US 12,257,285 B2
Composition of BL-8040
Efrat Halbfinger, RaAnana (IL); Amnon Peled, Tel-Aviv (IL); and Ella Sorani, Kadima (IL)
Assigned to BioLineRx Ltd., Modiln (IL); and Biokine Therapeutics Ltd., Nes Ziona (IL)
Filed by BioLineRx Ltd., Modiln (IL); and Biokine Therapeutics Ltd., Nes Ziona (IL)
Filed on Dec. 13, 2023, as Appl. No. 18/537,973.
Application 18/537,973 is a continuation of application No. 18/270,521, previously published as PCT/IL2021/051548, filed on Dec. 29, 2021.
Claims priority of provisional application 63/131,871, filed on Dec. 30, 2020.
Prior Publication US 2024/0131111 A1, Apr. 25, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/12 (2006.01); A61P 35/00 (2006.01)
CPC A61K 38/12 (2013.01) [A61P 35/00 (2018.01)] 26 Claims
 
1. A composition-of-matter comprising BL-8040 (SEQ ID NO: 1) and at least one compound characterized by a relative retention time in a range of from 0.86 to 0.88,
wherein said relative retention time is determined using a first mobile phase which is an aqueous solution of 0.017 M perchlorate at a pH in a range of from about 3.0 to about 3.3, a second mobile phase which is acetonitrile, a gradient whereby a concentration of said second mobile phase increases by about 10% in about 50 minutes from an initial concentration of about 20%, a C18 reverse phase column, an injection volume in a range of from about 5 to about 20 μl, and a flow rate of about 1 ml per minute, at a temperature of about 40° C., and wherein a relative retention time of said BL-8040 (SEQ ID NO: 1) is defined as 1,
the composition-of-matter being produced by a process of preparing said BL-8040 (SEQ ID NO: 1) which comprises:
(a) sequentially coupling amino acids and 4-fluorobenzoic acid to a resin by solid phase peptide synthesis, thereby obtaining a linear peptide coupled to said resin;
(b) cleaving said linear peptide from said resin, thereby obtaining a free linear peptide;
(c) oxidizing cysteine residues of said linear peptide to form an intramolecular disulfide bond, thereby obtaining the cyclic peptide having SEQ ID NO: 1 in solution; and
(d) isolating the cyclic peptide having SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof.