Xoma Corporation

Other

Xoma Technology Ltd.

Trigen Gmbh

Shau-Ping Lei

Marc D Better

Randy R Robinson

Arnold H Horwitz

Gary L Wilcox

Alvin Y Liu

Randolph Wall

Changtung Paul Chang

Hun-Chi Lin

Susan L Bernhard

Steve F Carroll

Julie A Lane

Arnold H Horowitz

The invention is directed to chimeric immunoglobulins that recognize a human tumor antigen bound by antibody, ING-2, ING-3, ING-4 or KM10, the production of such chimeric immunoglobulins, and their use.

Production of chimeric antibodies with specificity to human tumor antigens

Modular assembly of antibody genes, antibodies prepared thereby and use

The invention is directed to the pectate lyase B secretion signal and its use to express operably linked sequences in bacterial hosts.

Pectate lyase signal sequence

The invention is directed to a chimeric immunoglobulin that recognizes the human tumor antigen bound by antibody ING-1, its production, and use.

Production of chimeric mouse-human antibodies with specificity to human

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. The invention also relates to the secretion of chimeric antibodies and fragments thereof from yeast in functional form.

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.

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. The invention also relates to the secretion of chimeric antibodies and fragments thereof from yeast in functional form.

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.

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.

Vectors with pectate lyase signal sequence

Genetically engineered E. coli carry vectors containing inserts that code for Clostridium histolyticum collagenase. These inserts code for: (a) a form of collagenase having a molecular weight of about 68,000 daltons in the essential absence of larger forms of collagenase; (b) the 68 kd form of collagenase and a fusion polypeptide consisting of the collagenase protein fused to at least a portion of the .beta.-galactosidase protein of E. coli or (3) the 68 kd form of collagenase and polypeptides of molecular weight of from above about 68,000 daltons to about 100,000 daltons and having the enzymatic activity of C. histolyticum collagenase as indicated by digestion of .sup.3 H-acetylated collagen and by specific inhibition by 1,10-phenanthroline plus EDTA. The collagenase genes in the transformed E. coli are expressed efficiently in the transformed cells to yield enzymatically active and immunologically cross-reactive collagenase. In particular, the 68 kd form of collagenase is resistant to autocatalytic degradation and is stable to long-term storage. Genetically engineered collagenase, especially the 68 kd form that is resistant to autocatalytic degradation, can be used for isolation of pancreatic islets, for the isolation of dispersed tumor cells, or for treatment of 'slipped disc.'

Recombinant 68,000 dalton collagenase of Clostridium histolyticum

The present invention provides purified and isolated polynucleotides encoding Type I ribosome-inactivating proteins (RIPs) such as gelonin 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.

Materials comprising and methods of preparation and use for

Genetically engineered E. coli carry vectors containing inserts that code for Clostridium histolyticum collagenase. These inserts code for: (a) a form of collagenase having a molecular weight of about 68,000 daltons in the essential absence of larger forms of collagenase; (b) the 68 kd form of collagenase and a fusion polypeptide consisting of the collagenase protein fused to at least a portion of the .beta.-galactosidase protein of E. coli; or (3) the 68 kd form of collagenase and polypeptides of molecular weight of from above about 68,000 daltons to about 100,000 daltons and having the enzymatic activity of C. histolyticum collagenase as indicated by digestion of .sup.3 H-acetylated collagen and by specific inhibition by 1,10-phenanthroline plus EDTA. The collagenase genes in the transformed E. coli are expressed efficiently in the transformed cells to yield enzymatically active and immunologically cross-reactive collagenase. In particular, the 68 kd form of collagenase is resistant to autocatalytic degradation and is stable to long-term storage. Genetically engineered collagenase, especia

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Los Angeles, CA, United States of America

Shau-Ping Lei