US2021189368A1PendingUtilityA1

Recombinant fusion proteins for preventing or treating adhesions of tissues or organs

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Assignee: AKESION GMBHPriority: Aug 26, 2014Filed: Nov 13, 2020Published: Jun 24, 2021
Est. expiryAug 26, 2034(~8.1 yrs left)· nominal 20-yr term from priority
Inventors:Klaus RübsamenStephan Witte
C12Y 304/21074A61K 38/482C07K 2319/31C07K 2319/30C12N 9/6424C12N 9/6418C12N 9/50A61K 38/00A61L 31/047A61P 43/00A61P 41/00C07K 14/765
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Claims

Abstract

The invention relates to recombinant fusion proteins comprising a fibrinogenolytic enzyme having an amino acid sequence that is C-terminally and/or N-terminally linked to the amino acid sequence of at least one high-molecular inert stabilization domain with a molecular weight of >50 kDa, for the prevention or treatment of adhesions at tissues or organs, in particular peritoneal adhesions following surgical interventions.

Claims

exact text as granted — not AI-modified
1 - 15 . (canceled) 
     
     
         16 . A recombinant fusion protein comprising a fibrinogenolytic enzyme having an amino acid sequence that is C-terminally and/or N-terminally linked to the amino acid sequence of at least one high-molecular inert stabilization domain with a molecular weight of >50 kDa, for the prevention or treatment of peritoneal adhesions following surgical interventions in the peritoneal cavity. 
     
     
         17 . The recombinant fusion protein for use according to  claim 16 , characterized in that the inert stabilization domain is connected via a linker to the fibrinogenolytic enzyme. 
     
     
         18 . The recombinant fusion protein for use according to  claim 17 , characterized in that the linker relates to a glycine-serine linker having the sequence (GGGGGS)x, or glycine-alanine linker with the sequence (GGGGA)xR, where A=alanine; G=glycine; R=arginine; S=serine; x=number of repetitions >1. 
     
     
         19 . The recombinant fusion protein for use according to  claim 16 , characterized in that a plurality of inert stabilization domains are linked to the C-terminus of the fibrinogenolytic enzyme. 
     
     
         20 . The recombinant fusion protein for use according to  claim 16 , characterized in that a plurality of inert stabilization domains are linked to the N-terminus of the fibrinogenolytic enzyme. 
     
     
         21 . The recombinant fusion protein for use according to  claim 16 , characterized in that the stabilization domain has a molecular weight between 50 and 150 kDa. 
     
     
         22 . The recombinant fusion protein for use according to  claim 16 , characterized in that the fibrinogenolytic enzyme relates to a thrombin-like serine protease. 
     
     
         23 . The recombinant fusion protein for use according to  claim 16 , characterized in that the fibrinogenolytic enzyme relates to ancrod or batroxobin, or a recombinant variant of ancrod or batroxobin. 
     
     
         24 . The recombinant fusion protein for use according to  claim 16 , characterized in that the high molecular inert stabilization domain relates to a protein or peptide domain, in particular serum albumin, transferrin, a monoclonal or humanized antibody or an antibody fragment, or an artificial domain, e.g. PAS or XTEN. 
     
     
         25 . The recombinant fusion protein for use according to  claim 16 , characterized in that the amino acid sequence of human serum albumin, or a part of this sequence having a molecular weight of >50 kDa, is linked as inert stabilizing domain to the C-terminus or N-terminus of ancrod or batroxobin as fibrinogenolytic enzyme. 
     
     
         26 . The recombinant fusion protein for use according to  claim 25 , characterized in that the fusion protein comprises an amino acid sequence set forth in SEQ ID NO. 2 (N-terminal fusion) or SEQ ID NO. 4 (C-terminal fusion), or fibrinogenolytically effective parts of this sequence. 
     
     
         27 . The recombinant fusion protein for use according to  claim 16 , characterized in that the fusion protein is embedded in a biodegradable matrix for continuous intraperitoneal release. 
     
     
         28 . A pharmaceutical composition comprising a recombinant fusion protein according to  claim 16  for use in the prevention or treatment of peritoneal adhesions following surgical interventions in the peritoneal cavity. 
     
     
         29 . The pharmaceutical composition for use according to  claim 28 , characterized in that the recombinant fusion protein is present in an osmotically active medium, preferably Ico-dextrin solution.

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