Bococizumab

Bococizumab
PF-04950615, RN-316, RN316
PCSK9 (proprotein convertase subtilisin/kexin type 9, neural apoptosis-regulated convertase 1, NARC1, NARC-1, proproteine convertase 9, PC9) [Homo sapiens]
IgG2 – kappa
Hypercholesterolemia
Cardiovascular diseases
STRUCTURAL FORMULA
Heavy chain
QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGE 50
ISPFGGRTNY NEKFKSRVTM TRDTSTSTVY MELSSLRSED TAVYYCARER 100
PLYASDLWGQ GTTVTVSSAS TKGPSVFPLA PCSRSTSEST AALGCLVKDY 150
FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSNFGTQTYT 200
CNVDHKPSNT KVDKTVERKC CVECPPCPAP PVAGPSVFLF PPKPKDTLMI 250
SRTPEVTCVV VDVSHEDPEV QFNWYVDGVE VHNAKTKPRE EQFNSTFRVV 300
SVLTVVHQDW LNGKEYKCKV SNKGLPSSIE KTISKTKGQP REPQVYTLPP 350
SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPMLDSDGS 400
FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 444
Light chain
DIQMTQSPSS LSASVGDRVT ITCRASQGIS SALAWYQQKP GKAPKLLIYS 50′
ASYRYTGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQQ RYSLWRTFGQ 100′
GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150′
DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200′
LSSPVTKSFN RGEC 214′
Disulfide bridges location
22-96 22”-96” 23′-88′ 23”’-88”’ 132-214′ 132”-214”’
134′-194′ 134”’-194”’ 145-201 145”-201” 220-220” 221-221”
224-224” 227-227” 258-318 258”-318” 364-422 364”-422”

Bococizumab nonproprietary drug name

bococizumab
RN-316, PF-04950615
target-PC9
USAN (AB-55) BOCOCIZUMAB
PRONUNCIATION boe” koe siz’ ue mab
THERAPEUTIC CLAIM Treatment of dyslipidemia
CHEMICAL NAME
1. Immunoglobulin G2, anti-(human neural apoptosis-regulated proteinase
1)(human-Mus musculus monoclonal PF-04950615 heavy chain), disulfide
with human-Mus musculus monoclonal PF-04950615 light chain, dimer
2. Immunoglobulin G2-kappa, anti-[human proprotein convertase subtilisin/hexin type 9 (neural apoptosis-regulated convertase 1, PC9)], humanized mouse monoclonal antibody; gamma 2 heavy chain (1-444) [humanized VH (Homo sapiens IGHV1-46-1*03 (90.8%) -(IGHD)-IGHJ6*01) [8.8.11] (1-118)-Homo sapiens IGHG2*01 CH2A100>S(327),CH2P101>S(328) (119-444)] (132-214′)-
disulfide with kappa light chain (1′-214′) [humanized V-KAPPA (Homo sapiensIGKV1-39*01 (88.2%)-IGKJ2*01 [6.3.9] (1′-107′)-IGKC*01 (108′-214′)]; dimer
(220-220”:221-221”:224-224”:227-227”)-tetrakisdisulfide
MOLECULAR FORMULA C6414H9918N1722O2012S54
MOLECULAR WEIGHT 145.1 kDa
TRADEMARK None as yet
SPONSOR Pfizer, Inc.
CODE DESIGNATIONS RN316, PF-04950615
CAS REGISTRY NUMBER 1407495-02-6
WHO NUMBER 9840
Bococizumab^[1] (RN316)^[2] is a drug in development by Pfizer targeting PCSK9 to reduce LDL cholesterol.^[3]

Description

Bococizumab is a monoclonal antibody that inhibits PCSK9, a protein that interferes with the removal of LDL. LDL levels are a major risk factor for cardiovascular disease.

Clinical trials

A phase 2b study of statin patients was presented at the 2014 American College of Cardiology. Monthly or bimonthly injections resulted in significantly reduced LDL-C at week 12.
The Phase 3 SPIRE trials plan to enroll 17,000 patients to measure cardiovascular risk. High risk and statin intolerant subjects will be included.

References

1. “Statement On A Nonproprietary Name Adopted By The USAN Council: Bococizumab” (PDF). American Medical Association.
2.  World Health Organization (2013). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 110”(PDF). WHO Drug Information 27 (4).
3.  “Bococizumab (RN316) Significantly Reduced LDL Cholesterol In Statin-Treated Adults With High Cholesterol In A Phase 2b Study”. Retrieved 29 December 2014.

Bococizumab^?

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Clinical data
Legal status	Investigational
Routes of administration	Subcutaneous injection
Identifiers
CAS Registry Number	1407495-02-6
ATC code	None
PubChem	SID: 194168554
IUPHAR/BPS	7730
ChEMBL	CHEMBL3137349
Chemical data
Formula	C6414H9918N1722O2012S54
Molecular mass	145.1 kDa

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