US2021024581A1PendingUtilityA1
Conjugates containing hydrophilic spacer linkers
Est. expiryJun 25, 2027(~1 yrs left)· nominal 20-yr term from priority
Inventors:Christopher Paul LeamonIontcho Radoslavov VlahovHari Krishna R. SanthapuramPaul Joseph KleindlKevin Yu WangFei You
A61K 47/545C07H 15/24A61K 47/65A61P 35/00C07K 9/003A61K 47/60A61P 35/02A61P 31/04A61P 31/10A61P 33/02A61P 33/10A61P 31/00A61P 33/04A61P 33/00A61P 31/12
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Claims
Abstract
Described herein are compositions and methods for use in targeted drug delivery using cell receptor binding drug delivery conjugates containing hydrophilic spacer linkers for use in imaging, diagnosing, and/or treating diseases and disease states caused by pathogenic cell populations.
Claims
exact text as granted — not AI-modified1 .- 39 . (canceled)
40 . A compound of the formula
B-L-A wherein
B is of the formula
wherein ** represents a covalent bond to L;
L is a releasable linker comprising a first hydrophilic spacer linker portion is of the formula
wherein R is H, alkyl, cycloalkyl, or arylalkyl; m is an independently selected integer from 1 to 3; n is an integer from 1 to 6, p is an integer from 1 to 5, ** represents a covalent bond to B; and
* represents a covalent bond a first spacer linker portion of the formula
wherein * represents a covalent bond to the first hydrophilic spacer linker portion, and *** represents a covalent bond to a second hydrophilic spacer linker portion of the formula
wherein R is H, alkyl, cycloalkyl, or arylalkyl; m is an integer from 1 to 3; n is an integer from 1 to 6, p is an integer from 1 to 5, *** represents a covalent bond to the first spacer linker portion, and * represents a covalent bond to a second spacer linker portion of the formula
wherein * represents a covalent bond to the second hydrophilic spacer linker portion, and **** represents a covalent bond to an additional hydrophilic spacer linker portion or an additional spacer linker portion; and a releasable disulfide portion of the formula
wherein ** represents a covalent bond to in the additional hydrophilic spacer linker portion or the additional spacer linker portion, and * represents a covalent bond to the rest of the compound; and
A is therapeutic agent selected from the group consisting of DAVLBH, bortezomib, thiobortezomib, a tubulysin, aminopterin, rapamycin, paclitaxel, docetaxel, doxorubicin, daunorubicin, everolimus, α-amanatin, verucarin, didemnin B, geldanomycin, purvalanol A, everolimus, ispinesib, budesonide, and dasatinib.
41 . The compound of claim 40 , wherein p in the first hydrophilic spacer linker portion is 1.
42 . The compound of claim 41 , wherein p in the second hydrophilic spacer linker portion is 1.
43 . The compound of claim 42 , wherein m in the first hydrophilic spacer linker portion is 2.
44 . The compound of claim 43 , wherein m in the second hydrophilic spacer linker portion is 2.
45 . The compound of claim 44 , wherein n in the first hydrophilic spacer linker portion, when present, is 5.
46 . The compound of claim 45 , wherein n in the second hydrophilic spacer linker portion, when present, is 5.
47 . The compound of claim 46 , wherein R in the first hydrophilic spacer linker portion, when present, is H.
48 . The compound of claim 47 , wherein R in the second hydrophilic spacer linker portion, when present, is H.
49 . The compound of claim 48 , wherein A is DAVLBH.
50 . The compound of claim 48 , wherein A is a tubulysin.
51 . A compound of the formula
B-L-A wherein
B is of the formula
wherein ** represents a covalent bond to L;
L is a releasable linker comprising a first hydrophilic spacer linker portion is of the formula
wherein R is H; m is 2; n is 5, p is 1, ** represents a covalent bond to B; and * represents a covalent bond a first spacer linker portion of the formula
wherein * represents a covalent bond to the first hydrophilic spacer linker portion, and *** represents a covalent bond to a second hydrophilic spacer linker portion of the formula
wherein R is H; m is 2; n is 5, p is 1, *** represents a covalent bond to the first spacer linker portion, and * represents a covalent bond to a second spacer linker portion of the formula
wherein * represents a covalent bond to the second hydrophilic spacer linker portion, and **** represents a covalent bond to an additional hydrophilic spacer linker portion or an additional spacer linker portion; and a releasable-disulfide portion of the formula
wherein ** represents a covalent bond to in the additional hydrophilic spacer linker portion or the additional spacer linker portion, and * represents a covalent bond to the rest of the compound; and
A is an anti-inflammatory agent.
52 . A pharmaceutical composition comprising (a) an effective amount of a compound of claim 40 , and optionally one or more of a carrier, a diluent, or an excipient.
53 . A pharmaceutical composition comprising (a) an effective amount of a compound of claim 48 , and optionally one or more of a carrier, a diluent, or an excipient.
54 . A pharmaceutical composition comprising (a) an effective amount of a compound of claim 51 , and optionally one or more of a carrier, a diluent, or an excipient.
55 . A method for treating a disease in a patient comprising administering an effective amount of the compound of claim 40 to the patient.
56 . The method of claim 55 , wherein the disease is inflammation.
57 . A method for treating a disease in a patient comprising administering an effective amount of the compound of claim 48 to the patient.
58 . The method of claim 57 , wherein the disease is inflammation.
59 . A method for treating inflammation in a patient comprising administering an effective amount of the compound of claim 51 to the patient.Cited by (0)
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