SORTILIN BINDING CONJUGATE COMPOUNDS, COMPOSITIONS AND USES THEREOF FOR TREATING CANCER
The present disclosure relates to compositions comprising a solubilizing agent and a peptide compound and/or a conjugate compound, processes, methods and uses thereof for treatment of cancer or aggressive cancer. For example, the conjugate compounds can comprise the formula of A-(B)n, wherein A is a peptide compound; and B is at least one therapeutic agent, and the peptide compounds can comprise compounds of formula X 1 X 2 X 3 X 4 X 5 GVX 6 AKAGVX 7 NX 8 FKSESY (I) (SEQ ID NO: 1) (X 9 ) n GVX 10 AKAGVX 11 NX 12 FKSESY (II) (SEQ ID NO: 2) YKX 13 LRRX 14 APRWDX 15 PLRDPALRX 16 X 17 L (III) (SEQ ID NO: 3) YKX 18 LRR(X 19 ) n PLRDPALRX 20 X 21 L (IV) (SEQ ID NO: 4) IKLSGGVQAKAGVINMDKSESM (V) (SEQ ID NO: 5) IKLSGGVQAKAGVINMFKSESY (VI) (SEQ ID NO: 6) IKLSGGVQAKAGVINMFKSESYK (VII) (SEQ ID NO: 7) GVQAKAGVINMFKSES Y (VIII) (SEQ ID NO: 8) GVRAKAGVRNMFKSESY (IX) (SEQ ID NO: 9) GVRAKAGVRN(Nle)FKSESY (X) (SEQ ID NO: 10) YKSLRRKAPRWDAPLRDPALRQLL (XI) (SEQ ID NO: 11) YKSLRRKAPRWDAYLRDPALRQLL (XII) (SEQ ID NO: 12) YKSLRRKAPRWDAYLRDPALRPLL (XIII) (SEQ ID NO: 13) wherein X 1 to X 21 and n can have various different values and wherein at least one protecting group and/or at least one labelling agent is optionally connected to said peptide compound at an N- and/or C-terminal end.
1 - 138 . (canceled)
139 . A composition comprising
(i) a conjugate compound or a pharmaceutically acceptable salt, solvate or prodrug thereof, said conjugate compound having the formula of A-(B) n ,
wherein
A is a peptide compound comprising a sequence having at least 60% sequence identity with the sequence GVRAKAGVRN(Nle)FKSESY (SEQ ID NO: 10), optionally protected by a protecting group;
B is at least one therapeutic agent; and
n is 1, 2, 3 or 4; and
(ii) a polysorbate.
140 . The composition of claim 139 , wherein the peptide compound comprises a sequence having at least 90% sequence identity with the sequence
(SEQ ID NO: 10)
GVRAKAGVRN(Nle)FKSESY
141 . The composition of claim 139 , wherein the peptide compound comprises or consists of the sequence GVRAKAGVRN(Nle)FKSESY (SEQ ID NO: 10).
142 . The composition of claim 139 , wherein the peptide compound comprises at least one protecting group that is acetyl or succinyl.
143 . The composition of claim 139 , wherein the peptide compound is represented by Formula (XXXIX):
(XXXIX)
(SEQ ID NO: 15)
Acetyl-GVRAKAGVRN(Nle)FKSESY
144 . The composition of claim 139 , wherein B is connected to A via a linker.
145 . The composition of claim 139 , wherein the at least one therapeutic agent is an anticancer agent.
146 . The composition of claim 145 , wherein the anticancer agent is docetaxel, doxorubicin, cabazitaxel, maytansinoids, auristatins, calicheamicins, amatoxins, amanitin, or aldoxorubicin.
147 . The composition of claim 146 , wherein the conjugate compound is represented by formula (XIX) or (XXIII):
Formula (XIX)
GVRAK(docetaxel)AGVRN(Nle)FK(docetaxel)SESY;
Formula (XXIII)
Acetyl-GVRAK(docetaxel)AGVRN(Nle)FK(docetaxel)
SESY
148 . The composition of claim 139 , wherein the conjugate compound is present in an amount from about 0.1% to about 5% by w/w % based on the total weight of the composition.
149 . The composition of claim 139 , wherein the polysorbate is polysorbate 80.
150 . The composition of claim 139 , wherein the polysorbate is present in an amount from about 5% to about 15% by weight per total volume of the composition.
151 . The composition of claim 139 , further comprising dextrose.
152 . The composition of claim 151 , wherein the dextrose is present in an amount from about 2% to about 8% by weight per total volume of the composition.
153 . The composition of claim 151 , wherein the dextrose is present in an amount of about 5% by weight per total volume of the composition.
154 . The composition of claim 139 , further comprising a buffering agent.
155 . The composition of claim 154 , wherein the buffering agent is formic acid.
156 . The composition of claim 139 , wherein the composition is an aqueous solution having a pH of about 3.5 to about 4.5.
157 . The composition of claim 139 , wherein said conjugate compound is in the form of a pharmaceutically acceptable acid addition salt.
158 . The composition of claim 157 , wherein said pharmaceutically acceptable acid addition salt is acetate or formate.
159 . A method of treating a Sortilin-expressing cancer comprising administering to a subject in need thereof a therapeutically effective amount of the composition as defined in claim 139 .