Medical Research Council

Cambridge Antibody Technology Limited

Medimmune Limited

Other

Anthony Richard Pope

James David Marks

Gregory Paul Winter

Andrew David Griffiths

Kevin Stuart Johnson

John Gerald McCafferty

Ronald Henry Jackson

David John Chiswell

Timothy Peter Bonnert

Timothy Piers Clackson

Kaspar Philipp Holliger

Henricus Renerus Jacobus Mattheus Hoogenboom

Brian Timothy McGuinness

Magnus Malmqvist

Terence Derek Prospero

Hendricus Renerus Jacobus Matheus Hoogenboom

Kaspar-Philipp Holliger

Hendricus Renerus Jacobus Mattheus Hoogenboom

Andrew James Williams

Hendricus Renerus Hoogenboom

Kaspar-Philip Holliger

Hendricus Reneus Jacobus Mattheus Hoogenboom

Kasper Philipp Holliger

Kevin Pritchard

Henricus Renerus Hoogenboom

A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a filamentous bacteriophage particle containing DNA encoding the sbp member, wherein the sbp member has a binding domain that consists of a dAb fragment. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected filamentous bacteriophage particles for expression of the selected sbp members.

Methods for producing members of specific binding pairs

A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA. Using this method libraries of DNA encoding respective chains of such multimeric sbp members may be combined, thereby obtaining a much greater genetic diversity in the sbp members than could easily be obtained by conventional methods.

A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA.

Polypeptides comprising a first domain, which comprises a binding region of an immunoglobulin heavy chain variable region, and a second domain, which comprises a binding region of an immunoglobulin light chain variable region, the domains being linked but incapable of associating with each other to form an antigen binding site, associate to form antigen binding multimers, such as dimers, which may be multivalent or have multispecificity. The domains may be linked by a short peptide linker or may be joined directly together. Bispecific dimers may have longer linkers. Methods of preparation of the polypeptides and multimers and diverse repertoires thereof, and their display on the surface of bacteriophage for easy selection of binders of interest, are disclosed, along with many utilities.

Multivalent and multispecific binding proteins, their manufacture and use

Multivalent and multispecific binding proteins and their use

The invention relates to specific binding members for estradiol and materials and methods relating thereto, in particular antibodies or binding domains thereof which have high affinities (low dissociation constants) for estradiol and low cross-reactivity for other steroids. The invention further provides means to make such binding members, assay methods for the detection and/or quantitation of estradiol, and nucleic acid encoding said binding members, which nucleic acid may be used for their production. Preferred binding members include those with CDR regions of the D12 antibody heavy and light chain domains (SEQ ID NO:2 and SEQ ID NO:12 respectively).

Specific binding members for estradiol; materials and methods

Growing community of inventors

Cambridge, United Kingdom

Anthony Richard Pope