DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
This office action is in response to the remarks filed on 08/12/2025.
The amendment filed 08/12/2025 has been entered. Claims 1, 4, 6-8, 11, 19-20, 24-27, 34, 36-37, 40, and 43-44 remain pending in the application, claims 2-3, 5, 9-10, 12-18, 21-23, 28-33, 35, 38-39, 41-42, and 46-51 have been canceled, and claims 9-20, 24-27, 34, 36-37, 40, and 43-44 have been withdrawn.
The claim objections are withdrawn in light of claim amendments.
The 112(b) rejection is withdrawn in light of claim amendments.
Information Disclosure Statement
The information disclosure statement filed 07/29/2022 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Copies of the non-patent literature documents citation number 4, 13, and 15 on the IDS filed 07/29/2022 have not been provided and have not been considered.
Claim Objections
Claims 1 is objected to because of the following informalities:
Claim 1 recites the acronym “pHLIPs” rather this should recite --“pH low insertion peptide (pHLIPs)--.
Appropriate correction is required.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kircher et al. (WO 2016028749 A1, hereinafter "Kircher") in view of Zheng (US 20140193837 A1) and Dutta (US 10973456 B1) .
Regarding claim 1, Kircher teaches a method of determining the presence or absence of a mass of cancerous cells in vivo within a tissue body of a subject ([0119] discloses targeting cancer), the method comprising:
performing an examination of the tissue body using a non-invasive diagnostic method operable to determine a presence or an absence of a suspect tissue mass within the tissue body, and determining a location of the suspect tissue mass determined to be present within the tissue body ([0150] discloses that imaging modalities including MRI, ultrasound, etc. can be used in combination of Raman reported detection to identify tissue that needs to be resected or ablated, i.e. suspect tissue mass);
administering a solution containing cancer targeting elements (CTEs) conjugated with Raman reporters (RR), said conjugates referred to as "RR-CTEs" ([0119] discloses a Raman nanoparticle/reporter for targeting cancer, and use of Raman reporters for cancer targeting is disclosed in [0006]);
wherein said RR-CTEs are configured to target and bind with cancerous cells within a predetermined period of time (Raman reporters binding to cancer within a predetermined period of time is disclosed in [0119]);
interrogating the tissue body with a coherent beam of light impinging on an exposed skin surface of the tissue body at an impingement position ([0276] discloses subjecting target skin/cells with a laser beam/i.e. coherent beam of light) after said predetermined period of time (Raman reporters binding within a predetermined period of time is disclosed in [0119]), the coherent beam of light configured to interrogate subcutaneous layers body (0029] and [0031] disclose applications regarding application through the skin to reach cancerous cells/i.e. subcutaneous tissue) of the tissue body (optics for directing an excitation light onto a target sample 2630 (e.g., cells, or tissue) [0225]; excitation light source for interrogating an area of a tissue for the presence of the Raman reporter [0228]; detectors and associated components for detecting Raman spectra from cells and/or tissues and implements for treating (e.g., ablating and/or resecting) cells and/or tissues from which Raman spectra are detected [0223]; [0239] discloses the method for operating the device, including treatment/scanning of the sample/tissue)
wherein the RR-CTEs are configured to produce Raman scattered light ([0234] discloses scattering of light by the Raman reporter) with a known Raman signature upon impingement by the coherent beam of light (citation light source at an interrogation power level sufficient to penetrate the tissue to a desired depth for detection of the Raman reporter in that region yet not high enough to cause damage…Other power levels may be employed for the interrogation and may be selected based on, for example, but not limited to, the type and/or density of the tissue, the depth of the intended interrogation, the type of Raman reporter used, and the wavelength/frequency of the outputted excitation light source [0233]);
collecting the Raman scattered light at a surface of the tissue body (a detector for detecting a signal from target [0226]; [0234] discloses scattering of light by the Raman reporter);
processing the collected Raman scattered light to determine a presence or an absence of the known Raman signature, wherein the presence of said Raman scattered light with the known Raman signature produced from the tissue body as a result of said impingement is indicative of the presence of said mass of cancerous cells within the interrogated tissue body, the processing including determining a location of said mass of cancerous cells within the interrogated tissue body determined to be present ([0034]-[0036] disclose that the Raman scatter photons are detected from a given location/tissue, which are then treated [0006] disclose that it is used for precise removal of cancer, [0026] further states that the Raman particles accumulate around cancerous tissue), and wherein the absence of said Raman scattered light with the known Raman signature produced from the tissue body as a result of said impingement is indicative of the absence of said mass of cancerous cells within the tissue body ([0226] discloses detection of a Raman signature; [0239] discloses detection of the Raman light and signature, and [0239] discloses acquiring results from the tissue that was treated/injected with the Raman reporter; [0029] discloses that only cancerous/abnormal tissue is targeted in this process, i.e. absence of said mass of cancerous cells are not targeted); and
comparing the determined location of the suspect tissue mass with the determined location of the mass of cancerous cells to determine the presence of the mass of cancerous cells within the tissue body ([0150] discloses that imaging modalities including MRI, ultrasound, etc. can be used in combination of Raman reported detection to identify tissue that needs to be resected or ablated, i.e. suspect tissue mass; [0295]-[0296] discloses that auxiliary imaging systems can be used to image target tissue, and to guide the Raman system, and both the auxiliary imaging system data can be co-registered/i.e. compared with the image with the detected Raman signals).
Kircher however, does not teach:
wherein the cancer targeting elements are pHLIPs, and the RR-CTE conjugates are referred to as "RR-pHLIPs", and the step of interrogating the tissue body with the coherent beam includes interrogating the tissue body with the coherent beam of light at one or more impingement positions at one or more angles relative to the skin surface and wherein the step of processing the collected Raman scattered light to determine said presence or said absence of the known Raman signature includes creating a multidimensional map identifying spatial locations of the RR-pHLIPs disposed within the tissue body.
Zheng is considered analogous to the instant application as “Luminescent nanoparticle compositions” is disclosed (title).
Zheng teaches
wherein the cancer targeting elements are pHLIPs, and the RR-CTE conjugates are referred to as "RR-pHLIPs", (the nanoparticle further comprises a pH-dependent peptide such as pH low insertion peptide (pHLIP) [0008]; [0021] discloses conjugation of the pHLIP/cancer targeting element);
wherein the step of processing the collected Raman scattered light to determine said presence or said absence of the known Raman signature includes creating a multidimensional map identifying spatial locations of the RR-pHLIPs disposed within the tissue body (To obtain three-dimensional luminescence imaging of live cells, HeLa cells were rinsed with PBS buffer and incubated with GC-AuNPs in PBS at pH 5.3 at 25° C., and then Z stack imaging was performed… Fluorescence microscopy was used to probe the interactions between NPs and live cells and to investigate how the changes in the surface chemistry of the NPs and the local pH environment influence the NP-cell membrane interaction [0049]-[0050]; [0051]-[0053] further discloses locating the cancer targeting elements within the 3D image).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kircher to include wherein the cancer targeting elements are pHLIPs, and the RR-CTE conjugates are referred to as "RR-pHLIPs" abd wherein the step of processing the collected Raman scattered light to determine said presence or said absence of the known Raman signature includes creating a multidimensional map identifying spatial locations of the RR-pHLIPs disposed within the tissue body, as taught by Zheng. Doing so would allow to monitor the surface of cell membranes, as suggested by Zheng ([0034]).
The combined invention still does not teach the step of interrogating the tissue body with the coherent beam includes interrogating the tissue body with the coherent beam of light at one or more impingement positions at one or more angles relative to the skin surface.
Dutta is considered analogous to the instant application as cancer diagnosis is disclosed (abstract).
Dutta teaches the step of interrogating the tissue body with the coherent beam includes interrogating the tissue body with the coherent beam of light at one or more impingement positions at one or more angles relative to the skin surface (The scan spatially covers the skin tissue by emitting broadband light, coherent, or incoherent sources, and then collecting any returning light, Col. 8 lines 37-39; FIG. 9A is emitting multispectral light 908 at arbitrary angles toward the patch of skin, Col. 15 lines 6-8).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Kircher to include the step of interrogating the tissue body with the coherent beam includes interrogating the tissue body with the coherent beam of light at one or more impingement positions at one or more angles relative to the skin surface, as taught by Dutta. Doing so would raise the accuracy of diagnosis and reduce the rate of false positives and false negatives, as suggested by Dutta (Col. 3 lines 13-15).
Regarding claim 4, modified Kircher teaches the method of claim 2, as discussed above. Kircher further teaches wherein the step of collecting the Raman scattered light includes collecting the Raman scattered light at one or more detector positions, each detector position separated from the impingement positions. ([0016] The system includes a detector for detecting scattered photons emanating from the scanning point of the target tissue in which the scattered photons results from illumination with the electromagnetic radiation).
Regarding claim 6, modified Kircher teaches the method of claim 2, as discussed above. Kircher further teaches where the Raman signature produced by the RR- pHLIPs includes at least one spectral peak in a Raman silent region ([0145] Raman peak that both is distinctive of a substance of interest (e.g., a Raman nanoparticle or intrinsic species described herein) and exhibits an acceptable signal-to- noise ratio can be selected. Multiple Raman shift values characteristic of the substance (e.g., Raman nanoparticle or intrinsic species) can be assessed, as can the shape of a Raman spectral region that may include multiple Raman peaks; [0149] further discloses that analysis of Raman nanoparticle frequencies, wavelengths, peaks, etc.; several peaks are interpreted during the data collection process).
Regarding claim 7, modified Kircher teaches the method of claim 2, as discussed above. Kircher further teaches wherein the step of processing the collected Raman scattered light to determine said presence or said absence of the known Raman signature includes using a spectrometer ([0032] a processor (e.g., a Raman spectrometer and associated computer processor and/or software) configured to process data corresponding to the Raman scattered photons detected from the target tissue).
Regarding claim 8, modified Kircher teaches the method of claim 2, as discussed above. Kircher further teaches wherein the step of processing the collected Raman scattered light to determine said presence or said absence of the known Raman signature is performed without a spectrometer or a monochromator, and is performed with a light filter configured to selectively pass the known Raman signature ([0137] Raman scattered photons are filtered using a 785 nm bandpass filter and are spectrally separated using a prism. Raman scattered photons are detected using a detector, e.g., a CCD detector. Detected Raman scattered photons are then analyzed using an analyzer (e.g., a computer with Raman analysis software) to determine if a Raman reporter is present).
Claim 11 rejected under 35 U.S.C. 103 as being unpatentable over Kircher et al. (WO 2016028749 A1, hereinafter "Kircher") in view of Zheng (US 20140193837 A1), Dutta (US 10973456 B1), and Huang et al. (US 20210190774 A1, of record, hereinafter “Huang”).
Regarding claim 11, Kircher teaches the method of claim 1, as discussed above. Kircher, however does not teach wherein the Raman reporters (RR) are bound to plasmonic nanoparticles.
Huang is considered analogous to the instant application as “COMPOSITIONS AND METHODS FOR THE DETECTION AND MOLECULAR PROFILING OF MEMBRANE BOUND VESICLES” is disclosed (title).
Huang teaches wherein the Raman reporters (RR) are bound to plasmonic nanoparticles ([0010] discloses Raman reporters bound to a plasmonic nanoparticle).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kircher to include wherein the Raman reporters (RR) are bound to plasmonic nanoparticle, as taught by Huang. Doing so would facilitate molecular analysis, as suggested by Huang ([0076]).
Response to Arguments
Applicant's arguments filed 08/12/2025 have been fully considered but they are not persuasive.
Regarding the 35 USC 102 rejection of claim 1, applicant argues on pages 9-11 that Kircher does not teach the newly added amendment to claim 1 regarding “wherein the cancer targeting elements are pHLIPs, and the RR-CTE conjugates are referred to as "RR-pHLIPs", and the step of interrogating the tissue body with the coherent beam includes interrogating the tissue body with the coherent beam of light at one or more impingement positions at one or more angles relative to the skin surface and wherein the step of processing the collected Raman scattered light to determine said presence or said absence of the known Raman signature includes creating a multidimensional map identifying spatial locations of the RR-pHLIPs disposed within the tissue body”. These arguments are moot in view of new grounds of rejection which relies upon Zheng (US 20140193837 A1) and Dutta (US 10973456 B1) .
Regarding the 35 USC 103 rejection of the remaining dependent claims, applicant arguments on pages 10-11 are premised upon the assertion that the claims are allowable due to dependance on an allowable claim. The examiner respectfully disagrees for the reasons stated above. Accordingly, the arguments are not persuasive.
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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/N.B./Examiner, Art Unit 3798
/PASCAL M BUI PHO/Supervisory Patent Examiner, Art Unit 3798