Genentech, Inc.

Avidbiotics Corporation

Xyphos Biosciences Inc.

New York University

Other

University of California

University of Texas System

David W Martin, Jr

Steven R Williams

Ingrid W Caras

Victor N Nussenzweig

Michael A Davitz

Dean M Scholl

Dana Gebhart

Kyle Landgraf

Daniel P Steiger

William I Wood

Joseph L Goldstein

Michael S Brown

David W Leung

Andrew Jamieson

David W Russell

R Glenn Hammonds, Jr

Thomas C Sudhof

Steven A Spencer

Jeffery F Miller

Gregory Govoni

Kaman C Kim

Tarah Baron

Min Xu

Mari Gingery

Sergei Doulatov

Asher Hodes

Andrew C Jamieson

The present disclosure relates to non-natural NKG2D receptors attached to mammalian cell surfaces wherein the non-natural receptors do not directly signal or directly activate the cell when the receptor is bound by cognate non-natural α1-α2 domains of NKG2D ligands modified to specifically bind the non-natural NKG2D receptors. The non-natural α1-α2 domains of NKG2D ligands may be attached to heterologous atoms or molecules including polypeptides, in some embodiments cytokines or modified cytokines, antibodies or fragments of antibodies.

Non-natural NKG2D receptors that do not directly signal the cells to which they are attached

This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified &#x3b1;1-&#x3b1;2 domains of NKG2D ligands.

Insertable variable fragments of antibodies and modified A1-A2 domains of NKG2D ligands

This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified &#x3b1;1-&#x3b1;2 domains of NKG2D ligands. This application further relates to modified &#x3b1;1-&#x3b1;2 domains of NKG2D ligands attached to polypeptides, in some embodiments antibodies or fragments of antibodies. This application further relates to antigen-binding peptides derived from light and heavy chain antibody variable domains, which contain two linker regions and a split variable domain.

Insertable variable fragments of antibodies and modified &#x3b1;1-&#x3b1;2 domains of NKG2D ligands

This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their &#x3b1;1-&#x3b1;2 platform domain, to the intended target cell specifically. The &#x3b1;1-&#x3b1;2 domain is contiguous with a heterologous &#x3b1;3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the &#x3b1;3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified &#x3b1;3 domain of a MIC protein.

Non-natural MIC proteins

This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically killbacteria, dangerous human pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous producer cells that, unlike, do not die in the presence of oxygen. Disclosed also is the specific gene of the isolated gene cluster that determines the killing spectrum of the R-type bacteriocin and the demonstration that the killing spectra of diffocins can be altered by engineering orf1374 of the diffocin genetic locus. This invention offers a potent bactericidal agent and a means to make it in order to kill selectivelybacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.

Diffocin and methods of use thereof

Modified forms of naturally occurring bacteriocins, such as the R-type pyocins of, are disclosed. The bacteriocins are modified at the ends of their tail fibers in a region responsible for binding specificity and affinity to their cognate binding partners, or receptors, such as those on the surface of bacteria. Methods for the use of the modified bacteriocins, such as to bind receptors, including virulence or fitness factors, on the surfaces of bacteria, are also described.

Modified bacteriocins and methods for their use

This invention relates to the diversification of nucleic acid sequences by use of a nucleic acid molecule containing a region of sequence that acts as a template for diversification. The invention thus provides nucleic acid molecules to be diversified, as well as those which act as the template region (TR) and in concert with the TR for directional, site-specific diversification. Further provided are methods of preparing and using these nucleic acid sequences.

Site specific system for generating diversity protein sequences

Novel fusions of a GPI signal domain and a polypeptide heterologous to the GPI signal domain donor polypeptide are provided for industrial use. Therapeutic administration of the GPI-linked product of the fusions enables the targeting of biological activity to cell membrane surfaces.

Decay accelerating factor (DAF) and nucleic acid encoding it

This application relates to nucleic acids encoding decay accelerating factor (hereinafter abbreviated as DAF), as well as vectors and cells which comprise such nucleic acids. Additionally, nucleic acids which encode variants of DAF, such as insertion, deletion or substitution variants, are described. This application also relates to the preparation of DAF in recombinant cell culture. In particular, it is concerned with the large scale manufacture of DAF suitable for pharmaceutical or diagnostic use.

Decay accelerating factor (DAF) and nucleic acids encoding it

Biological effects of agents for diagnostic or therapeutic use are evaluated by administration of the agents to transgenic animals which are transformed with heterologous DNA and which are immune tolerant to the expression product of the heterologous DNA. In a further embodiment, preparations that are immunogenic in the transgenic animal model are purified by reverse immunoaffinity chromatography on antibody obtained from responding transgenic animals.

Method for evaluating and modifying biological activity

Method for evaluating immunogenicity

Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's) , which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeats 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.

Method and composition for identifying substances which activate

Growing community of inventors

San Francisco, CA, United States of America

David W Martin, Jr