Patent ID: 8546532

Claim:
A process for manufacturing a composition comprising directed-sequence polymers (DSPs), comprising the steps of: (1) selecting a first base peptide sequence, wherein the sequence is an amino acid sequence of an epitope of an antigen associated with a protein conformational disorder; (2) synthesizing by solid phase peptide synthesis a first cassette of the DSPs, the cassette having a sequence of amino acid positions corresponding to each amino acid of the base peptide sequence, wherein, for at least one amino acid position of the first cassette of the DSPs, an amino acid is added, said amino acid randomly selected from a mixture of amino acids comprising an original amino acid found at the corresponding amino acid position of the base peptide sequence, alanine (A), and, optionally, at least one amino acid serving as a conserved substitution, wherein the amino acids in the mixture are present in a fixed molar input ratio relative to each other, determined prior to starting synthesis, wherein the relative molar amount of A is more than 10% and less than 90% of the total amino acid concentration of the DSPs; (3) optionally extending the length of the DSPs by (a) repeating step (2) for 1 to 15 cycles and elongating the DSP under the same condition including the input ratio of amino acids in the mixture; (b) repeating step (2) for 1 to 15 cycles and elongating the DSP, for each cycle, using a different input ratio of amino acids in the mixture; (c) repeating steps (1) and (2) for 1 to 15 cycles and elongating the DSP using cassettes based on more than one base peptide; (d) assembling 1 to 15 cassettes synthesized in a single cycle of step (2); or (e) assembling 1 to 15 cassettes, the first cassette synthesized under one condition of step (2), and second and more cassettes synthesized under one or more different conditions of step (2); wherein the number of cycles selected in steps (3) is selected so that the final length of the DSP is about 10 to 300 amino acid residues, and wherein the complexity of the linear DSP composition is greater than 5×10 2 different peptides.