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 .
Response to Amendment
This action is in response to the remarks filed on 01/02/2026.
The amendments filed on 01/02/2026 have been entered. Accordingly claims 1-4 and 12-24 remain pending. Independent claim 1 is presently amended. Claims 12-24 were previously withdrawn from consideration.
The previous rejections of claim 1-4 under 35 U.S.C 112(b) have been withdrawn in light of applicant's amendments to claim 1, however the amendments introduce new issues of indefiniteness that are detailed below.
Response to Arguments
Applicant's arguments filed 01/02/2026 have been fully considered but they are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., calculating functional capillary area based on the actual movement distance of blood cells or detecting a single red blood cell) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Claim Objections
Claim 1 is objected to because of the following informalities:
Regarding claim 1, the limitation “the three images” in the last line of the claim should be changed to –the three consecutive images—in order to have proper antecedent basis.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-4 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 recites the limitation “identical first target factors” in lines 18-19 and line 22 which renders the claim indefinite. It is unclear if these identical first target factors are the same or different as the first target factors previously recited in the claim. It is also unclear if each instance of the recitation is the same or different identical first target factors. For the present purposes of examination, they have all been interpreted as being the same. Further clarification is required.
Claims dependent upon a claim rejected under 35 U.S.C. 112(b) are also rejected under the same statute because they each inherit the indefiniteness of the claim(s) they respectively depend upon.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Najarian et al. (US 2012/0269420, October 25, 2012, applicant submitted prior art via the IDS, hereinafter “Najarian”) in view of Kvernebo (US 2015/0359440, December 17, 2015).
Regarding claim 1, as best understood in light of the 35 U.S.C. rejections stated above, Najarian discloses a method for providing information for diagnosis of sepsis-induced acute lung injury in a subject (“The results of quantitatively monitoring and assessing the changes that occur in microcirculation during resuscitation period assist physicians in making diagnostically and therapeutically important decisions” Abstract; also see “Study of microcirculation has shown potential diagnostic value in diseases such as sepsis” [0004]), comprising:
quantitating microcirculation in the subject (“quantitative analysis of microcirculation” Abstract), comprising:
obtaining a plurality of motion images of first target factors over time in a blood stream passing through capillaries of the subject (“An embodiment of the invention detects the presence and density of active capillaries in SDF video recordings, quantitatively monitor and assess the flow of red blood cells [i.e. first target factors] in the detected capillaries” [0007]; also see “Referring to FIG. 1, video of capillaries are captured by a handheld microscan device 10. As illustrated, the device is pressed against the patient's tongue to obtain video images of the capillaries and small blood vessels in the lingual surface. While the lingual surface is the preferred surface to obtain these video images because of the profusion of capillaries and small blood vessels in the tongue, other body surfaces could also be used to generate these video images, including but not limited to the ear lobe and whites of the eye. These video images are converted to digital images by analog-to-digital (A/D) converter 11, which are then input to a computer or data processing system, here illustrated as a desk top computer 12.” [0026]);
measuring functional capillary area in which the first target factors move in the blood stream from the plurality of motion images (“An embodiment of the invention detects the presence and density of active [i.e. functional] capillaries in SDF video recordings” [0007]; also see “total area covered by the active vessels” in [0057]; also see [0055]-[0062]); and
calculating functional capillary ratio (FCR) (“Functional Capillary Density (FCD) is calculated by Area” [0055]) according to the formula:
Functional capillary ratio = functional capillary area / total capillary area (“Three measures are obtained: FCD by Area, FCD by Length, and the Proportion of Perfused Vessels (PPV). These are calculated as follows: F C D By Area = A av/ A v [...] where: A.sub.av is the total area covered by the active vessels A.sub.v is the total area covered by all vessels” [0056]-[0058]), and
wherein the functional capillary area is defined as a spatial region generated by accumulated displacement trajectories of identical first target factors over time (“a threshold is applied to the intensity variation matrix to identify vessels without blood-flow. As blood moves through a vessel, the vessel pixels show intensity variation across video frames [over time]. A low degree of variation indicates a lack of flow, so pixel locations with variation below the specified threshold are recorded as non-active” [0052]; also see [0055]-[0062), and
wherein the functional capillary area is measured by identifying the first target factors in three consecutive images (M-1, M, M+1) imaged with a same time interval (t) corresponding to time points (T-1, T, T+1), such that a flow path of identical first target factors in a blood stream passing through the capillaries of the subject is observable across the three images (“averaged frames over ten-frame windows” [0031]; also see “The next stage 65 in the image processing shown in FIG. 6 is the identification of active capillaries. This process is shown in more detail in FIG. 12. The input is the raw microcirculation video and a set of binary images showing identified vessel pixels. In steps 121 and 122, intensity differences are calculated and summed across consecutive frames. Using the raw microcirculation video, an intensity variation matrix is constructed which records how much the intensity value for each pixel location varies throughout the video. For example, consider location [i,j]. The difference in pixel intensity at this location will be calculated over consecutive frames of the video.” in [0051]; also see “As blood moves through a vessel, the vessel pixels show intensity variation across video frames.” [0052]).
Although Najarian suggests (b) acquiring the information for diagnosing sepsis-induced acute lung injury in the subject from the FCR (“Study of microcirculation has shown potential diagnostic value in diseases such as sepsis (see, for example, R. M. Bateman, M. D. Sharpe, and C. G. Ellis, "Bench-to-bedside review: microvascular dysfunction in sepsis: hemodynamics, oxygen transport and nitric oxide". Crit Care Med 7: 359-373, 2003)” [0004]), Najarian fails to explicitly disclose (b) acquiring the information for diagnosing sepsis-induced acute lung injury in the subject from the FCR, wherein the information is that probability of being diagnosed with sepsis-induced acute lung injury in the subject is higher than a control group when the FCR of the subject is lower than FCR of the control group; or probability of being diagnosed with sepsis-induced acute lung injury in the subject is equal to or lower than the control group when the FCR of the subject is equal to or higher than the FCR of the control group.
However, Kvernebo teaches, in the same field of endeavor, (b) acquiring the information for diagnosing sepsis-induced acute lung injury in the subject (“disease processes in the heart, the lungs and the transport vessels, as well as in the microcirculation can cause circulatory failure. These conditions may develop acutely or over time. Lack of oxygen delivery may lead to cellular dysfunction or death, and may proceed to organ failure and death of an individual. Circulatory failure can be local or systemic. Generalized (i.e. systemic) and clinically evident failure, i.e. shock, may be central (e.g. caused by heart failure or hypervolemia) or peripheral (e.g. distributive failure caused by sepsis)” [0003]; also see “with lung infections, sepsis episodes,” [0198]) from the FCR (“assessing the subject's microcirculation in respect of the following parameters: (a) functional capillary density (FCD)” Abstract), wherein the information is that probability of being diagnosed with sepsis-induced acute lung injury in the subject is higher than a control group when the FCR of the subject is lower than FCR of the control group; or probability of being diagnosed with sepsis-induced acute lung injury in the subject is equal to or lower than the control group when the FCR of the subject is equal to or higher than the FCR of the control group (“the results of analysis may be quantified by comparison to reference values based upon values obtained from corresponding examinations of healthy subjects, with a significant deviation from those values being indicative of circulatory failure” [0052]).
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to modify the invention of Najarian with (b) acquiring the information for diagnosing sepsis-induced acute lung injury in the subject from the FCR, wherein the information is that probability of being diagnosed with sepsis-induced acute lung injury in the subject is higher than a control group when the FCR of the subject is lower than FCR of the control group; or probability of being diagnosed with sepsis-induced acute lung injury in the subject is equal to or lower than the control group when the FCR of the subject is equal to or higher than the FCR of the control group as taught by Kvernebo in order to provide the appropriate interventional therapy needed to treat the diagnosed condition ([0049] of Kvernebo).
Regarding claim 2, Najarian modified by Kvernebo discloses the limitations of claim 1 as stated above and Najarian further discloses wherein the first target factors in the blood stream are one or more selected from a group consisting of leukocytes, erythrocytes, blood platelets and lymphocytes (“quantitatively monitor and assess the flow of red blood cells in the detected capillaries” [0007]).
Regarding claim 4, Najarian modified by Kvernebo discloses the limitations of claim 1 as stated above and Najarian further discloses wherein the plurality of motion images over time are a plurality of images imaged at a frame rate of 1-900 frames/second (“The raw microcirculation videos are captured at a rate of 30 frames/second.” [0038]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Najarian in view of Kvernebo as applied to claims 1-2 above and further in view of Horesh et al. (US 2019/0099081, filed October 3, 2018, hereinafter “Horesh”).
Regarding claim 3, Najarian modified by Kvernebo discloses the limitations of claim 2 as stated above but fails to disclose wherein the first target factors in the blood stream are fluorescence-stained first target factors in the blood stream.
However, Horesh teaches, in the same field of endeavor, wherein the first target factors in the blood stream are fluorescence-stained first target factors in the blood stream (“Fluorescence imaging is a known in the art technique for medical diagnostics. To image tissue in vivo, a fluorescent dye or stain is added to the blood flowing within the tissue. The fluorescent molecules of the dye, or ‘fluorophores’, bind with the blood cells, fluorescently labelling them. During surgery, the tissue is illuminated with a light source selected to excite the fluorophores, causing them to emit fluorescent light. A fluorescent microscope collects the emitted light using optical filters selected to match the emission spectrum of the fluorophores. The filtered light is detected by an electronic imaging sensor, such as a CMOS or CCD camera, and the resulting fluorescent image is displayed for further analysis. The fluorescent microscope may acquire multiple images over a given timespan to produce an in vivo video of the blood flow in real time. In this manner, the internal blood flow through the tissue may be imaged during surgery, and tissue perfusion and vessel patency may be evaluated.” [0003]).
Najarian and Horesh both teach video imaging of blood flow. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to substitute one type of imaging for another to achieve the predictable result of obtaining video images of blood flow.
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.
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/A.A./Examiner, Art Unit 3797
/CHRISTOPHER KOHARSKI/Supervisory Patent Examiner, Art Unit 3797
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