Relatlimab is a recombinant humanized IgG4 monoclonal antibody that targets lymphocyte activation gene-3 (LAG-3/CD223), an immune-checkpoint receptor expressed on activated T cells. It is an immune checkpoint inhibitor used in combination with nivolumab as nivolumab and relatlimab-rmbw (Opdualag) for unresectable or metastatic melanoma.
The FDA substance record identifies Relatlimab as a monoclonal antibody of the IgG4 subtype and gives CAS 1673516-98-7 as the primary CAS number. The FDA record reports an average molecular weight of approximately 145,300 Da, while the FDA clinical pharmacology review reports approximately 148 kDa for the therapeutic antibody.
| Parameter | Details |
|---|---|
| Product Name | Relatlimab |
| CAS Number | 1673516-98-7 |
| Alternative/Superseded CAS | 1683572-29-3 |
| FDA UNII | AF75XOF6W3 |
| DrugBank | DB14851 |
| NCI Thesaurus | C111999 |
| Molecular Type | Recombinant monoclonal antibody |
| Antibody Subtype | Humanized IgG4 |
| Target | LAG-3 / CD223 |
| Approx. Molecular Weight | 145.3–148 kDa |
| Expression System | Recombinant CHO cell line |
| Therapeutic Class | Antineoplastic / immune checkpoint inhibitor |
| Route | Intravenous |
The FDA GSRS record identifies Relatlimab as a humanized-mouse-derived IgG4 monoclonal antibody and assigns UNII AF75XOF6W3.
Relatlimab is a large biological macromolecule, so conventional small-molecule parameters such as a simple molecular formula, melting point, logP and exact molecular mass are not appropriate primary API quality descriptors.
KEGG reports a calculated molecular composition of C6472H9922N1710O2024S38 and molecular weight of approximately 145,286.80 Da, while FDA characterizes the therapeutic antibody at approximately 148 kDa.
Key characteristics:
Relatlimab is used as part of the fixed-dose combination nivolumab and relatlimab-rmbw.
The current FDA labeling indicates the combination for:
The current U.S. presentation contains 240 mg nivolumab and 80 mg relatlimab in 20 mL, corresponding to 12 mg/mL nivolumab and 4 mg/mL relatlimab.
Relatlimab binds to LAG-3, an inhibitory receptor expressed on T lymphocytes. Blocking LAG-3 signaling can restore or enhance T-cell activity against tumor cells.
Relatlimab therefore works through a different immune-checkpoint pathway from nivolumab, which blocks PD-1. Their combination provides simultaneous blockade of the LAG-3 and PD-1 pathways. FDA classifies Relatlimab as a LAG-3-blocking antibody.
Because Relatlimab is a recombinant monoclonal antibody, its quality evaluation should focus on biological and protein-specific critical quality attributes.
Typical analytical controls include:
Small-molecule tests such as conventional HPLC assay expressed as a percentage of molecular weight, melting point and logP should not be substituted for biologic-specific characterization.
Relatlimab is produced as a recombinant monoclonal antibody in a CHO cell expression system. FDA documentation identifies the antibody as a humanized IgG4 LAG-3-specific monoclonal antibody expressed in recombinant CHO cells.
A pharmaceutical biologics manufacturing process should include:
| Property | Value |
|---|---|
| Protein Type | Monoclonal antibody |
| Isotype | IgG4 |
| Origin | Humanized mouse |
| Molecular Weight | Approximately 145.3–148 kDa |
| Target | LAG-3/CD223 |
| Expression System | Recombinant CHO cell line |
| Molecular Formula | Not appropriate as a conventional API descriptor; estimated composition available |
| LogP | N/A |
| Melting Point | N/A |
| Exact Mass | N/A as a conventional small-molecule parameter |
| pH | Product/formulation-specific |
| Physical Form | Protein solution for the marketed drug product |
FDA identifies Relatlimab at approximately 148 kDa and confirms its recombinant CHO-cell production.
The current U.S. Opdualag presentation is a single-dose vial containing 240 mg nivolumab and 80 mg relatlimab in 20 mL. The solution is sterile, preservative-free, clear to opalescent and colorless to slightly yellow, with potentially a few translucent-to-white particles.
For the finished product, storage is controlled under refrigerated conditions. Prepared solutions may have specified stability periods under refrigeration or room-temperature conditions depending on preparation and applicable labeling. The product must not be frozen.
Bulk Relatlimab drug substance should instead be stored according to its validated API/biologics stability program and approved specification.
Typical documentation for Relatlimab biologic API/manufacturing programs may include:
Relatlimab requires specialized biologics manufacturing and analytical capabilities because it is a recombinant monoclonal antibody rather than a conventional synthetic API.
Key quality considerations include:
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.50% |
| Water Content | NMT 1.0% |