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.

Methods for producing members of specific binding pairs

Methods are disclosed for the production of anti-self antibodies and antibody fragments, being antibodies or fragments of a particular species of mammal which bind self-antigens of that species. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface a member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Anti-self antibody fragments are selected by binding with a self antigen from the said species of mammal. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding antigen. Nucleic acid libraries used may be derived from a rearranged V-gene sequences of unimmunised mammal. Synthetic or artificial libraries are described and shown to be useful.

Production of anti-self antibodies from antibody segment repertoires and displayed on phage

HUMAN MONOCLONAL ANTIBODIES TO PROGRAMMED DEATH 1(PD-1) AND METHODS FOR TREATING CANCER USING ANTI-PD-1 ANTIBODIES ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPEUTICS 5 Abstract The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells 1a and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides is methods for using a combination immunotherapy, such as the combination of anti-CT LA 4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Albumin Fusion Proteins

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Dual variable domain immunoglobulins and uses thereof

Methods are disclosed for the production of anti-self antibodies and antibody fragments, being antibodies or fragments of a particular species of mammal which bind self antigens of that species. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface a member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Anti-self antibody fragments are selected by binding with a self antigen from the said species of mammal. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding antigen. Nucleic acid libraries used may be derived from a rearranged V-gene sequences of unimmunised mammal. Synthetic or artificial libraries are described and shown to be useful.

Production of anti-self bodies from antibody segment repertories and displayed on phage

Production of chimeric antibodies from antibody segment repertoires and displayed on phage

Herstellung von Autoantikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken

L'invention decrit des procedes servant a la production d'anticorps anti-antigenes et de fragments d'anticorps qui sont des anticorps ou des fragments d'une espece particuliere de mammifere se fixant sur les auto-antigenes de ladite espece. Lesdits procedes comprennent la constitution de groupements d'affichage genetique reproductibles (rgdps), tels qu'un phage filamenteux, chaque rgdp affichant sur sa surface un element d'une paire de fixation specifique qui est un anticorps ou un fragment d'anticorps et chaque rgdp contenant une sequence d'acides nucleiques derivee d'une espece de mammifere. Ladite sequence d'acides nucleiques de chaque rgdp code une chaine de polypeptides qui est une partie constituante de l'element de sbp affiche sur la surface dudit rgdp. Des fragments d'anticorps anti-auto-antigenes sont selectionnes au moyen de la fixation avec un auto-antigene provenant desdites especes de mammifere. Les fragments d'anticorps affiches peuvent etre scFv, Fd, Fab ou tout autre fragment possedant une caracteristique de fixation a un antigene. Les banques d'acides nucleiques utilisees peuvent etre derivees d'une sequence redisposee de genes V d'un mammifere non immunise. L'invention decrit des banques synthetiques ou artificielles s'averant presenter une efficacite.

Geoffrey Walter Grigg

Papers

Production of anti-self antibodies from antibody segment repertoires and displayed on phage

Production of anti-self bodies from antibody segment repertories and displayed on phage

Production of chimeric antibodies from antibody segment repertoires and displayed on phage

Herstellung von Autoantikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken

Production d'anticorps anti-auto-antigenes a partir de repertoires de segments d'anticorps affiches sur phage