# US 7,612,168 B2 · Modified HIV peptides, antigens, compositions, immunoassay kit and a method of detecting antibodies induced by HIV

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- Number: US 7,612,168 B2
- Document ID: US7612168B2
- Status: Granted
- Kind: B2
- Application number: 11/211,576
- Filed: 2005-08-26
- Published: 2007-10-11
- Granted: 2009-11-03
- Earliest claimed: 2000-09-04
- Assignees: Bionor Immuno AS
- Inventors: Birger Sorensen
- Web page: https://patentgrep.com/patent/US7612168B2

## CPC

- C07K 14/005: from viruses
- A61P 31/18: for HIV
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- C12N 2740/16222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention comprises novel and modified peptides capable of inducing a HIV-1 specific immune response without antagonizing the cytotoxic T-cell activity in order to achieve an effective prophylactic and therapeutic vaccine against HIV. The peptides are based on conserved regions of HIV gag p17 and p24 proteins. Antigens in free- or carrier-bound form comprising at least one of the said peptides, vaccine compositions containing at least one of the antigens, immunoassay kits and a method of detecting antibodies induced by HIV or HIV specific peptides using such antigens, are described.

## Claims

### Claim 1

An isolated peptide from HIV-1 Gag p24 protein, which comprises at least one amino acid sequence which contains modifications compared with the native sequence and is selected from the group consisting of:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Gly Xaa9 Leu Val Xaa12 Xaa13 Xaa14 Tyr Xaa16 Xaa17 Xaa18 Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Ala Xaa25 Xaa26 Xaa27 Xaa28 (SEQ ID NO: 4), wherein
Xaa1 is Pro, Tyr or Phe,
Xaa2 is Ile, Val or Leu,
Xaa3 is Ile, Leu, Val, Ala or Met,
Xaa4 is Gln, Ser, Thr or Val,
Xaa5 is Asn, Asp or Thr,
Xaa6 is Ile, Ala, Leu or Met,
Xaa7 is Gln, Glu, Lys or Gly,
Xaa9 is Gln or Ile,
Xaa12 is none,
Xaa13 is none,
Xaa14 is none,
Xaa16 is Ala, Ser, Asn, Val or Pro,
Xaa17 is Ile, Leu, Met or Val,
Xaa18 is Ser or Thr,
Xaa19 is Pro or Ala,
Xaa20 is Arg or Lys,
Xaa21 is Thr or Ser,
Xaa22 is Leu or Ser,
Xaa23 is Asn, Phe or Val,
Xaa25 is Trp, Tyr, Gly or none,
Xaa26 is Val, Leu, Gly or none,
Xaa27 is Lys, Arg, Gly or none,
Xaa28 is Val, Ala, Cys, Gly or none;
Xaa1 Ala Xaa3 Xaa4 Xaa5 Ala Xaa7 Xaa8 Xaa9 Leu Leu Xaa12 Xaa13 Xaa14 Xaa15 Xaa16 Xaa17 Xaa18 Xaa19 His Gln Xaa22 Ala Xaa24 Xaa25 (SEQ ID NO: 9), wherein
Xaa1 is Tyr, Trp, Phe or Gly,
Xaa3 is Thr, Ala, Val, Ile or Leu,
Xaa4 is Pro or Ser,
Xaa5 is Gln, His, Gly, Thr, Ser or Tyr,
Xaa7 is Leu, Ile or Val,
Xaa8 is Asn or Tyr,
Xaa9 is Thr, Met, Leu or Ala,
Xaa12 is Ser, Thr or Asn,
Xaa13 is Thr, Ile, Val or Ala,
Xaa14 is Val or Ile,
Xaa15 is none,
Xaa16 is none,
Xaa17 is none,
Xaa18 is Gly or none,
Xaa19 is Gly or none,
Xaa22 is Ala or Gly,
Xaa24 is Met, Leu, Cys or none,
Xaa25 is Gln, Glu, His, Gly or none;
Xaa1 Xaa2 Ala Leu Ala Gly Xaa7 Xaa8 Xaa9 Leu Xaa11 Xaa12 Xaa13 Xaa14 Xaa15 Xaa16 Xaa17 Xaa18 Xaa19 Xaa20 Xaa21 (SEQ ID NO: 15), wherein
Xaa1 is Trp or Tyr,
Xaa2 is Ser or Ala,
Xaa7 is Thr, Ala or Ser,
Xaa8 is Ser or Thr,
Xaa9 is Ser or Thr,
Xaa11 is Leu, Pro, Val or Gln,
Xaa12 is Gin, Ala or His,
Xaa13 is Glu or Gly,
Xaa14 is Gin or His,
Xaa15 is Ile, Leu, Val or Met,
Xaa16 is Gly, Ala, Gln, Thr, Asn, Arg, His or Ile,
Xaa17 is Trp or Tyr,
Xaa18 is Thr, Met, Leu or Ile,
Xaa19 is Thr or Ser,
Xaa20 is Cys, Gly or none,
Xaa21 is Gly or none
wherein the terminal ends of the sequences may be free carboxyl- or amino groups, amides, acyls, acetyls or salts thereof,
two or more of the Cys residues may form part of an interchain disulphide binding, a —S—(CH2)p—S— or a —(CH2)p—-bridge wherein p=1-8 optionally intervened by one or more hetero atoms such as O, N and S and/or the said peptide sequences are immobilized to a solid support.

### Claim 2 (depends on 1)

The isolated peptide according to claim 1, wherein the amino acid sequence of SEQ ID NO 4 is selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 8.

### Claim 3 (depends on 1)

The isolated peptide according to claim 1, wherein the amino acid sequence of SEQ ID NO: 9 is SEQ ID NO: 11.

### Claim 4 (depends on 1)

The isolated peptide according to claim 1, wherein the amino acid sequence of SEQ ID NO: 15 is SEQ ID NO: 14.

### Claim 5 (depends on 1)

An antigen comprising at least one peptide according to claim 1.

### Claim 6 (depends on 5)

The antigen according to claim 5, which comprises at least one peptide selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 9 and SEQ ID NO: 15.

### Claim 7 (depends on 5)

An immunogenic composition, comprising the antigen according to claim 5 with a pharmaceutically acceptable diluent and optionally an adjuvant, carrier and/or vehicle and optionally additional immunostimulatory compound(s).

### Claim 8 (depends on 7)

The immunogenic composition according to claim 7, which comprises at least one peptide selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 9 and SEQ ID NO: 15.

### Claim 9 (depends on 7)

The immunogenic composition according to claim 7, which comprises the peptides of SEQ ID NO: 11.

### Claim 10 (depends on 7)

The immunogenic composition according to claim 7, wherein the peptides are dissolved in a sterile water solution and the optional immunostimulatory compound is a granulocyte macrophage colony stimulating factor.

### Claim 11 (depends on 7)

The immunogenic composition according to claim 7, wherein the composition comprises an adjuvant selected from the group consisting of Monophosphoryl Lipid A (MPL), Freund's complete adjuvant or Freund's incomplete adjuvant and aluminum hydroxide.

### Claim 12 (depends on 5)

An immunogenic composition, comprising the antigen according to claim 5, wherein the antigen is formulated as a lipopeptide and/or a liposome formulation.

### Claim 13 (depends on 1)

A method of detecting antibodies, induced by a HIV or HIV-specific peptide(s) or protein(s), in a sample of body fluid, comprising subjecting the sample to an immunoassay, wherein the antigen(s) is/are selected from the peptides of claim 1.

### Claim 14 (depends on 1)

An immunoassay kit for the detection of antibodies, induced by a HIV or HIV-specific peptides or proteins, in a sample of body fluid, comprising a diagnostic antigen which is the peptide of claim 1.

### Claim 15 (depends on 8)

The immunogenic composition according to claim 8, which comprises at least one peptide of SEQ ID NO: 11.