WO 2024/074685 A1 — HSA Isoform Etiology Profiling
Bibliographic Data
| Field | Value |
|---|---|
| Publication number | WO 2024/074685 A1 |
| Type | PCT Application (A1 = first publication before grant) |
| Published | 2024 |
| Filed | ~2023 (PCT filing date) |
| Inventors | Souleiman El Balkhi et al. (Limoges, FR) |
| Applicants | INSERM, CHU Limoges, Université de Limoges |
| Image-based (no text layer) — key content reconstructed from technology-transfer strategic report |
Title
“Use of Albumin Isoform Profiles for the Characterization of the Etiology and Severity of Hepatic Lesions”
Core Innovation
This patent establishes that the PTM profile of HSA is disease-etiology-specific — different liver diseases leave distinct “fingerprints” on the albumin molecule that can be read by Top-Down LC-MS. Up to 14 isoforms are resolved.
The key clinical application: non-invasive differentiation of MASH/NASH vs. ALD (alcohol-associated liver disease) — two conditions that require completely different treatment strategies but look identical on standard blood tests.
Disease-Specific Isoform Signatures
| Signature | Isoform(s) | Δmass | Mechanism | Disease |
|---|---|---|---|---|
| ALD (alcohol) | HSA-DA | −186 Da | N-terminal dipeptide truncation (Asp¹-Ala²); protease/oxidative cleavage driven by ethanol metabolism | Alcohol-associated liver disease |
| MASH/NASH | HSA-SGGS | +305 Da | S-glutathionylation (tripeptide adduct on Cys34); reflects glutathione depletion and metabolic oxidative stress | Metabolic steatohepatitis |
| MASH/NASH | HSA-2Glyc | +324 Da | Double glycation (two hexose adducts on Lys residues); reflects chronic hyperglycemia + metabolic syndrome | Metabolic steatohepatitis |
| Mixed / severe | HSA-DA+Cys + HSA-SO₂H | Combined | Synergy of alcohol damage + irreversible sulfinic acid oxidation | ALD + metabolic overlap |
Key Applications
1. Etiological Liquid Biopsy
Replaces the need for liver biopsy to determine why the liver is damaged (ALD vs MASH vs mixed). Clinically critical because:
- ALD → abstinence + alcohol addiction treatment + liver support
- MASH → metabolic intervention (weight, diabetes, Resmetirom)
- Wrong etiology = wrong treatment
2. Clinical Trial Cohort Purity (MASH Trials)
High-value commercial application: patients enrolled in MASH pharmaceutical trials (e.g., Resmetirom, obeticholic acid) must not have significant alcohol intake. However, patients systematically underreport alcohol consumption. The HSA-DA isoform is an objective, quantitative alcohol exposure marker that:
- Disqualifies patients with hidden alcohol consumption before randomization
- Saves millions of dollars by preventing trial contamination
- Already relevant to LabCorp/Covance business (sponsor services for MASH trials)
3. Severity Stratification
The total isoform distribution (all 14 isoforms) provides a severity score orthogonal to MELD, fibrosis stage, or enzyme levels.
Relationship to Published Work
- el-balkhi-2025 — ALBOM study: the clinical proof-of-concept for multi-isoform profiling across MASH, ALD, PBC, PSC cohorts (validates the patent’s differentiation claims)
- naldi-2016-ah — early identification of distinct oxidative products in alcoholic hepatitis (methodological precedent)
- montomoli-2026-aah — AH cohort isoform data (HSA-DA observed; Aarhus/Bologna)
- WO2025099157 — absolute quantification patent that enables precise isoform quantification
Relationship to Other Patent Levels
| Level | What it adds |
|---|---|
| US20220018852 (SEB) | Asks “is the albumin functional?” — binary (yes/no) |
| WO2024074685 (this patent) | Asks “why is it damaged, and how severely?” — etiological |
| WO2025099157 (quantification) | Asks “exactly how much of each isoform?” — absolute quantity |
Commercialization Angle
Primary targets per technology-transfer:
- LabCorp/Covance — MASH trial purity screening (HSA-DA biomarker as enrollment filter)
- BioPredictive — integrate ALD/NASH differentiation into next-generation FibroTest
- Bruker — timsTOF Pro demonstration content for clinical Top-Down proteomics