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, 1995
Date of Patent:
September 8, 1998
Assignee:
Xoma Corporation
Inventors:
Mark Leslie White, Stephen Fitzhugh Carroll, Jeremy Kam-kuen Ma
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:
November 25, 1996
Date of Patent:
July 21, 1998
Assignee:
XOMA Corporation
Inventors:
Arnold Horwitz, Lewis H. Lambert, Jr., Roger G. Little, II
Abstract: Methods are described for identifying the amino acid residues of an antibody variable domain which may be modified without diminishing the native affinity of the domain for antigen while reducing its immunogenicity with respect to a heterologous species and for preparing so modified antibody variable domains which are useful for administration to heterologous species. Antibody variable regions prepared by the methods of the invention are also described.
Abstract: The present invention provides methods of potentiating the gram-negative bactericidal activity of BPI protein products by means of administering LBP protein products.
Abstract: Methods are described for identifying the amino acid residues of an antibody variable domain which may be modified without diminishing the native affinity of the domain for antigen while reducing its immunogenicity with respect to a heterologous species and for preparing so modified antibody variable domains which are useful for administration to heterologous species. Antibody variable regions prepared by the methods of the invention are also described.
Type:
Grant
Filed:
August 13, 1993
Date of Patent:
June 16, 1998
Assignee:
Xoma Corporation
Inventors:
Gary M. Studnicka, Roger G. Little, II, Dianne M. Fishwild, Fred R. Kohn
Abstract: The present invention provides peptides having an amino acid sequence that is the amino acid sequence of a human bactericidal/permeability-increasing protein (BPI) functional domain or a subsequence thereof, and variants of the sequence or subsequence thereof, having at least one of the BPI biological activities, such as heparin binding, heparin neutralization, LPS binding, LPS neutralization or bactericidal activity. The invention provides peptides and pharmaceutical compositions of such peptides for a variety of therapeutic uses.
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:
June 7, 1995
Date of Patent:
May 26, 1998
Assignee:
Xoma Corporation
Inventors:
Marc D. Better, Stephen F. Carroll, Gary M. Studnicka
Abstract: Methods and materials for the treatment of humans suffering from hemorrhage due to trauma are provided, in which therapeutically effective amounts of BPI protein products are administered.
Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).
Type:
Grant
Filed:
January 24, 1995
Date of Patent:
May 19, 1998
Assignee:
XOMA Corporation
Inventors:
Nadav Friedmann, Patrick J. Scannon, Sander J. H. van Deventer, Marijke A. M. von der Mohlen, Nancy Wedel
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:
June 7, 1995
Date of Patent:
April 28, 1998
Assignee:
Xoma Corporation
Inventors:
Marc D. Better, Stephen F. Carroll, Gary M. Studnicka
Abstract: Antithrombotic materials and methods are provided for the treatment of thrombotic disorders, in which therapeutically effective amounts of BPI protein products are administered.
Abstract: The present invention provides peptides having an amino acid sequence that is the amino acid sequence of a human bactericidal/permeability-increasing protein (BPI) functional domain or a subsequence thereof, and variants of the sequence or subsequence thereof, having at least one of the BPI biological activities, such as heparin binding, heparin neutralization, LPS binding, LPS neutralization or bactericidal activity. The invention provides peptides and pharmaceutical compositions of such peptides for a variety of therapeutic uses.
Abstract: Disclosed are novel biologically active lipopolysaccharide binding protein (LBP) derivatives including LBP derivative hybrid proteins which are characterized by the ability to bind to and neutralize LPS and which lack the CD14-mediated immunostimulatory properties of holo-LBP.
Type:
Grant
Filed:
June 17, 1994
Date of Patent:
March 24, 1998
Assignee:
XOMA Corporation
Inventors:
Helene Gazzano-Santoro, Georgia Theofan, Patrick W. Trown
Abstract: The present invention relates to 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 use for such antibody.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
February 24, 1998
Assignee:
XOMA Corporation
Inventors:
Randy R. Robinson, Alvin Y. Liu, Jeffrey A. Ledbetter
Abstract: Improved therapeutic uses of bactericidal/permeability-increasing protein (BPI) involve use of BPI protein product formulations in the form of physiologically stable dimeric associations of BPI protein product monomers characterized by enhanced in vivo biological activity. Preferred formulations include 50 percent or more by weight dimeric product.
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:
June 6, 1995
Date of Patent:
December 16, 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:
June 6, 1995
Date of Patent:
December 16, 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: Polypeptide pharmaceutical compositions having improved stability and resistance to aggregation, particle formation and precipitation comprising a polypeptide pharmaceutical and poloxamer surfactants alone, or in combination with polysorbate surfactants. Preferred polypeptides stabilized are bactericidal/permeability increasing (BPI) protein, biologically active fragments of BPI, biologically active analogs of BPI, and biologically active variants of BPI.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
December 9, 1997
Assignee:
Xoma Corporation
Inventors:
Weldon Courtney McGregor, James Stubstad, C. Paul Chang
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:
May 25, 1995
Date of Patent:
December 2, 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 provides methods of treating a subject suffering from adverse effects, complications or conditions, associated with or resulting from corneal transplantation, by topical administration of suitable ophthalmic preparations of bactericidal/permeability-increasing (BPI) protein products.