Abstract: An expression library comprising a repertoire of nucleic acid sequences cloned from a non-immunised source, each nucleic acid sequence encoding at least part of a variable domain of a heavy chain derived from an immunoglobulin naturally devoid of light chains (VHH) wherein the extent of sequence variability in the library is enhanced compared to the corresponding naïve expression library by introducing mutations in one or more of the complementarity determining regions (CDRs) of the nucleic acid sequences or by generating alternative combinations of CDR and framework sequences not naturally present in the naïve library repertoire. Also disclosed is the use of such a library in preparing antibodies, more particularly antibody fragments.

Abstract: A process is provided for the production of an antibody or a fragment or functionalized fragment thereof using a transformed lower eukaryotic host containing an example DNA sequence encoding the antibody or (functionalized) fragment thereof, wherein the antibody or (functionalized) fragment thereof is derived from a heavy chain immunoglobulin of Camelidae and is devoid of light chains, and wherein the lower eukaryotic host is a mould, preferably belonging to the genera Aspergillus or Trichoderma, or a yeast, preferably belonging to the yeast genera Saccharomyces, Kluyveromyces, Hansenula, or Pichia. The heavy chain fragment can contain at least the whole variable domain. A complementary determining region (CDR) different from the CDR belonging to the natural antibody ex Camelidae can be grafted on the framework of the variable domain of the heavy chain immunoglobulin. The catalytic antibodies can be raised in Camelidae against transition state molecules.

Abstract: An expression library comprising a repertoire of nucleic acid sequences cloned from a non-immunized source, each nucleic acid sequence encoding at least part of a variable domain of a heavy chain derived from an immunoglobulin naturally devoid of light chains (VHH) wherein the extent of sequence variability in said library is enhanced compared to the corresponding naive expression library by introducing mutations in one or more of the complementarity determining regions (CDRs) of said nucleic acid sequences or by generating alternative combinations of CDR and framework sequences not naturally present in the naive library repertoire. Also disclosed is the use of such a library in preparing antibodies, more particularly antibody fragments.

Abstract: An expression library comprising a repertoire of nucleic acid sequences cloned from a non-immunized source, each nucleic acid sequence encoding at least part of a variable domain of a heavy chain derived from an immunoglobulin naturally devoid of light chains (VHH) wherein the extent of sequence variability in the library is enhanced compared to the corresponding naive expression library by introducing mutations in one or more of the complementarity determining regions (CDRs) of the nucleic acid sequences or by generating alternative combinations of CDR and framework sequences not naturally present in the naive library repertoire. Also disclosed is the use of such a library in preparing antibodies, more particularly antibody fragments.