{"doi":"10.1111/hae.14855","title":"Characterization of a recombinant factor IX molecule fused to coagulation factor XIII‐B subunit","abstract":"INTRODUCTION AND AIM: Severe haemophilia B (HB) is characterized by spontaneous bleeding episodes, mostly into joints. Recurrent bleeds lead to progressive joint destruction called haemophilic arthropathy. The current concept of prophylaxis aims at maintaining the FIX level >3-5 IU/dL, which is effective at reducing the incidence of haemophilic arthropathy. Extended half-life FIX molecules make it easier to achieve these target trough levels compared to standard FIX concentrates. We previously reported that the fusion of a recombinant FIX (rFIX) to factor XIII-B (FXIIIB) subunit prolonged the half-life of the rFIX-LXa-FXIIIB fusion molecule in mice and rats 3.9- and 2.2-fold, respectively, compared with rFIX-WT. However, the mechanism behind the extended half-life was not known. MATERIALS AND METHODS: Mass spectrometry and ITC were used to study interactions of rFIX-LXa-FXIIIB with albumin. Pharmacokinetic analyses in fibrinogen-KO and FcRn-KO mice were performed to evaluate the effect of albumin and fibrinogen on in-vivo half-life of rFIX-LXa-FXIIIB. Finally saphenous vein bleeding model was used to assess in-vivo haemostatic activity of rFIX-LXa-FXIIIB. RESULTS AND CONCLUSION: We report here the key interactions that rFIX-LXa-FXIIIB may have in plasma are with fibrinogen and albumin which may mediate its prolonged half-life. In addition, using the saphenous vein bleeding model, we demonstrate that rFIX-FXIIIB elicits functional clot formation that is indistinguishable from that of rFIX-WT.","journal":"Haemophilia","year":2023,"id":388796,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1158276,"name":"Alexandre Leuci","orcid":"0000-0001-9329-8165","position":1,"is_corresponding":false},{"id":1158277,"name":"Nathalie Enjolras","orcid":"0000-0002-4778-0724","position":2,"is_corresponding":false},{"id":468242,"name":"Lori A. Holle","orcid":"0000-0003-1399-2689","position":3,"is_corresponding":false},{"id":623886,"name":"Sneha Singh","orcid":"0000-0003-2983-5733","position":4,"is_corresponding":false},{"id":1158278,"name":"Xavier Delavenne","orcid":"0000-0001-7134-0713","position":5,"is_corresponding":false},{"id":249625,"name":"Alisa S. Wolberg","orcid":"0000-0002-2845-2303","position":6,"is_corresponding":false},{"id":1158279,"name":"Arijit Biswas","orcid":"0009-0009-3347-058X","position":7,"is_corresponding":false},{"id":1158280,"name":"Yesim Dargaud","orcid":"0000-0002-4888-1463","position":8,"is_corresponding":false},{"id":1158275,"name":"Stéphanie Desage","orcid":"0000-0003-0455-0248","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T01:18:18.214733Z","pmid":"37707428","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}