DETAILED ACTION
This Office action is responsive to communications filed on 08/18/2025. Claims 1, 3-10, 12-16, 18-20 have been amended. Claims 11 & 17 are canceled. Presently, Claims 1-10, 12-16, and 18-20 remain pending and are hereinafter examined on the merits.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Previous rejections under 35 USC § 112(b) and claim objections are withdrawn in view of the amendments filed on 08/18/2025.
Applicant’s arguments with respect to claim(s) under 35 USC § 103 have been considered but are moot because the new ground of rejection does not rely on Sampson et al (“Diagnostic Accuracy of Rubidium-82 Myocardial Perfusion Imaging With Hybrid Positron Emission Tomography/Computed Tomography in the Detection of Coronary Artery Disease. JACC. 2007 Mar, 49 (10) 1052–1058”) in view of de Groot et al (Optimized dose regimen for whole-body FDG-PET imaging. EJNMMI Res 3, 63 (2013)); or Sampson et al (“Diagnostic Accuracy of Rubidium-82 Myocardial Perfusion Imaging With Hybrid Positron Emission Tomography/Computed Tomography in the Detection of Coronary Artery Disease. JACC. 2007 Mar, 49 (10) 1052–1058”) in view of de Groot et al (Optimized dose regimen for whole-body FDG-PET imaging. EJNMMI Res 3, 63 (2013)) in view of van Dijk et al (Body weight-dependent Rubidium-82 activity results in constant image quality in myocardial perfusion imaging with PET. J Nucl Cardiol. 2021 Aug;28(4):1536-1544. doi: 10.1007/s12350-019-01875-w. Epub 2019 Sep 4). applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The grounds of rejection now rely on Sampson et al (“Diagnostic Accuracy of Rubidium-82 Myocardial Perfusion Imaging With Hybrid Positron Emission Tomography/Computed Tomography in the Detection of Coronary Artery Disease. JACC. 2007 Mar, 49 (10) 1052–1058”) in view of de Groot et al (Optimized dose regimen for whole-body FDG-PET imaging. EJNMMI Res 3, 63 (2013)) in view of Koopman et al (Technical note: how to determine the FDG activity for tumour PET imaging that satisfies European guidelines. EJNMMI Phys. 2016 Dec;3(1):22. doi: 10.1186/s40658-016-0158-z. Epub 2016 Sep 29).
Drawings
The drawings are objected to because several are of poor image quality. Specifically, FIG. 1, FIG. 2, FIG. 7, FIG. 8, FIG. 13, FIG. 14, FIG. 15, FIG. 16, & FIG. 17, are not legible. 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. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. 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.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10, 12-16, and 18-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1 of the subject matter eligibility test (see MPEP 2106.03).
Claims 1-10, 12-13 is directed to a “method” which describes one of the four statutory categories of patentable subject matter, i.e., a process.
Claims 14-16, 18-19 is directed to a “method” which describes one of the four statutory categories of patentable subject matter, i.e., a process.
Claim 20 is directed to a “method” which describes one of the four statutory categories of patentable subject matter, i.e., a process.
Step 2A of the subject matter eligibility test (see MPEP 2106.04).
Prong One:
Claims 1 recite (“sets forth” or “describes”) the abstract idea of “a mental process” (MPEP 2106.04(a)(2).III.) and the abstract idea of “mathematical concepts” (MPEP 2106.04(a)(2).I.), substantially as follows:
“ wherein the dose is calculated based on an exponential squared function of body habitus of the subject;
[...]
wherein the exponential function based dosing is calculated by activity = 0.1 x weight2: and
wherein the method of the imaging processing of the subject is an iterative ordered-subset expectation maximization (OSEM) reconstruction method. ”
Claims 14 recite (“sets forth” or “describes”) the abstract idea of “a mental process” (MPEP 2106.04(a)(2).III.) and the abstract idea of “mathematical concepts” (MPEP 2106.04(a)(2).I.), substantially as follows:
“ wherein the dose of Rubidium-82 imaging agent is calculated based on an exponential squared function of the subject's body habitus;
[...]
wherein the exponential squared function based dosing is calculated by activity = 0.1 x weight2. ”
Claims 20 recite (“sets forth” or “describes”) the abstract idea of “a mental process” (MPEP 2106.04(a)(2).III.) and the abstract idea of “mathematical concepts” (MPEP 2106.04(a)(2).I.), substantially as follows:
“ a) calculating a dose of Rubidium-82 based on an exponential squared function of a body habitus of the subject;
[...]
[...]
[...]
e) performing an assessment of the obtained images to diagnose a disease state;
[...]
wherein the exponential function based dosing is calculated by activity = 0.1 x weight2; and
wherein the method of the imaging of the subject is an iterative ordered-subset expectation maximization (OSEM) reconstruction method in order to exhibit qualitative visual image quality scoring (IQS) and quantitative contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as an exponential function of body weight. “
In claims (1, 14, 20), the above recited steps can be practically performed in the human mind, with the aid of a pen and paper to perform the steps. The limitations identified in claims (1, 14, 20) expressly present operation whose character is mathematical and whose performance depends on evaluative or reasoning that ca be carried out by the human mind, even if the claims are placed in a medical imaging setting.
For claim 1, the recited method announces that the dose is “calculated based on an exponential squared function of body habitus” and later defines that relationship as “activity = 0.1 x weight2 ”, and employs an OSEM technique. The act of apply an exponential square relationship or even a quadratic or power law to arrive at a numeric dose reflect the type of quantitative relationship that falls squarely within the mathematical concepts. At the same time, determine a dose by applying that relationship, and using that output to form an additional step of reconstruction via additional mathematical concepts (i.e., OSEM), reflects evaluative reasoning that can be carried out mathematical and mentally. Namely, identifying the relevant input, applying a known formula, and interpreting the results, those operations expressly align with mental processes with mathematical concepts because they are steps that can be performed mentally and mathematically.
Claim 14, also proceeds along the same lines. The method requires first determining body habitus based on quantifying Rb-82 by applying the same exponential squared relationship. Because the claim hinges on deriving a value though an explicitly defined algebraic relationship, the claim text expressly presents a mathematical operation. And the determination of habitus, the selection of appropriate values, and the use of that value to set a dose are all steps that can be executed though mental reasoning. Thus the claim places a mathematical formula and mental evaluation at the center of the method process.
Claim 20 re-presents the mathematical relationship even more overtly. Step (a) requires calculating a dose “based on the exponential squared function of a body habitus of the subject” and the body of the abstract idea of the claim reiterates the explicit formula “activity = 0.1 x weight2”. The later steps of “performing an assessment” of images is written at such a high level of generality to diagnose a disease states a cognitive evaluation, (i.e., interpreting images, drawing conclusions, and/or classifying the subject’ condition). The recited OSEM reconstruction is an algorithmic mathematical procedure grounded in interactive numerical operations. Collectively, these features place mathematical constructs in the claim and rely on assessments and reasoning that can be executed mentally and mathematically, thus fitting both types of abstract ideas. There is nothing recited in the claim to suggest an undue level of complexity in how identified steps are conducted. Therefore, a person would be able to perform the identification and selection mentally or with a generic computer.
Prong Two: Claims (1, 14, 20) do not include additional elements that integrate the mental process into a practical application.
This judicial exception is not integrated into a practical application. In particular, the claims recites (1) additional steps of “administering a dose of Rubidium-82 to a subject,”-(claim 1), “obtaining Rubidium-82 positron emission tomography images of a region of interest of a subject having consistent image quality, the method comprising calculating a body habitus of the subject, administering a dose of Rubidium-82 imaging agent to the subject, and taking positron emission tomography images of the subject;”-(claim 14), “imaging a subject having coronary artery disease or at a risk of developing a coronary artery disease comprising: [...] b) generating the calculated dose of Rubidium-82 by an automated elution system to produce a generated dose of Ruidium-82; c) administering the generated dose of Rubidium-82 to the subject; d) performing positron emission tomography imaging to obtain images; and”-(claim 20);
(2) further an addition step of outputting desired results “wherein the exponential function based dosing provides a consistent signal to noise ratio and a consistent contrast to noise ratio;”-(claim 1), “wherein the exponential squared function based dosing provides a consistent signal to noise ratio and a consistent contrast to noise ratio; and”-(claim 14), “wherein the exponential function based dosing provides a consistent signal to noise and a consistent contrast to noise ratio;”-(claim 20)
The steps in (1) represent merely data gathering or pre-solution activities that are necessary for use of the recited judicial exception and are recited at a high level of generality with conventionally used tools (see below Step IIB for further details). Data gathering and mere instructions to implement an abstract idea on a computer do not integrate a judicial exception into a practical application (MPEP 2106.05 (f and g)).
The step in (2) represents merely notification outputting by a processor as a post-solution activity and is recited at a high level of generality. Those steps in (2) do not describe any additional technological mechanism, any structural modification of an imaging device, or any particular processing technique that achieves the stated image quality characteristics. They simply announce the outcome that is desired outcome based on mathematical dosing to achieve it. The statement is an intended results, (i.e., consistent SNR and CNR) which does not convert a mathematical computation into a technological improvement. It adds no operative steps, beyond the calculation identified as the abstract idea, and it does not impose any meaningful limit on how the mathematical relationship is implemented. Instead, the language is characterize as a desired hope for performance of the selected dose based on the formula, without tying that performance to any contrate technical means. Hence these recited steps at (2) are not a practical application, see MPEP 2106.04(d)(2).
As a whole, the additional elements merely serve to gather and feed information to the abstract idea and to output a notification based on the abstract idea, while generically implementing it on conventionally used tools. There is no practical application because the abstract idea is not applied, relied on, or used in a meaningful way. No improvement to the technology is evident, and the estimated of dosage information is not outputted in any way such that a practical benefit is realized. Therefore, the additional elements, alone or in combination, do not integrate the abstract idea into a practical application.
Accordingly, these additional elements do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. Further, there is no evidence of record that would support the assertion that this step is an improvement to a computer or technological solution to a technological problem. Ultimately, the Applicant’s describe improvement in the process of using dosage techniques with imaging, but this is not an improvement in the function of a computer or other technology (See MPEP 2106.05(a)(ii); “the court determined that the claimed user interface simply provided a trader with more information to facilitate market trades, which improved the business process of market trading but did not improve computers or technology”; See MPEP 2106.04(d)(1); 2106.05(a); and 2106.05(f)). The claims are directed to the abstract idea. Also, there does not appear to be any particular structure or machine, treatment or prophylaxis, transformation, or any other meaningful application that would render the claim eligible at step 2A, prong 2.
Step 2B of the subject matter eligibility test (see MPEP 2106.05).
Claims (1, 14, 20) do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above, the claims recite additional steps of administering a dose of Rb-82 and performing positron emission tomography on a region of interest. These steps represents mere data gathering, data outputting or pre/post/extra-solution activities that are necessary for use of the recited judicial exception and are recited at a high level of generality. Furthermore, as discussed above, limitations with respect to the processor languages/terms, respectively, amount to mere instructions to implement the abstract idea on a computer. As discussed with respect to Step 2A Prong Two, the additional elements in the claims amount to no more than insignificant extra solution activity and mere instructions to apply the exception using a generic computer component. The same analysis applies here in 2B and does not provide an inventive concept. The data gathering steps that were considered insignificant extra-solution activity in Step 2A Prong Two, have been re-evaluated in Step 2B and determined to be well-understood, routine, conventional activity in the field.
As an evidence, Ben-Haim (US 2015/0366523 A1) discloses:
¶0210, ‘Radioactive isotopes which decay, at least in part, by positron emission are suitable for use in PET (positron emission tomography) techniques (e.g., as described herein). Such isotopes are known in the art, and include, for example, carbon-11 (C-11), nitrogen-13 (N-13), oxygen-15 (O-15), fluorine-18 (F-18), gallium-68 (Ga-68) bromine-76 (Br-76), rubidium-82 (Rb-82), iodine-124 (I-124) and iodine-131 (I-131). C-11, N-13, O-15, F-18, Rb-82 and I-124 are examples of isotopes commonly used for PET.’
For these reasons, there is no inventive concept. The claim is not patent eligible. Even when viewed as a whole, nothing in the claim adds significantly more to the abstract idea.
Dependent Claims
The following dependent claims merely further define the abstract idea and are, therefore, recite an abstract idea for similar reasons:
Defining wherein the method of the imaging processing is based on artificial intelligence (Al), deep learning, machine learning, artificial neural network and/or combinations thereof-(claim 4) directed to the abstract idea of mathematical concepts.
defining the wherein the iterative OESM reconstruction method is based on a time-of-flight (TOF) model –(claim 5) directed to the abstract idea of mathematical concepts.
defining wherein the TOF model includes five subsets, four iterations, and a 128 matrix size with 4x4x3 mm voxels – (claim 6) directed to the abstract idea of mathematical concepts.
defining wherein the TOF model includes 6 mm gaussian post-filtering – (claim 7) directed to the abstract idea of mathematical concepts.
Defining wherein the dose is based on the exponential squared function of the subject weight – (claim 10) directed to the abstract idea of mathematical concepts.
Defining wherein the method of imaging processing is used to measure a visual image quality scoring (IQS) in a region of interest of the subject – (claim 18) directed to the abstract idea of mathematical concepts.
The following dependent claims merely further describe the extra-solution activities and therefore, do not amount to significantly more than the judicial exception or integrate the abstract idea into a practical application for similar reasons:
describing wherein the body habitus comprises body weight, body height body surface area, lean body mass, body mass index, and thoracic or abdominal circumference or combinations thereof-(claim 2) The data gathering steps and pre-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
describing wherein the Rubidium-82 is administered via an automated generation and infusion system – (claim 8) The data gathering steps and pre-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
describing wherein the Rubidium-82 is ghenerated from an automated radioisotope generation and infusion system comprising a Rubidium-82 elution system. – (claim 9). The data gathering steps and pre-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
Describing wherein an image quality is observed in a dose range of 1 megabecquerel (MBq) to 10,000 MBq and wherein the subject weight is in a range of from 1 kilogram (kg) to 300 kg – (claim 12) The data gathering steps and pre-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
describing wherein the method further comprises administering a stress agent to the subject and wherein the stress agent is selected from a group consisting of adenosine, adenosine triphosphate, regadenoson, dobutamine, dipyridamole, exercise and/or combinations thereof. – (claim 13) The data gathering steps and pre-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
Describing wherein the quality of the positron emission tomography images is independent of a variation in body habitus between subjects – (claim 15) The data gathering steps and post-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
Describing wherein the consistency of the image quality is measured by a coefficient of a variation of a signal to noise ratio and/or contrast to noise ratio measured over a subject habitus in a range of 10 kilograms (kg) to 200 kg for exponential squared weight based dosing and linear weight based dosing – (claim 16). The data gathering steps and post-solution activity are conventional and recited at high level of generality. As such, the abstract idea is not applied, relied on, or used in a meaningful way. No improved to the technology is evident, and the determined visualization of context is not outputted in any way such that the practical benefit is realized.
Describing wherein the method of the imaging is selected from a group consisting of positron emission tomography imaging (PET), dynamic positron emission tomography imaging (dynamic-PET), single-photon emission computed tomography (SPECT) imaging and/or combinations thereof – (claim 19).
Taken alone and in combination, the additional elements do not integrate the judicial exception into a practical application at least because the abstract idea is not applied, relied on, or used in a meaningful way. They also do not add anything significantly more than the abstract idea. Their collective functions merely provide computer/electronic implementation and processing, and no additional elements beyond those of the abstract idea. Looking at the limitations as an ordered combination adds nothing that is not already present when looking at the elements individually. There is no indication that the combination of elements improves the functioning of a computer, output device, improves technology other than the technical field of the claimed invention, etc. Therefore, the claims are rejected as being directed to non-statutory subject matter.
Examiner Notes
The formula “the exponential function based dosing is calculated by activity = 0.1 x weight2 ”, is by definition a quadratic formula (i.e., power function or power law), not an exponential function or a exponential squared function. In this formula, the variable weight is the base and the exponent is a fixed number (2). An exponential function is the opposite: the variable appears in the exponent, such as 2weight. Therefore, this formula represents a squared relation, not exponential growth. A person of ordinary skill in mathematics would not characterize the expressed formula as an “exponential function” or an “exponential squared function”. In other words, its “administered as a squared function of weight (A = ε × Weight2)”. For examination purposes, the Examiner interprets this formula as an optimized formula characterized by a squared function as known in the art. The phrase associated with the formula is therefore mathematically counterintuitive.
Moreover, Claim 20, though rejected under 35 U.S.C § 101 and 35 USC § 112(a) are not rejected under the prior arts. The claims are statutorily ineligible for indication of allowable subject matter. Note; a change in scope in view of the requested corrections will require further search and consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 20 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 20 recites: “wherein the method of the imaging of the subject is an iterative ordered-subset expectation maximization (OSEM) reconstruction method in order to exhibit qualitative visual image quality scoring (IQS) and quantitative contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as an exponential function of body weight.”
The claim is rejected under 35 USC § 112(a) for a lack of written description. Proper written description cannot be identified in the specification, claims, and drawings directed the full scope of the steps defining exponential function of body weight with respect to OSEM to exhibit IQS | CNR | SNR. Specifically, the specification lacks a step-by-step description or any algorithmic or flowchart-based disclosure of how these steps are implemented using a computing device. Indeed, the specification provides the formula: “SNRTarget =✓At×k×Weightβ (1)” and FIGs 4A-4B, 11, 15-17 also provide formulas. However, these formulas are not an “exponential function” or “an exponential squared function”. In other words, the specification and drawings, do not provide (i.e., proper formula/algorithmic formula) for this to be “exponential function of body weight”. The only attempt for support for this exponential function of body weight is mathematical formula (1), ¶0142, which does not suggest: IQS|CNR|SNR= 𝛼 x Weightβ. Even if the specification did support IQS|CNR|SNR= 𝛼 x Weightβ , this formula and the formulas in FIGs 4A-4B, 11, 15-17 and the mathematical formula (1), ¶0142, are labeled as Exponential, but in mathematical terms these are by definition power functions rather than exponential functions. At best, there is “a function [emphasis added] of body weight”. This functional form (Y = A x XB) is defined mathematically as a power function or power law.
An algorithm is defined, for example, as "a finite sequence of steps for solving a logical or mathematical problem or performing a task." Microsoft Computer Dictionary (5th ed., 2002). Applicant may "express that algorithm in any understandable terms including as a mathematical formula, in prose, or as a flow chart, or in any other manner that provides sufficient structure." Finisar Corp. v. DirecTV Grp., Inc., 523 F.3d 1323, 1340 (Fed. Cir. 2008) (internal citation omitted). This can occur when the algorithm or steps/procedure for performing the computer function are not explained at all or are not explained in sufficient detail (simply restating the function recited in the claim is not necessarily sufficient). In other words, the algorithm or steps/procedure taken to perform the function must be described with sufficient detail so that one of ordinary skill in the art would understand how the inventor intended the function to be performed. It is not enough that one skilled in the art could write a program to achieve the claimed function because the specification must explain how the inventor intends to achieve the claimed function to satisfy the written description requirement. See, e.g., Vasudevan Software, Inc. v. MicroStrategy, Inc., 782 F.3d 671, 681-683, 114 USPQ2d 1349, 1356, 1357 (Fed. Cir. 2015), see MPEP § 2161(I).
Consequently, one of ordinary skill in the art would not deem the instant specification having sufficient detail so that they could understand how the inventor intended to achieve the aforementioned recitation. Since the instant specification fails to provide a finite sequence of steps for performing steps c-g, the aforementioned claim fails to meet the written description requirement under 35 U.S.C. 112(a).
Dependent claims are rejected by virtue of their dependency to abovementioned claims.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9-10, 12, 14-16, & 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claim 9:
the phrase, “automated radioisotope generation and infusion system” renders the claim indefinite. The antecedent claim 8 refers to “an automated generation and infusion system”, as such it is unclear if the phrase refers to the automated generation and infusion system or a different system(s). The phrase is interpreted as “the automated generation and infusion system”. For examination purposes, the Examiner assumes the are the same. Consistent claim language is required when referring to the same term. Accordingly, proper ordinal numbering and/or antecedent basis is required.
Claim 10:
the phrase, “the subject weight” lacks antecedent basis. The phrase is interpreted as “a weight of the subject”. Accordingly, proper ordinal numbering and/or antecedent basis is required.
Claim 12:
the phrase, “the subjects weight” lacks antecedent basis. Accordingly, proper ordinal numbering and/or antecedent basis is required.
Claim 14:
line 4, “taking positron emission tomography images of the subject”. it is unclear if taking positron emission tomography images of the subject refers to the previous recitation of obtaining Rubidium-82 positron emission tomography images. It is further unclear what the difference is between obtaining and taking images. For examination purposes, the Examiner assumes they are the same images and not a subsequent step of taking additional images. Consistent claim language is required when referring to the same term. Appropriate correction is required.
Claim 15:
line 1-2, “of the positron emission tomograph images”. It is unclear if the recitation of positron emission tomograph images refers to the obtained PET images or the taken PET images as recited in claim 14. For examination purposes, the Examiner assumes they are the same. Consistent claim language is required when referring to the same term. Appropriate correction is required.
Claim 16:
line 3-4, “contrast to noise ratio measured over a subject habitus in a range of 10 kilograms (kg) to 200 kg for exponential squared weight based dosing and linear weight based dosing”, renders the claim indefinite. Specifically, it is unclear if a subject habitus refers to or is separate from the body habitus recited in claim 14. For examination purposes, the Examiner assumes they are the same. Consistent claim language is required when referring to the same term. Furthermore, it is unclear if the exponential squared weight refers to “weight2 ” recited in claim 14 or some other weight referring to a different formula. For examination purposes, the Examiner assumes they are the same. Appropriate correction is required.
Claim 20:
lines 11-14, “as an exponential function of body weight”. Its unclear if the Applicant’s intended scope is directed to a different mathematical equation than the exponential squared function. The claim consistently interchanges from exponential squared function to then the exponential function and then to an exponential function. This inconsistency leads to ambiguity regarding the scope of the claim. The specification provides no support (i.e., proper formula/algorithmic formula) for this to be “exponential function of body weight”. The only attempt for support for this exponential function of body weight is mathematical formula (1), ¶0142, which does not suggest: IQS|CNR|SNR= 𝛼 x Weightβ. Even if the specification did support IQS|CNR|SNR= 𝛼 x Weightβ , this formula and the formulas in FIGs 4A-4B, 11, 15-17 and the mathematical formula (1), ¶0142, are labeled as Exponential, but in mathematical terms these are by definition power functions rather than exponential functions.. This functional form (Y = A x XB) is defined mathematically as a power function or power law. For examination purposes, the Examiner assumes it another exponential function different from the exponential squared function. Appropriate correction is required.
The dependent claims of the above rejected claims are rejected due to their dependency.
Claim Objections
The followings claims are objected to because of the following informalities:
Claim 1:
line 6, “the exponential squared function
line 8, “the exponential squared function”.
lines 10-11, “wherein the method of the imaging processing used for [[of]] the subject employs
Claim 6:
line 3, “4 x 4 x 3 mm3 ”. The matrix does not have voxels 4 x 4 x 3 mm. The matrix has 4 x 4 x 3 mm3.
Claim 9: line 2, “generated”.
Claim 12: line 3, “a range of [[from]] kilogram”.
Claim 14:
line 4, “the Rubidium-82”.
line 6, “the Rubidium-82”.
Claim 15: “the consistency of the image quality of the positron emission tomograph images ”.
Claim 18: line 2: “the imaging processing.
Claim 20:
line 5, “the Rubidium-82”.
line 6, “the Rubidium-82”.
line 7, “the Rubidium-82”.
line 10, ““the exponential squared function”.
line, 12, “wherein”.
line 12, ““the exponential squared function”
lines 14-15: “wherein the method of the imaging used for employs
Consistent claim language is required when referring to the same term. Proper spelling and grammar is needed. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 5, 10, 12-14, 16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Sampson et al (“Diagnostic Accuracy of Rubidium-82 Myocardial Perfusion Imaging With Hybrid Positron Emission Tomography/Computed Tomography in the Detection of Coronary Artery Disease. JACC. 2007 Mar, 49 (10) 1052–1058”) in view of de Groot et al (Optimized dose regimen for whole-body FDG-PET imaging. EJNMMI Res 3, 63 (2013)) in view of Koopman et al (Technical note: how to determine the FDG activity for tumour PET imaging that satisfies European guidelines. EJNMMI Phys. 2016 Dec;3(1):22. doi: 10.1186/s40658-016-0158-z. Epub 2016 Sep 29).
Claim 1: Sampson discloses, A method of imaging processing for diagnosing and/or identifying a risk of developing a coronary artery disease (Title: ‘Diagnostic Accuracy of Rubidium-82 Myocardial Perfusion Imaging With Hybrid Positron Emission Tomography/Computed Tomography in the Detection of Coronary Artery Disease”) comprising administering a dose of Rubidium-82 to a subject, ([Methods/pg. 1052], ‘We evaluated 64 consecutive patients with suspected CAD undergoing rest-stress rubidium-82 cardiac PET-CT (CT was only used for attenuation correction)’; [Introduction/pg1/right col], ‘we sought to determine the diagnostic accuracy of rubidium-82 myocardial perfusion imaging for detecting obstructive CAD in subjects referred for diagnosis of chest pain or nonclassic symptoms with multiple risk factors using an integrated PET-CT system’)
wherein the dose is calculated ([page 1053/Methods/left col], ‘The patients were then injected with 40 to 60 mCi of rubidium-82 at rest, and after a 90- to 120-s delay (to allow for adequate blood pool clearance), gated emission images were obtained for 5 min. Immediately after rest imaging, patients underwent pharmacologic stress testing using standard infusions of dipyridamole (0.14 mg/kg/min for 4 min, n = 40), adenosine (0.14 mg/kg/min for 6 min, n = 20), or dobutamine (10 μg/kg/min increments to a maximum of 40 μg/kg/min or until achieving 85% of maximum predictive heart rate, n = 4). At peak stress, a second dose of 40 to 60 mCi of rubidium-82 was administered and emission images were acquired as previously described.)
wherein the method of the imaging processing of the subject is an iterative ordered- subset expectation maximization (OSEM) reconstruction method. ([Methods/pg.1053/left col], ‘The gated PET images were reconstructed using an ordered subset expectation maximization algorithm (2 iterations, 30 subsets)’)
Sampson fails to disclose: the does is calculated based on an exponential squared function of body habitus of the subject; wherein the exponential function based dosing is calculated by activity = 0.023 x weight2.047; wherein the exponential function based dosing provides a consistent signal to noise ratio
However, de Groot in the context of optimal dose regimen in PET imaging discloses, wherein the dose is calculated based on an exponential squared function of body habitus of the subject; wherein the exponential function based dosing is calculated by activity = 0.023 x weight2.047 (i.e., using the formula -> activity = c/t x weight2); wherein the exponential function based dosing provides a consistent signal to noise ratio ([page 1/Abstract/Results], ‘As expected, both PET systems showed a significant decrease in SNR with increasing patient’s body mass when using a linear dosage. When image quality was fitted to the patient-dependent parameters, the fit with the patient’s body mass had the highest R2. The optimized dose regimen was found to be A new = c/t × m2, where m is the body mass, t is the acquisition time per bed position and c is a constant (depending on scanner type). Using this relation, SNR no longer varied with the patient’s body mass. This quadratic relation between dose and body mass was confirmed by the simulation study.’).
More specifically, de Groot calculation results was simplified to:
A = 0.023 * m2.047 MBq, pg 6.
Further teaching:
The squared function “2.047”, the optimal relation is mathematically the equivalent value of 2.
“c is a constant” which is dependent on scanner type (i.e., can vary), [page 1/Abstract/Results].
“t” – “Therefore, the acquisition time per bed position can, in principle, be varied without influencing the image quality, as long as the administered FDG dose is changed accordingly.”, [Discussion, pg. 9]
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the method of dosing of Sampson to be based on an exponential squared function of body habitus of the subject; wherein the exponential function based dosing is calculated by activity = 0.023 x weight2.047; wherein the exponential function based dosing provides a consistent signal to noise ratio in view of the teachings of de Groot for the advantage of achieving a more uniform noise level as a function of patient body mass, as suggested by de Groot [pg. 10/right col/Discussion].
Sampson in view of de Groot fail to disclose 0.1 (i.e., activity = 0.1 x weight2), as required by the claim. Note; The constant c/t or (c) just depends on the scanner type and acquisition time, which can merely be modified to achieve similar results (i.e. 0.1). The value of 0.1 is just k/t or c/t, [MBq / kg2], tuned to hit the desired result (the studies specific conductions to achieve a goal) for the population used in the experiment.
Therefore, it would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the exponential squared function of modified Sampson to be an calculated based on an exponential squared function of activity by 0.1 x weight2 in view of the teachings of de Groot, because the value of 0.1 is a selected value corresponding to the scanner type i.e., the value for “c” and “t” (time) can merely be varied. Since the body weight, time and scanner type varies by subjects and experiment, the value of 0.1 would be varied accordingly; hence, this is not a fixed value. Its only a study specific value to achieve a desired goal for the population used. The value of 0.1 in view of Sampson in view of de Groot is therefore considered a mere variance. One of ordinary skill in the art would be able to obtain the value of 0.1 through routine experimentation with reasonable expectation of success for the advantage of adequate image quality in all patients, thus making image quality independent of patient physical characteristics.
Sampson in view of de Groot fail to disclose: wherein the exponential function based dosing provides a consistent contrast to noise ratio;
However, Koopman in the context of consistent PET image quality based dosing calculated by an optimized formula characterized by a squared function, discloses, wherein the exponential function based dosing provides a consistent contrast to noise ratio; ([¶Abstract [results] pg.1], ‘Finally, the FDG activity (in MBq) to administer can be described by 𝐴 =c ⋅w 2⋅ Tmin/T with c a constant that is typically 0.0533 (MBq/kg2), w the patient’s body weight (in kg), and t the scan time per bed position that is chosen in a clinical setting (in seconds).’;
-The methodology of Koopman provides the formula for administered dosage activity that delivers a constant image quality across patients in several weight categorizes, achieved by the activity, time, and quadratically on the patients body weight, ¶Abstract & [Discussion pg. 8] - ‘The FDG activity formula presented in this paper provides a constant and standardized PET image quality for all patients’. Contrast to noise ratio (CNR) is defined as the contrast related to RC (recovery coefficient (i.e., image accuracy)) divided by the noise related to COV. Since Koopman standardizes both the noise level by limiting COV and the quantification contrast recovery, the derived function dosing achieves a consistent CNR across varying patient weights. Therefore, by standardizing noise (COV) and the quantification accuracy (RC), the method of Koopman ensures that the image quality and thus CNR is maintained regardless of the patient’s body weight, ¶Abstract, [¶Discussion, pg 8] - “The FDG activity formula presented in this paper provides a constant and standardized PET image quality for all patients [7]-[de Groot et al]. Changing the value of COVmax will impact image quality and quantification accuracy. Ideally, its value should be chosen in such way that it provides the highest diagnostic accuracy. Note, however, that according to [10], COVmax should remain below 15 %, to keep image quality and quantification accuracy within acceptable limits.”).
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the exponential function of modified Sampson in view of Groot based dosing in view of the teachings of Koopman to provide consistent contrast to noise ratio for the advantage of providing an improved methodology for impacting image quality and quantification accuracy as suggested by Koopman, [¶Discussion, pg 8].
Claim 2: Sampson as modified discloses all the elements above in claim 1, Sampson fails to disclose: wherein the body habitus comprises body weight, body height body surface area, lean body mass, body mass index, and thoracic or abdominal circumference or combinations thereof.
However, de Groot is relied upon above disclose: wherein the body habitus comprises body weight, body height body surface area, lean body mass ([page 1/Abstract/Results], ‘As expected, both PET systems showed a significant decrease in SNR with increasing patient’s body mass when using a linear dosage. When image quality was fitted to the patient-dependent parameters, the fit with the patient’s body mass had the highest R2. The optimized dose regimen was found to be A new = c/t × m2, where m is the body mass, t is the acquisition time per bed position and c is a constant (depending on scanner type). Using this relation, SNR no longer varied with the patient’s body mass. This quadratic relation between dose and body mass was confirmed by the simulation study.’), body mass index ([pg. 1/Background], ‘. Thus, a different relationship between dose and body mass or a different patient-dependent parameter, e.g. body mass index (BMI) or lean mass, might be required to obtain an even more constant image quality’), and thoracic or abdominal circumference or combinations thereof.
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the body habitus of modified Sampson to comprise body mass or body mass index in view of the teachings of de Groot for the advantage of achieving a more uniform noise level as a function of patient body mass, as suggested by de Groot [pg. 10/right col/Discussion].
Claim 3: Sampson as modified discloses all the elements above in claim 1, Sampson fails to disclose, wherein the dose can be further adjusted based on additional parameters selected from a group of parameters consisting of left ventricle ejection fraction, infusion time, infusion rate, imaging scanner sensitivity, type of radionuclide, imaging scanner/camera resolution and radionuclide generator age, generator yield or combinations thereof.
However, de Groot is relied upon above disclose: wherein the dose ([page 1/Abstract/Results], ‘As expected, both PET systems showed a significant decrease in SNR with increasing patient’s body mass when using a linear dosage. When image quality was fitted to the patient-dependent parameters, the fit with the patient’s body mass had the highest R2. The optimized dose regimen was found to be A new = c/t × m2, where m is the body mass, t is the acquisition time per bed position and c is a constant (depending on scanner type). Using this relation, SNR no longer varied with the patient’s body mass. This quadratic relation between dose and body mass was confirmed by the simulation study.’) can be further adjusted based on additional parameters selected from a group of parameters consisting of left ventricle ejection fraction, infusion time, infusion rate, imaging scanner sensitivity, type of radionuclide, imaging scanner/camera resolution ([pg 2-3], ‘The value of the constant… equals an acceptable SNRL (SNRacc), which is the value of the SNRL corresponding to the highest body mass for which the image quality is still acceptable.’) and radionuclide generator age, generator yield or combinations thereof.
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the dose of modified Sampson to be further adjusted based on parameters selected from imaging scanner/camera resolution in view of the teachings of de Groot for the advantage of achieving a more uniform noise level as a function of patient body mass, as suggested by de Groot [pg. 10/right col/Discussion].
Claim 5: Sampson as modified discloses all the elements above in claim 1, Sampson discloses, wherein the iterative (OSEM) reconstruction method ([Methods/pg.1053/left col], ‘The gated PET images were reconstructed using an ordered subset