The University of Texas System

Barrett R Harvey

George Georgiou

Brent L Iverson

Kenneth L Pinkston

Ali Azhdarina

Ki Jun Jeong

Brent I Iverson

Embodiments of the invention provide high affinity recombinant EpCAM-binding antibodies. Methods of using a such antibodies as imaging agents, diagnostics and therapeutics are also provided. Dual-nuclear and fluorescently labeled or singly fluorescently labeled contrast agents promise the advantage of molecularly-guided surgical resection via surgical field near-infrared fluorescence (NIRF) imaging following (in the case of dual labeled agents) nuclear imaging for general localization. Currently, nodal staging of most cancers is performed following lymph node (LN) biopsy and dissection for subsequent pathological examination.

Monoclonal antibodies targeting EpCAM for detection of prostate cancer lymph node metastases

The invention overcomes the deficiencies of the prior art by providing antibody compositions having improved affinities forantigens. The compositions have important thereapeutic and diagnostic applications, including treatment or detection of infection by

Antibodies with increased affinities for anthrax antigens

The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FACS).

Selection of bacterial inner-membrane anchor polypeptides

The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in the periplasm of gram negative bacteria and mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the outer surface-expression of ligand fusion proteins employed with phage display.

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Austin, TX, United States of America

Barrett R Harvey