BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

 Bead Extraction and Heat Dissociation (BEHD) For Mitigation of Drug Interference BEHD is the method developed for mitigating drug interference. BEHD method utilizes heat denaturation for the dissociation of the ADA-drug complex present in the samples. The samples are subsequently incubated with the sample and ADA is allowed to bind with Biotin-Drug and captured using streptavidin coated magnetic beads.  Next, the samples are eluted using weak acids such as acetic acid or glycine, neutralized, and assayed in the ADA or NAb assay. The heat denaturation steps become critical when the drugs that are used to capture ADAs are susceptible to harsher acid-base conditions. This BEHD is used for the detection of ADA for cytokine therapy.  Protocol For BEHD : i) Heat Denaturation for Dissociation for ADA-Drug Complex 50ul to 100 ul of the serum samples containing ADAs are treated with mild heat at 62 degrees Celsius for 1 hour in thermocycler and allow the dissociation of ...

CRESEMBA (isavuconazonium sulfate) is an azole antifungal indicated for use in the treatment of Aspergillosis & Mucor mycosis Indication of CRESEMBA Invasive aspergillosis Invasive mucormycosis Contraindications of CRESEMBA Hypersensitivity to CRESEMBA  Coadministration with strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir Coadministration with strong CYP3A4 inducers, such as rifampin, carbamazepine, St. John’s wort, or long acting barbiturates  Use in patients with familial short QT syndrome  Warning & Precautions for Use of CRESEMBA Hepatic Adverse Drug Reactions: Serious hepatic reactions have been reported. Evaluate liver-related laboratory tests at the start and during the course of CRESEMBA therapyInfusion-related reactions were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur Hypersensitivity Reactions: Serious hypersensitivity and severe skin reactions, such as anaphylaxi...

Anifrolumab is the FDA approved antibody therapy for Systemic Lupus Erythematosus Anifrolumab-fnia is a type I interferon (IFN) receptor antagonist, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced in mouse myeloma cells (NS0) by recombinant DNA technology. The molecular weight is approximately 148 kDa.  Indication of SAPHNELO/Anifrolumab: SAPHNELO is a type I interferon (IFN) receptor antagonist indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy. Limitations of Use:  The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. The use of SAPHNELO is not recommended in these situations. Contraindications SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia Warning and Precautions Serious Infections: Serious and sometimes fatal infections have occu...

Evinacumab is FDA Approved Antibody Therapy for Homozygous Familial Hypercholesterolemia EVKEEZA/Evinacumab-dgnb is a recombinant human monoclonal antibody that binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab-dgnb inhibition of ANGPTL3 leads to a reduction in LDL-C, HDL-C, and triglycerides (TG). Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor (LDLR) by promoting very-low-density lipoprotein (VLDL) processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively Indication of EVKEEZA: EVKEEZA is an ANGPTL3 (angiopoietin-like 3) inhibitor indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of ...

RYBREVANT / Amivantamab-vmjw is FDA approved Bispecific Antibodies Immunotherapy For Non-Small Cell Lung Cancer RYBREVANT / Amivantamab-vmjw is a low-fucose human immunoglobulin G1-based bispecific antibody directed against the EGF and MET receptors, produced by mammalian cell line (Chinese Hamster Ovary [CHO]) using recombinant DNA technology that has a molecular weight of approximately 148 kDa. Indication of RYBREVANT/Amivantamab: RYBREVANT/Amivantamab is a bispecific EGF receptor-directed and MET receptor directed antibody indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.  This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be con...

Immune checkpoint inhibiting immunotherapies: These are the class of monoclonal antibody therapies that prevents T-cell inhibition and promotes the activation and proliferation of effector T cells. Two such receptors CTLA-4 & PD-1 that are expressed in T cells transduce inhibitory signals after binding to its ligand.  The monoclonal antibodies targeted against these receptors or their ligands have been shown to increase the tumor-killing activity of T cells.  Figure 1: Immune Check Point Inhibiting Monoclonal Antibodies and its Target in T cells and Tumors. Pembrolizumab (Keytruda), Nivolumab (Opdivo), and cemiplimab (Libtayo) block PD-1 expressed in T cells. Atezolizumab (Tecentriq), Avelumab (Bavencio), and Durvalumab (Imfinzi) block PD-L1 expressed in tumor cells. Ipilimumab (Yervoy) blocks CTLA-4 antigen present in T cells   PD-1 inhibiting antibodies:  These monoclonal antibodies block the PD-1 signaling by binding to its ligand PD-1 expressed i...

Durvalumab (IMFINZI) is FDA approved immunotherapy that blocks PD-L1 Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules. Durvalumab is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture. Indication of Durvalumab (IMFINZI)  IMFINZI is a programmed death-ligand 1 (PD-L1) blocking antibody indicated for the treatment of patients with:   Locally advanced or metastatic urothelial carcinoma who:  have disease progression during or following platinum-containing chemotherapy. have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinic...

Avelumab is FDA approved Immunotherapy that blocks a programmed death ligand1 (PD-L1)  Avelumab (BAVENCIO)- is a human IgG1 lambda monoclonal antibody produced in Chinese hamster ovary cells and has a molecular weight of approximately 147 kDa.  Indication of Aveluman (BAVENCIO) BAVENCIO is a programmed death ligand-1 (PD-L1) blocking antibody indicated for: Merkel Cell Carcinoma (MCC)  • Adults and pediatric patients 12 years and older with metastatic MCC. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Urothelial Carcinoma (UC)  Maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing chemotherapy.   Patients with locally advanced or metastatic UC who:  Have disease progressio...

Atezolizumab is a checkpoint inhibiting immunotherapy Atezolizumab is an Fc-engineered, humanized, monoclonal antibody that binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors. Atezolizumab is a non-glycosylated IgG1 kappa immunoglobulin that has a calculated molecular mass of 145 kDa. Indication of Atezolizumab (TECENTRIQ) TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated for the treatment of patients with:  Advanced or metastatic urothelial carcinoma: Locally advanced or metastatic urothelial carcinoma who:  have disease progression during or following platinum-containing chemotherapy. have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in ...

            Solid Phase with Extraction  Acid Dissociation (SPEAD) is a plate-based method for reducing drug interference in the ADA assay. This method utilizes weak organic acids (Glycine, Acetic acid) to dissociate the drug-ADA complex. The sample is neutralized and allowed the bind to a biotinylated drug and captured on the streptavidin-coated 96 well plate.  After the ADA is captured, the plate is washed to remove any unbound drug present in the sample. The second acid treatment is used to elute the ADA bound to the plate. The ADA sample is transferred, neutralized with Tris-HCl base, and processed in the ADA detection assay.  Procedure: 1) Coating of the plate with a drug: Streptavidin-precoated 96 well high binding plate is widely used for capturing the biotinylated drug / ADA complex. For the optimization of drug concentration,  Test different concentrations of biotinylated drug ( 0.5, 1.0, 5.0 ug / ml, and 10 ug/ml ) and ch...

Ipilimumab (Yervoy) is FDA Approved Immune Check Point Inhibitors For Certain Cancers Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Ipilimumab is an IgG1 kappa immunoglobulin with an approximate molecular weight of 148 kDa. Ipilimumab is produced in mammalian (Chinese hamster ovary) cell culture.  Indication of Ipilimumab (YERVOY) Ipilimumab (YERVOY) is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for:  Metastatic Melanoma - treatment of unresectable or metastatic melanoma in adults and pediatric patients (12 years and older).   Cutaneous Melonama - adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.  Advanced Renal Cell Carcinoma : Treatment of patients with intermediate or poor risk, previously untrea...

Cemiplimab a-k-a LIBTAYO FDA-approved checkpoint inhibitor drug for the treatment of certain cancers Cemiplimab-rwlc a-k-a LIBTAYO is a human programmed death receptor-1 (PD-1) blocking antibody. Cemiplimab-rwlc is a recombinant human IgG4 monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2. Cemiplimab-rwlc is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Cemiplimab-rwlc has an approximate molecular weight of 146 kDa. LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated:  Cutaneous Squamous Cell Carcinoma (CSCC):  for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.  Basal Cell Carcinoma (BCC):  for the treatment of patients with locally advanced BCC (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a...

KEYTRUDA a-k-a Pembrolizumab is a programmed death receptor-1 (PD 1)-blocking antibody Pembrolizumab is a humanized monoclonal IgG4 kappa antibody with an approximate molecular weight of 149 kDa. Pembrolizumab is produced in recombinant Chinese hamster ovary (CHO) cells.  KEYTRUDA (Pembrolizumab) Indications KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:  Melanoma- for the treatment of patients with unresectable or metastatic melanoma Non-Small Cell Lung Cancer (NSCLC) Small Cell Lung Cancer (SCLC)- for the treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy Head and Neck Squamous Cell Cancer (HNSCC) -in combination with platinum and FU for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC Classical Hodgkin Lymphoma (cHL)- for the treatment of adult patients with relapsed or refractory cHL & for the...

REPATHA (evolocumab) injection, for subcutaneous use  DESCRIPTION Evolocumab is a human monoclonal immunoglobulin G2 (IgG2) directed against human proprotein convertase subtilisin Kexin 9 (PCSK9). Evolocumab has an approximate molecular weight (MW) of 144 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. REPATHA is a sterile, preservative-free, clear to opalescent, colorless to pale yellow solution for subcutaneous administration.  CLINICAL PHARMACOLOGY Mechanism of Action Evolocumab is a human monoclonal IgG2 directed against human proprotein convertase subtilisin Kexin 9 (PCSK9). Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the low density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby low...

KYMRIAH (tisagenlecleucel) For Treatment of B-cell precursor acute lymphoblastic leukemia (ALL) INDICATIONS AND USAGE KYMRIAH is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of:   Patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.  Limitation of Use: KYMRIAH is not indicated for the treatment of patients with primary central nervous system lymphoma.  MECHANISM OF ACTION KYMRIAH is a CD19-directed genetically modified autologous T cell immunotherapy that involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to i...

          Bispecific antibodies consist of two small-chain fragments variable (scFv) of the antibody that has binding affinities to different target antigens. T cell engagers are a class of bispecific antibodies that selectively recruit and activate T cytotoxic cells in the tumor tissue and mediate cytotoxicity. In T cell engagers, one scFv domain is designed to bind to CD3 molecules in the T cell, and the second scFv domain binds to a tumor-associated antigen expressed in the tumor tissue. Certain tumor-associated antigens are known to express in specific cancer types. These tumor-associated antigens have been targeted for the treatment of these specific cancers.  These tumor antigens include CD19, BCMA, PSMA, HER2, TROP2, etc.            Bispecific antibodies, similar to any protein therapeutics, can evoke the generation of anti-drug antibodies. Therefore, detection and monitoring of anti-drug antibodies is an i...