Avidbiotics Corporation

Cell Genesys, Inc.

Xyphos Biosciences Inc.

Steven R Williams

David W Martin, Jr

Dean M Scholl

Robert B Dubridge

Daniel J Capon

Raju S Kucherlapati

Oliver Smithies

Beverly H Koller

Dana Gebhart

Andrew Jamieson

Daniel Steiger

Gary Greenburg

Kyle Landgraf

Daniel P Steiger

Mariona Lourdes De Rafael

Gregory Govoni

Kaman C Kim

Tarah Baron

Mariona Lourdes Arbones De Rafael

David W Martin

Gregory R Govoni

Dana M Gebhart

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

Recombinant P4 bacteriophage containing modified tail fibers having a base plate attachment region (BPAR) from a P2 bacteriophage gene H product and a heterologous receptor binding domain (RBD) are disclosed. Methods for the use of the recombinant P4 bacteriophage, such as to detect the presence of a target bacterium in a sample, are also described.

Recombinant bacteriophage and methods for their use

Modified forms of naturally occurring bacteriocins, such as the R-type pyocins of, are disclosed as are methods for producing them in GRAS organisms. 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

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.

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the &bgr; -microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Homologous recombination for universal donor cells and chimeric mammalian hosts

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2- microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as allogeneic donor cells. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Homologous recombination for allogeneic donor cells

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, each of the .beta..sub.2- microglobulin gene and the IFN-.gamma.R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

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San Francisco, CA, United States of America

Steven R Williams