US 11,230,706 B2 · Method of generating a synthetic antibody library, said library and application(s) thereof

Abstract

The present disclosure relates to a method of generating an antibody library, not limiting to a synthetic antibody gene expression library built on pool of consensus nucleic acid sequences by using codon replacement technology. The present disclosure also relates to a synthetic antibody library generated by employing the method of the present disclosure and application(s) of said antibody library.

A synthetic gene expression library encoding first fusion proteins, wherein each first fusion protein comprises a fusion of a display peptide, a human antibody, and an expression tag, the synthetic gene expression library comprising:

a repertoire of 1010 to 1011 unique synthetic nucleic acid sequences encoding first fusion proteins,
wherein each of the encoded first fusion proteins comprises:
a human antibody variable heavy chain with a polypeptide sequence selected from the group consisting of SEQ ID NOs. 2, 4, 6, 8, 10, 12 and 14 encoded by corresponding nucleic acid sequence selected from SEQ ID NOs. 1, 3, 5, 7, 9, 11 or 13;
a display peptide derived from a nucleotide sequence encoded in a display vector;
and
at least one expression tag peptide selected from the group consisting of FLAG, c-Myc, (His)6-tag and V5-tag;
wherein within each of the variable heavy chains, the CDR3 region of the heavy chain (CDRH3) has been modified from the respective SEQ ID NO;
wherein the synthetic gene expression library encodes modified CDRH3s with lengths of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and 23 amino acid residues,
wherein:
when the length of the modified CDRH3 is 4 amino acid residues, the amino acid sequence is X1X2X3X4 (SEQ ID NO. 113),
wherein X1 encodes such that G is 36.83%, D is 10.18%, E is 9.33%, V is 8.80%, R is 5.38%, Y is 5.22%, A is 0.21%, C is 0.05%, F is 4.21%, H is 0.94%, I is 3.09%, K is 4.14%, L is 2.93%, M is 0.05%, N is 2.42%, P is 0.05%, S is 1.15%, T is 0.07% and W is 4.90%,
wherein X2 encodes such that L is 22.64%, Y is 20.29%, D is 19.97%, R is 19.12%, T is 16.51%, A is 0.09%, F is 0.18%, G is 0.44%, I is 0.05%, M is 0.27%, N is 0.09%, P is 0.09%, Q is 0.04%, S is 0.16%, and W is 0.05%,
wherein X3 encodes such that A is 23.97%, E is 21.57%, R is 19.44%, Y is 17.18%, G is 16.29%, D is 0.60%, F is 0.04%, L is 0.21%, M is 0.05%, N is 0.04%, P is 0.05%, Q is 0.04%, S is 0.14%, T is 0.12%, V is 0.09%, C is 0.05% and W is 0.05%, and
wherein X4 encodes such that N is 24.57%, Y is 22.44%, R is 20.42%, S is 18.19%, P is 13.24%, D is 0.07%, F is 0.11%, G is 0.25%, I is 0.21%, L is 0.14%, V is 0.20% and W is 0.04%;
when the length of the modified CDRH3 is 5 amino acid residues, the amino acid sequence is X1X2X3X4X5 (SEQ ID NO. 114),
wherein X1 encodes such that G is 35.44%, D is 9.98%, E is 8.42%, V is 7.44%, R is 6.81%, A is 0.39%, C is 0.08%, F is 3.55%, H is 1.60%, I is 3.93%, K is 4.88%, L is 4.32%, N is 2.98%, S is 1.40%, T is 0.19%, W is 4.25% and Y is 4.29%,
wherein X2 encodes such that G is 37.64%, R is 16.75%, M is 11.46%, N is 9.28%, V is 8.83%, H is 7.30%, T is 7.02%, A is 0.31%, D is 0.18%, E is 0.07%, F is 0.07%, I is 0.10%, K is 0.07%, L is 0.15%, P is 0.18%, Q is 4.00%, S is 0.18%, W is 0.10% and Y is 0.26%,
wherein X3 encodes such that M is 24.29%, G is 22.40%, F is 18.08%, E is 10.74%, L is 8.38%, W is 7.62%, S is 7.30%, A is 0.08%, C is 0.07%, D is 0.11%, H is 0.07%, I is 0.19%, Q is 0.04%, R is 0.18%, T is 0.04%, V is 0.17% and Y is 0.19%,
wherein X4 encodes such that D is 41.08%, A is 34.90%, L is 15.65%, V is 6.99%, C is 0.04%, E is 0.17%, F is 0.08%, G is 0.33%, H is 0.07%, M is 0.08%, P is 0.06%, Q is 0.06%, R is 0.10%, S is 0.17%, T is 0.04%, and Y is 0.11%, and
wherein X5 encodes such that Y is 65.74%, N is 15.00%, I is 9.60%, L is 6.56%, V is 6.22%, F is 5.91%, C is 0.12%, D is 0.12%, G is 0.15%, M is 0.04%, P is 0.11%, R is 0.07%, S is 0.12% and T is 4.94%;
when the length of the modified CDRH3 is 6 amino acid residues, the amino acid sequence is X1X2X3X4X5X6 (SEQ ID NO. 115),
wherein X1 encodes such that G is 32.77%, D is 9.78%, E is 9.04%, V is 7.72%, R is 7.15%, K is 5.11%, Y is 4.53%, W is 4.34%, I is 4.33%, L is 4.20%, N is 3.43%, F is 3.40%, S is 1.76%, H is 1.54%, A is 0.37%, T is 0.31%, C is 0.09%, P is 0.05%, Q is 0.05% and M is 0.03%,
wherein X2 encodes such that A is 17.54%, Y is 23.01%, G is 11.00%, S is 9.44%, P is 7.78%, N is 5.61%, K is 5.44%, V is 4.53%, L is 4.02%, T is 3.85%, R is 2.06%, D is 2.00%, W is 1.62%, H is 1.36%, F is 0.15%, E is 0.14%, I is 0.14%, M is 0.14%, and Q is 0.14%,
wherein X3 encodes such that G is 34.05%, Y is 12.12%, A is 9.75%, S is 8.13%, P is 7.48%, V is 6.92%, E is 6.36%, D is 4.77%, K is 2.25%, F is 1.93%, R is 1.57%, L is 1.56%, H is 1.43%, T is 0.95%, I is 0.14%, M is 0.14%, C is 0.11%, W is 0.11%, N is 0.09% and Q is 0.08%,
wherein X4 encodes such that F is 23.18%, G is 12.64%, M is 9.18%, S is 8.93%, E is 7.42%, D is 7.25%, L is 6.75%, V is 5.28%, P is 4.37%, Y is 2.77%, H is 2.71%, I is 2.71%, A is 2.53%, W is 1.71%, T is 1.28%, Q is 0.92%, R is 0.14%, K is 0.08%, N is 0.06% and C is 0.05%,
wherein X5 encodes such that D is 59.06%, A is 10.04%, G is 7.96%, N is 7.79%, P is 4.53%, I is 2.19%, M is 2.05%, R is 1.60%, V is 1.39%, H is 1.36%, T is 0.95%, Y is 0.28%, S is 0.26%, L is 0.17%, E is 0.11%, F is 0.09%, K is 0.09%, Q is 0.03%, and W is 0.03%, and
wherein X6 encodes such that Y is 63.36%, C is 7.85%, V is 7.76%, G is 3.94%, L is 3.73%, D is 3.45%, F is 3.39%, P is 1.77%, R is 1.51%, S is 1.43%, H is 0.95%, I is 0.46%, N is 0.08%, A is 0.05%, Q is 0.05%, K is 0.03%, and M is 0.03%;
when the length of the modified CDRH3 is 7 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7 (SEQ ID NO. 116),
wherein X1 encodes such that G is 31.73%, D is 10.11%, E is 8.67%, V is 7.43%, R is 6.98%, K is 5.49%, Y is 4.88%, L is 4.30%, W is 4.06%, I is 4.01%, F is 3.65%, N is 3.33%, S is 1.87%, H is 1.69%, A is 0.85%, T is 0.58%, Q is 0.14%, P is 0.09%, C is 0.08% and M is 0.08%,
wherein X2 encodes such that R is 15.99%, G is 12.37%, A is 9.55%, Y is 9.41%, N is 7.19%, D is 6.98%, S is 5.72%, H is 4.93%, P is 4.68%, E is 3.97%, I is 3.86%, V is 3.85%, L is 3.39%, Q is 2.81%, T is 2.52%, K is 1.34%, W is 1.08%, F is 0.18%, M is 0.12% and C is 0.06%,
wherein X3 encodes such that G is 21.33%, D is 14.56%, Y is 13.01%, N is 12.74%, S is 7.39%, A is 6.55%, L is 5.93%, W is 4.67%, T is 4.07%, R is 3.98%, E is 1.40%, K is 1.32%, V is 1.09%, H is 1.06%, I is 0.23%, P is 0.23%, Q is 0.12%, C is 0.11%, M is 0.11% and F is 0.08%,
wherein X4 encodes such that G is 37.46%, A is 13.29%, Y is 10.44%, W is 6.05%, D is 5.29%, E is 5.15%, R is 4.13%, S is 3.16%, F is 3.09%, P is 2.74%, H is 2.30%, T is 1.72%, L is 1.25%, M is 1.17%, N is 1.11%, V is 1.08%, K is 0.20%, I is 0.18%, C is 0.09% and Q is 0.08%,
wherein X5 encodes such that F is 43.63%, M is 18.58%, L is 8.83%, G is 6.34%, P is 3.95%, I is 3.39%, W is 2.48%, S is 2.34%, V is 2.23%, Q is 1.58%, Y is 1.49%, A is 1.26%, R is 1.00%, C is 0.99%, H is 0.62%, T is 0.62%, D is 0.24%, N is 0.21%, E is 0.15% and K is 0.03%,
wherein X6 encodes such that D is 77.08%, G is 5.05%, A is 3.75%, K is 3.07%, Y is 2.84%, S is 2.40%, T is 1.32%, R is 1.16%, E is 1.12%, V is 0.94%, L is 0.59%, F is 0.15%, H is 0.14%, N is 0.09%, M is 0.08%, P is 0.06%, I is 0.05%, C is 0.03% and Q is 0.03%, and
wherein X7 encodes such that Y is 49.26%, V is 20.01%, I is 8.62%, S is 3.92%, P is 3.53%, N is 3.34%, F is 3.01%, L is 2.98%, G is 1.84%, D is 1.28%, R is 0.67%, H is 0.55%, T is 0.55%, A is 0.12%, K is 0.08%, M is 0.08%, C is 0.06% and W is 0.05%;
when the length of the modified CDRH3 is 8 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8 (SEQ ID NO. 117),
wherein X1 encodes such that G is 33.76%, D is 10.40%, E is 9.17%, V is 8.12%, R is 6.24%, Y is 4.95%, K is 4.73%, F is 4.56%, I is 3.98%, W is 3.93%, L is 3.54%, N is 3.17%, H is 1.54%, S is 1.29%, A is 0.18%, C is 0.13%, T is 0.11%, P is 0.05% and M is 0.04%,
wherein X2 encodes such that G is 18.07%, L is 10.46%, S is 7.48%, T is 6.21%, P is 6.05%, F is 6.02%, R is 5.58%, Y is 5.51%, D is 5.22%, E is 4.27%, A is 3.90%, I is 3.51%, N is 3.28%, W is 3.27%, V is 2.77%, M is 2.62%, K is 2.25%, H is 2.00%, Q is 1.46% and C is 0.05%,
wherein X3 encodes such that G is 14.48%, S is 9.89%, R is 8.88%, Y is 7.85%, L is 7.23%, H is 6.09%, I is 5.98%, A is 4.41%, D is 3.99%, P is 3.76%, E is 3.72%, Q is 3.56%, W is 3.46%, N is 3.30%, T is 2.82%, M is 2.71%, F is 2.69%, V is 2.15%, C is 1.73% and K is 1.28%,
wherein X4 encodes such that G is 28.59%, S is 8.39%, R is 8.36%, W is 7.71%, A is 6.07%, V is 6.04%, N is 5.44%, D is 4.55%, F is 4.00%, Y is 3.53%, K is 2.65%, T is 2.63%, H is 2.22%, Q is 2.20%, L is 1.93%, M is 1.60%, E is 1.52%, I is 1.39%, P is 1.04% and C is 0.13%,
wherein X5 encodes such that A is 18.48%, G is 17.93%, S is 9.53%, Y is 8.37%, L is 6.58%, R is 5.24%, D is 4.89%, P is 3.79%, V is 3.72%, T is 3.20%, M is 2.73%, H is 2.61%, W is 2.57%, E is 2.43%, N is 2.19%, F is 1.82%, C is 1.60%, Q is 1.12%, I is 1.08% and K is 0.09%,
wherein X6 encodes such that F is 35.24%, L is 12.91%, A is 9.55%, I is 7.50%, G is 4.40%, Y is 4.38%, V is 3.54%, S is 3.48%, D is 3.13%, N is 2.99%, H is 2.91%, W is 2.28%, E is 2.27%, M is 1.58%, P is 1.47%, C is 0.78%, Q is 0.75%, T is 0.68%, R is 0.10% and K is 0.06%,
wherein X7 encodes such that D is 78.56%, G is 4.18%, E is 2.32%, A is 1.94%, H is 1.84%, S is 1.39%, V is 1.34%, K is 1.04%, Y is 1.03%, F is 0.98%, L is 0.94%, N is 0.93%, R is 0.88%, C is 0.76%, P is 0.68%, Q is 0.56%, T is 0.56% and I is 0.06%, and
wherein X8 encodes such that Y is 53.04%, G is 11.28%, S is 5.38%, N is 4.74%, P is 4.64%, D is 3.78%, V is 3.23%, R is 3.18%, I is 3.03%, F is 2.61%, K is 1.02%, L is 1.01%, H is 0.90%, A is 0.89%, W is 0.58%, T is 0.53% and C is 0.06%;
when the length of the modified CDRH3 is 9 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9 (SEQ ID NO. 118),
wherein X1 encodes such that G is 43.79%, D is 20.00%, S is 5.55%, E is 5.28%, R is 4.93%, L is 3.53%, V is 3.44%, K is 2.25%, H is 1.92%, I is 1.78%, Q is 1.51%, M is 1.29%, P is 0.98%, F is 0.96%, W is 0.93%, N is 0.68%, A is 0.55%, Y is 0.37%, T is 0.20% and C is 0.03%,
wherein X2 encodes such that G is 17.08%, S is 9.50%, R is 9.19%, Y is 7.46%, L is 6.35%, H is 5.60%, I is 5.54%, A is 4.66%, E is 4.51%, D is 4.20%, Q is 3.63%, P is 3.49%, W is 3.49%, T is 2.87%, N is 2.83%, V is 2.52%, M is 2.41%, F is 1.92%, C is 1.69% and K is 1.04%,
wherein X3 encodes such that G is 14.76%, S is 10.20%, R is 9.45%, Y is 7.77%, L is 6.64%, I is 6.01%, H is 5.34%, A is 4.14%, D is 3.96%, Q is 3.93%, E is 3.89%, W is 3.73%, P is 3.57%, N is 3.24%, M is 2.88%, T is 2.88%, F is 2.31%, V is 2.18%, C is 1.92% and K is 1.19%,
wherein X4 encodes such that G is 15.10%, S is 9.89%, R is 9.10%, Y is 8.27%, L is 6.55%, I is 6.14%, H is 5.83%, D is 4.32%, E is 4.04%, P is 3.96%, A is 3.89%, Q is 3.66%, N is 3.36%, W is 3.21%, M is 2.72%, T is 2.54%, V is 2.15%, F is 2.13%, C is 2.04% and K is 1.06%,
wherein X5 encodes such that G is 15.44%, S is 9.76%, R is 9.50%, Y is 8.03%, L is 6.30%, I is 5.78%, H is 5.55%, D is 4.27%, A is 4.14%, E is 3.79%, P is 3.79%, Q is 3.75%, N is 3.13%, W is 3.05%, M is 2.82%, T is 2.75%, V is 2.52%, F is 2.36%, C is 2.13% and K is 1.07%,
wherein X6 encodes such that A is 24.67%, G is 12.08%, P is 9.19%, Y is 9.02%, S is 7.51%, W is 4.71%, D is 4.17%, N is 3.94%, L is 3.84%, H is 3.44%, R is 3.21%, T is 2.51%, F is 2.05%, E is 1.94%, V is 1.78%, I is 1.53%, M is 1.45%, K is 1.09%, C is 1.01% and Q is 0.85%,
wherein X7 encodes such that F is 44.15%, L is 11.63%, Y is 8.50%, I is 6.87%, S is 5.49%, M is 4.61%, P is 3.71%, V is 3.11%, A is 2.65%, G is 2.13%, H is 1.55%, Q is 1.55%, N is 1.12%, D is 0.99%, W is 0.85%, T is 0.80%, E is 0.15%, R is 0.07% and C is 0.03%,
wherein X8 encodes such that D is 76.27%, G is 4.51%, E is 2.20%, H is 2.12%, A is 1.94%, S is 1.82%, V is 1.66%, L is 1.12%, Y is 1.07%, K is 1.06%, P is 1.06%, C is 0.96%, N is 0.93%, F is 0.86%, R is 0.83%, Q is 0.77%, T is 0.75% and I is 0.05%, and
wherein X9 encodes such that Y is 50.77%, G is 10.94%, S is 5.41%, P is 5.26%, N is 4.74%, D is 4.10%, R is 3.97%, V is 3.83%, I is 3.11%, F is 2.59%, L is 1.17%, H is 1.04%, K is 0.94%, A is 0.88%, W is 0.55%, T is 0.44%, C is 0.10%, M is 0.03% and Q is 0.03%;
when the length of the modified CDRH3 is 10 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10 (SEQ ID NO. 119),
wherein X1 encodes such that G is 27.45%, D is 23.76%, E is 14.63%, V is 7.40%, R is 5.28%, Y is 3.59%, S is 2.96%, L is 2.25%, H is 1.88%, M is 1.81%, K is 1.68%, Q is 1.61%, W is 1.51%, P is 1.42%, I is 0.91%, A is 0.69%, N is 0.66%, T is 0.34%, F is 0.12% and C is 0.05%,
wherein X2 encodes such that G is 16.66%, S is 9.67%, R is 9.13%, Y is 7.84%, L is 6.40%, I is 5.96%, D is 5.13%, H is 4.91%, E is 4.59%, A is 4.11%, Q is 3.45%, W is 3.40%, P is 3.12%, N is 2.95%, M is 2.78%, T is 2.74%, F is 2.44%, V is 1.93%, C is 1.79% and K is 0.97%,
wherein X3 encodes such that G is 16.34%, S is 10.57%, R is 9.97%, Y is 7.87%, L is 6.01%, H is 5.52%, I is 5.08%, D is 3.98%, E is 3.86%, A is 3.71%, Q is 3.71%, P is 3.57%, W is 3.44%, N is 3.25%, T is 2.86%, M is 2.79%, V is 2.47%, F is 2.27%, C is 1.51% and K is 1.20%,
wherein X4 encodes such that G is 16.80%, S is 10.43%, R is 9.70%, Y is 8.04%, I is 5.94%, L is 5.38%, H is 5.16%, D is 4.33%, E is 4.18%, A is 3.88%, W is 3.79%, Q is 3.52%, N is 3.15%, P is 2.78%, F is 2.49%, M is 2.42%, T is 2.40%, V is 2.35%, C is 1.76% and K is 1.44%,
wherein X5 encodes such that G is 14.66%, S is 10.29%, R is 10.04%, Y is 8.36%, L is 5.79%, H is 5.28%, I is 5.20%, E is 4.61%, D is 4.15%, W is 4.01%, A is 4.00%, Q is 3.93%, M is 3.22%, N is 3.22%, P is 3.00%, T is 2.54%, V is 2.40%, F is 2.18%, C is 1.86% and K is 1.19%,
wherein X6 encodes such that G is 15.31%, S is 10.45%, R is 9.91%, Y is 9.13%, I is 5.44%, H is 5.35%, L is 4.72%, D is 4.71%, A is 4.20%, E is 4.18%, W is 3.40%, Q is 3.20%, M is 3.18%, N is 3.10%, P is 2.81%, F is 2.78%, V is 2.62%, T is 2.56%, C is 1.73% and K is 1.22%,
wherein X7 encodes such that A is 26.92%, G is 16.10%, Y is 11.80%, D is 5.98%, W is 5.79%, S is 4.45%, R is 4.20%, P is 4.00%, L is 3.42%, H is 2.79%, F is 2.64%, E is 2.62%, I is 2.57%, V is 2.17%, T is 1.98%, N is 1.22%, Q is 1.02%, K is 0.10%, M is 0.10% and C is 0.07%,
wherein X8 encodes such that F is 55.93%, L is 8.74%, M is 5.33%, Y is 5.15%, G is 5.11%, I is 5.05%, S is 3.78%, E is 2.30%, V is 1.78%, N is 1.35%, P is 1.22%, C is 1.15%, W is 1.15%, H is 0.91%, T is 0.54%, D is 0.22%, A is 0.17%, R is 0.07% and Q is 0.03%
wherein X9 encodes such that D is 79.00%, G is 3.86%, E is 2.13%, H is 1.98%, A is 1.74%, S is 1.54%, K is 1.32%, R is 1.12%, V is 1.10%, Y is 1.08%, N is 0.91%, L is 0.90%, C is 0.85%, P is 0.78%, Q is 0.66%, F is 0.56%, T is 0.37%, I is 0.05% and M is 0.03%, and
wherein X10 encodes such that Y is 50.54%, G is 12.58%, S is 6.42%, N is 4.76%, P is 4.08%, D is 4.05%, R is 3.81%, V is 3.61%, I is 3.03%, F is 2.32%, K is 1.02%, A is 0.98%, H is 0.85%, W is 0.81%, L is 0.61%, T is 0.44% and C is 0.03%;
when the length of the modified CDRH3 is 11 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11 (SEQ ID NO. 120),
wherein X1 encodes such that G is 26.14%, D is 24.10%, E is 13.67%, V is 7.72%, R is 5.62%, A is 0.58%, C is 0.16%, F is 0.10%, H is 2.04%, I is 0.80%, K is 1.93%, L is 2.37%, M is 1.83%, N is 0.68%, P is 1.61%, Q is 1.96%, S is 2.53%, T is 0.29%, W is 1.67% and Y is 4.10%,
wherein X2 encodes such that G is 15.23%, S is 9.80%, R is 9.57%, Y is 7.08%, L is 6.77%, I is 6.30%, H is 5.17%, A is 4.53%, C is 1.60%, D is 4.03%, E is 4.79%, F is 2.30%, K is 1.30%, M is 2.55%, N is 2.74%, P is 3.72%, Q is 3.79%, T is 2.66%, V is 2.51% and W is 3.56%,
wherein X3 encodes such that G is 14.63%, S is 10.56%, R is 10.06%, Y is 7.37%, L is 6.21%, I is 6.13%, H is 5.15%, A is 4.34%, C is 2.06%, D is 4.01%, E is 4.08%, F is 2.51%, K is 1.21%, M is 3.01%, N is 2.98%, P is 2.90%, Q is 3.70%, T is 3.25%, V is 2.16% and W is 3.66%,
wherein X4 encodes such that G is 15.29%, R is 10.35%, S is 9.76%, Y is 8.99%, L is 5.56%, I is 5.49%, H is 5.15%, A is 4.01%, C is 1.61%, D is 4.05%, E is 4.47%, F is 2.24%, K is 1.03%, M is 2.82%, N is 3.40%, P is 3.27%, Q is 3.85%, T is 2.82%, V is 2.24% and W is 3.54%,
wherein X5 encodes such that G is 14.88%, S is 11.42%, R is 9.61%, Y is 8.34%, L is 6.05%, I is 5.41%, H is 5.14%, A is 4.53%, C is 1.54%, D is 4.53%, E is 3.93%, F is 2.47%, K is 1.44%, M is 2.74%, N is 2.98%, P is 3.07%, Q is 3.81%, T is 2.49%, V is 2.26% and W is 3.37%,
wherein X6 encodes such that G is 16.13%, S is 10.60%, R is 9.14%, Y is 8.52%, I is 5.84%, H is 5.31%, L is 5.27%, A is 3.66%, C is 1.81%, D is 4.28%, E is 4.45%, F is 2.43%, K is 1.23%, M is 2.82%, N is 3.33%, P is 2.90%, Q is 3.38%, T is 2.70%, V is 2.14% and W is 4.01%,
wherein X7 encodes such that G is 14.84%, S is 10.37%, R is 10.00%, Y is 8.87%, I is 5.89%, H is 5.21%, L is 5.21%, A is 4.32%, C is 1.63%, D is 4.98%, E is 4.30%, F is 2.24%, K is 1.19%, M is 3.07%, N is 3.54%, P is 2.98%, Q is 3.29%, T is 2.43%, V is 2.41% and W is 3.17%,
wherein X8 encodes such that A is 20.31%, Y is 19.12%, G is 14.26%, S is 6.17%, P is 5.78%, C is 1.07%, D is 4.90%, E is 1.21%, F is 2.10%, H is 1.52%, I is 2.22%, K is 1.52%, L is 2.74%, M is 0.06%, N is 4.20%, Q is 0.95%, R is 2.18%, T is 3.85%, V is 1.07% and W is 4.77%,
wherein X9 encodes such that F is 54.27%, M is 12.12%, L is 11.52%, A is 0.04%, C is 0.91%, D is 1.09%, E is 1.17%, G is 2.61%, H is 0.10%, I is 4.34%, N is 0.97%, P is 3.05%, Q is 0.78%, S is 1.13%, T is 0.54%, V is 2.63%, W is 0.93% and Y is 1.77%,
wherein X10 encodes such that D is 77.57%, A is 1.65%, C is 0.54%, E is 2.04%, F is 0.58%, G is 3.93%, H is 2.28%, K is 1.21%, L is 1.09%, N is 1.26%, P is 0.99%, Q is 0.66%, R is 1.11%, S is 1.95%, T is 0.62%, V is 1.34%, and Y is 1.11%, and
wherein X11 encodes such that Y is 49.60%, G is 11.15%, S is 6.21%, A is 0.82%, C is 0.04%, D is 4.49%, F is 2.76%, H is 0.78%, I is 3.42%, K is 1.34%, L is 0.70%, M is 0.08%, N is 4.40%, P is 4.22%, R is 4.14%, T is 0.47%, V is 4.71% and W is 0.62%;
when the length of the modified CDRH3 is 12 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12 (SEQ ID NO. 121),
wherein X1 encodes such that G is 26.20%, D is 24.18%, E is 14.76%, V is 7.81%, R is 5.18%, Y is 3.56%, S is 2.82%, L is 2.21%, H is 2.11%, M is 1.96%, Q is 1.83%, P is 1.62%, W is 1.58%, K is 1.47%, I is 0.95%, A is 0.72%, N is 0.59%, T is 0.23%, C is 0.13% and F is 0.06%,
wherein X2 encodes such that G is 16.11%, R is 10.28%, S is 10.09%, Y is 7.31%, L is 5.96%, I is 5.73%, H is 5.31%, E is 4.74%, D is 4.51%, Q is 3.98%, A is 3.60%, P is 3.52%, N is 3.31%, W is 2.82%, M is 2.67%, T is 2.63%, F is 2.42%, V is 2.09%, C is 1.71% and K is 1.16%,
wherein X3 encodes such that G is 15.16%, S is 10.21%, R is 10.15%, Y is 8.19%, L is 6.55%, I is 6.19%, H is 5.69%, E is 4.17%, Q is 4.02%, D is 3.77%, N is 3.58%, P is 3.50%, A is 3.43%, W is 3.18%, T is 2.65%, M is 2.51%, F is 2.08%, V is 2.04%, C is 1.90% and K is 1.01%,
wherein X4 encodes such that G is 16.07%, R is 10.64%, S is 9.77%, Y is 7.25%, L is 6.13%, I is 5.92%, H is 4.59%, E is 4.57%, D is 4.09%, A is 4.04%, W is 3.62%, P is 3.43%, Q is 3.43%, N is 3.12%, M is 2.99%, T is 2.91%, F is 2.44%, V is 2.04%, C is 1.77% and K is 1.10%,
wherein X5 encodes such that G is 15.00%, S is 10.43%, R is 10.28%, Y is 8.13%, L is 5.79%, H is 5.48%, I is 5.37%, Q is 4.36%, E is 4.25%, D is 4.23%, A is 3.96%, W is 3.67%, P is 3.64%, N is 3.24%, M is 2.68%, T is 2.23%, V is 2.21%, F is 1.88%, C is 1.79% and K is 1.33%,
wherein X6 encodes such that G is 15.16%, S is 10.47%, R is 10.11%, Y is 7.79%, I is 6.55%, L is 5.69%, H is 5.20%, E is 4.53%, D is 4.49%, A is 4.17%, W is 3.66%, Q is 3.37%, N is 3.27%, M is 2.78%, P is 2.72%, F is 2.46%, T is 2.38%, V is 2.19%, C is 1.66% and K is 1.35%,
wherein X7 encodes such that G is 14.95%, R is 10.11%, S is 10.03%, Y is 8.57%, H is 6.68%, I is 5.60%, L is 5.35%, D is 4.07%, A is 3.96%, E is 3.96%, N is 3.62%, P is 3.35%, W is 3.16%, Q is 3.03%, M is 2.97%, F is 2.59%, T is 2.55%, V is 2.32%, C is 1.81% and K is 1.28%,
wherein X8 encodes such that G is 18.74%, Y is 18.39%, D is 13.25%, N is 6.42%, S is 5.69%, R is 5.52%, P is 4.82%, H is 3.26%, E is 2.74%, T is 2.68%, V is 2.59%, A is 2.51%, I is 2.36%, F is 2.34%, C is 1.87%, W is 1.47%, K is 1.45%, L is 1.41%, Q is 1.22% and M is 1.14%,
wherein X9 encodes such that G is 20.39%, A is 18.34%, Y is 17.65%, W is 9.03%, P is 6.23%, S is 4.34%, R is 2.88%, L is 2.74%, C is 2.48%, T is 2.38%, F is 2.17%, H is 2.02%, M is 1.81%, D is 1.58%, V is 1.37%, N is 1.28%, I is 1.16%, E is 1.09%, Q is 0.80% and K is 0.15%,
wherein X10 encodes such that F is 52.70%, L is 12.64%, M is 11.69%, I is 4.76%, P is 3.16%, G is 3.03%, V is 2.44%, Y is 1.73%, S is 1.31%, E is 1.16%, D is 1.10%, W is 0.93%, N is 0.89%, Q is 0.86%, T is 0.74%, C is 0.65% and A is 0.15%,
wherein X11 encodes such that D is 78.03%, G is 4.09%, E is 2.06%, A is 1.87%, H is 1.87%, S is 1.58%, K is 1.43%, V is 1.41%, N is 1.14%, L is 1.01%, Y is 0.99%, T is 0.88%, P is 0.82%, R is 0.80%, Q is 0.67%, F is 0.65%, C is 0.57%, I is 0.06% and M is 0.04%, and
wherein X12 encodes such that Y is 49.52%, G is 11.90%, S is 6.26%, N is 4.65%, D is 4.36%, V is 4.27%, P is 3.96%, I is 3.60%, R is 3.50%, F is 2.49%, K is 1.20%, A is 0.95%, W is 0.88%, L is 0.86%, H is 0.84%, T is 0.48%, M is 0.11%, C is 0.06% and E is 0.04%;
when the length of the modified CDRH3 is 13 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13 (SEQ ID NO. 122),
wherein X1 encodes such that G is 25.88%, D is 22.97%, E is 14.18%, V is 7.62%, R is 5.85%, A is 0.73%, C is 0.10%, F is 0.02%, H is 2.15%, I is 0.79%, K is 2.03%, L is 2.46%, M is 2.09%, N is 0.61%, P is 1.86%, Q is 1.80%, S is 3.49%, T is 0.31%, W is 1.65% and Y is 3.34%,
wherein X2 encodes such that G is 16.85%, S is 10.07%, R is 9.77%, Y is 7.60%, L is 5.83%, H is 5.41%, I is 5.24%, A is 4.72%, C is 1.92%, D is 4.39%, E is 4.43%, F is 2.09%, K is 1.04%, M is 2.46%, N is 3.28%, P is 3.70%, Q is 3.05%, T is 2.69%, V is 2.13% and W is 3.24%,
wherein X3 encodes such that G is 15.48%, S is 10.67%, R is 9.46%, Y is 7.41%, I is 6.52%, L is 6.45%, H is 5.03%, A is 4.39%, C is 1.86%, D is 4.03%, E is 3.78%, F is 2.13%, K is 1.42%, M is 2.78%, N is 3.34%, P is 3.49%, Q is 3.53%, T is 2.92%, V is 2.07% and W is 3.20%,
wherein X4 encodes such that G is 15.20%, S is 10.44%, R is 9.38%, Y is 7.54%, L is 6.10%, H is 5.91%, I is 5.51%, A is 4.18%, C is 1.71%, D is 4.51%, E is 4.26%, F is 2.28%, K is 1.25%, M is 2.90%, N is 3.07%, P is 3.53%, Q is 3.43%, T is 2.74%, V is 2.51% and W is 3.45%,
wherein X5 encodes such that G is 16.10%, S is 10.23%, R is 9.86%, Y is 7.58%, L is 5.64%, H is 5.53%, I is 5.24%, A is 4.43%, C is 1.84%, D is 4.62%, E is 4.22%, F is 2.44%, K is 1.50%, M is 2.57%, N is 3.47%, P is 3.07%, Q is 3.82%, T is 2.46%, V is 2.28% and W is 3.03%,
wherein X6 encodes such that G is 15.39%, S is 10.36%, R is 9.94%, Y is 7.81%, I is 6.58%, H is 5.60%, L is 5.33%, A is 3.47%, C is 1.75%, D is 4.47%, E is 4.55%, F is 2.32%, K is 1.34%, M is 2.59%, N is 3.22%, P is 3.07%, Q is 3.72%, T is 2.84%, V is 2.28% and W is 3.38%,
wherein X7 encodes such that G is 15.12%, S is 10.36%, R is 9.90%, Y is 8.67%, L is 6.24%, I is 5.45%, H is 5.05%, A is 3.76%, C is 1.78%, D is 4.72%, E is 4.62%, F is 2.49%, K is 1.27%, M is 2.53%, N is 3.32%, P is 3.24%, Q is 3.51%, T is 2.59%, V is 1.86% and W is 3.51%,
wherein X8 encodes such that G is 13.99%, S is 10.32%, R is 9.54%, Y is 9.31%, L is 6.12%, I is 5.68%, H is 5.30%, A is 4.09%, C is 1.73%, D is 4.80%, E is 3.97%, F is 2.40%, K is 1.67%, M is 2.88%, N is 3.34%, P is 3.24%, Q is 3.22%, T is 2.49%, V is 2.23% and W is 3.63%,
wherein X9 encodes such that Y is 18.73%, G is 17.44%, D is 10.42%, N is 9.54%, S is 7.31%, R is 5.14%, A is 2.67%, C is 1.78%, E is 3.84%, F is 4.51%, H is 3.40%, I is 1.61%, K is 2.72%, L is 2.38%, M is 0.06%, P is 1.98%, Q is 0.81%, T is 2.36%, V is 2.42 and W is 0.86%,
wherein X10 encodes such that A is 21.07%, Y is 19.84%, G is 18.30%, W is 6.83%, C is 2.17%, D is 2.32%, E is at 1.59%, F is 4.85%, H is 1.46%, I is 2.11%, K is 1.52%, L is 2.07%, M is 1.44%, N is 2.13%, P is 4.26%, Q is 0.08%, R is 1.34%, S is 3.72%, T is 1.02% and V is 1.86%,
wherein X11 encodes such that F is 54.39%, L is 12.43%, M is 11.51%, C is 0.81%, D is 1.21%, E is 1.11%, G is 2.74%, H is 0.06%, I is 4.34%, N is 0.94%, P is 2.61%, Q is 0.94%, S is 0.98%, T is 0.48%, V is 2.23%, W is 1.00% and Y is 2.13%,
wherein X12 encodes such that D is 77.80%, A is 1.92%, C is 0.50%, E is 2.19%, F is 0.86%, G is 4.03%, H is 1.84%, I is 0.10%, K is 1.27%, L is 1.11%, N is 1.11%, P is 0.75%, Q is 0.69%, R is 0.81%, S is 1.98%, T is 0.69%, V is 1.44%, and Y is 0.81%, and
wherein X13 encodes such that Y is 51.23%, G is 11.28%, S is 5.43%, V is 5.43%, A is 0.81%, C is 0.02%, D is 4.39%, F is 2.65%, H is 1.11%, I is 3.86%, K is 0.86%, L is 0.96%, M is 0.04%, N is 4.16%, P is 3.38%, Q is 0.04%, R is 3.13%, T is 0.52% and W is 0.56%:
when the length of the modified CDRH3 is 14 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14 (SEQ ID NO. 123),
wherein X1 encodes such that G is 24.96%, D is 23.95%, E is 15.20%, V is 6.94%, R is 5.78%, Y is 3.32%, S is 3.08%, L is 2.72%, M is 2.26%, H is 2.22%, Q is 2.17%, P is 1.82%, W is 1.63%, K is 1.49%, A is 0.81%, I is 0.70%, N is 0.46%, T is 0.35% and C is 0.07%,
wherein X2 encodes such that G is 17.46%, R is 9.69%, S is 9.42%, Y is 7.05%, L is 5.76%, I is 5.47%, E is 4.68%, D is 4.66%, H is 4.66%, A is 4.46%, P is 3.58%, N is 3.49%, W is 3.25%, Q is 2.99%, M is 2.77%, T is 2.64%, F is 2.48%, V is 2.37%, C is 1.80% and K is 1.30%,
wherein X3 encodes such that G is 16.37%, S is 10.22%, R is 8.94%, Y is 7.10%, L is 6.85%, I is 6.24%, H is 5.16%, E is 4.15%, D is 3.91%, W is 3.80%, Q is 3.65%, A is 3.58%, N is 3.56%, P is 3.41%, M is 3.12%, F is 2.33%, T is 2.26%, C is 2.02%, V is 1.89% and K is 1.41%,
wherein X4 encodes such that G is 14.54%, S is 10.61%, R is 9.53%, Y is 7.54%, I is 6.41%, L is 6.26%, H is 5.43%, D is 4.35%, E is 4.04%, A is 3.62%, N is 3.41%, Q is 3.41%, T is 3.25%, M is 3.16%, P is 3.10%, W is 2.94%, V is 2.55%, F is 2.42%, C is 2.00% and K is 1.43%,
wherein X5 encodes such that G is 15.69%, S is 10.76%, R is 10.04%, Y is 7.89%, L is 5.89%, I is 5.78%, H is 5.40%, D is 4.96%, E is 4.28%, A is 4.26%, Q is 3.30%, N is 3.23%, W is 3.01%, P is 2.86%, M is 2.70%, F is 2.37%, T is 2.33%, V is 2.17%, C is 1.58% and K is 1.45%,
wherein X6 encodes such that G is 15.03%, S is 10.35%, R is 9.89%, Y is 7.86%, L is 5.82%, I is 5.76%, H is 5.27%, D is 4.59%, E is 4.15%, A is 4.02%, N is 3.58%, P is 3.45%, Q is 3.45%, W is 3.41%, F is 3.01%, T is 2.64%, M is 2.59%, V is 2.17%, C is 1.49% and K is 1.38%,
wherein X7 encodes such that G is 14.63%, S is 11.47%, R is 9.82%, Y is 7.91%, I is 6.37%, L is 5.62%, H is 5.16%, E is 4.75%, D is 4.42%, A is 4.20%, Q is 3.32%, W is 3.32%, N is 3.27%, M is 2.75%, P is 2.50%, T is 2.50%, F is 2.42%, V is 2.24%, C is 1.87% and K is 1.36%,
wherein X8 encodes such that G is 14.78%, S is 11.07%, R is 10.26%, Y is 8.72%, I is 5.60%, L is 5.40%, H is 5.03%, D is 4.81%, E is 4.81%, A is 4.11%, W is 3.38%, N is 3.25%, P is 3.05%, Q is 2.88%, M is 2.83%, V is 2.42%, T is 2.37%, F is 2.22%, C is 1.49% and K is 1.47%,
wherein X9 encodes such that G is 14.10%, S is 11.16%, R is 10.22%, Y is 8.72%, I is 5.56%, H is 5.43%, L is 5.14%, D is 4.92%, E is 4.92%, A is 3.76%, Q is 3.49%, N is 3.19%, W is 3.08%, M is 2.86%, F is 2.79%, P is 2.53%, T is 2.17%, V is 2.17%, C is 2.09% and K is 1.60%,
wherein X10 encodes such that Y is 15.55%, R is 10.26%, G is 8.88%, P is 7.32%, D is 6.57%, I is 5.93%, E is 5.78%, A is 5.16%, S is 4.75%, V is 4.57%, L is 4.22%, F is 4.02%, Q is 3.98%, T is 3.03%, W is 2.11%, N is 2.04%, C is 1.93%, M is 1.41%, K is 1.27% and H is 1.16%,
wherein X11 encodes such that A is 20.45%, G is 19.46%, Y is 16.61%, W is 9.47%, P is 5.36%, F is 4.09%, S is 3.30%, L is 3.19%, H is 2.77%, T is 2.57%, V is 2.57%, N is 2.37%, C is 2.17%, R is 1.82%, K is 1.58%, D is 1.19%, I is 0.70%, E is 0.15% and Q is 0.09%,
wherein X12 encodes such that F is 54.77%, L is 11.97%, M is 10.79%, I is 4.88%, G is 3.12%, P is 3.05%, V is 2.33%, Y is 1.78%, D is 1.23%, E is 1.05%, N is 0.92%, S is 0.90%, W is 0.88%, C is 0.83%, Q is 0.77%, T is 0.59% and A is 0.09%,
wherein X13 encodes such that D is 77.07%, G is 4.37%, E is 2.11%, H is 1.98%, A is 1.93%, S is 1.85%, N is 1.54%, V is 1.45%, K is 1.05%, L is 1.05%, Q is 0.90%, R is 0.90%, Y is 0.86%, C is 0.81%, P is 0.81%, F is 0.70%, T is 0.57% and I is 0.04%, and
wherein X14 encodes such that Y is 46.09%, V is 17.38%, I is 16.17%, S is 4.88%, H is 3.21%, N is 2.94%, D is 2.66%, F is 1.96%, A is 1.16%, R is 1.14%, L is 0.83%, T is 0.75%, G is 0.26%, P is 0.26% and M is 0.13%;
when the length of the modified CDRH3 is 15 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15 (SEQ ID NO. 124),
wherein X1 encodes such that G is 24.51%, D is 24.03%, E is 14.58%, V is 7.89%, R is 5.96%, Y is 2.98%, S is 2.91%, L is 2.82%, Q is 2.43%, H is 2.18%, M is 2.13%, P is 1.65%, K is 1.63%, W is 1.22%, A is 0.92%, N is 0.80%, I is 0.78%, T is 0.37%, C is 0.07%, F is 0.07%,
wherein X2 encodes such that G is 17.63%, S is 10.41%, R is 10.13%, Y is 7.06%, L is 6.19%, I is 5.89%, H is 4.75%, D is 4.03%, A is 4.01%, E is 3.85%, P is 3.44%, W is 3.42%, N is 3.32%, Q is 3.23%, M is 2.89%, T is 2.75%, F is 2.02%, V is 1.97%, C is 1.63% and K is 1.35%,
wherein X3 encodes such that G is 15.77%, S is 9.74%, R is 9.26%, Y is 7.75%, L is 6.05%, I is 5.73%, H is 5.64%, E is 4.79%, D is 4.49%, A is 4.45%, P is 3.62%, Q is 3.62%, W is 3.44%, M is 3.03%, N is 2.91%, T is 2.45%, F is 2.25%, C is 1.88%, V is 1.74% and K is 1.28%,
wherein X4 encodes such that G is 15.41%, S is 11.03%, R is 9.58%, Y is 7.82%, L is 6.21%, I is 5.46%, H is 5.14%, D is 4.03%, Q is 4.01%, A is 3.92%, E is 3.76%, P is 3.58%, W is 3.48%, N is 2.98%, M is 2.93%, T is 2.66%, V is 2.48%, F is 2.29%, C is 1.99% and K is 1.17%,
wherein X5 encodes such that G is 15.06%, S is 10.84%, R is 10.32%, Y is 7.40%, I is 5.75%, L is 5.43%, H is 4.75%, D is 4.49%, E is 4.42%, A is 3.99%, N is 3.42%, Q is 3.42%, W is 3.42%, P is 3.09%, F is 2.82%, M is 2.75%, T is 2.73%, V is 2.29%, C is 2.02% and K is 1.56%,
wherein X6 encodes such that G is 15.15%, S is 10.80%, R is 10.09%, Y is 7.15%, L is 6.12%, I is 5.96%, H is 5.59%, E is 4.26%, D is 4.15%, A is 4.10%, W is 3.69%, N is 3.46%, P is 3.12%, Q is 3.00%, M is 2.98%, T is 2.45%, F is 2.43%, V is 2.20%, C is 2.04% and K is 1.19%,
wherein X7 encodes such that G is 15.77%, S is 11.33%, R is 9.01%, Y is 7.91%, I is 6.28%, L is 5.82%, H is 4.86, A is 4.68%, E is 4.29%, D is 4.24%, W is 3.65%, Q is 3.23%, M is 3.14%, N is 2.89%, P is 2.66%, F is 2.38%, V is 2.18%, C is 2.13%, T is 1.97% and K is 1.54%,
wherein X8 encodes such that G is 14.51%, S is 11.65%, R is 9.67%, Y is 7.29%, I is 5.91%, H is 5.82%, L is 4.91%, D is 4.68%, E is 4.49%, A is 4.36%, W is 4.15%, N is 3.44%, Q is 3.14%, T is 3.03%, M is 2.73%, P is 2.61%, F is 2.32%, V is 2.32%, K is 1.54% and C is 1.38%,
wherein X9 encodes such that Y is 14.24%, R is 11.10%, G is 9.67%, P is 7.66%, D is 6.17%, E is 5.50%, A is 5.48%, I is 5.34%, S is 5.20%, V is 4.86%, L is 4.70%, Q is 4.15%, F is 3.74%, T is 3.12%, N is 1.93%, C is 1.79%, W is 1.77%, M is 1.35%, K is 1.17%, H is 1.01%,
wherein X10 encodes such that Y is 15.13%, R is 10.45%, G is 9.31%, P is 6.92%, D is 6.79%, E is 5.66%, I is 5.32%, S is 5.18%, L is 4.86%, A is 4.84%, Q is 4.72%, V is 4.72%, F is 3.23%, T is 2.84%, N is 2.34%, W is 1.77%, C is 1.70%, M is 1.54%, H is 1.33% and K is 1.31%,
wherein X11 encodes such that Y is 16.25%, R is 9.67%, G is 8.78%, P is 7.40%, D is 6.63%, I is 5.64%, A is 5.14%, E is 5.02%, V is 4.97%, S is 4.91%, L is 4.47%, Q is 4.10%, F is 4.03%, T is 2.82%, N is 2.73%, C is 2.06%, W is 1.51%, M is 1.44%, K is 1.33% and H is 0.92%,
wherein X12 encodes such that G is 28.40%, A is 22.01%, Y is 13.78%, W is 6.12%, S is 5.11%, F is 4.38%, R is 3.42%, P is 3.12%, N is 2.77%, L is 2.75%, I is 1.90%, V is 1.83%, D is 1.77%, T is 1.10%, Q is 0.99%, C is 0.21%, E is 0.18%, H is 0.09% and K is 0.05%
wherein X13 encodes such that F is 54.81%, M is 12.10%, L is 11.23%, I is 4.42%, G is 3.21%, V is 2.80%, P is 2.43%, Y is 1.74%, E is 1.22%, D is 1.05%, S is 1.01%, W is 0.94%, C is 0.87%, Q is 0.83%, N is 0.78%, T is 0.48% and A is 0.05%,
wherein X14 encodes such that D is 77.42%, G is 4.08%, S is 2.04%, E is 2.02%, H is 2.02%, A is 1.65%, V is 1.44%, K is 1.38%, N is 1.33%, Q is 1.03%, C is 0.94%, L is 0.87%, R is 0.83%, F is 0.80%, Y is 0.80%, P is 0.69%, T is 0.57% and I is 0.07%, and
wherein X15 encodes such that Y is 45.62%, I is 17.08%, V is 16.46%, S is 5.23%, H is 2.98%, D is 2.96%, N is 2.54%, F is 2.29%, L is 1.44%, T is 1.01%, A is 0.99%, R is 0.85%, P is 0.23%, M is 0.09%, G is 0.07% and C is 0.05%;
when the length of the modified CDRH3 is 16 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16 (SEQ ID NO. 125),
wherein X1 encodes such that G is 23.28%, D is 21.54%, E is 12.51%, R is 6.40%, V is 6.34%, S is 3.90%, H is 3.49%, Q is 3.26%, Y is 3.20%, L is 3.03%, A is 2.44%, P is 2.44%, M is 2.39%, K is 1.86%, W is 1.11%, I is 0.93%, N is 0.87%, T is 0.70%, C is 0.12% and F is 0.12%,
wherein X2 encodes such that G is 19.85%, P is 16.94%, R is 9.72%, Y is 6.40%, S is 6.17%, L is 5.70%, A is 4.71%, K is 4.48%, Q is 3.90%, V is 3.84%, I is 3.26%, E is 2.50%, D is 2.33%, N is 2.33%, T is 2.10%, M is 1.75%, F is 1.57%, H is 1.28%, W is 0.81% and C is 0.35%,
wherein X3 encodes such that G is 13.85%, S is 10.48%, R is 8.91%, Y is 8.91%, L is 6.58%, H is 6.29%, I is 5.94%, A is 4.71%, E is 4.54%, D is 4.42%, Q is 4.13%, P is 3.61%, N is 3.03%, T is 2.97%, W is 2.56%, C is 2.39%, V is 2.04%, M is 1.92%, F is 1.75% and K is 0.99%,
wherein X4 encodes such that G is 13.85%, R is 9.84%, Y is 9.66%, S is 9.02%, L is 7.92%, P is 6.00%, I is 5.41%, H is 5.18%, Q is 4.31%, D is 4.19%, E is 3.20%, A is 3.08%, W is 3.03%, N is 2.85%, T is 2.74%, F is 2.62%, M is 2.39%, V is 1.86%, C is 1.69% and K is 1.11%,
wherein X5 encodes such that G is 12.86%, R is 10.01%, Y is 9.84%, S is 9.78%, L is 7.68%, A is 4.95%, H is 4.89%, I is 4.89%, Q is 3.90%, E is 3.78%, D is 3.73%, N is 3.67%, P is 3.61%, W is 3.61%, T is 3.08%, F is 2.85%, M is 2.04%, C is 1.98%, V is 1.63% and K is 1.16%,
wherein X6 encodes such that G is 12.92%, S is 11.29%, R is 9.14%, Y is 8.79%, I is 7.33%, H is 5.88%, L is 5.76%, W is 4.19%, A is 4.13%, D is 4.07%, Q is 3.78%, E is 3.61%, P is 3.61%, M is 2.79%, N is 2.56%, F is 2.50%, T is 2.27%, V is 2.21%, C is 1.92% and K is 1.22%,
wherein X7 encodes such that G is 13.80%, S is 10.54%, R is 9.66%, Y is 7.97%, H is 6.69%, I is 5.88%, L is 5.76%, E is 4.95%, D is 4.42%, A is 3.78%, P is 3.73%, Q is 3.43%, N is 3.32%, F is 2.85%, W is 2.85%, T is 2.74%, M is 2.10%, V is 2.10%, C is 2.04% and K is 1.28%,
wherein X8 encodes such that G is 13.39%, S is 10.36%, R is 9.49%, Y is 7.80%, L is 6.75%, I is 5.94%, H is 5.59% D is 4.95%, A is 4.77%, T is 3.96%, M is 3.73%, Q is 3.73%, E is 3.67%, P is 3.38%, W is 2.79%, N is 2.74%, F is 2.21%, V is 2.10%, C is 1.51% and K is 1.16%,
wherein X9 encodes such that Y is 15.83%, G is 8.91%, R is 8.21%, P is 7.51%, A is 6.46%, L is 5.94%, D is 5.82%, I is 5.59%, V is 4.89%, S is 4.77%, E is 4.37%, Q is 4.13%, T is 3.96%, F is 2.97%, N is 2.68%, C is 2.39%, M is 1.63%, W is 1.40%, H is 1.28% and K is 1.28%,
wherein X10 encodes such that Y is 16.94%, P is 10.30%, R is 9.60%, G is 7.16%, Q is 6.11%, D is 5.59%, I is 5.41%, S is 5.06%, A is 4.95%, V is 4.66%, L is 4.07%, T is 4.02%, E is 3.73%, F is 2.74%, W is 2.15%, N is 1.98%, C is 1.80%, H is 1.34%, M is 1.16% and K is 1.11%,
wherein X11 encodes such that Y is 15.77%, P is 11.76%, R is 8.15%, G is 7.22%, L is 6.46%, I is 6.00%, S is 5.18%, D is 5.12%, E is 4.77%, V is 4.66%, A is 4.60%, Q is 3.96%, F is 3.38%, T is 3.14%, N is 2.39%, C is 1.75%, K is 1.63%, H is 1.40%, W is 1.40% and M is 1.22%,
wherein X12 encodes such that Y is 16.41%, R is 8.96%, P is 8.21%, G is 7.74%, I is 5.70%, L is 5.70%, A is 5.47%, D is 5.47%, S is 5.24%, V is 5.24%, E is 4.77%, Q is 4.42%, T is 3.55%, F is 3.38%, N is 2.27%, W is 2.04%, C is 1.98%, H is 1.46%, K is 0.93% and M is 0.87%,
wherein X13 encodes such that G is 34.52%, A is 20.20%, Y is 13.10%, W is 8.15%, P is 4.95%, V is 3.14%, D is 2.62%, F is 2.39%, H is 2.39%, L is 1.92%, S is 1.69%, T is 1.69%, E is 0.99%, C is 0.87%, R is 0.58%, I is 0.47%, N is 0.17% and Q is 0.06%,
wherein X14 encodes such that F is 50.47%, M is 16.01%, L is 12.69%, I is 4.66%, V is 2.62%, P is 2.56%, Y is 2.04%, G is 1.92%, D is 1.57%, Q is 0.93%, E is 0.81%, C is 0.76%, T is 0.70%, W is 0.70%, N is 0.64%, S is 0.47%, A is 0.29%, and H is 0.17%,
wherein X15 encodes such that D is 76.37%, G is 4.19%, H is 2.27%, A is 2.21%, S is 1.69%, Y is 1.63%, V is 1.51%, E is 1.40%, R is 1.34%, K is 1.28%, F is 1.22%, T is 0.87%, N is 0.81%, P is 0.81%, C is 0.64%, L is 0.64%, Q is 0.52%, I is 0.29% and M is 0.29%, and
wherein X16 encodes such that Y is 40.28%, V is 21.42%, I is 15.48%, S is 5.18%, H is 3.73%, F is 2.91%, N is 2.79%, D is 2.21%, L is 1.57%, P is 1.34%, R is 0.99%, T is 0.99%, A is 0.64%, M is 0.17%, C is 0.06%, G is 0.06%, and K is 0.06%;
when the length of the modified CDRH3 is 17 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17 (SEQ ID NO. 126),
wherein X1 encodes such that D is 23.68%, G is 22.67%, E is 14.15%, V is 7.09%, R is 5.81%, Y is 3.46%, S is 3.40%, Q is 2.91%, P is 2.79%, H is 2.67%, L is 2.64%, M is 2.03%, K is 1.60%, A is 1.57%, W is 1.57%, T is 0.67%, N is 0.64%, I is 0.46%, C is 0.09% and F is 0.06%,
wherein X2 encodes such that R is 14.44%, L is 12.06%, G is 11.30%, P is 7.29%, A is 6.25%, Y is 6.16%, I is 5.87%, H is 4.88%, N is 4.56%, T is 4.48%, V is 4.10%, Q is 3.55%, K is 3.28%, S is 2.73%, E is 2.15%, D is 1.89%, W is 1.54%, F is 1.37%, M is 1.31% and C is 0.67%,
wherein X3 encodes such that G is 14.50%, S is 10.96%, R is 9.97%, Y is 7.47%, L is 6.77%, I is 6.66%, H is 5.90%, D is 4.48%, A is 3.89%, E is 3.49%, Q is 3.49%, P is 3.31%, T is 3.17%, N is 3.14%, W is 2.91%, M is 2.56%, F is 2.47%, C is 2.01%, V is 1.60% and K is 1.28%,
wherein X4 encodes such that Y is 14.71%, P is 10.52%, G is 9.01%, R is 8.95%, I is 6.66%, L is 5.58%, D is 5.55%, S is 5.26%, A is 5.17%, E is 4.45%, V is 4.30%, Q is 4.01%, T is 3.49%, F is 2.96%, N is 2.47%, W is 1.71%, M is 1.63%, C is 1.37%, H is 1.08% and K is 1.02%,
wherein X5 encodes such that G is 17.44%, Y is 11.10%, R is 8.78%, S is 8.02%, I is 4.85%, L is 4.80%, A is 4.33%, E is 4.33%, W is 4.18%, D is 4.04%, H is 3.69%, N is 3.69%, T is 3.08%, M is 2.96%, F is 2.91%, V is 2.70%, Q is 2.64%, P is 2.44%, C is 2.41% and K is 1.48%,
wherein X6 encodes such that G is 14.41%, R is 9.47%, S is 8.57%, Y is 8.31%, L is 7.67%, H is 6.48%, I is 5.38%, P is 4.50%, A is 4.04%, E is 3.89%, Q is 3.87%, W is 3.60%, N is 3.25%, D is 3.23%, T is 3.11%, M is 2.94%, V is 2.18%, C is 2.01%, F is 2.01% and K is 1.02%,
wherein X7 encodes such that G is 15.00%, S is 8.92%, R is 8.37%, Y is 8.34%, H is 6.89%, L is 6.86%, I is 5.03%, A is 4.24%, C is 2.47%, D is 2.79%, E is 4.53%, F is 2.85%, K is 1.60%, M is 2.76%, N is 3.11%, P is 3.89%, Q is 4.27%, T is 2.67%, V is 1.66% and W is 3.69%,
wherein X8 encodes such that G is 13.34%, R is 9.47%, Y is 8.08%, S is 8.05%, L is 7.47%, H is 6.19%, I is 5.09%, A is 4.88%, C is 1.83%, D is 3.37%, E is 4.18%, F is 2.44%, K is 1.13%, M is 2.67%, N is 3.84%, P is 4.53%, Q is 3.95%, T is 3.63%, V is 2.32%, W is 3.43%,
wherein X9 encodes such that G is 14.94%, R is 9.33%, Y is 9.13%, S is 7.15%, L is 6.77%, H is 6.07%, I is 5.14%, A is 4.45%, C is 2.15%, D is 3.34%, E is 3.57%, F is 3.05%, K is 1.25%, M is 2.73%, N is 3.55%, P is 3.95%, Q is 3.57%, T is 3.46%, V is 3.02% and W is 3.37%,
wherein X10 encodes such that Y is 14.82%, R is 9.82%, P is 9.79%, G is 8.25%, D is 6.19%, I is 6.07%, Q is 5.55%, L is 5.32%, A is 4.85%, C is 2.15%, E is 4.53%, F is 2.59%, H is 1.51%, K is 0.93%, M is 1.22%, N is 2.27%, S is 4.68%, T is 3.72%, V is 4.21% and W is 1.45%,
wherein X11 encodes such that Y is 14.68%, R is 10.29%, P is 9.82%, G is 7.73%, L is 6.25%, I is 5.70%, S is 5.49%, D is 5.32%, A is 5.26%, Q is 5.03%, C is 1.92%, E is 4.33%, F is 3.31%, H is 1.31%, K is 1.13%, M is 1.16%, N is 1.95%, T is 3.81%, V is 4.10% and W is 1.39%,
wherein X12 encodes such that Y is 15.02%, P is 10.20%, R is 9.76%, G is 7.79%, I is 5.73%, A is 5.38%, S is 5.32%, D is 5.14%, C is 1.71%, E is 4.88%, F is 3.37%, H is 1.31%, K is 1.51%, L is 4.97%, M is 1.19%, N is 1.74%, Q is 4.91%, T is 3.95%, V is 4.33% and W is 1.71%,
wherein X13 encodes such that Y is 16.54%, P is 10.32%, R is 9.85%, G is 8.49%, D is 5.90%, I is 5.78%, L is 5.26%, S is 5.06%, A is 5.00%, C is 1.54%, E is 4.27%, F is 2.59%, H is 1.08%, K is 1.28%, M is 1.39%, N is 2.35%, Q is 3.78%, T is 3.63%, V is 4.18% and W is 1.63%,
wherein X14 encodes such that G is 35.89%, A is 24.38%, Y is 12.67%, W is 7.70%, C is 0.17%, D is 2.41%, E is 1.28%, F is 0.64%, H is 0.15%, I is 1.39%, L is 2.35%, N is 1.71%, P is 2.32%, Q is 0.44%, R is 1.31%, S is 1.08%, T is 2.12% and V is 1.89%,
wherein X15 encodes such that M is 41.88%, F is 37.93%, L is 9.68%, D is 0.06%, E is 0.06%, G is 1.19%, H is 0.81%, I is 1.83%, P is 1.63%, S is 0.70%, T is 0.55%, V is 1.86%, W is 0.70% and Y is 1.08%,
wherein X16 encodes such that D is 76.23%, A is 1.80%, C is 0.67%, E is 2.03%, F is 0.70%, G is 4.36%, H is 2.01%, K is 1.45%, L is 1.16%, N is 1.28%, P is 1.25%, Q is 0.93%, R is 1.16%, S is 1.92%, T is 0.90%, V is 1.05%, and Y is 1.05%, and
wherein X17 encodes such that V is 33.97%, Y is 22.03%, I is 17.67%, P is 7.90%, A is 1.28%, C is 0.09%, D is 0.32%, F is 3.31%, G is 0.15%, H is 2.06%, L is 1.69%, M is 2.62%, N is 1.39%, Q is 0.81%, R is 1.02%, S is 3.55% and T is 0.09%;
when the length of the modified CDRH3 is 18 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18 (SEQ ID NO. 127),
wherein X1 encodes such that D is 23.99%, G is 22.77%, E is 14.07%, V is 6.83%, R is 5.97%, S is 4.00%, L is 2.83%, H is 2.68%, Y is 2.63%, Q is 2.38%, A is 2.13%, P is 2.02%, M is 1.92%, K is 1.72%, W is 1.42%, T is 1.06%, I is 0.76%, N is 0.66%, C is 0.05% and F is 0.05%,
wherein X2 encodes such that G is 16.75%, S is 11.54%, R is 9.77%, Y is 7.84%, L is 6.22%, I is 6.02%, H is 5.82%, P is 4.35%, E is 4.10%, D is 4.00%, Q is 3.64%, A is 3.09%, N is 2.78%, W is 2.53%, M is 2.38%, T is 2.38%, V is 2.33%, C is 1.77%, F is 1.37% and K is 1.32%,
wherein X3 encodes such that G is 14.57%, S is 10.22%, R is 9.01%, Y is 8.30%, L is 6.48%, I is 6.43%, H is 6.02%, Q is 4.15%, A is 4.05%, T is 4.00%, D is 3.90%, P is 3.64%, E is 3.54%, W is 3.09%, N is 2.83%, V is 2.53%, M is 2.28%, F is 2.07%, C is 1.62% and K is 1.21%,
wherein X4 encodes such that Y is 12.55%, P is 11.69%, G is 10.12%, R is 9.56%, L is 6.38%, I is 6.02%, D is 5.72%, S is 5.31%, Q is 5.01%, E is 4.71%, A is 4.30%, V is 3.90%, T is 3.69%, F is 2.43%, W is 2.07%, N is 1.52%, H is 1.47%, M is 1.32%, C is 1.16% and K is 1.06%,
wherein X5 encodes such that Y is 14.93%, P is 11.03%, R is 8.50%, G is 7.24%, I is 6.22%, L is 5.92%, A is 5.26%, Q is 5.16%, S is 4.76%, E is 4.55%, D is 4.25%, V is 4.25%, T is 3.54%, F is 3.39%, C is 2.53%, N is 2.33%, M is 1.87%, W is 1.82%, K is 1.42% and H is 0.96%,
wherein X6 encodes such that G is 15.08%, Y is 9.46%, S is 9.11%, R is 8.96%, L is 6.12%, H is 5.41%, I is 5.41%, A is 4.35%, E is 4.25%, Q is 4.05%, D is 3.85%, N is 3.64%, T is 3.44%, P is 3.29%, M is 2.63%, W is 2.53%, V is 2.43%, C is 2.38%, F is 2.28% and K is 1.32%,
wherein X7 encodes such that G is 14.32%, R is 9.36%, Y is 8.40%, S is 8.00%, L is 7.79%, H is 5.52%, P is 4.61%, A is 4.45%, I is 4.15%, Q is 3.95%, T is 3.95%, N is 3.90%, W is 3.69%, D is 3.44%, E is 3.34%, V is 2.94%, F is 2.73%, M is 2.63%, C is 1.62% and K is 1.16%,
wherein X8 encodes such that G is 13.92%, Y is 9.16%, R is 9.11%, S is 8.65%, L is 7.79%, H is 5.41%, I is 5.21%, A is 4.96%, E is 4.35%, Q is 4.35%, W is 3.74%, P is 3.54%, F is 3.39%, T is 3.04%, M is 2.99%, D is 2.78%, N is 2.73%, V is 2.13%, C is 1.82% and K is 0.91%,
wherein X9 encodes such that G is 14.78%, R is 10.98%, Y is 8.50%, S is 8.10%, L is 6.53%, H is 6.17%, P is 5.31%, I is 4.55%, A is 4.15%, D is 3.80%, T is 3.74%, N is 3.64%, W is 3.49%, E is 3.44%, Q is 3.19%, F is 2.83%, M is 2.33%, V is 1.77%, C is 1.57% and K is 1.11%,
wherein X10 encodes such that G is 14.12%, R is 9.46%, Y is 8.91%, L is 7.74%, S is 7.59%, H is 6.33%, A is 4.76%, I is 4.71%, P is 4.55%, N is 4.25%, Q is 3.85%, E is 3.64%, D is 3.29%, W is 3.29%, T is 3.24%, F is 2.53%, V is 2.48%, M is 2.43%, C is 1.82% and K is 1.01%,
wherein X11 encodes such that Y is 13.87%, P is 11.39%, R is 10.58%, G is 7.89%, A is 6.12%, D is 5.62%, I is 5.16%, V is 5.11%, E is 4.81%, S is 4.61%, L is 4.45%, Q is 4.10%, T is 3.95%, F is 3.59%, N is 2.02%, C is 1.97%, M is 1.42%, H is 1.21%, W is 1.06% and K is 1.01%,
wherein X12 encodes such that Y is 15.94%, R is 8.96%, P is 8.76%, G is 8.60%, L is 5.92%, D is 5.82%, Q is 5.52%, I is 4.91%, S is 4.71%, A is 4.66%, E is 4.35%, V is 4.10%, T is 3.59%, F is 3.19%, N is 2.53%, W is 2.53%, C is 1.92%, K is 1.42%, M is 1.42% and H is 1.06%,
wherein X13 encodes such that Y is 16.95%, P is 10.17%, R is 9.36%, G is 7.34%, D is 5.47%, A is 5.41%, L is 5.16%, I is 4.81%, Q is 4.81%, V is 4.76%, E is 4.25%, S is 4.05%, T is 3.59%, F is 3.14%, N is 2.63%, C is 1.92%, W is 1.67%, H is 1.62%, M is 1.57% and K is 1.27%,
wherein X14 encodes such that Y is 18.37%, G is 9.01%, P is 8.76%, R is 8.25%, I is 6.02%, D is 5.57%, A is 5.47%, L is 4.71%, E is 4.55%, V is 4.50%, S is 4.25%, Q is 3.74%, T is 3.39%, F is 3.14%, N is 2.94%, W is 2.02%, M is 1.62%, C is 1.37%, H is 1.37% and K is 0.91%,
wherein X15 encodes such that G is 30.57%, A is 20.70%, W is 12.80%, Y is 10.32%, P is 5.11%, S is 5.01%, T is 3.54%, V is 2.58%, D is 2.28%, R is 2.23%, L is 1.27%, K is 0.91%, I is 0.71%, F is 0.56%, N is 0.51%, C is 0.30%, M is 0.20%, E is 0.15%, H is 0.15% and Q is 0.05%,
wherein X16 encodes such that M is 40.59%, F is 37.96%, L is 9.16%, I is 2.58%, P is 2.13%, V is 2.02%, G is 1.47%, H is 1.01%, Y is 1.01%, W is 0.81%, S is 0.51%, A is 0.20%, D is 0.20%, T is 0.20%, C is 0.05%, N is 0.05% and R is 0.05%,
wherein X17 encodes such that D is 76.62%, G is 4.35%, E is 2.13%, S is 1.97%, A is 1.92%, H is 1.77%, V is 1.42%, K is 1.37%, N is 1.32%, F is 1.11%, L is 1.06%, P is 0.91%, Q is 0.86%, Y is 0.81%, R is 0.76%, T is 0.76%, C is 0.51%, M is 0.25% and I is 0.05%, and
wherein X18 encodes such that V is 32.59%, Y is 20.65%, I is 18.12%, P is 9.67%, S is 4.50%, F is 3.39%, M is 2.38%, L is 2.18%, H is 1.62%, N is 1.42%, A is 1.01%, Q is 0.86%, R is 0.86%, D is at 0.66% and G is 0.05%;
when the length of the modified CDRH3 is 19 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19 (SEQ ID NO. 128),
wherein X1 encodes such that D is 23.33%, G is 22.55%, E is 13.92%, V is 6.81%, R is 5.38%, A is 2.44%, C is 0.24%, F is 0.17%, H is 3.28%, I is 0.85%, K is 2.27%, L is 2.30%, M is 2.24%, N is 0.98%, P is 2.54%, Q is 2.57%, S is 3.79%, T is 0.37%, W is 1.05% and Y is 2.88%,
wherein X2 encodes such that G is 19.67%, R is 12.09%, D is 11.48%, P is 10.26%, I is 8.74%, S is 6.16%, L is 5.89%, A is 5.79%, E is 5.08%, C is 0.88%, F is 0.81%, H is 2.40%, K is 0.27%, M is 0.14%, N is 1.69%, Q is 2.24%, T is 2.51%, V is 0.24%, W is 1.66% and Y is 2.00%,
wherein X3 encodes such that G is 14.05%, S is 10.43%, R is 7.92%, Y is 7.69%, L is 7.55%, I is 6.30%, H is 5.62%, A is 3.76%, C is 2.30%, D is 4.47%, E is 4.00%, F is 2.20%, K is 1.22%, M is 2.71%, N is 2.88%, P is 3.66%, Q is 4.54%, T is 3.25%, V is 2.20% and W is 3.18%,
wherein X4 encodes such that Y is 12.83%, P is 11.62%, R is 9.04%, G is 8.50%, L is 6.30%, I is 5.66%, A is 5.55%, D is 5.49%, S is 5.49%, C is 1.59%, E is 4.67%, F is 3.08%, H is 1.42%, K is 1.25%, M is 1.46%, N is 2.84%, Q is 3.79%, T is 3.79%, V is 4.13% and W is 1.49%,
wherein X5 encodes such that Y is 14.02%, P is 9.82%, R is 9.21%, G is 7.48%, L is 6.23%, E is 5.69%, I is 5.69%, D is 5.35%, S is 5.05%, A is 4.88%, C is 1.59%, F is 2.84%, H is 1.42%, K is 0.85%, M is 1.52%, N is 2.64%, Q is 4.91%, T is 4.20%, V is 4.81% and W is 1.76%,
wherein X6 encodes such that Y is 14.39%, P is 9.92%, G is 9.01%, R is 8.53%, S is 6.06%, I is 5.99%, D is 5.93%, A is 5.11%, E is 5.01%, C is 1.63%, F is 3.28%, H is 1.02%, K is 0.91%, L is 4.64%, M is 1.52%, N is 1.76%, Q is 4.44%, T is 4.44%, V is 4.37% and W is 1.93%,
wherein X7 encodes such that Y is 14.26%, S is 12.26%, V is 10.13%, D is 9.89%, G is 9.08%, I is 7.75%, F is 6.30%, E is 5.86%, A is 4.61%, C is 1.86%, H is 0.37%, K is 0.27%, L is 1.63%, M is 1.59%, N is 4.03%, P is 0.44%, Q is 0.78%, R is 0.61%, T is 4.20% and W is 4.00%,
wherein X8 encodes such that G is 14.39%, W is 10.36%, S is 9.14%, F is 8.97%, V is 8.03%, I is 7.38%, H is 6.64%, T is 6.50%, D is 5.32%, A is 5.28%, C is 1.73%, E is 2.61%, K is 0.10%, L is 0.95%, M is 0.27%, N is 2.57%, P is 4.03%, Q is 0.37%, R is 1.76% and Y is 3.56%,
wherein X9 encodes such that G is 14.32%, R is 9.18%, S is 8.09%, Y is 8.09%, L is 7.04%, H is 6.23%, I is 5.25%, A is 4.37%, C is 2.07%, D is 3.66%, E is 4.44%, F is 2.40%, K is 1.32%, M is 2.40%, N is 4.30%, P is 4.27%, Q is 3.83%, T is 2.78%, V is 2.44% and W is 3.42%,
wherein X10 encodes such that G is 13.92%, R is 8.91%, Y is 8.20%, S is 8.16%, L is 7.38%, H is 5.99%, P is 5.25%, I is 5.15%, A is 4.54%, C is 1.86%, D is 3.28%, E is 3.73%, F is 3.08%, K is 1.15%, M is 2.91%, N is 3.12%, Q is 3.93%, T is 3.15%, V is 2.47% and W is 3.79%,
wherein X11 encodes such that Y is 13.65%, R is 10.19%, P is 9.85%, G is 7.65%, D is 5.76%, Q is 5.69%, E is 5.35%, I is 5.32%, L is 5.18%, A is 4.88%, C is 1.90%, F is 3.39%, H is 1.25%, K is 0.95%, M is 0.98%, N is 2.47%, S is 4.88%, T is 3.93%, V is 4.74% and W is 1.96%,
wherein X12 encodes such that Y is 14.22%, P is 9.99%, R is 8.77%, G is 8.16%, D is 6.13%, I is 5.82%, S is 5.72%, L is 5.49%, A is 5.05%, Q is 5.05%, C is 1.69%, E is 4.84%, F is 3.73%, H is 1.39%, K is 0.95%, M is 1.56%, N is 2.10%, T is 3.45%, V is 4.00% and W is 1.83%,
wherein X13 encodes such that Y is 16.59%, R is 9.11%, P is 8.84%, G is 8.70%, D is 5.89%, I is 5.76%, S is 5.05%, A is 4.94%, C is 2.00%, E is 4.57%, F is 3.45%, H is 1.15%, K is 1.29%, L is 4.61%, M is 1.69%, N is 2.64%, Q is 4.17%, T is 3.73%, V is 4.17% and W is 1.52%,
wherein X14 encodes such that Y is 41.62%, N is 11.45%, G is 10.02%, A is 4.17%, C is 0.24%, D is 1.56%, E is 1.25%, F is 1.19%, H is 4.17%, I is 2.84%, K is 1.19%, L is 4.57%, M is 0.10%, P is 2.44%, Q is 0.24%, R is 3.93%, S is 4.17%, T is 1.56%, V is 1.86% and W is 1.35%,
wherein X15 encodes such that Y is 49.44%, D is 14.63%, G is 8.57%, N is 7.31%, A is 0.30%, C is 0.14%, E is 0.17%, F is 4.20%, H is 1.02%, I is 0.34%, K is 0.03%, L is 0.24%, M is 0.03%, P is 3.05%, Q is 0.81%, R is 0.54%, S is 3.83%, T is 2.81%, V is 1.66% and W is 0.81%,
wherein X16 encodes such that G is 45.38%, A is 20.72%, Y is 13.27%, C is 0.85%, D is 1.19%, E is 0.07%, F is 0.44%, H is 1.22%, I is 1.49%, K is 0.07%, L is 0.95%, N is 0.03%, P is 2.78%, R is 1.08%, S is 1.63%, T is 0.88%, V is 4.00% and W is 3.96%,
wherein X17 encodes such that F is 40.09%, M is 39.45%, L is 8.57%, A is 0.07%, D is 0.07%, G is 1.05%, H is 1.02%, I is 2.37%, P is 1.42%, S is 0.85%, T is 0.68%, V is 2.17%, W is 0.91% and Y is 1.29%,
wherein X18 encodes such that D is 75.72%, A is 1.83%, C is 0.91%, E is 2.20%, F is 1.02%, G is 4.81%, H is 1.93%, K is 1.22%, L is 1.19%, M is 0.20%, N is 1.46%, P is 0.81%, Q is 0.85%, R is 0.95%, S is 1.83%, T is 0.71%, V is 1.35%, and Y is 0.98%, and
wherein X19 encodes such that V is 33.12%, I is 20.01%, Y is 19.13%, P is 9.72%, A is 1.22%, C is 0.03%, D is 0.37%, E is 0.03%, F is 3.49%, G is 0.03%, H is 1.90%, L is 1.56%, M is 2.71%, N is 1.19%, Q is 0.47%, R is 1.05%, S is 3.89% and T is 0.03%;
when the length of the modified CDRH3 is 20 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20 (SEQ ID NO. 129),
wherein X1 encodes such that D is 24.17%, G is 22.63%, E is 15.56%, V is 7.04%, R is 5.41%, S is 3.27%, H is 2.99%, Y is 2.80%, L is 2.58%, P is 2.39%, Q is 2.33%, K is 1.89%, M is 1.76%, A is 1.67%, W is 1.16%, I is 0.88%, N is 0.66%, T is 0.63%, C is 0.09% and F is 0.09%,
wherein X2 encodes such that G is 15.46%, S is 11.53%, R is 8.67%, Y is 7.79%, L is 6.19%, H is 5.85%, I is 5.78%, D is 4.68%, E is 4.65%, A is 3.77%, Q is 3.52%, P is 3.49%, T is 3.11%, M is 2.95%, W is 2.70%, N is 2.67%, F is 2.36%, V is 1.82%, C is 1.73% and K is 1.23%,
wherein X3 encodes such that G is 13.70%, S is 10.40%, R is 9.71%, Y is 7.64%, L is 6.63%, I is 6.00%, H is 5.15%, D is 4.49%, A is 4.40%, Q is 4.18%, E is 3.96%, P is 3.61%, W is 3.33%, N is 3.17%, T is 3.14%, M is 2.70%, V is 2.39%, F is 2.14%, C is 1.82% and K is 1.41%,
wherein X4 encodes such that L is 11.00%, I is 9.49%, G is 8.89%, Y is 8.42%, S is 8.08%, E is 7.86%, D is 7.13%, A is 6.95%, F is 6.73%, V is 5.28%, R is 4.87%, P is 3.11%, T is 2.70%, W is 2.36%, M is 2.11%, C is 1.89%, K is 1.16%, N is 1.13%, Q is 0.41% and H is 0.38%,
wherein X5 encodes such that Y is 13.70%, P is 11.44%, R is 9.37%, G is 8.36%, I is 5.72%, D is 5.63%, Q is 5.31%, S is 5.28%, L is 5.12%, E is 4.75%, A is 4.62%, V is 4.56%, T is 3.55%, F is 2.73%, N is 2.01%, C is 1.98%, W is 1.73%, H is 1.41%, M is 1.35% and K is 1.29%,
wherein X6 encodes such that D is 16.25%, Y is 13.89%, I is 11.35%, S is 10.03%, G is 8.80%, V is 5.81%, L is 5.59%, F is 5.50%, T is 5.22%, C is 3.99%, A is 3.21%, W is 2.55%, E is 2.14%, R is 1.98%, P is 1.76%, Q is 1.04%, M is 0.35%, N is 0.31%, H is 0.19% and K is 0.06%,
wherein X7 encodes such that Y is 17.38%, S is 16.59%, F is 14.11%, G is 9.49%, D is 7.01%, I is 4.53%, K is 4.15%, T is 4.09%, C is 4.05%, V is 3.58%, N is 3.52%, R is 3.49%, L is 2.33%, A is 1.54%, P is 1.38%, H is 1.10%, E is 0.82%, M is 0.35%, W is 0.28% and Q is 0.09%,
wherein X8 encodes such that G is 15.24%, R is 8.74%, L is 7.95%, S is 7.89%, Y is 7.35%, H is 6.16%, I is 4.75%, A is 4.40%, P is 4.37%, D is 4.21%, E is 3.96%, Q is 3.96%, N is 3.49%, W is 3.39%, T is 3.08%, V is 3.05%, M is 2.58%, C is 2.17%, F is 1.95% and K is 1.29%,
wherein X9 encodes such that G is 14.24%, R is 9.21%, S is 8.45%, Y is 8.33%, L is 7.83%, I is 5.34%, H is 5.28%, E is 4.59%, A is 4.56%, P is 3.71%, T is 3.68%, Q is 3.49%, W is 3.46%, N is 3.36%, D is 3.05%, M is 2.92%, F is 2.73%, V is 2.42%, C is 1.89% and K is 1.45%,
wherein X10 encodes such that G is 13.92%, R is 8.89%, Y is 8.89%, S is 7.86%, L is 7.54%, H is 6.79%, I is 5.06%, P is 5.00%, A is 4.78%, E is 3.99%, Q is 3.71%, D is 3.33%, N is 3.21%, T is 3.14%, W is 3.11%, F is 2.92%, V is 2.48%, M is 2.33%, C is 1.89% and K is 1.13%,
wherein X11 encodes such that Y is 12.82%, P is 10.09%, R is 8.96%, G is 8.11%, D is 5.85%, I is 5.59%, L is 5.31%, E is 5.19%, A is 5.15%, S is 5.09%, V is 4.71%, Q is 4.68%, T is 4.53%, F is 3.87%, W is 2.39%, N is 2.36%, C is 1.79%, H is 1.51%, M is 1.23% and K is 0.79%,
wherein X12 encodes such that Y is 13.26%, P is 9.90%, R is 9.87%, G is 7.54%, L is 5.78%, A is 5.66%, I is 5.41%, S is 5.37%, D is 5.03%, V is 4.93%, Q is 4.87%, E is 4.71%, T is 3.68%, F is 3.33%, N is 2.64%, W is 2.11%, C is 1.57%, M is 1.54%, K is 1.45% and H is 1.32%,
wherein X13 encodes such that Y is 15.71%, R is 10.47%, P is 9.90%, G is 7.54%, L is 5.50%, S is 5.47%, D is 5.44%, E is 5.03%, I is 4.84%, A is 4.65%, V is 4.65%, Q is 4.62%, T is 3.52%, F is 2.99%, N is 2.42%, C is 1.92%, W is 1.70%, M is 1.35%, H is 1.13% and K is 1.13%,
wherein X14 encodes such that Y is 48.52%, G is 9.62%, P is 6.38%, S is 5.94%, R is 4.43%, N is 4.34%, D is 3.74%, I is 3.71%, V is 2.99%, F is 2.48%, K is 1.48%, A is 1.35%, H is 1.23%, L is 1.10%, T is 0.94%, W is 0.94%, E is 0.31%, Q is 0.25%, C is 0.09% and M is 0.06%,
wherein X15 encodes such that Y is 46.48%, S is 7.73%, P is 4.87%, V is 4.27%, H is 4.18%, N is 4.09%, E is 3.99%, I is 3.36%, A is 3.33%, G is 3.30%, W is 3.21%, T is 2.45%, C is 2.29%, D is 1.89%, R is 1.67%, M is 0.97%, L is 0.94%, F is 0.41%, K is 0.35% and Q is 0.16%,
wherein X16 encodes such that Y is 47.49%, G is 10.78%, P is 6.44%, S is 6.07%, R is 4.09%, D is 4.02%, N is 3.96%, I is 3.68%, V is 3.36%, F is 3.08%, H is 1.41%, A is 1.23%, W is 1.07%, K is 1.01%, L is 1.01%, T is 0.85%, C is 0.06%, E is 0.06%, Q is 0.06% and M is 0.03%,
wherein X17 encodes such that G is 43.84%, A is 17.38%, Y is 10.78%, W is 8.64%, T is 3.90%, R is 2.83%, S is 2.80%, F is 2.51%, V is 2.36%, D is 1.60%, K is 1.41%, N is 1.16%, P is 0.31%, I is 0.19%, L is 0.09%, E is 0.06%, H is 0.06% and M is 0.06%,
wherein X18 encodes such that M is 40.19%, F is 39.79%, L is 7.35%, V is 2.77%, I is 2.20%, Y is 1.35%, P is 1.19%, G is 1.13%, H is 1.13%, W is 0.91%, S is 0.82%, T is 0.72%, D is 0.19%, C is 0.13%, N is 0.09% and A is 0.03%,
wherein X19 encodes such that D is 74.67%, G is 4.31%, E is 2.39%, A is 2.23%, H is 2.23%, S is 1.89%, V is 1.51%, N is 1.45%, K is 1.32%, Q is 1.19%, Y is 1.19%, F is 1.10%, L is 1.04%, R is 0.97%, P is 0.91%, T is 0.66%, C is 0.63%, M is 0.19% and W is 0.06%, and
wherein X20 encodes such that V is 34.51%, Y is 20.05%, I is 18.48%, P is 9.55%, S is 3.68%, F is 3.05%, M is 2.42%, H is 1.76%, L is 1.57%, R is 1.26%, N is 1.07%, Q is 1.01%, A is 0.94%, D is 0.41%, G is 0.13%, C is 0.03% and T is 0.03%;
when the length of the modified CDRH3 is 21 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21 (SEQ ID NO. 130),
wherein X1 encodes such that D is 24.63%, E is 14.85%, G is 21.67%, V is 7.17%, R is 5.99%, I is 0.86%, K is 1.62%, L is 2.34%, M is 1.86%, N is 0.65%, P is 2.20%, Q is 2.65%, S is 2.72%, T is 0.65%, W is 1.62%, Y is 2.79%, C is 0.07%, H is 3.10% and A is 2.48%,
wherein X2 encodes such that G is 25.32%, S is 20.22%, P is 9.06%, Y is 8.72%, K is 6.92%, A is 6.27%, L is 5.20%, C is 0.24%, D is 3.79%, E is 0.62%, F is 2.07%, H is 0.41%, I is 2.34%, M is 0.55%, N is 0.14%, Q is 0.28%, R is 3.82%, T is 0.28%, V is 1.86% and W is 1.86%,
wherein X3 encodes such that A is 11.78%, S is 10.54%, R is 8.96%, Y is 8.75%, G is 8.47%, L is 8.10%, E is 7.13%, I is 7.13%, D is 5.82%, V is 5.75%, C is 3.31%, F is 0.28%, H is 0.38%, K is 2.82%, M is 0.14%, N is 4.17%, P is 4.48%, Q is 0.28%, T is 1.45% and W is 0.14%,
wherein X4 encodes such that G is 14.50%, S is 10.02%, R is 9.20%, Y is 7.68%, L is 6.10%, I is 5.58%, E is 5.37%, H is 5.03%, A is 3.79%, C is 2.10%, D is 3.79%, F is 2.93%, K is 1.31%, M is 3.20%, N is 2.79%, P is 4.24%, Q is 3.07%, T is 3.34%, V is 2.34% and W is 3.58%,
wherein X5 encodes such that G is 13.26%, R is 9.20%, S is 8.89%, Y is 7.51%, H is 6.72%, L is 6.41%, D is 5.96%, I is 5.96%, A is 3.96%, C is 1.76%, E is 3.55%, F is 2.31%, K is 1.31%, M is 2.41%, N is 3.44%, P is 4.13%, Q is 4.00%, T is 3.41%, V is 2.65% and W is 3.10%,
wherein X6 encodes such that I is 10.54%, L is 10.47%, Y is 8.85%, A is 8.51%, S is 8.47%, G is 8.34%, D is 8.23%, E is 6.72%, V is 5.99%, F is 5.82%, C is 2.10%, H is 0.34%, K is 0.83%, M is 1.58%, N is 1.52%, P is 2.86%, Q is 0.24%, R is 4.27%, T is 1.65% and W is 2.58%,
wherein X7 encodes such that L is 11.26%, I is 10.99%, G is 9.09%, S is 7.99%, Y is 7.68%, A is 7.58%, E is 7.51%, D is 7.44%, F is 6.92%, V is 5.79%, C is 1.48%, K is 1.62%, M is 1.65%, N is 1.31%, P is 2.55%, Q is 0.17%, R is 4.13%, T is 2.45% and W is 2.27%,
wherein X8 encodes such that L is 10.78%, I is 9.75%, G is 8.75%, Y is 8.34%, D is 8.30%, E is 8.06%, A is 7.75%, S is 7.68%, F is 7.44%, V is 5.72%, C is 2.03%, H is 0.14%, K is 1.10%, M is 1.79%, N is 0.93%, P is 2.24%, Q is 0.10%, R is 4.68%, T is 2.10% and W is 2.20%,
wherein X9 encodes such that L is 10.68%, I is 9.75%, A is 8.47%, G is 8.13%, Y is 7.82%, D is 7.65%, E is 7.65%, S is 7.41%, F is 7.10%, V is 5.27%, C is 1.76%, H is 0.24%, K is 1.76%, M is 1.72%, N is 1.17%, P is 3.10%, Q is 0.07%, R is 4.99%, T is 2.27% and W is 2.93%,
wherein X10 encodes such that L is 11.75%, I is 9.85%, D is 8.34%, Y is 7.99%, A is 7.85%, E is 7.48%, G is 7.48%, S is 7.17%, F is 7.13%, V is 5.03%, C is 1.89%, H is 0.41%, K is 1.45%, M is 1.31%, N is 1.38%, P is 3.38%, Q is 0.55%, R is 4.62%, T is 2.55% and W is 2.41%,
wherein X11 encodes such that L is 11.23%, I is 10.02%, G is 8.99%, Y is 8.37%, A is 7.58%, D is 7.37%, F is 7.20%, E is 6.96%, S is 6.85%, V is 5.34%, C is 2.00%, H is 0.28%, K is 1.21%, M is 2.03%, N is 1.76%, P is 3.31%, Q is 0.38%, R is 4.00%, T is 2.62% and W is 2.48%,
wherein X12 encodes such that P is 18.05%, G is 14.88%, S is 12.09%, F is 11.47%, R is 10.27%, H is 9.37%, A is 0.59%, C is 0.24%, D is 2.51%, E is 0.62%, I is 1.21%, K is 0.03%, L is 2.62%, M is 0.14%, N is 2.89%, Q is 2.79%, T is 3.07%, V is 2.24%, W is 0.28% and Y is 4.65%,
wherein X13 encodes such that G is 17.57%, Y is 13.02%, D is 12.19%, T is 8.89%, S is 7.51%, N is 6.48%, P is 6.44%, R is 6.30%, L is 5.34%, A is 2.24%, C is 0.34%, E is 2.48%, F is 0.59%, H is 0.10%, I is 3.17%, K is 2.79%, M is 3.10%, Q is 0.31%, V is 0.83% and W is 0.31%,
wherein X14 encodes such that Y is 35.62%, S is 13.64%, R is 9.68%, P is 8.54%, V is 6.41%, A is 0.90%, C is 2.14%, D is 0.79%, E is 2.51%, F is 0.65%, G is 3.89%, H is 3.55%, I is 0.59%, K is 2.58%, L is 4.31%, M is 0.14%, N is 0.41%, Q is 0.28%, T is 1.65% and W is 1.62%,
wherein X15 encodes such that Y is 50.43%, A is 9.65%, R is 5.99%, C is 1.89%, D is 2.79%, E is 2.17%, F is 4.34%, G is 1.96%, H is 0.17%, I is 2.89%, K is 2.27%, L is 0.48%, N is 4.20%, P is 2.79%, Q is 0.17%, S is 2.20%, T is 2.89%, V is 0.17% and W is 2.38%,
wherein X16 encodes such that Y is 54.98%, G is 10.71%, F is 6.17%, S is 5.65%, A is 0.31%, C is 0.07%, D is 4.44%, E is 0.31%, H is 3.03%, I is 2.38%, K is 0.21%, L is 2.20%, M is 2.34%, N is 0.24%, P is 2.89%, Q is 1.03%, R is 1.79%, T is 0.45%, V is 0.45% and W is 0.21%,
wherein X17 encodes such that Y is 48.33%, G is 10.27%, P is 8.27%, S is 5.20%, A is 1.24%, C is 0.14%, D is 3.93%, E is 0.14%, F is 2.20%, H is 1.45%, I is 3.41%, K is 1.38%, L is 1.27%, N is 4.51%, Q is 0.10%, R is 3.41%, T is 0.83%, V is 3.13% and W is 0.79%,
wherein X18 encodes such that G is 43.82%, Y is 19.57%, A is 11.44%, C is 1.69%, D is 4.86%, E is 0.03%, F is 0.17%, H is 0.24%, I is 2.14%, K is 0.07%, L is 4.06%, M is 0.07%, N is 0.34%, P is 1.10%, Q is 0.03%, R is 1.72%, S is 0.14%, T is 0.83%, V is 0.21% and W is 7.41%,
wherein X19 encodes such that M is 39.03%, F is 35.45%, L is 10.16%, A is 0.21%, C is 0.07%, D is 0.24%, G is 2.93%, H is 1.14%, I is 2.07%, K is 0.03%, P is 1.83%, Q is 0.03%, R is 0.24%, S is 0.86%, T is 0.38%, V is 2.96%, W is 1.17% and Y is 1.21%,
wherein X20 encodes such that D is 71.96%, A is 2.03%, C is 0.69%, E is 1.38%, F is 2.17%, G is 4.79%, H is 2.79%, I is 0.03%, K is 0.86%, L is 1.38%, M is 1.62%, N is 1.03%, P is 1.55%, Q is 1.03%, R is 1.00%, S is 1.58%, T is 1.10%, V is 2.00% and Y is 1.00%, and
wherein X21 encodes such that V is 53.57%, Y is 8.44%, H is 8.37%, P is 8.23%, A is 0.07%, D is 4.72%, E is 0.03%, F is 2.58%, G is 0.24%, I is 3.17%, K is 0.03%, L is 0.03%, M is 2.27%, N is 2.17%, Q is 2.69%, R is 0.03% and S is 3.31%;
when the length of the modified CDRH3 is 22 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21X22 (SEQ ID NO. 131),
wherein X1 encodes such that D is 23.37%, E is 14.91%, G is 21.75%, V is 8.46%, R is 5.83%, A is 3.13%, C is 0.04%, F is 0.04%, H is 2.74%, I is 0.70%, K is 1.89%, L is 2.51%, M is 1.97%, N is 0.50%, P is 2.74%, Q is 2.05%, S is 2.94%, T is 0.46%, W is 1.04% and Y is 2.94%,
wherein X2 encodes such that F is 5.37%, G is 17.19%, L is 18.89%, P is 7.96%, R is 17.50%, S is 7.34%, A is 3.79%, C is 0.04%, D is 0.54%, E is 4.87%, H is 0.27%, I is 4.06%, K is 0.35%, M is 4.94%, Q is 0.58%, T is 2.28%, V is 0.58%, W is 2.97% and Y is 0.46%,
wherein X3 encodes such that A is 16.22%, G is 8.30%, K is 8.85%, L is 8.96%, R is 8.42%, S is 7.26%, Y is 8.03%, C is 3.59%, D is 3.17%, E is 4.52%, F is 3.13%, H is 0.08%, I is 4.44%, M is 0.08%, N is 4.21%, P is 4.75%, Q is 0.23%, T is 3.21%, V is 2.39% and W is 0.12%,
wherein X4 encodes such that E is 12.98%, F is 6.33%, G is 11.09%, I is 9.81%, P is 18.23%, R is 5.06%, S is 15.22%, T is 5.60%, Y is 5.37%, A is 0.42%, C is 0.19%, D is 3.79%, H is 0.08%, K is 0.19%, L is 3.94%, M is 0.46%, N is 0.19%, Q is 0.35%, V is 0.39% and W is 0.31%,
wherein X5 encodes such that D is 17.77%, H is 6.22%, P is 8.50%, S is 7.88%, T is 5.99%, Y is 14.41%, A is 4.98%, C is 3.82%, E is 0.50%, F is 3.67%, G is 4.40%, I is 0.42%, K is 4.94%, L is 0.46%, M is 0.35%, N is 4.17%, Q is 0.12%, R is 4.52%, V is 3.86% and W is 2.94%,
wherein X6 encodes such that D is 16.11%, G is 17.15%, M is 5.10%, V is 9.69%, Y is 13.13%, C is 3.36%, A is 0.70%, E is 4.48%, F is 0.27%, H is 4.79%, I is 1.16%, K is 0.19%, L is 0.42%, N is 4.21%, P is 3.59%, Q is 0.04%, R is 4.79%, S is 4.75%, T is 0.39% and W is 5.68%,
wherein X7 encodes such that A is 7.57%, D is 6.80%, E is 9.19%, F is 6.95%, G is 9.46%, I is 10.04%, L is 11.16%, S is 7.11%, V is 5.79%, W is 1.89%, C is 2.01%, H is 0.27%, K is 1.16%, M is 1.78%, N is 1.04%, P is 2.47%, Q is 0.23%, R is 4.91%, T is 2.24% and Y is 7.80%,
wherein X8 encodes such that A is 9.31%, D is 6.80%, E is 7.57%, I is 10.20%, F is 6.49%, G is 7.07%, L is 11.94%, S is 8.07%, V is 5.21%, Y is 8.96%, C is 1.58%, K is 1.08%, M is 1.93%, N is 1.43%, P is 2.94%, H is 0.08%, Q is 0.08%, R is 4.48%, T is 2.05% and W is 2.70%,
wherein X9 encodes such that A is 8.19%, D is 6.53%, E is 7.61%, F is 7.34%, G is 8.07%, I is 10.81%, L is 10.27%, S is 7.49%, V is 5.25%, Y is 8.96%, C is 1.89%, H is 0.12%, K is 1.51%, M is 1.85%, N is 1.51%, P is 2.74%, Q is 0.08%, R is 4.60%, T is 2.51% and W is 2.67%,
wherein X10 encodes such that Y is 13.02%, P is 10.31%, R is 9.39%, G is 9.31%, L is 6.30%, I is 6.10%, D is 5.33%, A is 4.87%, S is 4.87%, V is 4.67%, Q is 4.56%, E is 4.29%, T is 4.09%, F is 3.79%, N is 1.85%, C is 1.78%, W is 1.74%, H is 1.39%, M is 1.27% and K is 1.00%,
wherein X11 encodes such that Y is 13.44%, P is 10.35%, G is 8.65%, R is 8.42%, L is 6.49%, I is 5.52%, D is 5.29%, E is 5.29%, S is 4.91%, T is 4.87%, A is 4.75%, V is 4.75%, Q is 3.86%, F is 3.28%, N is 2.90%, W is 1.82%, C is 1.78%, H is 1.39%, K is 1.12% and M is 1.08%,
wherein X12 encodes such that Y is 13.75%, P is 9.62%, G is 9.04%, R is 8.57%, I is 7.72%, L is 6.10%, Q is 5.21%, S is 5.10%, A is 5.06%, D is 4.52%, E is 4.48%, F is 3.79%, V is 3.67%, T is 3.51%, N is 2.01%, W is 1.85%, H is 1.74%, C is 1.66%, M is 1.51% and K is 1.04%,
wherein X13 encodes such that L is 12.55%, I is 9.62%, S is 8.38%, Y is 8.27%, G is 7.84%, E is 7.61%, A is 7.45%, D is 7.26%, V is 6.06%, F is 5.99%, R is 4.36%, P is 3.13%, Tis 2.82%, W is 2.36%, Cis 1.78%, M is 1.66%, K is 1.27%, N is 1.27%, Q is 0.15% and H is 0.12%,
wherein X14 encodes such that L is 11.36%, I is 10.54%, Y is 8.38%, E is 8.15%, G is 8.07%, S is 8.00%, A is 7.84%, F is 7.34%, D is 7.26%, V is 5.21%, R is 4.44%, P is 3.05%, T is 2.36%, W is 2.09%, C is 2.01%, K is 1.43%, M is 1.31%, N is 1.08% and H is 0.08%,
wherein X15 encodes such that Y is 55.62%, P is 13.90%, T is 4.98%, S is 4.13%, D is 4.09%, E is 4.06%, L is 3.86%, G is 3.82%, Q is 3.24%, R is 0.58%, N is 0.39%, I is 0.35%, F is 0.19%, V is 0.19%, C is 0.15%, K is 0.15%, A is 0.12%, W is 0.08% and H is 0.04%,
wherein X16 encodes such that Y is 60.22%, G is 6.33%, T is 5.48%, K is 4.60%, L is 3.82%, V is 3.79%, E is 3.67%, R is 3.59%, S is 2.90%, W is 2.43%, I is 0.73%, A is 0.50%, D is 0.50%, F is 0.27%, N is 0.27%, P is 0.27%, Q is 0.19%, C is 0.15%, H is 0.04% and M is 0.04%,
wherein X17 encodes such that Y is 62.50%, R is 6.06%, P is 5.37%, K is 5.25%, H is 4.21%, D is 4.02%, S is 3.82%, G is 3.67%, T is 3.28%, L is 0.62%, F is 0.19%, V is 0.19%, C is 0.12%, M is 0.12%, N is 0.12%, A is 0.08%, I is 0.08% and Q is 0.08%,
wherein X18 encodes such that Y is 69.83%, N is 7.61%, G is 5.52%, D is 3.98%, A is 3.90%, H is 3.71%, E is 2.94%, S is 0.50%, F is 0.31%, K is 0.27%, C is 0.23%, P is 0.23%, R is 0.23%, L is 0.15%, W is 0.15%, V is 0.12%, I is 0.08%, Q is 0.04% and T is 0.04%,
wherein X19 encodes such that G is 57.44%, A is 10.12%, Y is 9.19%, R is 6.30%, D is 4.79%, W is 4.17%, H is 3.32%, F is 3.24%, P is 0.31%, I is 0.19%, M is 0.19%, C is 0.12%, E is 0.12%, L is 0.12%, N is 0.12%, S is 0.12%, T is 0.12% and K is 0.04%,
wherein X20 encodes such that M is 41.10%, F is 36.27%, L is 9.81%, I is 2.74%, V is 2.59%, P is 1.78%, G is 1.27%, H is 1.20%, Y is 1.08%, W is 0.89%, S is 0.54%, T is 0.46%, A is 0.08%, D is 0.08%, N is 0.08% and R is 0.04%,
wherein X21 encodes such that D is 74.55%, M is 0.23%, F is 0.85%, L is 1.27%, V is 1.16%, P is 1.39%, G is 4.25%, H is 2.16%, Y is 1.12%, S is 1.97%, T is 1.16%, A is 2.39%, N is 1.47%, R is 0.77%, C is 1.00%, E is 2.12%, K is 1.08% and Q is 1.04%, and
wherein X22 encodes such that V is 67.59%, Y is 10.97%, F is 9.35%, I is 8.42%, P is 2.47%, H is 0.42%, D is 0.35%, C is 0.12%, S is 0.12%, Q is 0.08%, A is 0.04%, L is 0.04% and T is 0.04%;
and
when the length of the modified CDRH3 is 23 amino acid residues, the amino acid sequence is X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21X22X23 (SEQ ID NO. 132),
wherein X1 encodes such that D is 46.36%, E is 9.86%, G is 22.89%, H is 8.78%, V is 7.32%, I is 0.10%, K is 0.10%, L is 0.24%, M is 0.05%, N is 0.24%, P is 0.24%, Q is 0.10%, R is 0.44%, S is 0.34%, A is 1.81%, W is 0.05%, Y is 0.20% and T is 0.88%,
wherein X2 encodes such that A is 5.32%, E is 6.54%, D is 11.91%, H is 10.05%, L is 12.01%, Q is 8.64%, V is 10.44%, P is 9.91%, G is 14.79%, F is 0.29%, I is 0.34%, K is 0.20%, M is 0.39%, N is 0.05%, R is 4.39%, S is 4.15%, T is 0.10%, W is 0.29% and Y is 0.15%,
wherein X3 encodes such that A is 15.57%, G is 11.13%, I is 15.32%, L is 12.84%, R is 8.69%, S is 17.33%, C is 0.29%, D is 0.34%, E is 0.29%, F is 0.15%, H is 0.10%, K is 4.59%, M is 0.05%, N is 0.15%, P is 3.71%, Q is 2.83%, T is 0.24%, V is 2.64%, and Y is 3.71%,
wherein X4 encodes such that G is 15.71%, M is 10.98%, R is 22.40%, S is 6.54%, T is 6.39%, Y is 9.32%, A is 0.29%, C is 0.10%, D is 4.78%, E is 0.98%, F is 0.49%, H is 0.05%, I is 4.93%, K is 4.25%, L is 0.39%, N is 0.15%, P is 3.61%, Q is 2.88%, V is 2.88% and W is 2.83%,
wherein X5 encodes such that A is 10.69%, D is 17.33%, F is 8.00%, P is 5.32%, R is 7.76%, T is 5.91%, V is 5.91%, Y is 10.40%, C is 0.20%, E is 4.29%, G is 4.83%, H is 0.44%, I is 0.24%, K is 0.24%, L is 4.59%, M is 4.39%, N is 4.69%, Q is 0.05%, S is 4.54% and W is 0.15%,
wherein X6 encodes such that Y is 10.49%, S is 21.33%, N is 5.32%, I is 15.18%, G is 5.12%, D is 5.08%, T is 7.61%, A is 3.42%, C is 0.49%, E is 0.34%, F is 3.07%, H is 3.51%, L is 3.51%, M is 4.05%, P is 2.73%, Q is 0.05%, R is 4.49%, V is 3.76% and W is 0.39%,
wherein X7 encodes such that E is 19.72%, G is 13.52%, I is 5.12%, K is 5.37%, M is 5.17%, S is 6.88%, Y is 10.00%, A is 4.39%, C is 2.93%, D is 0.78%, F is 3.76%, H is 4.78%, L is 0.49%, N is 0.10%, P is 3.61%, Q is 2.54%, R is 4.05%, T is 3.22%, V is 3.22% and W is 0.34%,
wherein X8 encodes such that A is 10.30%, D is 9.52%, G is 11.22%, I is 11.71%, L is 14.98%, V is 11.47%, C is 0.05%, E is 3.86%, F is 0.59%, H is 3.76%, K is 0.05%, N is 0.15%, P is 3.81%, Q is 0.10%, R is 3.42%, S is 4.73%, T is 3.22%, W is 2.98% and Y is 4.10%,
wherein X9 encodes such that A is 11.22%, E is 5.32%, F is 9.03%, I is 5.76%, N is 14.84%, P is 7.42%, S is 11.03%, V is 11.22%, C is 0.15%, D is 4.20%, G is 0.44%, H is 0.05%, K is 0.15%, L is 4.83%, M is 0.05%, Q is 2.34%, R is 0.78%, T is 2.78%, W is 3.56% and Y is 4.83%,
wherein X10 encodes such that G is 24.79%, I is 14.40%, R is 9.13%, S is 7.91%, W is 10.83%, Y is 14.30%, A is 4.59%, C is 0.34%, D is 0.24%, E is 0.88%, F is 3.90%, K is 0.10%, L is 0.73%, M is 0.15%, N is 0.20%, P is 2.10%, Q is 0.20%, T is 0.44% and V is 4.78%,
wherein X11 encodes such that G is 9.86%, K is 5.61%, P is 6.69%, R is 10.35%, S is 8.59%, T is 9.37%, V is 16.40%, Y is 6.78%, A is 0.34%, C is 0.15%, D is 4.88%, E is 0.34%, F is 4.25%, H is 3.42%, I is 0.59%, L is 4.00%, M is 0.10%, N is 4.49%, Q is 0.34%, and W is 3.42%,
wherein X12 encodes such that F is 9.42%, G is 12.10%, I is 14.25%, S is 15.96%, T is 6.69%, Y is 12.10%, A is 0.29%, C is 4.05%, D is 0.15%, E is 0.24%, H is 0.29%, K is 0.15%, L is 4.83%, M is 0.10%, N is 4.64%, P is 4.34%, Q is 2.68%, R is 3.66%, V is 3.90% and W is 0.10%,
wherein X13 encodes such that A is 9.03%, G is 12.15%, I is 19.52%, L is 6.98%, R is 11.52%, Y is 21.28%, C is 0.15%, D is 0.68%, E is 0.20%, F is 0.44%, H is 0.15%, K is 0.10%, M is 0.15%, N is 4.25%, P is 2.93%, Q is 0.15%, S is 3.17%, T is 0.20%, V is 3.56% and W is 3.27%,
wherein X14 encodes such that A is 5.12%, G is 8.44%, I is 5.51%, N is 5.42%, P is 8.39%, S is 22.65%, T is 10.35%, V is 11.57%, Y is 5.71%, C is 0.24%, D is 3.76%, E is 0.20%, F is 3.90%, H is 0.29%, K is 0.20%, L is 0.68%, Q is 0.10%, R is 3.95% and W is 3.47%,
wherein X15 encodes such that I is 19.18%, L is 10.15%, P is 11.27%, Y is 25.48%, G is 14.20%, A is 0.29%, C is 0.10%, D is 4.34%, E is 0.39%, F is 0.34%, K is 4.34%, M is 0.05%, N is 0.10%, Q is 0.10%, R is 0.29%, S is 4.05%, T is 2.20%, V is 2.83%, and W is 0.29%,
wherein X16 encodes such that E is 16.35%, N is 8.30%, R is 8.25%, Y is 45.63%, C is 0.05%, D is 4.15%, F is 3.32%, G is 2.88%, H is 0.15%, I is 0.20%, K is 0.20%, L is 0.24%, M is 0.05%, P is 3.17%, Q is 0.34%, S is 3.47%, T is 0.39%, V is 2.64% and W is 0.05%,
wherein X17 encodes such that D is 8.00%, G is 6.34%, I is 8.49%, Y is 56.66%, A is 0.10%, C is 0.10%, E is 0.34%, F is 3.51%, H is 0.10%, K is 3.42%, L is 4.93%, N is 0.05%, P is 0.20%, Q is 3.32%, R is 0.20%, S is 0.29%, T is 3.66%, V is 0.10% and W is 0.10%,
wherein X18 encodes such that G is 7.81%, K is 9.18%, L is 8.39%, S is 19.67%, Y is 37.73%, A is 0.05%, C is 0.05%, D is 2.59%, E is 0.10%, F is 0.10%, H is 4.20%, I is 0.15%, M is 0.10%, N is 0.10%, P is 0.24%, Q is 0.05%, R is 6.69%, T is 0.24%, V is 2.54% and W is 0.05%,
wherein X19 encodes such that D is 15.52%, G is 8.10%, Y is 59.64%, A is 0.44%, C is 0.15%, E is 0.34%, F is 3.90%, H is 0.29%, I is 0.15%, K is 0.10%, L is 0.10%, N is 4.69%, P is 0.34%, R is 0.20%, S is 2.59%, T is 0.10%, V is 0.29% and W is 2.98%,
wherein X20 encodes such that A is 25.72%, G is 52.71%, W is 10.59%, D is 4.34%, E is 0.05%, F is 0.39%, H is 0.10%, L is 0.24%, P is 4.05%, R is 0.44%, S is 0.05%, T is 0.15%, V is 0.20% and Y is 0.93%,
wherein X21 encodes such that F is 43.24%, L is 7.61%, M is 37.48%, A is 0.05%, C is 0.05%, D is 0.05%, G is 1.07%, H is 1.27%, I is 2.24%, P is 0.88%, S is 0.98%, T is 0.93%, V is 2.39%, W is 0.93% and Y is 0.83%,
wherein X22 encodes such that D is 74.18%, A is 2.59%, C is 0.63%, E is 1.90%, F is 0.83%, G is 4.93%, H is 2.05%, I is 0.10%, K is 1.61%, L is 0.88%, M is 0.05%, N is 1.12%, P is 1.22%, Q is 0.63%, R is 1.95%, S is 1.90%, T is 1.12%, V is 1.12%, and Y is 1.17%, and
wherein X23 encodes such that V is 59.15%, I is 25.33%, D is 0.05%, F is 4.73%, H is 0.15%, L is 0.05%, M is 0.05%, P is 9.22%, Q is 0.05%, R is 0.05%, S is 0.15%, T is 0.05% and Y is 0.98%.

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Method of generating a synthetic antibody library, said library and application(s) thereof

Life of this patent

Method of generating a synthetic antibody library, said library and application(s) thereof

Life of this patent

Abstract

Claims14