Abstract: The present invention relates to a eukaryotic host cell that contains DNA encoding a chimeric antibody molecule comprising two heavy chains and two light chains, each of the chains comprising a variable region and a human constant region, said antibody having specificity for the antigen bound by the 2H7 murine monoclonal antibody. The invention is also related to methods of producing the antibody.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
October 14, 1997
Assignee:
Xoma Corporation
Inventors:
Randy R. Robinson, Alvin Y. Liu, Jeffrey A. Ledbetter
Abstract: Disclosed are novel bactericidal/permeability-increasing (BPI) protein products wherein cysteine residue number 132 or 135 is replaced by another amino acid residue, preferably an alanine or serine residue and/or wherein the leucine residue at position 193 is the carboxy terminal residue. Also disclosed are DNA sequences encoding methods for the production of the same in appropriate host cells, and stable homogeneous pharmaceutical compositions containing the analogs suitable for use treatment of gram negative bacterial infection and its sequelae.
Type:
Grant
Filed:
April 28, 1995
Date of Patent:
October 7, 1997
Assignee:
XOMA Corporation
Inventors:
Georgia Theofan, Arnold Horwitz, David Burke, Manik Baltaian, Lynn Grinna
Abstract: The present invention relates to methods for treating protozoan infections comprising administering to a subject suffering from protozoan infection, a bacteriocidal/permeability-inducing (BPI) protein product.
Abstract: Disclosed are novel hybrid fusion proteins comprising at their amino terminus, bactericidal/permeability-increasing protein or a biologically active fragment thereof and, at their carboxy terminus, at least one immunoglobulin heavy chain constant domain useful in treating bacterial infection. Also disclosed are DNA sequences encoding such proteins, recombinant methods for production of the proteins, and pharmaceutical preparations containing the recombinant products.
Type:
Grant
Filed:
May 19, 1993
Date of Patent:
July 1, 1997
Assignee:
XOMA Corporation
Inventors:
Georgia Theofan, Lynn S. Grinna, Arnold Horwitz
Abstract: The present invention provides therapeutic methods for treatment of conditions including the neutralization of the anti-coagulant activity of heparin, inhibition of angiogenesis, tumor and endothelial cell proliferation, and treatment of chronic inflammatory diseases by administration of bactericidal/permeability-increasing (BPI) protein products.
Abstract: The present invention relates to methods for treating fungal infection comprising administering to a subject suffering from a fungal infection a bactericidal/permeability-inducing (BPI) protein product.
Type:
Grant
Filed:
January 13, 1995
Date of Patent:
May 6, 1997
Assignee:
Xoma Corporation
Inventors:
Roger G. Little, II, Edward Lim, Patrick J. Scannon, Lewis J. Lambert, Jr.
Abstract: The present invention provides purified and isolated polynucleotides encoding Type I ribosome-inactivating proteins (RIPs) and analogs of the RIPs having a cysteine available for disulfide bonding to targeting molecules. Vectors comprising the polynucleotides and host cells transformed with the vectors are also provided. The RIPs and RIP analogs are particularly suited for use as components of cytotoxic therapeutic agents of the invention which include gene fusion products and immunoconjugates. Cytotoxic therapeutic agents or immunotoxins according to the present invention may be used to selectively eliminate any cell type to which the RIP component is targeted by the specific binding capacity of the second component of the agent, and are suited for treatment of diseases where the elimination of a particular cell type is a goal, such as autoimmune disease, cancer and graft-versus-host disease.
Type:
Grant
Filed:
April 18, 1995
Date of Patent:
April 15, 1997
Assignee:
XOMA Corporation
Inventors:
Marc D. Better, Stephen F. Carroll, Gary M. Studnicka
Abstract: The invention relates to the secretion of heavy chain immunoglobulin fragments and light chain immunoglobulins from prokaryotic hosts using a prokaryotic secretion signal peptide wherein the heavy chain fragments and light chains are capable of associating to form an antigen binding antibody fragment.
Type:
Grant
Filed:
April 29, 1994
Date of Patent:
April 8, 1997
Assignee:
Xoma Corporation
Inventors:
Randy R. Robinson, Alvin Y. Liu, Arnold H. Horwitz, Marc Better, Randolph Wall, Shau-Ping Lei, Gary L. Wilcox
Abstract: The invention relates to cDNA genetic sequences, vehicles containing same as well as hosts transformed therewith, for the production of chimeric immunoglobulin molecules, functional fragments thereof and immunoglobulin derivatives exhibiting novel functional properties comprising human constant region modules and non-human variable region modules, or for class switching antibody molecules and/or chains.The invention also relates to DNA coding for pectate lyase signal peptide has been cloned on a plasmid to create a secretion vector which is capable of producing a chosen protein which is transported across the bacterial membrane. The secretion vector has been used to secrete extracellular thaumatin and extracellular chimeric antibody fragments. The proteins produced by this vector have biological activity. The thaumatin is properly folded and the antibody fragments are capable-of binding antigens on target cancer cells.
Type:
Grant
Filed:
August 18, 1994
Date of Patent:
January 21, 1997
Assignee:
Xoma Corporation
Inventors:
Randy R. Robinson, Alvin Y. Liu, Arnold H. Horwitz, Marc Better, Randolph Wall, Shau-Ping Lei, Gary L. Wilcox
Abstract: The present invention relates to methods of treating gram-positive bacterial infections by administration of a BPI protein product alone, or in combination with an antibiotic. BPI protein product alone has a bactericidal or growth inhibitory effect on selected gram-positive organisms. BPI protein product also increases the susceptibility of gram-positive organisms to antibiotics and can even reverse resistance of gram-positive organisms to antibiotic.
Type:
Grant
Filed:
January 13, 1995
Date of Patent:
November 26, 1996
Assignee:
Xoma Corporation
Inventors:
Arnold Horwitz, Lewis H. Lambert, Jr., Roger G. Little, II
Abstract: The present invention provides methods of treating adverse physiological effects associated with intestinal ischemia reperfusion by administering to a subject suffering from the effects of intestinal ischemia reperfusion an effective amount of a BPI protein product.
Type:
Grant
Filed:
April 22, 1994
Date of Patent:
November 26, 1996
Assignee:
XOMA Corporation
Inventors:
William S. Ammons, K aroly M. M esz aros
Abstract: Gene expression elements and their use in production of chimeric antibodies with human constant regions and murine variable regions, and mouse human chimeric antibodies having specificity to human tumor cells, methods of their production, and their use.
Type:
Grant
Filed:
December 27, 1994
Date of Patent:
November 19, 1996
Assignee:
Xoma Corporation
Inventors:
Marc D. Better, Arnold H. Horwitz, Randy R. Robinson, Shau-Ping Lei, Changtung P. Chang
Abstract: The invention relates to DNA coding for a pectate lyase signal peptide which has been inserted into plasmids to create secretion vectors which are capable of producing a chosen protein by directing transport across the bacterial membrane. The secretion vectors have been used to secrete extracellular thaumatin and extracellular antibody fragments. The proteins produced by these vectors have biological activity. The thaumatin is properly folded and the antibody fragments are capable of binding antigens on target cancer cells.
Type:
Grant
Filed:
December 9, 1994
Date of Patent:
November 19, 1996
Assignee:
Xoma Corporation
Inventors:
Randy R. Robinson, Marc Better, Shau-Ping Lei, Gary L. Wilcox
Abstract: The present invention relates to methods and compositions for treating gram-negative bacterial infections, using BPI protein products. Co-treatment, or concurrent administration, of BPI protein product with an antibiotic in treatment of gram-negative bacterial infections improves the therapeutic effectiveness of the antibiotic, including increasing antibiotic susceptibility of gram-negative bacteria and reversing resistance of the bacteria to antibiotics.
Type:
Grant
Filed:
September 22, 1994
Date of Patent:
June 4, 1996
Assignee:
Xoma Corporation
Inventors:
Jonathan Cohen, Ada H. C. Kung, Lewis H. Lambert, Jr., Roger G. Little, II
Abstract: The present invention provides osteogenically active protein preparations comprising a heterodimer of P3 OF 31-34 subunit B and P3 OF 31-34 subunit D, which subunits are linked with at least one disulfide bond and methods for their preparation. The invention further provides cell lines transformed with nucleotide sequences encoding P3 OF 31-34 subunit B and P3 OF 31-34 subunit D and vectors comprising those sequences in operative association with an expression control sequence.
Type:
Grant
Filed:
August 29, 1994
Date of Patent:
April 16, 1996
Assignee:
Xoma Corporation
Inventors:
Lynn Grinna, Georgia Theofan, Thomas F. Parsons
Abstract: The present invention relates to a chimeric IgG1 antibody molecule comprising two heavy chains and two light chains, each of the chains comprising a human constant region and a variable region, said antibody having specificity for the antigen bound by the 2H7 murine monoclonal antibody. The invention also relates to the increased ADCC and CDC cytolytic activities of the chimeric antibody, methods of production by recombinant DNA techniques, and uses.
Type:
Grant
Filed:
March 5, 1991
Date of Patent:
March 19, 1996
Assignee:
XOMA Corporation
Inventors:
Randy R. Robinson, Alvin Y. Liu, Jeffrey A. Ledbetter
Abstract: The present invention provides methods of preventing or treating conditions associated with burn injuries by administering bactericidal/permeability-increasing (BPI) protein product.
Abstract: Bactericidal/permeability increasing (BPI) polypeptide pharmaceutical compositions having improved stability and resistance to aggregation, particle formation and precipitation comprising the polypeptide pharmaceutical and poloxamer surfactants alone, or in combination with polysorbate suractants. Preferred BPI polypeptides stabilized are bactericidal/permeability increasing (BPI) protein, biologically active fragments of BPI, and biologically active analogs of BPI.
Type:
Grant
Filed:
February 2, 1994
Date of Patent:
January 30, 1996
Assignee:
XOMA Corporation
Inventors:
Weldon C. McGregor, James Stubstad, C. Paul Chang
Abstract: The present invention provides a method for quantifying the presence of extracellular LBP in body fluids including blood in a subject comprising conducting an LBP immunoassay on plasma obtained from said subject.
Type:
Grant
Filed:
January 24, 1994
Date of Patent:
January 16, 1996
Assignee:
XOMA Corporation
Inventors:
Mark L. White, Stephen F. Carroll, Jeremy K. Ma
Abstract: The present invention provides a method for quantifying the presence of extracellular BPI in body fluids including blood in a subject comprising conducting a BPI immunoassay on plasma obtained from said subject.
Type:
Grant
Filed:
September 22, 1993
Date of Patent:
November 14, 1995
Assignee:
XOMA Corporation
Inventors:
Mark L. White, Stephen F. Carroll, Jeremy K. Ma