Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Reexamination Certificate
1999-12-02
2002-01-15
Jones, Dameron L. (Department: 1616)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
C424S001110, C424S001650
Reexamination Certificate
active
06338835
ABSTRACT:
INTRODUCTION
1. Technical Field
This invention relates to the use of protectants for radiolabeled peptides, including antibodies and other proteins as well as small peptides.
2. Background
Radioimmunotherapy and radioimmunodiagnosis deliver critical treatment or imaging agents preferentially to the necessary areas of the body. This focused approach is especially promising because it reduces deleterious side effects. Antibodies, and particularly monoclonal antibodies, are often the critical agents that deliver a payload of radioactivity to tumors or to specific tissue areas within the body of the patient that will benefit most from the therapeutic or diagnostic radioactive emissions. Other peptides are also used in this manner for targeted delivery of radioisotopes through ligand-receptor coupling.
A common problem encountered with radiolabeled antibodies, as well as with other peptides, however, is that the integrity of the radiolabeled product may be short-lived. The radioisotope carried by the peptide contributes to the degradation of the peptide, a process known as autoradiolysis, beginning immediately after the peptide is radiolabeled and often causing unacceptable levels of degradation before the radiolabeled product can be administered to the patient to provide beneficial effect. This has proven to be a particular problem with large peptides, usually referred to as proteins, such as antibodies. Since the structure and conformation of the molecule is relevant to its activity, even a single modification of its original structure can result in deleterious effects on the functionality. For example, sensitive, and sometimes difficult to obtain, proteins or peptides such as monoclonal antibodies may suffer damage caused by the particle emissions of the radioisotopes or by the generation of free radicals in an aqueous environment in the presence of radioisotopes.
The propensity to autoradiolysis has contributed to difficulty with storage and shipping of radiolabeled products and often necessitates that the actual radiolabeling of the product be conducted at the site of patient administration rather than at a central radiolabeling facility. Many radiopharmacies are unable to perform high dose radiolabeling, thus limiting availability to patients. In those radiopharmacies equipped to perform such radiolabeling, specialized training of personnel is required. Furthermore, under these circumstances, the likelihood of reproducible product is reduced and the cost of treatment is substantially increased. The on-site radiolabeling must also generally be performed on the same day as the patient is to be treated.
Human serum albumin (HSA) has been previously used to protect radiolabeled antibodies. The use of HSA in a drug formulation is problematic, however, because of cost, supply difficulties, and most importantly, the potential for contamination with viruses and other pathogens. For instance, commercial supplies of HSA have been recalled due to possible transmission of diseases such as Creutzfeldt-Jakob Disease. Other materials, such as gentisic acid (see U.S. Pat. No. 5,384,113) and propylene glycol, have been proposed as alternatives. However, considerations such as patient acceptance, costs, and incompatibility with drugs administered for other purposes continually call for alternatives to existing radioprotectants. Accordingly, there is a need for additional materials and techniques for the radioprotection of peptides.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the invention to provide a method and composition for the radioprotection of peptides using a material of different structure and activities than those previously used for this purpose.
The above object has been met by the use of povidone, also widely known as polyvinylpyrrolidone or PVP, as a radioprotectant to ameliorate the degradation of radiolabeled peptides, especially radiolabeled proteins such as antibodies. The povidone may be used alone or in combination with ascorbic acid or another secondary stabilizer as a radioprotectant.
Another aspect of the invention is a stable peptide-radioisotope composition comprising a radiolabeled peptide protected by either povidone alone or povidone in combination with ascorbic acid or another secondary stabilizer.
A further aspect of the invention is a method for making a stable peptide-radioisotope composition by labeling the peptide with a radioisotope and then contacting the radiolabeled peptide with a povidone radioprotectant.
An article of manufacture wherein a radioprotectant is provided together with instructions for its use to ameliorate the degradation of radiolabeled peptides is also included.
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Buckley Michael J.
Chan Albert S. K.
Colcher David
Shochat Dan
Cooley & Godward LLP
Coulter Pharmaceutical, Inc.
Jones Dameron L.
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