DETAILED ACTION
Applicant' s arguments, filed 10/30/2025 have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Applicants have amended their claims, filed 04/07/2025, and therefore rejections newly made in the instant office action have been necessitated by amendment.
Claims 1-5 and 7-8 are the current claims hereby under examination.
Examiner’s Note: Al references to Applicant’s specification are made using the paragraph numbers assigned in the US publication of the present application US 2023/0131712 A1.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
a) instructions to measure fluorescence in a sample of whole blood from the subject in a counting cassette with the measurement device to determine a background level of fluorescence in claim 1
b) instructions to inject the subject with the fluorescent tracer in claim 1
c) instructions to measure fluorescence in the plurality of calibration cassettes and create a calibration curve relating the measured amount of fluorescence to concentration of fluorescent activity in claim 1
d) instructions to, at one or more timed intervals after the injection, place a sample of whole blood from the subject in a counting cassette and measure a post- injection level of fluorescence in claim 1
f) instructions to calculate by the one or more processors using the results of a) - e) and a user-provided hematocrit (Hct) value, a blood volume (BV), plasma volume (PV), and red cell volume (RCV) for the subject
g) instructions to calculate by the one or more processors, an ideal blood volume (iBV), ideal plasma volume (iPV), and ideal red cell volume (iRCV) for the subject based on user provided subject descriptive data of height, weight, and gender
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
a) instructions to measure fluorescence in a sample of whole blood from the subject in a counting cassette with the measurement device to determine a background level of fluorescence in claim 1 is interpreted as the particular algorithm and structure for carrying out the recited function of measuring fluorescence in a counting cassette to determine a background level of fluorescence and their equivalents. The measurement of fluorescence is described in paragraphs 0052 and 0058 where the specification recites that the reader excited the sample with a 780nm focused beam to cause the sample to fluoresce with a peak intensity of 820 nm. The reader measures the amount of fluorescence over a precise period of time and uses the calibration data to calculate the volume of fluorescent tracer in the blood sample. Paragraph 0072 recites that the calculation is performed via interpolation. The “reader” and/or “measurement device” are described in purely functional language as a being capable of making fluorescence readings (Paragraphs 0026, 0043, 0052, and 0058). The structure of the reader is not explicitly described. The algorithm for carrying out the measurement is described as the particular excitation wavelength and fluorescence measurement (Paragraphs 0052 and 0058). The algorithm for determining the background level of fluorescence is described as interpolation (Paragraph 0072). Thus the algorithm for carrying out the recited function is disclosed but the particular structure for carrying out the recited function, the structure of the measurement device, is not.
b) instructions to inject the subject with the fluorescent tracer in claim 1 is interpreted as the particular algorithm and structure for carrying out the recited function and their equivalents. The instructions are described in purely functional language in paragraphs 0028 and 0069. It would appear that no algorithm or structure is described for carrying out this function.
c) instructions to measure fluorescence in the plurality of calibration cassettes and create a calibration curve relating the measured amount of fluorescence to concentration of fluorescent activity in claim 1 is interpreted as the particular algorithm and structure for carrying out the recited function and their equivalents. Paragraphs 0035 and 0063 describe how the calibration cassettes are associated with a given volume of dilution and that the fluorescence level of the cassette is associated with that volume of dilution. Paragraph 0066 recites that the processor constructs a calibration curve but does not detail how the curve is constructed. The specification does not appear to explicitly describe the algorithm or steps take to create the calibration curve.
d) instructions to, at one or more timed intervals after the injection, place a sample of whole blood from the subject in a counting cassette and measure a post- injection level of fluorescence in claim 1 is interpreted as the particular algorithm and structure for carrying out the recited function and their equivalents. Paragraphs 0030, 0066, and 0070 recite this step but do not detail the structure for carrying out the step or the particular algorithm used to carry out the step.
f) instructions to calculate by the one or more processors using the results of a) - e) and a user-provided hematocrit (Hct) value, a blood volume (BV), plasma volume (PV), and red cell volume (RCV) for the subject in claim 1 is interpreted as the particular algorithm for carrying out the recited function and its equivalents. In particular, paragraph 0037 recites the equation utilized to carry out the recited function. The limitation is interpreted as this equation and its equivalents for calculating the same parameters from the same inputs.
g) instructions to calculate by the one or more processors, an ideal blood volume (iBV), ideal plasma volume (iPV), and ideal red cell volume (iRCV) for the subject based on user provided subject descriptive data of height, weight, and gender in claim 1 is interpreted as the particular algorithm for carrying out the recited function and its equivalents. In particular, paragraphs 0039-0040 recites the equations utilized to carry out the recited function. The limitation is interpreted as these equations and their equivalents for calculating the same parameters from the same inputs.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
It is noted that step e) “instructions to quantify the volume of dilution of each sample from a) and d) using interpolation of the measured fluorescence of each sample between the measured fluorescence of the calibration cassettes in c) and the respective volume of dilution corresponding to their known concentrations” is not interpreted under 35 USC 112(f) because the limitation includes all the of necessary steps for the algorithm to carry out the recited function. In particular, the algorithm uses interpolation to determine the volume of dilution of the samples using the measured fluorescence as compared to the measured fluorescence and known volume of dilutions of the calibration cassettes.
It is noted that step h) “instructions to display by the one or more processors, at the user interface, the calculated values from f) and g)” is not interpreted under 35 USC 112(f) because the limitation includes all of the structure required to carry out the recited function. The processor and the user interface structures are included in the limitation and are the only required structures to carry out the claimed step.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, the claim limitations “a) instructions to measure fluorescence in a sample of whole blood from the subject in a counting cassette with the measurement device to determine a background level of fluorescence”, “b) instructions to inject the subject with the fluorescent tracer”, ” c) instructions to measure fluorescence in the plurality of calibration cassettes and create a calibration curve relating the measured amount of fluorescence to concentration of fluorescent activity”, and “d) instructions to, at one or more timed intervals after the injection, place a sample of whole blood from the subject in a counting cassette and measure a post- injection level of fluorescence” each invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function as described in the above presented claim interpretation section for each of the listed limitations. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claim 1 recites “a system of apparatus” in line 1. It is unclear if this limitation is meant to convey that the claim is directed towards a system, an apparatus, or a system comprising multiple apparatuses. For the purposes of this examination, the limitation will be interpreted as being drawn towards a system comprising multiple apparatuses.
Claim 1 recites “the apparatus comprising … an integrated device” in lines 2-5. It is unclear which of the recited limitations between and after these recitations are considered to comprise the “apparatus” and which are considered to comprise the “integrated device” it is further unclear if there is any relationship between the integrated device and the apparatus. For the purposes of this examination, the apparatus and integrated device will be considered to be the same device.
Claim 1 recites “a measurement device capable of making measurements of fluorescence levels” but it is unclear if this limitation is the same as, related to, or different from “a reader capable of making readings of fluorescence levels” of claim 1 lines 4-5. For the purposes of this examination, the limitations will be interpreted as referring to the same device.
Claim 1 recites “cassettes to be measured” in line 6 but is unclear what relationship, if any, is present between these cassettes and the plurality of concentration measuring and calibration cassettes of line 3.
Claim 1 recites “a user interface” in line 7 but it is unclear if this limitation is the same as, related to, or different from “a touchscreen for input and display of results” of claim 1 line 5. For the purposes of this examination, the limitation will be interpreted as referring to the same interface.
Claim 1 recites “a counting cassette” in steps a) and d) but it is unclear if these steps are the same as, related to, or different from “a plurality of concentration measuring cassettes of lines 2-3. For the purposes of this examination, these limitations will all be interpreted as referring to the same cassettes.
Claim 1 recites “b) instructions to inject the subject with the fluorescent tracer” but it is unclear what element of the claimed system performs this step. Furthermore this step is recited as being performed by the processor and it is unclear how a processor could carry out this function. For the purposes of this examination, the limitation will be interpreted as any form of injection to the user whether made by a system or clinician.
Claim 1 steps c) and d) each include a step of measuring fluorescence but it is unclear if this measurement is performed with “a reader” of line 4 and/or “a measurement device” of line 6. For the purposes of this examination, the measurement device and the reader are considered the same device and thus perform all the measurements.
Claim 1 recites the limitation "the fluorescence in the plurality of calibration cassettes” in step c). There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites “create a calibration curve relating the measured amount of fluorescence to concentration of fluorescent activity” in step c) but it is unclear if “ the measured amount of fluorescence” is referring to the fluorescence measured as a background, the fluorescence measured in the calibration cassettes, or the fluorescence measured in the counting cassettes. For the purposes of this examination, these limitations will be interpreted as referring to the fluorescence of the calibration cassettes.
Claim 1 recites “concentration of fluorescent activity” in step c) but it is unclear if this limitation is intended to refer to “known concentrations of fluorescent activity” of lines 3-4. For the purposes of this examination, the limitation will be interpreted as referring to the known concentrations of fluorescent activity.
Claim 1 recites “d) instructions to, at one or more timed intervals after the injection, place a sample of whole blood from the subject in a counting cassette and measure a post-injection level of fluorescence” but it is unclear if the sample of the user’s whole blood must be drawn at the timed interval or if the samples may be drawn anything after injection and only placed into the appropriate cassettes at the given time. It is further unclear what element of the system is performing this action. For the purposes of this examination, the limitation will be interpreted as the sample being drawn and placed into a cassette at the specified time interval.
Claim 1 recites “a sample of whole blood from the subject in a counting cassette” in step d) but it is unclear if “a sample of whole blood” or “a counting cassette” are the same as, related to or different from “a sample of whole blood” or “a counting cassette” of claim 1 step a) For the purposes of this examination, these limitation will be treated as referring to different elements.
Claim 1 step e) recites “ instructions to quantify the volume of dilution of each sample from a) and d) using interpolation of the measured fluorescence of each sample between the measured fluorescence of the calibration cassettes in c) and the respective volume of dilution corresponding to their known concentrations” but this limitations of “the volume of dilution of each sample” lacks proper antecedent basis. It is further unclear what “the respective volume of dilution corresponding to their known concentrations” is meant to convey. The calibration cassettes are described in lines 3-4 as having “known concentrations of fluorescent activity” but it is unclear how this relates to “volumes of dilution” since it has not been established that the concentration of fluorescent activity is related to volume of dilution or that the volume of dilution of the calibration cassettes are known and used in the calibration curve. For the purposes of this examination, the limitation will be interpreted as the volume of dilution of the calibration cassettes being known and used for this interpolation.
Claims 2-5 and 7-8 are rejected by virtue of their dependency on claim 1.
Claim 2 recites “one or more sample collection cassettes” but it is unclear if these cassettes are the same as, related to, or different from “a plurality of concentration measuring cassettes” of claim 1 lines 2-3.
Claim 2 recites “a second membrane that is capable of making a simultaneous hematocrit determination” which implies more than one membrane in the cassette but no other membrane has been established. It is unclear if there is one, or more than one membrane in the cassette. Additionally, it is unclear how the membrane is capable of performing the hematocrit determination. It is further unclear if the determined hematocrit using the membrane serves to replace or is in addition to the “user provided hematocrit” of claim 1 step f). For the purposes of this examination, the cassette will be interpreted as a cassette with two membranes.
Claim 3 recites “the results” in line 2, this limitation lacks proper antecedent basis and it is unclear if it relates to the levels of fluorescence measured in claim 1. For the purposes of this examination, the limitation will be interpreted as referring to the measurements of fluorescence.
Claim 3 recites “the viewing window” but it is unclear if this limitation is the same as, related to, or different from “an opening for viewing the results”. For the purposes of this examination, these features will be considered to refer to the same opening
Claims 4-5 are rejected by virtue of their dependance on claim 3.
Claim 4 recites the limitation "the entire membrane surface visible through the opening in the cassette" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites “the full-wicking principle” but it is unclear what mode of operation this principle is meant to convey. Moreover it would seem that lateral flow utilizes wicking to spread the sample to the opposite end of the test strip. It is unclear what the difference between lateral flow and full-wicking is. For the purposes of this examination, lateral flow and “full-wicking” will be interpreted as the same effect.
Claim 5 recites the limitation "the area" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites “a barcode reader” in line 1 but it is unclear if this limitation is the same as, related to, or different from “a reader capable of making readings of fluorescence levels” of claim 1 lines 4-5. For the purposes of this examination, the limitations will be interpreted as referring to the same reader.
Claim 8 recites “barcoded information on the cassettes and fluorescent tracer” but it is unclear if this limitation is meant to convey that the barcoded information is physically located on these elements or if the barcode information is located elsewhere but pertains to these elements. It is further unclear how barcoded information could be physically present on the fluorescent tracer. For the purposes of this examination, the limitation will be interpreted as referring to a barcode containing information regarding these elements regardless of its location.
Claim 8 recites “the dilution volumes for each cassette” in lines 1-2 but it is unclear which dilution volume is being referenced and or which cassette. For the purposes of this examination, the limitation will be interpreted as referring to dilution volumes of the calibration cassettes.
Claim 8 recites “the barcodes imprinted on the calibration cassettes” but this limitation lacks proper antecedent basis.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1, the claim limitations “a) instructions to measure fluorescence in a sample of whole blood from the subject in a counting cassette with the measurement device to determine a background level of fluorescence”, “b) instructions to inject the subject with the fluorescent tracer”, ” c) instructions to measure fluorescence in the plurality of calibration cassettes and create a calibration curve relating the measured amount of fluorescence to concentration of fluorescent activity”, and “d) instructions to, at one or more timed intervals after the injection, place a sample of whole blood from the subject in a counting cassette and measure a post- injection level of fluorescence” each invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function as described in the above presented claim interpretation section for each of the listed limitations. Therefore, the claim lacks sufficient written description support and is rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph.
Claim 2 recites “wherein one or more sample collection cassettes include a separate membrane that is capable of making a simultaneous hematocrit determination for use in the calculations in f) and g)” in lines 1-3 which appears to indicate that the cassette is used to determine the hematocrit of the blood but the specification does not describe how the hematocrit is determined using the cassette. Paragraph 0041 of the published application describes how it is known that higher hematocrit values move slower on cellulose test strips but does not describe how this principle is utilized to determine the hematocrit levels. It does not appear that the specification describes a particular method where this principle or some other form of analysis is utilized to quantify hematocrit.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Feldschuh US Patent Number US 5024231 A hereinafter Feldschuh in view if Holschneider US Patent Application publication Number US 2010/0099992 A1 hereinafter Hol and further in view of Fleming US Patent Application publication Number US 2014/0227681 A1 hereinafter Fleming.
The below prior art rejections are made using the interpretations of the claims as best understood given the clarity rejections set forth under 35 USC 112(b) above. Changes in interpretation may necessitate new grounds of rejection.
Regarding 1, Feldschuh discloses, a system of apparatus for automatically analyzing blood of a living subject (Abstract), comprising a plurality of measuring tubes, a plurality of calibration standards containing known concentrations of radioactivity activity (Col 5 lines 44-68: the standards; Col 6 lines 37-64: the tubes used for samples and standards), a reader capable of making readings of radioactivity levels (Col 4 lines 27-38: the analyzer for determining indicator levels), a user interface configured for entry and display of information, one or more processors operatively coupled to a memory and configured to execute programmed instructions stored in the memory (Col 5 lines 4-14: the keyboard, display, and microcomputer running software) wherein the programmed instructions stored in the memory comprise:
a) instructions to measure radioactivity in a sample of whole blood from the subject in a tube with the measurement device to determine a background level of radioactivity (Col 6 lines 37-64: the control sample for background radioactivity in the patient’s blood);
b) instructions to inject the subject with the radioactive tracer (Col 5 lines 44-68: the pre-calibrated injectate and standards; the injectate is injected into the patient);
c) instructions to measure the radioactivity in the plurality of calibration standards and create a calibration curve relating the measured amount of radioactivity to concentration of radioactive tracer (Col 6 lines 37-64: the standard specimens of known concentration used to provide reference points for the analyzer, or a calibration curve; Col 5 lines 44-68; the standards may be provided with the injectate and be pre-calibrated );
d) instructions to, at one or more timed intervals after the injection, place a sample of plasma from the subject in a sample tube and measure a post-injection level of radioactivity (Col 6 lines 1-24: the samples are placed in sample tubes);
e) instructions to quantify the volume of dilution of each sample from a) and d) using interpolation of the measured radioactivity of each sample between the measured radioactivity of the calibration standards via in step c) and the respective volume of dilution corresponding to their known concentrations (Col 5 line 44 – Col 6 line 64: the standards are a known volume of dilution and used as a reference to determine the volume of dilution of the patient samples.);
f) instructions to calculate, by the one or more processors using the results of a) - e) and a user-provided hematocrit (Hct) value, a blood volume (BV), plasma volume (PV), and red cell volume (RCV) for the subject (Col 5 lines 15-29: the plasma volume and hematocrit, or red cell volume, is used to calculate whole blood volume);
g) instructions to calculate, by the one or more processors, an ideal blood volume (iBV), ideal plasma volume (iPV), and red cell volume (iRCV) for the subject based on user provided subject descriptive data of height, weight, and gender (Col 8 lines 30-68: ideal volume calculations based on user information of height, weight, and sex); and
h) instructions to display, by the one or more processors, at the user interface, the calculated values from f) and g) (Col 9 lines 1-17; Claim 12: the final report contains the results and it would seem the final report is displayed).
Feldschuh fails to disclose the system which includes a precise amount of fluorescent tracer, an integrated device with a touchscreen for input and display of results, a receptacle for introduction of cassettes to be measured by a measurement device capable of making measurements of fluorescence levels, the system utilizing fluorescence rather than radioactivity, and the system utilizing cassettes rather than tubes or wells.
Hol teaches a non-invasive system and method for determination of cardiac output and blood volume of a patient includes compensating for a change in the fluorescence of an indicator circulating in the bloodstream of a tissue or organ that is caused by a variation of the blood content at the site of the measurement (Abstract). Thus, Hol falls within the same field of endeavor as Applicant’s invention.
Hol teaches that blood volume may be measured by using fluorescent dye and the level of fluorescence of whole blood (Paragraphs 0169-0170; Fig. 10). While Hold is directed towards the continuous non-invasive measurement of fluorescent dye, Hol teaches that multiple blood samples may be drawn after injection and the level of fluorescence can be measured to determine a level of the fluorescent marker by comparing the sample fluorescence to a standard calibration curve established by measuring the fluorescence of blood samples containing known concentrations of the dye (Paragraph 0192).Hol uses the drawn samples as a calibration metric for the transcutaneous fluorescence measurements but the drawn samples themselves are indicative of a level of dilution of the dye at the time of drawing. Thus, Hold teaches that fluorescence may be measured in whole blood and further teaches the use of a calibration curve for making such measurements.
It would have been obvious to one of ordinary skill in the art prior to the effective filling date of the invention to modify the system and method of Feldschuh to operate using a fluorescent tracer and calibration curve for whole blood measurement because the underlying principles of the method are the same regardless of what form of tracer, dye, or other form of dilutant is injected into the blood. Thus such a change from a radioactive tracer in plasma to a fluorescent tracer in whole blood is considered a combination of prior art elements according to known methods to yield predictable results. The particular tracer utilized does not alter the fundamental method of Feldschuh, only the type of detection system required to make the concentration measurements is altered. Indeed it would seem any tracer type with a suitable concentration detection mechanism would be suitable to carry out the method of Feldschuh.
Feldschuh in view of Hol fails to further teach the system which includes an integrated device with a touchscreen for input and display of results, a receptacle for introduction of cassettes to be measured by a measurement device capable of making measurements of fluorescence levels, and the system utilizing cassettes rather than tubes or wells.
Fleming teaches systems and methods for determining the presence and/or amount of analytes in a fluid sample (Abstract). Thus, Fleming is reasonably pertinent to the problem at hand.
Fleming teaches a system which utilizes an optical imaging system to detect a fluorescent signal emitted by a reporter or tracer molecule, such as a fluorophore, to determine the presence and/or amount of analytes in a fluid (Paragraphs 0050-0051). The system utilizes cassettes or other sample carrying structures which are inserted into a housing and imaged by the optical sensors (Paragraph 0052). Fleming teaches that fluorescence measurement are made using an integrated device with an optical detection system and a receiving member, or receptacle, for the introduction of cassettes (Paragraphs 0050-0053). The device may further include a touchscreen configured to receive and display information (Paragraph 0054). The cassettes may include calibration zones and may come with a lot-specific calibration curve for predicting analyte concentration (Paragraphs 0061-0062)
It would have been obvious to one of ordinary skill in the art prior to the effective filling date of the invention to adapt the system of Feldschuh in view of Hol to operate with the cassettes and associated measurement devices described by Fleming because cassettes can be provided with lot-specific calibration curves (Fleming: Paragraph 0062) and may be more convenient to use than test tubes or other fluorescent measurement vessels.
Regarding claim 3, Feldschuh in view of Hol further in view of Fleming teaches the system of apparatus of claim 1. Modified Feldschuh fails to further disclose the system wherein all the cassettes are membrane-based, and have a shell with an opening for viewing the results, a well for receiving blood samples, and a membrane for transporting the blood across the length of the shell and through the viewing window,
Fleming teaches that the cassettes are membrane-based (Paragraph 0070: the test strips may have a membrane), and have a shell with an opening for viewing the results, a well for receiving blood samples (Paragraphs 0100-0101 and 0104; Figs. 14 and 15: illustrates a cassette with multiple test strips being capable of being read at the same time through an opening in a housing and each having separate wells; Paragraph 0106: the cassettes have housings), and a membrane for transporting the blood across the length of the shell and through the viewing window (Paragraphs 0070 and 0080; Fig. 8: the membrane serves to transport the sample).
It would have been further obvious to one of ordinary skill in the art prior to the effective filling date of the invention to utilize membrane based cassettes having multiple test strips as taught by the system of Feldschuh in view of Hol further in view of Fleming because membrane based strips can have multiple lines for testing and control (Fleming: paragraph 0070) which may improve reading accuracy and having multiple test strips in a single cassette may allow for simultaneous analysis which speeds up the measurement procedure.
Regarding claim 4, Feldschuh in view of Hol further in view of Fleming teaches the system of apparatus of claim 3. Modified Feldschuh fails to further disclose the system wherein all the cassettes use the full-wicking principle, and the measurement device reads the fluorescence level from the entire surface visible through the opening in the cassette.
Fleming teaches that the imaging system field of view is capable of detecting the entire detection zone (Paragraph 0057; Fig. 6 reference 32). Fleming also teaches method of compensating for non-uniform illumination and detector sensitivity across the entire field of view to improve accuracy (Paragraph 0063). This compensation can include a calibration target which provides the imaging system with a reference to make adjustments for non-uniform lighting across the entire field of view so that the fluorescence across the entire field of view can be captured more accurately (Paragraphs 0064-0065). The cassette includes a detection zone where the sample fluid is able to interact with a detection agent to indicate a presence and/or quantity of the analyte (Paragraph 0068). The reader may detect and quantify the analyte in lines or areas in a lateral flow assay (Paragraph 0089)
It would have been further obvious to one of ordinary skill in the art prior to the effective filling date of the invention to incorporate the fluorescence readings being taken across an entire detection zone and corrected for non-uniform lighting and detection as taught by Fleming into the system of Feldschuh in view of Hol further in view of Fleming because detecting the desired analyte across an entire region and correcting the detection for non-uniform lighting may provide a more accurate total quantification of an analyte.
Regarding claim 5, Feldschuh in view of Hol further in view of Fleming teaches the system of apparatus of claim 3. Modified Feldschuh fails to further disclose the system wherein all the cassettes use lateral flow methodology, whereby a monoclonal antibody to the fluorescent tracer is applied to a line across the membrane, and fluorescent measurements are made from only the area of said line.
Fleming teaches that the cassettes may utilize lateral flow (Paragraph 0068). The cassettes may further include a line with an antibody for binding to the desired analyte (Paragraph 0070). The system then obtains values from the line and an area of reference (Paragraphs 0073-0074).
It would have been further obvious to one of ordinary skill in the art prior to the effective filling date of the invention to incorporate the fluorescence readings being from a line as taught by Fleming into the system of Feldschuh in view of Hol further in view of Fleming because using lines as the capture areas may reduce the need for compensating for non-uniform lighting and detection across a field of view since the sample detection area is smaller.
Regarding claim 7, Feldschuh in view of Hol further in view of Fleming teaches the system of claim 6. Modified Feldschuh fails to further disclose the system of apparatus wherein the cassettes are measured at defined frequencies of excitation and emission for fluorescent quantification.
Fleming teaches a system where cassettes are measured using an optical system with defined frequencies of excitation and emission for fluorescent quantification (Paragraph 0065: the illumination and emission wavelength).
It would have been further obvious to one of ordinary skill in the art prior to the effective filling date of the invention to utilize known illumination and emission wavelengths as taught by Fleming in the system of Feldschuh in view of Hol further in view of Fleming because the imaging system sensitivity may be different for differing wavelengths so knowing the illumination and emission wavelengths can help improve sensitivity (Fleming: paragraph 0060).
Regarding claim 8, Feldschuh in view of Hol further in view of Fleming teaches the system of apparatus of claim 6. Modified Feldschuh fails to further disclose the system wherein the system of apparatus includes a barcode reader and barcoded information on the cassettes and fluorescent tracer to input the dilution volumes for each cassette from the barcodes imprinted on the calibration cassettes and ensure that the calibration cassettes and fluorescent tracer have matching id numbers on their respective barcodes.
Fleming teaches that the imaging system can serve as a barcode reader and that the barcode man provide information including calibration settings for a given lot so that the calibration settings are appropriate for the given cassette. The bar code may include any information that is necessary or useful for consistent operation of the system including data that defines calibration settings (Paragraphs 0102-0105). An obvious variation of the data that defines calibration settings is data degrading the particular dilution volume of a cassette to be used in generating a calibration curve. Such a variation is obvious because the information regarding the dilution volume is considered data that defines calibration setting since it is directly used to establish a calibration curve.
It would have been further obvious to one of ordinary skill in the art prior to the effective filling date of the invention to implement the barcode reader functionality and information containing barcodes on the cassettes as taught by the obvious variation of Fleming into the system of Feldschuh in view of Hol further in view of Fleming because the barcode for the current cassette being read by the system will ensure that the calibration settings are correct for the current cassette being utilized (Fleming: Paragraphs 0103-0105).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Feldschuh US Patent Number US 5024231 A hereinafter Feldschuh in view if Holschneider US Patent Application publication Number US 2010/0099992 A1 hereinafter Hol and in view of Fleming US Patent Application publication Number US 2014/0227681 A1 hereinafter Fleming as applied to claim 1 above and further in view of Fant US Patent Application publication Number US 2022/0074956 A1 hereinafter Fant
Regarding claim 2, Feldschuh in view of Hol further in view of Fleming teaches the system of apparatus of claim 1. Feldschuh fails to further disclose the system wherein the sample collection cassettes include a second membrane that is capable of making a simultaneous hematocrit determination, for use in the calculations in f) and g)
Fleming teaches a system where the cassettes may have multiple test strips and corresponding wells (Paragraphs 0100-0101 and 0104; Figs. 14 and 15: illustrates a cassette with multiple test strips being capable of being read at the same time and have separate wells)
It would have been further obvious to one of ordinary skill in the art prior to the effective filling date of the invention to utilize the cassettes taught by Fleming in the system of Feldschuh in view of Hol further in view of Fleming because cassettes can be easier to use than sample tubes and may also come with a lot-specific calibration curves (Fleming: Paragraph 0062) which can improve measurement accuracy.
Feldschuh in view of Hol further in view of Fleming fails to further teach the cassette include a second membrane that is capable of making a simultaneous hematocrit determination, for use in the calculations in f) and g).
Fant teaches that a hematocrit level in a sample of whole blood can be determined in a lateral flow assay setting. The measurement includes applying a sample of whole blood to a substrate on which a blood spot is formed; taking an image of said blood spot within 1-300 seconds from application, subjecting said image to image analysis, and determining the hematocrit level based on a value of at least one parameter extracted from said image. Such reagent-free hematocrit measurement can be integrated in lateral flow assay devices for the measurement of an analyte and contribute to significantly improved precision of such assays (Abstract). Thus, Fant is reasonably pertinent tot eh problem at hand.
Fant teaches a lateral flow assay strip for measuring hematocrit using image analysis (Paragraphs 0029-0034 and 0096). Fant teaches that the strip may include a membrane (Paragraph 0057).
It would have been obvious to one of ordinary skill in the art prior to the effective filling date of the invention to implement the hematocrit assay strip and image analysis method taught by Fant into the system of Feldschuh in view of Hol further in view of Fleming because Feldschuh in view of Hol requires a measurement of hematocrit to determine the plasma volume and red blood cell volume from the total blood volume measurement and the assay strip of Fant is well suited for the assay analysis system of Fleming which may optically analyze multiple strips simultaneously (Fleming: Paragraphs 0100-0101 and 0104; Figs. 14 and 15) and Fant teaches that the hematocrit measurement strip is fast and accurate (Fant: Paragraph 0140).
Response to Arguments
Applicant's arguments filed 10/30/2025 have been fully considered but they are not persuasive.
In particular, Applicant’s arguments directed towards the substitution of whole blood for plasma in Feldschuh is not found to be persuasive because, as taught by newly cited Hol, the measurement of fluorescence in whole blood for blood volume determination is known. The principle of operation of Feldschuh is not altered by such a change from radioactive tracers in plasma to fluorescent tracers in whole blood. While the measurement modality and specifics regarding calibration would be changed, such changes are readily apparent to one of ordinary skill in the art in light of the teachings of Hol and Fleming. One of ordinary skill in the art would be well equipped to adapt the methodology of Feldschuh to fluorescent measurement in light of the teachings of Hol and Fleming. Additionally, Applicant’s arguments directed towards the challenges of precise aliquoting of whole blood and the specifically engineered membrane-based cassette are not found to be persuasive because such arguments are not commensurate in scope with the claimed invention. The technical ability of those performing the measurements is not within the scope of the invention and the claimed invention does not particularly define the membrane of the cassette.
Applicant’s arguments that one or ordinary skill in the art when faced with the challenge of quantifying whole blood, would not find it obvious to look to a plasma-based assay (which avoids the problem) and a membrane and combine them, is not found to be persuasive because both whole blood quantification and plasma based quantification are dye-dilution techniques which simply use different dyes are require different processing methodologies based on the properties of the dyes used. Both methods involve the same principles of measurement where a known quantity of dye is injected and samples are taken periodically to evaluate the concentration of the dye in the user’s blood so that the volume of dilution may be determined.
Applicant’s arguments that the change from a radioactive to fluorescent dye is not a simple substitution and introduces new and complex problems not previously considered by Feldschuh are not found to be persuasive. In particular, Applicant points to the non-linearity of and self-quenching of fluorescent dyes but such effects are readily compensated for by using a calibration curve such as described in Hol. The fluorescence of various known concentrations of tracer in blood can be measured and used to extrapolate the concentration of a given sample.
Applicant’s arguments directed to the resulting system being inaccurate are not found to be persuasive because the claims do not require any particular degree of accuracy.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The provided reasons to combine references uses only knowledge that was within the level of ordinary skill at the time the claimed invention was made. Both radioactivity and fluorescent tracers follow the principles used in dye-dilution blood volume determination methods and thus their combination is a combination of prior art elements according to known methods to yield predictable results. Feldschuh’s use of plasma and radioactive tracers are not considered to teach away from the use of fluorescence and whole blood because both techniques use the same principles of dilution and Feldschuh does not explicitly recite any teachings against the use of fluorescence.
Applicant’s arguments directed towards the unexpected achievement of quantitative precision does not appear to be supported by the specification. The specification does not appear to indicate that the invention removes a requirement for precise pipetting of whole blood. Indeed, paragraphs 0046-0048 require that the user pipette 10 microliters of whole blood into the cassette and the specification does not appear to elaborate on how the particular membrane obviates a need for a precise amount of sample. Applicant’s specification does not appear to describe or provide evident to support that the membrane in combination with a calibration curve result in unexpectedly precise measurements.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW ERIC OGLES whose telephone number is (571)272-7313. The examiner can normally be reached M-F 8:00AM - 5:30PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jason Sims can be reached on Monday-Friday from 9:00AM – 4:00PM at (571) 272 – 7540. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MATTHEW ERIC OGLES/Examiner, Art Unit 3791
/JASON M SIMS/Supervisory Patent Examiner, Art Unit 3791