Penpulimab is a recombinant, humanized monoclonal antibody developed to target programmed cell death protein 1 (PD-1), an immune checkpoint receptor involved in regulating T-cell activity. It is also known by its development code AK105 and is classified as an Fc-engineered humanized IgG1 anti-PD-1 monoclonal antibody. Penpulimab works by binding to PD-1 and blocking the PD-1 signaling pathway, helping restore immune-cell activity against tumor cells.
Penpulimab is a biologic pharmaceutical API rather than a conventional small-molecule chemical compound. Because of its large protein structure, its quality evaluation requires specialized analytical methods for protein identity, purity, aggregation, charge variants, glycosylation, biological activity and process-related impurities.
The CAS Number of Penpulimab is 2350298-92-7. The reported molecular weight is approximately 145.0 kDa. The molecular formula reported by the USAN statement is C6434H9922N1718O2012S46.
Penpulimab was developed as an Fc-engineered antibody. Its IgG1 framework contains modifications intended to reduce Fc receptor interactions and minimize unwanted Fc-mediated effector functions. Published characterization has reported no apparent ADCC or ADCP activity associated with the engineered antibody.
PD-1 is an immune checkpoint receptor expressed primarily on activated T cells. Interaction between PD-1 and its ligands can reduce T-cell signaling and contribute to immune suppression within the tumor microenvironment.
Penpulimab binds to PD-1 and interferes with this inhibitory signaling pathway. By blocking PD-1-mediated immune suppression, the antibody can help support T-cell activity against cancer cells. This mechanism places Penpulimab within the important class of immune checkpoint inhibitor biologics.
Published research has characterized Penpulimab's interaction with human PD-1 and reported high-affinity binding, with a reported dissociation constant of approximately 0.59 nM.
Penpulimab is a recombinant monoclonal antibody requiring controlled biologic manufacturing processes. Production generally involves recombinant expression followed by purification and formulation steps designed to maintain protein integrity and biological activity.
Important quality attributes include protein identity, molecular integrity, purity, aggregation, charge heterogeneity, glycosylation pattern, host-cell proteins, residual host-cell DNA, endotoxin and biological potency.
Because monoclonal antibodies are sensitive to environmental conditions, manufacturing and storage require appropriate controls for temperature, pH, light exposure, agitation and other factors that can affect protein stability.
Penpulimab requires a combination of orthogonal analytical techniques. Protein identity can be evaluated through peptide mapping, mass spectrometry and chromatographic characterization. Protein purity and related species can be evaluated using appropriate HPLC or electrophoretic methods.
Size-exclusion chromatography can be used to monitor high-molecular-weight aggregates and other size variants. Ion-exchange chromatography or equivalent analytical methods can be used for charge-variant characterization. Glycan analysis can be used to monitor the antibody's glycosylation profile.
Biological potency is particularly important because physicochemical purity alone does not demonstrate functional activity. A validated PD-1 binding assay and/or suitable cell-based functional assay can therefore be used to evaluate biological activity.
Penpulimab is associated with oncology and immuno-oncology pharmaceutical development. As an anti-PD-1 monoclonal antibody, it has been investigated in several cancer indications, including nasopharyngeal carcinoma and relapsed or refractory classical Hodgkin lymphoma.
For pharmaceutical development, Penpulimab is considered a specialized biologic API requiring stringent control of critical quality attributes.
Quality control for Penpulimab should include identity, purity, molecular integrity, aggregates, charge variants, glycosylation, biological potency and process-related impurities. Host-cell protein and residual DNA testing are important for recombinant biologics, while endotoxin and bioburden testing support microbiological safety.
Unlike small-molecule APIs, Penpulimab does not have universally applicable specifications for parameters such as melting point, residue on ignition or specific rotation. These fields should therefore be treated as not applicable, while critical biologic attributes should be controlled using validated product-specific methods.
CAS Number: 2350298-92-7
Alternate CAS / CAS 2: N/A
Grade: Pharmaceutical / Biologic Grade
Category: Monoclonal Antibody API / Biologic API / Anti-PD-1 API
Appearance: Protein biologic; product-specific physical description
Molecular Weight: Approximately 145.0 kDa
Molecular Formula: C6434H9922N1718O2012S46
Development Code: AK105
Target: Programmed cell death protein 1 (PD-1)
Antibody Type: Humanized IgG1 monoclonal antibody with Fc engineering
Standards Compliance: Applicable biologic/pharmaceutical GMP and validated product-specific specifications
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | ≤ 1.5% |
| Water Content | NMT 1.0% |