Cell Genesys, Inc.

Abgenix, Inc.

Biomolecular Holdings LLC

Other

Virologic, Inc.

University of California

Monogram Biosciences, Inc.

Shimadzu Corporation

Capon, Daniel J.

Daniel J Capon

Raju S Kucherlapati

Aya Jakobovits

Daniel G Brenner

Sue Klapholz

Christos J Petropoulos

Douglas H Smith

Huan Tian

Genine A Winslow

Miriam Siekevitz

Robert B Dubridge

Krisztina M Zsebo

Koichi Tanaka

Steven R Williams

Margo R Roberts

Taka-Aki Sato

Oliver Smithies

Beverly H Koller

Arthur Weiss

Brian A Irving

Gary Greenburg

Mariona Lourdes De Rafael

Sue Kalpholz

Mariona Lourdes Arbones De Rafael

This invention provides a tetrahedral antibody comprising a first domain, a second domain, a third domain, a fourth, a fifth domain, and a sixth domain, wherein the first domain and the second domain are each a Fc domain of an IgG antibody, wherein the third domain and the fourth domain are each a Fab domain of an anti-CD20 antibody wherein the fifth domain and the sixth domain are each a Fab domain of an anti-CD-19 antibody. This invention also provides methods of producing the tetrahedral antibody of the invention, pharmaceutical compositions comprising the tetrahedral antibody of the invention, and methods of treating B cell cancer, inflammatory disease, and B cell disease by administering the pharmaceutical compositions of the invention.

NK/monocyte engagers

The present invention provides an antibody that can bind to targets with greater affinity. A flexible antibody-like molecule having a nonpeptide hinge part comprising: a group having a nonpeptide hinge part represented by a general formula (I): XY-Asp-Lys-Thr-His-Thr (SEQ ID No. 1)- wherein X represents an amino acid or a peptide composed of 2 to 50 amino acid residues, and Y represents for a group having an alkyleneoxide; and an antibody Fc fragment bound to the group having a nonpeptide hinge part.

Peptide-hinge-free flexible antibody-like molecule

The present invention provides an antibody that can bind to targets with greater affinity. A flexible antibody-like molecule having a nonpeptide hinge part comprising: a group having a nonpeptide hinge part represented by a general formula (I): XY-Asp-Lys-Thr-His-Thr (SEQ ID No. 1)&#x2014;wherein X represents an amino acid or a peptide composed of 2 to 50 amino acid residues, and Y represents for a group having an alkyleneoxide; and an antibody Fc fragment bound to the group having a nonpeptide hinge part.

The present invention provides compounds producing compounds having the structure (I). Wherein A is a first polypeptide component of the compound; wherein C is a second polypeptide component of the compound, which polypeptide component comprises consecutive amino acids which (i) are identical to a stretch of consecutive amino acids present in a chain of an Fdomain of an antibody; (ii) bind to an Freceptor; and (iii) have at their N-terminus a sequence selected from the group consisting of a cysteine, selenocysteine, CP, CPXCP (where X=P, R, or S) (SEQ ID NOs: 128-130), CDKTHTCPPCP (SEQ ID NO: 131), CVECPPCP (SEQ ID NO 132), CCVECPPCP (SEQ ID NO 133) and CDTPPPCPRCP (SEQ ID NO 134), wherein B is a chemical structure linking A and C; wherein the dashed line between B and C represents a peptidyl linkage; wherein the solid line between A and B represents a nonpeptidyl linkage comprising the structure (II). 

Hybrid immunoglobulin containing non-peptidyl linkage

The present invention provides a compound having the structure:A-B - - - Zwherein A is a biologically active structure of the compound; wherein Z is a protein component of the compound, which protein component comprises one or more polypeptides, wherein at least one of the one or more polypeptides comprises consecutive amino acids which (i) are identical to a stretch of consecutive amino acids present in a chain of an Fdomain of an antibody; (ii) bind to an Freceptor; and (iii) have at their N-terminus a sequence selected from the group consisting of a cysteine or selenocysteine; wherein the dashed line between B and Z represents a peptidyl linkage; and wherein the solid line between A and B represents a nonpeptidyl linkage, as well as intermediates dimers thereof, and processes of producing the compounds of the invention.

Problems to be Solved The present invention provides an affinity support capable of trapping a substance by cooperative binding that is less likely to cause dissociation even when the substance is a molecule other than an antibody, and a trapping method using the same. Means to Solve the Problems A method of trapping a substance comprising the step of contacting an objective to be trapped with an affinity support comprising a support, a spacer bound to the support and an affinity substance bound to the spacer, so as to bind the objective to be trapped to the affinity substance, wherein each one of the objective to be trapped has a plural of affinity sites and the affinity substance binds to at least two of the affinity sites simultaneously.

Affinity support and method for trapping substance using the same

Hybrid immunoglobulins containing moving parts are provided as well as related compositions and methods of use and methods of production. In addition, analogous genetic devices are provided as well as related compositions and methods of use and methods of production.

Hybrid immunoglobulins with moving parts

This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector Comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c). This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time; (b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient.

Compositions and methods for determining anti-viral drug susceptibility and resistance and anti-viral drug screening

This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c). This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time; (b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient. This invention also provides a method for evaluating the biological effectiveness of a candidate anti-viral drug compound. Compositions including resistance test vectors comprising a patient-derived segment and an indicator gene and host cells transformed with the resistance test vectors are provided.

Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Human antibodies derived from immunized xenomice

The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Generation of xenogeneic antibodies

Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

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

Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Growing community of inventors

Hillsborough, CA, United States of America

Daniel J Capon