Methods of generating variant antibodies with increased host string content
First Claim
1. 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;
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Abstract
The present invention relates to novel methods for generating variant proteins with increased host string content by comparing a parent protein sequence with two or more natural protein sequences from a host species, analyzing one or more amino acid strings of the parent protein sequence with a structurally corresponding amino acid string of each of said natural protein sequences, substituting one or more amino acid strings of the parent protein sequence with a structurally corresponding amino acid string of one of the two or more natural protein sequences on an amino acid string by amino acid string basis so that the variant protein has increased host string content, and, synthesizing and screening the variant protein.
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Citations
47 Claims
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1. A method of generating a variant host species antibody variable region as compared to a non-host species antibody variable region, comprising:
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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; - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)
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24. A method of generating a variant host species antibody variable region as compared to a non-host species antibody variable region, comprising:
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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; 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 relative to said non-host species antibody variable region, and, where said host species string content (HSC) is measured by an equation functionally equivatent to; - View Dependent Claims (25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
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Specification