Maxygen, Inc.

Codexis Mayflower Holdings, LLC

Dna Twopointo Inc.

Pfizer Corporation

Kosan Biosciences Incorporated

Pfizer Products Inc.

Codexis, Inc.

Codexis Mayflower Holding, LLC

Claes Gustafsson

Jeremy S Minshull

Phillip A Patten

Willem P C Stemmer

Mark D Welch

Sridhar Govindarajan

Jon Edward Ness

Steven Henry Bass

Andreas Crameri

Robin A Emig

Matthew B Tobin

Sergey A Selifonov

Stephen B Del Cardayre

Lorraine Joan Giver

Richard John Fox

S Christopher Davis

Linda A Castle

Rebecca Lynne Gorton

Daniel Siehl

Anthony Cox

Sun Ai Raillard

Teddy Chen

Ajoy K Roy

Yan Chen

Anke Krebber

Kim Jonelle Stutzman-Engwall

Emily C Mundorff

Mary C Betlach

Guy Cavet

Seran Kim

Brian S Carr

Gary W Ashley

Stephane J Jenne

Joseph A Affholter

Bryan Julien

Rainer Ziermann

Willem Pc Stemmer

Stanley Goldman

Pascal Longchamp

Alan Marco Villalobos

Daniel L Siehl

John E Ness

Jeremy Minshull

Phil Patten

Sridar Govindarajan

Ajoy Apt120 Roy

Rebecca Lynne Apt819 Gorton

Christopher S Davis

The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.

Methods, systems, and software for identifying functional bio-molecules

Methods, systems, and software for identifying functional biomolecules

Methods, computer systems, and computer program products for biopolymer engineering. A variant set for a biopolymer of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the biopolymer of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space. A variant set comprising a plurality of variants of the biopolymer of interest is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set. The variant set is redefined to comprise variants that include substitutions in the plurality of positions that are selected based on a function of the sequence-activity relationship.

Systems and methods for biopolymer engineering

Computer processing methods and/or systems for minimizing and/or optimizing data strings in accordance with rules and options. Minimized data strings can represent data sequences important in certain biologic analyses and/or syntheses. In specific embodiments, a request is generated by a user at a client system and received by a server system. The server system accesses initial data indicated or provided by the client system. The server system then performs an analysis to minimize the data needed for further reactions. In specific embodiments, a server can use proprietary methods or data at the server side while protecting those proprietary methods and data from access by the client system.

Method and/or apparatus for determining codons

Methods, computer systems, and computer program products for antibody engineering. A variant set for an antibody of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the antibody of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of position collectively define an antibody sequence space. A variant set comprising a plurality of variants of the antibody is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the antibody of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set. The variant set is redefined to comprise variants that include substitutions in the plurality of positions that are selected based on a function of the sequence-activity relationship.

Systems and methods for antibody engineering

Methods for determining a property that affects expression of polynucleotides are provided. A plurality of polynucleotides each encoding a polypeptide sequence is constructed. A frequency that a sequence element is used in a first polynucleotide is different than in a second polynucleotide. Each polynucleotide is expressed in an expression system to obtain an expression property value thereby constructing a dataset that contains, for each respective polynucleotide, sequence element occurrence in the respective polynucleotide and the measured expression property value of the respective polynucleotide. A model is computed that describes variation in the measured expression property values as a function of a plurality of variables and weights. From the model, a property that affects expression of polynucleotides in the expression system is determined, where the property is an effect that the frequency of occurrence of one or more sequence elements has on the expression property of polynucleotides in the expression system.

Systems and methods for constructing frequency lookup tables for expression systems

Methods and devices for more efficiently engineering diversity into recombinant polypeptides and/or nucleic acids are provided herein. For example, a variety of methods of selecting and/or assessing potential crossover sites in an amino acid sequence or a nucleotide sequence are provided, as well as the resulting chimeric product sequences. These methods include, e.g., consideration of structural, functional and/or statistical data in the selection and assessment of sequences and crossover sites for use in recombination.

Optimization of crossover points for directed evolution

A method of determining a property that affects expression of polynucleotides in an expression system. A plurality of polynucleotides, each encoding a polypeptide sequence, is constructed. An amino acid is encoded a plurality of times in both a first and second polynucleotide in the plurality. The amino acid is encodable by a plurality of synonymous codons including a first codon. The first codon is in the first polynucleotide at a first frequency relative to other synonymous codons, and is in the second polynucleotide at a second frequency relative to other synonymous codons. The first and second frequencies are different. Each polynucleotide is individually expressed in the expression system to measure an expression property value of the polynucleotides, thereby determining a property that affects expression of polynucleotides. The property is an effect that a frequency of use of one or more codons has on expression of polynucleotides in the expression system.

Synthetic nucleic acids for expression of encoded proteins

Methods of recombining nucleic acids, including homologous nucleic acids, are provided. Families of gene shuffling oligonucleotides and their use in recombination procedures, as well as polymerase and ligase mediated recombination methods are also provided.

Oligonucleotide mediated nucleic acid recombination

The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding an aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of. The present invention further relates to vectors, host cells, and mutant strains ofin which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.

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In silico nucleic acid recombination methods, related integrated systems utilizing genetic operators and libraries made by in silico shuffling methods are provided. One disclosed method involves identifying and producing a polypeptide. The method may involve (a) receiving data identifying sequences of two or more parental polypeptides or parental nucleic acids that encode the polypeptides; (b) selecting one or more cross-over sites on the sequences thereby defining one or more recombinant polypeptides or recombinant nucleic acids; (c) selecting at least one of the recombinant polypeptides or recombinant nucleic acids; (d) recombining one or more oligonucleotides, at least one of which has a sequence matching some or all of that of the recombinant polypeptides or recombinant nucleic acids selected in (c); (e) selecting at least some of the recombined oligonucleotides produced in (d); and (f) producing a polypeptide encoded by the selected nucleic acid.

Methods for identifying and producing polypeptides

In silico nucleic acid recombination methods, related integrated systems utilizing genetic operators are used to identify sets of oligonucleotides for in vitro recombination. In certain embodiments, the methods involve inputting amino acid sequence character strings into a digital system and back-translating the amino acid character strings into a plurality of nucleic acid character strings. The nucleic acid character strings are then processed to define and select at least one recombinant nucleic acid for use in identifying one or more oligonucleotides for in vitro recombination.

Methods for identifying sets of oligonucleotides for use in an in vitro recombination procedures

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Belmont, CA, United States of America

Claes Gustafsson