Maxygen, Inc.

Codexis Mayflower Holdings, LLC

Codexis, Inc.

Amgen Mountain View, Inc.

Pioneer Hi-bred International, Inc.

Novozymes A/s

Amunix Operating Inc.

Amunix Pharmaceuticals, Inc

Maxygar, Inc.

Codexis Mayflower Holding, LLC

Willem P C Stemmer

Phillip A Patten

Jeremy S Minshull

Claes Gustafsson

Steven Henry Bass

Matthew B Tobin

Andreas Crameri

Jon Edward Ness

Sergey A Selifonov

Mark D Welch

Lorraine Joan Giver

Stephen B Del Cardayre

Linda A Castle

Joseph A Affholter

Claus M Krebber

Gjalt W Huisman

Stephen DelCardayre

Joshua A Silverman

Juha Punnonen

Sun Ai Raillard

Robert Gerald Whalen

Venkiteswatan Mani Subramanian

Russell J Howard

Ying-Xin Zhang

Ling Yuan

Volker Heinrichs

Anthony Cox

Brian S Carr

Volker Schellenberger

Robin A Emig

Sanjeev Satyal

Chia-wei Wang

Nathan C Geething

Benjamin Spink

D Victor Perlroth

Alice Bakker

Amy N Duguay

Venkiteswaran Subramanian

Candace Swimmer

Richard Smith

Benjamin M Alba

Stanley Goldman

Pascal Longchamp

Torben Vedel Borchert

Joel R Cherry

Stephane J Jenne

Yong Hong Chen

Stephan Jenne

S Christopher Davis

Qiang Liu

Simon Christopher Davis

Steve Bass

Takashi Yamamoto

John E Ness

Claus Gustafsson

Qiang Lui

Tony Cox

Venkitswaran Subramanian

Nay Wei Soong

Andreas M Cramieri

The present invention relates to binding fusion protein compositions comprising targeting moieties linked to extended recombinant polypeptide (XTEN), binding fusion protein-drug conjugate compositions, and XTEN-drug conjugate compositions, isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of diseases, disorders, and conditions.

Binding fusion proteins, binding fusion protein-drug conjugates, XTEN-drug conjugates and methods of making and using same

In particular, this invention provides novel methods of populating data structures for use in evolutionary modeling. In particular, this invention provides methods of populating a data structure with a plurality of character strings. The methods involve encoding two or more biological molecules into character strings to provide a collection of two or more different initial character strings; selecting at least two substrings from the pool of character strings; concatenating the substrings to form one or more product strings about the same length as one or more of the initial character strings; adding the product strings to a collection of strings; and optionally repeating this process using one or more of the product strings as an initial string in the collection of initial character strings.

Methods of populating data structures for use in evolutionary simulations

The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.

Evolution of whole cells and organisms by recursive sequence recombination

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 is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to 'evolve' individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.

Methods and compositions for cellular and metabolic engineering

Integrated systems and methods for diversity generation and screening are provided. The systems use common fluid and array handling components to provide nucleic acid diversification, transcription, translation, product screening and subsequent diversification reactions.

Integrated systems and methods for diversity generation and screening

A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

Methods for generating polynucleotides having desired characteristics by iterative selection and recombination

Polypeptides comprising monomer domains that bind to c-MET, or portions thereof, are provided.

c-MET kinase binding proteins

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

In particular, this invention provides novel methods of populating data structures for use in evolutionary modeling. In particular, this invention provides methods of populating a data structure with a plurality of character strings. The methods involve encoding two or more a biological molecules into character strings to provide a collection of two or more different initial character strings; selecting at least two substrings from the pool of character strings; concatenating the substrings to form one or more product strings about the same length as one or more of the initial character strings; adding the product strings to a collection of strings; and optionally repeating this process using one or more of the product strings as an initial string in the collection of initial character strings.

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Los Gatos, CA, United States of America

Willem P C Stemmer