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Identification
NameAbatacept
Accession NumberDB01281
TypeBiotech
GroupsApproved
DescriptionAbatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).
Protein structureNo structure small
Related Articles
Protein chemical formulaC3498H5458N922O1090S32
Protein average weight92300.0 Da (with glycosylation)
Sequences
>Abatacept monomer sequence
MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTF
LDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPC
PDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED
PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
CTLA4-Ig
CTLA4-IgG4m
CTLA4Ig
CTLA4IgG4m
External Identifiers
  • BMS-188667
  • RG-1046
  • RG-2077
  • RG1046
  • RG2077
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Orenciainjection, powder, lyophilized, for solution250 mg/15mLintravenousE.R. Squibb & Sons, L.L.C.2009-01-01Not applicableUs
Orenciainjection, solution125 mg/mLsubcutaneousE.R. Squibb & Sons, L.L.C.2011-07-29Not applicableUs
Orenciapowder for solution250 mgintravenousBristol Myers Squibb Canada2006-08-08Not applicableCanada
Orenciasolution125 mgsubcutaneousBristol Myers Squibb Canada2013-05-09Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII7D0YB67S97
CAS number332348-12-6
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients. It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists). Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.
PharmacodynamicsAbatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1. The Fc portion of the drug consists of the hinge region, the CH2 domain, and the CH3 domain of IgG1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy.
Mechanism of actionAbatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis.
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AbsorptionWhen a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%.
Volume of distribution
  • 0.07 L/kg [RA Patients, IV administration]
  • 0.09 L/kg [Healthy Subjects, IV administration]
  • 0.11 L/kg [RA patients, subcutaneous administration]
Protein bindingNot Available
MetabolismNot Available
Route of eliminationkidney and liver
Half life16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients.
Clearance
  • 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion]
  • 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions]
  • 0.4 mL/h/kg [juvenile idiopathic arthritis patients].
    The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients.
    The clearance of abatacept increases with increasing body weight.
ToxicityMost common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous250 mg/15mL
Injection, solutionsubcutaneous125 mg/mL
Powder for solutionintravenous250 mg
Solutionsubcutaneous125 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2110518 No2007-05-222012-06-16Canada
Properties
StateLiquid
Experimental PropertiesNot Available
References
Synthesis Reference

Sang-Lin Kim, Hyun-Kwang Tan, Sang-Min Lim, Wuk-Sang Ryu, Hahn-Sun Jung, Song-Jae Lee, Cheon-Ik Park, Seung-Hoon Kang, Dong Il Kim, “Plant Recombinant Human CTLA4IG and a Method for Producing the Same.” U.S. Patent US20100189717, issued July 29, 2010.

US20100189717
General References
  1. Dall'Era M, Davis J: CTLA4Ig: a novel inhibitor of costimulation. Lupus. 2004;13(5):372-6. [PubMed:15230295 ]
  2. Moreland L, Bate G, Kirkpatrick P: Abatacept. Nat Rev Drug Discov. 2006 Mar;5(3):185-6. [PubMed:16557658 ]
  3. Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, Vratsanos G, Zhou Y, Moreland LW: Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006 Nov;33(11):2162-6. Epub 2006 Oct 1. [PubMed:17014006 ]
  4. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [PubMed:16932686 ]
  5. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [PubMed:16971318 ]
  6. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [PubMed:20080922 ]
  7. Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007277. doi: 10.1002/14651858.CD007277.pub2. [PubMed:19821401 ]
  8. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [PubMed:17212998 ]
  9. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [PubMed:16573350 ]
  10. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [PubMed:18041889 ]
External Links
ATC CodesL04AA24
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (108 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Abatacept.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Abatacept.
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Abatacept.
BelimumabThe risk or severity of adverse effects can be increased when Abatacept is combined with Belimumab.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Abatacept.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Abatacept.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Abatacept.
FingolimodAbatacept may increase the immunosuppressive activities of Fingolimod.
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Abatacept.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Abatacept.
LeflunomideThe risk or severity of adverse effects can be increased when Abatacept is combined with Leflunomide.
NatalizumabThe risk or severity of adverse effects can be increased when Abatacept is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Abatacept.
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Abatacept.
Rabies vaccineThe risk or severity of adverse effects can be increased when Abatacept is combined with Rabies vaccine.
RituximabThe risk or severity of adverse effects can be increased when Rituximab is combined with Abatacept.
RoflumilastRoflumilast may increase the immunosuppressive activities of Abatacept.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Abatacept.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Abatacept.
TocilizumabThe risk or severity of adverse effects can be increased when Tocilizumab is combined with Abatacept.
TofacitinibAbatacept may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Abatacept.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Virus receptor activity
Specific Function:
Involved in the costimulatory signal essential for T-lymphocyte activation. T-cell proliferation and cytokine production is induced by the binding of CD28, binding to CTLA-4 has opposite effects and inhibits T-cell activation.(Microbial infection) Acts as a receptor for adenovirus subgroup B.
Gene Name:
CD80
Uniprot ID:
P33681
Molecular Weight:
33047.625 Da
References
  1. Kremer JM: Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62. [PubMed:16357751 ]
  2. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [PubMed:16932686 ]
  3. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [PubMed:16971318 ]
  4. Vincenti F, Luggen M: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med. 2007;58:347-58. [PubMed:17020493 ]
  5. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [PubMed:20080922 ]
  6. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [PubMed:17212998 ]
  7. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [PubMed:16573350 ]
  8. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [PubMed:18041889 ]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Virus receptor activity
Specific Function:
Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Isoform 2 interferes with the formation of CD86 ...
Gene Name:
CD86
Uniprot ID:
P42081
Molecular Weight:
37681.97 Da
References
  1. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [PubMed:16971318 ]
  2. Vincenti F, Luggen M: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med. 2007;58:347-58. [PubMed:17020493 ]
  3. Kremer JM: Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62. [PubMed:16357751 ]
  4. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [PubMed:16932686 ]
  5. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [PubMed:20080922 ]
  6. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [PubMed:17212998 ]
  7. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [PubMed:16573350 ]
  8. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [PubMed:18041889 ]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on May 16, 2007 16:55 / Updated on August 17, 2016 12:23