Bio-technology General Corporation

Savient Pharmaceuticals, Inc.

Bio-technology General (israel) Ltd.

Avigdor Levanon

Tikva Vogel

Amos B Oppenheim

Moshe M Werber

Marian Gorecki

Elisha P Zeelon

Rachel Guy

Amos Panet

Haim Aviv

Menachem Zeevi

Jacob R Hartman

Hilla Locker-Giladi

Hilla Locker-Galadi

Hadassa Shaked

Daniel Plaksin

Meir Fischer

Tuvia Peretz

Meir Rigbi

Janette Lazarovits

Tikva Vogil

Arie Goldlust

Orly Lifshitz

Pinhas E Zeelon

Yocheved Hagay

Esther Szanton

The present invention is directed to novel peptides and polypeptides that specifically bind to target cells and may have anti-cancer activity, especially blood-related cancers. The present invention includes a peptide or polypeptide comprising an Fv molecule, having a heavy variable chain comprising CDR3, CDR2 and CDR1 regions comprising the amino acid sequences SEQ ID NOS:8, 115 and 114, respectively.

Specific human antibodies for selective cancer therapy

This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides. The invention also provides for purified polypeptides substantially free of other substances of human origin which have an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and which are capable of binding to fibrin.

Fibrin binding domain polypeptides and uses and methods of producing same

The present invention provides an antibody which specifically reacts with an epitope of a polypeptide comprising the amino acid sequence X-Y-CYS GLN GLU GLU GLU CYS PRO ASP PRO TYR LEU CYS SER PRO VAL THR ASN ARG CYS GLU CYS THR PRO VAL LEU CYS ARG MET TYR CYS LYS PHE TRP ALA LYS ASP GLU LYS GLY CYS GLU ILE CYS LYS CYS GLU GLU LEU CYS GLN ASN GLN ASN CYS THR LYS ASP MET LEU CYS SER SER VAL THR ASN ARG CYS ASP CYS GLN ASP PHE LYS CYS PRO GLN SER TYR CYS-Z (SEQ. ID NO. 1) wherein X is MET or absent; Y is 0-28 amino acids of the sequence LYS MET CYS TRP ASN LYS GLY CYS PRO CYS GLY GLN ARG CYS ASN LEU HIS ARG ASN GLU CYS GLU VAL ILE ALA GLU ASN ILE GLU, (SEQ. ID NO. 2) with the proviso that if part of the sequence is present, it is a carboxy-terminal part of the sequence including the carboxy-terminal GLU and wherein Val may be preceded by Gly; and Z is absent or all or a part of the sequence Pro,-Lys,shown in FIG.,(SEQ. ID NO. 24), with the proviso that if part of the sequence is present, it is the amino part of the sequence. The present invention also provides a monoclonal antibody as described above.

Polypeptide having factor Xa inhibitory activity

An improved vector upon introduction into a suitable bacterial host containing the thermolabile repressor C.sub.I renders the host cell capable, upon increasing the temperature of the host cell to a temperature at which the repressor is destroyed, of effecting expression of a desired gene inserted into the vector and production of polypeptide encoded by the gene. The vector is a double-stranded DNA molecule which includes in 5' to 3' order the following: a DNA sequence which contains the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site for binding antiterminator N protein produced by the host cell; a DNA sequence which contains a ribosomal binding site for rendering the mRNA of the desired gene capable of binding to ribosomes within the host cell; an ATG initiation codon or a DNA sequence which is converted into an ATG initiation codon upon insertion of the desired gene into the vector; a restriction enzyme site for inserting the desired gene into the vector in phase with the ATG initiation codon; and additionally a DNA sequence which contains an origin of replication from a bacterial plasmid capable of autonomous replication in the host cell and a DNA sequence which contains a gene associated with a selectable or identifiable trait which is manifested when the vector is present in the host cell.

Expression vectors for enhanced production of polypeptides, plasmids

This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus-or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides. The invention also provides for purified polypeptides substantially free of other substances of human origin which have an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and which are capable of binding to fibrin.

A novel polypeptide derived from the leech Hirudo medicinalis was found to be able to inhibit Factor Xa thereby reducing the extent of blood coagulation. The polypeptide is useful in treating conditions of excessive blood coagulation. A recombinant organism containing cDNA encoding the polypeptide has been deposited in the ATCC under Accession No. 69134. Recombinant microorganisms able to produce the polypeptide have been deposited in the ATCC under Accession Nos. 69135, 69137 and 69269.

Polypeptide having factor Xa inhibitory method of reducing blood

Polypeptide having Factor Xa inhibitory activity

Method of treating of preventing influenza

The present invention provides a recombinant polypeptide having the amino acid sequence X-tyr.sup.26 -gly.sup.110 where tyr.sup.26 -gly.sup.110 is identical to the sequence shown in FIG. 10, and wherein X is methionine or absent and wherein asn.sup.72 may be substituted by pro. The invention further provides a method of producing the polypeptide which comprises transforming a host cell with an expression plasmid encoding the polypeptide, culturing the transformed host cell so that the cell produces the polypeptide encoded by the plasmid, and a method of recovering the polypeptide so produced.

Production of recombinant factor Xa inhibitor of leech Hirudo

DNA encoding novel polypeptide having Factor Xa inhibitory activity

An improved vector upon introduction into a suitable host containing the thermolabile repressor C.sub.I renders the host capable of effecting expression of a desired gene. The vector is a double-stranded DNA molecule which includes in 5' to 3' order the following: the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site; a first restriction enzyme site permitting replacement of the ribosomal binding site which follows thereafter; a ribosomal binding site; an ATG initiation codon or DNA which is converted into an ATG initiation codon upon insertion of the desired gene into the vector; a second restriction enzyme site for inserting the gene in phase with the ATG codon; a T.sub.1 T.sub.2 rRNA transcription termination sequence; an origin of replication and a gene associated with a selectable or identifiable phenotypic trait manifested when the vector is present in the host. The distance between the 3' end of the P.sub.L O.sub.L promoter and operator sequence and the 5' end of the N utilization site is less than about 80 base pairs and the distance between the 3' end of the N utilization site and the 5' end of the ribosomal binding site is less than about 300 base pairs. Plasmids have been constructed from the vectors and used to produce bovine, chicken and porcine growth hormones, human apolipoprotein E and human superoxide dismutase.

Expression vectors containing .lambda.P.sub.L promoter and T.sub.1

This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imagifig a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides. The invention also provides for purified polypeptides substantially free of other substances of human origin which have an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and which are capable of binding to fibrin.

A plasmid for the production of superoxide dismutase or an analog thereof which upon introduction into a suitable bacterial host containing the thermolabile repressor C.sub.I renders the host cell capable, upon increasing the temperature of the host cell to a temperature at which the repressor is destroyed, of effecting expression of DNA encoding superoxide dismutase and production of superoxide dismutase. The plasmid is a double-stranded DNA molecule which includes in 5' to 3' order the following: a DNA sequence which contains the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site for binding antiterminator N protein produced by the host cell; a DNA sequence which contains a ribosomal binding site for rendering the mRNA of the gene encoding superoxide dismutase capable of binding to ribosomes within the host cell; an ATG initiation codon; a restriction enzyme site for inserting the gene encoding superoxide dismutase into the plasmid in phase with the ATG initiation codon; a gene encoding superoxide dismutase; and additionally a DNA sequence which contains an origin of replication from a bacterial plasmid capable of autonomous replication in the host cell and a DNA sequence which contains a gene associated with a selectable or identifiable trait which is manifested when the plasmid is present in the host cell.

Growing community of inventors

Rehovot, Israel

Avigdor Levanon