Nipocalimab is a fully human monoclonal antibody designed to selectively bind the neonatal Fc receptor (FcRn). It is a recombinant human IgG1 lambda (IgG1λ) antibody produced using a genetically engineered Chinese hamster ovary (CHO) cell line. Nipocalimab binds to the IgG-binding site of FcRn and inhibits FcRn-mediated recycling of IgG, resulting in reduction of circulating IgG levels.
Nipocalimab is a specialized biological active pharmaceutical ingredient relevant to the development of therapies for IgG-mediated autoimmune and alloimmune disorders.
Nipocalimab is a complex recombinant biologic rather than a conventional small-molecule API. Its quality assessment therefore focuses on biological and molecular attributes such as identity, purity, protein concentration, molecular-size distribution, charge variants, glycosylation characteristics, FcRn-binding activity and biological potency.
FDA identifies nipocalimab-aahu as a recombinant human IgG1 lambda monoclonal antibody with an approximate molecular weight of 142 kDa.
CAS Number: 2211985-36-1
Molecular Type: Fully Human Recombinant Monoclonal Antibody
Immunoglobulin Class: IgG1 Lambda (IgG1λ)
Approximate Molecular Weight: 142 kDa
Target: Neonatal Fc Receptor (FcRn / FCGRT)
Drug Class: FcRn Antagonist / FcRn Blocker
Therapeutic Class: Immunomodulator
Therapeutic Area: Immunology / Autoimmune and Alloimmune Diseases
Production System: Chinese Hamster Ovary (CHO) Cells
Code Names: M281, M-281, JNJ-80202135
FDA UNII: 87M90CV8NC
WHO describes nipocalimab as an IgG1-lambda monoclonal antibody directed against the human neonatal Fc receptor and produced in CHO cells. FDA's substance database identifies CAS 2211985-36-1.
Nipocalimab binds with high affinity and selectivity to the IgG-binding site of FcRn.
Its mechanism includes:
Nipocalimab binds FcRn at both neutral and acidic pH, a property associated with its ability to inhibit IgG recycling.
Nipocalimab API is relevant to:
Nipocalimab is designed to reduce circulating IgG, including pathogenic autoantibodies. This mechanism makes it relevant to therapeutic development for IgG-mediated autoimmune and alloimmune diseases.
Nipocalimab has been clinically evaluated in conditions including generalized myasthenia gravis, maternal-fetal alloimmune disorders and rheumatologic diseases.
The neonatal Fc receptor (FcRn) plays an important role in protecting IgG from intracellular degradation and maintaining circulating IgG levels.
Nipocalimab occupies the IgG-binding site on FcRn and prevents IgG from undergoing FcRn-mediated recycling. This results in increased IgG clearance and decreased circulating IgG concentrations.
Nipocalimab is a large recombinant protein rather than a crystalline small molecule. FDA describes nipocalimab-aahu as an approximately 142 kDa human IgG1λ monoclonal antibody. It contains an aglycosylated Fc region, resulting in a lack of Fc effector functions.
Consequently, conventional small-molecule parameters such as melting point, residue on ignition and specific rotation are not appropriate primary quality attributes for Nipocalimab.
The approved IMAAVY formulation contains nipocalimab-aahu at 185 mg/mL and has a pH of 6.0. The formulation is a sterile, preservative-free, clear to slightly opalescent solution.
Important: The pH 6.0 and 185 mg/mL values describe the approved formulated drug product and should not be presented as universal drug-substance specifications.
A controlled recombinant Nipocalimab manufacturing process may involve:
Typical Nipocalimab biological API characterization may include:
These tests are more appropriate for a monoclonal antibody than conventional small-molecule API tests.
Store Nipocalimab according to the approved product specification and validated stability program.
For the marketed IMAAVY drug product, storage is under controlled refrigerated conditions; the exact commercial storage requirement should be taken from the current approved labeling rather than applying a generic API storage statement.
Nipocalimab is relevant to research involving:
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| pH (1% Solution) | 5.0 – 6.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |