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US Patent 5714142 - Method and compositions for increasing the serum half-life of pharmacologically active agents by binding to transthyretin-selective ligands

US Patent Issued on February 3, 1998
Estimated Patent Expiration Date: Icon_subject June 13, 2016Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.
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Abstract

Compositions and methods are provided for increasing the serum half-life of a pharmacologically active agent. The novel compositions are covalent conjugates of the selected pharmacologically active agent and a transthyretin-binding ligand such as tetraiiodothyroacetic acid, 2,4,6-triiodophenol, flufenamic acid, or the like.

Other References

  • Bickel et al., "Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery," Proc. Natl. Acad. Sci., USA 90:2618-2622 (1993)
  • Brouwer et al., "Competitive inhibition of thyroxine binding to transthyretin by monohydroxy metabolites of 3,4,3',4'-tetrachlorobiphenyl," Chemosphere 20(7-9):1257-1262 (1990)
  • Cavalieri et al., "The effects of drugs on the distribution and metabolism of thyroid hormones," Pharmacological Reviews 33(2):55-80 (1981)
  • Divino et al., "Receptor-mediated uptake and internalization of transthyretin," J. Biol. Chem. 265(3):1425-1429 (1990)
  • Divino et al., "Transthyretin Receptors on Human Astrocytoma Cells," J. Clin. Endocrin. Metab. 71(5):1265-1268 (1990)
  • Edgington et al., "The anatomy of access: Peptide drug delivery," Bio/Technology 9:1327-1331 (Dec. 1991)
  • Leamon et al., "Delivery of macromolecules into living cells: A method that exploits folate receptor endocytosis," Proc. Natl. Acad. Sci., USA 88:5572-5576 (1991)
  • Mao et al., "Superoxide dismutase: Improving its pharmacological properties by conjugation with human serum albumin," Biomat., Art. Cells, Art. Org. 17:229-244 (1989)
  • Munro et al., "Drug competition for thyroxine binding to transthyretin (prealbumin): Comparison with effects on thyroxine-binding globulin," J. Clin. Endocrin. Metabol. 68(6):1141-1147 (1989)
  • Ogino, "Chemical modification of superoxide dismutase," Int. J. Peptide Protein Res. 32:153-159 (1988)
  • Van Den Berg, "Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin," Chem.-Biol. Interactions 76:63-75 (1990)
  • Arano et al., "A Novel Bifunctional Metabolizable Linker for the Conjugation of Antibodies with Radionuclides," Bioconjugate Chem. 2:71-76 (1991)
  • Bank, "Effects of Polyhalogenated Aromatic Hydrocarbons on Vitamin A Catabolism and the Regulation of Vitamin A Homeostatis in Rats (Hydrocarbons)," Database: Dissertation Abstracts AN:AAI9013852 (1989)
  • Bhattacharya et al., "Homogeneous Enzyme Immunoassay of Thyroxine and Triiodothyronine Using Glucose-6-phosphate Dehydrogenase and Horse Radish Peroxidase," Indian Journal of Experimental Biology 26:990-992 (1988)
  • Blondeau et al., "Characterization of the Thyroid Hormone Transport System of Isolated Hepatocytes," The Journal of Biological Chemistry 263(6):2685-2692 (1988)
  • Busche et al., "Preparation and Utility of a Radioiodinated Analogue of Daunomycin in the Study of Multidrug Resistance," Mol. Pharmacol. 35(4): 414-421 (1989)
  • McKinney et al., "Molecular Interactions of Toxic Chlorinated Dibenzo-p-dioxins and Dibenzofurans with Thyroxine Binding Prealbumin," J. Med. Chem. 28:375-381 (1985)
  • Melhus, "Studies of the Vitamin A Transporting Protein Complex Retinol-Binding Protein--Transthyretin," Database: Dissertation Abstracts AN: AAIC220221 (1990)
  • Nichols, "Molecular Genetic Studies of Autosomal Dominant, Systemic Amyloidosis (Amyloidosis)," Database: Disssertation Abstracts AN: AAI9020740 (1989)
  • Place et al., "A Colorimetric Immunoassay Based on an Enzyme Inhibitor Method," J. Immunol. Methods 61(2):209-216 (1983)
  • van den Berg et al., "A New Radioimmunoassay for the Determiniation of the Angiotensin-converting Enzyme Inhibitor Perindopril and its Active Metabolite in Plasma and Urine: Advantages of a Lysine Derivative as Immunogen to Improve the Assay Specificity," J. Pharm. Biomed. Anal. 9(7):517-524 (1991

Inventors

Application

No. 664372 filed on 06/13/1996

US Classes:

424/85.2, Interleukin424/85.4, Interferon514/11, Monocyclic514/16, 7 or 8 peptide repeating units in known peptide chain514/263.22, The additional hetero ring is six-membered consisting of one nitrogen and five carbons514/263.24, The additional chalcogen containing hetero ring is part of a polycyclo ring system514/263.3, Chalcogen bonded directly to a ring carbon of the purine ring system514/274, Chalcogen bonded directly to pyrimidine at 2-position514/335, Chalcogen bonded directly to a ring carbon of the six-membered hetero ring514/368, Ring nitrogen is shared by the cyclos of the bicyclo ring system (e.g., tetramisole, etc.)514/421, Chalcogen bonded directly to ring carbon of the five-membered hetero ring (e.g., adrenochrome, etc.)514/423, C=X bonded directly to the five-membered hetero ring by nonionic bonding (X is chalcogen)514/460, Chalcogen bonded directly to ring carbon of the hetero ring514/471, Nitrogen containing514/567, Benzene ring nonionically bonded514/568, Benzene ring nonionically bonded514/571, Ether oxygen single bonded to carboxylic acid, percarboxylic acid or salt thereof through an acyclic carbon or acyclic carbon chain514/620, The nitrogen in R is an amino nitrogen attached indirectly to a ring by acyclic bonding514/626, Nitrogen in R514/737, Nuclear halogenated514/772, DESIGNATED ORGANIC NONACTIVE INGREDIENT CONTAINING OTHER THAN HYDROCARBON514/776Albumin or derivative

Field of Search

424/85.2, Interleukin424/85.4, Interferon514/776, Albumin or derivative514/772, DESIGNATED ORGANIC NONACTIVE INGREDIENT CONTAINING OTHER THAN HYDROCARBON514/11, Monocyclic514/16, 7 or 8 peptide repeating units in known peptide chain514/274, Chalcogen bonded directly to pyrimidine at 2-position514/335, Chalcogen bonded directly to a ring carbon of the six-membered hetero ring514/368, Ring nitrogen is shared by the cyclos of the bicyclo ring system (e.g., tetramisole, etc.)514/421, Chalcogen bonded directly to ring carbon of the five-membered hetero ring (e.g., adrenochrome, etc.)514/423, C=X bonded directly to the five-membered hetero ring by nonionic bonding (X is chalcogen)514/460, Chalcogen bonded directly to ring carbon of the hetero ring514/471, Nitrogen containing514/567, Benzene ring nonionically bonded514/568, Benzene ring nonionically bonded514/571, Ether oxygen single bonded to carboxylic acid, percarboxylic acid or salt thereof through an acyclic carbon or acyclic carbon chain514/620, The nitrogen in R is an amino nitrogen attached indirectly to a ring by acyclic bonding514/626, Nitrogen in R514/737Nuclear halogenated

Examiners

Primary: Clardy, S. Mark

Attorney, Agent or Firm

US Patent References

5068227, Cyclodextrins as carriers
Issued on: 11/26/1991
Inventor: Weinshenker
5273885Conjugates of monophenyl thyroid analogs useful in assays
Issued on: 12/28/1993
Inventor: Visor, et al.

Foreign Patent References

  • 2 085 160 GB. 04/09/1982
  • WO91/01743 WO. 02/09/1991

International Class

A61K 047/48

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