US2010234283A1PendingUtilityA1
Immunogenic epitopes, peptidomimetics, and anti-peptide antibodies, and methods of their use
Est. expiryFeb 4, 2029(~2.5 yrs left)· nominal 20-yr term from priority
Inventors:Pravin Kaumaya
A61K 2039/505C07K 14/71C07K 2317/732C07K 16/22A61K 2039/507C07K 14/52A61K 38/00C07K 16/32A61P 35/00A61K 39/001135
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Claims
Abstract
Provided herein are compositions and methods for the treatment of cancers. The compositions comprise at least one VEGF peptide mimic, HER-2 epitope, immunogenic VEGF peptides, and HER-2 immunogenic epitopes. The peptides and epitopes may be linear, cyclized, retro-inverso, or a combination of such forms. Also provided herein are antibodies raised to VEGF peptide mimics, HER-2 epitopes, immunogenic VEGF peptides, and HER-2 immunogenic epitopes.
Claims
exact text as granted — not AI-modified1 . A composition comprising a VEGF peptide that comprises an amino acid sequence ITMQCGIHQGQHPKIMICEMSF (SEQ ID NO: 1) (VEGF-P3(NC)).
2 . The composition of claim 1 wherein the two cysteine residues of the VEGF peptide are linked by a disulfide bond (VEGF-P3(CYC)).
3 . The composition of claim 2 wherein the VEGF peptide forms a twisted, anti-parallel, β-sheet structure.
4 . The composition of claim 3 wherein the VEGF peptide mimics the structure of amino acids 102 to 122 in native VEGF.
5 . The composition of claim 4 wherein the VEGF peptide mimic binds to a VEGF receptor.
6 . The composition of claim 5 wherein the VEGF receptor is selected from the group consisting of VEGFR-1, VEGFR-2, and VEGFR-3.
7 . The composition of claim 6 wherein the VEGF receptor is VEGFR-2.
8 . The composition of claim 1 wherein the VEGF peptide further comprises a T-cell epitope selected from the group consisting of:
KLLSLIKGVIVHRLEGVE;
(SEQ ID NO: 2)
NSVDDALINSTIYSYFPSV;
(SEQ ID NO: 3)
PGINGKAIHLVNNQSSE;
(SEQ ID NO: 4)
QYIKANSKFIGITEL;
(SEQ ID NO: 5)
FNNFTVSFWLRVPKVSASHLE;
(SEQ ID NO: 6)
LSEIKGVIVHRLEGV;
(SEQ ID NO: 7)
FFLLTRILTIPQSLN;
(SEQ ID NO: 8)
and
TCGVGVRVRSRVNAANKKPE.
(SEQ ID NO: 9)
9 . The composition of claim 8 wherein the VEGF peptide further comprises a linker between the VEGF peptide and T-cell epitope.
10 . The composition of claim 9 wherein the linker comprises a sequence that is between 1 and 15 amino acids in length.
11 . The composition of claim 10 wherein the linker comprises an amino acid sequence GPSL (SEQ ID NO: 10).
12 . The composition of claim 1 wherein the VEGF peptide is in retro-inverso form (VEGF-RI-P4).
13 . The composition of claim 12 wherein the two cysteine residues of the retro-inverso VEGF peptide are linked by a disulfide bond (VEGF-RI-P4(CYC)).
14 . The composition of claim 1 further comprising at least one HER-2 epitope selected from the group consisting of:
(SEQ ID NO: 11)
TGTDMKLRLPASPETHLDM;
(SEQ ID NO: 12)
AVLDNGDPLNNTTPVTGASPGG;
(SEQ ID NO: 13)
LWKDIFHKNNQLALTLIDTNRS;
(SEQ ID NO: 14)
TLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLT;
(SEQ ID NO: 15)
ALVTYNTDTFESMPNPEGRYT;
(SEQ ID NO: 16)
PLHNQEVTAEDGTQRAEKCSKPCA;
(SEQ ID NO: 17)
PESFDGDPASNTAPLQPE;
(SEQ ID NO: 18)
LYISAWPDSLPDLSVFQNLQ;
(SEQ ID NO: 19)
LFRNPHQALLHTANRPEDE;
(SEQ ID NO: 20)
CLPCHPECQPQNGSVTCFGPEADQCVACAHYKDP;
(SEQ ID NO: 21)
KPDLSYMPIWKFPDEEGA;
(SEQ ID NO: 22)
INGTHSCVDLDDKGCPAEQRAS;
(SEQ ID NO: 23)
CHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVA;
(SEQ ID NO: 24)
VACAHYKDPPFCVA;
(SEQ ID NO: 25)
VARCPSGVKPDLSYMPIWKFPDEEGACQPL;
(SEQ ID NO: 26)
IWKFPDEEGACQPL;
(SEQ ID NO: 27)
LHCPALVTYNTDTFESMPNPEGRYTFGASCV;
(SEQ ID NO: 28)
ACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEK;
(SEQ ID NO: 29)
CPLHNQEVTAEDGTQRCEK;
and
(SEQ ID NO: 30)
CPINCTHSCVDLDDKGCPAEQRAS.
15 . The composition of claim 14 wherein the HER-2 epitope is cyclized.
16 . The composition of claim 14 wherein the HER-2 epitope is in retro-inverso form.
17 . The composition of claim 14 wherein the HER-2 epitope is immunogenic.
18 . The composition of claim 14 wherein the HER-2 epitope further comprises a T-cell epitope selected from the group consisting of:
KLLSLIKGVIVHRLEGVE;
(SEQ ID NO: 31)
NSVDDALINSTIYSYFPSV;
(SEQ ID NO: 32)
PGINGKAIHLVNNQSSE;
(SEQ ID NO: 33)
QYIKANSKFIGITEL;
(SEQ ID NO: 34)
FNNFTVSFWLRVPKVSASHLE;
(SEQ ID NO: 35)
LSEIKGVIVHRLEGV;
(SEQ ID NO: 36)
FFLLTRILTIPQSLN;
(SEQ ID NO: 37)
and
TCGVGVRVRSRVNAANKKPE.
(SEQ ID NO: 38)
19 . The composition of claim 18 wherein the HER-2 epitope further comprises a linker of from 1 to 15 amino acids in length.
20 . The composition of claim 19 wherein the linker comprises GPSL (SEQ ID NO: 10).
21 . The composition of claim 8 further comprising at least one HER-2 epitope according to claim 18 .
22 . An isolated antibody that specifically binds to a polypeptide according to claim 8 .
23 . The antibody of claim 22 which is a monoclonal antibody.
24 . The antibody of claim 22 which is a humanized antibody.
25 . An antigen-binding fragment of the antibody of claim 22 .
26 . A method of treating cancer in a subject comprising administering a pharmaceutical composition to the subject, the pharmaceutical composition comprising a pharmaceutically acceptable vehicle, and at least one composition of claim 1 , 8 , 14 , 18 , or 21 .Join the waitlist — get patent alerts
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