytokine production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If plasma-derived AAT is used for therapy, then immunomodulatory effects are achieved, but production costs are high and side effects occur

Engineering Contradiction:

Improveimmunomodulatory effectsVSAvoidproduction costs

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates a recombinant human AAT protein that copies the structure and function of plasma-derived AAT, including its immunomodulatory properties. The recombinant protein is produced in CHO cells with engineered N-glycosylation pathways to replicate the complex carbohydrate side chains essential for biological activity, thereby achieving therapeutic effects without relying on plasma derivation

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent modifies the glycosylation parameters of AAT by engineering CHO cells to produce complex N-glycans with specific structures (including core fucosylation and terminal sialylation). These parameter changes in carbohydrate composition enhance the immunomodulatory activity of the recombinant AAT, making it comparable or superior to plasma-derived AAT

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If recombinant AAT is produced without enhanced glycosylation, then production is simpler, but immunomodulatory activity is reduced

Engineering Contradiction:

Improveproduction simplicityVSAvoidimmunomodulatory activity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent applies local quality modification by specifically engineering the N-glycosylation sites on the AAT protein. The CHO cells are modified to produce complex N-glycans with specific structures at the three N-glycosylation positions (Asn46, Asn83, and Asn247), while the rest of the protein structure remains unchanged. This localized enhancement of glycosylation quality delivers the immunomodulatory activity without complicating the overall production process

Inventive Principle:

Principle #3Local quality

3Reliability

If AAT is administered weekly via intravenous infusion, then therapeutic levels are maintained, but treatment burden increases

Engineering Contradiction:

Improvetherapeutic levelsVSAvoidtreatment burden

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent modifies the pharmacokinetic parameters of AAT by enhancing its immunomodulatory activity through improved glycosylation. The engineered complex N-glycans with specific structures increase the protein's half-life and potency, potentially allowing for less frequent administration or lower doses while maintaining therapeutic levels, thereby reducing treatment burden

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260015410A1Highly fucosylated recombinant human alpha 1 antitrypsin (AAT) protein having immunomodulatory activity and compositions comprising the same

Publication Date: 2026.01.15 KAMADA LTD

AI summary

Provided herein are recombinant AAT proteins having high fucosylation levels and enhanced immunomodulatory biological activity as compared to a plasma derived AAT. Further provided are compositions including the same and methods for preparation thereof.