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HLA binding peptides and their uses

a technology of binding peptides and peptides, which is applied in the field of hla binding peptides, can solve the problems of providing a useful human peptide-based vaccine or therapeutic agent, and achieve the effect of improving the safety and efficacy of human peptide-based vaccines

Inactive Publication Date: 2009-01-08
OSE PHARMA INT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]The present invention provides compositions comprising immunogenic peptides having binding motifs for HLA-A2.1 molecules. The immunogenic peptides, which bind to the appropriate MHC allele, are preferably 9 to 10 residues in length and comprise conserved residues at certain positions such as positions 2 and 9. Moreover, the peptides do not comprise negative binding residues as defined herein at other positions such as positions 1, 3, 6 and / or 7 in the case of peptides 9 amino acids in length and positions 1, 3, 4, 5, 7, 8 and / or 9 in the case of peptides 10 amino acids in length. The present invention defines positions within a motif enabling the selection of peptides which will bind efficiently to HLA A2.1.
[0019]The present invention also provides compositions comprising immunogenic peptides having binding motifs for non-A HLA alleles. The immunogenic peptides are preferably about 9 to 10 residues in length and comprise conserved residues at certain positions such as proline at position 2 and an aromatic residue (e.g., Y, W, F) or hydrophobic residue (e.g., L, I, V, M, or A) at the carboxy terminus. In particular, an advantage of the peptides of the invention is their ability to bind to two or more different HLA alleles.

Problems solved by technology

Despite the developments in the art, the prior art has yet to provide a useful human peptide-based vaccine or therapeutic agent based on this work.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0093]Class I antigen isolation was carried out as described in the related applications, noted above. Naturally processed peptides were then isolated and sequenced as described there. An allele-specific motif and algorithms were determined and quantitative binding assays were carried out.

[0094]Using the motifs identified above for the HLA-A2.1 allele amino acid sequences from a number of antigens were analyzed for the presence of these motifs. Table 3 provides the results of these searches. The letter “J” represents norleucine.

[0095]The above examples are provided to illustrate the invention but not to limit its scope. Other variants of the invention will be readily apparent to one of ordinary skill in the art and are encompassed by the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference.

TABLE 3PeptideAASequenceSourceA*0201SEQ ID NO:17.03179LQIGNIISIFlu.240.0130138.01039NLSLSCHAACEA.4320.011021233.119YLSGANLNVCEA.605...

example 2

Identification of Immunogenic Peptides

[0172]Using the motifs identified above for various MHC class I allele amino acid sequences from various pathogens and tumor-related proteins were analyzed for the presence of these motifs. Screening was carried out described in the related applications. Table 12 provides the results of searches of the antigens.

TABLE 12SEQPeptideAASequenceSourceA*0301A*1101ID NO:  28.071910ILEQWVAGRKHDV.nuc.160.01700.0012219  28.072710LSAGGKNLSKHDV.nuc.1150.00970.01502201259.0211STDTVDTVLEKFlu.HA.290.00010.06702211259.049GIAPLQLGKFlu.HA.630.61000.20002221259.0610VTAACSHAGKFlu.HA.1490.03800.04902231259.089GIHHPSNSKFlu.HA.1950.13000.01402241259.1010RMNYYWTLLKFlu.HA.2432.50002.30002251259.1211ITNKVNSVIEKFlu.HA.3920.02000.06702261259.1311KMNIQFTAVGKFlu.HA.4020.02800.00922271259.149NIQFTAVGKFlu.HA.4040.00170.03302281259.1611AVGKEFNKLEKFlu.HA.4090.02100.04602291259.1911KVKSQLKNNAKFlu.HA.4650.04700.00312301259.2011SVRNGTYDYPKFlu.HA.4950.04100.14002311259.219SIIPSGPLKFl...

example 3

Identification of Immunogenic Peptides

[0173]Using the B7-like supermotifs identified in the related applications described above, sequences from various pathogens and tumor-related proteins were analyzed for the presence of these motifs. Screening was carried out described in the related applications. Table 13 provides the results of searches of the antigens.

TABLE 13SEQPeptideSequenceSourceID NO:40.0013SPGLSAGICEA.680I829640.0022KPYDGIPAHer2 / neu.92129740.0023KPYDGIPIHer2 / neu.921I829840.0050APRMPEAAp53.6329940.0051APRMPEAIp53.63I830040.0055APAAPTPIp53.76I830140.0057APTPAAPIp53.79I830240.0059TPAAPAPIp53.81I830340.0061APAPAPSIp53.84I830440.0062SPALNKMFp53.12730540.0063SPALNKMIp53.127I830640.0117SPSAPPHRICEA.3I930740.0119PPHRWCIPICEA.7I930840.0120GPAYSGREICEA.9230940.0156MPNQAQMRILIHer2 / neu.706I1031040.0157MPYGCLLDHVIHer2 / neu.801I1031140.0161APPHRWCIPWCEA.631240.0162APPHRWCIPICEA.6I1031340.0163IPWQRLLLTACEA.1331440.0164IPWQRLLLTICEA.13I1031540.0166LPQHLFGYSICEA.58I1031640.0201RPRFRELVSE...

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Abstract

The present invention provides the means and methods for selecting immunogenic peptides and the immunogenic peptide compositions capable of specifically binding glycoproteins encoded by HLA alleles and inducing T cell activation in T cells restricted by the allele. The peptides are useful to elicit an immune response against a desired antigen. The immunogenic peptide compositions of the present invention comprise immunogenic peptides having an HLA binding motif, where the peptide is from a target antigen. Target antigens of the present invention include prostate specific antigen (PSA), hepatitis B core and surface antigens (HBVc, HBVs) hepatitis C antigens, Epstein-Barr virus antigens, melanoma antigens (e.g., MAGE-1), human immunodeficiency virus (HIV) antigens, human papilloma virus (HPV) antigens, Lassa virus, mycobacterium tuberculosis (MT), p53, CEA, trypanosome surface antigen (TSA) and Her2 / neu.

Description

REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation of U.S. application Ser. No. 09 / 189,702, filed Nov. 10, 1998, which is a continuation-in-part of U.S. application Ser. No. 08 / 205,713 filed Mar. 4, 1994. The present application is also related to U.S. Ser. No. 09 / 017,735, U.S. Ser. No. 08 / 753,622, U.S. Ser. No. 08 / 822,382, U.S. Ser. No. 60 / 013,980, U.S. Ser. No. 08 / 589,108, U.S. Ser. No. 08 / 454,033, U.S. Ser. No. 08 / 349,177, U.S. Ser. No. 08 / 073,205, and U.S. Ser. No. 08 / 027,146. The present application is also related to U.S. Ser. No. 09 / 017,524, U.S. Ser. No. 08 / 821,739, U.S. Ser. No. 60 / 013,833, U.S. Ser. No. 08 / 758,409, U.S. Ser. No. 08 / 589,107, U.S. Ser. No. 08 / 451,913 and to U.S. Ser. No. 08 / 347,610, U.S. Ser. No. 08 / 186,266, U.S. Ser. No. 08 / 159,339, U.S. Ser. No. 09 / 116,061, U.S. Ser. No. 08 / 103,396, U.S. Ser. No. 08 / 027,746, and U.S. Ser. No. 07 / 926,666. The present application is also related to U.S. Ser. No. 09 / 017,743; U.S. Ser. No. 08 / 753,...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00C07K7/00A61P37/00A61K38/08C07K14/02C07K14/18C07K14/74
CPCA61K38/08A61K39/00A61K2039/55555C07K14/005C07K14/4748C07K14/70539C12N2730/10122C12N2770/24222A61P37/00
Inventor SETTE, ALESSANDROSIDNEY, JOHNSOUTHWOOD, SCOTTCELIS, ESTEBAN
Owner OSE PHARMA INT
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