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

Patent metadata

Field	Value
Publication number	US-9504738-B2
Application number	US-201213662024-A
Country	US
Kind code	B2
Filing date	Oct 26, 2012
Priority date	Feb 4, 2009
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

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.

First claim

What is claimed is:

1. A composition comprising a VEGF peptide, wherein the VEGF peptide comprises ITMQCGIHQGQHPKIRMICEMSF (SEQ ID NO: 41), wherein the two cysteine residues of the VEGF peptide are linked by a disulfide bond.

2. The composition of claim 1 , wherein the VEGF peptide forms a twisted, anti-parallel, β-sheet structure.

3. The composition of claim 2 , wherein the VEGF peptide mimics the structure of amino acids 102 to 122 in native VEGF.

4. The composition of claim 3 , wherein the VEGF peptide mimic binds to a VEGF receptor.

5. The composition of claim 4 , wherein the VEGF receptor is selected from the group consisting of VEGFR-1, VEGFR-2, and VEGFR-3.

6. The composition of claim 5 , wherein the VEGF receptor is VEGFR-2.

7. The composition of claim 1 , wherein the VEGF peptide further comprises a T-cell epitope selected from the group consisting of:

(SEQ ID NO: 2)

KLLSLIKGVIVHRLEGVE; 

(SEQ ID NO: 3)

NSVDDALINSTIYSYFPSV; 

(SEQ ID NO: 4)

PGINGKAIHLVNNQSSE; 

(SEQ ID NO: 5)

QYIKANSKFIGITEL; 

(SEQ ID NO: 6)

FNNFTVSFWLRVPKVSASHLE; 

(SEQ ID NO: 7)

LSEIKGVIVHRLEGV; 

(SEQ ID NO: 8)

FFLLTRILTIPQSLN;

and

(SEQ ID NO: 9)

TCGVGVRVRSRVNAANKKPE.

8. The composition of claim 7 , wherein the VEGF peptide further comprises a linker between the VEGF peptide and T-cell epitope.

9. The composition of claim 8 , wherein the linker comprises a sequence that is between 1 and 15 amino acids in length.

10. The composition of claim 9 , wherein the linker comprises an amino acid sequence of GPSL (SEQ ID NO: 10).

11. A composition comprising a VEGF peptide, wherein the VEGF peptide comprises ITMQCGIHQGQHPKIRMICEMSF (SEQ ID NO: 41) in retro-inverso form (VEGF-RI-P4) or the retro-inverso form wherein the two cysteine residues are linked by a disulfide bond.

12. The composition of claim 11 , wherein the two cysteine residues of the retro-inverso VEGF peptide are linked by a disulfide bond (VEGF-RI-P4(CYC)).

13. The composition of claim 1 , further comprising at least one HER-2 epitope or a cyclized form or its retro-inverso form, wherein the HER-2 epitope is 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)

CHPECQPQNGSVTCFGPEADQVACAHYKDPPFCVA;

(SEQ ID NO: 24)

VACAHYKDPPFCVA;

(SEQ ID NO: 25)

VARCPSGVKPDLSYMPIWKFPDEEGACQPL;

(SEQ ID NO: 26)

IWKFPDEEGACQPL;

Assignees

• Ohio State Innovation Foundation

Inventors

• Pravin Kaumaya

Classifications

• C07K14/71

  for growth factors; for growth regulators · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title