Creative Biomolecules, Inc.

Chiron Corporation

Momenta Pharmaceuticals, Inc.

The United States of America As Represented by the Department of Health

Janssen Biotech, Inc.

Sepracor, Inc.

Curis, Inc.

Micromet Ag

Creative Biomoelcules, Inc.

James S Huston

Hermann Oppermann

Charles M Cohen

Peter C Keck

Richard J Ridge

Carlos J Bosques

David B Ring

Jonathan C Lansing

James Meador, Iii

Leona E Ling

L L Houston

Daniel Ortiz

Laura Rutitzky

David C Rueger

Marc F Charette

Roberto Crea

David M Segal

Lynn Baird

Herman Oppermann

Charles M Zepp

David R Dodds

Birgit Corinna Schultes

Robert L Bratzler

Robert A Dishman

Serge N Timasheff

Carolina R Jost

Andrew J George

Brigit C Schultes

The present invention relates to methods of using biologically active Fc domain-containing therapeutic constructs (Fc constructs) to induce immune cell activation of the immune response in a subject, and for example, to treat diseases such as cancers and infections in a subject. Such Fc constructs may include 5 or more Fc domains.

Methods related to engineered Fc constructs

The present invention relates to compositions and methods of engineered IgG Fc constructs, wherein said Fc constructs include one or more Fc domains.

Compositions and methods related to engineered Fc constructs

Disclosed is a method for the isolation and purification of polypeptides expressed in host cells by recombinant DNA techniques. A fused polypeptide is produced containing a desired polypeptide fused to additional amino acids. The additional amino acids define a leader sequence having properties exploitable in purification, a hinge region, and a cleavage site. The hinge region is cysteine-free and has a secondary structure which serves to expose the cleavage site to a selected endopeptidase. The method of the invention involves the production of a fused polypeptide which may be efficiently isolated by exploiting the properties of the leader sequence, and then efficiently cleaved at the cleavage site in an appropriate aqueous environment by virtue of the influence of the hinge on the cleavage agent/cleavage site reaction and other properties of the fused polypeptide.

Product and process for the production, isolation, and purification of recombinant polypeptide

Disclosed are a family of synthetic proteins having affinity for a preselected antigen. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic V,and V,dimers, 2) V,-V,or V,-V,single chains wherein the V,and V,are attached by a polypeptide linker, or 3) individual V,or V,domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.

Genetically engineered antibody analogues and fusion proteins thereof

The invention relates to a method of producing single-chain Fv molecules in eukaryotic cells, and to secretable sFv proteins having at least one non-naturally occurring glycosylation site. The single-chain Fv molecules produced by this method are biologically active and capable of being secreted from eukaryotic cells into the cell culture medium.

Method of producing single-chain Fv molecules

Disclosed is DNA encoding a single-chain Fv (sFv) polypeptide defining a binding site which exhibits the immunological binding properties of an immunoglobulin molecule which binds c-erbB-2 or a c-erbB-2-related tumor antigen, the sFv includes at least two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each of the polypeptide domains includes a set of complementarity determining regions (CDRs) interposed between a set of framework regions (FRs), the CDRs conferring immunological binding to the c-erbB-2 or c-erbB-2-related tumor antigen.

DNA encoding biosynthetic binding protein for cancer marker

Methods of delivering agents to target cells including methods of immunotherapy, are disclosed in which monospecific binding proteins are administered to a host and bind to target cells followed by administration of multivalent antibodies to direct the agents to the target cells.

Methods of delivering agents to target cells

Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Biosynthetic binding proteins for immuno-targeting

Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a preselected antigen by the binding site of each polypeptide chain when administered to a mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Biosynthetic binding proteins for immunotargeting

Disclosed are serine-rich peptide linkers for linking two or more protein domains to form a fused protein. The peptide linkers contains at least 40% serine residues and preferably have the formula (Ser, Ser,Ser,Ser,Gly).sub.y where y is .gtoreq.1. The resulting fused domains are biologically active together or individually, have improved solubility in physiological media, and improved resistance to proteolysis.

Serine-rich peptide linkers

Disclosed are a family of synthetic proteins having binding affinity for a preselected antigen, and multifunctional proteins having such affinity. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise V.sub.H -V.sub.L or V.sub.L -V.sub.H -like single chains wherein the V.sub.H and V.sub.L -like sequences are attached by a polypeptide linker, or individual V.sub.H or V.sub.L -like domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site for attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, for producing analogs thereof, and for producing multifunctional synthetic proteins which are self-targeted by virtue of their binding site region.

Polypeptide linkers for production of biosynthetic proteins

Disclosed are a family of synthetic proteins having affinity for a preselected antigen. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic V.sub.H and V.sub.L dimers, 2) V.sub.H -V.sub.L or V.sub.L -V.sub.H single chains wherein the V.sub.H and V.sub.L are attached by a polypeptide linker, or 3) individual V.sub.H or V.sub.L domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.

Biosynthetic antibody binding sites

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Chestnut Hill, MA, United States of America

James S Huston