DETAILED ACTION
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 .
Status of the Objections and Rejections pending
since the Office Action mailed on September 17, 2025
The objection to the specification is withdrawn.
The drawing objections are withdrawn.
The objection to claim 4 is withdrawn.
All of the rejections under 35 U.S.C 112(b) are withdrawn.
All of the rejections under 35 U.S.C 103 are withdrawn, but have been rewritten below in light of Applicant’s latest Amendment.
Response to Arguments
Applicant's arguments filed December 22, 2025 have been fully considered but they are not persuasive. Regarding the rejections of independent claims 1 and 14 under 35 U.S.C 103 Applicant argues the following, on pages 13-14 of the latest Amendment,
PNG
media_image1.png
220
710
media_image1.png
Greyscale
PNG
media_image2.png
474
690
media_image2.png
Greyscale
The Examiner respectfully submits that Applicant has misunderstood or overlooked various disclosures in the prior art applied in the rejections of independent claims 1 and 14. As a first matter, though, the Examiner notes that Applicant’s new “optimization” limitation1 is in practice, as best understood by the Examiner, nothing more than a matter of selecting an excitation or exposure wavelength or wavelength band that will cause the target compound to generate a distinguishable optical signal (absorbance or fluorescence):
PNG
media_image3.png
168
442
media_image3.png
Greyscale
(see Applicant’s pre-grant publication US 2024/0201132 A1 (hereafter “Applicant’s PG-PUB”) paragraph [0024]), and
PNG
media_image4.png
190
450
media_image4.png
Greyscale
(see Applicant’s PG-PUB paragraph [0029]).
The Examiner does not see any disclosure by Applicant of a special algorithm or procedure or guidelines for this optimization other than the implied common sense looking up (computer data retrieval) of inherent excitation and absorbance or fluorescence information about the target compound.
Turning now to the prior art of record, the Examiner would like to point out that at least three of the applied references (Galen, Kober, and Hasan) disclose imaging during the active run of the electrophoresis test:
Galen
While Applicant is correct that Galen Figure 3A shows an electrophoresis strip before the active run begins and Figure 3B shows the electrophoresis strip that is imaged after the run is complete, Galen nevertheless discloses imaging during the electrophoresis run:
PNG
media_image5.png
238
416
media_image5.png
Greyscale
(see Galen paragraph [0045]);
Kober
PNG
media_image6.png
176
526
media_image6.png
Greyscale
PNG
media_image7.png
846
856
media_image7.png
Greyscale
; and
Hasan
PNG
media_image8.png
90
638
media_image8.png
Greyscale
(see Hasan page 8),
PNG
media_image9.png
100
670
media_image9.png
Greyscale
(see Hasan page 11), and
PNG
media_image10.png
860
806
media_image10.png
Greyscale
Moreover, Galen discloses
PNG
media_image11.png
222
434
media_image11.png
Greyscale
Also, recall from the previous Office Action, pages 10-11,
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to, in the method of Galen, determine absorption or fluorescence characteristics of the compound; and select an imaging wavelength of light based on the absorption or fluorescence characteristics because (1) since Galen does disclose using optical characteristics detection to identify various hemoglobin types in a blood sample and the proportions of each determine some optical characteristics, if not specifically absorption or fluorescence characteristics, of the compound; and selecting an imaging feature of light based on the optical characteristics is already implied, and (2) in light of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan absorption or fluorescence characteristics of hemoglobin and its variants may be used to identify them. It should be noted that providing a white light source ana UV light source together in an electrophoresis device was not unknown at the time of Applicant’s effective filing date. See, for example, Tamari the title, Abstract, paragraph [0005], last sentence; paragraph [0007], last sentence; paragraph [0021], and claim 15. Also see Kober the title, Abstract, Figure 4 and col. 9:58 – col. 10:21, which discloses providing a UV light source and a separate IR light source in an electrophoresis device.
[underlining added]
Thus, in light of these disclosures in already applied prior art, Applicant’s new “optimization” limitations added to claims 1 and 14 are obvious as just due to routine optimization of known result effective variables – the absorbance and/or fluorescence properties of the target compound for best recognizing it and perhaps quantifying it while in the electrophoresis strip - during real-time monitoring of the electrophoresis run, which is disclosed by the prior art. See MPEP 2144.05(II). This is especially so as Applicant has not disclosed any special procedure for such optimization – just the desired result of, “The imaging wavelength is the wavelength of light that produces the optimal image characteristics to analyze to detect the compound in the patient sample.“ See Applicant’s Pg-PUB paragraph [0028].
Regarding the 35 U.S.C. 103 rejections of the dependent claims, Applicant relies only upon her argument against the rejections of claims 1 and 14, which the Examiner has just responded to
Claim Rejections - 35 USC § 112
Note that dependent claims will have the deficiencies of base and intervening claims.
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 1-27 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:
a) independent claim 1 requires the step of “creating a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile based on the determined absorption or fluorescence characteristic of the compound; . . . . [italicizing by the Examiner]” Independent claim 14 similarly requires “a processor configured to: during an active run of an electrophoresis test, receive data that includes absorption or fluorescence characteristics of the compound;
create a compound profile that optimizes the image produced when a band
with the compound is imaged during the active run of the electrophoresis test, the compound profile created for the compound based on the received absorption or
fluorescence characteristics during the active run of the electrophoresis test, . . . .” The phrase “compound profile” is indefinite as it is not clear what information may be in this compound profile other than what would be in an absorbance or fluorescence spectrum over a certain excitation or illumination wavelength range for the target compound (see , for example, Zwart Figure 1). If something other than such a spectrum is meant, Applicant requested to explain what it may and provide an example, if possible. If Applicant is being her own lexicographer, please heed MPEP 2173.05(a).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-6, 9-11, 13-19, 22-24, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over. Galen et al. US 2018/0064384 A1 (hereafter “Galen”) in view of ThermoFisher, Application Note- “A custom method for hemoglobin measurements,” 2018 (hereafter “ThermoFisher”), Zwart et al., “ A Multi-Wavelength Spectrophotometric Method for the Simultaneous Determination of Five Haemoglobin Derivatives,” J. Clin. Chem. Clin. Biochem. Vol. 19,1981, pp. 457-463 (hereafter “Zwart”), Horecker et al., “THE ABSORPTION SPECTRA OF HEMOGLOBIN AND ITS DERIVATIVES IN THE VISIBLE AND NEAR INFRA-RED REGIONS,” Journal of Biological Chemistry, Volume 148, Issue 1, 1 April 1943, Pages 173-183 (hereafter “Horecker”), Lillard et al., “Separation of hemoglobin variants in single human erythrocytes by capillary electrophoresis with laser-induced native fluorescence detection,” Journal of Chromatography A, 718 (1995) 397-404 )hereafter “Lillard”), Hicks et al.,” Comparison of Electrophoresis on Citrate Agar, Cellulose Acetate, or Starch for Hemoglobin Identification,” CUN. Cl-EM. 21/8, 1072-1076 (1975) (hereafter “Hicks”), Hirsch et al., “Conformational Studies of Hemoglobins using Intrinsic Fluorescence Measurements*,” THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 2.56, No 3, Issue of February 10, pp. 1080-1083, 1981 (hereafter “Hirsch”), Hasan et al., “Paper-based microchip electrophoresis for point-of-care hemoglobin testing,” Analyst, 2020, 145, 2525 (hereafter “Hasan”), Tamari et al. US 2013/0199930 A1 (hereafter “Tamari”), and Kober et al. US 7,967,968 B2 (hereafter “Kober”).
Addressing claim 1, Galen discloses a method of detecting a compound in a patient sample in a point-of-care diagnostic device (see the title, Abstract,
Figures 1 and 9, and the claim 1 preamble), comprising:
during the active run of the electrophoresis test, causing emission of light towards an electrophoresis strip (302 in Figure 3A; paragraph [0044]) having the patient sample (this step is implied by the following, “A patient sample 310, such as a blood sample, is placed on the electrophoresis strip 302 in a controlled manner. In the example shown in FIG. 3A, the patient sample 310 is shown deposited as a line, the more precise and/or controlled the sample is deposited onto the electrophoresis strip 302 the more clearly the banding can be visualized…” (paragraph [0044]) together with “Results of the electrophoresis analysis can be optically captured by imaging. A light source, not shown, can be used to assist the capture of the results, with the light source emitting light that is then reflected and/or transmitted through the electrophoresis strip 302 to assist with imaging and/or visualizing the electrophoresis results thereon…”(paragraph [0043]).);
generating an image of a band on an electrophoresis strip during an active run of an electrophoresis test (this step is implied by the following, “A patient sample 310, such as a blood sample, is placed on the electrophoresis strip 302 in a controlled manner. In the example shown in FIG. 3A, the patient sample 310 is shown deposited as a line, the more precise and/or controlled the sample is deposited onto the electrophoresis strip 302 the more clearly the banding can be visualized…” (paragraph [0044]) together with “Results of the electrophoresis analysis can be optically captured by imaging. A light source, not shown, can be used to assist the capture of the results, with the light source emitting light that is then reflected and/or transmitted through the electrophoresis strip 302 to assist with imaging and/or visualizing the electrophoresis results thereon…”(paragraph [0043]).); and
determining presence of the compound in the patient sample based on the imaging and/or visualization (see the last two sentences in paragraph [0043] and paragraphs [0047], [0059], and [0060]).
Galen, though, does not disclose the claim 1 steps “determining absorption or fluorescence characteristics of the compound; [and] selecting an imaging wavelength of light based on the absorption or fluorescence characteristics; . . . .” However, Galen clearly does disclose using optical detection to identify various hemoglobin types in a blood sample and the proportions of each. See the last two sentences of paragraph [0039], the last two sentences of paragraph [0043], and paragraphs [0058]-[0060]. Also, Galen discloses that if markers are used, “. . . ., the markers can be selected to fluoresce in certain lighting conditions, . . . .” See paragraph [0134].
ThermoFisher discloses that while methemoglobin has an absorbance peak at 406 nm, it lacks peaks at 541 nm and 576 nm unlike oxyhemoglobin. See Figure 1.
Zwart discloses a multi-wavelength spectrophotometric method for the simultaneous determination of five haemoglobin derivatives. Using the absorbances for these five haemoglobin derivatives at five different wavelengths the haemoglobins could be differentiated form each other and quantified. See the title, Methods, which is on pages 458-460, and Results, which is on pages 460-461.
Horecker discloses the absorption spectra of hemoglobin and its derivatives in the visible and near infra-red regions. See the title and Figures 1-4.
Lillard discloses separation of hemoglobin variants in single human erythrocytes by capillary electrophoresis with laser-induced native fluorescence detection. See the title and Abstract.
Hicks discloses comparing electrophoresis of samples comprising hemoglobin sub-variants2 om different electrophoresis separation media. The absorbance of each fraction was collected at 280 nm to identify the various isolated hemoglobin peaks. The hemoglobin sub-variants were quantitated by measuring absorbance at 415 nm. See Hicks the title, Abstract, and the first full paragraph in the right column on page1073.
Hirsch has determined the fluorescence emission spectra for at least HB A,
Hb H, and Hb in various liganded states. See the title, abstract, and Figures 1, 3, and 4.
Hassan discloses a microchip electrophoresis for point-of-care hemoglobin testing. Hemoglobin sub-variants related to hemoglobin disorders may be identified and quantified using white light imaging and transmission imaging3. See the title, Abstract, Figures 1-5, the first paragraph of Introduction, on page 2529 the two sentences immediately above the header User interface and automated image analysis, which is on page 2529, and three sentences immediately above the header HemeChip automatically identifies hemoglobin variants and determines their relative percentages, which is on page 2533.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to, in the method of Galen, determine absorption or fluorescence characteristics of the compound; and select an imaging wavelength of light based on the absorption or fluorescence characteristics because (1) since Galen does disclose using optical characteristics detection to identify various hemoglobin types in a blood sample and the proportions of each determine some optical characteristics, if not specifically absorption or fluorescence characteristics, of the compound; and selecting an imaging feature of light based on the optical characteristics is already implied, and (2) in light of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan absorption or fluorescence characteristics of hemoglobin and its variants may be used to identify them. It should be noted that providing a white light source ana UV light source together in an electrophoresis device was not unknown at the time of Applicant’s effective filing date. See, for example, Tamari the title, Abstract, paragraph [0005], last sentence; paragraph [0007], last sentence; paragraph [0021], and claim 15. Also see Kober the title, Abstract, Figure 4 and col. 9:58 – col. 10:21, which discloses providing a UV light source and a separate IR light source in an electrophoresis device.
As for the claim 1 limitation “during the active run of the electrophoresis test, causing emission of light at the imaging wavelength and at a second wavelength towards an electrophoresis strip having the patient sample… [italicizing by the Examiner]”, as a first matter note this feature is arguably already implied by Galen:
“ The electrophoresis strip can be imaged using one or more light sources emitting one or more spectrums of light. [italicizing by the Examiner]” See Galen paragraph [0058]. In any event, in light of the absorbance or fluorescence spectra or key peaks for various hemoglobins shown or otherwise disclosed in ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan one of ordinary skill in the art would recognize that absorbance or fluorescence at more than one wavelength would be helpful in distinguishing certain hemoglobin variants from each other. This is most apparent in Zwart Figure 1, reproduced below, in which while HbCO has a quite distinctive peak between 600-650 nm form all of the other hemoglobins, Hi and HbO2 show considerable peak overlap between 500-550, but at least some peak separation between 550-600 nm.
PNG
media_image12.png
312
788
media_image12.png
Greyscale
Alternatively, in light of Hicks one wavelength (280 nm) could be used for identifying a hemoglobin sub-variant in a particular separated fraction and another
(405 nm) could be used for quantitating the hemoglobin sub-variant. See the first full paragraph in the right column on page1073.
As for the claim 1 limitation “during the active run of the electrophoresis test, determining an absorption characteristic or a fluorescence characteristic of absorbed or fluoresced light, respectively, from the imaged band on the electrophoresis strip; . . . . [italicizing by the Examiner]”, as a first matter recall from above, regarding Galen, “during the active run of the electrophoresis test, causing emission of light towards an electrophoresis strip (. . . .” It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to, in the method of Galen, to, during the active run of the electrophoresis test, determine an absorption characteristic or a fluorescence characteristic of absorbed or fluoresced light, respectively, from the imaged band on the electrophoresis strip because as from the discussion of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan this will be helpful in distinguishing hemoglobin variants, which is consistent with the purpose of the method of Galen (see Galen paragraphs [0058]-[0060]).
As for the claim 1 limitations, “during an active run of an electrophoresis test, determining absorption or fluorescence characteristics of the compound; creating a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile based on the determined absorption or fluorescence characteristic of the compound; during the active run of the electrophoresis test, . . . .”, as a first matter, the Examiner notes
(1) that it is not clear what information may be in this compound profile other than what would be in an absorbance or fluorescence spectrum over a certain excitation or illumination wavelength range for the target compound (see , for example, Zwart Figure 1). So, for prior art examination purposes the Examiner assumes that claimed “compound profile” is just the absorbance or fluorescence spectrum for the compound in either graphical or tabular form; and
(2) that Applicant’s new “optimization” limitations are in practice, as best understood by the Examiner, nothing more than a matter of selecting an excitation or exposure wavelength or wavelength band that will cause the target compound to generate a distinguishable optical signal (absorbance or fluorescence):
PNG
media_image3.png
168
442
media_image3.png
Greyscale
(see Applicant’s pre-grant publication US 2024/0201132 A1 (hereafter “Applicant’s PG-PUB”) paragraph [0024]), and
PNG
media_image4.png
190
450
media_image4.png
Greyscale
(see Applicant’s PG-PUB paragraph [0029]).
The Examiner does not see any disclosure by Applicant of a special algorithm or procedure or guidelines for this optimization other than the implied common sense looking up (computer data retrieval) of inherent excitation and absorbance or fluorescence information about the target compound.
Turning now to the prior art of record, the Examiner would like to point out that at least three of the applied references (Galen, Kober, and Hasan) disclose imaging during the active run of the electrophoresis test:
Galen
While Galen Figure 3A shows an electrophoresis strip before the active run begins and Figure 3B shows the electrophoresis strip that is imaged after the run is complete, Galen nevertheless discloses imaging during the electrophoresis run:
PNG
media_image5.png
238
416
media_image5.png
Greyscale
(see Galen paragraph [0045]);
Kober
PNG
media_image6.png
176
526
media_image6.png
Greyscale
PNG
media_image7.png
846
856
media_image7.png
Greyscale
; and
Hasan
PNG
media_image8.png
90
638
media_image8.png
Greyscale
(see Hasan page 8),
PNG
media_image9.png
100
670
media_image9.png
Greyscale
(see Hasan page 11), and
PNG
media_image10.png
860
806
media_image10.png
Greyscale
Moreover, Galen discloses multiple imaging using more than one light source emitting more than one spectrum of light:
PNG
media_image11.png
222
434
media_image11.png
Greyscale
Also, recall from earlier in this claim rejection (page 16),
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to, in the method of Galen, determine absorption or fluorescence characteristics of the compound; and select an imaging wavelength of light based on the absorption or fluorescence characteristics because (1) since Galen does disclose using optical characteristics detection to identify various hemoglobin types in a blood sample and the proportions of each determine some optical characteristics, if not specifically absorption or fluorescence characteristics, of the compound; and selecting an imaging feature of light based on the optical characteristics is already implied, and (2) in light of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan absorption or fluorescence characteristics of hemoglobin and its variants may be used to identify them. It should be noted that providing a white light source ana UV light source together in an electrophoresis device was not unknown at the time of Applicant’s effective filing date. See, for example, Tamari the title, Abstract, paragraph [0005], last sentence; paragraph [0007], last sentence; paragraph [0021], and claim 15. Also see Kober the title, Abstract, Figure 4 and col. 9:58 – col. 10:21, which discloses providing a UV light source and a separate IR light source in an electrophoresis device.
[underlining added]
Thus, in light of these additional disclosures in Galen, Kober, and Hasan, Applicant’s claim 1 steps of “during an active run of an electrophoresis test, determining absorption or fluorescence characteristics of the compound; creating a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile based on the determined absorption or fluorescence characteristic of the compound; during the active run of the electrophoresis test, . . . .”, is prima facie obvious as just routine optimization of known result effective variables – the absorbance and/or fluorescence properties of the target compound for best recognizing and perhaps quantifying it while in the electrophoresis strip - during real-time monitoring of the electrophoresis run, which is disclosed by the prior art. See MPEP 2144.05(II). This is especially so as Applicant has not disclosed any special procedure for such optimization – just the desired result of, “The imaging wavelength is the wavelength of light that produces the optimal image characteristics to analyze to detect the compound in the patient sample.“ See Applicant’s Pg-PUB paragraph [0028].
Addressing claim 2, as a first matter note that the additional limitation of this claim expresses inherent properties of an unspecified in the claim and apparently neither in Applicant’s specification. It has been held that if he composition in the prior art is physically the same as claimed, it must have the same properties. See MPEP 2112.01(II). In any event, for the additional limitation of this claim consider as, an example, Horecker. Horecker states the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration:
PNG
media_image13.png
224
568
media_image13.png
Greyscale
See Horecker page 174.
Referring now to the absorption spectra of HbO2 and HbCO in the visible region (
PNG
media_image14.png
408
590
media_image14.png
Greyscale
), it may be inferred that HbO2 has a limit of detection (LoD) in the patient sample when imaged during emission of the light at the imaging wavelength of 5000 Å that is lower than an LoD of the compound when imaged light at a wavelength other than the imaging wavelength, such as at 6000 Å. It should be noted that when one looks at absorption spectra of HbO2 and HbCO in the visible region together with the absorption spectra of HbO2 and HbCO in the infra-red region (
PNG
media_image15.png
478
604
media_image15.png
Greyscale
) it may be inferred that HbO2 and HbCO each have a limit of detection (LoD) in the patient sample when imaged during emission of the light at the imaging wavelength of 7000 Å, which is in the infra-ed spectra, that is lower than an LoD of the compound when imaged light during emission of white light, such as at 5000 Å.
Addressing claim 3, as already discussed in the rejection of claim 1 absorption characteristics of hemoglobin and its variants may be used to recognize and quantify them. Although not need to meet this claim it will be noted that determining a variant type or a sub-variant type of hemoglobin in the patient sample based a position over time of a band indicative of the variant type or the sub-variant type of the compound may be inferred from Galen Figure 4, noting especially step 420, and paragraph [0045], and from Hasan the Abstract, and Figures 1, 4, and 5.
Addressing claim 4, based on the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration (see the first full paragraph on Horecker page 174), it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to select the imaging wavelength of light based on the absorption characteristics includes select a wavelength of maximum absorption or fluoresce of the compound.(hemoglobin) because this will provide the lowest limit of detection and the highest signal-to-noise ratio.
Addressing claim 5, based on the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration (see the first full paragraph on Horecker page 174), it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the selecting the imaging wavelength of light based on the absorption characteristics include selecting a wavelength of maximum absorption or fluoresce of the compound of within a range of 390-430 nanometers (nm) because as may be inferred by the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration (see the first full paragraph on Horecker page 174), along with ThermoFisher this will provide the lowest limit of detection and the highest signal-to-noise ratio for quantifying the hemoglobin variant methemoglobin.
Addressing claim 6, as for “during the active run of the electrophoresis test, causing emission of light at the imaging wavelength at a first time during the active run and causing emission of light at the second wavelength at a second time during the active run…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to do so because as appears to be suggested by Tanari paragraph [0020], instead of providing two light sources, each having a different spectral range, it may be possible to provide a single light source with wide spectral range, but also use sliding (removable) optical filters to set the imaging wavelength. Alternatively, it would be obvious to perform the claim limitation at issue because one may want to avoid absorbance or fluorescence spectral cross-talk or peak overlap.
Addressing claim 9, for the additional limitation of this claim see Galen Figure 4, noting especially steps 418 and 422, paragraph [0048](“ FIG. 4 is an example analysis method 400 The analysis of a patient sample, which is patient blood in this example, is performed to determine a blood characteristic, which can include the presence of a disease or condition, quantification of a disease or condition, likelihood of the presence of a disease or condition, . . . [italicizing by the Examiner]“), and paragraph [0089](“ The output 514 can output data, including the collected analysis data and/or interpretative data indicative of the presence or absence of a disorder, condition, infection and/or disease within the patient and/or the patient sample. An example can include the identification and proportions of the various hemoglobin types within the patient sample.”). Also see the last sentence in Galen paragraph [0059].
Addressing claim 10, for the additional limitation of this claim see Galen paragraph [0058] noting especially, “Multiple images of the electrophoresis strip can be captured in various lighting conditions in order to assist with analyzing/evaluating the bands.” Also see Galen paragraph [0134] noting especially, “Multiple captured images can be composited and/or used for the analysis process to increase the effectiveness and/or accuracy of the band analysis/evaluation.”
Addressing claim 11, as for the claim limitation, “during the active run of the electrophoresis test, causing emission of white light towards the electrophoresis strip having the patient sample; during the active run of the electrophoresis test, . . . .”, recall from the rejection of underlying claim 1 that at least Tamari and Horecker disclose causing emission of white light towards an electrophoresis strip during the active run of the electrophoresis test.
As for “generating a first of the multiple images of the band on the electrophoresis strip during the emission of light at the imaging wavelength; and generating a second of the multiple images of the band on the electrophoresis strip during the emission of white light…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to do so because Galen paragraph [0058] discloses, “Multiple images of the electrophoresis strip can be captured in various lighting conditions in order to assist with analyzing/evaluating the bands…”, and Galen paragraph [0134] discloses, “Multiple captured images can be composited and/or used for the analysis process to increase the effectiveness and/or accuracy of the band analysis/evaluation.”
Addressing claim 13, as for the claim limitation, “wherein causing emission of light within a range of wavelengths that includes the imaging wavelength, the light emitted towards the electrophoresis strip having the patient sample, . . . .”, see Galen Abstract and paragraphs [0046] and [0059], which disclose having the electrophoresed sample be a patient sample that be imaged and the images analyzed for a compound indicative of a disease such as a hemoglobin variant or sub-variant indicative of hemoglobin disorder. As for causing emission of light within a range of wavelengths recall form the rejection of underlying claim 1 that Galen discloses that more than one light source may be provide and that ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan disclose multiple peaks and wavelength ranges in different portions of the electromagnetic spectrum useful for recognizing different hemoglobin variants and sub-variants.
As for the claim 13 limitation, “. . . ., and further comprising applying a filter to the emitted light to limit the light emitted towards the band to be the light with the imaging wavelength…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to apply a filter as claimed when practicing the method of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober because as noted in the rejection of underlying claim 1 Tamari discloses providing a sliding filter (paragraph [0020]), which as best understood by the Examiner will allow (through appropriate filters) a single light source, instead of two light sources, to be used to emit a first wavelength and a second wavelength. Alternatively, note the filters in 114A and 114B in Kober Figure 4. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to apply a filter as taught by Kober when practicing the method of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober because one of ordinary skill in the art oud understand that such a filter(s) will ensure the light source(s) to emits only the desired first wavelength (and second wavelength). See Kober Figure 4 (again the filters in 114A and 114B),
col. 9:8-11, and claim 10.
Addressing claim 14, Galen discloses a system for detecting a compound in a patient sample in a point-of-care diagnostic device (see the title, Abstract,
Figures 1 and 9, and the claim 1 preamble), comprising:
a processor (see Figure 5 noting therein “Processing Circuitry” 530) configured to:
receive optical characteristics of the compound (see Figure 4, noting step 416, and see Figures 3A and 3B, noting optical imaging device 330. Also see the last three sentences in paragraph [0039] and the last two sentences in paragraph [0046].);
during the active run of the electrophoresis test, generate an instruction to cause emission of light towards an electrophoresis strip (302 in Figure 3A; paragraph [0044]) having the patient sample (this step is implied by the following, “A patient sample 310, such as a blood sample, is placed on the electrophoresis strip 302 in a controlled manner. In the example shown in FIG. 3A, the patient sample 310 is shown deposited as a line, the more precise and/or controlled the sample is deposited onto the electrophoresis strip 302 the more clearly the banding can be visualized…” (paragraph [0044]) together with “Results of the electrophoresis analysis can be optically captured by imaging. A light source, not shown, can be used to assist the capture of the results, with the light source emitting light that is then reflected and/or transmitted through the electrophoresis strip 302 to assist with imaging and/or visualizing the electrophoresis results thereon…”(paragraph [0043]).);
generate an image of a band on an electrophoresis strip during an active run of an electrophoresis test (this step is implied by the following, “A patient sample 310, such as a blood sample, is placed on the electrophoresis strip 302 in a controlled manner. In the example shown in FIG. 3A, the patient sample 310 is shown deposited as a line, the more precise and/or controlled the sample is deposited onto the electrophoresis strip 302 the more clearly the banding can be visualized…” (paragraph [0044]) together with “Results of the electrophoresis analysis can be optically captured by imaging. A light source, not shown, can be used to assist the capture of the results, with the light source emitting light that is then reflected and/or transmitted through the electrophoresis strip 302 to assist with imaging and/or visualizing the electrophoresis results thereon…”(paragraph [0043]).); and
determine presence of the compound in the patient sample based on the imaging and/or visualization (see the last two sentences in paragraph [0043] and paragraphs [0047], [0059], and [0060]); and
an output configured to output data that indicates the presence of the compound in the patient sample (see Figure 5, noting “Output” 514; and see Figure 4, noting steps 418 and 422. Also see paragraph [0089].).
Galen, though, does not disclose “[the processor is configured to] receive absorption characteristics of the compound; [and] select an imaging wavelength of light based on the absorption characteristics; . . . . [italicizing by the Examiner” However, Galen clearly does disclose using optical detection to identify various hemoglobin types in a blood sample and the proportions of each. See the last two sentences of paragraph [0039], the last two sentences of paragraph [0043], and paragraphs [0058]-[0060]. Also, Galen discloses that if markers are used, “. . . ., the markers can be selected to fluoresce in certain lighting conditions, . . . .” See paragraph [0134].
ThermoFisher discloses that while methemoglobin has an absorbance peak at 406 nm, it lacks peaks at 541 nm and 576 nm unlike oxyhemoglobin. See Figure 1.
Zwart discloses a multi-wavelength spectrophotometric method for the simultaneous determination of five haemoglobin derivatives. Using the absorbances for these five haemoglobin derivatives at five different wavelengths the haemoglobins could be differentiated form each other and quantified. See the title, Methods, which is on pages 458-460, and Results, which is on pages 460-461.
Horecker discloses the absorption spectra of hemoglobin and its derivatives in the visible and near infra-red regions. See the title and Figures 1-4.
Lillard discloses separation of hemoglobin variants in single human erythrocytes by capillary electrophoresis with laser-induced native fluorescence detection. See the title and Abstract.
Hicks discloses comparing electrophoresis of samples comprising hemoglobin sub-variants4 om different electrophoresis separation media. The absorbance of each fraction was collected at 280 nm to identify the various isolated hemoglobin peaks. The hemoglobin sub-variants were quantitated by measuring absorbance at 415 nm. See Hicks the title, Abstract, and the first full paragraph in the right column on page1073.
Hirsch has determined the fluorescence emission spectra for at least HB A,
Hb H, and Hb in various liganded states. See the title, abstract, and Figures 1, 3, and 4.
Hassan discloses a microchip electrophoresis for point-of-care hemoglobin testing. Hemoglobin sub-variants related to hemoglobin disorders may be identified and quantified using white light imaging and transmission imaging5. See the title, Abstract, Figures 1-5, the first paragraph of Introduction, on page 2529 the two sentences immediately above the header User interface and automated image analysis, which is on page 2529, and three sentences immediately above the header HemeChip automatically identifies hemoglobin variants and determines their relative percentages, which is on page 2533.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the processor of Galen configured to determine absorption (and fluorescence characteristics6) of the compound; and select an imaging wavelength of light based on the absorption (or absorption and fluorescence) characteristics because (1) since Galen does using optical detection to identify various hemoglobin types in a blood sample and the proportions of each determine some optical characteristics, if not specifically absorption (or absorption and fluorescence) characteristics, of the compound; and selecting an imaging feature of light based on the optical characteristics is already implied, and (2) in light of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan absorption or fluorescence characteristics of hemoglobin and its variants may be used to identify them. It should be noted that providing a white light source and a UV light source together in an electrophoresis device was not unknown at the time of Applicant’s effective filing date. See, for example, Tamari the title, Abstract, paragraph [0005], last sentence; paragraph [0007], last sentence; paragraph [0021], and claim 15. Also see Kober the title, Abstract, Figure 4 and col. 9:58 – col. 10:21, which discloses providing a UV light source and a separate IR light source in an electrophoresis device.
As for the claim 14 limitation “during the active run of the electrophoresis test, generate an instruction to cause emission of light at the imaging wavelength and at a second wavelength towards an electrophoresis strip having the patient sample… [italicizing by the Examiner]”, as a first matter note this feature is arguably already implied by Galen: “ The electrophoresis strip can be imaged using one or more light sources emitting one or more spectrums of light. [italicizing by the Examiner]” See Galen paragraph [0058]. In any event, in light of the absorbance or fluorescence spectra or key peaks for various hemoglobins shown or otherwise disclosed in ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan, one of ordinary skill in the art would recognize that absorbance or fluorescence at more than one wavelength would be helpful in distinguishing certain hemoglobin variants from each other. This is most apparent in Zwart Figure 1, reproduced below, in which while HbCO has a quite distinctive peak between 600-650 nm form all of the other hemoglobins, Hi and HbO2 show considerable peak overlap between 500-550, but at least some peak separation between 550-600 nm.
PNG
media_image12.png
312
788
media_image12.png
Greyscale
Alternatively, in light of Hicks one wavelength (280 nm) could be used for identifying a hemoglobin sub-variant in a particular separated fraction and another
(405 nm) could be sued for quantitating the hemoglobin sub-variant. See the first full paragraph in the right column on page1073.
As for the claim 14 limitation “during the active run of the electrophoresis test, adjust the absorption characteristic or a fluorescence characteristic of the absorbed or fluoresced light, respectively; . . . . [italicizing by the Examiner]”, as a first matter recall from above, regarding Galen, “during the active run of the electrophoresis test, causing emission of light towards an electrophoresis strip (. . . .” It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to, in the method of Galen, to, during the active run of the electrophoresis test, adjust an absorption characteristic or a fluorescence characteristic of the absorbed or fluoresced light, respectively, from the imaged band on the electrophoresis strip because from the discussion of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan this will be helpful in distinguishing hemoglobin variants, which is consistent with the purpose of the method of Galen (see Galen paragraphs [0058]-[0060]).
As for the claim 14 limitations, “a processor configured to: during an active run of an electrophoresis test, receive data that includes absorption or fluorescence characteristics of the compound; create a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile created for the compound based on the received absorption or fluorescence characteristics during the active run of the electrophoresis test, . . . . during an active run of an electrophoresis test, generate an image of a band on an electrophoresis strip during emission of light at the imaging
wavelength during an active run of an electrophoresis test; during the active run of the electrophoresis test, determine an adjust the absorption characteristic or the fluorescence characteristic of absorbed or fluoresced light, respectively, from the imaged band on the electrophoresis strip and update the compound profile based on the adjusted absorption characteristic or fluorescence characteristic; . . . .”, as a first matter, the Examiner notes
(1) that it is not clear what information may be in this compound profile other than what would be in an absorbance or fluorescence spectrum over a certain excitation or illumination wavelength range for the target compound (see , for example, Zwart Figure 1). So, for prior art examination purposes the Examiner assumes that claimed “compound profile” is just the absorbance or fluorescence spectrum for the compound in either graphical or tabular form; and
(2) that Applicant’s new “optimization” limitations are in practice, as best understood by the Examiner, nothing more than a matter of selecting an excitation or exposure wavelength or wavelength band that will cause the target compound to generate a distinguishable optical signal (absorbance or fluorescence):
PNG
media_image3.png
168
442
media_image3.png
Greyscale
(see Applicant’s pre-grant publication US 2024/0201132 A1 (hereafter “Applicant’s PG-PUB”) paragraph [0024]), and
PNG
media_image4.png
190
450
media_image4.png
Greyscale
(see Applicant’s PG-PUB paragraph [0029]).
The Examiner does not see any disclosure by Applicant of a special algorithm or procedure or guidelines for this optimization other than the implied common sense looking up (computer data retrieval) of inherent excitation and absorbance or fluorescence information about the target compound.
Turning now to the prior art of record, the Examiner would like to point out that at least three of the applied references (Galen, Kober, and Hasan) disclose imaging during the active run of the electrophoresis test:
Galen
While Galen Figure 3A shows an electrophoresis strip before the active run begins and Figure 3B shows the electrophoresis strip that is imaged after the run is complete, Galen nevertheless discloses imaging during the electrophoresis run:
PNG
media_image5.png
238
416
media_image5.png
Greyscale
(see Galen paragraph [0045]);
Kober
PNG
media_image6.png
176
526
media_image6.png
Greyscale
PNG
media_image7.png
846
856
media_image7.png
Greyscale
; and
Hasan
PNG
media_image8.png
90
638
media_image8.png
Greyscale
(see Hasan page 8),
PNG
media_image9.png
100
670
media_image9.png
Greyscale
(see Hasan page 11), and
PNG
media_image10.png
860
806
media_image10.png
Greyscale
Moreover, Galen discloses multiple imaging using more than one light source emitting more than one spectrum of light:
PNG
media_image11.png
222
434
media_image11.png
Greyscale
Also, recall from earlier in this claim rejection (pages 36-37),
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the processor of Galen configured to determine absorption (and fluorescence characteristics ) of the compound; and select an imaging wavelength of light based on the absorption (or absorption and fluorescence) characteristics because (1) since Galen does using optical detection to identify various hemoglobin types in a blood sample and the proportions of each determine some optical characteristics, if not specifically absorption (or absorption and fluorescence) characteristics, of the compound; and selecting an imaging feature of light based on the optical characteristics is already implied, and (2) in light of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan absorption or fluorescence characteristics of hemoglobin and its variants may be used to identify them. It should be noted that providing a white light source and a UV light source together in an electrophoresis device was not unknown at the time of Applicant’s effective filing date. See, for example, Tamari the title, Abstract, paragraph [0005], last sentence; paragraph [0007], last sentence; paragraph [0021], and claim 15. Also see Kober the title, Abstract, Figure 4 and col. 9:58 – col. 10:21, which discloses providing a UV light source and a separate IR light source in an electrophoresis device.
[underlining added]
Thus, in light of these additional disclosures in Galen, Kober, and Hasan, Applicant’s claim 14 processor features of “a processor configured to: during an active run of an electrophoresis test, receive data that includes absorption or fluorescence characteristics of the compound; create a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile created for the compound based on the received absorption or fluorescence characteristics during the active run of the electrophoresis test, . . . . during an active run of an electrophoresis test, generate an image of a band on an electrophoresis strip during emission of light at the imaging
wavelength during an active run of an electrophoresis test; during the active run of the electrophoresis test, determine an adjust the absorption characteristic or the fluorescence characteristic of absorbed or fluoresced light, respectively, from the imaged band on the electrophoresis strip and update the compound profile based on the adjusted absorption characteristic or fluorescence characteristic; . . . .”, are prima facie obvious as just configuring the processor to perform routine optimization of known result effective variables – the absorbance and/or fluorescence properties of the target compound for best recognizing and perhaps quantifying it while in the electrophoresis strip - during real-time monitoring of the electrophoresis run, which is disclosed by the prior art. See MPEP 2144.05(II). This is especially so as Applicant has not disclosed any special procedure for such optimization – just the desired result of, “The imaging wavelength is the wavelength of light that produces the optimal image characteristics to analyze to detect the compound in the patient sample.“ See Applicant’s Pg-PUB paragraph [0028].
Addressing claim 15, as a first matter note that the additional limitation of this claim expresses inherent properties of an unspecified in the claim and apparently neither in Applicant’s specification. It has been held that if he composition in the prior art is physically the same as claimed, it must have the same properties. See MPEP 2112.01(II). In any event, for the additional limitation of this claim consider as, an example, Horecker. Horecker states the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration:
PNG
media_image13.png
224
568
media_image13.png
Greyscale
See Horecker page 174.
Referring now to the absorption spectra of HbO2 and HbCO in the visible region (
PNG
media_image14.png
408
590
media_image14.png
Greyscale
), it may be inferred that HbO2 has a limit of detection (LoD) in the patient sample when imaged during emission of the light at the imaging wavelength of 5000 Å that is lower than an LoD of the compound when imaged light at a wavelength other than the imaging wavelength, such as at 6000 Å. It should be noted that when one looks at absorption spectra of HbO2 and HbCO in the visible region together with the absorption spectra of HbO2 and HbCO in the infra-red region (
PNG
media_image15.png
478
604
media_image15.png
Greyscale
) it may be inferred that HbO2 and HbCO each have a limit of detection (LoD) in the patient sample when imaged during emission of the light at the imaging wavelength of 7000 Å, which is in the infra-ed spectra, that is lower than an LoD of the compound when imaged light during emission of white light, such as at 5000 Å.
Addressing claim 16, as already discussed in the rejection of claim 14 the compound profile of hemoglobin (which is assumed not different from the absorption characteristics of hemoglobin and its variants) may be used to recognize and quantify them. Although not need to meet this claim it will be noted that determining a variant type or a sub-variant type of hemoglobin in the patient sample based a position over time of a band indicative of the variant type or the sub-variant type of the compound may be inferred from Galen Figure 4, noting especially step 420, and paragraph [0045], and from Nasr the Abstract, and Figures 1, 4, and 5.
Addressing claim 17, based on the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration (see the first full paragraph on Horecker page 174), it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to select the imaging wavelength of light based on the compound profile of hemoglobin (which is assumed not different from the absorption characteristics of hemoglobin and its variants) as the compound profile comprises, if not is identical with, absorption characteristics (such as its absorption spectrum), so selecting a wavelength of maximum absorption or fluorescence intensity of the compound.(hemoglobin) will provide the lowest limit of detection and the highest signal-to-noise ratio.
Addressing claim 18, based on the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration (see the first full paragraph on Horecker page 174), it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the selecting the imaging wavelength of light based on the compound profile of hemoglobin (which is assumed not different from the absorption characteristics of hemoglobin and its variants) as the compound profile comprises, if not is identical with, its absorption characteristics (such as it absorption spectrum), so selecting a wavelength of maximum absorption or fluorescence of the compound of within a range of 390-430 nanometers (nm) may be inferred by the well-known Beer-Lambert law, which relates the specific absorption coefficient of a compound at a particular wavelength to its concentration (see the first full paragraph on Horecker page 174), along with ThermoFisher as providing the lowest limit of detection and the highest signal-to-noise ratio for quantifying the hemoglobin variant methemoglobin.
Addressing claim 19, as for “wherein the processor is further configured to generate an instruction to cause emission of light at the imaging wavelength at a first time during the active run and causing emission of light at the second wavelength at a second time during the active run…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to do so because as appears to be suggested by Tanari paragraph [0020], instead of providing two light sources, each having a different spectral range, it may be possible to provide a single light source with wide spectral range, but also use sliding (removable) optical filters to set the imaging wavelength. Alternatively, it would be obvious to perform the claim limitation at issue because one may want to avoid absorbance or fluorescence spectral cross-talk or peak overlap.
Addressing claim 22, for the additional limitation of this claim see Galen Figure 4, noting especially steps 418 and 422, paragraph [0048](“ FIG. 4 is an example analysis method 400 The analysis of a patient sample, which is patient blood in this example, is performed to determine a blood characteristic, which can include the presence of a disease or condition, quantification of a disease or condition, likelihood of the presence of a disease or condition, . . . [italicizing by the Examiner]“), and paragraph [0089](“ The output 514 can output data, including the collected analysis data and/or interpretative data indicative of the presence or absence of a disorder, condition, infection and/or disease within the patient and/or the patient sample. An example can include the identification and proportions of the various hemoglobin types within the patient sample.”). Also see the last sentence in Galen paragraph [0059].
Addressing claim 23, for the additional limitations of this claim see Galen paragraph [0058] noting especially, “Multiple images of the electrophoresis strip can be captured in various lighting conditions in order to assist with analyzing/evaluating the bands.” Also see Galen paragraph [0134] noting especially, “Multiple captured images can be composited and/or used for the analysis process to increase the effectiveness and/or accuracy of the band analysis/evaluation.”
Regarding the new processor claim feature of a “the processor further configured to: . . create the compound profile from the multiple images of the determined absorption characteristics or fluorescence characteristics of the absorbed or fluoresced light: . . .”, recall for the following from the rejection of underlying claim 14
“Moreover, Galen discloses multiple imaging using more than one light source emitting more than one spectrum of light:
PNG
media_image11.png
222
434
media_image11.png
Greyscale
“
Also from the claim 14 rejection, “It should be noted that providing a white light source and a UV light source together in an electrophoresis device was not unknown at the time of Applicant’s effective filing date. See, for example, Tamari the title, Abstract, paragraph [0005], last sentence; paragraph [0007], last sentence; paragraph [0021], and claim 15. Also see Kober the title, Abstract, Figure 4 and col. 9:58 – col. 10:21, which discloses providing a UV light source and a separate IR light source in an electrophoresis device. “
Addressing claim 26, as for the claim limitation, “wherein the processor is further configured to; cause emission of light within a range of wavelengths that includes the imaging wavelength, the light emitted towards the electrophoresis strip having the patient sample, . . . .”, see Galen Abstract and paragraphs [0046] and [0059], which disclose having the electrophoresed sample be a patient sample that be imaged and the images analyzed for a compound indicative of a disease such as a hemoglobin variant or sub-variant indicative of hemoglobin disorder. As for causing emission of light within a range of wavelengths recall from the rejection of underlying claim 14 that Galen discloses that more than one light source may be provide and that ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, and Hasan disclose multiple peaks and wavelength ranges in different portions of the electromagnetic spectrum useful for recognizing different hemoglobin variants and sub-variants.
As for the claim 26 limitation, “wherein the processor is further configured to; . . . ., and apply a filter to the emitted light to limit the light emitted towards the band to be the light with the imaging wavelength…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to the processor of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober be so configured because as noted in the rejection of underlying claim 14 Tamari discloses providing a sliding filter (paragraph [0020]), which as best understood by the Examiner will allow (through appropriate filters) a single light source, instead of two light sources, to be used to emit a first wavelength and a second wavelength. Alternatively, note the filters in 114A and 114B in Kober Figure 4. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the prcocessor be configured to apply a filter as taught by Kober because one of ordinary skill in the art would understand that such a filter(s) will ensure the light source(s) to emits only the desired first wavelength (and second wavelength). See Kober Figure 4 (again the filters in 114A and 114B), col. 9:8-11, and claim 10.
Addressing claim 27, Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober at least discloses having the compound include an analyte (such as hemoglobin variants). See Galen paragraphs [0047] and [0059]. Note that although Galen does not mention having the compound include a label Galen does disclose using markers. See Galen paragraphs [0044] and [0045].
Claims 7, 20, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Galen in view of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hassan, Tamari, and Kober as applied to claims 1-6, 9-11, and 13-19 above, and further in view of Carl Merril US 4,555,490 (hereafter “Merril”) and the Quantity One® User Guide for Version 4.6.3 Windows and Macintosh, 2006 (hereafter “QuantityOne”).
Addressing claim 7, as a first matter note the following in Galen paragraph [0046], “The intensity, location and/or other band detection characteristics of the various bands 312, 314, 316 and 318 can be used to identify the components, and their relative proportions, of the initial patient sample 310. [italicizing by the Examiner]” As is known in the electrophoresis art, to quantify the amount or concentration of a compound within an electrophoresis band the optical density of the band must be known along with its area. See, for example, Merril col. 5:53 – col. 617, especially col. 6:14-17. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to determine a shape of the band on the electrophoresis strip; and quantifying the compound based on a characteristic of the shape and location of the band because it is necessary to determine the shape of the band in order to calculate its area and then the amount or concentration of the compound (hemoglobin) within the band using optical density data In this regard note that it was known at the time of the effective filing date of the application how to define irregularly shaped bands in electrophoresis lanes. See, for example, 5.8 Irregularly Shaped Bands in Lanes on pages 5-21 to 5-26 of QuantityOne. As for utilizing the location of the band, it is necessary because the location can be used in order to identify the compound within the band (see Galen paragraphs [0045] and [0046]; QuantityOne 6. Standards and Band Matching, which is on pages 6-1 to 6-13; and Hasan Figures 1D and 5) so that the appropriate compound optical density coefficient may be used in the amount or concentration calculation.
Addressing claim 20, as a first matter note the following in Galen paragraph [0046], “The intensity, location and/or other band detection characteristics of the various bands 312, 314, 316 and 318 can be used to identify the components, and their relative proportions, of the initial patient sample 310. [italicizing by the Examiner]” As is known in the electrophoresis art, to quantify the amount or concentration of a compound within an electrophoresis band the optical density of the band must be known along with its area. See, for example, Merril col. 5:53 – col. 617, especially col. 6:14-17. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to determine a shape of the band on the electrophoresis strip; and quantifying the compound based on a characteristic of the shape and location of the band because it is necessary to determine the shape of the band in order to calculate its area and then the amount or concentration of the compound (hemoglobin) within the band using optical density data In this regard note that it was known at the time of the effective filing date of the application how to define irregularly shaped bands in electrophoresis lanes. See, for example, 5.8 Irregularly Shaped Bands in Lanes on pages 5-21 to 5-26 of QuantityOne. As for utilizing the location of the band, it is necessary because the location can be used in order to identify the compound within the band (see Galen paragraphs [0045] and [0046]; QuantityOne 6. Standards and Band Matching, which is on pages 6-1 to 6-13; and Hasan Figures 1D and 5) so that the appropriate compound optical density coefficient may be used in the amount or concentration calculation.
Addressing claim 24, as for the claim limitation, “wherein the processor is further configured to: during the active run of the electrophoresis test, causing emission of white light towards the electrophoresis strip having the patient sample; during the active run of the electrophoresis test, . . . .”, recall from the rejection of underlying claim 14 that at least Tamari and Horecker disclose causing emission of white light towards an electrophoresis strip during the active run of the electrophoresis test.
As for “wherein the processor is further configured to: . . . .; and generate a first of the multiple images of the band on the electrophoresis strip during the emission of light at the imaging wavelength; and generating a second of the multiple images of the band on the electrophoresis strip during the emission of white light…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to do so because Galen paragraph [0058] discloses, “Multiple images of the electrophoresis strip can be captured in various lighting conditions in order to assist with analyzing/evaluating the bands…”, and Galen paragraph [0134] discloses, “Multiple captured images can be composited and/or used for the analysis process to increase the effectiveness and/or accuracy of the band analysis/evaluation.”
Claims 8 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Galen in view of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober as applied to claims 1-6, 9-11, 13-19, 22-24, 26, and 27 above, and further in view of Thomas Lee US 5,268,568 (hereafter “Lee”) or Miller et al.
US 2020/0326284 A1 (hereafter “Miller”).
Addressing claim 8, as a first matter note the following in Galen paragraph [0082], “Additionally, the light emitted by the light source 555 can have constant and/or varying properties, such as a wavelength, intensity and/or a frequency of the emitted light. [italicizing by the Examiner]”
Lee discloses an electrophoresis detection method involving adjusting an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity. See the title, Abstract, and col. 3:5-29 (note especially, “The sine waves, which are 180 degrees out of phase with one another, can cancel when their amplitudes are the same.” This implies a first intensity of emission light of, for example, a sine maximum peak height amplitude, and a second intensity of emission light of, for example, a sine minimum peak height amplitude.).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to adjust an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity as taught by Lee in the method of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober because Lee discloses
PNG
media_image16.png
388
424
media_image16.png
Greyscale
See Lee col. 1:11-32.
Note that the stated benefit would clearly also occur even if a marker dye was not used and detection was solely based on intrinsic optical properties (absorbance or fluorescence) of the compound(s) in the electrophoresed sample.
Alternatively, Miller an electrophoresis detection method involving adjusting an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity. See7 the title, Abstract, Figures 4 and 12, paragraphs [0048], [0057], and [0068]-[0071], and claim 1 (note especially, “perform multiple tests of the control sample at different laser powers applied to the microfluidic channel; . . . .”).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to adjust an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity as taught by Miller in the method of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober because Miller discloses (1) that peak area is function of light intensity (paragraph [0058] and Figures 4 and 12), and (2) variation (error) in determined peak area due to variation in light intensity or other factors such as focusing an optical alignment may be reduced with data about the relationship light intensity and peak area (or peak height and width)for example, through curve fitting. See Miller paragraphs [0059] and [0067]-[0069], and claims 11 and 12.
Addressing claim 21, as a first matter note the following in Galen paragraph [0082], “Additionally, the light emitted by the light source 555 can have constant and/or varying properties, such as a wavelength, intensity and/or a frequency of the emitted light. [italicizing by the Examiner]”
Lee discloses an electrophoresis detection method involving adjusting an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity. See the title, Abstract, and col. 3:5-29 (note especially, “The sine waves, which are 180 degrees out of phase with one another, can cancel when their amplitudes are the same.” This implies a first intensity of emission light of, for example, a sine maximum peak height amplitude, and a second intensity of emission light of, for example, a sine minimum peak height amplitude.).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have in the system of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober the prcessor be configured to adjust an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determine presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity as taught by Lee because Lee discloses
PNG
media_image16.png
388
424
media_image16.png
Greyscale
See Lee col. 1:11-32.
Note that the stated benefit would clearly also occur even if a marker dye was not used and detection was solely based on intrinsic optical properties (absorbance or fluorescence) of the compound(s) in the electrophoresed sample.
Alternatively, Miller an electrophoresis detection method involving adjusting an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity. See8 the title, Abstract, Figures 4 and 12, paragraphs [0048], [0057], and [0068]-[0071], and claim 1 (note especially, “perform multiple tests of the control sample at different laser powers applied to the microfluidic channel; . . . .”).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application have in the system of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober the processor be configured to adjust an intensity of the emission of the light at the imaging wavelength from a first intensity to a second intensity; and determining presence of the compound in the patient sample based on a difference between the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, respectively, at the first intensity and the second intensity as taught by Miller because Miller discloses (1) that peak area is function of light intensity (paragraph [0058] and Figures 4 and 12), and (2) variation (error) in determined peak area due to variation in light intensity or other factors such as focusing an optical alignment may be reduced with data about the relationship light intensity and peak area (or peak height and width)for example, through curve fitting. See Miller paragraphs [0059] and [0067]-[0069], and claims 11 and 12.
Claims 12 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Galen in view of ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober as applied to claims 1-6, 9-11, 13-19, 22-24, 26, and 27 above, and further in view of Berry et al. US 9,230,186 B1 (hereafter “Berry”).
Addressing claim 12, Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober does not appear to disclose generating a compiled image that overlays the first of the multiple images and the second of the multiple images, although, as already discussed in the rejection of underlying claim 11 Galen does disclose generating multiple images.
Berry discloses analysis of electrophoretic bands in a substrate that involves generating a compiled image that overlays multiple images. See the title, Abstract, Figure 2, noting especially 220 (“creating a layered Composite Image”); and claim 1, second step (“creating a layered composite image . . . .”).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to compile multiple images as taught by Berry in the method of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober because as taught by Berry discloses
PNG
media_image17.png
202
456
media_image17.png
Greyscale
(see Berry col. 2:33-43), and
PNG
media_image18.png
262
440
media_image18.png
Greyscale
(see Berry col. 4:6-19).
Addressing claim 25, Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober does not appear to disclose the processor being further configured to generate a compiled image that overlays the first of the multiple images captured at the imaging wavelength and the second of the multiple images captured during emission of white light, although, as already discussed in the rejection of underlying claim 23 Galen does disclose generating multiple images.
Berry discloses analysis of electrophoretic bands in a substrate that involves generating a compiled image that overlays multiple images. See the title, Abstract, Figure 2, noting especially 220 (“creating a layered Composite Image”); and claim 1, second step (“creating a layered composite image . . . .”).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the processor be configured to compile multiple images as taught by Berry in the method of Galen as modified by ThermoFisher, Zwart, Horecker, Lillard, Hicks, Hirsch, Hasan, Tamari, and Kober because as taught by Berry discloses
PNG
media_image17.png
202
456
media_image17.png
Greyscale
(see Berry col. 2:33-43), and
PNG
media_image18.png
262
440
media_image18.png
Greyscale
(see Berry col. 4:6-19).
Regarding the claim limitation “the second of the multiple images captured during emission of white light”, first recall the following from the rejection of underlying claim 23 ‘recall for the following from the rejection of underlying claim 14
“Moreover, Galen discloses multiple imaging using more than one light source emitting more than one spectrum of light:
PNG
media_image11.png
222
434
media_image11.png
Greyscale
“ ‘
Now note that Berry discloses only white light illumination or alternatively using multiple illumination means, such as white light, fluorescence or chemiluminescence. See Berry col. 1:27-28, col. 2:6-8, and col. 3:17-19. Also see Kober col. 13:47-51, and Tamari the Abstract and paragraph [0021], which discloses provided both a UV light source and white source. The choice of light (illumination) source such as a white light source, is prima facie obvious as routine optimization of a known result effective variable (MPEP 2144.05(II) in order to achieve optimum optical recognition of the compound (separation band) with maximum signal-to-noise ratio while it is in the electrophoresis strip.
Final Rejection
Applicant's amendment necessitated the new grounds 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 ALEXANDER STEPHAN NOGUEROLA whose telephone number is (571)272-1343. The examiner can normally be reached on Monday - Friday 9:00AM-5:30 PM EST.
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, Luan Van can be reached on 571 272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEXANDER S NOGUEROLA/ Primary Examiner, Art Unit 1795
1 In claim 1,“creating a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile based on the determined absorption or fluorescence characteristic of the compound; . . . .” In claim 14, “a processor configured to: during an active run of an electrophoresis test, receive data that includes absorption or fluorescence characteristics of the compound; create a compound profile that optimizes the image produced when a band with the compound is imaged during the active run of the electrophoresis test, the compound profile created for the compound based on the received absorption or fluorescence characteristics during the active run of the electrophoresis test, . . . .”
2 Note that the Examiner considers “subtypes” in Hicks to be synonymous with “sub-variants”.
3 The Examiner considers transmission imaging here to be clearly analogous to, if he same as, absorbance imaging.
4 Note that the Examiner considers “subtypes” in Hicks to be synonymous with “sub-variants”.
5 The Examiner considers transmission imaging here to be clearly analogous to, if he same as, absorbance imaging.
6 Fluorescence is mentioned here because this claim later requires “determine presence of the compound in the patient sample based on the absorption characteristic or the fluorescence characteristic of the absorbed or fluoresced light, . . . . [italicizing by the Examiner]”
7 Note that the Examiner views “laser p[power” in Miller as being equivalent to if not synonymous with “laser intensity”.
8 Note that the Examiner views “laser p[power” in Miller as being equivalent to if not synonymous with “laser intensity”.