# US 7,608,263 B2 · RG1 antibodies and uses thereof

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- Number: US 7,608,263 B2
- Document ID: US7608263B2
- Status: Granted
- Kind: B2
- Application number: 11/981,123
- Filed: 2007-10-30
- Published: 2008-06-12
- Granted: 2009-10-27
- Earliest claimed: 2003-07-22
- Assignees: Bayer Schering Pharma Aktiengesellschaft
- Inventors: Richard Harkins; Deborah Parkes; Gordon Parry; Renate Parry; Douglas Schneider
- Web page: https://patentgrep.com/patent/US7608263B2

## CPC

- G01N 33/57555: of the prostate
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 51/1045: {against animal or human tumor cells or tumor cell determinants}
- A61P 13/08: of the prostate
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- C07K 16/3076: {against structure-related tumour-associated moieties}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention relates to antibodies, and antigen-binding antibody fragments, directed against an RG1 polypeptide. The invention further relates to methods for utilizing the antibodies, and antibody fragments, for diagnostic and therapeutic applications.

## Claims

### Claim 1

A method for selectively destroying a cell expressing a human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, which method comprises reacting an effective amount of an immunoconjugate with the cell wherein
(i) the immunoconjugate comprises an isolated antibody or a fragment thereof that binds to RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, conjugated to a therapeutic agent, and
(ii) the isolated antibody or a fragment thereof comprises
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 29, or
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, or SEQ ID NO: 31 or
c) a light chain variable region having the amino acid sequence of SEQ ID NO: 26 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 27 or SEQ ID NO: 28, or
d) a light chain variable region having the amino acid sequence of SEQ ID NO: 29 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 31,
thereby selectively destroying the cells expressing human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2.

### Claim 2

A method for selectively destroying a cell expressing a human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, which method comprises reacting the cell with an effective amount of an immunoconjugate, wherein
(i) the immunoconjugate comprises an isolated antibody or a fragment thereof, that binds to RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, conjugated to a therapeutic agent and
(ii) the isolated antibody or a fragment thereof comprises:
a) a light chain CDR3 sequence comprising the amino acid residues 110 to 117 of SEQ ID NO: 26,
b) a heavy chain CDR3 sequence comprising the amino acid residues 117 to 132 of SEQ ID NO: 27,
c) a light chain CDR1 sequence and CDR2 sequence, wherein the sequences comprise the amino acid residues 44 to 55 of SEQ ID NO: 26 and 71 to 77 of SEQ ID NO: 26, respectively, and
d) a heavy chain CDR1 sequence and CDR2 sequence, wherein the sequences comprise the amino acid residues 50 to 54 of SEQ ID NO: 27 and 69 to 84 of SEQ ID NO: 27, respectively,
thereby selectively destroy the cell expressing human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2.

### Claim 3

A method for selectively destroying a cell expressing a human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, which method comprises reacting the cell with an effective amount of an immunoconjugate, wherein
(i) the immunoconjugate comprises an isolated antibody or a fragment thereof, that binds to RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, conjugated to a therapeutic agent, and
(ii) the isolated antibody or a fragment thereof comprises:
a) a light chain CDR3 sequence comprising the amino acid residues 110 to 117 of SEQ ID NO: 29,
b) a heavy chain CDR3 sequence comprising the amino acid residues 117 to 126 of SEQ ID NO: 30,
c) a light chain CDR1 sequence and CDR2 sequence, wherein the sequences comprise the amino acid residues 44 to 55 of SEQ ID NO: 29 and 71 to 77 of SEQ ID NO: 29, respectively, and
d) a heavy chain CDR1 sequence and CDR2 sequence, wherein the sequences comprise the amino acid residues 50 to 54 of SEQ ID NO: 30 and 69 to 84 of SEQ ID NO: 30, respectively,
thereby selectively destroy the cell expressing human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2.

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

The method of claims 1, 2 or 3, wherein the therapeutic agent of the immunoconjugate is a cytotoxic agent.

### Claim 5 (depends on 4)

The method of claim 4, wherein the cytotoxic agent of the immunoconjugate is selected from the group consisting of ricin, doxorubicin, daunorubicin, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin D, diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, ricin, abrin, glucocorticoid and radioisotopes.

### Claim 6 (depends on 5)

The method of claim 5, wherein the radioisotope is selected from the group consisting of 46Sc, 47Sc, 48Sc, 72Ga, 73Ga, 90Y, 67Cu, 109Pd, 11Ag, 149Pm, 153Sm, 166Ho, 177Lu, 186Re, 188Re, 211At, 211Bi, 212Bi, 213Bi and 214Bi.

### Claim 7 (depends on 1, 2, 3)

The method of claims 1, 2 or 3, wherein the conjugation of the antibody with the therapeutic agent utilizes a chelator selected from the group consisting of p-SCN-Benzyl-DTPA and derivatives thereof, 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetra-cetic acid (DOTA) and derivatives thereof, and 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) and derivatives thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the chelator used is cyclohexyl-DTPA (CHX-A″-DTPA) or MX-DTPA (1B4M-DTPA).

### Claim 9 (depends on 1, 2, 3)

The method of claims 1, 2 or 3, wherein the antibody fragment is selected from the group consisting of Fv, F(ab′), F(ab′)2, scFv, single chain antibodies and F(ab′)2 fragments.

### Claim 10

A method for inhibiting a cell expressing a human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2, which method comprises reacting an effective amount of an antibody with the cell, wherein the antibody comprises:
(i) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 29,
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, or SEQ ID NO: 31,
(iii) a light chain variable region having the amino acid sequence of SEQ ID NO: 26 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 27 or SEQ ID NO: 28,
(iv) a light chain variable region having the amino acid sequence of SEQ ID NO: 29 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 31,
(v) a light chain CDR3 sequence comprising the amino acid residues 110 to 117 of SEQ ID NO: 26 a heavy chain CDR3 sequence comprising the amino acid residues 117 to 132 of SEQ ID NO: 30, a light chain CDR1 sequence and CDR2 sequence wherein the sequences comprise the amino acid residues 44 to 55 of SEQ ID NO: 26 and 71 to 77 of SEQ ID NO: 26 respectively, and a heavy chain CDR1 sequence and CDR2 sequence wherein the sequences comprise the amino acid residues 50 to 54 of SEQ ID NO: 27 and 69 to 84 of SEQ ID NO: 27, respectively, or
(vi) a light chain CDR3 sequence comprising the amino acid residues 110 to 117 of SEQ ID NO: 29, a heavy chain CDR3 sequence comprising the amino acid residues 117 to 126 of SEQ ID NO: 30, a light chain CDR1 sequence and CDR2 sequence wherein the sequences comprise the amino acid residues 44 to 55 of SEQ ID NO: 29 and 71 to 77 of SEQ ID NO: 29, respectively, and a heavy chain CDR1 sequence and CDR2 sequence wherein the sequences comprise the amino acid residues 50 to 54 of SEQ ID NO: 30 and 69 to 84 of SEQ ID NO: 30, respectively,
thereby inhibiting the cell expressing the human RG1 polypeptide having the amino acid sequence of SEQ ID NO: 2.