# US 8,540,991 B2 · Monoclonal antibodies against PCBP-1 antigens, and uses therefor

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- Number: US 8,540,991 B2
- Document ID: US8540991B2
- Status: Granted
- Kind: B2
- Application number: 13/568,969
- Filed: 2012-08-07
- Published: 2012-11-29
- Granted: 2013-09-24
- Earliest claimed: 2009-04-24
- Assignees: Alper Biotech, LLC
- Applicants: Özge Alper
- Inventors: Özge Alper
- Web page: https://patentgrep.com/patent/US8540991B2

## CPC

- G01N 33/57595: {involving intracellular compounds}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61K 51/1045: {against animal or human tumor cells or tumor cell determinants}
- A61P 35/00: Antineoplastic agents
- C07K 16/30: from tumour cells
- G01N 33/575: for cancer
- 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}
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- 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)

## Abstract

The present invention provides and includes monoclonal antibodies (MoAbs or mAbs) specific or preferentially selective for PCBP-1 antigens, hybridoma lines that secrete these PCBP-1 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect PCBP-1 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble form of PCBP-1. The present invention further includes chimeric and humanized antibodies, processes for producing monoclonal, chimeric, and humanized antibodies using recombinant DNA technology, and their therapeutic uses, particularly in the treatment of cancer. The present invention further includes methods and kits for the immunodetection and immunotherapy of cells for samples which express PCBP-1 antigens.

## Claims

### Claim 1

A pharmaceutical composition comprising an antibody or antibody fragment specific for a PCBP-1 antigen, comprising a heavy chain variable domain comprising three complemenarity determining regions (CDRs) comprising the amino acid sequences of SEQ ID NO: 45, SEQ ID NO: 46 and SEQ ID NO: 47, and a light chain variable domain comprising three CDRs comprising the amino acid sequences of SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50 and a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The pharmaceutical composition according to claim 1 wherein said PCBP-1 antigen is a soluble protein having a molecular weight of about 40 kilodaltons as measured by gradient polyacrylamide gel electrophoresis.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the antibody or antibody fragment is detectably labeled.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1 conjugated to a cytotoxic radionuclide, a cytotoxic drug, a cytotoxic protein, cytokine, radionuclide, drug, immunomodulator, therapeutic enzyme, or anti-proliferative agent.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1 capable of preferentially binding to a soluble or secreted form of PCBP-1 antigen, relative to a membrane form of PCBP-1.

### Claim 6 (depends on 1)

An isolated DNA sequence which encodes the antibody or the antibody fragment of claim 1.

### Claim 7 (depends on 6)

A vector comprising the DNA sequence of claim 6.

### Claim 8 (depends on 7)

A host cell transformed with the vector of claim 7.

### Claim 9 (depends on 8)

A process for the production of an antibody that binds to PCBP-1, comprising culturing the host cell of claim 8 and isolating the antibody.

### Claim 10

A kit for the immunohistochemical detection of carcinoma comprising: (a) a monoclonal antibody specific for a PCBP-1 antigen comprising a heavy chain variable domain comprising three complemenarity determining regions (CDRs) comprising the amino acid sequences of SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, and a light chain variable domain comprising three CDRs comprising the amino acid sequences of SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50 and (b) a secondary antibody conjugated to a detectable label.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, capable of binding to a soluble form of PCBP-1 with a specific affinity of between 10−8 M and 10−11 M.

### Claim 12 (depends on 1)

The pharmaceutical composition of claim 1, capable of selectively reducing the activity of a soluble PCBP-1 in a cell.

### Claim 13 (depends on 1)

The pharmaceutical composition of claim 1, capable of recognizing an epitope selected from the group consisting of SEQ ID NOs: 1-14, and fragments thereof.

### Claim 14 (depends on 1)

The pharmaceutical composition of claim 1 wherein the antibody or antibody fragment is humanized.

### Claim 15 (depends on 1)

The pharmaceutical composition of claim 1, wherein the antibody or antibody fragment is conjugated to another protein or protein fragment to form a fusion protein.
