United States Patent 5,633,169: Claim Scope, Expiration, Enforceability, and Patent Landscape

US Patent 5,633,169 covers a method for calculating total carbon dioxide concentration in the plasma fraction of an uncentrifuged whole-blood sample. The method measures total CO2 in whole blood, measures hematocrit, derives a plasma-volume dilution factor, and corrects the CO2 result to estimate plasma total CO2.

The patent is a diagnostic-method patent, not a drug patent. It has no conventional Orange Book, Paragraph IV, biosimilar, or pharmaceutical exclusivity relevance. Its practical value was tied to blood-gas and blood-chemistry analyzers capable of measuring CO2 and hematocrit from the same uncentrifuged sample. Based on the ordinary 20-year U.S. patent term applicable to the relevant filing period, the patent expired in approximately 2014-2015 and is no longer an enforceable barrier to current products. [1][2]

What does US Patent 5,633,169 claim?

The patent has one independent method claim and seven dependent claims.

Claim	Principal limitation	Scope
1	Measures total CO2 and hematocrit in uncentrifuged whole blood, calculates a volume dilution factor, and corrects CO2 to plasma concentration	Broadest claim
2	Uses acidification to liberate CO2 gas and quantifies the gas with a detector	Narrows claim 1
3	Acidifying agent is more acidic than carbonic acid	Narrows claim 2
4	Acidifying agent contains citric acid	Specific acid embodiment
5	Acidifying agent contains sulfuric acid	Alternative specific acid embodiment
6	Detector is a manometer	Specific detector
7	Detector is a pH glass electrode	Alternative detector
8	Hematocrit is measured by impedance or conductance	Specific hematocrit technique

Claim 1 is the commercially important claim. Claims 2 through 8 provide narrower fallback positions but do not expand the invention beyond the core correction method.

How does the patented CO2 correction method work?

The claimed method addresses the fact that a whole-blood CO2 measurement is diluted by the cellular fraction of blood. The method uses hematocrit to estimate the plasma fraction.

A simplified expression of the claimed correction is:

[ C{\text{plasma}} = \frac{C{\text{whole blood}}}{1-H} ]

where:

(C_{\text{plasma}}) is the calculated total CO2 concentration in plasma;
(C_{\text{whole blood}}) is the measured total CO2 concentration in the whole-blood sample;
(H) is the hematocrit expressed as a fraction of whole-blood volume.

For example, if measured whole-blood total CO2 is 16 mmol/L and hematocrit is 40%, the calculated plasma concentration would be approximately:

[ 16 / 0.60 = 26.7 \text{ mmol/L} ]

The patent language refers to a “volume dilution factor,” rather than requiring a particular mathematical formula. That language may permit equivalent calculations that use hematocrit to correct the measured whole-blood result.

What are the essential limitations of independent claim 1?

A method must satisfy each limitation of claim 1 to fall within its literal scope. The principal limitations are:

The specimen is a whole-blood sample.
The sample contains red blood cells and plasma.
The sample is uncentrifuged.
The sample is loaded into a blood chemistry analyzer.
The analyzer includes a CO2 sensor.
The analyzer includes a hematocrit-measuring station.
Total CO2 is measured in the uncentrifuged whole-blood sample.
Hematocrit is measured in the same uncentrifuged whole-blood sample.
A volume dilution factor is generated from hematocrit.
The measured total CO2 is adjusted using that factor to produce total CO2 concentration in plasma.

The claim does not require:

a particular analyzer manufacturer;
a particular CO2 sensor;
a particular sample volume;
a particular timing sequence between CO2 and hematocrit measurements;
a particular software algorithm;
a particular reference range;
a particular clinical use;
a particular acidifying agent;
a particular detector; or
a particular hematocrit measurement technology.

The requirement for an uncentrifuged whole-blood sample is central. A system that first separates plasma and then measures CO2 in the separated plasma would not practice the claimed method literally because it would not measure and correct an uncentrifuged whole-blood sample.

What does claim 1 exclude?

Claim 1 is broad within its technical concept, but several systems fall outside its express language.

Direct plasma measurement

An analyzer that separates plasma from cells and directly measures total CO2 in the plasma may avoid the claim because it does not use hematocrit as a volume dilution correction for an uncentrifuged sample.

CO2 measurement without hematocrit correction

An analyzer that measures whole-blood CO2 but does not measure hematocrit or generate a hematocrit-derived dilution factor does not meet claim 1.

Hematocrit measured from a separate specimen

The claim repeatedly links the hematocrit measurement to the uncentrifuged whole-blood sample. Use of a separate blood specimen could create a noninfringement position, although the precise result would depend on claim construction and the system’s operating protocol.

Calculated hematocrit without a hematocrit station

A system that obtains hematocrit solely from an external laboratory information system, a historical patient record, or an unrelated measurement may argue that it lacks the claimed “hematocrit-measuring station.” The risk depends on whether the system itself performs the claimed measurement and whether an equivalent architecture is asserted.

Blood-gas systems measuring dissolved CO2 only

A blood-gas analyzer that measures pCO2 without determining total CO2 by the claimed correction method would not necessarily practice the patent. The patent is directed to total CO2 concentration and the plasma correction, not merely to partial pressure of CO2.

How do the dependent claims narrow the patent?

Claims 2 through 8 impose additional technical restrictions.

Claims 2 and 3: acidification

Claim 2 requires adding an acidifying agent to liberate CO2 gas and quantifying the liberated gas. Claim 3 requires the acid to be more acidic than carbonic acid.

These claims cover a chemical conversion approach in which bicarbonate and related carbon dioxide species are acidified to produce measurable CO2 gas. They do not require a particular acid concentration, volume, mixing mechanism, temperature, or gas-transfer structure.

Claims 4 and 5: citric acid and sulfuric acid

Claim 4 requires citric acid. Claim 5 requires sulfuric acid. The claims are alternatives, not cumulative requirements.

A product using hydrochloric acid, phosphoric acid, or another acid could fall within claim 2 and potentially claim 3, but it would not literally satisfy claim 4 or claim 5 unless the formulation also contained the specified acid.

Claims 6 and 7: detector type

Claim 6 covers a manometer for detecting liberated CO2 gas. Claim 7 covers a pH glass electrode.

The claims do not expressly cover every possible CO2 detector. A detector based on infrared absorption, thermal conductivity, mass spectrometry, or another technology might avoid claims 6 and 7, but it could still raise claim 1 or claim 2 issues depending on how the measurement is performed.

Claim 8: impedance or conductance hematocrit

Claim 8 narrows the hematocrit measurement to impedance or conductance. Optical hematocrit measurement is outside the literal scope of claim 8, although an optical system could still fall within claim 1.

What is the likely patent expiration date?

US Patent 5,633,169 issued on May 27, 1997. Patents filed under the pre-June 8, 1995 regime generally received a term of 17 years from issuance, while later applications generally received 20 years from the earliest effective nonprovisional filing date. The patent’s enforceable term ended no later than the mid-2010s under the applicable statutory framework. [1][2]

Event	Date or period
Patent issued	May 27, 1997
Statutory term	Ended approximately 2014-2015
Current enforceability	Expired
Current blocking value	None for new commercial products
Historical relevance	Prior-art and freedom-to-operate background

A terminal disclaimer, patent-term adjustment, patent-term extension, or continuation relationship could affect the precise expiration calculation. Those mechanisms do not generally extend an ordinary diagnostic-method patent into the present period without an identifiable statutory basis.

What is the Orange Book status of US Patent 5,633,169?

US Patent 5,633,169 is not an Orange Book patent in the conventional pharmaceutical sense.

The FDA Orange Book lists patents and exclusivity associated with approved drug products. A patent directed to a blood-analysis method is not ordinarily listed against an approved drug product. The patent therefore does not create:

an Orange Book-listed drug patent;
a Hatch-Waxman Paragraph IV challenge pathway;
a generic-drug stay;
an ANDA litigation framework; or
a pharmaceutical market-exclusivity period.

The relevant regulatory products would be medical devices, such as blood chemistry analyzers, rather than drug products. Device clearance typically proceeds through the FDA 510(k), de novo, or premarket approval pathways, depending on the product and classification. The patent itself does not establish FDA clearance or approval status. [3][4]

Are Paragraph IV challenges relevant?

No. Paragraph IV certifications apply to patents listed in the Orange Book for reference-listed drugs. US Patent 5,633,169 claims a laboratory testing method and is not a drug-substance, drug-product, or drug-use patent for Hatch-Waxman purposes.

A competing analyzer manufacturer would instead address the patent through ordinary patent-validity, infringement, licensing, or freedom-to-operate analysis. A generic-drug filing would not be the relevant competitive pathway.

Are biosimilar risks relevant to this patent?

No. Biosimilar applicants address biologic products under the Biologics Price Competition and Innovation Act. US Patent 5,633,169 does not claim a biologic, a biologic formulation, a manufacturing process for a biologic, or a therapeutic use of a biologic.

The patent has no biosimilar patent dance, reference-product exclusivity, or biologic interchangeability relevance.

What products and technologies could historically have implicated the patent?

The highest-risk products would have been integrated blood analyzers that:

accept uncentrifuged whole blood;
quantify total CO2 from that sample;
independently measure hematocrit;
calculate plasma volume from hematocrit; and
report a corrected plasma total CO2 value.

Potentially relevant product categories include:

Product category	Potential claim risk
Integrated blood chemistry analyzers	High if all claim 1 steps are performed
Point-of-care whole-blood analyzers	High if CO2 and hematocrit are measured in the same sample
Electrochemical blood analyzers	Depends on CO2 measurement and correction algorithm
Gasometric CO2 analyzers	Potentially relevant to claims 1-3
Manometric systems	Potentially relevant to claim 6
pH-electrode systems	Potentially relevant to claim 7
Optical hematocrit systems	Possible claim 1 exposure, lower claim 8 exposure
Direct plasma analyzers	Lower literal claim 1 exposure
Stand-alone hematology analyzers	Usually outside the claim without CO2 measurement
Blood-gas analyzers reporting pCO2 only	Usually outside the claimed total-CO2 correction method

The key infringement question would be what the analyzer actually does, not merely whether it measures CO2 and hematocrit somewhere in its workflow.

How strong was the patent estate?

The patent estate appears narrow in portfolio breadth but potentially direct in product coverage.

Strengths

Claim 1 captures the functional sequence that converts whole-blood CO2 into a plasma-referenced result.
The claim does not depend on a narrowly specified acid, detector, or hematocrit technology.
The claim covers integrated analyzer operation rather than only a reagent composition.
Software-controlled implementation could still implicate the method if the analyzer performs each claimed step.

Weaknesses

The claim requires an uncentrifuged whole-blood sample.
It requires both CO2 and hematocrit measurements.
It requires a hematocrit-derived correction.
The term “blood chemistry analyzer” may create an equipment-context limitation.
The claim is vulnerable to prior art showing hematocrit-based correction of whole-blood measurements.
The specification and prosecution history would control the interpretation of “volume dilution factor,” “adjusting,” and “total CO2 concentration in plasma.”
The patent is expired.

The dependent claims are narrower and easier to design around. For example, a product using an optical hematocrit measurement would not literally meet claim 8, and a product using an infrared CO2 detector would not literally meet claims 6 or 7.

What prior-art and patent-landscape categories matter?

A proper historical landscape would include five technology groups:

Whole-blood total CO2 analyzers.
Acidification systems that liberate CO2 from blood.
Hematocrit measurement by impedance or conductance.
Algorithms correcting whole-blood analytes for plasma volume.
Integrated point-of-care blood chemistry analyzers.

The strongest invalidity theories would likely focus on anticipation or obviousness combinations involving:

known total-CO2 measurement in whole blood;
known hematocrit measurement in the same sample; and
known correction of a whole-blood concentration using the plasma fraction.

The claim’s vulnerability would depend on whether a single prior-art reference disclosed the complete sequence, or whether a skilled person would have combined the references with a reasonable expectation of success. Patent validity would also depend on the actual priority chain, prosecution amendments, cited references, and any disclaimer or reexamination history. [1][5]

What litigation, licensing, or settlement issues affect the patent?

The supplied claims do not identify litigation, licensing agreements, or settlement terms. Because the patent expired in the mid-2010s, current infringement litigation would generally lack prospective enforcement value unless a specific historical dispute involved damages accrued before expiration.

Potential historical disputes would have centered on:

whether a device measured total CO2 or only pCO2;
whether the sample remained uncentrifuged;
whether hematocrit was measured from the same sample;
whether the analyzer generated a plasma dilution factor;
whether correction occurred automatically or through external software; and
whether the accused system used an equivalent measurement sequence.

No Paragraph IV settlement or biosimilar settlement framework applies.

What generic launch risks exist?

There is no generic-drug launch risk. For diagnostic analyzers, the relevant commercial risk would have been a competitor’s launch of an integrated instrument practicing claim 1 before expiration.

That risk has ended for future launches because the patent term has expired. Current competitors can use the claimed correction concept without obtaining a license, subject to other active patents covering:

analyzer hardware;
disposable cartridges;
reagent formulations;
sensor membranes;
calibration systems;
sample handling;
hematocrit algorithms;
data-processing software; and
specific clinical reporting functions.

Those later patents, rather than US 5,633,169, would determine current freedom to operate.

What is the competitive landscape today?

The competitive landscape is defined by integrated point-of-care and central-laboratory blood analyzers from major diagnostics manufacturers, including companies historically active in blood-gas, electrolyte, and critical-care testing. Relevant competitive products may use different technical architectures:

electrochemical sensors;
optical or fluorescent CO2 detection;
conductometric or impedance hematocrit measurement;
cartridge-based sample handling;
direct plasma separation; or
software-based correction and reporting.

The expired patent remains relevant as historical prior art and as a technical antecedent for hematocrit-based correction. It does not provide current exclusionary rights.

Key Takeaways

US Patent 5,633,169 claims a method for correcting whole-blood total CO2 to obtain a plasma total CO2 value.
Claim 1 is the principal claim and requires an uncentrifuged whole-blood sample, CO2 measurement, hematocrit measurement, calculation of a dilution factor, and correction of the CO2 result.
Claims 2 through 8 narrow the method by specifying acidification, citric acid, sulfuric acid, manometry, pH-electrode detection, and impedance or conductance hematocrit measurement.
Direct plasma testing, CO2 measurement without hematocrit correction, or measurement of pCO2 alone may fall outside the literal scope.
The patent is a diagnostic-method patent, not a pharmaceutical patent.
Orange Book listing, Paragraph IV litigation, biosimilar risk, and drug exclusivity are not relevant.
The patent expired in approximately 2014-2015 under the applicable U.S. patent-term rules.
Current freedom to operate depends on later patents covering analyzer hardware, sensors, reagents, cartridges, software, and sample handling.

FAQs About US Patent 5,633,169

Does US Patent 5,633,169 cover a CO2 sensor by itself?

No. The patent claims a testing method that combines CO2 measurement with hematocrit measurement and a plasma-volume correction. It does not broadly claim every CO2 sensor.

Does measuring hematocrit and CO2 in the same analyzer infringe the patent?

Not necessarily. The analyzer must perform all material limitations of claim 1, including use of an uncentrifuged whole-blood sample and hematocrit-based correction of total CO2 to a plasma concentration.

Does the patent cover a blood-gas analyzer that reports pCO2?

Not necessarily. The claims concern total CO2 concentration and correction to plasma concentration. Measurement of pCO2 alone does not satisfy the claimed method.

Can a company use the claimed correction formula today?

Yes, the patent’s term has expired. A company must still evaluate later patents covering the specific analyzer, sensor, reagent, software, or cartridge implementation.

Is US Patent 5,633,169 relevant to clinical laboratory reimbursement?

No. The patent does not establish reimbursement rights, coding rules, FDA authorization, or clinical-utility requirements. It concerns the technical method used to generate a laboratory measurement.

References

United States Patent and Trademark Office. (1997). United States Patent No. 5,633,169.
United States Code, 35 U.S.C. §§ 154, 156, and 173.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Device classification and the 510(k) process.
United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, chapters concerning claim interpretation, prior art, and patent term.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0801743	⤷ Start Trial
World Intellectual Property Organization (WIPO)	9715829	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,633,169

Summary for Patent: 5,633,169