Ocrelizumab

Specification

• Cat#: THA-0083
• Product Name: Ocrelizumab
• Description: Ocrelizumab is a CD20 specific monoclonal antibody used to treat relapsing remitting multiple sclerosis.
• Sequences: CDR L1 sequence (SEQ ID 1): RASSSVSYMH CDR L2 sequence (SEQ ID 2): APSNLAS CDR L3 sequence (SEQ ID 3): QQWSFNPPT CDR H1 sequence (SEQ ID 4): GYTFTSYNMH CDR H2 sequence (SEQ ID 5): AIYPGNGDTSYNQKFKG CDR H3 sequence (SEQ ID 6): VVYYSNSYWYFDV Variable light chain sequence (SEQ ID 7): DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKR Variable heavy chain sequence (SEQ ID 8): EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSYNQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTVSS Light chain amino acid sequence (SEQ ID 9): DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Heavy chain amino acid sequence (SEQ ID 10): EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSYNQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Heavy chain amino acid sequence (SEQ ID 11): EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSYNQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
• Molecular Weight: 145000.0 Da (Approximate, glycosylated)
• Introduction: Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of patients with primary progressive or relapsing forms of multiple sclerosis (MS). It is a second-generation recombinant humanized monoclonal IgG1 antibody that selectively targets B-cells that express the CD20 antigen. Compared to non-humanized CD20 antibodies such as rituximab, ocrelizumab is expected to be less immunogenic with repeated infusions, improving the benefit-to-risk profile for patients with MS. MS is a chronic, inflammatory, autoimmune disease of the central nervous system that leads to neurological disabilities and a significantly reduced quality of life. Most patients with MS experience episodes of relapses with worsening function, followed by recovery periods or remissions. Primary progressive multiple sclerosis (PPMS) accounts for 10-15% of the overall population of patients with MS, and leads to the gradual worsening of neurologic disability from symptom onset, often without early relapses or remissions. Developed by Genentech/Roche, ocrelizumab was approved by the FDA in March 2017 under the market name Ocrevus for intravenous injection. It was later approved by Health Canada in August 2017, making the drug the first available treatment for PPMS in both the US and Canada. In clinical trials of patients with relapsing forms of MS, treatment with ocrelizumab resulted in reduced relapse rates and reduced worsening of disability compared to interferon beta-1a. In phase 3 clinical trials of patients with PPMS, treatment with ocrelizumab led to lower clinical and MRI progression rates compared to placebo.
• Purity: >99% by SDS-Page and HPLC analysis
• Formula: C6494H9978N1718O2014S46
• Appearance: Solid

Pharmaceutical Information

• Pharmacodynamics: Since ocrelizumab interferes with the CD20 assay, CD19+B-cells are used to assess B-cell counts after treatment. Fourteen days following infusion, a reduction in CD19+B-cell counts was observed. In clinical studies, B-cell counts rose above the lower limit of normal (LLN) or baseline counts between infusions of ocrelizumab at least once in 0.3% to 4.1% of patients. In a clinical study involving 51 patients, the time for B-cell counts to return to baseline or LLN ranged from 27 to 125 weeks, with a median time of 72 weeks after the last infusion. Within 2.5 years after the last infusion, B-cell counts returned to either baseline or LNN in 90% of patients treated with ocrelizumab. Since ocrelizumab is a recombinant humanized antibody, it is expected to be less immunogenic than rituximab, a chimeric antibody. Compared to the ocrelizumab pivotal trial, a rituximab phase II trial had a higher proportion of anti-drug antibodies, suggesting greater immunogenicity. However, caution should be exercised since these studies used different assay methods, and the association between anti-drug antibody development and infusion reactions has not been fully elucidated.5 The use of ocrelizumab can cause infusion reactions, and lead to a higher risk of respiratory tract infections and viral infections. Cases of progressive multifocal leukoencephalopathy (PML) and immune-mediated colitis have been reported in patients treated with ocrelizumab. Also, an increased risk of malignancy may exist.
• Targets: B-lymphocyte antigen CD20