US2005277588A1PendingUtilityA1
Compounds having affinity for the granulocyte-colony stimulating factor receptor (G-CSFR) and associated uses
Individually held — no corporate assignee on recordPriority: Jul 20, 2000Filed: Aug 30, 2004Published: Dec 15, 2005
Est. expiryJul 20, 2020(expired)· nominal 20-yr term from priority
Inventors:Steven E. CwirlaPalani BaluDavid J. DuffinSunila PiplaniBarbara Mceowen MerrillPeter J. Schatz
C07K 14/53A61K 38/00C07K 14/535
58
PatentIndex Score
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Claims
Abstract
Novel compounds are provided that bind to G-CSFR. The novel compounds have a peptide chain approximately 6 to 40 amino acids in length that binds to G-CSFR. The compounds are useful as probes for affinity screening. In addition, the compounds have demonstrated agonist or antagonist activity for the G-CSFR, and are therefore useful in treatment of diseases including patients who suffer from a low white blood cell titer. Pharmaceutical compositions and methods of use are provided as well.
Claims
exact text as granted — not AI-modified1 . A compound comprising a peptide chain approximately 10 to 40 amino acids in length that binds to G-CSFR and contains a sequence of amino acids of formula (I) CX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 C (SEQ ID NO: 1), wherein each amino acid is indicated by standard one-letter abbreviation, and wherein X 1 is A, N, S, F, D, G, L, T, E, V, P, Q, H, M or K; X 2 is M, G, R, H, D, I, V, A, S, E, N, F, Y, P, C, W or T; X 3 is E, V, W, F, M, A, N, S, L, T, Y, G or P; X 4 is V, I, G, Q, W, M, T, Y, L, P, D, C, E or A; X 5 is M, E, W, L, P, N, I, T, V, F, Y, Q, S, R, W, G, H or D; X 6 is H, A, W, Y, V, F, Q, M, N, E, S, D, P or G. X 7 is M, F, Y, V, N, L, H, D, S, W, G, Q, C or T; and X 8 is C, Y, R, I, K, W, L, E, M, H, A, T, F, D, P, G or Q:
2 . The compound of claim 1 wherein X 1 is D or P.
3 . The compound of claim 1 wherein X 2 is D or P.
4 . The ccmpound of claim 1 wherein X 3 is E or W.
5 . The compound of claim 1 wherein X 4 is V, I, or Y.
6 . The compound of claim 1 wherein X 5 is M or L.
7 . The compound of claim 1 wherein X 6 is W, Y or F.
8 . The compound of claim 1 wherein X 7 is M, Y or D.
9 . The compound of claim 1 wherein X 8 is C or M.
10 . The compound of claim 1 that comprises a sequence selected from the following group:
CNREIEAMCC;
(SEQ ID NO: 9)
CADEVMHFCC;
(SEQ ID NO: 10)
CNREIMWMCC;
(SEQ ID NO: 11)
CSHEVWWYCC;
(SEQ ID NO: 12)
CSREVLYYCC;
(SEQ ID NO: 13)
CFIEGPWVCC;
(SEQ ID NO: 14)
CFVEGNWYCC;
(SEQ ID NO: 15)
CAAEVMVNCC;
(SEQ ID NO: 16)
CSDEVIFYCC;
(SEQ ID NO: 17)
CDREIMWFCC;
(SEQ ID NO: 18)
CAHEVMWMCC;
(SEQ ID NO: 19)
CGSEVTFMCC;
(SEQ ID NO: 20)
CLEEIMWLCC;
(SEQ ID NO: 21)
CAREVLAMCC;
(SEQ ID NO: 22)
CSVEVMQMCC;
(SEQ ID NO: 23)
CTNVQLMHYC;
(SEQ ID NO: 24)
CDVWQLFDRC;
(SEQ ID NO: 25)
CSFVQLNSIC;
(SEQ ID NO: 26)
CDYWQWFDKC;
(SEQ ID NO: 27)
CESFWVELWC;
(SEQ ID NO: 28)
CVPWMFYDLC;
(SEQ ID NO: 29)
CDPWMFYDLC;
(SEQ ID NO: 30)
CDPWVLFDEC;
(SEQ ID NO: 31)
CDHWTYFDMC;
(SEQ ID NO: 32)
CVVWTLYDKC;
(SEQ ID NO: 33)
CPDWYQSYMC;
(SEQ ID NO: 34)
CPDWYSYYMC;
(SEQ ID NO: 35)
CPEWYTDVMC;
(SEQ ID NO: 36)
CPDWYLDYMC;
(SEQ ID NO: 37)
CPEWYLDYMC;
(SEQ ID NO: 38)
CPDWYLPYMC;
(SEQ ID NO: 39)
CPEWYLPYMC;
(SEQ ID NO: 40)
CQDWWVELWC;
(SEQ ID NO: 41)
CPDWYLPWMC;
(SEQ ID NO: 42)
CACMLRVVHC;
(SEQ ID NO: 43)
CQRAGYMLAC;
(SEQ ID NO: 44)
CHANPVWGEC;
(SEQ ID NO: 45)
CFWSDWGQTC;
(SEQ ID NO: 46)
CPHWTSYYMC;
(SEQ ID NO: 47)
CETLCGACFC;
(SEQ ID NO: 48)
CATTINDTLC;
(SEQ ID NO: 49)
CLNYPHPVFC;
(SEQ ID NO: 50)
CMDGEMAVDC;
(SEQ ID NO: 51)
CNMGWMSWPC
(SEQ ID NO: 52)
CETYADWLGC;
(SEQ ID NO: 53)
CDPWMFFDMC;
(SEQ ID NO: 54)
CDPWIWYDLC;
(SEQ ID NO: 55)
CDPWIMYDRC;
(SEQ ID NO: 56)
CDPWVFFDIC;
(SEQ ID NO: 57)
CDPWTYYDLC;
(SEQ ID NO: 58)
CDPWIFYDRC;
(SEQ ID NO: 59)
CDPWLFYDLC;
(SEQ ID NO: 60)
CDPWVWYDLC;
(SEQ ID NO: 61)
CDPWIFFDRC;
(SEQ ID NO: 62)
CDPWMFFDQC;
(SEQ ID NO: 63)
CDPWLWYDRC;
(SEQ ID NO: 64)
CDVWVWYDQC;
(SEQ ID NO: 65)
CDPWIYYDLC;
(SEQ ID NO: 66)
CVPWTLFDLC;
(SEQ ID NO: 67)
CPAWYLEYMC;
(SEQ ID NO: 68)
CPDWYLEYMC;
(SEQ ID NO: 69)
CKYWQWFDKC;
(SEQ ID NO: 70)
CDHWMWYDKC.
(SEQ ID NO: 71)
GCNREIEAMCCG;
(SEQ ID NO: 72)
GCPEWYTDVMCG;
(SEQ ID NO: 73)
NWYCMDGEMAVDCEAT;
(SEQ ID NO: 74)
WQSCNMGWMSWPCYFV;
(SEQ ID NO: 75)
HELCETYADWLGCVEW;
(SEQ ID NO: 76)
PCDPWMFFDMCERW;
(SEQ ID NO: 77)
LRGCDPWIWYDLCPAV;
(SEQ ID NO: 78)
GYLCDPWIFYDRCLGF;
(SEQ ID NO: 79)
RFACDPWVFFDICGYW;
(SEQ ID NO: 80)
GYWCDPWTYYDLCLTA;
(SEQ ID NO: 81)
MWTCDPWIFYDRCFLN;
(SEQ ID NO: 82)
GSSCDPWLFYDLCLLD;
(SEQ ID NO: 83)
GGGCDPWVWYDLCWCD;
(SEQ ID NO: 84)
YTSCDPWIFFDRCMSV;
(SEQ ID NO: 85)
DPYCDPWMFFDQCAYL;
(SEQ ID NO: 86)
REFCDPWLWYDRCL;
(SEQ ID NO: 87)
NTGCDVWVWYDQCFAM;
(SEQ ID NO: 88)
LVFCDPWIYYDLCMDT;
(SEQ ID NO: 89)
GCSFVQLNSICG;
(SEQ ID NO: 90)
GCPAWYLEYMCG;
(SEQ ID NO: 91)
GCPDWYLEYMCG;
(SEQ ID NO: 92)
GCKYWQWFDKCG;
(SEQ ID NO: 93)
and
GCDHWMWYDKCG.
(SEQ ID NO: 94)
11 . The compound of claim 1 , containing a disulfide bond.
12 . The compound of claims 1 wherein the N terminus of the peptide is coupled to a polyethylene glycol molecule.
13 . The compound of claim 1 wherein the N terminus of the peptide is acetylated.
14 . The compound of claim 1 , wherein the C terminus of the peptide is amidated.
15 . The compound of claim 1 having
16 . The compound of claim 1 having structure:
wherein R 1 and R 2 are independently selected from the sequences of amino acids of formula (V); βA is a β-alanine residue; n1, n2, n3, n4, x and y are independently zero or one with the proviso that the sum of x and y is either one or two; and Lk is a terminal linking moiety selected from the group consisting of a disulfide bond, a carbonyl moiety, a C1-12 linking moiety optionally terminated with one or two-NH-linkages and optionally substituted at one or more available carbon atoms with a lower alkyl substituent, a lysine residue or a lysine amide.
17 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 , in combination with a pharmaceutically acceptable carrier.
18 . A method for treating a patient who would benefit from administration of a GCSF modulator, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 .
19 . The method of claim 16 , wherein the G-CSF modulator is an agonist for the GCSFR.
20 . The method of claim 16 , wherein the patient suffers from a depressed neutrophil count.
21 . The method of claim 18 , wherein the depressed neutrophil count is associated with a condition selected from the group consisting of chemotherapy-induced neutropenia, AIDS induced neutropenia and community-acquired pneumonia-induced neutropenia.Join the waitlist — get patent alerts
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