Abbott Biotechnology Ltd.

Cambridge Antibody Technology Limited

Medimmune Limited

Basf Aktiengesellschaft

Medical Research Council

Abbvie Biotechnology Ltd

Louise Bacon

Jonathan Alexander Green

Julia Elizabeth Thompson

Anthony Richard Pope

Andrew James Williams

Philip Ronald Tempest

Ronald Henry Jackson

Tristan John Vaughan

Kevin Stuart Johnson

Alison Jane Wilton

Tristan J Vaughan

Boris Labkovsky

Jochen G Salfeld

Zehra Kaymakcalan

Michael White

Brian Timothy McGuinness

Paul Sakorafas

John A Mankovich

David Schoenhaut

Deborah J Allen

Andrew J Roberts

Hendricus R J M Hoogenboom

Stephen Smith

Sarah Helen Main

John Gerald McCafferty

Louise Conroy

Simon Nicholas Lennard

Peta Sally Helena Braddock

Sarah Leila Du Fou

Brian T Mcguinness

Gregory Paul Winter

Hendricus Renerus Hoogenboom

Raymond Paul Field

Steven Paul Ruddock

Hendricus Rjm Hoogenboom

Hendricus R Hoogenboom

Boris Labkovksy

Hendricus RJM Hoogenboom

Brian T Mcguiness

Specific binding members directed to eotaxin-1, in particular human antibodies and antibody fragments against human eotaxin-1 and especially those which neutralise eotaxin-1 activity. The antibodies VH and/or VL domain of the scFv fragment herein termed CAT-212 and of the IgG4 antibody herein termed CAT 213. One or more complementary determining regions (CDRs) of the CAT-213/-213 VH and/or VL domains especially VH CRD3 in other antibody framework regions. Compositions containing specific binding members and their use in methods of inhibiting or neutralising eotaxin, including methods of treatment or the human or animal body by therapy.

Human antibodies against eotaxin and their use

Specific binding members directed to eotaxin-1, in particular human antibodies and antibody fragments against human eotaxin-1 and especially those which neutralize eotaxin-1 activity. The antibodies VH and/or VL domain of the scFv fragment herein termed CAT-212 and of the IgG4 antibody herein termed CAT 213. One or more complementary determining regions (CDRs) of the CAT-212/-213 VH and/or VL domains, especially VH CRD3 in other antibody framework regions. Compositions containing specific binding members, and their use in methods of inhibiting or neutralizing eotaxin, including methods of treatment of the human or animal body by therapy.

Methods of obtaining a specific binding member that binds eotaxin

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;

Specific binding members directed to eotaxin-1, in particular human antibodies and antibody fragments against human eotaxin-1 and especially those which neutralize eotaxin-1 activity. The antibodies VH and/or VL domain of the scFv fragment herein termed CAT-212 and of the IgG4 antibody herein termed CAT 213. One or more complementary determining regions (CDRs) of the CAT-212-213 VH and/or VL domains, especially VH CRD3 in other antibody framework regions. Compositions containing specific binding members, and their use in methods of inhibiting or neutralizing eotaxin, including methods of treatment of the human or animal body by therapy.

Human antibodies that bind human TNF&#x3b1; and methods of using same

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;

Specific binding members comprising human antibody antigen binding domains specific for human transforming growth factor beta (TGF&#x3b2;) bind specifically isoforms TGF&#x3b2;2 and TGF&#x3b2;1 or both, preferentially compared with TGF&#x3b2;3. Specific binding members may be isolated and utilized in the treatment of disease, particularly fibrotic disease and also immune/inflammatory diseases. Therapeutic utility is demonstrated using in vitro and in vivo models. Full sequence and binding information is provided, including epitope sequence information for particularly advantageous specific binding member which binds the active form of TGF&#x3b2;2, neutralizing its activity, but does not bind the latent member.

Human antibodies specific for TGF&#x3b2;2

Specific binding members directed to eotaxin-1, in particular human antibodies and antibody fragments against human eotaxin-1 and especially those which neutralise eotaxin-1 activity. The antibodies VH and/or VL domain of the scFv fragment herein termed CAT-212 and of the IgG4 antibody herein termed CAT 213. One or more complementary determing regions (CDRs) of the CAT-212/-213 VH and/or VL domains, especially VH CRD3 in other antibody framework regions. Compositions containing specific binding members, and their use in methods of inhibiting or neutralising eotaxin, including methods of treatment of the human or animal body by therapy.

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.

The invention provides specific binding members, for example in the form of antibody variable domains, based on the CDR3 sequences of the antibody VH regions of SL15 (SEQ ID NO:4) and JT182 (SEQ ID NO:10). The antibodies have strong neutralising activity for TGF&#x3b2;and are useful in treating conditions associated with excess TGF&#x3b2;activity, such as fibrosis, immune responses and tumor progression.

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Cambridge, United Kingdom

Alison Jane Wilton