DETAILED ACTION
This Office Action is in response to Applicant’s Amendment filed on 06/22/2026.
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 .
Claim Objection
Following claims are objected to because of the following informalities:
Claim 5 “wherein said at least one XRF detector selected from a point-sized detector” needs to be corrected. A suggested correction is -- wherein said at least one XRF detector is selected from a point-sized detector--.
In each of claim 9 and claim 32 “dysprosium (Z=66) holmium (Z=67)” needs to be corrected to -- dysprosium (Z=66), holmium (Z=67)--.
Claim 19 “a simulation system for simulating a radiotherapy X-ray treatment procedure, and thus, to maximize the accuracy of the treatment” needs to be corrected. A suggested correction is -- a simulation system for simulating a radiotherapy X-ray treatment procedure
Claim 28 line 1 “hybrid radiotherapy system of any one of Claim 23” needs to be corrected to -- hybrid radiotherapy system of
Claim 39 “detecting the XRF photons ejecting out of a patient’s body, continuously in real time throughout said radiotherapy X-ray treatment to provide a distribution of said multiple high-Z nanoparticles in an area of interest in said target organ in real time, thus, for verifying in real time that said X-ray beam is focused on said area of interest in said target organ” needs to be corrected. A suggested correction is -- detecting the XRF photons ejecting out of a patient’s body, continuously in real time throughout said radiotherapy X-ray treatment to provide a distribution of said multiple high-Z nanoparticles in an area of interest in said target organ in real timewhich verifies in real time that said X-ray beam is focused on said area of interest in said target organ-- to avoid intended result/functional limitation interpretation (see MPEP 2111.04) which would raise question as to whether the limitation proceeding “thus” is even required or not required.
Claim 37 line 5 “non-healthycells” needs to be corrected to – [[non-healthycells]] non-healthy cells--.
Claim 1 and claim 23 need to be amended as follows to: [a] to avoid intended result/functional limitation interpretation (see MPEP 2111.04) which would raise question as to whether the intended result/functional limitation is even required or not required;[b] to avoid intended result/functional limitation interpretation (see MPEP 2111.04) which would raise question as to whether the limitation proceeding “thus” term is even required or not required;[c] minor typographical errors/informalities; [c] to avoid conditional/contingency limitation recitation which would raise question as to what occurs when the condition/contingency is not met.
PROPOSED AMENDMENT TO CLAIM 1. A radiotherapy system configured for conducting a radiotherapy X-ray treatment on a target organ and for monitoring said radiotherapy X-ray treatment continuously in real time, said radiotherapy system comprising:
(i) an x-ray beam source [[configurable]] configured to deliver an X-ray beam to a target organ,
(ii) at least one converging lens configured for converging said X-ray beam towards the target organ,
(iii) multiple high-Z nanoparticles or at least one high-Z fiducial marker [[attachable]] configured to be attached to said target organ, said multiple high-Z nanoparticles or at least one high-Z fiducial marker absorbing X-ray radiation and emitting X-ray fluorescence (XRF) photons, continuously throughout said radiotherapy X-ray treatment,
(iv) at least one XRF detector configured for detecting said XRF photons ejecting out of a patient’s body continuously in real time throughout said radiotherapy X-ray treatment to provide a distribution of said nanoparticles in an area of interest in said target organ in real time, [[thus,]] for verifying in real time that said X-ray beam is focused on said area of interest in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to emission of said XRF photons,
(v) control means configured for controlling at least one of components (i)-(iv) for controlling said radiotherapy X-ray treatment,
wherein said x-ray beam is focused on said area in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons, and
wherein [[if]] based on said detector detecting a decrease in the emission of said XRF photons, said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons.
PROPOSED AMENDMENT TO CLAIM 23. A hybrid radiotherapy system configured for conducting a radiotherapy X-ray treatment on a target organ for monitoring said radiotherapy X-ray treatment continuously in real time, and for simulating said radiotherapy X-ray treatment to maximize the accuracy of the treatment, said hybrid radiotherapy treatment system comprising:
(a) an x-ray beam source [[configurable]] configured to deliver an X-ray beam to a target organ,
(b) at least one converging lens configured for converging said X-ray beam towards the target organ,
(c) multiple high-Z nanoparticles [[attachable]] configured to be attached to said target organ, said multiple high-Z nanoparticles absorbing X-ray radiation and emitting X-ray fluorescence (XRF) photons continuously throughout said radiographic X-ray treatment,
(d) at least one XRF detector configured for detecting said XRF photons ejecting out of a patient’s body, continuously in real time throughout said radiographic X-ray treatment to provide a distribution of said nanoparticles in an area of interest in said target organ in real time, [[thus,]] for verifying in real time that said X-ray beam is focused on said area having a high density of the multiple high-Z nanoparticles or the at least one high-Z fiducial marker which lead to a desirable emission of said XRF photons,
(e) an x-ray detector configured for detecting said x-ray beam passing through said target organ for simulating said radiotherapy treatment,
(f) control means configured for controlling at least one of components (a)-(e), for controlling said simulation and radiotherapy treatment procedure,
wherein said x-ray beam is focused on said area in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons,
wherein [[if]] based on said detector detecting a decrease in the emission of said XRF photons, said x-ray beam is re-directed in real time to refocus on said section in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons,
wherein said hybrid radiotherapy system switches between a simulation mode and a radiotherapy treatment mode via said at least one converging lens without moving a patient and system components from one position to another, based upon running simulations, said at least one converging lens is manipulated to allow the X-ray beam to pass through said at least one converging lens, and based upon treating a patient, the at least one converging lens is manipulated to converge and focus the beam towards said area of interest in the target organ.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1, 3-39 and 41 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 applicant regards as the invention.
Claim 18 in lines 1-2 recites the limitation "said at least one X-ray detector". There is insufficient antecedent basis for this limitation in the claim.
Claim 23 in line 22 recites the limitation “said simulation and radiotherapy treatment procedure”. There is insufficient antecedent basis for this limitation in the claim.
Claim 24 in line 4 and claim 38 in line 2 each recite “said radiotherapy treatment procedure”. There is insufficient antecedent basis for this limitation in the claim.’
Claim 19 recites “said radiography treatment”. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 in line 2 recites “at least one converging lens” which renders this claim unclear. More specifically, it is unclear as to whether claim 4 lines 2 “at least one converging lens” is the same as, different than or in addition to or one among/subset of “at least one converging lens” recited in claim 1 line 6.
Claim 18 in line 3 recites “a distribution of said … nanoparticles” which renders this claim unclear. More specifically, it is unclear as to whether claim 18 line 3 “a distribution of said … nanoparticles” is the same as, different than or in addition to “a distribution of said nanoparticles” in claim 1 line 16.
Claim 27 in lines 1-2 recites “at least one converging lens” which renders this claim unclear. More specifically, it is unclear as to whether claim 27 lines 1-2 “at least one converging lens” is the same as, different than or in addition to or one among/subset of “at least one converging lens” recited in claim 23 line 7.
Claim 38 in line 3 recites “a distribution of said … nanoparticles” which renders this claim unclear. More specifically, it is unclear as to whether claim 38 line 3 “a distribution of said … nanoparticles” is the same as, different than or in addition to “a distribution of said nanoparticles” in claim 23 line 14-15.
Claim 36 “wherein at least one of said multiple high-Z nanoparticles comprising Hafnium oxide HfO2” needs to be corrected to -- wherein at least one of said multiple high-Z nanoparticles [[comprising]] comprises Hafnium oxide HfO2--.
Claim 39 in line 2 recites “a target organ” which renders this claim unclear. More specifically, it is unclear as to whether claim 39 line 2 “a target organ” is the same as, different than or in addition to “target organ” recited in claim 1 line 2 and if different in what way the two differ.
Claim 41 in line 3 recites “a distribution of said … nanoparticles” which renders this claim unclear. More specifically, it is unclear as to whether claim 18 line 3 “a distribution of said … nanoparticles” is the same as, different than or in addition to “a distribution of said nanoparticles” in claim 1 line 16.
Claim 1 in lines 25-29 and claim 23 in lines 26-30 recite “wherein if said detector detecting a decrease in the emission of said XRF photons, said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons” which renders the respective claim scope unclear. More specifically, due to the “if” term, the limitation i.e. “said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons” is rendered conditional and contingent and recited as occurring only if “said detector detecting a decrease in the emission of said XRF photons” condition or contingency occurs and, thus, “said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons” would NOT occur if said detector does not detect a decrease in the emission of said XRF photons. Here, the conditional “if” phrase causes a clarity issues as to whether the proceeding limitation i.e. “said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons” is required or not required rendering the claim scope unclear. Additionally, please note the “if” term creates at least two points of uncertainty: [a] if said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photonsit occurs only if said detector detects a decrease in the emission of said XRF photons, is unclear as to what occurs if said detector detects an increase or no change in the emission of said XRF photons. Examiner suggest amending “if” to “based on” to cure the noted issues.
Dependent claims 3-22, 24-39 and 41 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 112(b) because the additional recited limitations fail to cure the 35 U.S.C. 112 (b) issue in their respective base claims. Consequently, dependent claims 3-22, 24-39 and 41 are also rejected under 35 U.S.C. 112(b) based in their direct/indirect dependency on their respective base claims.
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 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 of this title, 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.
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 1-2, 3-12, 18-35, 38-39, 41 are rejected under 35 U.S.C. 103 as being unpatentable over Burshtein et al. (Pub. No.: US 20170197096 A1, hereinafter referred to as "Burshtein") in view of Guo et al. (Pub. No.: US 20160252471 A1, hereinafter referred to as “Guo”) as evidenced by Buechel et al. (Pub. Buechel RR, Herzog BA, Husmann L, Burger IA, Pazhenkottil AP, Treyer V, Valenta I, von Schulthess P, Nkoulou R, Wyss CA, Kaufmann PA. Ultrafast nuclear myocardial perfusion imaging on a new gamma camera with semiconductor detector technique: first clinical validation. Eur J Nucl Med Mol Imaging. 2010 Apr;37(4):773-8. doi: 10.1007/s00259-009-1375-7. Epub 2010 Jan 27. Erratum in: Eur J Nucl Med Mol Imaging. 2011 Jun;38(6):1172. PMID: 20107783, hereinafter referred to as “Buechel”).
As per independent Claim 1, Burshtein discloses a radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ and for monitoring said radiotherapy X-ray treatment continuously in real time (Here, limitation following “for conducting” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Burshtein in at least abstract, fig. 1-7, [0002], [0004-0019], [0021], [0023-0055] for example discloses relevant subject-matter. More specifically, Burshtein in at least fig. 2, [0011], [0019], [0023], [0030], [0032] for example discloses radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ and for monitoring said radiotherapy X-ray treatment continuously in real time. See at least Burshtein [0019] “imaging-guided delivery of X-ray radiation by using an X-ray imaging beam to image a target and using the obtained imaging information of the target to control and deliver another X-ray beam onto the desired location of the target… imaging information is used to accurately determine the location, size and other characteristics of a target during, before and after a radiation therapy or radiosurgery session while minimizing the associated complexity, cost and the time involved in acquiring such information”; [0030] “a system 200 that is configured to allow treatment as well as imaging of a target 106”), said radiotherapy system comprising:
(i) an x-ray beam source configurable to deliver an X-ray beam to a target organ (Here, limitation following “configurable to” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Burshtein in at least fig. 2, [0030] for example discloses an x-ray beam source 102 configurable to deliver an X-ray beam to a target organ 106. See at least Burshtein [0030] “system 200 enables imaging of the target 106 prior to, during and/or after treatment of the target 106 by allowing at least a portion of the X-ray radiation from the source 102 to directly reach the target 106”),
(ii) at least one converging lens for converging said X-ray beam towards the target organ (Here, limitation following “for converging” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants (also See MPEP 2111.04). Burshtein in at least fig. 2, [0026], [0031], [0035], [0038] for example discloses said optical means 104(a), 104(b), 104(c), 208, 210 comprising at least one converging lens for converging said X-ray beam to said target organ 106. See at least Burshtein [0031] “lenses 104(a), 104(b) and 104(c) of FIG. 2 can direct, focus and/or spectrally filter the incident X-ray that is delivered to the target 106”; [0035] “A variety of shutter designs for both the imaging and treatment radiation can be used, including designs that are typically used in photographic cameras… the treatment radiation shutter 210 is illustrated as having a hollow central portion 214 to allow the imaging radiation 107 from the source 102 to propagate towards the target 106.”),
(iv) at least one detector for detecting said at least a portion of the imaging radiation (Burshtein in at least fig. 2, [0032] for example discloses detector 212 for detecting said at least a portion of the imaging radiation 107. See at least Burshtein [0032] “a detector 212 that is located, for example, behind the patient and can capture at least a portion of the imaging radiation 107 after the imaging radiation has interacted with the target… detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array. Through the use of at least the imaging radiation shutter 208 and the detector 212, the system 200 of FIG. 2 becomes capable of acquiring images of the target 106 during a treatment session, while the treatment radiation is also being directed to the target 106”),
(v) control means for controlling at least one of components (i)-(iv) for controlling said radiotherapy X-ray treatment (Here, the limitation after “for controlling” is being interpreted as intended use/functional limitation and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04)Burshtein in at least fig. 2, [0038], [0053-0054] for example discloses control means 230 controlling at least one of components for controlling said radiotherapy treatment procedure. See at least Burshtein [0038] “a system control module 230 is provided in the system 200 to control the imaging-guided delivery of the treatment radiation onto the target 106… adjustment can be in the position, spectral contents, intensity, or focusing of the converged treatment radiation on the target 106.”),
Burshtein does not explicitly disclose the nanoparticle based features.
However, in an analogous nanoparticle based radiotherapy treatment and imaging system field of endeavor, Guo discloses a radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ (Guo in at least abstract, fig. 1-2, 5, 9-10, 15-16, 23, [0002], [0011-0015], [0044], [0047-0050], [0052], [0054-0061], [0064-0065], [0072-0075], [0077-0078], [0080-0083], [0089-0090], [0095] for example discloses relevant subject-matter. More specifically, Guo in at least fig. 23, abstract, [0002], [0011], [0054], [0059] for example discloses radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ. See at least Guo [0002] for example discloses See at least Guo [0002] “systems and methods for providing irradiation energy, imaging, and detecting X-ray fluorescence from a volume in a sample”; [0059] “imaging and treatment methods and/or systems … involve delivering X-ray irradiation to a sample”), comprising:
an x-ray beam source configurable to deliver an X-ray beam to a target organ (Guo in at least [0060] for example discloses x-ray beam source configurable to deliver an X-ray beam to a target organ. See at least Guo [0060] “Various X-ray sources and operation parameters … may be used in the methods … Filters in front of the X-ray source(s) may be used to control the X-ray spectrum entering the sample”),
at least one converging means for converging said X-ray beam towards the target organ (Guo in at least [0059], [0075] for example discloses functionally equivalent means for converging said X-ray beam towards the target organ. See at least Guo [0059] “X-ray focusing optics may be used”),
multiple high-Z nanoparticles or at least one high-Z fiducial marker attachable to said target organ (Here, limitation following “attachable” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04)), said multiple high-Z nanoparticles or at least one high-Z fiducial marker absorbing X-ray radiation and emitting X-ray fluorescence (XRF) photons, continuously throughout said radiotherapy X-ray treatment (Guo in at least [0065], [0011]. See at least Guo [0011]” detecting a target using X-ray fluorescence imaging, the method including: a) providing a sample including nanoparticles, where the nanoparticles are configured to be associated with a target, b) irradiating the sample with one or more X-ray beams, where the one or more X-ray beams have a defined cross-section and where nanoparticles in the sample contacted by the one or more X-ray beams reflect X-ray fluorescence, c) scanning a first i-voxel with a detector… where the detector is configured to detect reflected X-ray fluorescence in an i-voxel … determining if the sample includes the target. ”; [0065] “sample of the present disclosure may contain one or more nanoparticles. The nanoparticle may be a metal-based nanoparticle where the nanoparticle is composed, at least in part, of a metal.”),
at least one XRF detector for detecting said XRF photons ejecting out of a patient’s body continuously in real time throughout said radiotherapy X-ray treatment to provide a distribution of said nanoparticles in an area of interest in said target organ in real time, thus, for verifying in real time that said X-ray beam is focused on said area of interest in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to emission of said XRF photons (Here, “for detecting” said XRF photons ejecting out …in real time” is being interpreted as intended use/functional limitation and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). The limitation following “thus” is being interpreted as intended result/functional limitation interpretation (see MPEP 2111.04). Guo in at least fig. 23, [0011], [0048], [0061]. See at least Guo [0011]” the detector is configured to detect reflected X-ray fluorescence in an i-voxel … determining if the sample includes the target. ”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used … X-ray detectors may be an array of single element X-ray detectors … X-ray detectors may be equipped with highly collimated apertures.”),
control means for controlling at least one of components (i)-(iv) for controlling said radiotherapy X-ray treatment (Here, the limitation after “for controlling” is being interpreted as intended use/functional limitation and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Guo in at least [0095], [0160] for example discloses control means for controlling at least one of components for controlling said radiotherapy treatment procedure. See at least Guo [0095] “Imaging the target can be achieved by moving the sample (point by point) with respect the X-ray beam and detectors or vice versa”; [0106] “sample, together with the target inside, is rastered by the XYZ motion stages while the detectors collect the X-ray photons. Each detector is equipped with a multichannel analyzer and the processed signals are sent to a computer.”),
wherein said x-ray beam is focused on said area in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons, and wherein if said detector detecting a decrease in the emission of said XRF photons, said x-ray beam is re-directed in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons (Here, the “if” encompassing limitation is being interpreted as a conditional/contingent limitation and thus, if prior art structure is capable of the performing the recited conditional function if the condition event were to occur, prior art structures would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Guo in at least [0049-0050], [0054-0055]. See at least Guo [0050] “multiple i-voxels are scanned to detect reflected X-ray fluorescence in each of the scanned i-voxels…when the sample is an animal patient suspected of having cancer, scanning multiple i-voxels in the patient and comparing the respective detected reflected X-ray fluorescence from the multiple scanned i-voxels may allow for the detection of a cancerous region in a specific location in the patient.”).
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 radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ and for monitoring said radiotherapy X-ray treatment continuously in real time as taught by Burshtein, by further including nanoparticles, as taught by Guo. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage that since nanoparticles are taken up by the tumor (Guo, [0078]), further including nanoparticles increases the delivery of irradiation energy to a target in a target (Guo, abstract) and/or use of nanoparticles also enhances the absorption of X-rays in a t-voxel and thus, further including nanoparticles facilitates a combined cancer diagnosis and treatment approach (Guo, [0055]).
As per dependent Claim 3, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said at least one XRF detector is movable (Guo in at least [0095] for example discloses XRF detector is movable. Guo [0095] “Imaging the target can be achieved by moving the sample (point by point) with respect the X-ray beam and detectors or vice versa”. Burshtein in at least [0032-0033], [0038] discloses detector is movable. See at least Burshtein [0033] “the detector 212 may be implemented as part of a movable mechanism or platform that allows the detector 212 to move inside and outside of the treatment radiation and/or imaging radiation path…and the like”; [0038] “control module 230 can be in communications with the detector 212 enabling the movement of the detector 212 (if needed)…the X-ray source 102”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 4, the disclosure of combination of Burshtein and Guo as a whole further makes obvious radiotherapy system further comprising at least one converging lens for converging said XRF photons ejecting out of the patient’s body to said at least one XRF detector (Guo in at least discloses [0011], [0059], [0061] for example makes obvious converging lens that can be used as recited. See at least Guo [0059] “imaging and treatment methods and/or systems … involve delivering X-ray irradiation to a sample… X-ray focusing optics may be used to shorten the imaging time and increase the local X-ray dose in the treatment mode”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used in the methods … X-ray detectors may be an array of single element X-ray detectors … X-ray detectors may be equipped with highly collimated apertures.”. Burshtein in at least fig. 2, [0026], [0031], [0035], [0038] for example discloses at least one converging lens 104(a), 104(b), 104(c), 208, 210 for converging said X-ray beam to said target organ 106 to at least one detector 212. See at least Burshtein [0031] “lenses 104(a), 104(b) and 104(c) of FIG. 2 can direct, focus and/or spectrally filter the incident X-ray that is delivered to the target 106”; [0035] “A variety of shutter designs for both the imaging and treatment radiation can be used, including designs that are typically used in photographic cameras. In FIG. 2, the treatment radiation shutter 210 is illustrated as having a hollow central portion 214 to allow the imaging radiation 107 from the source 102 to propagate towards the target 106.”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 5, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said at least one XRF detector selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector (Guo in at least discloses [0011], [0048], [0055], [0061] for example discloses wherein said at least one XRF detector selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector. See Guo “Nanoparticle Assisted Three Dimensional Point Scan X-Ray Fluorescence Imaging”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used … X-ray detectors may be an array of single element X-ray detectors”. Also, Burshtein in at least fig. 2, [0032] discloses detectors selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector. Burshtein [0032] “detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 6, the combination of Burshtein and Guo as a whole further discloses radiotherapy system of Claim 5, wherein said point detector is selected from ion chamber type detectors, scintillation detectors and semi-conductor detectors (Guo in at least discloses [0011], [0055], [0061] for example discloses point detector is selected from ion chamber type detectors, scintillation detectors and semi-conductor detectors. See at least Guo [0061] “Various X-ray detectors and apertures are known in the art… may be used … X-ray detectors may be an array of single element X-ray detectors such as, for example, CZT detectors from Amtek.”).
As per dependent Claim 7, the combination of Burshtein and Guo as evidenced by Buechel as a whole further makes obvious radiotherapy system of Claim 6, wherein said two-dimensional array detector is a gamma camera (This well-known feature i.e. a gamma camera two-dimensional array detector is made obvious by Guo’s disclosure in at least [0061] stating “Various X-ray detectors and apertures are known in the art… may be used … X-ray detectors may be an array of single element X-ray detectors such as, for example, CZT detectors from Amtek. The X-ray detectors may be equipped with highly collimated apertures.” as also evidenced by Buechel abstract, page 774 col. 1 “gamma cameras …with a novel semiconductor cadmium-zinc-telluride (CZT) detector technology… incorporation of CZT detectors into …gamma cameras allow … shortening of scan time … enabled by the increased system sensitivity due to the use of semiconductors”).
As per dependent Claim 8, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said multiple high-Z nanoparticles are selected from metal elements with an atomic number of at least 22 (Guo in at least [0065] “the nanoparticles are composed, at least in part, of a metal, the metal may be, for example, silver (Ag), gold (Au), and/or uranium (U).”).
As per dependent Claim 9, the combination of Burshtein and Guo as a whole further discloses wherein said multiple high-Z nanoparticles are selected from titanium (Z=22), vanadium (Z=23), chromium (Z=24), manganese (Z=25), Iron (Z=26), cobalt (Z=27), Nickel (Z=28), copper (Z=29), zinc (Z=30), gallium (Z=31), germanium (Z=32), arsenic (Z=33), selenium (Z=34), bromine (Z=35), rubidium (Z=37), strontium (Z=38), yttrium (Z=39), zirconium (Z=40), niobium (Z=41), molybdenum (Z=42), technetium (Z=43), ruthenium (Z=44), rhodium (Z=45), palladium (Z=46), silver (Z=47), cadmium (Z=48), indium (Z=49), tin (Z=50), antimony (Z=51), tellurium (Z=52), iodine (Z=53), cesium (Z=55), barium (Z=56), lanthanum (Z=57), cerium (Z=58), praseodymium (Z=59), neodymium (Z=60), promethium (Z=61), samarium (Z=62), europium (Z=63), gadolinium (Z=64), terbium (z=65), dysprosium (Z=66) holmium (Z=67), erbium (Z=68), thulium (Z=69( ytterbium (Z=70), lutetium (Z=71), hafnium (Z=72), tantalum (Z=73), tungsten (Z=74), rhenium (Z=75), osmium (Z=76), iridium (Z=77), platinum (Z=78), gold (Z=79),thallium (Z=81), lead (Z=82), bismuth (Z=83), uranium (Z=92) (Guo in at least [0065] “the nanoparticles are composed, at least in part, of a metal, the metal may be, for example, silver (Ag), gold (Au), and/or uranium (U).”).
As per dependent Claim 10, the combination of Burshtein and Guo as a whole further discloses radiotherapy system of Claim 9, wherein said multiple high-Z nanoparticles are selected from Thulium (Z=69) and Erbium (Z=68) (Z=69) and Erbium (Z=68) (Examiner notes that a broad yet reasonable interpretation of this limitation would encompass the limitation “radiotherapy treatment system comprising …high-Z nanoparticles”. Guo in [0065] discloses use of high-Z nanoparticles. See at least Guo [0065] “sample … may contain one or more nanoparticles… Various nanoparticles are known in the art and may be used in the methods”).
As per dependent Claim 11, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said multiple high-Z nanoparticles comprising at least one non-metal element (Guo in at least [0065] “sample …may contain one or more nanoparticles… Various nanoparticles are known in the art and may be used in the methods…nanoparticles may include silica nanoparticles…other biocompatible nanoparticles such as dendrimers and polymers. Further, nanoparticles may be composed of an organic material, an inorganic material, or a combination of an organic material and an inorganic material.”).
As per dependent Claim 12, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said at least one non-metal element is selected from silicone, carbon, halogens, oxygen, and hydrogen (Guo in at least [0065] “sample …may contain one or more nanoparticles… Various nanoparticles are known in the art and may be used in the methods…nanoparticles may include silica nanoparticles…other biocompatible nanoparticles such as dendrimers and polymers. Further, nanoparticles may be composed of an organic material, an inorganic material, or a combination of an organic material and an inorganic material.”).
As per dependent Claim 18, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said at least one X-ray detector monitors in real-time said radiotherapy treatment which provides a distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment (Guo in at least [0054-0055] for example disclose wherein said at least one X-ray detector monitors in real-time said radiotherapy treatment which provides a distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment. See Guo [0055] “Combination Imaging and Treatment Methods..imaging systems and methods for providing irradiation energy to a sample followed by imaging and detection of X-ray fluorescence from a volume in the sample…provides treatment methods of delivering irradiation energy to a sample… an imaging and treatment method … may also be used in combination”. Burshtein in at least fig. 2, [0032] for example discloses X-ray detector monitoring in real-time said radiotherapy treatment which when extended to Guo’s high-Z nanoparticles in said target organ would generate the resulting functional limitation of providing the distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment as now explicitly, positively and specifically recited by the Applicants. See at least [0032] “a detector 212 that is located, for example, behind the patient and can capture at least a portion of the imaging radiation 107 after the imaging radiation has interacted with the target. Such an interaction can include, but is not limited to, reflection, scattering, transmission, and combinations thereof. The detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array. Through the use of at least the imaging radiation shutter 208 and the detector 212, the system 200 of FIG. 2 becomes capable of acquiring images of the target 106 during a treatment session, while the treatment radiation is also being directed to the target 106.”).
As per dependent Claim 19, the combination of Burshtein and Guo as a whole further discloses radiotherapy system further comprising a simulation system for simulating a radiotherapy X-ray treatment procedure, and thus, to maximize the accuracy of the treatment, said radiotherapy system together with said simulation system forming a hybrid radiotherapy treatment system for conducting a radiotherapy X-ray treatment on a target organ, for monitoring said radiotherapy X-ray treatment continuously in real time for verifying in real time that an X-ray beam is focused on an area of interest, and for simulating said radiography treatment to maximize the accuracy of the treatment (Here, in light of specification as-filed, the term “simulation system” is being interpreted as a imaging system. Guo in at least [0054], [0078] for example discloses recited subject-matter. See at least Guo [0054] “While the imaging methods and the treatment methods of the present disclosure may be used independently”; [0078] “3D imaging of the target in the sample can be obtained by scanning the i-voxel throughout the sample. … i-voxel can be scanned through only parts of the sample, likely those that have nanoparticles taken up by the tumor…regular computed tomography (CT) scan may be used to examine the whole sample, followed by NAXFI of the suspicious regions. No reconstruction is needed for NAXFI because signals from the detectors can be directly used to form images when they are coded with coordinates of the i-voxel.”Burshtein in at least fig. 2, [0035], [0040], [0053] for example discloses simulation/imaging system for simulating/imaging said radiographic treatment procedure to maximize the accuracy of the treatment, said simulation system operates independently of the radiotherapy treatment system. See at least Burshtein [0035] “The treatment radiation shutter 210 and the imaging radiation shutter 208 may be controlled independently from one another to enable simultaneous or time-multiplexed operations of the two shutters”;[0040] “two shutters can be controlled independently from one another to enable simultaneous or time-multiplexed gating and/or modulation of the imaging and treatment radiations”; [0053] “operation of the X-ray treatment/imaging systems that are described in the present application can require synchronous and/or asynchronous control of the treatment and imaging components, including but not limited to control of the X-ray source(s), filters, shutters, imaging detectors, focusing and targeting components, and the like. To this end, specific hardware, software and/or firmware components can be developed to provide the needed timing synchronization and control of the various components of the X-ray systems”).
As per dependent Claim 20, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said simulation system comprising an x-ray source, at least one x-ray detector, and multiple high-Z nanoparticles attachable to said target organ (Guo in at least fig. 1, 5, 15, [0020], [0080-0081], for example discloses simulation system comprising an x-ray source, at least one x-ray detector, and multiple high-Z nanoparticles attachable to said target organ. See Guo at least [0020] “simulated 3D imaging of the targets in the sample”; [0081] “simulation, a beam of X-rays is sent into the sample. The X-ray photons are scattered or absorbed by the sample or the target containing nanoparticles”; Burshtein in at least fig. 2 discloses simulation/imaging system comprising an x-ray source 102, at least one x-ray detector 212. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 21, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said radiotherapy system produces 3D diagnostic images of said target organ to enable precise treatments (Guo in at least [0078] for example discloses wherein said radiotherapy system produces 3D diagnostic images of said target organ to enable precise treatments. See at least Guo [0078] “3D imaging of the target in the sample can be obtained by scanning the i-voxel throughout the sample”. Burshtein in at least [0032] for example discloses said radiotherapy system producing 3D diagnostic images of said target organ. See at least Burshtein [0032] “radiation source 102, the lenses 104(a), 104(b) and 104(c), the shutter 208 and the detector 212 may be rotated around the body (and therefore the target) to irradiate the target 106 from different directions, thus enabling the acquisition of multiple images that can enable reconstruction of, for example, three-dimensional images of the target 106.”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 22, the combination of Burshtein and Guo as a whole further discloses radiotherapy system wherein said simulation system and said radiotherapy treatment system are usable interchangeably during a treatment to maximize the accuracy of the treatment (Here, in light of specification as-filed, the term “simulation system” is being interpreted as a imaging system. Burshtein in at least fig. 2, [0019], [0030], [0035], [0040-0041], [0053] for example discloses said simulation/imaging system and said radiotherapy treatment system are usable interchangeably during a treatment to maximize the accuracy of the treatment. See at least Burshtein [0019] “imaging-guided delivery of X-ray radiation by using an X-ray imaging beam to image a target and using the obtained imaging information of the target to control and deliver another X-ray beam onto the desired location of the target”; [0030] “system 200 enables imaging of the target 106 prior to, during and/or after treatment of the target 106 by allowing at least a portion of the X-ray radiation from the source 102 to directly reach the target 106.”;“[0040] “two shutters can be controlled independently from one another to enable simultaneous or time-multiplexed gating and/or modulation of the imaging and treatment radiations”; [0041] “a single radiation source for both treatment and imaging purposes. … by adding one or more shutters, one or more filters …, an imaging detector and the associated electronic circuitry, an X-ray treatment system can be utilized to also produce accurate data describing the location and the size of a target”; [0053] “operation of the X-ray treatment/imaging systems… can require synchronous and/or asynchronous control of the treatment and imaging components, including but not limited to control of the X-ray source(s), filters, shutters, imaging detectors, focusing and targeting components, and the like. To this end, specific hardware, software and/or firmware components can be developed to provide the needed timing synchronization and control of the various components of the X-ray systems”).
As per independent Claim 23, Burshtein discloses a hybrid radiotherapy system a hybrid radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ for monitoring said radiotherapy X-ray treatment continuously in real time, and for simulating said radiotherapy X-ray treatment to maximize the accuracy of the treatment (Here, limitation following “for conducting” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Burshtein in at least abstract, fig. 1-7, [0002], [0004-0019], [0021], [0023-0055] for example discloses relevant subject-matter. More specifically, Burshtein in at least fig. 2, [0011], [0019], [0023], [0030], [0032] for example discloses hybrid radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ for monitoring said radiotherapy X-ray treatment continuously in real time, and for simulating said radiotherapy X-ray treatment to maximize the accuracy of the treatment. See at least Burshtein [0019] “imaging-guided delivery of X-ray radiation by using an X-ray imaging beam to image a target and using the obtained imaging information of the target to control and deliver another X-ray beam onto the desired location of the target… imaging information is used to accurately determine the location, size and other characteristics of a target during, before and after a radiation therapy or radiosurgery session while minimizing the associated complexity, cost and the time involved in acquiring such information”; [0030] “a system 200 that is configured to allow treatment as well as imaging of a target 106”; [0035] “The treatment radiation shutter 210 and the imaging radiation shutter 208 may be controlled independently from one another to enable simultaneous or time-multiplexed operations of the two shutters”; [0041] “a single radiation source for both treatment and imaging purposes…by adding one or more shutters, one or more filters … an imaging detector and the associated electronic circuitry, an X-ray treatment system can be utilized to also produce accurate data describing the location and the size of a target”; [0053] “operation of the X-ray treatment/imaging systems …can require synchronous and/or asynchronous control of the treatment and imaging components, including but not limited to control of the X-ray source(s), filters, shutters, imaging detectors, focusing and targeting components, and the like. To this end, specific hardware, software and/or firmware components can be developed to provide the needed timing synchronization and control of the various components of the X-ray systems”), said hybrid radiotherapy treatment system comprising:
(a) an x-ray beam source configurable to deliver an X-ray beam to a target organ(Here, limitation following “configurable to” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04).)
(b) at least one converging lens for converging said X-ray beam towards the target organ (Here, limitation following “for converging” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants (also See MPEP 2111.04). Burshtein in at least fig. 2, [0026], [0031], [0035], [0038] for example discloses said optical means 104(a), 104(b), 104(c), 208, 210 comprising at least one converging lens for converging said X-ray beam to said target organ 106. See at least Burshtein [0031] “lenses 104(a), 104(b) and 104(c) of FIG. 2 can direct, focus and/or spectrally filter the incident X-ray that is delivered to the target 106” ;),
at least one detector for detecting said at least a portion of the imaging radiation (Burshtein in at least fig. 2, [0032] for example discloses at least one detector 212 for detecting said at least a portion of the imaging radiation 107. See at least Burshtein [0032] “a detector 212 that is located, for example, behind the patient and can capture at least a portion of the imaging radiation 107 after the imaging radiation has interacted with the target… detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array. Through the use of at least the imaging radiation shutter 208 and the detector 212, the system 200 of FIG. 2 becomes capable of acquiring images of the target 106 during a treatment session, while the treatment radiation is also being directed to the target 106”),
(e) an x-ray detector for detecting said x-ray beam passing through said target organ for simulating said radiotherapy treatment (Here, limitation following “for detecting” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Burshtein in at least fig. 2, [0019], [0032] for example discloses an x-ray detector/the other detector in the detector array for detecting said x-ray beam passing through said target organ for simulating said radiographic treatment. See at least Burshtein [0019] “imaging-guided delivery of X-ray radiation by using an X-ray imaging beam to image a target and using the obtained imaging information of the target to control and deliver another X-ray beam onto the desired location of the target”; [0032] “a detector 212 that is located, for example, behind the patient and can capture at least a portion of the imaging radiation 107 after the imaging radiation has interacted with the target… detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array. Through the use of at least the imaging radiation shutter 208 and the detector 212, the system 200 of FIG. 2 becomes capable of acquiring images of the target 106 during a treatment session, while the treatment radiation is also being directed to the target 106”),
(f) control means for controlling at least one of components (a)-(e), for controlling said simulation and radiotherapy treatment procedure (Here, the limitation after “for controlling” is being interpreted as intended use/functional limitation and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Burshtein in at least fig. 2, [0038], [0053-0054] for example discloses control means 230 for controlling at least one of components for controlling said simulation and radiotherapy treatment procedures. See at least Burshtein [0038] “a system control module 230 is provided in the system 200 to control the imaging-guided delivery of the treatment radiation onto the target 106… adjustment can be in the position, spectral contents, intensity, or focusing of the converged treatment radiation on the target 106.”),
wherein said hybrid radiotherapy system switches between a simulation mode and a radiotherapy treatment mode via said at least one converging lens without moving a patient and system components from one position to another, based upon running simulations, said at least one converging lens is manipulated to allow the X-ray beam to pass through said at least one converging lens, and based upon treating a patient, the at least one converging lens is manipulated to converge and focus the beam towards said area of interest in the target organ (Burshtein in at least fig. 2, [0019], [0030], [0032-0033], [0035], [0040], [0053]. See at least Burshtein [0019] “imaging-guided delivery of X-ray radiation by using an X-ray imaging beam to image a target and using the obtained imaging information of the target to control and deliver another X-ray beam onto the desired location of the target”; [0030] “system 200 enables imaging of the target 106 prior to, during and/or after treatment of the target 106 by allowing at least a portion of the X-ray radiation from the source 102 to directly reach the target 106.”;[0040] “two shutters can be controlled independently from one another to enable simultaneous or time-multiplexed gating and/or modulation of the imaging and treatment radiations”; [0041] “a single radiation source for both treatment and imaging purposes…by adding one or more shutters, one or more filters …an imaging detector and the associated electronic circuitry, an X-ray treatment system can be utilized to also produce accurate data describing the location and the size of a target”; [0053] “operation of the X-ray treatment/imaging systems… can require synchronous and/or asynchronous control of the treatment and imaging components, including but not limited to control of the X-ray source(s), filters, shutters, imaging detectors, focusing and targeting components, and the like. To this end, specific hardware, software and/or firmware components can be developed to provide the needed timing synchronization and control of the various components of the X-ray systems”)
Burshtein does not explicitly disclose the nanoparticle based features.
However, in an analogous nanoparticle based radiotherapy treatment and imaging system field of endeavor, Guo discloses a hybrid radiotherapy treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ and for simulating said radiography treatment to maximize the accuracy of the treatment (Here, in light of specification as-filed, the term “simulating” and “simulation system” is being interpreted as a imaging and imaging system. Guo in at least abstract, fig. 1-2, 5, 9-10, 15-16, 23, [0002], [0011-0015], [0044], [0047-0050], [0052], [0054-0061], [0064-0065], [0072-0075], [0077-0078], [0080-0083], [0089-0090], [0095] for example discloses relevant subject-matter. More specifically, Guo in at least fig. 23, abstract, [0002], [0011], [0054], [0059] for example discloses hybrid radiotherapy treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ and for simulating said radiography treatment to maximize the accuracy of the treatment. See at least Guo [0002] “systems and methods for providing irradiation energy, imaging, and detecting X-ray fluorescence from a volume in a sample”; [0059] “imaging and treatment methods and/or systems … involve delivering X-ray irradiation to a sample”), said hybrid radiotherapy treatment system comprising:
an x-ray beam source configurable to deliver an X-ray beam to a target organ (Guo in at least [0060] for example discloses x-ray beam source configurable to deliver an X-ray beam to a target organ. See at least Guo [0060] “Various X-ray sources and operation parameters … may be used in the methods … Filters in front of the X-ray source(s) may be used to control the X-ray spectrum entering the sample”),
at least one converging means for converging said X-ray beam towards the target organ (Guo in at least [0059], [0075] for example discloses functionally equivalent means for converging said X-ray beam towards the target organ. See at least Guo [0059] “X-ray focusing optics may be used”),
multiple high-Z nanoparticles attachable to said target organ (Here, limitation following “attachable” is being interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04)), said multiple high-Z nanoparticles absorbing X-ray radiation and emitting X-ray fluorescence (XRF) photons continuously throughout said radiographic X-ray treatment (Guo in at least [0065], [0011]. See at least Guo [0011]” detecting a target using X-ray fluorescence imaging, the method including: a) providing a sample including nanoparticles, where the nanoparticles are configured to be associated with a target, b) irradiating the sample with one or more X-ray beams, where the one or more X-ray beams have a defined cross-section and where nanoparticles in the sample contacted by the one or more X-ray beams reflect X-ray fluorescence, c) scanning a first i-voxel with a detector… where the detector is configured to detect reflected X-ray fluorescence in an i-voxel … determining if the sample includes the target. ”; [0065] “sample of the present disclosure may contain one or more nanoparticles. The nanoparticle may be a metal-based nanoparticle where the nanoparticle is composed, at least in part, of a metal.”),
at least one XRF detector for detecting said XRF photons ejecting out of a patient’s body, continuously in real time throughout said radiographic X-ray treatment to provide a distribution of said nanoparticles in an area of interest in said target organ in real time, thus, for verifying in real time that said X-ray beam is focused on said area having a high density of the multiple high-Z nanoparticles or the at least one high-Z fiducial marker which lead to a desirable emission of said XRF photons(Here, limitation after “for detecting” is being interpreted as intended use/functional limitation and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). The limitation of “thus” is being interpreted as intended result/functional limitation interpretation (see MPEP 2111.04). Guo in at least fig. 23, [0011], [0048], [0061] . See at least Guo [0011]” the detector is configured to detect reflected X-ray fluorescence in an i-voxel … determining if the sample includes the target. ”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used … X-ray detectors may be an array of single element X-ray detectors … X-ray detectors may be equipped with highly collimated apertures.”),
wherein said x-ray beam is focused on said area in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons, wherein if said detector detecting a decrease in the emission of said XRF photons, said x-ray beam is re-directed in real time to refocus on said section in said target organ where a concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons (Here, the “if” encompassing limitation is being interpreted as a conditional/contingent limitation and thus, if prior art structure is capable of the performing the recited conditional function if the condition event were to occur, prior art structures would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). (Guo in at least [0049-0050], [0054-0055]. See at least Guo [0050] “multiple i-voxels are scanned to detect reflected X-ray fluorescence in each of the scanned i-voxels…when the sample is an animal patient suspected of having cancer, scanning multiple i-voxels in the patient and comparing the respective detected reflected X-ray fluorescence from the multiple scanned i-voxels may allow for the detection of a cancerous region in a specific location in the patient.”)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify hybrid radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ for monitoring said radiotherapy X-ray treatment continuously in real time, and for simulating said radiotherapy X-ray treatment to maximize the accuracy of the treatment as taught by Burshtein, by further including nanoparticles, as taught by Guo. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage that since nanoparticles are taken up by the tumor (Guo, [0078]), further including nanoparticles increases the delivery of irradiation energy to a target in a target (Guo, abstract) and/or use of nanoparticles also enhances the absorption of X-rays in a t-voxel and thus, further including nanoparticles facilitates a combined cancer diagnosis and treatment approach (Guo, [0055]).
As per dependent Claim 24, the combination of Burshtein and Guo as a whole further discloses wherein said at least one converging lens (Burshtein in at least fig. 2, [0031-0032], [0035] for example discloses optical means 104a, 104b, 104c, 208, 210 comprising at least one lens. See at least Burshtein [0031] “lenses 104(a), 104(b) and 104(c) of FIG. 2 can direct, focus and/or spectrally filter the incident X-ray that is delivered to the target 106”), comprising an openable aperture, said openable aperture is maintained closed for converging said X-ray beam to said target organ during said radiotherapy treatment procedure, said aperture is maintained open to allow said beam to pass through said aperture for simulating said radiographic treatment (Burshtein in at least fig. 2, [0026], [0031-0032], [0035] for example disclose comprising an openable aperture, said openable aperture is maintained closed for converging said X-ray beam to said target organ during said radiotherapy treatment procedure, said aperture is maintained open to allow said beam to pass through said aperture for simulating said radiographic treatment. See at least Burshtein [0031] “imaging radiation shutter 208, when closed, operates similar to the stop 108 …in one mode of operation, the imaging radiation shutter 208 can block…the X-ray radiation in the direct path from the source 102 to the target 106.”; [0032] “When the imaging radiation shutter 208 is at least partially open, all or a portion of the X-ray radiation 107 from that is incident upon the imaging radiation shutter 208 can reach the target 106. FIG. 2 also illustrates a detector 212 that is located, for example, behind the patient and can capture at least a portion of the imaging radiation 107 after the imaging radiation has interacted with the target. Such an interaction can include, but is not limited to, reflection, scattering, transmission, and combinations thereof. The detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array.”; [0035] “a treatment radiation shutter 210 may be placed in the path between the X-ray source 102 and the lenses 104(a), 104(b) and 104(c) so as to block … the radiation that would normally reach the lenses 104(a), 104(b) and 104(c). A variety of shutter designs for both the imaging and treatment radiation can be used, including designs that are typically used in photographic cameras. In FIG. 2, the treatment radiation shutter 210 is illustrated as having a hollow central portion 214 to allow the imaging radiation 107 from the source 102 to propagate towards the target 106. The treatment radiation shutter 210 and the imaging radiation shutter 208 may be controlled independently from one another to enable simultaneous or time-multiplexed operations of the two shutters.”).
As per dependent Claim 25, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system of Claim 23, wherein said hybrid radiotherapy system produces 3D diagnostic images of said target organ enabling precise treatments (Guo in at least [0054-0055], [0078] for example discloses hybrid radiotherapy system wherein said hybrid radiotherapy system produces 3D diagnostic images of said target organ enabling precise treatments. Guo in at least [0054] “imaging and treatment method of the present disclosure may also be used in combination”; [0078] “3D imaging of the target in the sample can be obtained by scanning the i-voxel throughout the sample”. Burshtein in at least [0032] for example discloses said hybrid radiotherapy system producing 3D diagnostic images of said target organ. See at least Burshtein [0032] “radiation source 102, the lenses 104(a), 104(b) and 104(c), the shutter 208 and the detector 212 may be rotated around the body (and therefore the target) to irradiate the target 106 from different directions, thus enabling the acquisition of multiple images that can enable reconstruction of, for example, three-dimensional images of the target 106.”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 26, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system of Claim 23, wherein said at least one XRF detector is movable (Guo in at least [0054-0055], [0095] for example discloses XRF detector is movable. Guo [0095] “Imaging the target can be achieved by moving the sample (point by point) with respect the X-ray beam and detectors or vice versa”.Burshtein in at least [0032-0033], [0038] discloses detector is movable. See at least Burshtein [0033] “the detector 212 may be implemented as part of a movable mechanism or platform that allows the detector 212 to move inside and outside of the treatment radiation and/or imaging radiation path…and the like”; [0038] “control module 230 can be in communications with the detector 212 enabling the movement of the detector 212 (if needed)…the X-ray source 102”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 27, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system further comprising at least one converging lens for converging said XRF photons ejecting out of the patient’s body to said at least one XRF detector (Guo discloses [0011], [0054], [0059], [0061] for example makes obvious at least one converging lens for converging said XRF photons ejecting out of the patient's body to said at least one XRF detector. See at least Guo [0059] “imaging and treatment methods and/or systems … involve delivering X-ray irradiation to a sample… X-ray focusing optics may be used to shorten the imaging time and increase the local X-ray dose in the treatment mode”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used in the methods of the present disclosure. The X-ray detectors may be an array of single element X-ray detectors … X-ray detectors may be equipped with highly collimated apertures.”Burshtein in at least fig. 2, [0026], [0031], [0035], [0038] for example discloses at least one converging lens 104(a), 104(b), 104(c), 208, 210 for converging said X-ray beam to said target organ 106 to at least one detector 212. See at least Burshtein [0031] “lenses 104(a), 104(b) and 104(c) of FIG. 2 can direct, focus and/or spectrally filter the incident X-ray that is delivered to the target 106”; [0035] “A variety of shutter designs for both the imaging and treatment radiation can be used, including designs that are typically used in photographic cameras. In FIG. 2, the treatment radiation shutter 210 is illustrated as having a hollow central portion 214 to allow the imaging radiation 107 from the source 102 to propagate towards the target 106.”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants.).
As per dependent Claim 28, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system wherein said at least one XRF detector is selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector (Guo in at least discloses [0011], [0048], [0054-0055], [0061] for example discloses wherein said at least one XRF detector is selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector. See Guo “Nanoparticle Assisted Three Dimensional Point Scan X-Ray Fluorescence Imaging”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used … X-ray detectors may be an array of single element X-ray detectors”.Also Burshtein in at least fig. 2, [0032] discloses detector selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector. Burshtein [0032] “detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array”. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants).
As per dependent Claim 29, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system wherein said point-sized detector is selected from ion chamber type detectors, scintillation detectors and semi-conductor detectors (Guo in at least discloses [0011], [0055], [0061] for example discloses point detector is selected from ion chamber type detectors, scintillation detectors and semi-conductor detectors. See at least Guo [0061] “Various X-ray detectors and apertures are known in the art… may be used … X-ray detectors may be an array of single element X-ray detectors such as, for example, CZT detectors from Amtek.”).
As per dependent Claim 30, the combination of Burshtein and Guo as evidenced by Buechel as a whole further discloses hybrid radiotherapy system wherein said two-dimensional array detector is a gamma camera(This well-known feature i.e. a gamma camera two-dimensional array detector is made obvious by Guo’s disclosure in at least [0061] stating “Various X-ray detectors and apertures are known in the art… may be used … X-ray detectors may be an array of single element X-ray detectors such as, for example, CZT detectors from Amtek. The X-ray detectors may be equipped with highly collimated apertures.” as also evidenced by Buechel abstract, page 774 col. 1 “gamma cameras …with a novel semiconductor cadmium-zinc-telluride (CZT) detector technology… incorporation of CZT detectors into …gamma cameras allow … shortening of scan time … enabled by the increased system sensitivity due to the use of semiconductors”).
As per dependent Claim 31, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system wherein said multiple high-Z nanoparticles are selected from metal elements with an atomic number of at least 22 (Guo in at least [0065] “the nanoparticles are composed, at least in part, of a metal, the metal may be, for example, silver (Ag), gold (Au), and/or uranium (U).”).
As per dependent Claim 32, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system wherein said multiple high-Z nanoparticles are selected from titanium (Z=22), vanadium (Z=23), chromium (Z=24), manganese (Z=25), Iron (Z=26), cobalt (Z=27), Nickel (Z=28), copper (Z=29), zinc (Z=30), gallium (Z=31), germanium (Z=32), arsenic (Z=33), selenium (Z=34), bromine (Z=35), rubidium (Z=37), strontium (Z=38), yttrium (Z=39), zirconium (Z=40), niobium (Z=41), molybdenum (Z=42), technetium (Z=43), ruthenium (Z=44), rhodium (Z=45), palladium (Z=46), silver (Z=47), cadmium (Z=48), indium (Z=49), tin (Z=50), antimony (Z=51), tellurium (Z=52), iodine (Z=53), cesium (Z=55), barium (Z=56), lanthanum (Z=57), cerium (Z=58), praseodymium (Z=59), neodymium (Z=60), promethium (Z=61), samarium (Z=62), europium (Z=63), gadolinium (Z=64), terbium (z=65), dysprosium (Z=66) holmium (Z=67), erbium (Z=68), thulium (Z=69( ytterbium (Z=70), lutetium (Z=71), hafnium (Z=72), tantalum (Z=73), tungsten (Z=74), rhenium (Z=75), osmium (Z=76), iridium (Z=77), platinum (Z=78), gold (Z=79),thallium (Z=81), lead (Z=82), bismuth (Z=83), uranium (Z=92) (Guo in at least [0065] “the nanoparticles are composed, at least in part, of a metal, the metal may be, for example, silver (Ag), gold (Au), and/or uranium (U).”).
As per dependent Claim 33, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy treatment system wherein said multiple high-Z nanoparticles are selected from Thulium (Z=69) and Erbium (Z=68) (Examiner notes that a broad yet reasonable interpretation of this limitation would encompass the limitation “radiotherapy treatment system comprising …high-Z nanoparticles”. Guo in [0065] discloses use of high-Z nanoparticles. See at least Guo [0065] “sample … may contain one or more nanoparticles… Various nanoparticles are known in the art and may be used in the methods”)
As per dependent Claim 34, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system of any one of Claims 23, wherein said multiple high-Z nanoparticles comprises at least one non-metal element (Guo in at least [0065] “sample …may contain one or more nanoparticles… Various nanoparticles are known in the art and may be used in the methods…nanoparticles may include silica nanoparticles…other biocompatible nanoparticles such as dendrimers and polymers. Further, nanoparticles may be composed of an organic material, an inorganic material, or a combination of an organic material and an inorganic material.”).
As per dependent Claim 35, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system wherein said at least one non-metal element is selected from silicone, halogens, oxygen, and hydrogen (Guo in at least [0065] “sample …may contain one or more nanoparticles… Various nanoparticles are known in the art and may be used in the methods…nanoparticles may include silica nanoparticles…other biocompatible nanoparticles such as dendrimers and polymers. Further, nanoparticles may be composed of an organic material, an inorganic material, or a combination of an organic material and an inorganic material.”).
As per dependent Claim 38, the combination of Burshtein and Guo as a whole further discloses hybrid radiotherapy system, wherein said at least one X-ray detector monitors in real-time said radiotherapy treatment procedure which provides a distribution of said multiple high-Z nanoparticles in said target organ continuously throughout a radiotherapy treatment (Guo in at least [0054-0055] for example disclose said at least one X-ray detector monitoring in real-time said radiotherapy treatment, thus, providing the distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment. See Guo [0055] “Combination Imaging and Treatment Methods..imaging systems and methods for providing irradiation energy to a sample followed by imaging and detection of X-ray fluorescence from a volume in the sample…provides treatment methods of delivering irradiation energy to a sample… an imaging and treatment method … may also be used in combination”. Burshtein in at least fig. 2, [0032] for example discloses X-ray detector monitoring in real-time said radiotherapy treatment which when extended to Guo’s high-Z nanoparticles in said target organ would generate the resulting functional limitation of providing the distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment as now explicitly, positively and specifically recited by the Applicants. See at least [0032] “a detector 212 that is located, for example, behind the patient and can capture at least a portion of the imaging radiation 107 after the imaging radiation has interacted with the target. Such an interaction can include, but is not limited to, reflection, scattering, transmission, and combinations thereof. The detector 212 can include a single detector or a plurality of detector elements that are, for example, arranged to form a detector array. Through the use of at least the imaging radiation shutter 208 and the detector 212, the system 200 of FIG. 2 becomes capable of acquiring images of the target 106 during a treatment session, while the treatment radiation is also being directed to the target 106.”).
As per dependent Claim 39, the combination of Burshtein and Guo as a whole further discloses radiotherapy method for conducting a radiotherapy X-ray imaging treatment on a target organ and for monitoring said radiotherapy X-ray continuously in real time (Burshtein in at least [0019], [0030], [0032], [0053] and Guo in at least abstract, [0002], [0011], [0054], [0059] for example discloses radiotherapy treatment method for conducting a radiographic X-ray imaging on a target organ in real time during a radiation treatment procedure. see at least Burshtein [0032]“the system 200 of FIG. 2 becomes capable of acquiring images of the target 106 during a treatment session, while the treatment radiation is also being directed to the target 106.”; [0053] “operation of the X-ray treatment/imaging systems …can require synchronous … control of the treatment and imaging components, including but not limited to control of the X-ray source(s), filters, shutters, imaging detectors, focusing and targeting components, and the like. To this end, specific hardware, software and/or firmware components can be developed to provide the needed timing synchronization and control of the various components of the X-ray systems”; Guo [0002] “systems and methods for providing irradiation energy, imaging, and detecting X-ray fluorescence from a volume in a sample”; [0059] “imaging and treatment methods and/or systems of the present disclosure involve delivering X-ray irradiation to a sample”) comprising: providing the radiotherapy treatment system of claim 1 (see claim 1);
administrating multiple high-Z nanoparticles or the at least one high-Z fiducial marker to the target organ in the patient’s body; said multiple high-Z nanoparticles are attachable to said target organ, said multiple high-Z nanoparticles absorbing X-ray radiation and emitting X-ray fluorescence (XRF) photons, continuously throughout said radiotherapy X-ray treatment (Guo in at least [0011], [0065]. see at least Guo “providing a sample including nanoparticles, where the nanoparticles are configured to be associated with a target”);
delivering radiation via the X-ray beam to the target organ (Guo in at least [0011] “irradiating the sample with one or more X-ray beams, … where nanoparticles in the sample contacted by the one or more X-ray beams reflect X-ray fluorescence”. Burshtein in at least fig. 2, [0030] “system 200 enables imaging of the target 106 prior to, during and/or after treatment of the target 106 by allowing at least a portion of the X-ray radiation from the source 102 to directly reach the target 106”);
emitting the XRF photons from the multiple high-Z nanoparticles or the at least one high-Z fiducial marker (Guo in at least [0011], [0048], [0061] . See at least Guo [0011]” the detector is configured to detect reflected X-ray fluorescence in an i-voxel … determining if the sample includes the target. ”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used … X-ray detectors may be an array of single element X-ray detectors … X-ray detectors may be equipped with highly collimated apertures.” );
detecting the XRF photons ejecting out of a patient’s body, continuously in real time throughout said radiotherapy X-ray treatment to provide a distribution of said multiple high-Z nanoparticles in an area of interest in said target organ in real time, thus, for verifying in real time that said X-ray beam is focused on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons (The limitation following “thus” is being interpreted as intended result/functional limitation interpretation (see MPEP 2111.04). Guo in at least fig. 23, [0011], [0048], [0061] . See at least Guo [0011]” the detector is configured to detect reflected X-ray fluorescence in an i-voxel … determining if the sample includes the target. ”; [0061] “Various X-ray detectors and apertures are known in the art…and may be used … X-ray detectors may be an array of single element X-ray detectors … X-ray detectors may be equipped with highly collimated apertures.”); and
re-directing said X-ray beam’s focal point in real time to refocus on said area of interest in said target organ where the concentration of said multiple high-Z nanoparticles or the at least one high-Z fiducial marker lead to a desirable emission of said XRF photons (Guo in at least fig. 1-2, 10, 15-16, [0011], [0029], [0049-0050], [0054-0055], [0059], [0075] and Burshtein in at least fig. 2, [0026], [0031-0032], [0035]. See at least Guo [0011] “c) scanning a first i-voxel with a detector, where a path of detection is formed from the irradiated sample to the detector…d) scanning a second i-voxel adjacent to the first i-voxel with the detector”; [0029] “focusing configuration…continuous scanning configuration”; [0050] “multiple i-voxels are scanned to detect reflected X-ray fluorescence in each of the scanned i-voxels. For example, a first i-voxel may be scanned to detect the reflected X-ray fluorescence from this first i-voxel, and then a second i-voxel adjacent to the first i-voxel or otherwise located elsewhere in the sample at a location different from the first i-voxel may be scanned to detect the reflected X-ray fluorescence from this second i-voxel”; [0059] “X-ray focusing optics may be used”;).
As per dependent Claim 41, the combination of Burshtein and Guo as a whole further discloses method further comprising simulating said radiotherapy X-ray imaging treatment for obtaining a distribution of said multiple high-Z nanoparticles to maximize the accuracy of the treatment (Guo in at least fig. 5, [0011], [0054], [0078] for example discloses simulating/imaging said radiotherapy X-ray imaging treatment for obtaining a distribution of said multiple high-Z nanoparticles to maximize the accuracy of the treatment. See Guo [0011] “irradiating the sample with one or more X-ray beams…. where nanoparticles in the sample contacted by the one or more X-ray beams reflect X-ray fluorescence, c) scanning a first i-voxel with a detector…scanning a second i-voxel adjacent to the first i-voxel with the detector, e) comparing the detection of reflected X-ray fluorescence in the first i-voxel to the detection of reflected X-ray fluorescence in the second i-voxel, and, f) determining if the sample includes the target.”; [0078] “3D imaging of the target in the sample can be obtained by scanning the i-voxel throughout the sample. … i-voxel can be scanned through only parts of the sample, likely those that have nanoparticles taken up by the tumor…regular computed tomography (CT) scan may be used to examine the whole sample, followed by NAXFI of the suspicious regions. No reconstruction is needed for NAXFI because signals from the detectors can be directly used to form images when they are coded with coordinates of the i-voxel.”).
Claims 13 is rejected under 35 U.S.C. 103 as being unpatentable over Burshtein in view of Guo as evidenced by Buechel and further in view of Lin et al. (Pub. No.: US 20170231903 A1, hereinafter referred to as “Lin”).
As per dependent Claim 13, the combination of Burshtein and Guo as evidenced by Buechel a whole discloses radiotherapy system of claim 1 (see claim 1).
The combination of Burshtein and Guo as evidenced by Buechel a whole does not explicitly discloses or necessarily require wherein said multiple high-Z nanoparticles having a form of nanoscale metal-organic frameworks (nMOFs).
However, in an analogous nanoparticle based radiotherapy field of endeavor, Lin discloses radiotherapy system (Lin in at least abstract, [0003], [0063], [0133], [0195] for example discloses radiotherapy system. See at least Lin [0003] “a nanocarrier platform based on metal-organic frameworks (MOF) materials (including nanoscale metal-organic frameworks (NMOFs)), for photodynamic therapy (PDT), X-ray induced photodynamic therapy (X-PDT), radiotherapy (RT), chemotherapy, immunotherapy, or any combination thereof”) wherein said multiple high-Z nanoparticles having a form of nanoscale metal-organic frameworks (nMOFs) (Lin in at least abstract, [0133] for example discloses high-Z nanoparticles having a form of nanoscale metal-organic frameworks (nMOFs). See at least Lin [0133] “metal-organic frameworks (MOFs) … MOFs can also include moieties capable of absorbing X-rays …MOF can comprise inorganic nanoparticles in the cavities or channels of the MOF or can be used in combination with an inorganic nanoparticle… methods of using MOFs and/or inorganic nanoparticles … in X-ray induced photodynamic therapy”).
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 high-Z nanoparticles used in a radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ and for monitoring said radiotherapy X-ray treatment continuously in real timeof Burshtein, as modified with Guo, such that the high-Z nanoparticles have a form of nanoscale metal-organic frameworks as disclosed in Lin. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, in order to take advantage of the long penetration depth of X-ray and low optical auto-fluorescence background that provides a highly sensitive molecular imaging technique. (Lin, [0195]) and/or to provide delivery vehicles for improving the delivery (e.g., the targeted delivery) of tumor-localizing photosensitizer (PS) therapeutics that can deliver tumor-localizing photosensitizers (PS) in combination with other therapeutics such as immunotherapy agents in order to increase treatment efficacy (Lin, [0063]).
Claims 14 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Burshtein in view of Guo as evidenced by Buechel and further in view of Stock et al. (Pub. No.: US 20200276230 A1, hereinafter referred to as “Stock”).
As per dependent Claim 14, the combination of Burshtein and Guo as evidenced by Buechel a whole discloses radiotherapy system of claim 1(see claim 1)
The combination of Burshtein and Guo as evidenced by Buechel a whole does not explicitly disclose Hafnium oxide feature.
However, in an analogous nanoparticle based radiotherapy field of endeavor, Stock discloses radiotherapy system (Stock in at least abstract, [0001] for example discloses radiotherapy treatment system. See at least Stock [0001] “use of the particle or pharmaceutical composition in the treatment of cancer in combination with radiotherapy”) wherein at least one of said multiple high-Z nanoparticles comprises Hafnium oxide (HfO2) (Stock in abstract, [0017] discloses wherein at least one of said multiple high-Z nanoparticles comprises Hafnium oxide (HfO2). See Stock [0017] “use of high molecular weight …metal oxide, principally hafhium oxide, nanoparticles as radiotherapy enhancers in a similar way to gold.”).
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 high-Z nanoparticles composition used in radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ and for monitoring said radiotherapy X-ray treatment continuously in real time of Burshtein, as modified with Guo, in a manner that high-Z nanoparticles comprises Hafnium oxide as disclosed in Stock. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage that since radiotherapy enhancers and radioresistant cancer cells show a radiotherapy dose enhancement factor when hafhium oxide nanoparticles are combined with radiotherapy, including hafhium oxide nanoparticles renders treatment of cancer in combination with radiotherapy more effective (Stock, [0017]).
As per dependent Claim 36, the combination of Burshtein and Guo as evidenced by Buechel a whole discloses hybrid radiotherapy treatment system of claim 23(see claim 23)
The combination of Burshtein and Guo as evidenced by Buechel a whole does not explicitly disclose Hafnium oxide feature.
However, in an analogous nanoparticle based radiotherapy field of endeavor, Stock discloses hybrid radiotherapy treatment system (Stock in at least abstract, [0001] for example discloses hybrid/combination radiotherapy treatment system. See at least Stock [0001] “use of the particle … in the treatment of cancer in combination with radiotherapy”), wherein said at least one high-Z nanoparticles comprising Hafnium oxide HfO.sub.2 (Stock in abstract, [0017] discloses wherein said at least one high-Z nanoparticles comprising Hafnium oxide HfO.sub.2. See Stock [0017] “use of high molecular weight …metal oxide, principally hafhium oxide, nanoparticles as radiotherapy enhancers in a similar way to gold.”)
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 high-Z nanoparticles composition used in the hybrid radiotherapy system for conducting a radiotherapy X-ray treatment on a target organ for monitoring said radiotherapy X-ray treatment continuously in real time, and for simulating said radiotherapy X-ray treatment to maximize the accuracy of the treatment of Burshtein, as modified with Guo, in a manner that high-Z nanoparticles comprises Hafnium oxide as disclosed in Stock. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage that since radiotherapy enhancers and radioresistant cancer cells show a radiotherapy dose enhancement factor when hafhium oxide nanoparticles are combined with radiotherapy, including hafhium oxide nanoparticles renders treatment of cancer in combination with radiotherapy more effective (Stock, [0017]).
Contingently Allowable Subject-Matter
As per dependent claims 15-17, 37, dependent claims 15-17, 37 would be contingently allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims in addition to overcoming any other rejections/objections enumerated above.
Additionally, as per dependent claims 15-17, 37, dependent claims 15-17, 37are being 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 in addition to overcoming any other rejections/objections enumerated above.
The following is a statement of reasons for the indication of allowable subject matter:
As per dependent Claim 15, the prior art of record fails to disclose or render obvious < radiotherapy system wherein at least two different high-Z nanoparticles of said multiple high-Z nanoparticles are usable, high-Z nanoparticles A and high-Z nanoparticles B, said high-Z nanoparticles A are attachable to molecules having affinity to cells of a first type, said high-Z nanoparticles B are attachable to molecules having affinity to cells of a second type, wherein XRF radiation producible by said high-Z nanoparticles A is distinguishable from XRF radiation producible by said high-Z nanoparticles B including all the other features, structures, specific arrangement and combination of features, and structures in dependent claim 15 including all of the limitations of the respective base claim and any intervening claims.
As per dependent Claim 37, the prior art of record fails to disclose or render obvious a hybrid radiotherapy treatment system wherein at least two types, a first type and a second type, of said multiple high-Z nanoparticles are used, said high-Z nanoparticles of said first type being attached to molecules having affinity to healthy cells, said high-Z nanoparticles of said second type are attached to molecules having affinity to non-healthy cells, in a manner that, XRF radiation produced by said high-Z nanoparticles of said first type is distinguishable from XRF radiation produced by said high-Z nanoparticles of said second type including all the other features, structures, specific arrangement and combination of features, and structures in dependent claim 37 including all of the limitations of the respective base claim and any intervening claims.
However, none of the prior art discloses or renders obvious all the features, structures, steps, specific arrangement and combination of features and structures as in dependent claims 15 and 37.
Additionally, as per dependent claims 16-17 dependent claim 16-17 would be contingently allowable based on their direct/indirect dependency on respective contingently allowable base claim.
Response to Amendment
According to the Amendment, filed 06/22/2026, the status of the claims is as follows:
Claims 1, 3-26, 28, 31-34, 36-39, 41 are currently amended;
Claims 27, 29-30, 35 are as originally filed; and
Claims 2 and 40 are cancelled.
The Specification/Drawings has been amended in view of the Amendment, filed 06/22/2026. No new matter was introduced.
By the current amendment, as a result, claims 1, 3-39 and 41 are now pending in this application and are being examined on the merits.
Response to Arguments
Issues Raised and Arguments/Remarks to Rejections/Objections Not Based On Prior Art presented on Page 12-14 of Applicant’s Amendment dated 06/22/2026
[A]: The Examiner agrees with the Applicant, and in light of the amendments/arguments, withdraws the following non prior art related objections/rejections raised in Office Action dated 09/30/2025: [1] The objection to Specification/Drawings is withdrawn in view of the amendment and arguments, filed 06/22/2026; [2] The objection to claims as raised in para. [7a-7m], 7[o-y] and 7[n] with respect to claim 14 is withdrawn in view of the amendment and arguments, filed 06/22/2026; [3] The 35 U.S.C. 112(b), rejections to claims as raised in Office Action dated 09/30/2025 are withdrawn in view of the amendment, filed 06/22/2026.
[B]: The Examiner disagrees with the Applicant, and in light of the amendments/arguments, maintains the following non prior art related objections/rejections raised in Office Action dated 09/30/2025: [1] The objection to claim 36 as raised in 7[n] is maintained in view of the amendment and arguments, filed 06/22/2026 as the neither the amendments or remarks/arguments overcome the issue as raised in Office Action dated 09/30/2025. Please see detailed rejection/objection enumerated above.
Issues Raised and Arguments/Remarks to Rejections Based On Prior Art presented on Pages 14-19 of Applicant’s Amendment dated 06/22/2026 where Applicant’s’ remarks inter alia that:
35 U.S.C. § 103 Rejection of the Amended Independent Claim 1 and Amended Independent Claim 23[A] In the Office Action, Claims 1-12, 18-35, 38-41 are rejected under 35 U.S.C. 103 over Burshtein et al. (US20170197096 Al) in view of Guo et al. (US20160252471).In the Office Action, Claim 13 is rejected under 35 U.S.C. 103 over Burshtein et al. in view of Guo et al. and further in view of Lin.In the Office Action, Claims 14 and 36 are rejected under 35 U.S.C. 103 103 over Burshtein et al. in view of Guo et al. and further in view of Stock.In response, Applicant asserts the following
[B] US 2017/0197096 A l to Burshtein does not mention XRF radiation at all.
[C] Applicant asserts that US 2016/0252471 Al to Guo is entirely different from the radiotherapy system of the present invention which uses a converging lens for enverging the beam towards the target without moving the beam. Thus, Applicant contends that the US 2016/0252471 Al uses two straight beams and tries to mimic what a converging lens of the present application does.
[D] In view of the above amendments and arguments, Applicant asserts that either US 2017/0197096 Al and/or US 2016/0252471 Al fails to negate the inventive step of amended independent claims 1 and 22.
[F]Therefore, independent Claims 1 and 23 are both novel and inventive and so as the claims depending therefrom. Accordingly, withdrawal of the rejections under 35 U.S.C. §103(a) is respectfully requested. In view of the above, each of the presently pending claims is believed to be in an immediate condition for allowance. Accordingly, the Examiner is respectfully requested to withdraw the outstanding objections and rejections and pass this application to issue.
Applicant’s arguments [A-F] with respect to the above claim limitation in amended independent Claim 1 and amended independent Claim 23 have been considered but are not persuasive for the following reasons:
Examiner first notes that claims as now explicitly, positively and specifically recited use intended use/functional limitations, conditional/contingent limitations and intended result verbiage and are being broadly yet reasonably interpreted as such in light of MPEP 2111.04 and as detailed above. As an example, in claim 1 and claim 23 in the limitation “at least one converging lens for converging said X-ray beam towards the target organ” as now explicitly, positively and specifically recited by the Applicant’s, the limitation following “for converging” is being broadly yet reasonably interpreted as intended use/functional limitation, and thus, prior art structure that is capable of the recited function would read on the limitation as now explicitly, positively and specifically recited by the Applicants ( also See MPEP 2111.04). Examiner suggest amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
With respect to Applicant’s arguments [B-C] above, the Office Action dated 09/30/2025 explicitly stated that Burshtein discloses the convergent lens and Guo discloses XRF detector and does not assert what Applicant is contending in [B-C] above. Thus, with respect to Applicant’s arguments [B-C] above, in response to applicant's arguments against the references individually, Examiner notes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The combination of applied art, Burshtein and Guo, as a whole discloses the above limitations in clam 1 and claim 23 as now explicitly, positively and specifically recited by the Applicants. Examiner suggest amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
With respect to Applicant’s arguments [D-E] above, for the above reasons, the 35 U.S.C. § 103 rejection of clam 1 and claim 23 as now explicitly, positively and specifically recited by the Applicants’ amendments still properly applies and is being maintained at this time, and thus as now explicitly, positively and specifically recited by the Applicants are not allowable at this time. Please also cross-reference detailed claim 1 and claim 23 interpretations, claim limitation mapping to prior art disclosed features and method steps and detailed explanations above. Examiner suggest amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
Issues Raised and Arguments/Remarks to Rejections Based On Prior Art presented on Page 19 of Applicant’s Amendment dated 06/22/2026 where Applicant’s’ remarks inter alia that:
35 U.S.C. § 103 Rejection of Dependent Claims 3-22, 24-39 and 41.
[a] Therefore, independent Claims 1 and 23 are both novel and inventive and so as the claims depending therefrom. Accordingly, withdrawal of the rejections under 35 U.S.C. §103(a) is respectfully requested. In view of the above, each of the presently pending claims is believed to be in an immediate condition for allowance. Accordingly, the Examiner is respectfully requested to withdraw the outstanding objections and rejections and pass this application to issue.
Applicants’ arguments with respect to dependent claims 3-22, 24-39 and 41 have been considered but are not persuasive. Applicants’ arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the dependent claims 3-22, 24-39 and 41 define a patentable invention based on their dependency on base claims without specifically pointing out how the language of the dependent claims patentably distinguishes them from the references. Therefore, that argument above is not persuasive either.
For the above reasons, the 35 U.S.C. § 103 rejection of dependent claims 3-22, 24-39 and 41 still applies, is proper and is being maintained at this time. Please also cross-reference detailed claim 3-22, 24-39 and 41 interpretation, claim limitation mapping to prior art disclosed features and method steps and detailed explanations 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). Applicants are 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUNITA REDDY whose telephone number is (571)270-5151. The examiner can normally be reached on M-Thu 10-4 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHARLES A MARMOR II can be reached on (571)272-4730. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUNITA REDDY/Primary Examiner, Art Unit 3791
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