Antibody disulfide bond (DSB) reduction during the manufacturing process is a widely observed phenomenon is associated with the host cell reductase is present in the liquid cell culture harvest. Induced enzyme leads to a reduction in antibodies against fragments and aggregate products that increase the load of impurities in the purification process. The impact of the decline in the bivalent bispecific antibody (BisAbs), which are increasingly entering the clinic, unexplored. We focus on the reduction and reoxidation properties homologous library BisAb format has an additional bivalent Fv (scFv) single chain fragment with engineered DSBs.
Despite all BisAbs have the same susceptibility to enzymatic reduction, fragmentation pathway relies on scFv fusion site. reduced molecules were allowed to reoxidize with and without low pH virus inactivation treatment. Both studies indicate that some species reoxidation BisAb complex formed as a result of mis-pairing DSB. In addition, the aggregate rate of increase for all molecules when there is a low pH treatment is applied. Combined, our results suggest that complex DSB mis-pairing occurs during the downstream process while aggregate formation depends on sample treatment. These results are applicable to other novel mAb-like format containing engineered DSBs, thus highlighting the need to prevent the reduction of new protein therapeutics to avoid reduced product quality during manufacturing. This article is protected by copyright. All rights reserved.
biopharmaceutical drugs are complex molecules derived from living organisms (plant or animal cells) and may contain components of living organisms using biotechnology. Biosimilars are closely similar to biopharmaceutical products that have been approved to establish a new generation of drugs that are widely available at reasonable costs.
Expiration of the patent and data protection Remicade (infliximab) aggravated acceptance biosimilar on the open market. Analysis of the data package submitted for biosimilar infliximab and assessment report published by the institute show the importance of the European Medicines Agency (EMA) product-specific guidelines (monoclonal antibody) which is being followed by different regulatory agencies around the world.
Given the use of case-by-case basis for the development of a biosimilar, infliximab biosimilar product-evaluation reports indicate similarities in the nature and extent of the data required in analytical studies, nonclinical, clinical and even utilize different cell lines of this reference product
Impact of enzymatic reduction on bivalent bispecific antibody fragmentation and loss of product purity upon reoxidation.
Implementation of High-Resolution LC / MS Methods in Laboratory Quality Control for Release and Stability Testing Antibodies Commercial Products.
liquid chromatography / mass spectrometry (LC / MS) has been widely used throughout the biotherapeutic development. However, the implementation of GMP-compliant commercial quality control (QC) laboratory remains a challenge. In this publication, we describe the co-validation and implementation of automated, high-throughput, and GMP compliant subunit LC / MS method to monitor antibody oxidation for commercial product release and stability testing.
Description: A polyclonal antibody for detection of DcR1 from Human. This DcR1 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human DcR1
Description: A polyclonal antibody for detection of DcR1 from Human. This DcR1 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human DcR1
Description: A polyclonal antibody for detection of DcR1 from Human. This DcR1 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human DcR1
Description: TNF receptor superfamily member 10c encoded by TNFRSF10C is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL.
Description: TNF receptor superfamily member 10c encoded by TNFRSF10C is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL.
Description: TNF receptor superfamily member 10c encoded by TNFRSF10C is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human DcR1 . This antibody is tested and proven to work in the following applications:
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human DcR1 . This antibody is tested and proven to work in the following applications:
Description: DcR1 Antibody: Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors. TRAIL/Apo2L is a new member of the TNF family and induces apoptosis of a variety of tumor cell lines. DR4 and DR5 are the recently identified functional receptors for TRAIL. Two decoy receptors for TRAIL have been identified and designated DcR1/TRID/TRAIL-R3/LIT and DcR2/TRAIL-R4/TRUNDD. DcR1 has extracellular TRAIL-binding domain but lacks intracellular signaling domain. It is a glycophospholipid-anchored cell surface protein. DcR1 transcripts were expressed in many normal human tissues but not in most cancer cell lines. Overexpression of DcR1 did not induce apoptosis, but attenuated TRAIL-induced apoptosis.
Description: DcR1 Antibody: Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors. TRAIL/Apo2L is a new member of the TNF family and induces apoptosis of a variety of tumor cell lines. DR4 and DR5 are the recently identified functional receptors for TRAIL. Two decoy receptors for TRAIL have been identified and designated DcR1/TRID/TRAIL-R3/LIT and DcR2/TRAIL-R4/TRUNDD. DcR1 has extracellular TRAIL-binding domain but lacks intracellular signaling domain. It is a glycophospholipid-anchored cell surface protein. DcR1 transcripts were expressed in many normal human tissues but not in most cancer cell lines. Overexpression of DcR1 did not induce apoptosis, but attenuated TRAIL-induced apoptosis.
Description: DcR1 Antibody: Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors. TRAIL/Apo2L is a new member of the TNF family and induces apoptosis of a variety of tumor cell lines. DR4 and DR5 are the recently identified functional receptors for TRAIL. Two decoy receptors for TRAIL have been identified and designated DcR1/TRID/TRAIL-R3/LIT and DcR2/TRAIL-R4/TRUNDD. DcR1 has extracellular TRAIL-binding domain but lacks intracellular signaling domain. It is a glycophospholipid-anchored cell surface protein. DcR1 transcripts are expressed in many normal human tissues but not in most cancer cell lines. Overexpression of DcR1 did not induce apoptosis, but attenuated TRAIL-induced apoptosis.
Description: DcR1 Antibody: Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors. TRAIL/Apo2L is a new member of the TNF family and induces apoptosis of a variety of tumor cell lines. DR4 and DR5 are the recently identified functional receptors for TRAIL. Two decoy receptors for TRAIL have been identified and designated DcR1/TRID/TRAIL-R3/LIT and DcR2/TRAIL-R4/TRUNDD. DcR1 has extracellular TRAIL-binding domain but lacks intracellular signaling domain. It is a glycophospholipid-anchored cell surface protein. DcR1 transcripts are expressed in many normal human tissues but not in most cancer cell lines. Overexpression of DcR1 did not induce apoptosis, but attenuated TRAIL-induced apoptosis.
Description: A polyclonal antibody for detection of DcR3 from Human. This DcR3 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human DcR3 at AA range: 220-300
Description: A polyclonal antibody for detection of DcR3 from Human. This DcR3 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human DcR3 at AA range: 220-300
Description: A polyclonal antibody for detection of DcR3 from Human. This DcR3 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human DcR3 at AA range: 220-300
Description: TNFRSF6B belongs to the tumor necrosis factor receptor superfamily. TNF receptor superfamily member 6b is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript.
Description: TNFRSF6B belongs to the tumor necrosis factor receptor superfamily. TNF receptor superfamily member 6b is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript.
Description: TNFRSF6B belongs to the tumor necrosis factor receptor superfamily. TNF receptor superfamily member 6b is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human DcR3 . This antibody is tested and proven to work in the following applications:
Description: A Rabbit Polyclonal antibody against P2 from Human/Mouse. This antibody is tested and validated for WB, ELISA, WB, ELISA
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To our knowledge, this is the first report describing the implementation of high-resolution LC / MS method in commercial QC laboratories for product release and stability testing in the biopharmaceutical industry. This work paves the way for implementing additional LC / MS method to modernize commercial QC testing with targeted control over product quality.
Evelyn
