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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/24/2025 and 11/21/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description:
FIG. 2: Although the specification states “Referring now to Figures 1B and 2, there is shown one example embodiment of a portable tissue stabilizer 200 according to the invention positioned on a human subject 50” [00107], FIG. 2 does not include the label 200. Rather FIG. 2 includes the label 100 as shown in FIG. 1A.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description:
FIG. 2: Although this figure includes the labels 114 and 116, these labels are not found in the specification.
FIG. 24B: Although this figure includes the label 2590, this label is not found in the specification.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
[0011]: As written it reads “In one embodiment, the image detector is a CMOS sensor”. However, this is the first indication of the acronym “CMOS”, therefore, the term should be spelled out to provide clarity.
[00103]: As written it reads “mechanical holders that modify the natural position of the oral mucosa tissue with or without integrated optics (e.g., lenses) or light sources (e.g., LEDs)”. However, this is the first indication of the acronym “LEDs”, therefore, the term should be spelled out to provide clarity.
[00115]: As written it reads “The vacuum pressure varies between about 0.1 to 5 SCFH”. However, this is the first indication of the acronym “SCFH”, therefore, the term should be spelled out to provide clarity.
[00177]: As written it reads “Different CNN layer architectures, including but not limited to different versions of squeezeNet, ResNet, EfficientNet, MobileNet, R-CNN and YOLO mya be used. However, this is the first indication of the acronyms “R-CNN” and “YOLO”, therefore, the terms should be spelled out to provide clarity.
Appropriate correction is required.
Claim Objections
Claim 32 is objected to because of the following informalities:
Regarding claim 32, the claim reads “wherein: the imaging section further comprises an imaging tip that contains the objective lens, a vacuum device, an irrigation channel, and an illumination fiber of the illumination device, and the objective lens is gradient index (GRIN) lens”. However to be grammatically correct the word “a” should be inserted between “is” and “gradient”.
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.
Claims 14-15, 43 and 45 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Regarding claims 14, 15 and 45, as written the claims read “wherein: the adapter is dimensioned for contacting oral mucosa of the subject” (Claim 14) and “wherein: the adapter is dimensioned for contacting a lip of the subject” (Claim 15); “the adapter is moveable toward and away from the base” (Claim 45). However, there is a lack of antecedent basis for the term “the adapter” in claims 1 and 44 on which these claims depend. Therefore, it is unclear what is being referred to by this term. The examiner recommends clarifying this term and/or updating the dependence of these claims to be dependent on claim 2 if the adapter recited therein is indeed the same structure as that of claims 14, 15. Additionally, regarding claim 45, the examiner recommends clarifying this term and/or amending claim 44, on which this claim depends, to include the term “an adapter”.
Regarding claim 43, the claims reads “The system of claim 41, wherein the controller executes the program stored in the controller to: […]”, however, there is a lack of antecedent basis for the term “the controller” since claim 41, on which this claim depends was cancelled. Thus, it is unclear what is being referred to in this claim. The examiner notes that claim 42 recites “a controller”. If this is indeed the same controller as the one used in claim 43, the examiner would recommend updating the dependency of claim 43 to depend from claim 42.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 70 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception in the form of an abstract idea, specifically a mental process, without significantly more.
Regarding claim 70, the examiner notes that the claim is directed to a method for in vivo flow cytometry of a biological fluid in a subject. Therefore, the claims fall within one of the statutory categories of invention.
With reference to Step 2A, Prong One, the claim recites “analyzing the microscopic images to identify characteristics of a biological fluid in the biological structure”.
The limitation(s), under broadest reasonable interpretation, cover performance of the limitation in the mind and/or read on analyzing microscopic images. Analyzing microscopic images represents an action which can be practically performed in the human mind by a user viewing microscopic images and distinguishing/assessing characteristic of biological fluid in the biological structure. If a claim limitation under its broadest reasonable interpretation covers performance of the limitation in the mind but for the recitation of generic computer components (i.e. a processor), then it falls within the “mental processes” grouping of abstract ideas.
Following step 2A, Prong Two of the two-prong analysis, the claim recites the following additional elements: “contacting tissue of the subject with a tissue stabilizer to maintain a position of a biological structure of the subject; providing, using an illumination device, light to a portion of a region of the biological structure to continuously illuminate the region of the biological structure; continuously detecting, using an image detector, microscopic images from the region of the biological structure based on light scattered by the biological structure of the subject, wherein illumination is at an oblique angle due to offset geometry of the illumination device”. These additional elements do not integrate the judicial exception into a practical application because the claim as written does not include elements to 1) improve the functioning of a computer (See MPEP 2106.05(a)); 2) effect a particular treatment or prophylaxis (See MPEP 2106.04(d)(2)); 3) use a particular machine (See MPEP 2106.05(b)); 4) use the judicial exceptions in a meaningful way beyond generally linking the use to a particular technological environment (See MPEP 2106.05(h)). Furthermore, these steps do not integrate the judicial exception into a practical application because they add insignificant extra-solution activity, in the form of data gathering, to the judicial exception using a well-known device (i.e. illumination device and image detector) (See MPEP 2106.05(g)).
Following step 2B, the additional element(s) (i.e. “contacting tissue of the subject with a tissue stabilizer to maintain a position of a biological structure of the subject; providing, using an illumination device, light to a portion of a region of the biological structure to continuously illuminate the region of the biological structure; continuously detecting, using an image detector, microscopic images from the region of the biological structure based on light scattered by the biological structure of the subject, wherein illumination is at an oblique angle due to offset geometry of the illumination device”) do not amount to significantly more than the judicial exception the these limitations represent data gathering steps which utilize conventional tools (i.e. illumination device and image detector)) to perform well understood, routine and conventional activity (i.e. obtaining image data, see [Page 12, Line 27-Page 13, Line 1], [Page 13, Lines 3-4] and [Page 15, Lines 25-30] in Yokhai et al. WO 2021/144658 A1 “Yokhai”) in the field, to perform the abstract idea.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 13, 27, 44-45, 48, 51, and 70 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Yokhai et al. WO 2021/144658 A1 “Yokhai”.
Regarding claim 1, Yokhai teaches “A system for imaging of microvasculature of tissue of a subject, the system comprising:” (“An optical sensing system includes an optical detector, a rigid support structure for attaching the detector and a coherent light source to a patient and holding those in position, relative to soft tissue, while the coherent light forms a speckle pattern within the tissue in view of the detector. […] The detector and light source may be communicatively coupled to a computer station such that the system is operable for: continuous, hands-free monitoring, by laser speckle imaging, of microcirculation while the patient is in shock, and to guide fluid delivery to treat shock or avoid fluid overload” [Page 12, Lines 17-26] and “FIG. 1A shows components of an optical sensing system 101. The system 101 includes a sensor 102 that includes an optical detector 121 and a rigid support housing 105 connected to a mounting tab 106 for attaching the detector 121 to an anchor 104” [Page 12, Lines 27-29]. Therefore, since the optical sensing system (i.e. 101 as shown in FIG. 1A) is operable for continuous, hands-free monitoring of microcirculation (i.e. within microvasculature) of a patient, the optical sensing system 101 represents a system for imaging microvasculature of tissue of a subject.).;
“(a) a tissue stabilizer structured to contact the tissue of the subject to maintain a position of the region of the microvasculature being imaged” (“The anchor 104 is configured for attaching to a patient and holding the sensor 121 in position relative to tissue 109 of a patient. The anchor 104 includes a clamp 139 or other suitable mechanism for attaching the anchor 104 to teeth or bone of the patient” [Page 12, Lines 29-Page 13, Line 1]. Therefore, the anchor 104 represents a tissue stabilizer structured to contact the tissue (see FIG. 1A) of the subject to maintain a position of the region of the microvasculature being imaged (i.e. by the optical detector 121).); and
“(b) an imaging instrument including:” (See [Page 12, Lines 27-29] above. Since the optical sensing system 101 includes a sensor 102 that includes an optical detector 121 and a rigid support housing 105 connected to a mounting tab 106 for attaching the detector 121 to an anchor 104 (i.e. tissue stabilizer), the optical sensing system 101 represents an imaging instrument.);
“a housing having an imaging section” (See rigid support housing 105 in FIG. 1A and [Page 12, Lines 27-29]. Therefore, since the rigid support housing 105 attaches the optical detector 121 to the anchor 104, the rigid support housing represents a housing having an imaging section (i.e. in which the light source 125 and optical detector 121 are positioned). Thus, the imaging instrument includes a housing (i.e. 105) having an imaging section.),
“an illumination device having a light-outputting end positioned in the imaging section of the housing for illuminating a region of the microvasculature with light, wherein the light-outputting end is offset relative to an optical axis of the imaging section” (“The system 101 includes a light source 125 positioned on the rigid support housing 105 to emit coherent light into the tissue 109 to form a speckle pattern within the tissue 109 in view of the detector 121” [Page 13, Lines 5-7]; “FIG. 1B shows the sensor 102 within the housing 105 drawn in wire-frame view to illustrate placement of optical elements within the sensor 102” [Page 13, Lines 9-10]. As shown in FIG. 6, the light-outputting end of the light source 125 is offset relative to an optical axis of the imaging section (i.e. the detector 121). Therefore, the light source 125 represents an illumination device having a light-outputting end positioned in the imaging section of the housing for illuminating a region of the microvasculature with light, wherein the light-outputting end is offset relative to an optical axis of the imaging section.),
“an objective lens positioned in the imaging section of the housing such that the objective lens receives at least a portion of light scattered by the region of the microvasculature” (“The Detector/Receiver lens may include an optical objective that focuses the region of interest upon the detector” [Page 25, Lines 3-4]. Therefore, the imaging instrument includes an objective lens (i.e. detector/receiver lens) positioned on the imaging section of the housing (i.e. rigid support housing 105) such that the objective lens receives at least a portion of light scattered by the region of the microvasculature (i.e. and focuses it on the detector (i.e. 121).), and
“an image detector positioned in the imaging section of the housing such that the image detector receives light redirected by the objective lens and detects microscopic images of the region of the microvasculature” (See [Page 12, Lines 27-29] above and “Preferably, the rigid support housing 105 carries a detector 121 for imaging the soft tissue 109 and the light source 125. The detector 121 and the light source 125 may be mounted to, or connected to, one or more boards (such as printed circuit boards) mounted in the housing 105” [Page 13, Lines 22-24]; “Systems and methods of this disclosure provide a reliable continuous and real-time measurement and analysis of blood flow parameters, for example, flow rate in the capillaries, microvascular flow index (MFI), proportion of perfused small vessels (PPV), and inverse decorrelation time (ICT). The system is adapted to measure those parameters in a small noninvasive anatomical window, for example, the oral cavity area, such as a sublingual or buccal area” [Page 15, Lines 25-30]. Therefore, the imaging instrument includes an image detector (i.e. optical detector 121) positioned in the imaging section of the housing (i.e. rigid support housing 105) such that the image detector receives light redirected by the objective lens (i.e. Detector/Receiver lens, see [Page 25, Lines 3-4]) and detects microscopic images of the region of the microvasculature (i.e. imaging of soft tissue 109, [Page 13, Lines 22-24] and continuous/real-time measurement).).
Regarding claim 2, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, and Yokhai teach “wherein: the tissue stabilizer comprises a base, a sliding mechanism mounted on the base, an adapter for contacting the tissue, the adapter being mounted on the sliding mechanism, and the adapter is moveable toward and away from the base” (See FIG. 1A below
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“The anchor 104 includes a clamp 139 or other suitable mechanism for attaching the anchor 104 to teeth or bone of the patient. Suitable mechanisms may include a press-fit (e.g., a tapered tooth sleeve), cement, a dental screw or other bone screw. In the depicted embodiments, a clamp 139 includes a screw to drive two opposed plates towards each other to securely grip one or more teeth of the patient” [Page 12, Line 31-Page 13, Line 4]. Therefore, the tissue stabilizer (i.e. anchor 104) comprises a base (i.e. see annotated FIG. 1A above), a sliding mechanism mounted on the base (i.e. clamp 39 including screw to drive two opposed plates towards each other, see [Page 12, Line 31-Page 13, Line 4]), an adapter for contacting the tissue (see annotated FIG. 1A above), the adapter being mounted on the sliding mechanism (i.e. clamp 139), and the adapter is moveable toward and away (i.e. via the clamp 139/screw) from the base (i.e. see annotated FIG. 1A above.).
Regarding claim 13, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, and Yokhai further teaches “wherein: the tissue stabilizer comprises a base, a sliding mechanism mounted on the base, an adapter for contacting the tissue, the adapter being mounted on the sliding mechanism, and the adapter is moveable laterally with respect to the base” (See annotated FIG. 1A as disclosed with respect to claim 2 above and [Page 12, Line 31-Page 13, Line 4] as discussed in claim 2 above. Therefore, the tissue stabilizer (i.e. anchor 104) comprises a base (see annotated FIG. 1A), a sliding mechanism mounted on the base (i.e. clamp 139/screw), an adapter for contacting the tissue (See annotated FIG. 1A above), the adapter being mounted on the sliding mechanism (See annotated FIG. 1A), and the adapter is moveable laterally (i.e. horizontally) with respect to the base.).
Regarding claim 27, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, and Yokhai further teaches “further comprising: the imaging section further comprises an irrigation channel for supplying a fluid to keep the tissue being imaged moist” (“wherein, when anchored to the teeth via the anchor, the sensor comprises no flexible or moveable part other than the focusing module and any one or more flexible tubes or wires extending from the rigid structure and from the mouth of the [patient], the tubes or wires passing fluid, suction, power, or data to or from the sensor” [Claim 24]. In this case, the anchor 104 (i.e. tissue stabilizer) is positioned such that the sensor/detector faces soft tissue in the oral cavity (see [Claim 22]). Therefore, when anchored to the teeth (i.e. within the oral cavity), the sensor also includes one or more flexible tubes or wires to supply fluid and therefore, keep the tissue being imaged moist. Therefore, the system further comprises that the imaging section further comprises an irrigation channel (i.e. one or more flexible tubes or wires) for supplying a fluid to keep the tissue being imaged moist.).
Regarding claim 44, Yokhai teaches “A system for imaging of microvasculature of tissue of a subject, the system comprising:” (See [Page 12, Lines 17-26] and [Page 12, Lines 27-29] as discussed in claim 1 above. Therefore, since the optical sensing system (i.e. 101 as shown in FIG. 1A) is operable for continuous, hands-free monitoring of microcirculation (i.e. within microvasculature) of a patient, the optical sensing system 101 represents a system for imaging microvasculature of tissue of a subject.);
“an imaging instrument including a housing having an imaging section” (See rigid support housing 105 within the optical sensing system 101 (i.e. imaging instrument) in FIG. 1A and [Page 12, Lines 27-29] as discussed with respect to claim 1 above. Therefore, the system includes an imaging instrument (i.e. optical sensing system 101) including a housing (i.e. rigid support housing 105) having an imaging section (i.e. in which the light source 125 and optical detector 121 are positioned).);
“a tissue stabilizer structured to contact the tissue of the subject to maintain a position of the region of the microvasculature being imaged by the imaging instrument” (See [Page 12, Lines 29-Page 13, Line 1] as discussed with respect to claim 1 above. The anchor 104 represents a tissue stabilizer structured to contact the tissue of the subject to maintain a position of the region of the microvasculature being imaged by the imaging instrument.);
“an illumination device having a light-outputting end positioned in the tissue stabilizer for illuminating a region of the microvasculature with light” (See [Page 13, Lines 5-7] as discussed with respect to claim 1 above. Therefore, the system includes an illumination device (i.e. light source 125) having a light-outputting end positioned in the tissue stabilizer (i.e. anchor 104 via the rigid housing 105) for illuminating a region of the microvasculature with light.);
“an objective lens positioned in the imaging section of the housing such that the objective lens receives at least a portion of light scattered by the region of the microvasculature” (See [Page 25, Lines 3-4] as discussed in claim 1 above. Therefore, the system includes an objective lens (i.e. detector/receiver lens) positioned on the tissue stabilizer (i.e. anchor 104 via the rigid support housing 105) such that the objective lens receives at least a portion of light scattered by the region of the microvasculature (i.e. and focuses it on the detector (i.e. 121).); and
“an image detector positioned in the imaging section of the housing such that the image detector receives light redirected by the objective lens and detects microscopic images of the region of the microvasculature” (See [Page 12, Lines 27-29]; [Page 13, Lines 22-24]; and [Page 15, Lines 25-30] as discussed with respect to claim 1 above. Therefore, the system includes an image detector (i.e. 112) positioned in the tissue stabilizer (i.e. adapter 104 via the rigid support housing 105) such that the image detector receives light redirected by the objective lens (i.e. Detector/Receiver lens in [Page 25, Lines 3-4]) and detects microscopic images of the region of the microvasculature (i.e. imaging the soft tissue 109, and [Page 15, Lines 25-30]).
Regarding claim 45, Yokhai discloses all features of the claimed invention as discussed with respect to claim 44 above, and Yokhai further teaches “wherein: the tissue stabilizer comprises a base, a sliding mechanism mounted on the base, an adapter for contacting the tissue, the adapter being mounted on the sliding mechanism, and the adapter is moveable toward and away from the base” (See annotated FIG. 1A as disclosed with respect to claim 2 above and [Page 12, Line 31-Page 13, Line 4] as discussed in claim 2 above. Therefore, the tissue stabilizer (i.e. anchor 104) comprises a base (see annotated FIG. 1A), a sliding mechanism mounted on the base (i.e. clamp 139/screw), an adapter for contacting the tissue (See annotated FIG. 1A above), the adapter being mounted on the sliding mechanism (See annotated FIG. 1A), and the adapter is moveable toward and away from the base (See annotated FIG. 1A).).
Regarding claim 48, Yokhai teaches “A system for imaging of microvasculature of tissue of a subject, the system comprising:” (See [Page 12, Lines 17-26] and [Page 12, Lines 27-29] as discussed in claim 1 above. Therefore, since the optical sensing system (i.e. 101 as shown in FIG. 1A) is operable for continuous, hands-free monitoring of microcirculation (i.e. within microvasculature) of a patient, the optical sensing system 101 represents a system for imaging microvasculature of tissue of a subject.);
“a tissue stabilizer structured to contact the tissue of the subject to maintain a position of the region of the microvasculature being imaged” (See [Page 12, Lines 29-Page 13, Line 1] as discussed with respect to claim 1 above. The anchor 104 represents a tissue stabilizer structured to contact the tissue of the subject to maintain a position of the region of the microvasculature being imaged. Therefore, the system includes a tissue stabilizer (i.e. anchor 104) structured to contact the tissue of the subject to maintain a position of the region of the microvasculature being imaged.);
“an illumination device having a light-outputting end positioned in the tissue stabilizer for illuminating a region of the microvasculature with light” (See [Page 13, Lines 5-7] as discussed with respect to claim 1 above. Therefore, the system includes an illumination device (i.e. light source 125) having a light-outputting end positioned in the tissue stabilizer (i.e. the anchor 104 via the rigid support housing 105) for illuminating a region of the microvasculature with light.);
“an objective lens positioned in the tissue stabilizer such that the objective lens receives at least a portion of light scattered by the region of the microvasculature” (See [Page 25, Lines 3-4] as discussed in claim 1 above. Therefore, the system includes an objective lens (i.e. detector/receiver lens) positioned on the tissue stabilizer (i.e. anchor 104 via the rigid support housing 105) such that the objective lens receives at least a portion of light scattered by the region of the microvasculature (i.e. and focuses it on the detector (i.e. 121).); and
“an image detector positioned in the tissue stabilizer such that the image detector receives light redirected by the objective lens and detects microscopic images of the region of the microvasculature” (See [Page 12, Lines 27-29]; [Page 13, Lines 22-24]; and [Page 15, Lines 25-30] as discussed with respect to claim 1 above. Therefore, the system includes an image detector (i.e. 112) positioned in the tissue stabilizer (i.e. adapter 104 via the rigid support housing 105) such that the image detector receives light redirected by the objective lens (i.e. Detector/Receiver lens [Page 25, Lines 3-4]) and detects microscopic images of the region of the microvasculature (i.e. imaging the soft tissue 109, and [Page 15, Lines 25-30]).).
Regarding claim 51, Yokhai discloses all features of the claimed invention as discussed with respect to claim 48 above, and Yokhai further teaches “wherein: the tissue stabilizer comprises a first arm, an opposed second arm, and a hinge connecting the first arm and the second arm such that a variable size space is created between the first arm and the second arm for receiving the tissue” (See annotated FIG. 1A above and [Page 12, Line 31-Page 13, Line 4] as discussed with respect to claim 2 above. Therefore, the tissue stabilizer (i.e. anchor 104) comprises a first arm, an opposed second arm (i.e. two plates, see annotated FIG. 1A above), and a hinge connecting the first arm and the second arm (i.e. see annotated FIG. 1A) such that a variable size space is created (i.e. facilitated by moving the clamp 139 and adapter along the hinge, see annotated FIG. 1A and [Page 12, Line 29-Page 13, Line 1]) is created between the first and the second arm for receiving the tissue.).
Regarding claim 70, Yokhai teaches “A method for in vivo flow cytometry of a biological fluid in a subject, the method comprising:” (“Systems and methods of this disclosure provide a reliable continuous and real-time measurement and analysis of blood flow parameters, for example, flow rate in the capillaries, microvasculature flow index (MFI), proportion of perfused small vessels (PPV), and inverse decorrelation time (ICT). The system is adapted to measure those parameters in a small noninvasive anatomical window, for example, the oral cavity area, such as a sublingual or buccal area” [Page 15, Lines 25-30]. Therefore, Yokhai discloses a method for in vivo flow cytometry (i.e. real-time measurement and analysis of blood flow parameters) of a biological fluid in a subject.);
“(a) contacting tissue of the subject with a tissue stabilizer to maintain a position of a biological structure of the subject” (See [Page 12, Line 27, Page 13, Line 1] as disclosed in claim 1 above. Therefore, since the anchor 104 is attached to a patient to hold the sensor 121 in position relative to the tissue of a patient, the method involves contacting tissue of the subject with a tissue stabilizer (i.e. anchor 104) to maintain a position of a biological structure of the subject.);
“(b) providing, using an illumination device, light to a portion of a region of the biological structure to continuously illuminate the region of the biological structure” (See [Page 13, Lines 5-7] as discussed with respect to claim 1 above. Therefore, the method involves, providing, using an illumination device (i.e. light source 125), light to a portion of a region of the biological structure to continuously illuminate the region of the biological structure.);
“(c) continuously detecting, using an image detector, microscopic images from the region of the biological structure based on light scattered by the biological structure of the subject, wherein illumination is at an oblique angle due to offset geometry of the illumination device” (See [Page 12, Line 27-Page 13, Line 1], [Page 15, Lines 25-30] and [Page 25, Lines 3-4] as discussed with respect to claim 1 above. As shown in FIG. 6, the light source 125 (i.e. illumination device) is offset from the detector 121. Therefore, the method involves continuously detecting (i.e. see [Page 15, Lines 25-30]), using an image detector (i.e. optical detector 121), microscopic images from the region of the biological structure based on light scattered by the biological structure of the subject, wherein the illumination is at an oblique angle due to offset geometry of the illumination device (see FIG. 6).); and
“(d) analyzing the microscopic images to identify characteristics of a biological fluid in the biological structure” (See [Page 15, Lines 25-30] as discussed above. Therefore, the method involves analyzing the microscopic images to identify characteristics of a biological fluid in the biological structure.).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai” as applied to claim 2 above, and further in view of Weinlaender US 2010/0217130 A1 “Weinlaender”.
Regarding claim 3, Yokhai discloses all features of the claimed invention as discussed with respect to claim 2 above, however, Yokhai does not teach “wherein: the base comprises a chin holder, and the tissue stabilizer further comprises a frame, the chin holder and a forehead holder being mounted on the frame”.
Weinlaender is within a related field of endeavor to the claimed invention because it involves a device for securing a patient such that imaging can be performed (see FIG. 1).
Weinlaender teaches “wherein: the base comprises a chin holder, and the tissue stabilizer further comprises a frame, the chin holder and a forehead holder being mounted on the frame” (“At the front edge 10 is located the cranium restraint 1 of the apparatus with a chin rest 11 and a cranium contact surface 12. By means of the adjusting screw 13 the chin rest 11 can be moved upward or downward, wherein a measurement scale 14 is provided at one edge of the cranium restraint 1, on which the adjusted height of the chin rest 11 can be read off and reproduced at any time” [0012]. Therefore, the baseplate 4 (i.e. base) comprises a chin holder (i.e. chin rest 11), the tissue stabilizer (i.e. cranium restraint 1) comprising a frame (i.e. 1), the chin holder (i.e. 11) and a forehead holder (i.e. cranium contact surface 12) being mounted on the frame.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai such that the base comprises a chin holder and the tissue stabilizer further comprises a frame, the chin holder and a forehead holder being mounted on the frame as disclosed by Weinlaender in order to effectively secure the patient such that imaging can be performed (i.e. by camera 5 of Weinlaender: FIG. 1). Providing a chin holder, forehead holder on a base is one of a finite number of techniques which can be used to fix a patient’s head to a specific position such that imaging can be performed with a reasonable expectation of success. Thus, modifying the system of Yokhai such that the base comprises a chin holder and the tissue stabilizer further comprises a frame, the chin holder and a forehead holder being mounted on the frame as disclosed by Weinlaender would yield the predictable result of securing a patient such that imaging can be performed.
Claim(s) 14-15, and 50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai”.
Regarding claims 14 and 15, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, and Yokhai further teaches “wherein: the adapter is dimensioned for contacting oral mucosa of the subject” (Claim 14) and “wherein: the adapter is dimensioned for contacting a lip of the subject” (Claim 15) (See annotated FIG. 1A as discussed in claim 2 above and “Once positioned, the clinician may use a fixation mechanism (e.g., may tighten a set screw) to fix the optics in position within the oral cavity” [Page 14, Lines 6-7]; “The system is adapted to measure those parameters in a small noninvasive anatomical window, for example, the oral cavity area, such as a sublingual or buccal area” [Page 15, Lines 28-30].
The examiner notes that the lip of a subject represents the outer portion of the oral cavity of the patient. Although FIG. 1A shows the adapter surrounding a patient’s tooth, it would be obvious to one of ordinary skill in the art to modify the adapter such that it is dimensioned for contacting oral mucosa (i.e. oral cavity area, such as a sublingual or buccal area) of the subject or a lip (i.e. outer part of the oral cavity) of the subject in order to allow the user to effectively secure the tissue of a patient such that imaging can be performed.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the adapter such that it is dimensioned for contacting oral mucosa of the subject or dimensioned for contacting a lip of the subject in order to allow a user to effectively secure the tissue of a patient (i.e. either the oral mucosa or the lip) such that imaging can be performed with the optical detector 121.
Regarding claim 50, Yokhai discloses all features of the claimed invention as discussed with respect to claim 48 above, and Yokhai further teaches “wherein: the tissue stabilizer comprises a first arm and an opposed second arm, the first arm and the second arm defining a space therebetween for receiving the tissue, and the objective lens and the image detector are arranged on the first arm,” (See FIG. 1B and “The anchor 104 includes a clamp 139 or other suitable mechanism for attaching the anchor 104 to teeth or bone of the patient. Suitable mechanisms may include a press-fit (e.g., a tapered tooth sleeve), cement, a dental screw or other bone screw. In the depicted embodiments, a clamp 139 includes a screw to drive two opposed plates towards each other to securely grip one or more teeth of the patient” [Page 12, Line 31-Page 13, Line 4]. Therefore, the tissue stabilizer (i.e. anchor 104) comprises a first arm and an opposed second arm (i.e. two plates, see FIG. 1B) the first arm and the second arm defining a space therebetween for receiving the tissue.
Furthermore, as shown in FIGS. 1A and 1B, the objective lens (i.e. Detector/Receiver lens, see Page 25, Lines 3-4]), and the image detector (i.e. optical detector 121) are arranged on (i.e. connected to) the first arm (i.e. opposed plate of 104).). and
“the illumination device is arranged on the second arm such that the image detector detects microscopic images using offset trans-illumination (OTM)” (“FIG. 6 shows optical elements 601 of a sensor 102 placed in an oral cavity 138 of a patient. As shown, the rigid support housing 105 carries a detector 121 for imaging the soft tissue 109 and the light source 125” [Page 23, Lines 9-11]; “The light source 125 may include optical element(s) 605, such as a lens or prism, for directing coherent light onto the soft tissue 109” [Page 23, Lines 15-16]. As shown in FIG. 6, the illumination device (i.e. light source 125) is offset from the image detector (i.e. optical detector 121). Therefore, the illumination device (i.e. light source 125) is arranged on the second arm (i.e. separately) such that the image detector detects microscopic images using offset trans-illumination (OTM).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the tissue stabilizer (i.e. anchor 104) of Yokhai FIG. 1A/1B, such that the illumination device (i.e. light source 125) is arranged on the second arm (i.e. separately from the image detector) as disclosed in Yokhai FIG. 6 in order to enable imaging to be performed with offset trans-illumination (OTM). Performing offset trans-illumination (OTM) is one of a finite number of techniques which can be used to obtain imaging data from the tissue of a patient with a reasonable expectation of success. Thus, modifying the tissue stabilizer (i.e. anchor 104) of Yokhai FIG. 1A/1B, such that the illumination device (i.e. light source 125) is arranged on the second arm (i.e. separately from the image detector) as disclosed in Yokhai FIG. 6 in order to enable imaging to be performed with offset trans-illumination (OTM) such that characteristics of the patient’s tissue can be evaluated.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai” as applied to claim 1 above, and further in view of Barthe et al. JP 2016-104506 A “Barthe” as evidenced by Andeas DE 102007004724 A1 “Andreas”.
Regarding claim 23, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, however, Yokhai does not teach “wherein: the image detector is moveable with respect to the objective lens”.
Barthe is within a related field of endeavor to the claimed invention because it involves an apparatus with a camera unit which includes an objective lens (see [Abstract]).
Barthe teaches “wherein: the image detector is moveable with respect to the objective lens” (“The coupling mechanism has two predetermined movement capabilities that allow the coupling part to move on the one hand relative to the objective lens body and on the other hand relative to the component support. With two removable clamping mechanisms, two movement capabilities can be allowed or blocked independently of each other. This allows accurate adjustment of the image sensor relative to the objective lens in various directions” [Page 2, Background-Art: Para. 3]. Therefore, the image sensor (i.e. image detector) is moveable with respect to the objective lens. As evidenced by Andreas, “this configuration allows a first mobility with multiple degrees of freedom and thus a great flexibility when adjusting the image sensor relative to the lens” [Page 4, Para. 11] such that the image sensor 64 is centered relative to the lens 46 and therefore allows the image sensor to be positioned at a focal point of the lens (see Andreas: [Page 7, Para. 8].).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai such that the image detector is moveable with respect to the objective lens as disclosed by Barthe and evidenced by Andreas in order to allow for greater flexibility and accurate adjustment of the position of the image detector when performing imaging at a focal point of the objective lens. When an image detector is moveable with respect to an objective lens, the image detector can be accurately positioned such that an accurate image can be obtained from a focal point of the objective lens with a reasonable expectation of success. Thus, modifying the system of Yokhai such that the image detector is moveable with respect to the objective lens as disclosed by Barthe and evidenced by Andreas would yield the predictable result of allowing for accurate adjustment of the position of the image detector when performing imaging at a focal point of the objective lens.
Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai” as applied to claim 1 above, and further in view of Anderson et al. US 2006/0189964 A1 “Anderson”.
Regarding claim 26, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, however, Yokhai does not teach “wherein: the imaging section further comprises a vacuum device for stabilizing the tissue being imaged”.
Anderson is within a related field of endeavor as the claimed invention because it involves vacuum sealing a device to a biological tissue (see FIG. 13, [0053], [0054]).
Anderson teaches “wherein: the imaging section further comprises a vacuum device for stabilizing the tissue being imaged” (“FIG. 13 is a cutaway view 1300 of a device 1302 to treat a biological tissue 1301 according to one embodiment. As shown in FIG. 13, device 1302 has an outer portion 1311 and a cavity 1303 encompassed by the outer portion 1311. Device 1302 is applied over biological tissue 1301, such that vacuum seals 1305 are formed between outer portion 1311 and biological tissue 1301” [0053]; “In an embodiment, device 1302 has one or more ports to provide negative and positive pressures or substances to chamber 1303, e.g., port 1306, port 1308, and port 1314. As shown in FIG. 13, outer portion 1311 of device 1302 may have one or more panels, e.g. panels 1307, 1309, and 1312, connected to respective energy sources (not shown), sensors (not shown), and power regulators (not shown) to display data and information on operation of device 1302” [0054]. In this case, since the one or more panels 1307, 1309, 1312 may be connected to respective energy sources, sensor and power regulators to display data and information, the device 1302 includes an imaging section (i.e. sensor) to obtain information about the target 1304 (i.e. within tissue 1301). Therefore, since vacuum seals 1305 are created between the outer portion 1311 and the biological tissue 1301 and the device 1302 includes one or more ports to provide negative and positive pressures to chamber 1303, located therein, the imaging section further comprises a vacuum device (i.e. vacuum seals 1305 and/or ports to provide negative and positive pressures to chamber 1303) for stabilizing the tissue (i.e. 1301) being imaged.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai such that the imaging section further comprises a vacuum device for stabilizing the tissue being imaged (i.e. vacuum seals 1305) as disclosed in Anderson in order to ensure that the imaging section does not move when the tissue is being imaged by the optical detector 121. A vacuum device (i.e. seal) is one of a finite number of devices which can be used to secure a device to a biological tissue with a reasonable expectation of success. Thus, modifying the system of Yokhai such that the imaging section further comprises a vacuum device for stabilizing the tissue being imaged (i.e. vacuum seals 1305) as disclosed in Anderson would yield the predictable result of fixing the imaging section to a particular location on the tissue such that imaging can be performed at said location.
Claim(s) 31-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai” as applied to claim 1 above, and further in view of Bannick et al. JP 2006/521882 A “Bannick” and Ghosh et al. US 2021/0267458 A1 “Ghosh”.
Regarding claims 31 and 32, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, however, Yokhai does not teach “wherein: the imaging section further comprises an imaging tip that contains the objective lens, a vacuum device, an irrigation channel, and an illumination fiber of the illumination device, and the objective lens is a microlens” (Claim 31); “wherein: the imaging section further comprises an imaging tip that contains the objective lens, a vacuum device, an irrigation channel, and an illumination fiber of the illumination device, and the objective lens is [a] gradient index (GRIN) lens” (Claim 32).
Bannick is within a related field of endeavor to the claimed invention because it involves an endoscope with multiple output ports (see FIGS. 6A/6B).
Bannick teaches “wherein: the imaging section further comprises an imaging tip that contains the objective lens, a vacuum device, an irrigation channel, and an illumination fiber of the illumination device,” (“As shown in FIG. 6A, one embodiment of the distal end 400 comprises a cylinder having a distal end portion 402 and a proximal portion 404” [Page 11, Para. 6, Lines 3-4]; “The distal end face of the distal end 400 includes several ports including a camera port 406, one or more illumination ports 408, an access port for the actuation channel hole 410, and a directional wash port 412” [Page 11, Para. 6, Lines 7-8]; “The illumination port 408 houses one or more lenses and one or more light emitting diodes (LEDs) (not shown) […] As an alternative to LEDs, the light source is outside the illumination light supplied to the illumination port by an endoscope and fiber optic bundle” [Page 11, Para. 7, Lines 1-7]; “Access port 410 is the end point of the working channel or hole of the disposable endoscope” [Page 11, Para. 9, Line 1]; “Directional irrigation port 412 includes a cap 414 that directs liquid or air supplied through the irrigation and suction holes across the front surface of distal end 400 in the direction of camera port 406 and / or illumination port 408” [Page 11, Para. 10, Lines 1-2]; “Further, the connector 252 has a connection portion to the suction valve / cleaning valve 256 and the vacuum valve 258 to supply air, water, and vacuum to the endoscope” [Page 8, Para. 5, Lines 7-9]; “On the other side of the manifold, the connector 196 is connected to the working channel to supply water or apply a vacuum to the working channel” [Page 8, Para. 2, Lines 1-2].
Therefore, the imaging section (i.e. 400) includes an imaging tip (i.e. distal end portion 402) that contains the objective lens (i.e. one or more lenses, see [Page 11, Para. 7, Line 1]), a vacuum device (i.e. vacuum valve 258, for example, connected to the working channel, see [Page 8, Para. 2, Lines 1-2] of the access port 410, see [Page 11, Para. 9, Line 1]), an irrigation channel (i.e. directional irrigation port 412, see [Page 11, Para. 10, Lines 1-2]), and an illumination fiber of the illumination device (i.e. fiber optic bundle, see [Page 11, Para. 7, Lines 1-7]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai such that the imaging section further comprises an imaging tip that contains the objective lens a vacuum device, an irrigation channel and an illumination fiber of the illumination device as disclosed in Bannick in order to allow one device to be used to 1) supply/direct light to the tissue, 2) secure the device to the tissue (i.e. vacuum device), and 3) keep the tissue moist (i.e. irrigation device) when performing an imaging procedure.
Yokhai in view of Bannick does not explicitly teach that “the objective lens is a microlens” (Claim 31) or that “the objective lens is [a] gradient index (GRIN) lens” (Claim 32).
Ghosh is within the same field of endeavor as the claimed invention because it involves a micro-lens to focus illumination onto a sample (See [0049]).
Ghosh teaches that “the objective lens is a microlens” (Claim 31) or that “the objective lens is [a] gradient index (GRIN) lens” (Claim 32) (“A gradient refractive index (GRIN) objective micro-lens 318 focuses illumination onto the sample” [0049]. Therefore, the objective lens is a gradient refractive index (GRIN) micro-lens.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai in view of Bannick such that the objective lens is a microlens or a gradient index (GRIN) lens as disclosed in Ghosh in order to provide a lens with a small form factor, provide ease-of-integration with other micro-optics and/or reduce optical path length relative to other types of objective lenses (see Ghosh: [0052]: “A GRIN lens can be particularly useful due to the small form factor and ease-of-integration with other microoptics and/or for reducing optical path length relative to other types of objective lenses”).
Claim(s) 42-43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai” as applied to claim 1 above, and further in view of Lam et al. US 2020/0061153 A1 “Lam”.
Regarding claim 42, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, and Yokhai further teaches “wherein: the microscopic images include images of leukocytes in the microvasculature” (See [Page 13, Lines 22-24] as discussed with respect to claim 1 above and “The following are parameters which the device may measure: Sublingual microcirculation parameters such as: microvascular flow index (MFI), DeBacker score, total vascular density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), vessels heterogeneity, red blood cell velocity, flow patterns; Temperature; Blood pressure; Total peripheral resistance; Heart rate and arrhythmia detection; Respiratory rate and respiratory pattern analysis; Oxygen saturation; Oxygen extraction; Depth of anesthesia; Blood components: such as Hemoglobin concentration, white cell count, and platelets count.; Blood sugar levels; Blood analysis of chemistry components such electrolytes and clotting and coagulation and bleeding analysis; Humidity; Mechanical properties of blood such as blood viscosity; Red blood cell deformability; Blood vessel integrity; and Blood vessel calcification” [Page 30, Lines 21-30]. Leukocytes are a type of white blood cells. Since the device measures parameters such as the white cell count, the device must have performed this measurement based on microscopic images including images of leukocytes in the microvasculature. Therefore, the microscopic images includes images of leukocytes in the microvasculature.), and
“the system further comprises a controller in electrical communication with the illumination device and the image detector, the controller being configured to execute a program stored in the controller to: (i) receive the microscopic images from the image detector” (“The transceivers may include a plurality of light-directing lenses and optics. Systems and methods of the disclosure may include software capable of synchronically instructing the array of multiple electro-optical transceivers to form the speckle pattern, processing the reflection to reconstruct spatiotemporal data mapping perfusion in a plurality of sublingual capillaries located at the oral cavity base over time“ [Page 33, Lines 24-30]. In order to carry out the software operations to synchronically instruct the array of multiple electro-optical transceivers (i.e. the light source 125 and the optical detector 121) to form a speckle pattern and process the reflection to reconstruct spatiotemporal data mapping of the oral cavity over, the system must further comprise a controller in electrical communication with the illumination device (i.e. light source 125) and the image detector (i.e. 121), the controller being configured to execute a program stored in the controller to: (i) receive the microscopic images from the image detector (i.e. 121).).
However, Yokhai does not teach that the controller is configured to: “(ii) use automated frame-by-frame leukocyte tracking to calculate average rolling velocity of the leukocytes in the microvasculature”.
Lam is within a related field of endeavor to the claimed invention because it involves methods which involve measuring cell rolling (see [0129]).
Lam teaches that the controller is configured to: “(ii) use automated frame-by-frame leukocyte tracking to calculate average rolling velocity of the leukocytes in the microvasculature” (“2) Leukocyte rolling velocity in mice lacking vimentin is slower than in control mice” [0101]; “Both static and time-series images (100 frames) were captured. Images were analyzed using ImageJ software (NIH). PMN image[s] were counted as captured or adhered within identical areas of study. Rolling analyses were performed on 20 random PMN per channel and the results averaged based on distance traveled within 100 frames (200 ms per frame) or until the PMN was outside the field of view” [0129].
In this case PMN is a neutrophil, wherein neutrophils are a type of white blood cell/leukocyte. Therefore, since images were analyzed using ImageJ software and rolling analyses (i.e. which calculate rolling velocity, see [0101]) were performed on 20 random PMN (i.e. human neutrophil) images per channel and the results were averaged based on distance traveled within 100 frames, the controller is configured to (ii) use automated frame-by-frame leukocyte tracking to calculate average rolling velocity of the leukocytes in the microvasculature.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai such that the controller is configured to use automated frame-by-frame leukocyte tracking to calculate average rolling velocity of leukocytes in the microvasculature as disclosed in Lam in order to allow the characteristics of the leukocytes within the microvasculature to be analyzed effectively. Calculating the average rolling velocity of leukocytes is one of a finite number of techniques which can be used to characterize the leukocytes with a reasonable expectation of success. Thus, modifying the system of Yokhai such that the controller is configured to use automated frame-by-frame leukocyte tracking to calculate average rolling velocity of leukocytes in the microvasculature as disclosed in Lam would yield the predictable result of enabling the characteristics of the leukocytes within the vasculature to be effectively distinguished.
Regarding claim 43, Yokhai in view of Lam discloses all features of the claimed invention as discussed with respect to claim 41 above, and Lam further teaches “wherein the controller executes the program stored in the controller to: (iii) compare the average rolling velocity of the leukocytes in the microvasculature to an average rolling velocity of leukocytes in heathy tissue” (See [0101] as discussed in claim 42 above, and “(B) Leukocytes (WBC) in vimentin knockout (Vim.sup.−/−) mice have slower rolling velocities in venules than wildtype mice (FIG. 3): Using intravital microscopy of the cremaster muscle vascular bed, a blinded investigator calculated the average rolling velocity of WBC in post-capillary venules. WBC velocity was significantly slower in Vim.sup.−/− mice compared to WT controls” [0093]. Therefore, since the WBC velocity of vimentin knockout mice is slower than the rolling velocity in venules of wildtype mice (i.e. containing healthy tissue), the controller executes the program stored in the controller to: (iii) compare the average rolling velocity of the leukocytes in the microvasculature to an average rolling velocity of leukocytes in healthy tissue.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Yokhai such that the controller executes the program stored in the controller to: (iii) compare the average rolling velocity of the leukocytes in the microvasculature to an average rolling velocity of leukocytes in heathy tissue as disclosed in Lam in order to allow the characteristics of the leukocytes within the microvasculature to be analyzed effectively. Calculating the average rolling velocity of leukocytes and comparing that average rolling velocity to leukocytes in healthy tissue, is one of a finite number of techniques which can be used to characterize the leukocytes with a reasonable expectation of success. Thus, modifying the system of Yokhai such that the controller is configured to compare the average rolling velocity of the leukocytes in the microvasculature to an average rolling velocity of leukocytes in heathy tissue as disclosed in Lam would yield the predictable result of enabling the characteristics of the leukocytes within the vasculature to be effectively distinguished.
Claim(s) 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokhai et al. WO 2021/144658 A1 “Yokhai” as applied to claim 48 above, and further in view of Mertz et al. US 2015/0087902 A1 “Mertz”.
Regarding claim 49, Yokhai discloses all features of the claimed invention as discussed with respect to claim 48 above, and Yokhai further teaches “wherein: the tissue stabilizer comprises a first arm and an opposed second arm, the first arm and the second arm defining a space therebetween for receiving the tissue” (See FIG. 1B and “The anchor 104 includes a clamp 139 or other suitable mechanism for attaching the anchor 104 to teeth or bone of the patient. Suitable mechanisms may include a press-fit (e.g., a tapered tooth sleeve), cement, a dental screw or other bone screw. In the depicted embodiments, a clamp 139 includes a screw to drive two opposed plates towards each other to securely grip one or more teeth of the patient” [Page 12, Line 31-Page 13, Line 4]. Therefore, the tissue stabilizer (i.e. anchor 104) comprises a first arm and an opposed second arm (i.e. two plates, see FIG. 1B) the first arm and the second arm defining a space therebetween for receiving the tissue.), and
“the illumination device, the objective lens, and the image detector are arranged on the first arm” (See FIGS. 1A and 1B. As shown in FIGS. 1A and 1B, the illumination device (i.e. light source 125), the objective lens (i.e. Detector/Receiver lens, see Page 25, Lines 3-4]), and the image detector (i.e. optical detector 121) are arranged on (i.e. connected to) the first arm (i.e. opposed plate of 104).).
However, Yokhai does not teach “such that the image detector microscopic images using oblique back-illumination (OBM)”.
Mertz is within a related field of endeavor to the claimed invention because it involves utilizing oblique back-illumination microscopy (OBM) (See [0012]).
Mertz teaches “such that the image detector microscopic images using oblique back-illumination (OBM)” (“This disclosure describes a new phase contrast technique, sometimes referred to herein as oblique back-illumination microscopy (OBM). OBM works in a reflected light geometry (sometimes called epi-detection geometry), and is thus amenable to in-vivo endomicroscopy applications, among many others. OBM requires no labeling and provides high resolution DIC-like images of sub-surface sample morphology. As will become apparent from this disclosure, the methods and apparatus disclosed herein apply the new OBM technology in ways that offer useful improvements in various ways to other technologies currently available” [0012]; “Two examples of OBM designed that use recessed illumination are shown in FIGS. 28 and 29. FIG. 28 shows a design of OBM based on illumination and detection through a common microscope objective. Collimated, oblique illumination beams are (roughly) focused to off-axis spots on the sample surface. Imaging of the sample is restricted by a field stop (somewhere in the detection optics) to a field of view that does not encompass the illumination spots. FIG. 29 shows a design of miniature OBM endomicroscope probe. Proximal end is shown on left, where two collimated, off-axis illumination beams are (roughly) focused into an imaging fiber bundle with an objective (OBJ). Distal end is shown on right, where a GRIN lens is optically cemented to the fiber bundle, centered by a clear support ring. Imaging is performed in the reverse direction with the GRIN lens and central fiber-bundle cores. Total probe diameter can be as small as 1 mm” [0135].
Therefore, Mertz discloses a system which uses oblique back-illumination (OBM). Therefore, the system of Mertz which obtains microscopic images using oblique back-illumination (OBM).).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the image detector of Yokhai such that it detects microscopic images using oblique back-illumination OBM, as taught by Mertz in order to perform in-vivo endomicroscopy applications without having to perform labeling and obtain high resolution DIC-like images of sub-surface sample morphology (See Mertz: [0012]). Oblique back-illumination (OBM) is one of a finite number of techniques which can be used to obtain high resolution images with a reasonable expectation of success. Thus, modifying the image detector of Yokhai such that it detects microscopic images using oblique back-illumination OBM, as taught by Mertz, would yield the predictable result of performing in-vivo endomicroscopy applications without having to perform labeling and obtaining high resolution DIC-like images of sub-surface sample morphology.
Conclusion
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/KAITLYN E SEBASTIAN/Examiner, Art Unit 3797