FINAL REJECTION
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
On 12/2/2025, Applicant submitted an amendment to the application. The amendment contains a claim set, remarks, and a declaration submitted under 37 CFR 1.130(b). The amendment has been entered and considered for this Office Action.
Response to Arguments
Applicant's arguments filed 12/2/2025 have been fully considered but they are not persuasive.
Applicant argues against the rejection under §102(a)(1) based on the Lyu reference by attempting to invoke the exception under §102(b)(1)(B). In support of this argument, Applicant provides a declaration from a joint inventor.
The examiner notes, to successfully invoke the exception under §102(b)(1)(B), several points must be established. If any of the points are not established, the exception is deficient (i.e., not proper).
The disclosure being excepted (i.e., the Lyu reference in this case) must have been made within the one-year grace period starting from the effective filing date and going one year prior thereto; i.e., the disclosure must be made 1 year or less before the effective filing date of the claimed invention.
The subject matter of the disclosure had, before such disclosure, been publicly disclosed in an inventor-originated disclosure. In other words:
The subject matter of Lyu was separately disclosed in another disclosure.
Said another disclosure was an inventor-originated disclosure; i.e., the subject matter of Lyu was disclosed by the inventor or a joint inventor or another who obtained the subject matter disclosed directly or indirectly from the inventor or a joint inventor.
The inventor-originated disclosure was made before the Lyu reference.
In the discussion below, the examiner focuses on point 2c (i.e., whether the inventor-originated disclosure was made before the Lyu reference). Although Applicant’s attempt to invoke the exception may be deficient for other reasons (e.g., points 1 and/or 2a, especially when more critically assessing the content/subject matter of the provisional application and the inventor-originated disclosure), the examiner is focusing on point 2c because this point appears to be the primary focus of the declaration and Applicant’s overall argument.
In the declaration, joint inventor Piotr Zygmanski (hereinafter “declarant”) states that the “Posted” date of “the Lyu paper” as shown on the Research Square website is March 9, 2021 – not March 8, 2021 (see item 1 of the declaration). The declarant further makes reference to “the Inventors’ Paper”, which has a “Published” date of March 8, 2021 (see item 2 of the declaration). The declarant concludes that the publication time of “the Inventor’s Paper” (March 8, 2021) is before the publication time of “the Lyu Paper” (March 9, 2021) (see item 3 of the declaration).
Based on item 3 of the declaration, the declarant seems to implicitly take the position that word “posted” refers to the publication. This appears to be consistent with a Research Square Knowledge base solution article1 which states: “Manuscripts submitted directly to Research Square receive a range of ethical, biosecurity, and integrity checks and are posted within 24-48 hrs. We will email you when your preprint is posted online and ready to be shared.”
Regarding item 2 of the declaration, the aforementioned “Posted” date of March 9, 2021 on the webpage seems to be in direct conflict with the “Posted” date as shown on the PDF document itself. The copy the Lyu paper supplied by the Applicant shows a “Posted Date” of “March 8th, 2021”. Further, in the information disclosure statement (IDS) dated 5/10/2024, the date Applicant used in the form for the Lyu paper is “March 8, 2021”.
The examiner notes that neither the declarant nor the Applicant provides any reasoning or explanation as to why there are two “Posted” dates (March 8, 2021 and March 9, 2021). Further, neither the declarant nor the Applicant provides any reasoning or explanation resolving which date is correct beyond merely stating that March 9, 2021 is correct; i.e., neither the declarant nor the Applicant explains why the March 9, 2021 should be considered “correct” over the March 8, 2021 date. For example, assuming for argument’s sake the March 9, 2021 date is correct, neither the declarant nor the Applicant provides any reasoning or explanation as to why the IDS and the PDF document itself uses March 8, 2021 instead of March 9, 2021.
Upon further investigation, the Research Square webpage appears to have some sort of programming bug in how the “Posted” date is displayed on the webpage (at least as of the time the examiner is preparing this Office action). The bug appears to be related to how the webpage handles time zones of the device a user is using to view the webpage. The examiner has found out that when the page is viewed in Eastern time, the “Posted” date appears on the page as “08 Mar, 2021” which is consistent with the date that is shown in the document itself. The examiner asked multiple colleagues in Eastern time to open the webpage, and the “Posted” date shows as “08 Mar, 2021”. However, when the page is viewed in Central, Mountain, or Pacific time, for example, the “Posted” date appears on the page as “09 Mar, 2021”. The examiner was able to uncover this bug because the examiner discussed the case with several colleagues across different time zones and we were seeing different dates on our computer screens. The examiner was also able to reproduce this bug by simply changing the time zone settings on his computer.
The examiner notes the PDF document is a static document and therefore does not appear to exhibit this bug.
Given this bug in the webpage, the “Posted” date as shown on the webpage is not considered to be reliable in the examiner’s opinion. The only other place the “Posted” date is listed is on the document itself and the date listed in the IDS (i.e., March 8, 2021). The examiner has no reason to believe the “Posted” date as shown in the PDF document itself and the IDS is unreliable. Therefore, when considering the aforementioned evidence including reliability thereof, the “Posted” date as shown in the PDF document itself and the IDS (i.e., March 8, 2021) is considered to be the publication date of the Lyu paper.
Since “the Inventor’s Paper” and “the Lyu paper” were published on the same day (i.e., March 8, 2021), then the “the Inventor’s Paper” was not published before “the Lyu paper”. Therefore, the exception under §102(b)(1)(B) is deficient. Accordingly, the Lyu paper is still considered prior art.
The attempt to disqualify Lyu as prior art appears to be the only argument. Since Applicant makes no other argument regarding the contents of the prior art relative to the claims (e.g., Applicant makes no argument regarding what Lyu does and doesn’t teach relative to what is being claimed), the rejections over prior art are maintained.
It is noted that in item 4 of the declaration, the declarant states that the claims 1 and 5 find support in “the Inventors’ Paper” but does not point where in the Inventor’s Paper support can be found for each of the limitations. The examiner read through the Inventors’ Paper, however claims 1 and 5 (and dependent claims thereof) do not appear to be fully supported.
Claim Rejections - 35 USC § 102
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.
Claims 1-9, 12, 13, 16, 19, 21, 27, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lyu et al. “Pair production tomography imaging”, Research Square, 2021 (hereinafter, “Lyu”).
Regarding claim 1, Lyu discloses a system for detecting and imaging high Z agents within anatomy of a subject, the system comprising:
a therapeutic medical high energy photon source adapted to provide megavoltage ionizing radiation with an emitted photon energy of no lower than 1.02 MeV (“10 MV bremsstrahlung source”, “incident X-ray of sufficiently high energy (at least 1.022 MeV)” page 3, Fig. 1);
a fast photon counting detector array positioned so that at least two pixels are oriented to simultaneously measure two coincident, 511 keV photons with opposing directions originating from a location (ring detector array, page 3, Fig. 1);
a processor (implied); and
a memory having stored thereon instructions that, when executed by the processor, cause the processor to (implied):
a) initiate delivery of the megavoltage ionizing radiation from the therapeutic medical high energy photon source to the location (page 3);
b) initiate detection of the two coincident photons with opposing directions originating from the location (page 3);
c) determine photon trajectories of the two coincident photons with opposing directions, thereby providing a source location for the two coincident photons where the photon trajectories meet (LOR determination, page 6); and
d) generate a report including a high Z agent position within the anatomy of the subject derived from the trajectories of the two coincident photons with opposing directions within the subject's anatomy, wherein the high Z agent has an atomic number of greater than 7.4 and/or a density that is greater than surrounding tissue within the anatomy (see Fig. 3; trabecular and dense one have effective Z values that are greater than 7.4).
Regarding claim 2, the at least two pixels is a plurality of pixels and pairs of the plurality of pixels are oriented to simultaneously measure two coincident, 511 keV photons with opposing directions originating from a number of locations that corresponds to the number of pairs (page 3; see ring detector in Fig 1).
Regarding claim 3, the report includes multiple high Z agent positions (see Fig. 3).
Regarding claim 4, the instructions, when executed by the processor, further cause the processor to generate an image including the locations and concentrations of the high Z agents within the anatomy of the subject (see Fig. 3).
Regarding claim 5, a method of detecting and imaging high Z agents within anatomy of a subject, the method comprising:
a) delivering megavoltage ionizing radiation from a therapeutic medical high energy photon source (“10 MV bremsstrahlung source”, “incident X-ray of sufficiently high energy (at least 1.022 MeV)” page 3, Fig. 1) to at least one high Z agent located within the anatomy of the subject (page 3);
b) subsequently, detecting two coincident photons with opposing directions originating from the high Z agent with a fast photon counting detector array (ring detector array, page 3, Fig. 1) positioned so that at least two pixels are oriented to simultaneously measure the coincident photons with opposing directions (page 3);
c) determining photon trajectories of the detected two coincident photons, thereby providing a source location for the two coincident photons where the photon trajectories meet (LOR determination, page 6); and
d) generating a report including a high Z agent position within the anatomy of the subject derived from the trajectories of the two coincident photons, wherein the high Z agent has an atomic number of greater than 7.4 and/or a density that is greater than surrounding tissue within the anatomy (see Fig. 3; trabecular and dense one have effective Z values that are greater than 7.4).
Regarding claim 6, the detecting of step b) comprises detecting a plurality of pairs of coincident photons with opposing directions originating from a plurality of high Z agents with the fast photon counting detector array, wherein the determining photon trajectories of step c) comprises determining photon trajectories from the detected plurality of pairs of coincident photons, thereby providing a plurality of source locations for the plurality of pairs of coincident photons where respective source trajectories meet (implied from the sinogram and image reconstruction, page 6).
Regarding claim 7, the report is an image of the anatomy of the subject (see Fig. 5).
Regarding claim 8, the image includes a concentration distribution of the high Z agents (the P2T images in Fig. 5 in a sense represent concentration distribution of high Z agents because high Z agents provide for signal contrast due to pair production).
Regarding claim 9, steps a), b), and c) are repeated at different orientations relative to the anatomy of the subject to produce a 3-dimensional image (implied from 3D map and the detector ring, page 3, because only a tomographic slice would be able to be reconstructed if the steps aren’t repeated for different orientations because LORs would be within the plane of the detector ring; thus, 3D maps implies that the detector ring is moved to different orientations to collect LORs in different planes).
Regarding claim 10, Lyu further discloses the subject is dosed with a radiosensitization/contrast agent (RCA) (see Fig 2).
Regarding claim 12, Lyu further discloses the high Z agent has an atomic number greater than 7.4 (e.g., see Fig. 3 and Table 2).
Regarding claim 13, Lyu further discloses the high Z agent has an atomic number of greater than 53 (e.g., see Fig. 2).
Regarding claim 16, Lyu further discloses the high Z agent is a nanoparticle (implied from high Z nanoparticle imaging, page 8).
Regarding claim 19, Lyu further discloses the high Z agent is present in the tissue in an amount by weight of between 0.10% and 10% (e.g., Ca which has an atomic number of 40 is 4% of trabecular, Table 2).
Regarding claim 21, Lyu further discloses the photons from the therapeutic medical high energy photon source has a beam energy of between 2 MV and 30 MV (10 MV, page 3).
Regarding claim 27, Lyu further discloses the two coincident photons with opposing direction are used to discriminate events that originate from RCA alone and are signatures of concentration of RCA in tissue (see Fig. 2).
Regarding claim 28, Lyu further discloses the fast photon counting detector array discriminates between photons arising from positron annihilation and photons arising from Compton scattering by their temporal, spatio-angular, and spectral distribution (page 3).
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.
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.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Lyu.
Regarding claim 22, Lyu further discloses the coincident photons are from a 10 MV (not 6 MV) beam and are generated with closed multileaf collimators (pages 3 and 14).
However, the ordinarily skilled artisan would have recognized that a 6 MV source would be adequate because a 6 MV source would still produce x-ray photons having an energies of at least 1.022 MeV.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Here, the general conditions of the claim are disclosed in the prior art except for the source voltage being different. However, the ordinarily skilled artisan would have recognized that the claimed voltage would be acceptable. The claim limitation in question therefore amounts to no more than merely a workable range that could have been arrived by routine experimentation (e.g., measuring energies of x-ray photons as a function of x-ray source voltage and comparing to the 1.022 MeV standard for pair production).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Lyu such that the x-ray source voltage is 6 MV because it is not inventive to discover a workable range by routine experimentation.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Lyu in view of Peng et al., “Compton PET: a layered structure PET detector with high performance” 2019 (hereinafter, “Peng”).
Lyu discloses the invention of claim 1 but does not disclose that the fast photon counting detector array comprise a Compton detector. However, this type of detector is known from Peng.
Peng further teaches that “the layered structure allows partial recovery of position information for events that undergo Compton scatter within the detector” (Abstract). The ordinarily skilled artisan would have recognized that use of such a detector would allow for Compton scattering to be useful instead of extraneous because the event can be localized, further increasing overall signal to noise ratio because more of the signal is usable (opposed to just ignoring Compton scattering).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Lyu such that the fast photon counting detector array comprise a Compton detector, as taught by Peng; and the ordinarily skilled artisan would have been motivated to make this modification in order to measure Compton scattering in a localized manner.
Allowable Subject Matter
Claim 26 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Within the context of claim 1, the prior art of record does not teach or reasonably suggest to ordinarily skilled artisan that the two coincident photons with opposing direction are used to discriminate events that originate from the subject's tissue alone and are signatures of RCA dose distribution inside the subject.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to COLIN T. SAKAMOTO whose telephone number is (571)272-4958. The examiner can normally be reached Monday - Friday, ~9AM-5PM Pacific.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, KEITH M. RAYMOND can be reached at (571) 270-1790. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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COLIN T. SAKAMOTO
Primary Examiner
Art Unit 3798
/COLIN T. SAKAMOTO/Primary Examiner, Art Unit 3798
1 “How long will it take for my preprint to be posted?” Research Square Preprints Help Center. https://support.researchsquare.com/support/solutions/articles/6000271860-how-long-will-it-take-for-my-preprint-to-be-posted-