US2010234283A1PendingUtilityA1

Immunogenic epitopes, peptidomimetics, and anti-peptide antibodies, and methods of their use

Assignee: UNIV OHIO STATE RES FOUNDPriority: Feb 4, 2009Filed: Feb 4, 2010Published: Sep 16, 2010
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
51
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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-modified
1 . 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 .

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