18-06-2020 дата публикации
Номер: US20200190157A1
The disclosure provides for new epidermal growth factor (EGF)-based reagents that have been modified by fatty acid conjugation. Method of using such agents to treatment Short Bowel Sydnrome (SBS) are also described. 1. A modified epidermal growth factor (EGF) molecule of the formula:{'br': None, 'sub': 'm', 'X—(Y)—Z\u2003\u2003(I)'} Z represents an EGF recombinant protein;', 'X represents a fatty acid;', 'Y represents a linker element between X and the N-terminus of EGF; and', 'm=0-8,, 'whereinor a pharmaceutically acceptable salt thereof.4. The EGF molecule of wherein X is —C(O)R claim 2 , wherein Ris alkyl claim 2 , alkenyl claim 2 , or a substituted version of both groups.6. The EGF molecule of claim 2 , wherein Y is a linker element comprising a first linking group and a spacer.7. The EGF molecule of claim 6 , wherein the spacer is a covalent bond claim 6 , a PEG group claim 6 , an alkanediyl claim 6 , a substituted alkanediyl claim 6 , an alkenediyl claim 6 , a substituted alkenediyl claim 6 , an alkoxydiyl claim 6 , or a substituted alkoxydiyl.10. The EGF molecule of claim 9 , wherein Y is selected from γ-L-Glu claim 9 , 2-(2-aminoethoxy)acetamide (AEA) claim 9 , 2-(2-(2-aminoethoxy)ethoxy)acetamide (AEEA) claim 9 , AEA-AEA claim 9 , AEA-AEEA claim 9 , AEEA-AEA claim 9 , AEEA-AEEA claim 9 , γ-L-Glu-AEA claim 9 , γ-L-Glu-AEEA claim 9 , γ-L-Glu-AEA-AEA claim 9 , γ-L-Glu-AEA-AEEA claim 9 , γ-L-Glu-AEEA-AEA claim 9 , γ-L-Glu-AEEA-AEEA claim 9 ,11. The EGF molecule of claim 1 , wherein m is 1 claim 1 , 2 claim 1 , or 3.13. A pharmaceutical composition comprising:{'claim-ref': [{'@idref': 'CLM-00001', 'claims 1'}, {'@idref': 'CLM-00012', '12'}], '(A) a EGF molecule according to any one of -; and'}(B) an excipient.14. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is formulated for administration: orally claim 13 , intraadiposally claim 13 , intraarterially claim 13 , intraarticularly claim 13 , intracranially claim 13 , ...
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