Patents Assigned to Enzon, Inc.
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Patent number: 5840900Abstract: The present invention is directed compositions of the formula: ##STR1## wherein: D is a biologically active moiety;X is an electron withdrawing group;Y and Y' are independently O or S;R.sub.1 is selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C.sub.1-6 alkyls;(n) is an integer from 1 to about 12; andR.sub.2 is a polyalkylene oxide.In preferred embodiments, the prodrugs contain a polyethylene glycol having a molecular weight of at least about 20,000.Type: GrantFiled: August 20, 1996Date of Patent: November 24, 1998Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Annapurna Pendri
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Patent number: 5824701Abstract: Taxane-based compositions of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of aryls, substituted aryls, aralkyls, substituted aralkyls, alkyls and substituted alkyls;R.sub.2 is an aryl or substituted aryl, preferably phenyl;R.sub.3 is H, a C.sub.1-10 alkoxy, SiEt.sub.3 or ##STR2## Y is O or S; (n) is zero or a positive integer;X is oxygen, S, SO.sub.2 or NL, where L is selected from the group consisting of H, C.sub.1-8 alkyls, aryls and aralkyls;R.sub.4 is H or an aroyl of the formula: ##STR3## wherein Ar is an aromatic, substituted aromatic or heteroaromatic group; R.sub.5 is H, CH.sub.3 CO or a substituted acetic acid derivative;Z is H or OR.sub.6 where R.sub.6 is selected from the group consisting of H, C.sub.1-8 alkyls, C.sub.1-8 substituted alkyls, C.sub.1-8 aralkyls, substituted aryls, aralkyls, substituted aralkyls, C.sub.1-10 alkoxy, SiEt.sub.3, ##STR4## P is O or OH; R.sub.8 is one of H, S(CH.sub.3).sub.3, Si(C.sub.2 H.sub.5).sub.3, CH.sub.Type: GrantFiled: February 3, 1997Date of Patent: October 20, 1998Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Annapurna Pendri
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Patent number: 5808096Abstract: Poly(ethylene glycol)-N-succinimide carbonate and its preparation are disclosed. Polyethylene glycol (PEG) is converted into its N-succinimide carbonate derivative. This form of the polymer reacts readily with amino groups of proteins in aqueous buffers. The modified proteins have PEG-chains grafted onto the polypeptide backbone by means of stable, hydrolysis-resistant urethane (carbamate) linkages.Type: GrantFiled: January 21, 1997Date of Patent: September 15, 1998Assignee: Enzon, Inc.Inventor: Shmuel Zalipsky
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Patent number: 5804183Abstract: A purified arginine deiminase (ADI) obtained from Mycoplasma arthritidis having the amino acid sequence of SEQ ID NO:2 as well as an isolated nucleic acid molecule containing a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO:1 are disclosed. Other aspects of the invention include an expression vector, a cloned gene for expressing the Mycoplasma arthritidis derived ADI, (recombinant) host cells useful in expressing the ADI of the present invention and substantially non-antigenic polymer conjugates containing the ADI of the present invention as well as methods of treating arginine deiminase susceptible conditions in mammals. The arginine deiminase-polymer conjugates have high levels of retained enzyme activity and relatively long circulating lives.Type: GrantFiled: January 31, 1997Date of Patent: September 8, 1998Assignee: Enzon, Inc.Inventors: David Ray Filpula, Maoliang Wang
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Patent number: 5767260Abstract: Compositions of, genetic constructions coding for, and methods for producing single-chain and multivalent immunoeffector antigen-binding fusion proteins are provided by the invention. Antigen-binding fusion proteins having phospholipase A activating protein and/or tumor necrosis factor fragments are also provided by the invention. Genetic sequences coding for single-chain and multivalent immunoeffector antigen-binding fusion proteins are disclosed.Type: GrantFiled: August 16, 1995Date of Patent: June 16, 1998Assignee: Enzon Inc.Inventors: Marc Whitlow, David Filpula, Robert Shorr
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Patent number: 5763733Abstract: Compositions of, genetic constructions coding for, and methods for producing single-chain and multivalent immunoeffector antigen-binding fusion proteins are provided by the invention. Antigen-binding fusion proteins having phospholipase A activating protein and/or tumor necrosis factor fragments are also provided by the invention. Genetic sequences coding for single-chain and multivalent immunoeffector antigen-binding fusion proteins are disclosed.Type: GrantFiled: October 13, 1994Date of Patent: June 9, 1998Assignee: Enzon, Inc.Inventors: Marc Whitlow, David Filpula, Robert Shorr
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Patent number: 5756593Abstract: The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifloroacetic acid. The resultant polymer carboxylic acids are of sufficient plurty so that expensive and time consuming purification steps required for pharmaceutical grade polymers are avoided.Type: GrantFiled: June 27, 1997Date of Patent: May 26, 1998Assignee: Enzon, Inc.Inventors: Anthony J. Martinez, Richard B. Greenwald
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Patent number: 5738846Abstract: Interferon-polymer conjugate containing compositions having high levels of retained interferon activity and relatively long circulating lives in vivo are disclosed. The compositions contain a mixture of mono-interferon-polymer conjugates and bis-interferon-polymer conjugates, with both species containing substantially a single polymer strand. The conjugate compositions are prepared by reacting about 1 mole of an interferon with from about 0.125 to about 1 mole of a bis-activated substantially non-antigenic polymer under conditions sufficient to effect covalent conjugation of the interferon and polymer. Methods of treating interferon-susceptible conditions with the compositions of the present invention are also disclosed.Type: GrantFiled: November 21, 1995Date of Patent: April 14, 1998Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Carl W. Gilbert
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Patent number: 5730990Abstract: Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.Type: GrantFiled: June 5, 1995Date of Patent: March 24, 1998Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Anthony Martinez, Annapurna Pendri
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Patent number: 5728560Abstract: The present invention is directed to methods of treating CD4+ T cell lymphopenia in HIV-infected patients. The methods include administering an effective mount of adenosine deaminase or related enzymatic material to a patient in need thereof. In preferred aspects of the invention, the method is employed in conjunction with HIV-infected patients having CD4+ T cell levels of less than about 200/.mu.l. Effective amounts of the enzyme range from about 5 to about 50 IU/kg/week. In one particularly preferred aspect of the invention, the adenosine deaminase is conjugated to one or more strands of polyethylene glycol to prolonged activity in vivo.Type: GrantFiled: June 14, 1996Date of Patent: March 17, 1998Assignee: Enzon, Inc.Inventors: Robert G. L. Shorr, Mike A. Clark, David H. Goddard
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Patent number: 5711944Abstract: A process is disclosed for preparing long-acting alpha interferon-containing compositions. Alpha interferon is contacted with a relatively small molar excess of a substantially non-antigenic polymer in the presence of a surfactant to preserve bioactivity. Isolation of the desired conjugate species having optimal activity is also disclosed.Type: GrantFiled: November 10, 1994Date of Patent: January 27, 1998Assignee: Enzon, Inc.Inventors: Carl W. Gilbert, Myung-Ok Cho
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Patent number: 5686110Abstract: A method for rendering water-insoluble materials water-soluble is provided. The method is useful for solubilizing substantially water-insoluble bioactive materials such as drugs. This is accomplished by forming a non-covalently bonded complex between the drug and a polyalkylene oxide polymer end capped with an alkyl or olefinic group which is soluble in both water and an organic solvent. This is carried out by combining the desired medicinal agent with the polymer is an organic solvent, removing the solvent and dissolving the complex in water or aqueous buffer. When the organic solvent is evaporated, a solid complex is recovered which is water-soluble. Methods of treatment with the complexes are also provided.Type: GrantFiled: June 2, 1995Date of Patent: November 11, 1997Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Robert G. L. Shorr, Mike Alan Clark, Alahari Arunakumari
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Patent number: 5681567Abstract: The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifluoroacetic acid. The resultant polymer carboxylic acids are of sufficient purity so that expensive and time containing purification steps required for pharmaceutical grade polymers are avoided.Type: GrantFiled: August 13, 1996Date of Patent: October 28, 1997Assignee: Enzon, Inc.Inventors: Anthony J. Martinez, Richard B. Greenwald
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Patent number: 5658879Abstract: The use of hemoglobin-polymer conjugates to enhance antitumor therapy in mammals is disclosed. The methods include administering an effective amount of an antitumor therapy such as radiation in combination with hemoglobin conjugated to a substantially non-antigenic polymer.Type: GrantFiled: October 16, 1995Date of Patent: August 19, 1997Assignee: Enzon, Inc.Inventor: Kwang Nho
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Patent number: 5656730Abstract: The present invention relates to a stabilized protein composition comprising a monomeric protein and a storage-stabilizing amount of sucrose, histidine or glycine, which is sufficient to inhibit aggregation of the protein molecules during freeze/thaw cycles, and methods therefor. More particularly, this invention relates to pharmaceutically-acceptable, single-chain antigen-binding protein compositions having increased frozen-storage stability, especially to freeze/thaw cycles.Type: GrantFiled: April 7, 1995Date of Patent: August 12, 1997Assignee: Enzon, Inc.Inventor: Lihsyng Stanford Lee
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Patent number: 5650388Abstract: Polyalkylene oxide-conjugated hemoglobin solutions having a molecular weight greater than about 85,000 daltons and a degree of substitution of which substantially avoids clinically significant nephrotoxicity associated with hemoglobinuria in mammals. A method of simultaneously fractionating and purifying polyalkylene oxide-conjugated hemoglobins is al so disclosed.Type: GrantFiled: June 30, 1995Date of Patent: July 22, 1997Assignee: Enzon, Inc.Inventors: Robert G. L. Shorr, Carl W. Gilbert
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Patent number: 5643575Abstract: 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: October 27, 1993Date of Patent: July 1, 1997Assignee: Enzon, Inc.Inventors: Anthony Martinez, Richard B. Greenwald
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Patent number: 5637749Abstract: Water-soluble aryl imidate activated polyalkylene oxides having improved hydrolytic stability and conjugates of the aryl imidate activated polyalkylene oxides with biologically active nucleophiles are disclosed. Methods of preparing the activated polyalkylene oxides and conjugates thereof are also disclosed.Type: GrantFiled: July 26, 1995Date of Patent: June 10, 1997Assignee: Enzon, Inc.Inventor: Richard B. Greenwald
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Patent number: 5622986Abstract: 2'- and/or 7'- substituted taxoid derivatives having improved water-solubility and/or enhanced therapeutic activity and methods of making the same are disclosed.Type: GrantFiled: December 12, 1994Date of Patent: April 22, 1997Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Durgadas Bolikal
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Patent number: 5620884Abstract: Conjugates containing glucocerebrosidase and non-antigenic polymers such as polyethylene glycol are disclosed. The conjugates circulate for extended times and have prolonged activity in vivo when compared to unmodified enzymes. The conjugates are useful in the treatment of Gaucher's Disease and have improved enzyme activity at the pH ranges associated with lysosomal, arterial and capillary regions.Type: GrantFiled: November 30, 1994Date of Patent: April 15, 1997Assignee: Enzon, Inc.Inventors: Robert G. L. Shorr, Myung-Ok Cho, Carl W. Gilbert, Edward J. Ginns, Brian M. Martin