DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Preliminary Amendment
Preliminary Amendment dated 08/09/2025 has been formally entered and claims 1-41 submitted with Preliminary Amendment dated 08/09/2025 are being examined on the merits.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: drawings do not include reference signs “108A” (see at least instant application specification as-filed page 12), “108b” (see at least instant application specification as-filed page 12) or “109” (see at least instant application specification as-filed page 11) mentioned in the description.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
“…simulating said radiographic a treatment procedure …” in page 8 needs to be corrected. A suggested correction is -- simulating said radiographic [[a]] treatment procedure --.
“location involves with scanning” in page 15 needs to be corrected. A suggested correction is -- location involves [[with]] scanning --.
“Compton electrons, or the like, is ejected from the NP and deliver their energy to the target organ” needs to be corrected to expand the abbreviation/acronym “NP”.
“x-ray beam is focusable on a section in the target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons” in abstract needs to corrected. A suggested correction is -- x-ray beam is focusable on a section in the target organ where the concentration of said high-Z nanoparticles [[leading]] lead to a desirable emission of said XRF photons—as in instant application specification as-filed page 15.
“wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons, and wherein in case the emission of said XRF photons decreasing, said x-ray beam is movable to refocus on said section in said target organ where the emission of said XRF photons is desirable” in at least page 2 needs to corrected. A suggested correction is -- wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles [[leading]] lead to a desirable emission of said XRF photons, and wherein in case the emission of said XRF photons is decreasing, said x-ray beam is movable to refocus on said section in said target organ where the emission of said XRF photons is desirable—as in instant application specification as-filed page 15.
Appropriate correction is required.
Specification does not include any line numbers or paragraph numbers which makes it harder to reference. Line numbers or paragraph numbers is suggested.
Claim Objections
Following claims are objected to because of the following informalities:
Claim 1 “the concentration” needs to be corrected. A suggested correction is –[[the]] a concentration – in light of lack of antecedent for this term in the claim.
Each of claim 18 and claim 38 “the distribution” needs to be corrected. A suggested correction is – [[the]] a distribution-- in light of lack of antecedent for this term in respective the claim or any of preceding claims of the respective claim.
Each of claim 18 and claim 38 “said/the radiotherapy treatment” needs to be corrected. A suggested correction is – [[said/the]] a radiotherapy treatment -- in light of lack of antecedent for this term in respective the claim or any of preceding claims of the respective claim.
Claim 23 “the concentration” needs to be corrected. A suggested correction is –[[the]] a concentration – in light of lack of antecedent for this term in the claim.
Claim 2 ends of sentence “,” needs to be corrected to --[[,]].--.
The term “producable” in claims 15-16 needs to be corrected. A suggested correction is to – [[producable]] producible--.
Claim 1 “wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons” needs to be corrected. A suggested correction is -- wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles [[leading]] lead to a desirable emission of said XRF photons-- in light of instant application specification as-filed page 15.
Claim 23 “wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons” needs to be corrected. A suggested correction is -- wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles [[leading]] lead to a desirable emission of said XRF photons-- in light of instant application specification as-filed page 15.
Claim 1 “wherein in case the emission of said XRF photons decreasing, said x-ray beam is movable to refocus on said section in said target organ where the emission of said XRF photons is desirable” needs to be corrected. A suggested correction is -- wherein based upon the emission of said XRF photons decreasing, said x-ray beam is movable to refocus on said section in said target organ where the emission of said XRF photons is desirable-- to avoid conditional limitation recitation which would raise question as to what occurs when the condition is not met.
Claim 16 “wherein in case the XRF radiation producable by said high-Z nanoparticles B decreases and/or the XRF radiation producable by said high-Z nanoparticles A increases during said radiographic treatment procedure, said X-ray beam has to be refocused” needs to be corrected. A suggested correction is --wherein based upon the XRF radiation [[producable]] producible by said high-Z nanoparticles B decreases and/or the XRF radiation [[producable]] producible by said high-Z nanoparticles A increases during said radiographic treatment procedure, said X-ray beam has to be refocused-- to avoid conditional limitation recitation which would raise question as to what occurs when the condition is not met.
Claim 23 “wherein in case the emission of said XRF photons decreasing, said x-ray beam is movable to refocus to said section in said target organ where the emission of said XRF photons is desirable” needs to be corrected. A suggested correction is --wherein based upon the emission of said XRF photons decreasing, said x-ray beam is movable to refocus to said section in said target organ where the emission of said XRF photons is desirable-- to avoid conditional limitation recitation which would raise question as to what occurs when the condition is not met.
Claim 39 “moving and refocusing said x-ray beam when detecting a decrease in the emission of said XRF photons” needs to be corrected in light of MPEP 2111.04(II) which states the broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent is not met. Here, the method step limitation “moving and refocusing said x-ray beam when detecting a decrease in the emission of said XRF photons” broadly yet reasonably interpreted under MPEP 2111.04(II) qualifies as a contingent limitation i.e. this step “moving and refocusing said x-ray beam” is not necessarily required to be performed if the condition “detecting a decrease in the emission of said XRF photons” is not met and thus applied art need not necessarily disclose this contingent/conditional method step. A suggested correction is --moving and refocusing said x-ray beam [[when]] based upon detecting a decrease in the emission of said XRF photons—instead.
Claim 37 “said high-Z nanoparticles of said second type being attached to molecules having affinity to other kind … of cells, so that, the XRF radiation produced by said high-Z nanoparticles of said first type is distinguishable from the XRF radiation produced by said high-Z nanoparticles of said second type” needs to be corrected. A suggested correction is --said high-Z nanoparticles of said second type being attached to molecules having affinity to other kind … of cells, [[so]] in a manner that, the XRF radiation produced by said high-Z nanoparticles of said first type is distinguishable from the XRF radiation produced by said high-Z nanoparticles of said second type-- to avoid intended result/functional limitation interpretation (see MPEP 2111.04) which would raise question as to whether the limitation proceeding “so that” is even required or not required.
Claim 14 and claim 36 “wherein said at least one high-Z nanoparticles comprising Hafnium oxide HfO.sub.2” needs to be corrected to -- wherein said at least one high-Z nanoparticles [[comprising]] comprises Hafnium oxide [[HfO₂]] (HfO₂)--.
Claim 18 “wherein 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” needs to be corrected. A suggested correction is -- wherein said at least one X-ray detector [[monitoring]]monitors in real-time said radiotherapy treatmentwhich provides the distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment-- 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 21 “wherein said radiotherapy system producing 3D diagnostic images of said target organ, thus, enabling precise treatments” needs to be corrected. A suggested correction is -- wherein said radiotherapy system [[producing]]produces 3D diagnostic images of said target organ, [[thus,]] enabling precise treatments-- 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 25 “wherein said hybrid radiotherapy system producing 3D diagnostic images of said target organ, thus, enabling precise treatments” needs to be corrected. A suggested correction is -- wherein said hybrid radiotherapy system [[producing]] produces 3D diagnostic images of said target organ, [[thus,]] enabling precise treatments-- 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 38 “wherein said at least one X-ray detector monitoring in real-time said radiotherapy treatment procedure, thus, providing the distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment” needs to be corrected. A suggested correction is -- wherein said at least one X-ray detector [[monitoring]]monitors in real-time said radiotherapy treatment procedurewhich provides the distribution of said high-Z nanoparticles in said target organ continuously throughout the radiotherapy treatment-- 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 24 “said openable aperture maintained closed for converging said X-ray beam to said target organ during said radiotherapy treatment procedure, said aperture maintained open to allow said beam to pass through said aperture for simulating said radiographic treatment” needs to be corrected. A suggested correction is -- 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--.
Claim 28 “wherein said at least one XRF detector selected from a point-sized detector, a one dimensional array detector, and a two-dimensional array detector” needs to be corrected. A suggested correction is -- 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--.
Claim 34 “wherein said high-Z nanoparticles comprising at least one non-metal element” needs to be corrected. A suggested correction is -- wherein said high-Z nanoparticles [[comprising]] comprises at least one non-metal element--.
Claim 37 “wherein at least two types, a first type and a second type, of said high-Z nanoparticles being used” needs to be corrected. A suggested correction is -- wherein at least two types, a first type and a second type, of said high-Z nanoparticles [[being]] are used--.
Claim 40 “wherein moving and refocusing” needs to be corrected. A suggested correction is -- wherein the moving and refocusing—in light of its antecedent in claim 39 lines 11-12.
Claim 33 line 1 “The radiotherapy treatment system” needs to be corrected to -- The hybrid radiotherapy treatment system—in light of its antecedent “A hybrid radiotherapy treatment system” in claim 23 line 1.
Claim 39 needs to be amended as follows in light of antecedent for claim 39 terms in base claim 1.
PROPOSED AMENDMENT CLAIM 39. A radiotherapy treatment method for conducting [[a]] the radiographic X-ray imaging on [[a]] the target organ in real time during the radiotherapy treatment procedure comprising: providing the radiotherapy treatment system of claim 1;
administrating at least one high-Z metal nanoparticle or the at least one high-Z fiducial marker to [[a]] the target organ in [[a]] the patient's body;
delivering radiation via [[an]] the X-ray beam to the target organ;
emitting the XRF photons from the high-Z nanoparticles/the at least one high-Z fiducial marker…
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.
Claim 1-41 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 1 recite the limitation “said radiotherapy treatment procedure". There is insufficient antecedent basis for this limitation in the claim.
Each of claim 15-16 recite the limitation “the XRF radiation". There is insufficient antecedent basis for this limitation in the claim.
Claim 37 recite the limitation “the XRF radiation". There is insufficient antecedent basis for this limitation in the claim.
Each of claim 16 and claim 19 recite the limitation "said radiographic treatment procedure". There is insufficient antecedent basis for this limitation in the claim.
Each of claim 1 and claim 23 recites “said X-ray radiation”. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 recites “said radiography treatment”. There is insufficient antecedent basis for this limitation in the claim.
Claim 39 in line 7 recites “the high-Z nanoparticles” which renders this claim unclear in light of claim 39 line 4 “at least one high-Z metal nanoparticle” and claim 1 line 6 “high-Z nanoparticles”. More specifically, it is unclear as to whether claim 39 line 7 “the high-Z nanoparticles” encompasses claim 39 line 4 “at least one high-Z metal nanoparticle” or just claim 1 line 6 “high-Z nanoparticles” or both.
Claim 24 recites “said radiotherapy treatment procedure” which renders this claim unclear in light of “radiotherapy treatment procedures” (plurality) recited in claim 23 step (f).More specifically, it is unclear as to claim 24 “said radiotherapy treatment procedure” is referencing each, any radiotherapy treatment procedure or a specific one such as first radiotherapy treatment procedure, last radiotherapy treatment procedure or some other radiotherapy treatment procedure in a time domain within the plurality of radiotherapy treatment procedures.
Claim 41 recites “said radiographic treatment procedure” which renders this claim unclear. More specifically, it is unclear as to whether claim 41 “said radiographic treatment procedure” is referencing “radiotherapy treatment procedure” in claim 39 line 2 and/or “radiotherapy treatment procedure” in claim 1 lines 11-12.
Claim 1 recites “wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons, and … said x-ray beam is movable to refocus on said section in said target organ where the emission of said XRF photons is desirable” which renders this claim unclear in light of instant application specification as-filed. More specifically, the term “desirable” in the context used is a relative/subjective term which renders the claim indefinite. The term “desirable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. More specifically, it is unclear as to whether the term “desirable” is with reference to any value, percentage or some other objective reference.
Claim 23 recites “wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons, … said x-ray beam is movable to refocus to said section in said target organ where the emission of said XRF photons is desirable”. which renders this claim unclear in light of instant application specification as-filed. More specifically, the term “desirable” in the context used is a relative/subjective term which renders the claim indefinite. The term “desirable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. More specifically, it is unclear as to whether the term “desirable” is with reference to any value, percentage or some other objective reference.
Claim 37 recites “(e.g. healthy cells), said high-Z nanoparticles of said second type being attached to molecules having affinity to other kind (e.g. non-healthy)” which renders this claim unclear. More specifically, the phrase e.g. or "for example" as is known in the art renders the claim indefinite because it is unclear whether the limitations within parenthesis following the phrase e.g. are part of the claimed invention. See MPEP § 2173.05(d).
Claim 37 “said high-Z nanoparticles of said first type being attached to molecules having affinity to one kind (e.g. healthy cells), said high-Z nanoparticles of said second type being attached to molecules having affinity to other kind (e.g. non-healthy) of cells” recitation also raises broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) indefiniteness issue. More specifically, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 37 recites the broad recitation “molecules having affinity to one kind” and “molecules having affinity to other kind”, and the claim also recites “healthy cells” and “non-healthy” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Examiner suggests amending to --said high-Z nanoparticles of said first type being attached to molecules having affinity to
Each of claim 1, 16, 23, 39 include the symbol “/” which renders this claim unclear. More specifically, it is unclear as to what is meant by “/” and how the symbol “/” would need to be interpreted in the context used i.e. mutually exclusively, mutually inclusive, combination, something else.
Each of claim 10 and claim 33 recite “preferably” which renders this claim unclear. More specifically, the use of the word preferably in the claim language renders the claim indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention since it raises a "range within a range" or "broader limitation followed by narrow limitation" indefiniteness type issue as it is not clear whether you have to have any high-Z nanoparticles to meet the claim or whether you have to have Thulium (Z=69) and Erbium (Z=68) that follows the word "preferably."
Dependent claims 2-22 and 24-41 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 2-22 and 24-41 are also rejected under 35 U.S.C. 112(b) based on their direct/indirect dependency on their respective base claims.
Claim Interpretation
Claims terms where relevant are being interpreted in light of definitions enumerated in instant application specification page 11, page 16.
Please note that the term "simulation" recited in claim 19-20, 22-23, when interpreted in light of the disclosure as-filed is used in a non-standard manner compared to as known in the relevant art. More specifically, the term "simulation" does not mean "computer modelling of the treatment process" which would be the standard meaning of this term in the relevant art. Rather, term "simulation" recited in claim 19-20, 22-23, when interpreted in light of the disclosure as-filed as a whole appears to be imaging system/method of organ to be treated.
Please note that USPTO personnel are to give claims their broadest reasonable interpretation in light of the supporting disclosure. In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997). Limitations appearing in the specification but not recited in the claim should not be read into the claim. E-Pass Techs., Inc. v. 3Com Corp., 343 F.3d 1364, 1369, 67 USPQ2d 1947, 1950 (Fed. Cir. 2003) (claims must be interpreted "in view of the specification" without importing limitations from the specification into the claims unnecessarily). In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-551 (CCPA 1969). See also In re Zletz, 893 F.2d 319, 321-22, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) ("During patent examination the pending claims must be interpreted as broadly as their terms reasonably allow.... The reason is simply that during patent prosecution when claims can be amended, ambiguities should be recognized, scope and breadth of language explored, and clarification imposed.... An essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.").
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 1-12, 18-35, 38-41 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 treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ (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 treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ . 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”) comprising:
(i) an x-ray beam source configurable to deliver an X-ray beam to a target organ (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) optical means for converging and shaping said beam to a cone-shaped X-ray beam of photons which hit the target organ simultaneously (Burshtein in at least fig. 2, [0026], [0031-0032], [0035] for example discloses optical means 104a, 104b, 104c, 208, 210 for converging and shaping said beam to a cone-shaped X-ray beam of photons which hit the target organ simultaneously. 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”),
(iv)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 treatment procedure (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 treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the 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 treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the 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”),
optical means for converging and shaping said beam to a cone-shaped X-ray beam of photons which hit the target organ simultaneously (Guo in at least [0059], [0075] for example discloses optical means for converging and shaping said beam to a cone-shaped X-ray beam of photons which hit the target organ simultaneously. See at least Guo [0059] “X-ray focusing optics may be used”),
multiple high-Z nanoparticles/at least one high-Z fiducial marker attachable to said target organ, said high-Z nanoparticles/at least one high-Z fiducial marker absorbing said X-ray radiation and emitting X-ray fluorescence (XRF) photons (Guo in at least [0065], [0011] for example discloses multiple high-Z nanoparticles/at least one high-Z fiducial marker attachable to said target organ, said high-Z nanoparticles/at least one high-Z fiducial marker absorbing said X-ray radiation and emitting X-ray fluorescence (XRF) photons. 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 (Guo in at least fig. 23, [0011], [0048], [0061] for example discloses XRF detector for detecting said XRF photons ejecting out of a patient's body. 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
control means for controlling at least one of components for controlling said radiotherapy treatment procedure (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 focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons, and wherein in case the emission of said XRF photons decreasing, said x-ray beam is movable to refocus on said section in said target organ where the emission of said XRF photons is desirable (Guo in at least [0049-0050], [0054-0055] for example discloses wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons. 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 treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ 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 2, the combination of Burshtein and Guo as a whole further discloses radiotherapy treatment system wherein said optical means comprising at least one converging lens for converging said X-ray beam to said target organ (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.”),
As per dependent Claim 3, the combination of Burshtein and Guo as a whole further discloses radiotherapy treatment 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 treatment 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 treatment 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 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 6, the combination of Burshtein and Guo as a whole further discloses radiotherapy treatment system, 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 treatment 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 8, the combination of Burshtein and Guo as a whole further discloses radiotherapy treatment system wherein said 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 radiotherapy treatment system wherein said 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 treatment system of claim 9, wherein said high-Z nanoparticles are preferably 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 11, the combination of Burshtein and Guo as a whole further discloses radiotherapy treatment system wherein said 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 treatment 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 treatment system wherein 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 (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 as a result. 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 treatment system of claim 1, further comprising a simulation system for simulating said radiographic treatment procedure to maximize the accuracy of the treatment, said simulation system operates independently of the radiotherapy treatment system (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 simulation/imaging system for simulating/imaging said radiographic treatment procedure to maximize the accuracy of the treatment, said simulation/imaging system operates independently of the radiotherapy treatment system. 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 treatment 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 treatment system of claim 18, wherein said radiotherapy system producing 3D diagnostic images of said target organ, thus, enabling precise treatments (Guo in at least [0078] for example discloses wherein said radiotherapy system producing 3D diagnostic images of said target organ, thus, enabling precise treatments as a result. 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 treatment 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 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 (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], [0035], [0040-0041], [0053] for example discloses a hybrid radiotherapy treatment system for conducting radiographic X-ray imaging on a target organ 106 during radiographic treatment to the target organ and for simulating said radiography 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 (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”),
(b) optical means for shaping said beam to a cone-shaped X-ray beam of photons which hit the target organ simultaneously (Burshtein in at least fig. 2, [0026], [0031-0032], [0035] for example discloses optical means 104a, 104b, 104c, 208, 210 for shaping said beam to a cone-shaped X-ray beam of photons which hit the target organ simultaneously. 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”),
(d) 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 radiographic treatment (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)-(d), for controlling said simulation and radiotherapy treatment procedures (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 switching between a simulation mode and a radiotherapy treatment mode without moving a patient from one position to another (Burshtein in at least fig. 2, [0019], [0030], [0032-0033], [0035], [0040], [0053] for example discloses said said hybrid radiotherapy system switching between a simulation mode and a radiotherapy treatment mode without moving a patient from one position to another. 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:
multiple high-Z nanoparticles/at least one high-Z fiducial marker attachable to said target organ, said multiple nanoparticles/at least one high-Z fiducial marker absorbing said X-ray radiation and emitting X-ray fluorescence (XRF) photons (Guo in at least [0065], [0011] for example discloses multiple high-Z nanoparticles/at least one high-Z fiducial marker attachable to said target organ, said multiple nanoparticles/at least one high-Z fiducial marker absorbing said X-ray radiation and emitting X-ray fluorescence (XRF) photons. 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 (Guo in at least fig. 23, [0011], [0048], [0061] for example discloses at least one XRF detector for detecting said XRF photons ejecting out of a patient's body. 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 focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons, wherein in case the emission of said XRF photons decreasing, said x-ray beam is movable to refocus to said section in said target organ where the emission of said XRF photons is desirable (Guo in at least [0049-0050], [0054-0055] for example discloses wherein said x-ray beam focusable on a section in said target organ where the concentration of said high-Z nanoparticles leading to a desirable emission of said XRF photons. 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 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 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 hybrid radiotherapy system of claim 23, wherein said optical means comprising at least one 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”), said at least one lens comprising an openable aperture, said openable aperture maintained closed for converging said X-ray beam to said target organ during said radiotherapy treatment procedure, said aperture 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 said at least one lens comprising an openable aperture, said openable aperture maintained closed for converging said X-ray beam to said target organ during said radiotherapy treatment procedure, said aperture 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 producing 3D diagnostic images of said target organ, thus, enabling precise treatments (Guo in at least [0054-0055], [0078] for example discloses wherein said hybrid radiotherapy system producing 3D diagnostic images of said target organ, thus, enabling precise treatments as a result. 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, 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 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 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 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 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 radiotherapy treatment system wherein said high-Z nanoparticles are preferably 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 wherein said 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 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 monitoring in real-time said radiotherapy treatment procedure, thus, providing the distribution of said high-Z nanoparticles in said target organ continuously throughout the 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 a radiotherapy treatment method for conducting a radiographic X-ray imaging on a target organ in real time during a radiation treatment procedure (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 at least one high-Z metal nanoparticle or at least one high-Z fiducial marker to a target organ in a patient's body(Guo in at least [0011], [0065] for example discloses administrating at least one high-Z metal nanoparticle or at least one high-Z fiducial marker to a target organ in a patient's body. see at least Guo “providing a sample including nanoparticles, where the nanoparticles are configured to be associated with a target”);
delivering radiation via an 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 XRF photons from the high-Z nanoparticles/the at least one high-Z fiducial marker; detecting said XRF photons (Guo in at least [0011], [0048], [0061] for example discloses emitting XRF photons from the high-Z nanoparticles/the at least one high-Z fiducial marker; detecting said XRF photons. 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.” );
directing said X-ray beam's focal point (Guo in at least fig. 1-2, 10, 15-16 for example disclose directing said X-ray beam's focal point. Burshtein in at least fig. 2, [0026], [0031-0032], [0035] for example discloses directing said X-ray beam's focal point. 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”); and
moving and refocusing said x-ray beam when detecting a decrease in the emission of said XRF photons (Guo in at least [0011], [0029], [0049-0050], [0054-0055], [0059], [0075] for example discloses moving and refocusing said x-ray beam when detecting a decrease in the emission of said XRF photons. 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 40, the combination of Burshtein and Guo as a whole further discloses radiotherapy treatment method wherein moving and refocusing said x-ray beam to a section in the target organ where the concentration of the high-Z metal nanoparticles is desirable(Guo in at least [0011], [0029], [0049-0050], [0054-0055], [0059], [0075] for example discloses moving and refocusing said x-ray beam to a section in the target organ where the concentration of the high-Z metal nanoparticles is desirable. See at least Guo [0011] “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… identifying a sample that includes the target”).
As per dependent Claim 41, the combination of Burshtein and Guo as a whole further discloses method further comprising simulating said radiographic treatment procedure for obtaining a distribution of said 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 radiographic treatment procedure for obtaining a distribution of said 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 treatment 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 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 treatment system (Lin in at least abstract, [0003], [0063], [0133], [0195] for example discloses radiotherapy treatment 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 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 the radiotherapy treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ of 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 treatment 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 treatment 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 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 radiotherapy treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ 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 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 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 <a radiotherapy treatment system for conducting radiographic X-ray imaging on a target organ during radiographic treatment to the target organ wherein at least two different high-Z nanoparticles are usable, high-Z nanoparticles A and high-Z nanoparticles B, said high-Z nanoparticles A attachable to molecules having affinity to cells of a first type, said high-Z nanoparticles B attachable to molecules having affinity to cells of a second type, wherein the XRF radiation producable by said high-Z nanoparticles A is distinguishable from the XRF radiation producable 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 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 wherein at least two types, a first type and a second type, of said high-Z nanoparticles being used, said high-Z nanoparticles of said first type being attached to molecules having affinity to one kind … said high-Z nanoparticles of said second type being attached to molecules having affinity to other kind … of cells, so that, the XRF radiation produced by said high-Z nanoparticles of said first type is distinguishable from the 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.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and/or the claims. US 20180033513 (see at least abstract, fig. 1-11, [0002-0003], [0010-0019]), US 20190329071 (see at least abstract, [0006-0093] ), US 20180250404 (see at least abstract, [0008]), US 20090161826 (see at least abstract, [0571], [0576]), US 20120307962 (see at least abstract, fig. 2, [0004-0006]), US 20060182217 (see at least abstract, [0001], [0003-0024] ), US 20130204121 (see at least abstract, [00078]), US 20070280418 (see at least abstract, fig. 1-6, [0026-0038]), US 20110064665 (see at least abstract, [0002-0003], [0011-0034]) for disclosing radiotherapy systems and methods and/or High-Z nanoparticle based therapies similar to that claimed and/or disclosed.
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.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
/SUNITA REDDY/Primary Examiner, Art Unit 3791
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