# US 8,541,008 B2 · Pharmaceutical compositions and methods to vaccinate against candidiasis

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- Number: US 8,541,008 B2
- Document ID: US8541008B2
- Status: Granted
- Kind: B2
- Application number: 10/245,802
- Filed: 2002-09-13
- Published: 2003-07-03
- Granted: 2013-09-24
- Earliest claimed: 1999-11-19
- Assignees: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
- Applicants: John E. Edwards, Jr.; Scott G. Filler; Donald C. Sheppard; Ashraf S. Ibrahim; Yue Fu; Bradley J. Spellberg
- Inventors: John E. Edwards, Jr.; Scott G. Filler; Donald C. Sheppard; Ashraf S. Ibrahim; Yue Fu; Bradley J. Spellberg
- Web page: https://patentgrep.com/patent/US8541008B2

## CPC

- A61K 39/39575: {against materials from other living beings excluding bacteria and viruses, e.g. protozoa, fungi, plants}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 39/0002: {Fungal antigens, e.g. Trichophyton, Aspergillus, Candida}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07K 14/40: from Candida
- C07K 16/14: against material from fungi, algea or lichens
- A61K 2039/505: {comprising antibodies}
- A61K 2039/53: {DNA (RNA) vaccination}
- 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)
- 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)

## Abstract

A Candida albicans bloodstream infections cause significant morbidity and mortality in hospitalized patients. Filament formation and adherence to host cells are critical virulence factors of C. albicans. Multiple filamentation regulatory pathways have been discovered, however the downstream effectors of these regulatory pathways remain unknown. The cell surface proteins in the ALS group are downstream effectors of the filamentation regulatory pathway. Particularly, Als1p mediates adherence to endothelial cells in vitro and is required for virulence. The blocking of adherence by the organism is described resulting from the use of a composition and method disclosed herein. Specifically, a pharmaceutical composition comprised of a gene, gene product, or specific antibody to the ALS gene family is administered as a vaccine to generate an immune response capable of blocking adherence of the organism.

## Claims

### Claim 1

A method of vaccinating a mammalian host against Candida albicans comprising administering to said host a pharmacologically effective amount of a vaccine comprising an isolated polypeptide consisting of the N-terminal domain of the Candida albicans agglutinin like sequence (ALS) polypeptide, Als1p, in a pharmaceutically acceptable excipient, wherein the N-terminal domain extends from the end of the signal peptide to the beginning of the tandem repeat of said Candida albicans Als1p, and wherein the method inhibits adhesion of the Candida albicans to endothelial cells in said host.

### Claim 2 (depends on 1)

The method of claim 1, wherein the immunogenic composition is administered subcutaneously.

### Claim 3 (depends on 1)

The method of claim 1, wherein the polypeptide is substantially pure.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition comprises an immunostimulating adjuvant.

### Claim 5 (depends on 3)

The method of claim 3, wherein the immunostimulating adjuvant is alum.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The method of any one of claims 1 to 5, wherein said administering comprises administering a booster dose of the immunogenic composition.

### Claim 7 (depends on 1)

The method of claim 1, wherein the polypeptide is produced in Saccharomyces cerevisiae.

### Claim 8 (depends on 1)

The method of claim 1, wherein the mammalian host is a human and said polypeptide is purified.

### Claim 9 (depends on 1)

The method of claim 1 wherein the polypeptide consists of amino acids 18 to 432 of the amino acid sequence of SEQ ID NO: 25.