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AssigneeMedical Research Council
InventorsAndrew David Griffiths, Hendricus Renerus Jacobus Mattheus Hoogenboom, James David Marks, John McCafferty, Gregory Paul Winter, Geoffrey Walter Grigg
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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 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.
A method of obtaining a member of a specific binding pair (sbp member), the sbp member being an antibody or antibody fragment and having an antigen binding site with binding specificity for an antigen which is a self antigen of a species of mammal, the method comprising:
A method according to any preceding claim wherein each said sbp member displayed at the surface of an rgdp is an scFv antibody fragment.
A method according to any one of the preceding claims wherein the nucleic acid is derived from rearranged V genes of an unimmunised;
A method according to any one of the preceding claims wherein said species of mammal is human.
A method according to any one of the preceding claims wherein sbp members selected in (b) displayed at the surface of rgdps are selected or screened to provide an individual rgdp displaying an sbp member or a mixed population of said rgdps, with each rgdp containing nucleic acid encoding the sbp member or a polypeptide chain thereof which is displayed at its surface.
A method according to any one of the preceding claims wherein nucleic acid which encodes a selected or screened sbp member and which is derived from an rgdp which displays at its surface a selected or screened sbp member is used to express an sbp member or a fragment or derivative thereof in a-recombinant host organism.
Use, in a method according to any one of the preceding claims, of a kit comprising a library of nucleic acid sequences capable of being packaged in rgdps and which encodes a polypeptide chain component part of an antobody for display at the surface of rgdps.
Dependencies are inferred from the claim text.