Generated: May 22, 2017
|Title:||Methods of using antibodies during anticoagulant therapy of dabigatran and/or related compounds|
|Abstract:||The present invention relates to antibody molecules against anticoagulants, in particular dabigatran, and their use as antidotes of such anticoagulants.|
|Inventor(s):||Van Ryn; Joanne (Warthausen, DE), Park; John Edward (Warthausen, DE), Hauel; Norbert (Schemmerhofen, DE), Kunz; Ulrich (Biberach an der Riss, DE), Litzenburger; Tobias (Mittelbiberach, DE), Canada; Keith (Southbury, CT), Singh; Sanjaya (Sandy Hook, CT), Waterman; Alisa (Weston, CT)|
|Assignee:||Boehringer Igelheim International GmbH (Ingelheim am Rhein, DE)|
1. A method for reversing the anticoagulant effect of dabigatran or 1-O-acylglucuronide of dabigatran in a patient being treated with dabigatran, dabigatran etexilate, a prodrug of
dabigatran or a pharmaceutically acceptable salt thereof, comprising administering an effective amount of an antibody molecule which comprises a heavy chain variable domain with a CDR1 of SEQ ID NO:1, a CDR2 of SEQ ID NO: 7, and a CDR3 of SEQ ID NO: 10,
and a light chain variable domain with a CDR1 of SEQ ID NO: 13, a CDR2 of SEQ ID NO: 14, and a CDR3 of SEQ ID NO: 15 to a patient in need thereof.
2. The method according to claim 1 which comprises a heavy chain variable domain of SEQ ID NO: 24 and a light chain variable domain of SEQ ID NO: 27.
3. The method of claim 1 wherein the antibody molecule is a polyclonal antibody, a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a fragment of an antibody, a single chain antibody, a Small Modular Immunopharmaceutical (SMIP) or a diabody.
4. The method of claim 3 wherein the antibody molecule is a scFv, wherein the heavy chain variable domain and the light chain variable domain are linked to each other through a linker peptide selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31.
5. The method according to claim 3 wherein the antibody molecule is a Fab molecule having an Fd fragment comprising SEQ ID NO: 36 and a light chain comprising SEQ ID NO: 37.
6. The method according to claim 3, wherein the antibody fragment is a Fab, Fab', or F(ab').sub.2 fragment.
7. The method according to claim 3, wherein the single chain antibody is a single chain variable fragment (scFv).
8. The method according to claim 1, wherein the effective amount of antibody to dabigatran or 1-O-acylglucuronide of dabigatran is at least an equimolar amount of antibody to dabigatran or 1-O-acylglucuronide of dabigatran.
9. The method according to claim 1, wherein the antibody molecule is given intravenously as a bolus.
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