The Scripps Research Institute

Other

Epicyte Pharmaceutical, Inc.

University of California

Phyton Holdings, LLC

Planet Biotechnology Inc.

Plantbodies Corporation

Biolex Newco I, Inc.

Epicyte Pharmaceuticals, Inc.

The Porkin-elmer Corporation

Andrew C Hiatt

Mich B Hein

Floyd D Rose

Julian K-c Ma

John H Fitchen

Keith E Mostov

Thomas Lehner

Wolfgang J Wrasidlo

Michael W Hunkapiller

Joseph F Petolino

Dayakar Reddy Pareddy

K C Nicolaou

W H Kerr Anderson

Beth C Rubin-Wilson

Kristen Briggs

Jean L Roberts

Anton S Karnoup

Doug Taylor

Todd Glancy

This invention provides for the plant production of immunoglobulins, wherein at least a portion of the glycans attached to the immunoglobulins lack fucose. The invention also provides the constructs; plasmids; vectors; transformed plant cells, transformed plant calli; transformed plant tissues (e.g., leaves, seeds, tubers, etc.); transformed whole plants used to produce such immunoglobulins; methods of producing the immunoglobulins; the immunoglobulins produced by the disclosed methods; and the use of such immunoglobulins.

Plant production of immunoglobulins with reduced fucosylation

Targeting molecules for use in delivering biological agents to epithelial tissue are disclosed. Upon delivery, the biological agent(s) may remain within an epithelial cell or may undergo transepithelial transport via transcytosis. The targeting molecules may be used, for example, for the delivery of therapeutic agents.

Epithelial tissue targeting agent

The present invention relates to expression and assembly of foreign multimeric proteins&#x2014;e.g., antibodies&#x2014;in plants, as well as to transgenic plants that express such proteins. In one of several preferred embodiments, the generation and assembly of functional secretory antibodies in plants is disclosed. The invention also discloses compositions produced by the transgenic plants of the present invention and methods of using same.

Method of producing single chain protein in plant cells

The immunoglobulins of the present invention are useful therapeutic immunoglobulins against mucosal pathogens such as. The immunoglobulins contain a protection protein that protects the immunoglobulins in the mucosal environment. The invention also includes the greatly improved method of producing immunoglobulins in plants by producing the protection protein in the same cell as the other components of the immunoglobulins. The components of the immunoglobulin are assembled at a much improved efficiency. The method of the invention allows the assembly and high efficiency production of such complex molecules. The invention also contemplates the production of immunoglobulins containing protection proteins in a variety of cells, including plant cells, that can be selected for useful additional properties. The use of immunoglobulins containing protection proteins as therapeutic antibodies against mucosal and other pathogens is also contemplated.

Method for producing immunoglobulins containing protection proteins and their use

Method of producing heteromultimeric mammalian proteins in plants

Transgenic plants expressing assembled secretory antibodies

Targeting molecules are provided for use in delivering imaging agents to epithelial tissue. The targeting molecule comprises a polypeptide that forms a closed covalent loop, contains at least three peptide domains having &#x3b2;-sheet character, each of the domains being separated by domains lacking &#x3b2;-sheet character. The targeting molecule specifically binds to a basolateral factor attached to a basolateral domain of an epithelial cell surface causing internalization of a linked imaging agent into the cells. The polypeptide or imaging agent may be linked to a peptide amino acid sequence that directs delivery of the imaging agent to a carcinoma cell, a nucleus, or an endoplasmic reticulum.

Targeting molecule linked to an imaging agent

Method of use of transgenic plant expressed antibodies

The immunoglobulins of the present invention are useful therapeutic immunoglobulins against mucosal pathogens such as The immunoglobulins contain a protection protein that protects the immunoglobulins in the mucosal environment. The invention also includes the greatly improved method of producing immunoglobulins in plants by producing the protection protein in the same cell as the other components of the immunoglobulins. The components of the immunoglobulin are assembled at a much improved efficiency. The method of the invention allows the assembly and high efficiency production of such complex molecules. The invention also contemplates he production of immunoglobulins containing protection proteins in a variety of cells, including plant cells, that can be selected for useful additional properties. The use of immunoglobulins containing protection proteins a therapeutic antibodies against mucosal and other pathogens is also contemplated.

Immunoglobulins containing protection proteins and their use

Arrays of immunoglobulin binding proteins in plants or plant cells are provided. Such arrays comprise plants or plant cells transformed with polynucleotides encoding multiple different immunoglobulin binding proteins, or polypeptide components thereof. Methods are further provided for genetic segregation of the transformation events such that each transformant in an array is capable of producing progeny capable of expressing one or more immunoglobulin binding proteins, including multi-subunit proteins.

Immunoglobulin binding protein arrays in eukaryotic cells

Targeting molecules for use in delivering biological agents to non-polarized epithelial cells are disclosed. Upon delivery, the biological agent(s) are lethal to the epithelial cell. The targeting molecules may be used, for example, for the eradication of metastatic epithelial cells.

Epithelial cell targeting agent

The present invention relates to expression and assembly of foreign multimeric proteins&mdash;e.g., antibodies&mdash;in plants, as well as to transgenic plants that express such proteins. In one of several preferred embodiments, the generation and assembly of functional secretory antibodies in plants is disclosed. The invention also discloses compositions produced by the transgenic plants of the present invention and methods of using same.

Polypeptide targeting molecules are provided for use in delivering imaging agents to epithelial tissue. Upon delivery, the imaging agent(s) may remain within an epithelial cell or may undergo transepithelial transport via transcytosis. The targeting molecules may be used, for example, for diagnostic techniques. The polypeptide may be produced by recombinant methods, and forms a closed covalent loop, contains at least three peptide domains having &bgr;-sheet character which are separated by domains lacking &bgr;-sheet character, specifically binds to a basolateral factor attached to a basolateral domain of an epithelial surface causing uptake of a linked imaging agent into cells of the epithelial surface, and is not a full length dimeric Iga. Preferably, the polypeptide is a J chain polypeptide, or a J chain polypeptide linked to an immunoglobulin heavy chain without an immunoglobulin light chain. The polypeptide or imaging agent may be linked to a peptide amino acid sequence that directs delivery of the imaging agent to a carcinoma cell, a nucleus, or an endoplasmic reticulum.

J chain polypeptide targeting molecule linked to an imaging agent

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San Diego, CA, United States of America

Andrew C Hiatt