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 .
Acknowledgement of Amendment
The following office action is in response to the applicant’s amendment filed on 04/20/2026. Claims 1-3, 13-15, 23,26-27, 31-32, 42-51, and 70 are pending. Claims 1, 14-15, 26, 31-32, 42, 44, 48-50 and 70 are amended. Claims 1-3, 13-15, 23, 26-27, 31-32, 42-51, and 70 are rejected under 35 U.S.C. 102/103 for the reasons stated in the Response to Arguments and 35 U.S.C. 103 sections below.
Response to Arguments
Applicant’s arguments, see Remarks page 12, filed 04/20/2026 with respect to the objections to the specification, drawings, and claims have been fully considered and are persuasive. The objections to the specification, drawings, and claims in the non-final rejection of 01/21/2026 have been withdrawn.
Applicant’s arguments, see Remarks page 13-14, filed 04/20/2026 with respect to the rejection of claim 70 under 35 U.S.C. 101 have been fully considered and are persuasive.
Regarding claim 70, the claim stands rejected under 35 U.S.C. 101 for allegedly being directed to an abstract idea. In particular, the Office has asserted that the claim is directed to a “mental processes that can be performed in the human mind. The Office further asserts that the judicial exception is not integrated into a practical application and does not recite additional elements that amount to significantly more than the alleged judicial exception.
The Applicant respectfully requests reconsideration of the claim in light of the amendments made to claim 70 and the remarks provided below:
Revised Step 2A - Prong One: Evaluate Whether the Claim Recites a Judicial Exception (i.e., an abstract idea):
With respect to abstract ideas and Prong One of Revised Step 2A, examiners must (a) identify the specific limitation(s) in the claim under examination (individually or in combination) that the examiner believes recites an abstract idea and (b) determine whether the identified limitation(s) falls within at least one of the three groupings of abstract ideas: (1) mathematical concepts; (2) certain methods of organizing human activity; and (3) mental processes. MPEP 2106.04(a). If the examiner determines that the claims do not recite subject matter falling within one of the three groupings of abstract ideas, then the claims should not be treated as reciting an abstract idea (i.e., are not directed to a judicial exception) (Step 2A: NO). MPEP 2106.04(a).
Applicant respectfully asserts that the recited claim limitations do not fall within one of the three groupings of abstract ideas, including the "mental processes" grouping, as asserted by the Office, and, thus, are not directed to the judicial exception of an abstract idea as alleged by the Office.
Upon reading through the Applicant’s amended claim 70, the examiner disagrees that the recited claim limitations do not fall within one of the three groupings of abstract ideas, including the “mental processes” grouping. The examiner agrees that the contacting, providing, and continuously detecting steps do not represent an abstract idea. However, the examiner respectfully maintains that the step of “analyzing the microscopic images to identify characteristics of a biological fluid in the biological structure” represents a step which can be practically performed in the human mind (i.e. is a mental process) involving a user viewing microscopic images to identify biological fluid characteristics in the biological structure.
"Mental Processes"
The "mental processes" grouping includes "concepts performed in the human mind (including an observation, evaluation, judgement, opinion)." MPEP 2106.04(a)(2)(III)(A). A claim with limitation(s) that cannot practically be performed in the human mind does not recite a mental process. Id. In particular, MPEP 2106.04(a)(2)(III)(A) expressly states that "[c]laims do not recite a mental process when they do not contain limitations that can practically be performed in the human mind, for instance when the human mind is not equipped to perform the claim limitations." See SRI Int'l, Inc. v. Cisco Systems, Inc., 930 F.3d 1295, 1304 (Fed. Cir. 2019) (declining to identify the claimed collection and analysis of network data as abstract because "the human mind is not equipped to detect suspicious activity by using network monitors and analyzing network packets as recited by the claims") and SiRF Tech., Inc. v. Int'l Trade Comm'n, 601 F.3d 1319, 94 USPQ2d 1607 (Fed. Cir. 2010), as directed to inventions that "could not, as a practical matter, be performed entirely in a human's mind") (Emphasis added).
Applicant respectfully asserts that the pending claims recite limitations that cannot practically be performed in the human mind, and, as such, do not recite a mental process (as alleged by the Office). For example, claim 1 is directed to a computer implemented method that includes a number of computer-implemented functions not practically performed in the human mind, including:
"contacting tissue of the subject with a tissue stabilizer to maintain a position of a
biological structure of the subject; and
"providing, using a non-coherent light source, light to a portion of a region of the
biological structure to continuously illuminate the region of the biological structure.
Emphasis added.
Accordingly, none of the pending claim limitations fall within the "mental processes" grouping of abstract ideas. For at least the reasons set forth above, none of the pending claim limitations fall within any of the three groupings of abstract ideas. Therefore, according to MPEP 2106.04(a), the pending claims recite eligible subject matter, and no further analysis is needed.
The examiner respectfully acknowledges that the pending claims recite limitations that cannot practically be performed in the human mind, and, as such, do not recite a mental process. The examiner recognizes that claim 1 is directed to a computer implemented method that includes a number of computer-implemented functions not practically performed in the human mind, including: “contacting tissue of the subject with a tissue stabilizer to maintain a position of a biological structure of the subject; and providing, using a non-coherent light source, light to a portion of a region of the biological structure to continuously illuminate the region of the biological structure”. Therefore, the claim is not directed to an invention is performed entirely in a human’s mind.
Therefore, the rejection of claim 70 under 35 U.S.C. 101 in the non-final rejection of 01/21/2026 has been withdrawn.
Applicant’s arguments, see Remarks page 14, filed 04/20/2026 with respect to the rejection of claims 14-15, 43 and 45 under 35 U.S.C. 112(b) have been fully considered and are partially persuasive given the amendments made thereto.
Regarding claims 14-15, the examiner acknowledges that these claims have been amended to depend from claim 13 in which the term “an adapter” is first used. Therefore, the claims have proper antecedent basis for the term “the adapter”.
Regarding claim 43, the examiner notes that this claim still depends on claim 41 which was previously cancelled. The examiner would therefore, recommend amending the claim to be dependent on claim 42 since claim 42 recites “a controller”.
Regarding claim 45, the examiner acknowledges that claim 44 recites a tissue stabilizer and that claim 45 further defines the structures included within the tissue stabilizer and establishes proper antecedent basis for the term “the adapter”.
The rejection of claims 14-15, and 45 under 35 U.S.C. 112(b) in the non-final rejection of 01/21/2026 have been withdrawn. The rejection of claim 43 under 35 U.S.C. 112(b) in the non-final rejection of 01/21/2026 is respectfully maintained for the reason stated above (see 35 U.S.C. 112 section below).
Applicant’s arguments, see Remarks page 15-17, filed 04/20/2026 with respect to the rejection of the claims under 35 U.S.C. 102 have been fully considered and are not persuasive.
Regarding claim 1, the claim has been amended to recite: “a non-coherent light source having a light-outputting end positioned in the imaging section of the housing for illuminating a region of the microvasculature with light, therein the light-outputting end is offset relative to an optical axis of the imaging section”.
Applicant respectfully asserts that Yokhai fails to teach or suggest at least the above- emphasized elements of claim 1. In particular, Yokhai fails to teach or suggest an imaging instrument including a coherent light source having a light-outputting end positioned in the image section of the housing for illuminating a region of microvasculature with light. For example, paragraph [0116] of the as-filed specification describes the use of data acquisition instructions with optical techniques, such as a non-coherent light source. Applicant respectfully asserts that Yokhai makes no mention of an imaging instrument with such a non-coherent light source, as required by amended claim 1.
The Office alleges that the light source 125 described on p. 13, lines 5-7 of Yokhai teaches the previously-claimed illumination device. See Office Action, p. 8. P. This referenced portion of Yokhai further describes that the light source 125 is "positioned on the rigid support housing 105 to emit coherent light into the tissue." (Emphasis added.) That is, Yokhai is directed to a system that uses a coherent light (i.e., a laser) for imaging. In fact, Yokhai makes no mention of an imaging system with a non-coherent light source.
Applicant further asserts that any interpretation of the light source 125 of Yokhai to teach the claimed non-coherent light source would conflate laser light with non-coherent light sources. Applicant respectfully asserts this is inconsistent with the understanding of one of ordinary skill in the art. As evidence, Applicant directs the Examiner's attention to Dall Agnol et al., "Comparative analysis of coherent light action (laser) versus non-coherent light (light-emitting diode) for tissue repair in diabetic rate," Laser Med Sci (2009) (hereinafter "Dall Agnol"), which is submitted herewith.
Dall Agnol establishes that a person of ordinary skill in the art would have understood laser light and non-coherent light to be fundamentally different. Specifically, Dall Agnol teaches:
"[C]oherent optical radiation produced by laser sources is intrinsically monochromatic and is expected to be more chromophore specific than the broadband light emitted by such non-coherent sources as LEDs. Broadband non- coherent light can simultaneously excite multiple chromophores and, therefore, might trigger multiple biochemical reactions," See Dall Agnol, p. 914, col. 1, par. 4; and
"the broad spectrum of the non-coherent light source" differs from "coherence or light-polarization issues. The availability of multiple wavelengths may simultaneously excite multiple chromophores and trigger multiple biochemical reactions at the same time, which may not happen with monochromatic laser radiation." See Dall Agnol, p. 915, col. 1, par. 3.
Accordingly, Dall Agnol demonstrates extrinsic evidence that confirms that one of ordinary skill in the art would not consider laser light and non-coherent light to be interchangeable. The claimed imaging instrument includes a non-coherent light source is therefore not disclosed by Yokhai.
For at least the above reasons, Applicant respectfully submits that independent claim 1 is patentable over Yokhai. Additionally, claims 2-3, 13-15, 23, 26-27, 31-32, and 42-43 depend from claim 1 and are also patentable over Yokhai, alone or in combination with any of the other cited references.
The examiner respectfully notes that Yokhai also discloses “A sensor of the disclosure may also separately include Non coherent illumination e.g., such as a Visible light source (e.g., LED)” [Page 25, Lines 12-13].
Therefore, the examiner respectfully maintains that it would be obvious to modify the sensor 102 to include a non-coherent light source. Thus, the examiner respectfully maintains that Yohai teaches the features of claim 1 for the reasons stated above. The rejection of claim 1 has been updated in the 35 U.S.C. 102 section below to reflect the amended claim limitations.
Independent Claims 44, 48, and 70
Applicant submits that the remarks above with respect to independent claim 1 similarly apply to independent claims 44, 47, and 70. In particular, Applicant respectfully asserts that Yokhai fails to teach or suggest the claimed non-coherent light source. For at least the above reasons, Applicant respectfully submits that independent claims 44, 48, and 70, and all claims dependent thereon are patentable, alone or in combination with any of the other cited references. Accordingly, Applicant respectfully requests withdrawal of the rejection of claims 44-45, 48-51, and 70, and allowance of claims 44-45, 48-51, and 70.
Regarding claims 44, 48 and 70, the examiner acknowledges that these claims have been amended in a similar manner to claim 1. Therefore, these claims are subject to the reasoning provided therein. Thus, the examiner respectfully maintains that Yokhai teaches the non-coherent light source for the reasons stated with respect to claim 1 above. The rejections of claims 44, 48 and 70 have therefore, been amended in the 35 U.S.C. 102 section below to reflect the amended claim limitations.
Applicant’s arguments, see Remarks page 17-19, filed 04/20/2026 with respect to the rejection of the claims under 35 U.S.C. 103 have been fully considered and are persuasive.
Dependent Claim 42
Claim 42 depends from independent claim 1 and, as amended, further recites:
The system of claim 1 wherein:
The microscopic images include images of blood cells in the microvasculature, and
the system further comprises a controller in electrical communication with the
non-coherent light source-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,
(ii) quantify one or more biological features comprising at least one of a
blood cell count, a blood cell movement, or a leukocyte-endothelial interaction; and
(iii) use automated frame-by-frame leukocyte tracking to calculate average
rolling velocity of the blood cells in the microvasculature.
Applicant respectfully asserts that Yokhai in view of Lam fail to teach or suggest the above- emphasized elements of claim 42. In particular, Yokhai in view of Lam fails to teach or suggest quantifying one or more biological features of blood cells including at least one of a blood cell count, a blood cell movement, or a leukocyte-endothelial interaction, as well as the use of automated frame-by-frame leukocyte tracking to calculate an average rolling velocity of the blood cells. The Office alleges that par. [0101] of Lam teaches automated frame-by-frame leukocyte tracking to calculate average rolling velocity of the leukocytes in microvasculature. See Office Action, p. 28. Paragraph [0101] of Lam describes various experimental findings, stating that "leukocyte rolling velocity in mice is slower than in control mice." Applicant respectfully asserts that Lam makes no mention of quantifying any of the claimed biological features of blood cells and using automated leukocyte tracking to calculate an average rolling velocity.
For at least the above reasons, Applicant respectfully submits that claim 42 is patentable over Yokhai in view of Lam.
The examiner respectfully asserts that the leukocyte rolling velocity represents a quantity which represents blood cell movement (i.e. a leukocyte being a type of white blood cell). In order to determine that the leukocyte rolling velocity in the mice lacking vimentin (i.e. recombinant human vimentin) is slower than in control mice, the leukocyte rolling velocity in each had to have been quantified/calculated.
Therefore, the examiner respectfully maintains that Yokhai in view of Lam teaches the amended limitations of claim 42 for the reasons stated above. The rejection of claim 42 has been updated in the 35 U.S.C. 103 section below.
Dependent Claim 49
Claim 49 depends from claim 48 and, as amended, further recites:
The system of claim 48 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 non-coherent light source, the objective lens, and the image detector are arranged on the first arm such that the image detector detects microscopic images using phase-contrast imaging.
Applicant respectfully asserts that Yokhai in view of Mertz fails to teach or suggest the above-emphasized elements of claim 49. In particular, Yokhai in view of Mertz fails to teach or suggest an image detector that detects microscopic images using phase-contrast imaging. For example, paragraph [0244] of the as-filed specification describes "enabling real-time, label-free phase contrast imaging." The Office references oblique back-illumination (OBM) of Mertz in the rejection of claim 49. See Office Action, p. 31. Applicant respectfully asserts the OBM described in Mertz differs from the claimed phase-contrast imaging.
For at least the above reasons, Applicant respectfully submits that claim 49 is patentable over Yokhai in view of Mertz.
The examiner respectfully asserts that Mertz discloses “a method of creating a phase contrast image” [Abstract]; “This disclosure also provides methods of creating a phase contrast image. In some embodiments the method comprises illuminating the target region of a sample with a first light source to provide a first oblique back illumination of the target region of the sample, and detecting a first phase contrast image from light originating from the first light source and back illuminating the target region of the sample” [0120]. Thus, the examiner respectfully asserts that Mertz teaches using “phase-contrast imaging”.
Thus, the rejection of claim 49 under 35 U.S.C. 103 is respectfully maintained for the reasons stated above. Furthermore, the rejection of claim 49 has been updated to reflect the amended limitations.
Claim Objections
Claim 26 is objected to because of the following informalities:
Regarding claim 26, as written it reads “a tip; the objective lens positions in the tip such that the objective lens receives at least a portion of light scattered by the region of the microvasculature; an annular vacuum, positioned in the tip and surrounding the object lens, wherein the annular vacuum stabilizes device for stabilizing the tissue being imaged”. The examiner notes that “the object lens” is a typo which should be “the objective lens” in order to maintain proper antecedent basis with “the objective lens” recited earlier in the claim.
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.
Claim 43 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 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 § 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.),
“a non-coherent light source 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” (“A sensor of the disclosure may also separately include Non coherent illumination e.g., such as a Visible light source (e.g., LED). Devices and methods of the disclosure provide a sensor 102 that comprises a coherent energy source transmitter 125, the detector 121 and the optical unit that are aligned in a spatial position that allows the reflected speckle interference transmitted from the transmitter to be collected by the optic unit and be detected by the detector 121” [Page 25, Lines 12-17]; “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” Attaching the sensor to the patient via the mounting tab 106 and the anchor 104 permits hands-free detection of the speckle pattern by the detector” [Page 13, Lines 5-8]; “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, since the sensor (i.e. sensor 102) may separate non coherent illumination source (i.e. visible light source (LED) the imaging instrument includes a non-coherent light source 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.);
“a non-coherent light source having a light-outputting end positioned in the tissue stabilizer for illuminating a region of the microvasculature with light” (See [Page 13, Lines 5-8] and [Page 25, Lines 12-17] as discussed with respect to claim 1 above. Therefore, the system includes an illumination device (i.e. sensor with separate non coherent illumination source/LED) 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.);
“a non-coherent light source having a light-outputting end positioned in the tissue stabilizer for illuminating a region of the microvasculature with light” (See [Page 13, Lines 5-8] and [Page 25, Lines 12-17] as discussed with respect to claim 1 above. Therefore, the system includes an illumination device (i.e. sensor with separate non coherent illumination source, LED) 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 a non-coherent light source, light to a portion of a region of the biological structure to continuously illuminate the region of the biological structure” (See [Page 13, Lines 5-8] and [Page 25, Lines 12-17] as discussed with respect to claim 1 above. Therefore, the method involves, providing, using an illumination device (i.e. sensor with separate non-coherent illumination source, LED), 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 non-coherent light source” (See [Page 12, Line 27-Page 13, Line 1], [Page 15, Lines 25-30] and [Page 25, Lines 3-4], [Page 25, Lines 12-17] 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 13 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 non-coherent light source is arranged on the second arm such that the image detector detects microscopic images using offset trans-illumination (OTM)” (See [Page 25, Lines 12-17] as discussed in claim 1 above and “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 Lee US 2020/0249456 A1 “Lee”.
Regarding claim 26, Yokhai discloses all features of the claimed invention as discussed with respect to claim 1 above, and Yokhai further teaches “wherein the imaging section further comprises: a tip; the objective lens positioned in the tip such that the objective lens receives at least a portion of light scattered by the region of the microvasculature” (See FIG. 6 and “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 detector 121 may include detection optical element(s) 606 for collecting the laser speckle image 201” [Page 23, Lines 25-26]; “The optical elements 606 may be a main camera lens and the detector 121 may further include one or more optical filter(s) 633” [Page 23, Lines 28-30]. Therefore, the imaging section (i.e. shown in FIG. 6 further comprises a tip (i.e. on which detector 121, optical elements 606, and optical filters 633 are attached), the objective lens (i.e. optical elements 606) positioned in the tip such that the objective lens receives at least a portion of light scattered by the region of the microvasculature (i.e. included within the illumination region 615 of the tissue 109).);
However, Yokhai does not teach wherein: the imaging section further comprises “an annular vacuum, positioned in the tip and surrounding the object lens, wherein the annular vacuum stabilizes device for stabilizing the tissue being imaged”.
Lee is within a related field of endeavor as the claimed invention because it involves liquid immersion microscope objective assembly with includes an objective lens and a V-shaped .
Lee teaches wherein: the imaging section further comprises “an annular vacuum, positioned in the tip and surrounding the object lens, wherein the annular vacuum stabilizes the tissue being imaged” (“As used herein, the term “sample” generally refers to one or more objects (or particles) capable of being imaged by a microscope. The sample may be, for example, biological material (e.g., a biological cell, multicellular tissue, single-cell organism, multicellular organism, etc.)” [0035]; “according to another embodiment, the liquid immersion microscope objective system includes a vacuum pump configured to establish a flow of liquid from the liquid return path to the liquid return line” [0015]; “For example, the fluid pump may create suction (vacuum) at the interface of the bottom of the annular V-shaped channel 196 and the return inlet 106.” [0061]; “To prevent contact between the residual liquid 122 and such components, the residual liquid 122 may be captured and removed by the annular V-shaped channel 196 as the residual liquid 122 drops onto the outer surface of the conical portion 192 of the liquid handling device 108, or drops directly into the annular V-shaped channel 196, or is otherwise drawn into the annular V-shaped channel 196 by suction” [0065]. As shown in FIG. 1, the annular V-shaped channel 196 surrounds the objective lens 116, the objective lens 116 facing the sample S (see FIG. 1). Therefore, since a vacuum/fluid pump is provided to create suction at the bottom of the annular V-shaped channel 196, the imaging section further comprises an annular vacuum (i.e. vacuum pump in connection with the annular V-shaped channel 196), positioned in the tip (i.e. of objective assembly 100) and surrounding the objective lens, wherein the annular vacuum stabilizes the tissue (i.e. sample S, see [0035] and FIG. 1) 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 an annular vacuum positioned in the tip and surrounding the objective lens, wherein the annular vacuum stabilizes the tissue being imaged as disclosed in Lee in order to ensure that the imaging section does not move when the tissue is being imaged. An annular vacuum 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 an annular vacuum positioned in the tip and surrounding the objective lens, wherein the annular vacuum stabilizes the tissue being imaged as disclosed in Lee would yield the predictable result of ensuring that the imaging section does not move when the tissue is being imaged.
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 non-coherent light source, 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 non-coherent light source, 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 non-coherent light source,” (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 non-coherent light source” (Claim 32) (“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 blood cells 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 non-coherent light source 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” (See [Page, 25, Lines 12-17] as discussed in claim 1 above, and “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) quantify one or more biological features comprising at least one of: a blood cell count, a blood cell movement, or a leukocyte-endothelial interaction; (iii) 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) quantify one or more biological features comprising at least one of: a blood cell count, a blood cell movement, or a leukocyte-endothelial interaction” (“2) Leukocyte rolling velocity in mice lacking vimentin is slower than in control mice” [0101]. A leukocyte is a type of white blood cell. In this case, the leukocyte rolling velocity represents a quantity which corresponds to blood cell movement. To compare the leukocyte rolling velocity in mice lacking vimentin to the control mice, the leukocyte rolling velocity must be quantified in each of these types of mice. Therefore, the controller is configured to quantify one or more biological features comprising at least one of: a blood cell count, a blood cell movement, or a leukocyte-endothelial interaction, specifically a blood cell movement in the form of leukocyte rolling velocity.);
“(iii) use automated frame-by-frame leukocyte tracking to calculate average rolling velocity of the blood cells in the microvasculature” (See [0101] above and “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 non-coherent light source, the objective lens, and the image detector are arranged on the first arm” (See FIGS. 1A and 1B; [Page 25, Lines 12-17] as discussed in claim 1. As shown in FIGS. 1A and 1B, the illumination device (i.e. sensor 102 containing light source 125 and separate non-coherent light source LED), 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 phase-contrast imaging”.
Mertz is within a related field of endeavor to the claimed invention because it involves “A method of creating a phase contrast image” [Abstract].
Mertz teaches “such that the image detector microscopic images using oblique back-illumination (OBM)” (“A method of creating a phase contrast image is provided” [Abstract]; “This disclosure also provides methods of creating a phase contrast image. In some embodiments the method comprises illuminating the target region of a sample with a first light source to provide a first oblique back illumination of the target region of the sample, and detecting a first phase contrast image from light originating from the first light source and back illuminating the target region of the sample” [0120]. Therefore, since phase contrast image is generated Mertz teaches obtaining microscopic images using phase contrast imaging.).
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
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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/KAITLYN E SEBASTIAN/Examiner, Art Unit 3797
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