Turoctocog alfa, Recombinant factor VIII (rFVIII)

Specification

• Cat#: THP-0098
• Product Name: Turoctocog alfa, Recombinant factor VIII (rFVIII)
• Description: The product is a recombinant factor VIII (rFVIII) with a truncated B-domain made from the sequence coding for 10 amino acids from the N-terminus and 11 amino acids from the C-terminus of the naturally occurring B-domain. The product is produced in Chinese hamster ovary (CHO) cells without addition of any human- or animal-derived materials. During secretion, some rFVIII molecules are cleaved at the C-terminal of the heavy chain (HC) at amino acid 720, and a monoclonal antibody binding C-terminal to this position is used in the purification process allowing isolation of the intact rFVIII.
• Sequences: ATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFNIAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNSRHPSQNPPVLKRHQREITRTTLQSDQEEIDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY
• Species: Human
• Molecular Weight: 166000.0 Da (Without post-translational modifications)
• Source: CHO
• Purity: >99% by SDS-Page and HPLC analysis
• Cas No: 1192451-26-5
• Formula: C7480H11379N1999O2194S68
• Endotoxin Level: <0.001 EU per 1 μg by the LAL method
• Biological Activity: 500U-3000U

Pharmaceutical Information

• Pharmaceutical Application: Turoctocog alfa
• Applications: The product is indicated for the treatment and prophylaxis of bleedings in patients presenting hemophilia A. The treatment with the product is related with its use to control bleeding episodes or as a perioperative management. Hemophilia A is a hereditary hemorrhagic disorder generated by the congenital deficit of the coagulation factor VIII. This disease is manifested as excessive spontaneous or trauma-driven bleeding. The coagulation factor VIII is a robust initiator of thrombin which is later required for the generation of fibrin to form a platelet plug and its gene is expressed in the X chromosome.
• Examples of Clinical Use: Hemophilia A
• Pharmacodynamics: After the product administration, it has been reported a significant improvement in hemostasis. This effect was observed by the amelioration on whole blood clotting time. In clinical trials, there were no reports of development of factor VIII inhibitors and even 90% of the ocurred bleeds were resolved with 1 or 2 infusions of the product. There are no reports of treatment failure. In vitro studies confirmed the ability of the product to improve clot formation and clot stability. All these studies prove that the product is fully functional and its activity is similar to the one showed by other recombinant factor VIII products.
• Mechanism of action: The B domain is known to perform the function of restrict the expression of the endogenous coagulation factor VIII but it has no direct relationship to the function of this factor. In normal conditions during hemostasis, the coagulation factor VIII will be activated by specific thrombin cleavages producing A1, A2 and A3-C1-C2 fragments of activated factor VIII (Factor VIIIa) which will form a complex with the factor IXa and activate the factor X leading to a stable haemostatic plug. Turoctocog contains all function-related domains with a considerably easier intact expression of the protein in mammalian cells by truncating the B domain. This recombinant structure allows it to replace the missing factor VIII and restore hemostasis.
• Affected organisms: Humans and other mammals
• Targets: Target 1. Coagulation factor IX; Target 2. Coagulation factor X; Target 3. Prothrombin