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US 5,668,110 AGranted
Peptides and compounds that bind to the IL-5 receptor
AssigneeAffymax Technologies N.V.
InventorsRonald W. Barrett, Bruce P. England, Peter J. Schatz, Derek Sloan, Min-Jia Chen
Life of this patent
Estimating the term…
Abstract
Described are peptides and peptide mimetics that bind to and the IL-5 receptor. Such peptides and peptide mimetics are useful in methods for treating disorders that involve improper production of or response to IL-5 and or the production and accumulation of eosinophils, such as asthma, as well as in diagnostic methods employing labeled peptides and peptide mimetics.
Claims18
A method for treating a patient suffering from a disorder that is mediated by IL-5, comprising administering to the patient, a therapeutically effective dose of a compound comprising:
- (1) a core sequence of amino acids:
- CX.sub.1 RX.sub.2 X.sub.7 X.sub.8 X.sub.3 X.sub.4 X.sub.5 WX.sub.6 C
- where X.sub.1 is D, E, I, S, T, W, or Y;
- X.sub.2 is D, F, G, I, L, S, V, W, or Y;
- X.sub.3 is D, E, G, L, N, S, T, or W;
- X.sub.4 is H or R;
- X.sub.5 is A, K, R, S, T, V, or W;
- X.sub.6 is D, E, F, L, M, P, Q, or V;
- X.sub.7 is I or V;
- (SEQ ID NO:1), and dimers and oligomers thereof, having
- (a) a molecular weight of less than about 5000 daltons, and
- (b) a binding affinity to IL5-R as expressed by an IC.sub.50 of no more than about 100 .mu.m,
- wherein from zero to all of the --C(O)NH-- linkages of the peptide have been replaced by a linkage selected from the group consisting of a --CH.sub.2 OC(O)NR-- linkage;
- a phosphonate linkage;
- a --CH.sub.2 S(O).sub.2 NR-- linkage;
- a --CH.sub.2 NR-- linkage;
- and a --C(O)NR.sup.6 -- linkage;
- and a --NHC(O)NH-- linkage where R is Hydrogen or lower alkyl and R.sup.6 is lower alkyl,
- further wherein the N-terminus of said peptide or peptide mimetic is selected from the group consisting of a --NRR.sup.1 group;
- a --NRC(O)R group;
- a --NRC(O)OR group;
- a --NRS(O).sub.2 R group;
- a --NHC(O)NHR group;
- a succinimide group;
- a benzyloxycarbonyl-NH-- group;
- and a benzyloxycarbonyl-NH-- group having from 1 to 3 substituents on the phenyl ring selected from the group consisting of lower alkyl, lower alkoxy, chloro, and bromo, where R and R.sup.1 are independently selected from the group consisting of hydrogen and lower alkyl,
- and still further wherein the C-terminus of said peptide or peptide mimetic has the formula --C(O)R.sup.2 where R.sup.2 is selected from the group consisting of hydroxy, lower alkoxy, and --NR.sup.3 R.sup.4 where R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen and lower alkyl and where the nitrogen atom of the --NR.sup.3 R.sup.4 group can optionally be amine group of the N-terminus of the peptide so as to form a cyclic peptide, or a physiologically acceptable salt thereof.
24 more elements
A method for treating a patient suffering from a disorder that involves the accumulation of eosinophils and is mediated by IL-5, comprising administering to the patient, a therapeutically effective dose of a compound comprising:
- (1) a core sequence of amino acids:
- C X.sub.1 R X.sub.2 X.sub.7 X.sub.8 X.sub.3 X.sub.4 X.sub.5 W X.sub.6 C
- where X.sub.1 is D, E, I, S, T, W, or Y;
- X.sub.2 is D, F, G, I, L, S, V, W, or Y;
- X.sub.3 is D, E, G, L, N, S, T, or W;
- X.sub.4 is H or R;
- X.sub.5 is A, K, R, S, T, V, or W;
- X.sub.6 is D, E, F, L, M, P, Q, or V;
- X.sub.7 is I or V;
- and X.sub.8 is A or R (SEQ ID NO:1), and dimers and oligomers thereof, having
- (a) a molecular weight of less than about 5000 daltons, and
- (b) a binding affinity to IL5-R as expressed by an IC.sub.50 of no more than about 100 .mu.m,
- wherein from zero to all of the --C(O)NH-- linkages of the peptide have been replaced by a linkage selected from the group consisting of a --CH.sub.2 OC(O)NR-- linkage;
- a phosphonate linkage;
- a --CH.sub.2 S(O).sub.2 NR-- linkage;
- a --CH.sub.2 NR-- linkage;
- and a --C(O)NR.sup.6 -- linkage;
- and a --NHC(O)NH-- linkage where R is hydrogen or lower alkyl and R.sup.6 is lower alkyl,
- further wherein the N-terminus of said peptide or peptide mimetic is selected from the group consisting of a --NRR.sup.1 group;
- a --NRC(O)R group;
- a --NRC(O)OR group;
- a --NRS(O).sub.2 R group;
- a --NHC(O)NHR group;
- a succinimide group;
- a benzyloxycarbonyl-NH-- group;
- and a benzyloxycarbonyl-NH-- group having from 1 to 3 substituents on the phenyl ring selected from the group consisting of lower alkyl, lower alkoxy, chloro, and bromo, where R and R.sup.1 are independently selected from the group consisting of hydrogen and lower alkyl,
- and still further wherein the C-terminus of said peptide or peptide mimetic has the formula --C(O)R.sup.2 where R.sup.2 is selected from the group consisting of hydroxy, lower alkoxy, and --NR.sup.3 R.sup.4 where R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen and lower alkyl and where the nitrogen atom of the --NR.sup.3 R.sup.4 group can optionally be the amine group of the N-terminus of the peptide so as to form a cyclic peptide,
- or a physiologically acceptable salt thereof.
25 more elements
A method for treating an inflammatory disorder of the respiratory tract that is mediated by IL-5, said method comprising administering to a patient an inhalant composition comprising a therapeutically effective dose or amount of a compound in an aerosolized pharmaceutically acceptable carrier solution or dry powder, wherein said compound comprises:
- (1) a core sequence of amino acids:
- C X.sub.1 R X.sub.2 X.sub.7 X.sub.8 X.sub.3 X.sub.4 X.sub.5 W X.sub.6 C
- where X.sub.1 is D, E, I, S, T, W, or Y;
- X.sub.2 is D, F, G, I, L, S, V, W, or Y;
- X.sub.3 is D, E, G, L, N, S, T, or W;
- X.sub.4 is H or R;
- X.sub.5 is A, K, R, S, T, V, or W;
- X.sub.6 is D, E, F, L, M, P, Q, or V;
- and X.sub.7 is I or V and X.sub.8 is A or R (SEQ ID NO:1), and dimers and oligomers thereof, having
- (a) a molecular weight of less than about 5000 daltons, and
- (b) a binding affinity to IL5-R as expressed by an IC.sub.50 of no more than about 100 .mu.m,
- wherein from zero to all of the --C(O)NH-- linkages of the peptide have been replaced by a linkage selected from the group consisting of a --CH.sub.2 OC(O)NR-- linkage;
- a phosphonate linkage;
- a --CH.sub.2 S(O).sub.2 NR-- linkage;
- a --CH.sub.2 NR-- linkage;
- and a --C(O)NR.sup.6 -- linkage;
- and a --NHC(O)NH-- linkage where R is hydrogen or lower alkyl and R.sup.6 is lower alkyl,
- further wherein the N-terminus of said peptide or peptide mimetic is selected from the group consisting of a --NRR.sup.1 group;
- a --NRC(O)R group;
- a --NRC(O)OR group;
- a --NRS(O).sub.2 R group;
- a --NHC(O)NHR group;
- a succinimide group;
- a benzyloxycarbonyl-NH-- group;
- and a benzyloxycarbonyl-NH-- group having from 1 to 3 substituents on the phenyl ring selected from the group consisting of lower alkyl, lower alkoxy, chloro, and bromo, where R and R.sup.1 are independently selected from the group consisting of hydrogen and lower alkyl,
- and still further wherein the C-terminus of said peptide or peptide mimetic has the formula --C(O)R.sup.2 where R.sup.2 is selected from the group consisting of hydroxy, lower alkoxy, and --NR.sup.3 R.sup.4 where R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen and lower alkyl and where the nitrogen atom of the --NR.sup.3 R.sup.4 group can optionally be the amine group of the N-terminus of the peptide so as to form a cyclic peptide, or a physiologically acceptable salt thereof.
23 more elements
Dependencies are inferred from the claim text.