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Friday, 9 November 2012

New Drug Approvals 2012 - Pt. XXIV - Ocriplasmin (JetreaTM)




On October 17, the FDA approved Ocriplasmin (tradename: Jetrea; Research Code: Microplasmin), a proteolytic enzyme indicated for the treatment of symptomatic vitreomacular adhesion (VMA). VMA is a condition of the eye that results from the liquefaction of the vitreous gel within the human eye and consequent adhesion to the retina. As the eye ages, the vitreous humor can naturally separate from the retina. However, if the separation is not complete, areas of adhesion can occur. The traction from these adhesion areas on the retinal surface is the underlying pathology of symptomatic VMA, which can lead to ocular damage. Ocriplasmin is the first drug approved to treat this condition and it exherts its therapeutic action by selectively breaking down the three major protein components, fibronectin, laminin and collagen, of the vitreous body and vitreoretinal interface, and thereby dissolving the protein matrix responsible for VMA. The only alternative treatment is a surgical procedure to remove the vitreous from the eye, known as vitrectomy.

Ocriplasmin is a recombinant truncated form of the human plasmin (ChEMBL: CHEMBL1801; Uniprot: P00747) with a molecular weight of 27.2 kDa produced by recombinat DNA technology in a Pichia pastoris expression system.

>PLMN_HUMAN Plasminogen (Ocriplasmin is displayed in bold)
MEHKEVVLLLLLFLKSGQGEPLDDYVNTQGASLFSVTKKQLGAGSIEECAAKCEEDEEFT
CRAFQYHSKEQQCVIMAENRKSSIIIRMRDVVLFEKKVYLSECKTGNGKNYRGTMSKTKN
GITCQKWSSTSPHRPRFSPATHPSEGLEENYCRNPDNDPQGPWCYTTDPEKRYDYCDILE
CEEECMHCSGENYDGKISKTMSGLECQAWDSQSPHAHGYIPSKFPNKNLKKNYCRNPDRE
LRPWCFTTDPNKRWELCDIPRCTTPPPSSGPTYQCLKGTGENYRGNVAVTVSGHTCQHWS
AQTPHTHNRTPENFPCKNLDENYCRNPDGKRAPWCHTTNSQVRWEYCKIPSCDSSPVSTE
QLAPTAPPELTPVVQDCYHGDGQSYRGTSSTTTTGKKCQSWSSMTPHRHQKTPENYPNAG
LTMNYCRNPDADKGPWCFTTDPSVRWEYCNLKKCSGTEASVVAPPPVVLLPDVETPSEED
CMFGNGKGYRGKRATTVTGTPCQDWAAQEPHRHSIFTPETNPRAGLEKNYCRNPDGDVGG
PWCYTTNPRKLYDYCDVPQCAAPSFDCGKPQVEPKKCPGRVVGGCVAHPHSWPWQVSLRT
RFGMHFCGGTLISPEWVLTAAHCLEKSPRPSSYKVILGAHQEVNLEPHVQEIEVSRLFLE
PTRKDIALLKLSSPAVITDKVIPACLPSPNYVVADRTECFITGWGETQGTFGAGLLKEAQ
LPVIENKVCNRYEFLNGRVQSTELCAGHLAGGTDSCQGDSGGPLVCFEKDKYILQGVTSW
GLGCARPNKPGVYVRVSRFVTWIEGVMRNN


The PDBe entry (PDBe:1bui) for the crystal structure of Ocriplasmin (in green) in complex with Staphylokinase (in red) is displayed below.


The recommended dosage of Ocriplasmin is 0.125 mg (0.1 mL of the diluted solution) administrated by intravitreal injection to the affected eye once as a single dose.

The license holder is ThromboGenics, Inc. and the full prescribing information of Linaclotide can be found here.

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