US2021371502A1PendingUtilityA1

Tgf- receptor ii isoform, fusion peptide, methods of treatment and methods in vitro

Assignee: CONSEJO NACIONAL DE INVESTIGACIONES CIENTIFICAS Y TECNPriority: Dec 19, 2013Filed: Apr 12, 2021Published: Dec 2, 2021
Est. expiryDec 19, 2033(~7.4 yrs left)· nominal 20-yr term from priority
C07K 2317/34A61K 9/5184C12N 2740/16043G01N 2333/71G01N 2800/102C12N 7/00A61P 1/16A61K 9/0019C07K 14/71C07K 2319/30C12N 2740/15043G01N 33/6872A61P 35/00G01N 33/6893A61K 38/00G01N 2800/56C07K 16/2863C07K 16/00
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Claims

Abstract

An isoform of the TGF beta receptor II comprising a sequence of about of 80 amino acids and lacking a transmembrane domain. The isoform comprises the amino acid sequence set forth in SEQ ID No. 12. The isoform may have the amino acid sequence set forth in SEQ ID No. 2 or sequences having at least 85% sequence identity to the sequence set forth in SEQ ID No. 2. A fusion peptide is provided comprising an isoform of the TGF beta II receptor fused to a ligand, wherein a vector comprising the fusion peptide is used to treat cancer and/or hepatic fibrosis. An antibody binding the soluble isoform of the TGF beta II receptor is provided. The antibody binds the amino acid sequence shown in SEQ ID No. 12 and is used in in vitro methods.

Claims

exact text as granted — not AI-modified
1 - 7 . (canceled) 
     
     
         8 . An antibody binding an isoform of the TGF beta receptor II (TβRII-SE) fused to a ligand wherein the isoform comprises an amino acid sequence having at least 85% sequence identity to SEQ ID No. 2. 
     
     
         9 . The antibody according to  claim 8 , wherein the antibody is selected from the groups consisting of monoclonal antibodies, polyclonal antibodies, and fragments thereof. 
     
     
         10 . The antibody according to  claim 8 , wherein binds to the amino acid sequence set forth in SEQ ID No. 12. 
     
     
         11 . A method of treating hepatic fibrosis or cancer diseases, comprising the step of administering to a mammal in need thereof a vector having peptide codified by a polynucleotide sequrnce set forth in SEQ ID No. 7. 
     
     
         12 . The method according to  claim 11 , when de disease is hepatic fibrosis the administration is intra-hepatic. 
     
     
         13 . The method according to  claim 11 , when the disease is cancer the administration is intra-tumoral. 
     
     
         14 . A method to establish rheumatoid arthritis disease activity, wherein said method comprises at least one of the following: the determination of the percentage of neutrophils expressing the isoform TβRII-SE or the intracellular concentration of the isoform TβRII-SE in neutrophils. 
     
     
         15 . The method according to  claim 14 , wherein the percentage of neutrophils expressing the isoform TβRII-SE is inversely proportional to rheumatoid arthritis disease activity levels. 
     
     
         16 . The method according to  claim 14 , wherein intracellular TβRII-SE concentration is inversely proportional to rheumatoid arthritis disease activity levels. 
     
     
         17 . A method to detect an isoform of the TGF beta receptor II (TβRII-SE) fused to a ligand, the isoform comprises an amino acid sequence havina at least 85% sequence identity to SEQ ID No. 2, the method comprisinq the steps of:
 a) isolation of blood cells; 
 b) permeabilization of these cells; 
 c) binding of an antibody recognizing the aminoacid sequence shown in SEQ ID N° 12 in the permeabilized cells of the previous stage, and 
 d) detection. 
 
     
     
         18 . The method according to  claim 17 , wherein blood cells are neutrophils. 
     
     
         19 . The method according to  claim 17 , wherein said method is selected from the group consisting of In-cell ELISA and flow cytometry. 
     
     
         20 . A method of treating diseases associated to TGF-β dysregulation comprising the step of administering to a mammal in need thereof a pepetide comprising an isoform of the TGF beta receptor II (TβRII-SE) fused to a ligand.

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