==== Reference: Usmani SS, Bedi G, Samuel JS, Singh S, Kalra S, Kumar P, et al. (2017) THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE 12(7) e0181748.====

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1537 details
Primary information
ThPP IDTh1116
Therapeutic Peptide/Protein NameCanakinumab
SequenceH-GAMMA-1 (VH(1-118)+CH1(119-216)+HINGE-REGION(217 view full sequnce in fasta
Functional ClassificationIIIb
Molecular Weight145200 (deglycosylated)
Chemical FormulaC6452H9958N1722O2010S42
Isoelectric PointN.A.
HydrophobicityN.A.
Melting Point (℃)N.A.
Half Life26 days
DescriptionCanakinumab is a recombinant (from murine Sp2/0-Ag14 cell line), human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It comprises of two 447- or 448-residue heavy chains and two 214-residue light chains. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at N298. It binds to human IL-1β, thereby neutralizing its inflammatory activity by preventing its interaction with IL-1 receptors. However it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). It is marketed under the brand name Ilaris.
Indication/DiseaseFor the treatment of patients aged 4 years and older, to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS). It is also used to treat systemic juvenile idiopathic arthritis (SJIA) in patients pf age 2 years and older . It can be effectively afe and effective, offerin and is therefore considered a significantly better option cted daily and which is often poorly tolerated by the young patients
PharmacodynamicsNovartis AG has developed canakinumab as a subcutaneous injection and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases.
Mechanism of ActionIn inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α± or IL-1 receptor antagonist (IL-1ra).
ToxicityThe most common adverse reactions involved the central nervous system (headache and vertigo), gastrointestinal system (diarrhea and nausea), neuromuscular and skeletal system (musculoskeletal pain), and respiratory system (rhinitis, nasopharyngitis and bronchitis). Influenza was also reported.
MetabolismThe metabolism of canakinumab is not yet determined.
AbsorptionThe absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.
Volume of Distribution6.01 L [typical CAPS patient weighing 70 kg]
Clearance0.174 L/day [typical CAPS patient weighing 70 kg]
CategoriesAnti-Inflammatory Agents and Monoclonal antibodies
Patents NumberN.A.
Date of IssueN.A.
Date of ExpiryN.A.
Drug InteractionN.A.
TargetInterleukin-1 beta
Information of corresponding available drug in the market
Brand NameILARIS 
CompanyNovartis Pharmaceuticals
Brand DiscriptionCanakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447-(or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298). The biological activity of canakinumab is measured by comparing its inhibition of IL-1β-dependent expression of the reporter gene luciferase to that of a canakinumab internal reference standard, using a stably transfected cell line.
Prescribed forCryopyrin-Associated Periodic Syndromes (CAPS), Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), Systemic Juvenile Idiopathic Arthritis (SJIA)
Chemical NameN.A.
FormulationReconstitution with 1 mL of preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug. The reconstituted canakinumab is a 150 mg/mL solution essentially free of particulates, clear to slightly opalescent, and is colorless or may have a slightly brownish-yellow tint. A volume of up to 1 mL can be withdrawn for delivery of 150 mg/mL canakinumab for subcutaneous administration. Each reconstituted vial contains 180 mg canakinumab, sucrose, L-histidine, L-histidine HCL monohydrate, polysorbate 80 and Sterile Water for Injection. No preservatives are present.
Physcial Appearnce180 mg of canakinumab as a white, preservative-free, lyophilized powder
Route of AdministrationSubcutaneous
Recommended DosageCryopyrin-Associated Periodic Syndromes (CAPS): The recommended dose of ILARIS is 150 mg for CAPS patients with body weight greater than 40 kg. For CAPS patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg, the recommended dose is 2 mg/kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Systemic Juvenile Idiopathic Arthritis (SJIA): The recommended dose of ILARIS for SJIA patients with a body weight greater than or equal to 7.5 kg is 4mg/kg (with a maximum of 300 mg) administered every four weeks via subcutaneous injection.
ContraindicationConfirmed hypersensitivity to the active substance or to any of the excipients.
Side EffectsILARIS has been associated with an increased risk of serious infections, Immunosuppression, Hypersensitivity , Live vaccines should not be given concurrently with ILARIS.
Useful Linkhttps://www.pharma.us.novartis.com/product/pi/pdf/ilaris.pdf http://www.rxlist.com/ilaris-drug/warnings-precautions.htm
PubMed ID23553601, 23319019, 19494217, 19169963
3-D StructureTh1116 A chain or (Download), Th1116 B chain (View) or (Download)