Dual targeting of TAFI and PAI-1
AssigneesKatholieke Universiteit Leuven, Inserm (Institut National De La Sante Et De La Recherche Medicale), Universite de Caen Basse Normandie, Centre Hospitalier Unviersitaire De Caen
InventorsPaul Declerck, Simon De Meyer, Nick Geukens, Ann Gils, Marina Rubio, Denis Vivien, Tine Wyseure
Life of this patent
Estimating the term…
Abstract
Disclosed herein is a bispecific inhibitor for use in treating thrombotic disorders, such as acute thrombotic disorders like stroke and thromboembolism. The bispecific inhibitor is based on monoclonal antibodies targeting TAFI and PAI-1, and shows efficacy in the presence or the absence of plasminogen activators such as tissue-type plasminogen activator (tPA).
Claims19
A method of treating a patient having, or at risk of developing, an acute thrombotic disorder, said method comprising a step of administering a bispecific antibody against TAFI and PAI-1, wherein said antibody comprises:
- a. a first targeting domain that specifically binds to Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and comprises complementary determining regions (CDRs) represented by the amino acid sequences SEQ ID NO:1 of CDR1H, SEQ ID NO:2 of CDR2H, SEQ ID NO:3 of CDR3H, SEQ ID NO:4 of CDR1L, SEQ ID NO:5 of CDR2L, and SEQ ID NO:6 of CDR3L, and
- b. a second targeting domain that specifically binds to Plasminogen Activator Inhibitor-1 (PAI-1) and comprises complementary determining regions (CDRs) represented by SEQ ID NO:7 of CDR1H, SEQ ID NO:8 of CDR2H, SEQ ID NO:9 of CDR3H, SEQ ID NO:10 of CDR1L, SEQ ID NO:11 of CDR2L and SEQ ID NO:12 of CDR3L,
- wherein the step of administering is performed:
- (i) without administration of tPA prior to the administration of the bispecific antibody,
- (ii) without administration of tPA concurrently with the administration of the bispecific antibody, or
- (iii) without administration of tPA after the administration of the bispecific antibody.
A method of treating a patient for a condition or risk of acute thrombotic disorder, said method comprising
- administering a bispecific antibody against TAFI and PAI-1 to the patient, said administering being performed without administration of tPA,
- wherein said bispecific antibody includes
- a. a first targeting domain that specifically binds to Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and comprises complementary determining regions (CDRs) represented by the amino acid sequences SEQ ID NO:1 of CDR1H, SEQ ID NO:2 of CDR2H, SEQ ID NO:3 of CDR3H, SEQ ID NO:4 of CDR1L, SEQ ID NO:5 of CDR2L, and SEQ ID NO:6 of CDR3L, and
- b. a second targeting domain that specifically binds to Plasminogen Activator Inhibitor-1 (PAI-1) and comprises complementary determining regions (CDRs) represented by SEQ ID NO:7 of CDR1H, SEQ ID NO:8 of CDR2H, SEQ ID NO:9 of CDR3H, SEQ ID NO:10 of CDR1L, SEQ ID NO:11 of CDR2L and SEQ ID NO:12 of CDR3L.
Dependencies are inferred from the claim text.