DETAILED ACTION
Response to Amendment
This Office Action is responsive to the amendment filed on 04/29/2025. As indicated by the amendment: claims 1-2, 4-5, 17 and 19-23 have been amended, claims 3, 18 and 24 have been cancelled, and new claims 26-28 have been added. Claims 1-2, 4-17, 19-23 and 25-28 are presently pending in the application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 4, 6-10 and 12-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kularatne et al. (US 2021/0353151 A1) in view of Suurs et al. (“Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model”, EJNMMI Research, (2020) 10:1 11) in view of Kim et al. (US 2020/0101175 A1).
Regarding claim 1, Kularatne disclose a method comprising: navigating an instrument (bronchoscope; par. [0005], [0011], [0061] and [0063]), via a minimally invasive route (par. [0005], [0011] and [0063]), into a human patient to whom a molecular imaging agent has been administered (par. [0011] and [0013]), to position the instrument in an area of a tissue abnormality (par. [0005], [0011] and [0063]); and visualizing, via the instrument, tissue in the area under near-infrared (NIR) light (par. [0049] and [0066]), wherein the molecular imaging agent, as administered, causes abnormal tissue in the area to fluoresce under the NIR light and enable the fluorescing abnormal tissue to be localized within the area (par. [0049] and [0066]), wherein the molecular imaging agent comprises a pharmaceutically acceptable salt (par. [0013]).
Although Kularatne teaches administering a pharmaceutically acceptable salt (par. [0013]), it does not specifically disclose that it is administered intravenously and that it comprises VGT-309. Suurs teaches an analogous method for visualizing cancerous tissue wherein the pharmaceutically acceptable salt comprises VGT-309 and is administered intravenously (materials and methods; page 2). Suurs teaches that it is known to administer pharmaceutically acceptable salt either topically or intravenously (introduction; page 2). Suurs also teaches that VGT-309 selectively targets cathepsins, the expression of which is frequently increased in cancerous tissue compared with normal tissue, and is used with a near-infrared ICG fluorophore (introduction and materials and methods; page 2). Moreover, Suurs teaches administering VGT-309 at 1, 2, 4, 8 and 24 hours post VGT-309 injection (page 8, bottom right, additional file 1). It would have been obvious to one having ordinary skill in the art to administer the pharmaceutically acceptable salt intravenously, as taught by Suurs as a known method of administration, and to administer VGT-309 between 2 hours and 4 days prior to navigation, as VGT-309 selectively targets cathepsins and is used with a near-infrared ICG fluorophore, thereby enabling viewing cancerous tissue using the near-infrared imaging instrument of Kularatne, and improving interoperative tumor detection.
Although Kularatne discloses administering the agent and allows time for it to distribute at an intervention site (par. [0011]) and that the effective amount to be administered to a patient is based on body surface area, patient weight, and physician assessment of patient condition (par. [0081]), it does not specifically disclose wherein the molecular imaging agent is administered to the patient at a dose from 0.1 mg/kg to 0.5 mg/kg. Kim teaches that an imaging agent, comprising indocyanine green (ICG), that that present in VGT-309, is administered to the patient in an amount of 0.1 mg to 0.5 mg per unit body weight (1kg) of the patient (par. [0025]). Kim teaches that if the dosage of the administered fluorescent contrast agent is less than 0.1 mg/kg, it is difficult to clearly distinguish the boundary of cancer (par. [0045]). And, if it is more than 1 mg/kg, the possibility of allergic reactions is increased (par. [0045]). It would have been obvious to one having ordinary skill in the art to administer a dose in an amount of 0.1 mg to 0.5 mg per unit body weight (1kg) of the patient, as taught by Kim, as the effective amount to distinguish the boundary of cancer and prevent allergic reactions, as taught by Kim.
Regarding claim 4, Kularatne in view of Suurs in view of Kim disclose the method of claim 1. It would have been obvious to one having ordinary skill in the art to provide a dose from 0.16 mg/kg to 0.4 mg/kg, since where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Additionally, as Kularatne discloses that the effective amount to be administered to a patient is based on body surface area, patient weight, and physician assessment of patient condition (par. [0081]), a smaller patient, in height and weight, would require a smaller dosage.
Regarding claim 6, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, wherein the fluorescing abnormal tissue is in the patient’s lungs (par. [0005], [0052] and [0063]).
Regarding claim 7, Kularatne in view of Suurs in view of Kim disclose the method of claim 6, wherein the fluorescing abnormal tissue comprises a nodule external to a bronchus (par. [0005], [0052] and [0063]).
Regarding claim 8, Kularatne in view of Suurs in view of Kim disclose the method of claim 6, wherein: the instrument comprises a flexible bronchoscope (par. [0061]), and the navigating comprises guiding the flexible bronchoscope through the patient’s airway (par. [0005], [0061] and [0063]).
Regarding claim 9, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, further comprising diagnosing and/or treating the fluorescing abnormal tissue (par. [0078]).
Regarding claim 10, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, wherein the navigating, via a minimally invasive route, is an endoluminal procedure (par. [0005], [0056] and [0063]).
Regarding claim 12, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, wherein: the instrument comprises a biopsy needle or other biopsy tool (par. [0062]); and the diagnosing and/or treating comprises collecting one or more biopsy samples from the fluorescing abnormal tissue (par. [0062] and [0078]).
Regarding claim 13, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, wherein the diagnosing and/or treating comprises resection or destruction of the fluorescing abnormal tissue (par. [0053], [0062]-[0063], [0062] and [0078]).
Regarding claim 14, Kularatne in view of Suurs in view of Kim disclose the method of claim 13, wherein the destruction of the fluorescing abnormal tissue comprise (i) ablation (par. [0062] and [0067]), and/or (it) local administration of a drug to the fluorescing abnormal tissue.
Regarding claim 15, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, which is done without a preoperative marking procedure (par. [0054]-[0056]).
Regarding claim 16, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, wherein the navigating the instrument comprises use of a robotic or robotically-assisted system (par. [0066]).
Claim(s) 2, 5 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kularatne in view of Suurs in view of Kim as applied to claim 1 above, and further in view of Zupkofska et al. (US 2016/0178519 A1).
Regarding claim 2, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, but does not specifically disclose wherein the molecular imaging agent is administered to the patient between 72 hours and 96 hours prior to the navigating. Zupkofska teaches an analogous method for visualizing cancerous tissue wherein a marking agent is administered to a patient (par. [0087]). Zupkofska teaches that once the marker has been delivered to the patient, the marker may be allowed to permeate into the nodule (par. [0087]). Zupkofska also teaches that in some instances, a time period in the range of 20-30 minutes, in the range of several hours, in the range of a day, in the range of several days, or more may be necessary to allow the marker to permeate into the nodule (par. [0087]). Zupkofska further teaches that the time period may be selected to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue. It would have been obvious to one having ordinary skill in the art to wait between 72 hour and 96 hours (several days or more), as taught by Zupkofska, prior to navigating, in order to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue thereby allowing clear viewing of the cancerous tissue, as taught by Zupkofska.
Regarding claim 5, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, but does not specifically disclose wherein the dose to the patient between 12 hours and 96 hours prior to the navigating. Zupkofska teaches an analogous method for visualizing cancerous tissue wherein a marking agent is administered to a patient (par. [0087]). Zupkofska teaches that once the marker has been delivered to the patient, the marker may be allowed to permeate into the nodule (par. [0087]). Zupkofska also teaches that in some instances, a time period in the range of 20-30 minutes, in the range of several hours, in the range of a day, in the range of several days, or more may be necessary to allow the marker to permeate into the nodule (par. [0087]). Zupkofska further teaches that the time period may be selected to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue. It would have been obvious to one having ordinary skill in the art to wait between 12 hours and 96 hours (several days or more), as taught by Zupkofska, prior to navigating, in order to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue thereby allowing clear viewing of the cancerous tissue, as taught by Zupkofska.
Regarding claim 11, Kularatne in view of Suurs in view of Kim disclose the method of claim 1, but does not specifically disclose wherein the area of the tissue abnormality is identified from one or more preoperative scans. Zupkofska teaches an analogous method for visualizing cancerous tissue wherein a preoperative scan (CT scan; par. [0085]) is taken prior to the procedure and the area of the tissue abnormality is identified from the preoperative scan (step 110; par. [0087]). It would have been obvious to one having ordinary skill in the art to take a preoperative scan and confirm that the area of tissue abnormality is the same as that as in the preoperative scan, as taught by Zupkofska, thereby allowing the surgeon to confirm that the tissue was taken from the desired region, as taught by Zupkofska (par. [0087]).
Claim(s) 17, 19-23 and 25-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kularatne et al. (US 2021/0353151 A1) in view of Suurs et al. (“Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model”, EJNMMI Research, (2020) 10:1 11) in view of Kim et al. (US 2020/0101175 A1) in view of Zupkofska et al. (US 2016/0178519 A1).
Regarding claim 17, Kularatne disclose a method comprising: navigating an instrument (bronchoscope; par. [0005], [0011], [0061] and [0063]), via an endoluminal invasive route (par. [0005], [0011], [0063], and [0066]), into a patient to whom a pharmaceutically acceptable salt has been administered (par. [0011] and [0013]), to position the instrument in a target area (par. [0005], [0011] and [0063]); and visualizing, via the instrument, tissue in the area under near-infrared (NIR) light (par. [0049] and [0066]), identifying in real time the location of any abnormal or cancerous tissue within
the target area by the florescence of the abnormal or cancerous tissue caused by the pharmaceutically acceptable salt under the NIR light (par. [0063], [0066] and [0078]).
Although Kularatne teaches administering a pharmaceutically acceptable salt (par. [0013]), it does not specifically disclose that it is administered intravenously and that it comprises VGT-309. Suurs teaches an analogous method for visualizing cancerous tissue wherein the pharmaceutically acceptable salt comprises VGT-309 and is administered intravenously (materials and methods; page 2). Suurs teaches that it is known to administer pharmaceutically acceptable salt either topically or intravenously (introduction; page 2). Suurs also teaches that VGT-309 selectively targets cathepsins, the expression of which is frequently increased in cancerous tissue compared with normal tissue, and is used with a near-infrared ICG fluorophore (introduction and materials and methods; page 2). It would have been obvious to one having ordinary skill in the art to administer the pharmaceutically acceptable salt intravenously, as taught by Suurs as a known method of administration, and to use VGT-309, as it selectively targets cathepsins and is used with a near-infrared ICG fluorophore, thereby enabling viewing cancerous tissue using the near-infrared imaging instrument of Kularatne.
Although Kularatne discloses administering the agent and allows time for it to distribute at an intervention site (par. [0011]) and that the effective amount to be administered to a patient is based on body surface area, patient weight, and physician assessment of patient condition (par. [0081]), it does not specifically disclose wherein the molecular imaging agent is administered to the patient at a dose from 0.1 mg/kg to 0.5 mg/kg. Kim teaches that an imaging agent, comprising indocyanine green (ICG), that that present in VGT-309, is administered to the patient in an amount of 0.1 mg to 0.5 mg per unit body weight (1kg) of the patient (par. [0025]). Kim teaches that if the dosage of the administered fluorescent contrast agent is less than 0.1 mg/kg, it is difficult to clearly distinguish the boundary of cancer (par. [0045]). And, if it is more than 1 mg/kg, the possibility of allergic reactions is increased (par. [0045]). It would have been obvious to one having ordinary skill in the art to administer a dose in an amount of 0.1 mg to 0.5 mg per unit body weight (1kg) of the patient, as taught by Kim, as the effective amount to distinguish the boundary of cancer and prevent allergic reactions, as taught by Kim.
Kularatne does not specifically disclose wherein the molecular imaging agent is administered to the patient between 12 hours and 96 hours prior to the navigating. Zupkofska teaches an analogous method for visualizing cancerous tissue wherein a marking agent is administered to a patient (par. [0087]). Zupkofska teaches that once the marker has been delivered to the patient, the marker may be allowed to permeate into the nodule (par. [0087]). Zupkofska also teaches that in some instances, a time period in the range of 20-30 minutes, in the range of several hours, in the range of a day, in the range of several days, or more may be necessary to allow the marker to permeate into the nodule (par. [0087]). Zupkofska further teaches that the time period may be selected to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue. It would have been obvious to one having ordinary skill in the art to wait between 12 hour and 96 hours (several days or more), as taught by Zupkofska, prior to navigating, in order to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue thereby allowing clear viewing of the cancerous tissue, as taught by Zupkofska.
Regarding claim 19, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 17, wherein the VGT-309 is administered to the patient between 12 hours and 36 hours prior to the navigating (Zupkofska: par. [0087]).
Regarding claim 20, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 17, wherein the VGT-309 is administered to the patient between 72 hours and 96 hours prior to the navigating (Zupkofska: par. [0087]).
Regarding claim 21, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 17, wherein the VGT-309 is administered to the patient at a dose from 0.3 mg/kg to 0.4 mg/kg (Kim: par. [0025]).
Regarding claim 22, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 17, wherein the VGT-309 is administered to the patient
Regarding claim 23, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 17, wherein the VGT-309 is administered to the patient at a dose from 0.16 mg/kg to 0.4 mg/kg (Kim: par. [0025]) between 48 hours and 96 hours prior to the navigating (Zupkofska: par. [0087]).
Regarding claim 25, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 17, wherein the navigating the instrument comprises use of a robotic or robotically-assisted system (par. [0066]).
Regarding claim 26, Kularatne disclose a method comprising: navigating an instrument (bronchoscope; par. [0005], [0011], [0061] and [0063]), via an endoluminal invasive route (par. [0005], [0011], [0063], and [0066]), into a patient to whom a pharmaceutically acceptable salt has been administered (par. [0011] and [0013]), to position the instrument in a target area (par. [0005], [0011] and [0063]); visualizing, via the instrument, tissue in the area under near-infrared (NIR) light (par. [0049] and [0066]), identifying in real time the location of any abnormal or cancerous tissue within
the target area by the florescence of the abnormal or cancerous tissue caused by the pharmaceutically acceptable salt under the NIR light (par. [0063], [0066] and [0078]).
Although Kularatne teaches administering a pharmaceutically acceptable salt (par. [0013]), it does not specifically disclose that it is administered intravenously and that it comprises VGT-309. Suurs teaches an analogous method for visualizing cancerous tissue wherein the pharmaceutically acceptable salt comprises VGT-309 and is administered intravenously (materials and methods; page 2). Suurs teaches that it is known to administer pharmaceutically acceptable salt either topically or intravenously (introduction; page 2). Suurs also teaches that VGT-309 selectively targets cathepsins, the expression of which is frequently increased in cancerous tissue compared with normal tissue, and is used with a near-infrared ICG fluorophore (introduction and materials and methods; page 2). It would have been obvious to one having ordinary skill in the art to administer the pharmaceutically acceptable salt intravenously, as taught by Suurs as a known method of administration, and to use VGT-309, as it selectively targets cathepsins and is used with a near-infrared ICG fluorophore, thereby enabling viewing cancerous tissue using the near-infrared imaging instrument of Kularatne and improving interoperative tumor detection.
Although modified Kularatne discloses administering the agent and allows time for it to distribute at an intervention site (par. [0011]) and that the effective amount to be administered to a patient is based on body surface area, patient weight, and physician assessment of patient condition (par. [0081]), it does not specifically disclose wherein the molecular imaging agent is administered to the patient at a dose from 0.16 mg/kg to 0.32 mg/kg. Kim teaches that an imaging agent, comprising indocyanine green (ICG), that that present in VGT-309, is administered to the patient in an amount of 0.1 mg to 0.5 mg per unit body weight (1kg) of the patient (par. [0025]). Kim teaches that if the dosage of the administered fluorescent contrast agent is less than 0.1 mg/kg, it is difficult to clearly distinguish the boundary of cancer (par. [0045]). And, if it is more than 1 mg/kg, the possibility of allergic reactions is increased (par. [0045]). It would have been obvious to one having ordinary skill in the art to administer a dose in an amount of 0.1 mg to 0.5 mg per unit body weight (1kg) of the patient, as taught by Kim, as the effective amount to distinguish the boundary of cancer and prevent allergic reactions, as taught by Kim.
Modified Kularatne teaches administration of VGT-309 to the patient between 1 hour and 24 hours (see Suurs: page 8, bottom right, additional file 1), it does not specifically disclose wherein the molecular imaging agent is administered to the patient between 25 hours and 96 hours prior to the navigating. Zupkofska teaches an analogous method for visualizing cancerous tissue wherein a marking agent is administered to a patient (par. [0087]). Zupkofska teaches that once the marker has been delivered to the patient, the marker may be allowed to permeate into the nodule (par. [0087]). Zupkofska also teaches that in some instances, a time period in the range of 20-30 minutes, in the range of several hours, in the range of a day, in the range of several days, or more may be necessary to allow the marker to permeate into the nodule (par. [0087]). Zupkofska further teaches that the time period may be selected to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue. It would have been obvious to one having ordinary skill in the art to wait between 25 hours and 96 hours (several days or more), as taught by Zupkofska, prior to navigating, in order to not only allow the marker to permeate into the nodule, but also allow the non-absorbed marker to clear from the healthy tissue thereby allowing clear viewing of the cancerous tissue, as taught by Zupkofska. Thus, the combination of the teaches disclose administering the VGT-309 between 2 hours and 96 hours.
Regarding claim 27, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 26, wherein the VGT-309 is administered to the patient between 12 hours and 96 hours prior to the navigating (Zupkofska: par. [0087]).
Regarding claim 28, Kularatne in view of Suurs in view of Kim in view of Zupkofska disclose the method of claim 26, wherein the instrument comprises a flexible bronchoscope (par. [0061] and [0066]), the navigating comprises guiding the flexible bronchoscope through the patient’s airway (par. [0066]), and the fluorescing abnormal tissue is in the patient’s lungs (par. [0066]-[0067] and [0075]).
Response to Arguments
Applicant’s arguments, see claim amendments and remarks, filed 04/29/2025, with respect to the rejection(s) of the claim(s) under 35 USC 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kim, as discussed above.
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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/RYNAE E BOLER/Examiner, Art Unit 3795
/ANH TUAN T NGUYEN/Supervisory Patent Examiner, Art Unit 3795
08/17/2025
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