Patents Assigned to Enzon, Inc.
  • Patent number: 7632504
    Abstract: 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: Grant
    Filed: August 2, 2004
    Date of Patent: December 15, 2009
    Assignee: Enzon, Inc.
    Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Standford Lee
  • Patent number: 7393953
    Abstract: 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: Grant
    Filed: March 31, 2003
    Date of Patent: July 1, 2008
    Assignee: Enzon, Inc.
    Inventors: Hong Zhao, Richard B. Greenwald
  • Patent number: 7262164
    Abstract: 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: Grant
    Filed: November 8, 2002
    Date of Patent: August 28, 2007
    Assignee: Enzon, Inc.
    Inventors: Yun H. Choe, Richard B. Greenwald
  • Patent number: 7150872
    Abstract: 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: Grant
    Filed: August 10, 2004
    Date of Patent: December 19, 2006
    Assignee: Enzon, Inc.
    Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Standford Lee
  • Patent number: 7122189
    Abstract: 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: Grant
    Filed: August 13, 2002
    Date of Patent: October 17, 2006
    Assignee: Enzon, Inc.
    Inventors: Hong Zhao, Richard B. Greenwald, Annapurna Pendri
  • Patent number: 6936597
    Abstract: 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: Grant
    Filed: March 21, 2002
    Date of Patent: August 30, 2005
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Yun H. Choe
  • Patent number: 6872393
    Abstract: 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: Grant
    Filed: February 26, 2001
    Date of Patent: March 29, 2005
    Assignee: Enzon, Inc.
    Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Standford Lee
  • Patent number: 6824766
    Abstract: 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: Grant
    Filed: June 22, 2001
    Date of Patent: November 30, 2004
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Hong Zhao
  • Patent number: 6824782
    Abstract: 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: Grant
    Filed: February 26, 2001
    Date of Patent: November 30, 2004
    Assignee: Enzon, Inc.
    Inventors: Marc Whitlow, Robert G. L. Shorr, David R. Filpula, Lihsyng Stanford Lee
  • Patent number: 6756037
    Abstract: 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: Grant
    Filed: March 29, 2001
    Date of Patent: June 29, 2004
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Yun H. Choe
  • Patent number: 6743896
    Abstract: 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: Grant
    Filed: September 20, 2001
    Date of Patent: June 1, 2004
    Assignee: Enzon, Inc.
    Inventors: David Filpula, Maoliang Wang, Robert Shorr, Marc Whitlow, Lihsyng S. Lee
  • Patent number: 6743908
    Abstract: 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: Grant
    Filed: September 20, 2001
    Date of Patent: June 1, 2004
    Assignee: Enzon, Inc.
    Inventors: David Filpula, Maoliang Wang, Robert Shorr, Marc Whitlow, Lihsyng S. Lee
  • Patent number: 6692942
    Abstract: 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: Grant
    Filed: November 2, 2001
    Date of Patent: February 17, 2004
    Assignee: Enzon, Inc.
    Inventors: David R. Filpula, Maoliang Wang, Marc D. Whitlow
  • Patent number: 6649778
    Abstract: 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: Grant
    Filed: September 20, 2002
    Date of Patent: November 18, 2003
    Assignee: Enzon, Inc.
    Inventors: Hong Zhao, Richard B. Greenwald
  • Patent number: 6638499
    Abstract: 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 fro
    Type: Grant
    Filed: February 6, 2002
    Date of Patent: October 28, 2003
    Assignee: Enzon, Inc.
    Inventors: Anthony J. Martinez, Annapurna Pendri, Richard B. Greenwald, Yun H. Choe
  • Patent number: 6624142
    Abstract: 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: Grant
    Filed: May 9, 2001
    Date of Patent: September 23, 2003
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Hong Zhao
  • Patent number: 6608076
    Abstract: 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: Grant
    Filed: May 16, 2002
    Date of Patent: August 19, 2003
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Hong Zhao
  • Patent number: 6566506
    Abstract: 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: Grant
    Filed: April 7, 2000
    Date of Patent: May 20, 2003
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Anthony J. Martinez
  • Patent number: 6515110
    Abstract: 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: Grant
    Filed: November 19, 1999
    Date of Patent: February 4, 2003
    Assignee: Enzon, Inc.
    Inventors: Marc D. Whitlow, James F. Wood, Karl D. Hardman, Robert E. Bird, David Filpula, Michele Rollence
  • Publication number: 20020161201
    Abstract: 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: Application
    Filed: September 20, 2001
    Publication date: October 31, 2002
    Applicant: Enzon, Inc.
    Inventors: David Filpula, Maoliang Wang, Robert Shorr, Marc Whitlow, Lihsyng S. Lee