Patent ID: 8921278

Claim:
A method of obtaining combimers that bind to a target at a desired binding affinity, comprising the steps (a) through (d) in the following order: (a) designing an oligonucleotide library comprising oligonucleotides or analogs thereof having known primary and secondary structure, each of which comprises a constant region and a variable region comprising N enumerated base positions in a combimer loop region of the oligonucleotide or analog thereof, wherein each enumerated base position comprises one of X selected nucleotide bases, such that the oligonucleotide library comprises up to X N different oligonucleotides or analogs thereof, and wherein the nucleotide sequence is systematically modified to create a family of sequence variants, and wherein the region of the nucleotide sequence which is varied is said to be enumerated; (b) synthesizing at least some of the oligonucleotides or analogs thereof of the oligonucleotide library; (c) classifying or quantifying the binding affinity of the combimer loop region of each oligonucleotide or analog thereof for the target; and (d) identifying combimers with the desired binding affinity from the library of oligonucleotides or analogs thereof, wherein the combimer of step (d) is a member of the oligonucleotide library of (a) which comprises the known primary and secondary structure of step (a) and wherein N enumerated base positions comprises 2-40 nucleotides, and wherein the oligonucleotide library of (a) is reusable with multiple targets.