Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals – Carrier is organic
Reexamination Certificate
2000-08-11
2002-05-14
Ceperley, Mary E. (Department: 1641)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
Carrier is organic
C436S526000, C436S804000, C436S817000
Reexamination Certificate
active
06387711
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the amino acid peptide hormone standards and, more specifically, to the use of parathyroid hormone (PTE), an 84 amino acid peptide hormone for diagnosing calcium metabolism disorders.
2. Description of the Related Art
Intact parathyroid hormone (PTH) is an 84 amino acid peptide hormone produced by the parathyroid gland. Since PTH maintains calcium homeostasis, its measurement is an important aid in the diagnosis of calcium metabolism disorders. Decreased serum calcium levels result in increased PTH secretion, causing increased absorption of dietary calcium, decreased renal clearance, and mobilization of skeletal calcium stores. In conjunction with calcium levels, PTH quantization can help distinguish between normal patients and patients with hyperparathyroidism, hypoparathryoidism or hypercalcemia of malignancy.
A diagnostic kit usually employs an immunometric method to measure an unknown sample read off a curve generated using a series of standards. For kits employing hormones as the standards, the hormones are prepared in a serum or buffered serum matrix.
Typically, PTH standards in a kit are constituted from freeze-dried PTH to achieve desired stability. Testing has shown that PTH spiked at 50, 500, and 1500 pg/mL into human serum and buffered bovine serum albumin matrix has a recovery of approximately 70% and 80%, respectively, after a three day, 37° C. stability test. The recoveries for acceptable standards are within 100+/−10%.
The prior art recognizes the limitations of using freeze-dried biological materials, such as PTH, for standards. The freeze-drying PTH results in a loss of activity. Errors in preparation of the standard occur due to reconstituting the lyophilized PTH in terms of volume and mixing to homogeneity.
Lyophilizing the material used as standards creates additional problems. Lyophilization is a capital and energy intensive process, making it costly. Further, the batch size of the lyophilizer also limits the quantity of the standard produced. Additionally, a low quality batch of freeze-dried product results in a large scrap cost.
Stability of standards may also be achieved through the use of additives that preserve biological material. For example, additives provide a protective function against the adverse effects of adsorption onto glass. Additives may preferentially bind metal ions or other functional groups, or displace water to preserve activity.
Unfortunately, the range of preservation additives is very wide and includes substance as diverse as substrates, specific ligand, glycerol, sugars, polyethylene glycols, detergents, and chelators. The wide range of preservation additives results in intensive research to determine appropriate combinations and quantities.
The prior art recognizes a need for a liquid PTH standard that has a long—at least nine months —shelf life that does not require freeze-dried PTH.
SUMMARY OF THE INVENTION
A solution comprising a non-reconstituted hormone and a preservative that has a useful shelf life of at least nine months at 4 degrees C. has been discovered. In aspects of the invention, the solution has a useful shelf life of at least six months at 4 degrees C.
In further aspects of the invention, the solution comprises a non-specific binding reducer. The solution may be a buffered aqueous solution with a pH greater than 7.0. The solution may be buffered with phosphate.
In a further aspect of the invention, the hormone is parathyroid hormone, but other aspects of the invention may have other hormones.
In a further aspect of the invention, the preservative is polyvinyl alcohol, dissolved EDTA di-sodium salt, or dissolved sodium molybdate. In a still further aspect of the invention, the preservative, expressed as a percentage of the solution, comprises less than 1% polyvinyl alcohol, less than 0.5% dissolved EDTA di-sodium salt, and less than 1% dissolved molybdate. In an even further aspect of the invention, the preservative, expressed as a percentage of the solution, comprises approximately 0.5% polyvinyl alcohol, approximately 0.17% dissolved EDTA di-sodium salt, and approximately 0.7% dissolved molybdate.
In an aspect of the invention, a diagnostic test kit comprises a plurality of standards of known percentages of a non-reconstituted hormone in a solution comprising a preservative, as described above. The kit also comprises a solid phase coated with anti-hormone antibody and a solution of labeled antibody of the hormone.
In a further aspect of the invention, the labeled antibody has acridinium ester label. Other aspects may have other suitable labels. The hormone may be parathyroid hormone or any other suitable hormone.
In an aspect of the invention, a process for assaying a sample for a hormone comprises the step of providing a plurality of standards having varying levels of a non-reconstituted version of the hormone and a preservative in a matrix wherein the standards have a useful shelf life of at least nine months at 4 degrees C. In other aspects of the invention, the standards may be any suitable variation of the solutions described above. In a next step of aspect of the invention, quantities of the plurality of standards and the sample are delivered to containers, respectively. Then, additional quantities of an labeled antibody of the hormone are delivered to the containers, respectively, whereby each container comprises a solution. A solid phase coated with an additional antibody of the hormone is placed into the solution in each container. The solutions are incubated and the solid phase is washed and measured for the labeled antibody of the hormone on the solid phase.
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Hoang Ann
Shimizu Stan
Sundaram Lata
Ceperley Mary E.
Quest Diagnostics Investments Incorporated
Stout Donald E.
Stout, Uxa Buyan & Mullins, LLP
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