Abbott Biotechnology Ltd.

Dyax Corporation

Basf Aktiengesellschaft

Abbvie Biotechnology Ltd

Hendricus R J M Hoogenboom

Boris Labkovsky

Tristan J Vaughan

Jochen G Salfeld

Zehra Kaymakcalan

Michael White

Brian Timothy McGuinness

Paul Sakorafas

John A Mankovich

David Schoenhaut

Deborah J Allen

Andrew J Roberts

Alison Jane Wilton

Simon E Hufton

Alison J Wilton

A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.

Multi-chain eukaryotic display vectors and uses thereof

Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &#x3b1; (hTNF&#x3b1;) are disclosed. These antibodies have high affinity for hTNF&#x3b1; (e.g., K=10M or less), a slow off rate for hTNF&#x3b1; dissociation (e.g., K=10secor less) and neutralize hTNF&#x3b1; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&#x3b1; and for inhibiting hTNF&#x3b1; activity, e.g., in a human subject suffering from a disorder in which hTNF&#x3b1; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Human antibodies that bind human TNF&#x3b1;

Methods of treating disorders using human antibodies that bind human TNF&#x3b1;

Methods for treating rheumatoid arthritis using human antibodies that bind human TNFa

Methods for treating rheumatoid arthritis using human antibodies that bind human TNF&#x3b1;

Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor a (hTNF&#x3b1;) are disclosed. These antibodies have high affinity for hTNF&#x3b1; (e.g., K=10M or less), a slow off rate for hTNF&#x3b1; dissociation (e.g., K=10secor less) and neutralize hTNF&#x3b1; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&#x3b1; and for inhibiting hTNF&#x3b1; activity, e.g., in a human subject suffering from a disorder in which hTNF&#x3b1; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &agr; (hTNF&agr;) are disclosed. These antibodies have high affinity for hTNF&agr; (e.g., K &equals;10 M or less), a slow off rate for hTNF&agr; dissociation (e.g., K &equals;10 sec or less) and neutralize hTNF&agr; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&agr; and for inhibiting hTNF&agr; activity, e.g., in a human subject suffering from a disorder in which hTNF&agr; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Human antibodies that bind human TNFa

Growing community of inventors

Hasselt, Belgium

Hendricus R J M Hoogenboom