# US 7,611,904 B2 · Serpentine transmembrane antigens expressed in human cancers and uses thereof

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- Number: US 7,611,904 B2
- Document ID: US7611904B2
- Status: Granted
- Kind: B2
- Application number: 11/580,538
- Filed: 2006-10-12
- Published: 2007-05-10
- Granted: 2009-11-03
- Earliest claimed: 1998-06-01
- Assignees: Agensys, Inc.
- Inventors: Daniel E. Afar; Rene S. Hubert; Kahan Leong; Arthur B. Raitano; Douglas C. Saffran; Stephen Chappell Mitchell
- Web page: https://patentgrep.com/patent/US7611904B2

## CPC

- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 13/08: of the prostate
- A61P 13/10: of the bladder
- A61P 35/00: Antineoplastic agents
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/723: {G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2319/00: Fusion polypeptide
- Y10T 436/143333: Saccharide [e.g., DNA, etc.]
- 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
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed “STEAP” (SIX Transmembrane Epithelial Antigens of the Prostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a “serpentine” manner into three extracellular and two intracellular loops. STEAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STEAP-1 is highly over-expressed in certain other human cancers.

## Claims

### Claim 1

A method for detecting the presence of a STEAP-1 protein in a biological sample comprising
contacting the sample with (a) a monoclonal antibody or antibody fragment that immunospecifically binds to the polypeptide shown in FIG. 1A (SEQ ID NO: 2), or (b) a recombinant protein comprising the antigen binding domain of said monoclonal antibody or antibody fragment, and
detecting the binding of STEAP-1 protein in the sample thereto.

### Claim 2

A method for determining an expression level for a STEAP-1 protein encoded by SEQ ID NO:1, comprising
determining the expression level of the STEAP-1 protein in a test sample obtained from a subject having or suspected of having a cancer cell expressing the STEAP-1 protein.

### Claim 3 (depends on 2)

The method of claim 2, further comprising comparing the expression level of the STEAP-1 protein in the test sample with the expression level of the STEAP-1 protein in a normal sample.

### Claim 4 (depends on 2)

The method of claim 2, wherein the test sample is peripheral blood.

### Claim 5

A method for determining an expression level for STEAP-1 in a test sample, comprising:
contacting a test sample obtained from a subject having or suspected of having a cancer cell expressing a STEAP-1 protein with an antibody or antibody fragment that binds specifically to the polypeptide of SEQ ID NO:2 or an extracellular domain of SEQ ID NO:2; and
quantifying an amount of STEAP-1 from the test sample bound to said antibody or antibody fragment,
whereby the expression level of STEAP-1 in the test sample is assessed.

### Claim 6 (depends on 1)

The method of claim 1, wherein the sample is from a human tissue.

### Claim 7 (depends on 6)

The method of claim 6, wherein the human tissue is prostate, colon, bladder, pancreas, ovary, cervix, testis, breast, bone, lymph node, lung, liver or brain.

### Claim 8 (depends on 6)

The method of claim 6 wherein the binding of the antibody or antibody fragment to the STEAP-1 protein in the sample is detected using a radioscintigraphic imaging apparatus.

### Claim 9 (depends on 1)

The method of claim 1, wherein the sample is blood, urine, semen, prostate, colon, bladder, pancreas, ovary, cervix, testis, breast, bone, lymph node, lung, liver, brain, serum, or a cell preparation.

### Claim 10 (depends on 1)

The method of claim 1 wherein the binding of the antibody or antibody fragment to the STEAP-1 protein in the sample is detected using fluorescence-activated cell sorting (FACS) or ELISA.

### Claim 11 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment is humanized.

### Claim 12 (depends on 1)

The method of claim 1, wherein the antibody fragment is an Fab, F(ab′)2, Fv or Sfv fragment.

### Claim 13 (depends on 1)

The method of claim 1, wherein the antibody is a human antibody.

### Claim 14 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment is recombinantly produced.

### Claim 15 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment binds immunospecifically to an extracellular domain of STEAP-1.

### Claim 16 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment is labeled with a detectable marker.

### Claim 17 (depends on 16)

The method of claim 16, wherein the detectable marker is a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound.

### Claim 18 (depends on 17)

The method of claim 17, wherein the detectable marker is a radioisotope selected from 212Bi, 131I, 111In, 90Y, 186Re, 211At, 125I, 188Re, 153Sm, 213Bi, 32P, and 177Lu.

### Claim 19 (depends on 1)

The method of claim 1, wherein the sample is bone tissue.

### Claim 20 (depends on 1)

The method of claim 1, wherein the sample is peripheral blood.

### Claim 21 (depends on 1)

The method of claim 1, wherein the sample is prostate tissue.

### Claim 22 (depends on 2)

The method of claim 2, wherein the sample is bone tissue, prostate tissue, urine, or semen.

### Claim 23 (depends on 5)

The method of claim 5, wherein the antibody or antibody fragment is humanized.

### Claim 24 (depends on 5)

The method of claim 5, wherein the antibody fragment is an Fab, F(ab′)2, Fv or Sfv fragment.

### Claim 25 (depends on 5)

The method of claim 5, wherein the antibody is a human antibody.

### Claim 26 (depends on 5)

The method of claim 5, wherein the antibody or antibody fragment is recombinantly produced.

### Claim 27 (depends on 5)

The method of claim 5, wherein the antibody is a monoclonal antibody.

### Claim 28 (depends on 5)

The method of claim 5, wherein the antibody or antibody fragment is conjugated to a detectable marker that comprises a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound.

### Claim 29 (depends on 28)

The method of claim 28, wherein the detectable marker is a radioisotope selected from 212Bi, 131I, 111In, 90Y, 186Re, 211At, 125I, 188Re, 153Sm, 213Bi, 32P, and 177Lu.

### Claim 30 (depends on 5)

The method of claim 5, wherein the test sample is bone tissue, prostate tissue, urine, peripheral blood, or semen.

### Claim 31 (depends on 30)

The method of claim 30, wherein the test sample is bone tissue.

### Claim 32 (depends on 30)

The method of claim 30, wherein the test sample is peripheral blood.

### Claim 33 (depends on 30)

The method of claim 30, wherein the test sample is prostate tissue.

### Claim 34 (depends on 2)

The method of claim 2, wherein the test sample is prostate tissue.

### Claim 35 (depends on 2)

The method of claim 2, wherein the test sample is bone tissue.

### Claim 36 (depends on 4)

The method of claim 4, wherein the peripheral blood comprises prostate cancer cells.

### Claim 37 (depends on 20)

The method of claim 20, wherein the peripheral blood comprises prostate cancer cells.

### Claim 38 (depends on 32)

The method of claim 32, wherein the peripheral blood comprises prostate cancer cells.

### Claim 39 (depends on 5)

The method of claim 5, further comprising comparing the amount of STEAP-1 bound to said antibody or antibody fragment from the test sample with the amount of STEAP-1 from a control sample.