Patent ID: 7657380

Claim:
A method of generating a variant host species antibody variable region as compared to a non-host species antibody variable region, comprising: A. aligning said non-host species antibody variable region sequence with two or more naturally occurring host species antibody variable region sequences; B. performing two or more times; i. comparing, for string impact on host species string content, one or more sequence segments of each of said host species antibody variable region sequences to the structurally corresponding sequence segment of said non-host species antibody variable region sequence; and, ii. substituting one sequence segment of said non-host species antibody variable region sequence with a structurally corresponding sequence segment of one of said two or more host species antibody variable region sequences, wherein said substituted sequence segment increases host species string content, wherein said variant host species antibody variable region has increased host species string content as compared to said non-host species antibody variable region, wherein said substituted sequence segments include a first sequence segment substitution from a first naturally occurring antibody variable region sequence from said two or more naturally occurring host species antibody variable region sequences, and a second sequence segment substitution from a second naturally occurring antibody variable region sequence from said two or more naturally occurring host species antibody variable region sequences, and, where said host species string content (HSC) is measured by an equation functionally equivalent to: HSC ⁡ ( s ) = 100 · 1 ( L - w + 1 ) · w ⁢ ∑ i = 1 L - w + 1 ⁢ max h ⁢ ε ⁢ H ⁢ ⁢ S ⁢ ( ∑ j = i i + w - 1 ⁢ δ aa j s , aa j h ) , where L is the length of the sequence and L is greater than or equal to 9, w is the string window size, HS is the set of homologous host species sequences, i is the first position in the string, aa j s is the amino acid at position j of sequence s, aa j h is the amino acid at position j of the host species sequence h, and the Kronecker delta function is used to return a value of 1 for a match and 0 if there is no match, and, where said string impact (SI) is measured by an equation functionally equivalent to: SI(x m (z)→y m (z))=HSC(s(y m ))−HSC(parent), where y m (z) is a host species segment of length z replacing segment x at position m, and s(y m ) is a variant of the non-host species sequence that include segment y m (z), and, C. physically synthesizing an antibody comprising said variant host species antibody variable region sequence and screening said antibody.