Enzon, Inc.

Enzon Labs Inc.

Genex Corporation

Karl D Hardman

Robert E Bird

David R Filpula

Marc D Whitlow

Robert Charles Ladner

James F Wood

Michele Rollence

Compositions of, genetic constructions coding for, and methods for producing multivalent antigen-binding proteins are described and claimed. The methods include purification of compositions containing both monomeric and multivalent forms of single polypeptide chain molecules, and production of multivalent proteins from purified monomers. Production of multivalent proteins may occur by a concentration-dependent association of monomeric proteins, or by rearrangement of regions involving dissociation followed by reassociation of different regions. Bivalent proteins, including homobivalent and heterobivalent proteins, are made in the present invention. Genetic sequences coding for bivalent single-chain antigen-binding proteins are disclosed. Uses include all those appropriate for monoclonal and polyclonal antibodies and fragments thereof, including use as a bispecific antigen-binding molecule.

Multivalent antigen-binding proteins

Nucleic acid molecules encoding single-chain antigen-binding proteins

Methods for producing multivalent antigen-binding proteins

The invention pertains to a single polypeptide chain binding molecule which has binding specificity and affinity substantially similar to the binding specificity and affinity of the light and heavy chain aggregate variable region of an antibody, to genetic sequences coding therefor, and to recombinant DNA methods of producing such molecule and uses for such molecule.

Immunoaffinity purification methods using single polypeptide chain

Immunoassay methods using single polypeptide chain binding molecules

Immunotheraphy using single chain polypeptide binding molecules

Single polypeptide chain binding molecules

A preferred embodiment of the invention is a method for constructing a polypeptide chain having a substantially predetermined conformation. Preferably a known stable well-mapped polypeptide structure is used as a starting point, and additional peptide units are incrementally added on while maintaining favorable enthalpic and entropic contributions to stability. Preferably a library of oligopeptide blocks is used to provide candidates for the additional peptide units. Preferably the library includes numerous precomputed parameters for each of the blocks, e.g. parameters for estimating energetic effects of varying the conformation parameters.

Incremental macromolecule construction methods

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Gaithersburg, MD, United States of America

Karl D Hardman