Water-Soluble Polymer-Linked Binding Moiety and Drug Compounds
Compounds comprising a binding moiety, water-soluble, non-peptidic polymer, and drug are provided. Also provided are methods preparing such compounds, compositions comprising such compounds and methods for administering and using such compounds and compositions.
1 . (canceled)
2 . A compound, according to the formula:
Ab-X 1 -POLY-X 2 -Dr Formula I
wherein:
Ab is a binding moiety;
X 1 is a first spacer moiety;
POLY is a water-soluble, non-peptidic polymer;
X 2 is a second spacer moiety; and
Dr is a pharmacologically active agent.
3 . A compound according to the formula:
[Ab-X 1 -POLY] a -Q 1 -R-Q 2 -[POLY-X 2 -Dr] b Formula II
wherein:
Ab is a binding moiety;
X 1 is a first spacer moiety;
POLY, for each occurrence, is a water-soluble, non-peptidic polymer;
X 2 is a second spacer moiety;
Dr is a pharmacologically active agent;
R is a residue of polyol, polythiol or polyamine bearing at from 3 to about 50 hydroxyl, thiol or amino groups;
Q 1 and Q 2 for each occurrence is a linker
(a) is an integer from 1 to 49; and
(b) is an integer from 1 to 49;
provided that (a)+(b) is not less than 4 and not greater than 50.
4 . The compound of claim 2 , wherein Ab is an Affibody® moiety.
5 . The compound of claim 3 , wherein the Affibody® moiety is a HER2 binding Affibody®.
6 . (canceled)
7 . The compound of claim 2 , wherein X 2 is physiologically cleavable.
8 . The compound of claim 2 , wherein X 1 is not physiologically cleavable.
9 . (canceled)
10 . The compound of claim 2 wherein Dr is selected from a pharmacologically active agent useful for the treatment of breast cancer, ovarian cancer, pancreatic cancer, stomach cancer, salivary cancer, lung cancer, and esophageal cancer.
11 . The compound of claim 2 wherein Dr is selected from docetaxel, topotecan, paclitaxel, anthracylcin, DM1, gemcitabine, and lapatinib.
12 . The compound of claim 2 , wherein the compound is selected from a compound of the formula
13 . (canceled)
14 . The compound of claim 2 , wherein POLY is a poly(alkylene oxide).
15 . The compound of claim 2 , wherein, POLY is poly(ethylene glycol).
16 . The compound of claim 2 , wherein the weight-average molecular weight of the water-soluble non-peptidic polymer in the compound is from about 100 Daltons to about 150,000 Daltons.
17 . The compound of claim 2 , wherein the weight-average molecular weight of the water-soluble non-peptidic polymer in the compound is from about 2,000 to about 25,000.
18 . The compound of claim 2 , wherein the weight-average molecular weight of the water-soluble non-peptidic polymer in the compound is from about 4,000 to about 20,000.
19 . The compound of claim 2 , wherein the compound is selected from a compound of the formula
n is an integer from about 2 to about 4000.
20 . The compound of claim 19 , wherein n is an integer from about 30 to about 500.
21 . The compound of claim 20 , wherein n is an integer from about 45 to about 460.
22 . (canceled)
23 . A pharmaceutical composition comprising a compound of any one claim 2 and a pharmaceutically acceptable excipient.
24 . (canceled)
25 . (canceled)
26 . A method of treating cancer in a patient comprising administering a therapeutically effective amount of a compound of claim 2 a patient in need thereof.
27 . (canceled)
28 . (canceled)