Patents Assigned to Enzon, Inc.
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Patent number: 7632504Abstract: The present invention relates to the chemical modification of single chain polypeptides by means of covalent attachment of strands of poly(ethylene glycol) PEG and similar poly(alkylene oxides) to single chain polypeptide binding molecules that have the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. Such preparations of modified single chain polypeptide binding molecules have reduced immugenicity and antigenicity as well as having a longer halflife in the bloodstream as compared to the parent polypeptide. These beneficial properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications. The invention also relates to multivalent antigen-binding molecules capable of PEGylation. Compositions of, genetic constructions for, methods of use, and methods for producing PEGylated antigen-binding proteins are disclosed.Type: GrantFiled: August 2, 2004Date of Patent: December 15, 2009Assignee: Enzon, Inc.Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Standford Lee
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Patent number: 7393953Abstract: Polymeric derivatives of indoles such as are disclosed. Methods of making and using the same as well as related polymeric conjugates are also disclosed.Type: GrantFiled: March 31, 2003Date of Patent: July 1, 2008Assignee: Enzon, Inc.Inventors: Hong Zhao, Richard B. Greenwald
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Patent number: 7262164Abstract: Thiol-linked polymeric prodrugs, methods of making and using the same are disclosed. The use of a sulfhydryl bond in combination with a benzyl elimination system results in the formation of prodrugs which can take advantage of plasma enzymes in vivo for regeneration of the parent molecule. A preferred prodrug in accordance with the invention is: where S-MP is 6-mercaptopurine.Type: GrantFiled: November 8, 2002Date of Patent: August 28, 2007Assignee: Enzon, Inc.Inventors: Yun H. Choe, Richard B. Greenwald
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Patent number: 7150872Abstract: The present invention relates to the chemical modification of single chain polypeptides by means of covalent attachment of strands of poly(ethylene glycol) PEG and similar poly(alkylene oxides) to single chain polypeptide binding molecules that have the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. Such preparations of modified single chain polypeptide binding molecules have reduced immugenicity and antigenicity as well as having a longer halflife in the bloodstream as compared to the parent polypeptide. These beneficial properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications. The invention also relates to multivalent antigen-binding molecules capable of PEGylation. Compositions of, genetic constructions for, methods of use, and methods for producing PEGylated antigen-binding proteins are disclosed.Type: GrantFiled: August 10, 2004Date of Patent: December 19, 2006Assignee: Enzon, Inc.Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Standford Lee
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Patent number: 7122189Abstract: Activated polymeric bicine derivatives such as as well as conjugates made therewith are disclosed. Methods of making and using the bicine derivatives are also disclosed.Type: GrantFiled: August 13, 2002Date of Patent: October 17, 2006Assignee: Enzon, Inc.Inventors: Hong Zhao, Richard B. Greenwald, Annapurna Pendri
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Patent number: 6936597Abstract: Polymeric prodrugs of the formula: wherein B is selected from the group consisting of OH, leaving groups, residues of amine-containing moieties and a residues of hydroxyl-containing moieties; Y1 is selected from the group consisting of O, S, and NR5; M is NR3, O or S; Ar is a moiety which when included in Formula I forms a multi-substituted aromatic or heteroaromatic hydrocarbon or a multi-substituted heterocyclic group; (m) is zero or a positive integer; R1-3 and R5 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy and C1-6 heteroalkoxy; and R4 is a polymeric residue; as well as methods of making and using the same are disclosed.Type: GrantFiled: March 21, 2002Date of Patent: August 30, 2005Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Yun H. Choe
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Patent number: 6872393Abstract: The present invention relates to the chemical modification of single chain polypeptides by means of covalent attachment of strands of poly(ethylene glycol) PEG and similar poly(alkylene oxides) to single chain polypeptide binding molecules that have the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. Such preparations of modified single chain polypeptide binding molecules have reduced immugenicity and antigenicity as well as having a longer halflife in the bloodstream as compared to the parent polypeptide. These beneficial properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications. The invention also relates to multivalent antigen-binding molecules capable of PEGylation. Compositions of, genetic constructions for, methods of use, and methods for producing PEGylated antigen-binding proteins are disclosed.Type: GrantFiled: February 26, 2001Date of Patent: March 29, 2005Assignee: Enzon, Inc.Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Standford Lee
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Patent number: 6824782Abstract: The present invention relates to the chemical modification of single chain polypeptides by means of covalent attachment of strands of poly(ethylene glycol) PEG and similar poly(alkylene oxides) to single chain polypeptide binding molecules that have the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. Such preparations of modified single chain polypeptide binding molecules have reduced immugenicity and antigenicity as well as having a longer halflife in the bloodstream as compared to the parent polypeptide. These beneficial properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications. The invention also relates to multivalent antigen-binding molecules capable of PEGylation. Compositions of, genetic constructions for, methods of use, and methods for producing PEGylated antigen-binding proteins are disclosed.Type: GrantFiled: February 26, 2001Date of Patent: November 30, 2004Assignee: Enzon, Inc.Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Stanford Lee
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Patent number: 6824766Abstract: The present invention includes polymeric transport systems corresponding to the formula: wherein: R31 is a linear or branched polymer residue; Y10 and Y11 are independently O, S, or NR40; X2 is O, S or NR41; R32-35, R37-41, R50 and R51 are independently selected among hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls; a, b and e are each independently selected positive integers; L is an amino acid residue or a bifunctional linker; X3 is wherein Y12 and Y13 are independently O, S, or NR41; Z is a bond, a moiety that is actively transported into a target cell, a hydrophobic moiety or combinations thereof; D1 and D2 are OH, a residue of a hydroxyl, a residue of an amine-containing moiety or a leaving group; and y1 and y2 are independently selected positive integers.Type: GrantFiled: June 22, 2001Date of Patent: November 30, 2004Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Hong Zhao
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Patent number: 6756037Abstract: The present invention is directed to polymer conjugates of biologically active agents and methods of preparing the same. In preferred aspects of the invention, the conjugates are of the formula wherein G is a linear or branched polymer residue such as a polyethylene glycol and B is a residue of an amine-containing or a hydroxyl-containing biologically active moiety such as Ara-C.Type: GrantFiled: March 29, 2001Date of Patent: June 29, 2004Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Yun H. Choe
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Patent number: 6743896Abstract: The present invention relates to single-chain antigen-binding molecules capable of glycosylation. Compositions of, genetic constructions coding for, and methods for producing monovalent and multivalent single-chain antigen-binding molecules capable of glycosylation are described and claimed. Composition of, genetic constructions coding for, and methods for producing glycosylated monovalent and multivalent single-chain antigen-binding molecules capable of polyalkylene oxide conjugation are described and claimed. The invention also relates to methods for producing a polypeptide having increased glycosylation and the polypeptide produced by the described method. Uses resulting from the multifunctionality of a glycosylated/polyalkylene oxide conjugated antigen-binding protein are also described and claimed.Type: GrantFiled: September 20, 2001Date of Patent: June 1, 2004Assignee: Enzon, Inc.Inventors: David Filpula, Maoliang Wang, Robert Shorr, Marc Whitlow, Lihsyng S. Lee
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Patent number: 6743908Abstract: The present invention relates to single-chain antigen-binding molecules capable of glycosylation. Compositions of, genetic constructions coding for, and methods for producing monovalent and multivalent single-chain antigen-binding molecules capable of glycosylation are described and claimed. Composition of, genetic constructions coding for, and methods for producing glycosylated monovalent and multivalent single-chain antigen-binding molecules capable of polyalkylene oxide conjugation are described and claimed. The invention also relates to methods for producing a polypeptide having increased glycosylation and the polypeptide produced by the described method. Uses resulting from the multifunctionality of a glycosylated/polyalkylene oxide conjugated antigen-binding protein are also described and claimed.Type: GrantFiled: September 20, 2001Date of Patent: June 1, 2004Assignee: Enzon, Inc.Inventors: David Filpula, Maoliang Wang, Robert Shorr, Marc Whitlow, Lihsyng S. Lee
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Patent number: 6692942Abstract: The present invention is directed to a method of in vivo and ex vivo gene delivery, for a variety of cells. More specifically, it relates to a novel carrier system and method for targeted delivery of nucleic acids to mammalian cells. More specifically, the present invention relates to carrier system comprising single-chain polypeptide binding molecules having an a region rich in basic amino acid and having the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. The basic amino acid rich region can comprise oligo-lysine, oligo-arginine or combinations thereof. Such preparations of modified single chain polypeptide binding molecules also have ability to bind nucleic acids at the region rich in basic amino acid residues. These properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications including gene therapy.Type: GrantFiled: November 2, 2001Date of Patent: February 17, 2004Assignee: Enzon, Inc.Inventors: David R. Filpula, Maoliang Wang, Marc D. Whitlow
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Patent number: 6649778Abstract: Methods of preparing amino acid-substituted taxanes such as: using selected blocked amino acids are disclosed. After coupling of the blocked amino acid to the taxane, deprotection is carried out with about an equimolar amount of a secondary amine thus substantially avoiding base-catalyzed hydrolysis of amino acid from the taxane. The preferred amino acid-taxanes are useful as intermediates in the production of polymer conjugated therapeutic compositions or as part of pharmaceutically acceptable formulations.Type: GrantFiled: September 20, 2002Date of Patent: November 18, 2003Assignee: Enzon, Inc.Inventors: Hong Zhao, Richard B. Greenwald
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Patent number: 6638499Abstract: The present invention is directed to polymeric-prodrug transport forms of the formula: wherein: E1-4 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, C1-6 heteroalkoxy, and at least one of E1-4 includes a B moiety, wherein B is a leaving group, OH, a residue of a hydroxyl-or amino-containing moiety or wherein J1 is the same as J, or another member of the group defining J and E5 is the same as E1-4, or another member of the group defining E1-4, Y1-2 are independently O, S or NR9; M is a heteroatom selected from either X or Q; wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(═Y2); R2-5 and R7-9 are independently selected froType: GrantFiled: February 6, 2002Date of Patent: October 28, 2003Assignee: Enzon, Inc.Inventors: Anthony J. Martinez, Annapurna Pendri, Richard B. Greenwald, Yun H. Choe
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Patent number: 6624142Abstract: The invention is directed primarily to compounds of Formula I: wherein: R1 is a polymeric residue; L1 is a bifunctional linking group; Y1 and Y2 are independently O, S or NR7; R2-7 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy and C1-6 heteroalkoxy; D is a moiety that is a leaving group or a residue of a compound to be delivered into a cell; Z is selected from the group consisting of: a moiety that is actively transported into a target cell, a hydrophobic moiety, and combinations thereof; Ar is a moiety which when included in Formula (I) forms a multi-substituted aromatic hydrocarbon or a multi-substituted heterocyclic group; and (y) is a positive integer greater than or equal to 1. Methods of making and using the same are also disclosed.Type: GrantFiled: May 9, 2001Date of Patent: September 23, 2003Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Hong Zhao
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Patent number: 6608076Abstract: Polymeric conjugates of camptothecin derivatives having increased circulating half-lives are disclosed. In preferred aspects, the E ring lactone of the camptothecin derivative is opened and functionalized to allow attachment of a polymer such as PEG in the 17- or 20-position thereof. A representative example of such compounds is Methods of preparing and using the same are also disclosed.Type: GrantFiled: May 16, 2002Date of Patent: August 19, 2003Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Hong Zhao
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Patent number: 6566506Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.Type: GrantFiled: April 7, 2000Date of Patent: May 20, 2003Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Anthony J. Martinez
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Patent number: 6515110Abstract: Compositions of, genetic constructions coding for, and methods for producing multivalent antigen-binding proteins are described and claimed. The methods include purification of compositions containing both monomeric and multivalent forms of single polypeptide chain molecules, and production of multivalent proteins from purified monomers. Production of multivalent proteins may occur by a concentration-dependent association of monomeric proteins, or by rearrangement of regions involving dissociation followed by reassociation of different regions. Bivalent proteins, including homobivalent and heterobivalent proteins, are made in the present invention. Genetic sequences coding for bivalent single-chain antigen-binding proteins are disclosed. Uses include all those appropriate for monoclonal and polyclonal antibodies and fragments thereof, including use as a bispecific antigen-binding molecule.Type: GrantFiled: November 19, 1999Date of Patent: February 4, 2003Assignee: Enzon, Inc.Inventors: Marc D. Whitlow, James F. Wood, Karl D. Hardman, Robert E. Bird, David Filpula, Michele Rollence
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Publication number: 20020161201Abstract: The present invention relates to single-chain antigen-binding molecules capable of glycosylation. Compositions of, genetic constructions coding for, and methods for producing monovalent and multivalent single-chain antigen-binding molecules capable of glycosylation are described and claimed. Composition of, genetic constructions coding for, and methods for producing glycosylated monovalent and multivalent single-chain antigen-binding molecules capable of polyalkylene oxide conjugation are described and claimed. The invention also relates to methods for producing a polypeptide having increased glycosylation and the polypeptide produced by the described method. Uses resulting from the multifunctionality of a glycosylated/polyalkylene oxide conjugated antigen-binding protein are also described and claimed.Type: ApplicationFiled: September 20, 2001Publication date: October 31, 2002Applicant: Enzon, Inc.Inventors: David Filpula, Maoliang Wang, Robert Shorr, Marc Whitlow, Lihsyng S. Lee