RANIBIZUMAB

 RANIBIZUMAB

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody Fab fragment, directed against human vascular endothelial growth factor A (VEFG-A). [1]

Brand name:- Lucentis, Byooviz, Cimerli,  Susvimo [1], Razumab

Generic name:- Ranibizumab [1]

Protein chemical formula:- C2158H3282N562O681S12 [1]


Protein size:- 48349.6111 Da [1]

Seuences:- >Ranibizumab Light Chain
DIQLTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Ranibizumab Heavy Chain
EVQLVESGGGLVQPGGSLRLSCAASGYDFTHYGMNWVRQAPGKGLEWVGWINTYTGEPTY
AADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPYYYGTSHWYFDVWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL              [1]

Defination:-

Humanized Antibody
Humanised antibodies (suffix -zumab) are produced by grafting murine hypervariable regions (CDR-complementry determining region) on amino acid domains into human antibodies. This results in a molecule of approximately 95% human origin.

Monoclonal antibody
Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body whereas monoclonal antibodies come from a single B cell lineage.

Fab fragment
Monovalent antiody fragment having variable and constant domain (VH,CH1 of heavy chain and VL,CL of light chain) but Fc (fragment of crystaliation) is not present.

Endothelial cell
Endothelial cells form the single cell layer that lines a blood vessels and regulates exchanges between the bloodstream and surrounding tissues.


Mechanisom of action:-

VEGF is produced by tumor cells, macrophages, keratinocytes, platelets and renal mesangial cells in body.

Role of VEGF
- Formation of blood vessels and lymph vessels,
- Formation of bones and blood
- Wound healing
- Embryonic development 

Action of VEGF
- VEGF binds with tyrosine kinase receptors or VEGF receptors (receptors available on cell surface) and receptors being activated by dimerization and transphosphorylation.[4]

- Vascular endothelial growth factor, VEGF A is binds with VEFG receptors on endothelial cells and increase in vascular permeability , migration, cell proliferation and causes angiogenesis (New blood vessel formation).

Cause for high level of VEGF

- Retinal hypoxia,
- Retinal vein occlusion (RVO),
- Tissue ischemia,
- Capillary non perfusion,  [2]

Action of Ranibizumab

Ranibizumab binds to the receptor-binding site of active VEGF-A. Thus, ranibizumab inhibits the interaction of VEGF-A with its receptors on endothelial cells, and preventing endothelial cell proliferation, vascular permeability, and neovascularization which cause angiogenesis. [3]

Ranibizumab has one binding site for VEGF, allowing two molecules of ranibizumab to bind to one VEGF dimer. The small size of ranibizumab allows for enhanced diffusion into the retina and choroid. [3]

Usage 

1) Wet age related macular degeneration (wMAD).

2) Maclaren edema following retinal vein occlusion (RVO).

3) Diabetic macular edema (DME).

4) Diabetic retinopathy (DR).

5) Myopic choroidal neovascularization (mCNV). [5]

Side effects

- Conjunctival hemorrhage, 

- Eye pain, 

- Vitreous floaters, 

- Short-term and long-term increase in ocular pressure.

Ranibizumab manufacturer and Brand name:

Manufacture

Brand name

Genetech, Novartis

Lucentis

Biogen, Samsung bioepis

Byooviz (Ranibizumab nuna)

Coherus Ltd., Bioeq AG (Polpharma biologics and Formycon AG)

Cimerli

Roche

Susvimo

Intas pharmaceutical Ltd.

Razumab

References:

[1] Ranibizumab blog, Drugbank.com

[2] Efficacy of intravitreal Lucentis injection on major and macular branch retinal vein occlusion, Jing Wang, Ying li, Shu Fen fang, Hong wang, (BMC OPTHOLMOLOGY).

[3] Vidhyanathan U, Moshirfar M: Ranibizumab, ( Europepmc.org)

[4] https://www.news-medical net/life-science/VEGF-Mechanism.aspx.

[5] Ref. WWW.GENE.COM





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