Central Admixture v. Advanced Cardiac: osmolarity v. osmolality
As wikipedia and the CAFC both note: osmolarity is a measure of the osmoles of solute per litre of solution, while the osmolality is a measure of the osmoles of solute per kilogram of solvent.
The Central Admixture case has a number of interesting dimensions including how a certificate of correction was used to change the term --osmolarity-- which was written into --osmolality-- which may have been intended. Although this is clearly a chemistry case, this particular problem, and how the CAFC resolved it (certificate of correction invalid) are relevant in other jargon-filled areas. The case Superior Fireplace, 270 F.3d 1358, gets a work-out.
There are a few Bayh-Dole issues of relevance.
There is mention of the word ischemia (lack of fresh blood). See US Patent 4,988,515.
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What is the solvent at issue here? The '515 patent notes:
These solutions are blood cardioplegia in which various ingredients are added in order to regulate the ionic calcium concentration, glucose concentration, osmolarity, pH, and potassium concentration. The actual cardioplegic solution (blood cardioplegia) which is introduced into the heart can be prepared by mixing various additives such as Tromethamine solution (THAM), Citrate-Phosphate-Dextrose solution (CPD), Dextrose, and Potassium Chloride, directly into the blood. More preferably, a concentrated aqueous solution of the various additives is prepared. This concentrated aqueous solution is then diluted with blood to provide a blood cardioplegic solution having the desired pH, osmolarity, and concentrations of calcium ion, amino acids, and glucose. Blood is the preferred diluant or carrier; however, other cardioplegia compatible diluants, such as stroma free hemaglobin, oxygenated plasma, crystalloids and fluorocarbons, may be used so long as a suitable source of oxygen is provided by the diluant. Other assanguineous or accellular carriers which are capable of becoming oxygenated may be used.
In a situation in which a fluorocarbon is the diluent (or generally wherein the diluent does not have a density near 1 g/cc), there will be numerical differences between osmolarity and osmolality. Separately, note that osmolarity is temperature-dependent and osmolality is not.
From the beginning of the '515 patent, in the abstract, one notes carelessness in units. Thus, the abstract talks about concentrations in moles, not in moles/liter:
An improved amino acid enriched cardioplegic solution adapted for use in preventing and treating heart muscle damage due to regional ischemia. The solution includes a calcium ion concentration of between about 50-300 umol, a metabolizable substrate concentration of 400-1000 mg % and an osmolarity of between about 400-500 mOsmols.
There is no such thing as a calcium ion concentration of between about 50-300 umol. This carelessness persists in claim 1, which includes the words: maintaining said calcium ion concentration of said cardioplegic solution at a lowered level of between about 50-300 umol. [See also footnote 1 of the decision.]
One might infer that concentrations are expressed "per liter" from wording such as:
The cardioplegic solution was prepared by initially preparing an aqueous concentrated solution and then diluting this solution 1 to 4 with blood. The basic ingredients used to formulate one liter batches of the concentrated solutions were: Monosodium Glutamate Monohydrate, Monosodium Aspartate Monohydrate, Citric Acid Monohydrate, Sodium Citrate Dihydrate, Sodium Phosphate Monobasic Monohydrate, Dextrose, (Anhydrous), Tromethamine, Potassium Chloride and Water USP (gs to 1000 ml).
Solution formulation is done by diluting in solvent on a volume, not a weight, basis.
The initial use of the term "osmolarity" is consistent with this. Why did patentee want to change FROM osmolarity [which seemed to be consistent with the other things were being measured (ie, per volume unit)] TO osmolality?
The CAFC got to the nub of the issue: "Because of the change in the range [going from osmolarity to osmolality], it is more likely that the accused solutions infringe the corrected claims, while they may not have infringed the original claims."
To determine whether the certificate of correction was appropriate, the CAFC tackled the issue of whether the claim had been broadened. Broadening to the CAFC in this case occurs if the new claim covers territory that the old claim did not.
***
Note that this patent was based on a continuation of a continuation:
This is a continuation of co-pending application Ser. No. 07/148,151 filed on Jan. 28, 1988, which is a continuation of Ser. No. 06/768,404, filed Aug. 21, 1985, both now abandoned.
The Central Admixture case has a number of interesting dimensions including how a certificate of correction was used to change the term --osmolarity-- which was written into --osmolality-- which may have been intended. Although this is clearly a chemistry case, this particular problem, and how the CAFC resolved it (certificate of correction invalid) are relevant in other jargon-filled areas. The case Superior Fireplace, 270 F.3d 1358, gets a work-out.
There are a few Bayh-Dole issues of relevance.
There is mention of the word ischemia (lack of fresh blood). See US Patent 4,988,515.
****
What is the solvent at issue here? The '515 patent notes:
These solutions are blood cardioplegia in which various ingredients are added in order to regulate the ionic calcium concentration, glucose concentration, osmolarity, pH, and potassium concentration. The actual cardioplegic solution (blood cardioplegia) which is introduced into the heart can be prepared by mixing various additives such as Tromethamine solution (THAM), Citrate-Phosphate-Dextrose solution (CPD), Dextrose, and Potassium Chloride, directly into the blood. More preferably, a concentrated aqueous solution of the various additives is prepared. This concentrated aqueous solution is then diluted with blood to provide a blood cardioplegic solution having the desired pH, osmolarity, and concentrations of calcium ion, amino acids, and glucose. Blood is the preferred diluant or carrier; however, other cardioplegia compatible diluants, such as stroma free hemaglobin, oxygenated plasma, crystalloids and fluorocarbons, may be used so long as a suitable source of oxygen is provided by the diluant. Other assanguineous or accellular carriers which are capable of becoming oxygenated may be used.
In a situation in which a fluorocarbon is the diluent (or generally wherein the diluent does not have a density near 1 g/cc), there will be numerical differences between osmolarity and osmolality. Separately, note that osmolarity is temperature-dependent and osmolality is not.
From the beginning of the '515 patent, in the abstract, one notes carelessness in units. Thus, the abstract talks about concentrations in moles, not in moles/liter:
An improved amino acid enriched cardioplegic solution adapted for use in preventing and treating heart muscle damage due to regional ischemia. The solution includes a calcium ion concentration of between about 50-300 umol, a metabolizable substrate concentration of 400-1000 mg % and an osmolarity of between about 400-500 mOsmols.
There is no such thing as a calcium ion concentration of between about 50-300 umol. This carelessness persists in claim 1, which includes the words: maintaining said calcium ion concentration of said cardioplegic solution at a lowered level of between about 50-300 umol. [See also footnote 1 of the decision.]
One might infer that concentrations are expressed "per liter" from wording such as:
The cardioplegic solution was prepared by initially preparing an aqueous concentrated solution and then diluting this solution 1 to 4 with blood. The basic ingredients used to formulate one liter batches of the concentrated solutions were: Monosodium Glutamate Monohydrate, Monosodium Aspartate Monohydrate, Citric Acid Monohydrate, Sodium Citrate Dihydrate, Sodium Phosphate Monobasic Monohydrate, Dextrose, (Anhydrous), Tromethamine, Potassium Chloride and Water USP (gs to 1000 ml).
Solution formulation is done by diluting in solvent on a volume, not a weight, basis.
The initial use of the term "osmolarity" is consistent with this. Why did patentee want to change FROM osmolarity [which seemed to be consistent with the other things were being measured (ie, per volume unit)] TO osmolality?
The CAFC got to the nub of the issue: "Because of the change in the range [going from osmolarity to osmolality], it is more likely that the accused solutions infringe the corrected claims, while they may not have infringed the original claims."
To determine whether the certificate of correction was appropriate, the CAFC tackled the issue of whether the claim had been broadened. Broadening to the CAFC in this case occurs if the new claim covers territory that the old claim did not.
***
Note that this patent was based on a continuation of a continuation:
This is a continuation of co-pending application Ser. No. 07/148,151 filed on Jan. 28, 1988, which is a continuation of Ser. No. 06/768,404, filed Aug. 21, 1985, both now abandoned.
posted by Lawrence B. Ebert at 8:37 AM
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