Methods for coating invasive devices with inhibitors of thrombin
AssigneeBiogen, Inc.
InventorsJohn M. Maraganore, John W. Fenton, II, Toni Kline
Life of this patent
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Abstract
This invention relates to novel biologically active molecules which bind to and inhibit thrombin. Specifically, these molecules are characterized by a thrombin anion-binding exosite association moiety (ABEAM); a linker portion of at least 18 .ANG. in length; and a thrombin catalytic site-directed moiety (CSDM). This invention also relates to compositions, combinations and methods which employ these molecules for therapeutic, prophylactic and diagnostic purposes.
Claims15
A method for coating the surface of an invasive device to be inserted into a patient, said method comprising the step of contacting said surface with a composition wherein said composition comprises
- a) a thrombin inhibitor consisting of
- i. a catalytic site-directed moiety that binds to and inhibits the active site of thrombin wherein said catalytic site-directed moiety is selected from general serine proteinase inhibitors, heterocyclic protease inhibitors, thrombin-specific inhibitors, transition state analogues, benzamidine, DAPA, NAPAP, argipidine, or moieties of the formulae:
- X-A.sub.1 -A.sub.2 -A.sub.3 Y or X-C.sub.1 -C.sub.2 -A.sub.3 Y,
- wherein X is hydrogen or is characterized by a backbone chain consisting of from 1 to 35 atoms;
- A.sub.1 is Arg, Lys or Orn;
- A.sub.2 is a non-amide bond;
- A.sub.3 is characterized by a backbone chain consisting of from 1 to 9 atoms;
- Y is a bond;
- C.sub.1 is a derivative of Arg, Lys or Orn comprising a carboxylate moiety that is reduced, or displaced from the .alpha.-carbon by a structure characterized by a backbone chain of from 1 to 10 atoms;
- and C.sub.2 is a non-cleavable bond;
- ii. a linker moiety characterized by a backbone chain having a calculated length of between 18 .ANG. and 42 .ANG.;
- and
- iii. an anion binding exosite associating moiety;
- said catalytic site-directed moiety being bound to said linked moiety and said linker moiety being bound to said anion binding exosite moiety;
- and
- b) a buffer suitable to promote the binding of said thrombin inhibitor to said invasive device.
Dependencies are inferred from the claim text.