Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Reexamination Certificate
1999-12-15
2001-12-18
Jones, Dameron L. (Department: 1619)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
C424S001110, C424S001650, C530S300000, C530S317000, C530S326000, C530S333000, C530S334000
Reexamination Certificate
active
06331285
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention (Technical Field)
The present invention relates to peptide, peptidomimetic, peptide-like and metallo-constructs, particularly for use in receptor-specific compositions for biological, pharmaceutical and radiopharmaceutical applications, in which the construct is conformationally fixed, with the biological-function domain generally having increased affinity for its target, upon labeling of the metal ion-binding backbone with a metal ion.
2. Background Art
Peptide Drugs. In recent years, a significant number of peptides with various biological effects have been discovered. These peptides are being explored for use as drugs, in treatment or prevention of a variety of diseases. There are significant limitations with use of peptide drugs, including extremely rapid clearance from the circulatory system, low target affinity with some peptides, immunogenicity of larger peptide constructs, and lack of stability against proteolytic enzymes. However, there are peptides in use or under investigation as therapeutic agents for a number of conditions, including somatostatin analogues, arginine vasopressin, oxytocin, luteinizing hormone releasing hormone, angiotensin-converting enzyme, renin and elastase inhibitors, as well as a variety of antagonists, including fibrinogen receptor antagonists, and the like. In addition, peptidomimetic antibiotics and peptide-based vaccines are also in use or development as human drugs.
The problems of immunogenicity and short circulatory half-life are well known, and various modifications to peptide-based drugs have been proposed in attempts to solve these problems. These include the modification of peptides or proteins with a variety of polymers, such as polyethylene glycol (PEG) and polypropylene glycol (PPG). Thus, in U.S. Pat. No. 5,091,176, Polymer-Modified Peptide Drugs Having Enhanced Biological and Pharmacological Activities, to Braatz J A and Heifetz A H, a method is set forth for making polymer-modified drugs, with reduced immunogenicity, increased circulation half-life, and enhanced potency. A different method is disclosed in U.S. Pat. No. 5,214,131, Polyethylene Glycol Derivatives, Modified Peptides and Production Thereof, to Sano A, Maeda H, Kai Y and One K.
Peptide-Based Radiopharmaceutical Drugs. Biologically active peptides, which are peptides which bind to specific cell surface receptors, have received some consideration for use as radiopharmaceuticals. Canadian Patent Application 2,016,235, Labeled Chemotactic Peptides to Image Focal Sites of Infection or Inflammation, teaches a method of detecting a site of infection or inflammation, and a method for treating such infection or inflammation, by administration of a labeled or therapeutically-conjugated chemotactic peptide. In this application, the chemotactic peptides are chemically conjugated to DTPA and subsequently labeled with
111
In. The utility of DTPA chelates covalently coupled to polypeptides and similar substances is well known in the art. See, for example, U.S. Pat. Nos. 4,479,930 and 4,668,503 to Hnatowich D J. Other bifunctional chelates for radiolabeling peptides, polypeptides and proteins are well known in the art. Biologically active peptides are described in U.S. Pat. No. 4,427,646, Use of Radiolabeled Peptide Derived From Crosslinked Fibrin to Locate Thrombi In Vivo, to Olexa S A, Knight L C and Budzynski A Z, in which iodination is discussed as a means of radiolabeling. In U.S. Pat. No. 5,371,184, Radiolabelled Peptide Compounds, to Rajagopalan R, Lyle L R and Dunn T J, hirudin receptor-specific peptides, radiolabeled via a chelate ligand, are disclosed. In U.S. Pat. No. 4,986,979, Imaging Tissue Sites of Inflammation, to Morgan C A Jr and Anderson D C, use of chelates and direct iodination is disclosed. In U.S. Pat. No. 4,732,864, Trace-Labeled Conjugates of Metallothionein and Target-Seeking Biologically Active Molecules, to Tolman G L, the use of metallothionein or metallothionein fragments conjugated to a biologically active molecule, including peptides, is disclosed. In Dean R T and Lister-James J, International Application No. PCT/US93/05372, Technetium-99m Labeled Peptides for Imaging; Dean R T and Lister-James J, International Application No. PCT/US93/04794, Technetium-99m Labeled Peptides for Thrombus Imaging; Dean R T, Buttram S, McBride W, Lister-James J, and Civitello E R, International Application No. PCT/US93/03687, Technetium-99m Labeled Peptides for Imaging; Dean R T, Lees R S, Buttram S and Lister-James J, International Application No. PCT/US93/02320, Technetium-99m Labeled Peptides for Imaging Inflammation; and Dean R T, McBride W and Buttram S, International Application No. PCT/US92/10716, Technetium-99m Labeled Peptides for Imaging a variety of peptide constructs are disclosed, all involving a Tc-99m binding moiety covalently or otherwise linked to the peptide, or to a polyvalent linker moiety, which is itself linked to one or more peptides. These previous methods all employ some conjugation means with a chelator in order to effectuate labeling with a radionuclide or other medically useful metal ion, such as a paramagnetic contrast agent. The only exception involves direct radioiodination; the iodine labeling of proteins or peptides containing tyrosine or histidine residues is well known, for example, by the chloramine-T, iodine monochloride, Iodogen or lactoperoxidase methods.
In U.S. Pat. No. 5,225,180, Technetium-99m Labeled Somatostatin-Derived Peptides for Imaging, to Dean R T, Lister-James J and Buttram S, technetium-99m labeling of peptides containing at least two cysteine residues capable of forming a disulfide bond through reduction of the disulfide is disclosed. Other somatostatin-based radiopharmaceuticals are disclosed in U.S. Pat. No. 5,382,654, Radiolabelled Peptide Compounds, to Lyle L R, Rajagopalan R, and Deutsch K; Albert R and Mäcke H, European Patent Application No. EP948 10008.6, Somatostatin Analogs Containing Chelating Groups and Their Radiolabeled Compositions; Dean R T, McBride W and Lister-James J, International Application No. PCT/US94/06274, Radiolabeled Somatostatin-Derived Peptides for Imaging and Therapeutic Uses; and McBride W and Dean R T, International Application No. PCT/US94/08335, Somatostatin Derivatives and Their Radiolabelled Products. Use of peptide radiopharmaceuticals in general, not limited to somatostatin analogues, and various examples thereof, are given in Fischman A J, Babich J W, Strauss H W: A Ticket to Ride: Peptide Radiopharmaceuticals.
J Nucl Med
34:2253-2263, 1993. A method of metal chelation, using amino acid sequences that are capable of forming metal complexes and which are directly incorporated into peptides at nonbiologically active locations has been disclosed. U.S. Pat. No. 5,464,934, Metal Chelates as Spacer Compounds in Biologically Active Peptides, to Dunn T J, Srivivasan A, Lyle L R, Rajagpalan R.
Other biologically active peptides include analogues of formyl peptide chemoattractants which bind to neutrophils. These peptides are based on the sequence N-formyl-Met-Leu-Phe. The clinical and diagnostic imaging potential of formylated chemotactic peptides has been demonstrated by Fischman et al. (Fischman A J, Pike M C, Kroon D, Fucello A J, Rexinger D, tenKate C, Wilkinson R, Rubin R H and Strauss H W: Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs.
J Nucl Med
32:483-491, 1991) using chemotactic peptides chemically conjugated to DTPA and subsequently labeled with
111
In. Chemotactic peptides have also been radioiodinated by synthesizing formylated peptides containing tyrosine amino acids. These peptides have been used in vitro and have the same biological function as unlabeled formylated peptides (Janeczek A H, Marasco W A, Van Alten P J and Walter R B: Autoradiographic analysis of formylpeptide chemoattractant binding, uptake and intracellular processing by neutrophils.
J Cell Sci
94:155-168, 1989). Finally, chemotactic peptides have also been labeled with
99m
Tc using a ni
Jones Dameron L.
Palatin Technologies Inc.
Peacock Myers & Adams
Slusher Stephen A.
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