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 .
Claim Status
Claims 1-20 are pending and under examination.
Claim 15 is objected to.
Claims 1-20 are rejected.
Claims 1 and 6 are independent.
No claims are allowed, amended, canceled, new, or withdrawn.
Office Action Outline
Rejections applied
Abbreviations
x
112/b Indefiniteness
PHOSITA
"a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention"
112/b "Means for"
BRI
Broadest Reasonable Interpretation
112/a Enablement,
Written description
CRM
"Computer-Readable Media" and equivalent language
112 Other
IDS
Information Disclosure Statement
x
102, 103
JE
Judicial Exception
x
101 JE(s)
112/a
35 USC 112(a) and similarly for 112/b, etc.
101 Other
N:N
page:line
x
Double Patenting
MM/DD/YYYY
date format
Priority
As detailed in the 08/25/2023 filing receipt, this application is a continuation-in-part (CIP) of 16/327,875 (Patent no. 11631502), filed 02/25/2019; which is a 371 of PCT/ES16/70609, filed 08/24/2016.
Claims 1-20 are being examined with an effective filing date of 04/17/2023, the filing date of the instant invention, because these claims recite limitations which are not supported by the disclosures of Application 16/327,875 and PCT/ES16/70609.
The claims at least recite the following limitations not clearly supported by the priority document (emphasis added to stress unsupported elements):
• "...wherein at least one of the reaction-diffusion equations is an equation representing dynamics of tumor cell density field N(x,t) ...and wherein a value N(x,t) of the tumor cell density field N represents a number of tumor cells per unit volume of tissue at position x and time t". (Recited in independent claim 1.)
• "at least one equation of mechanical equilibrium in the prostate gland." (Recited in independent claim 6.)
• "at least one equation for a mechanotransductive function that adjusts mobility and net proliferation in the evolution of the tumor." (Recited in independent claim 6.)
• "the reaction-diffusion equations include at least one equation representing the dynamics of the tumor cell density field for each tumor present in the prostate gland." (Recited in claim 2.)
• "wherein the tumor cell density field is initialized from apparent diffusion coefficient (ADC) maps obtained by diffusion-weighted magnetic resonance imaging (DW-MRI), and wherein the patient-specific parameters governing the equation describing the dynamics of the tumor cell density field are obtained by solving an inverse problem using one or more ADC maps.." (Recited in claim 3.)
• "determining an existence, risk, and/or probability of extracapsular extension." (Recited in claim 5.)
• "an equation representing dynamics of tumor cell density field N(x,t), wherein a value N(x,t) of the tumor cell density field N represents a number of tumor cells per unit volume of tissue at position x and time t." (Recited in claim 7.)
• "equation of mechanical equilibrium is implemented to account for the mechanical deformation of the prostate gland during the evolution of the tumor." (Recited in claim 8.)
• "the mechanical deformation of the prostate gland is due to coexisting prostate cancer and benign prostatic hyperplasia.." (Recited in claim 9.)
• "the equation for the mechanotransductive function.." (Recited in claims 10 and 11.)
• "one equation of mechanical equilibrium includes..." (Recited in claims 12 and 13.)
• "assessing effects of the 5-alpha reductase inhibitor..." (Recited in each of claims 14-17.)
• "developing a therapeutic plan for treatment of the subject using a 5-alpha reductase inhibitor based on the tumor growth model." (Recited in claim 18.)
• "planning the treatment of benign prostatic hyperplasia." (Recited in claim 19.)
• "assessing progression of benign prostatic hyperplasia." (Recited in claim 20.)
Drawings
The drawings submitted 04/17/2023 are objected to because Figures 1B, 1C, 1D, 3, and 4 are color drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
In claim 1, after "...include: simulating...," the single list of four "wherein" clauses recites two conjunctions, when only one is necessary and proper. Also, readability would be improved by indenting and placing each "wherein" clause on its own new line (MPEP 608.01(m) Form of Claims pertains). It is more useful to indent the list of "wherein" clauses than to indent "simulating," since "simulating" is singular and not part of a list.
In claim 6, after "simulating...," an "and" is needed between the two "wherein" clauses.
Claim 15 is objected to because of the following informalities: Claim 15 recites a grammatical error in "whether the tumor or the serum PSA exhibit faster dynamics," which should be corrected to "whether the tumor or the serum PSA exhibits faster dynamics." The verb should agree with the second half of the "or" expression. Appropriate correction is required.
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 1-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim 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. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate.
The following recitations require but lack clear antecedent. If these recitations refer to previously instantiated instances, then it is not clear which instances those are. If these recitations instantiate the claim elements, this is not clear.
• "the possible progression of prostate cancer" (claim 1)
• "the value s(x,t) " (claim 1)
• "the patient-specific parameters" (claim 3)
• "the tissue PSA field p" (claim 4)
• "the Gleason score" (claim 5)
• "the possible progression" (claim 6)
• "the dynamics of the tumor;" (claim 6)
• "the mechanical deformation" (claim 8)
• "the serum PSA" (claim 15)
• "the treatment of prostate cancer" (claims 19 and 20)
• "the treatment of benign prostatic hyperplasia" (claims 19 and 20)
Thes rejections might be overcome by for example amending "the" to "a" or by simply deleting "the" from the limitation lacking clear antecedent.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 details the following framework to analyze Subject Matter Eligibility:
• Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? (see MPEP § 2106.03)
• Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. an abstract idea, a law of nature, or a natural phenomenon? (see MPEP § 2106.04(a), 2106.04(a)(2) & 2106.04(b)).
• Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application? (see MPEP § 2106.04(d))
• Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? (see MPEP § 2106.05)
Step 1:
Claims 1-5 are directed to a 101 process, here a method. Claims 6-20 are also directed to a 101 process, here a method. As such, claims 1-20 are directed to methods, which fall under a category of statutory subject matter. (See MPEP § 2106.03). (Step 1: Yes.)
Step 2A, Prong One:
The claims are found to recite judicial exceptions (JEs) of abstract ideas in the form of mental processes and mathematical concepts as follows:
Independent claim 1 recites mental processes and mathematical concepts of:
• performing operations to generate a tumor growth model for a prostate gland of the subject
• simulating evolution of a tumor in the prostate gland based a coupled
system of reaction-diffusion equations and a patient-specific geometric
model of the prostate gland
• one of the reaction-diffusion equations is an equation representing dynamics of
tumor cell density field N(x,t) or an equation representing dynamics of a
nutrient field "s"
Claim 3 recites mental processes and mathematical concepts of initializing the tumor cell density field from apparent diffusion coefficient (ADC) maps, and solving an inverse problem using the ADC maps.
Claim 5 recites mental processes and mathematical concepts of determining prostate cancer progression; extracapsular extension; a personalized monitoring plan; the Gleason score; a spatial map of the Gleason score; a decision to prescribe treatment; and/or planning biopsies and design optimal treatment.
Independent claim 6 recites mental processes and mathematical concepts of:
• performing operations to generate a tumor growth model for a prostate gland of the subject
• simulating evolution of a tumor in the prostate gland based a coupled
system of reaction-diffusion equations and a patient-specific geometric
model of the prostate gland
• the reaction-diffusion equations include an equation representing the dynamics of the tumor, the dynamics of tissue prostate specific antigen (PSA), the mechanical equilibrium, and the mechanotransductive function.
Claim 14 recites a mental process of assessing effects of a 5-alpha reductase inhibitor.
Claim 18 recites a mental process of developing a therapeutic plan for treatment of the subject using a 5-alpha reductase inhibitor based on the tumor growth model.
Claim 19 recites mental processes of implementing model simulations to determine a personalized monitoring plan, to plan treatment of prostate cancer or benign prostatic hyperplasia, and/or to plan prostate biopsies.
Claim 20 recites mental processes and mathematical concepts of performing longitudinal, non-rigid registration of imaging data of the prostate of the subject based on the tumor growth model, which with personalized model simulations are used in assessing disease progression, determining personalized treatment plans, planning treatments and biopsies, and/or detecting undiagnosed prostate cancer.
Claims that further limit the abstract ideas of base claims:
Claims 2, 4, 7-8, and 10-13 further limit the abstract ideas of base claims by further limiting the equations.
Claim 9 further limits the mechanical deformation of the prostate.
Claims 15-17 further limit assessing effects of a 5-alpha reductase inhibitor.
Step 2A Prong One Summary: The claims recite mental processes and mathematical concepts. When considering the broadest reasonable interpretation (BRI) of the claims, the mental processes recited in independent claim 1 and 6 (e.g., "performing operations to generate a tumor growth model," "simulating evolution of a tumor in the prostate gland based a coupled system of reaction-diffusion equations," etc.) are directed to processes that may be performed in the human mind, or with pen and paper, as there are no particular limitations in claims 1 and 6 which would prevent the steps from being performed in the human mind or with pen and paper. The claims recite mathematical processes in e.g., basing simulation on reaction-diffusion equations, solving inverse problems, etc.; the equations themselves are disclosed in the Specification, pp. 13-14, 16, 41-42, 45, etc. Such analysis performed mentally, or with paper and pencil, may take considerable time and effort, and although a general-purpose computer can perform these calculations at a rate and accuracy that can far exceed the mental performance of a skilled artisan, the nature of the activity is essentially the same, and therefore constitutes an abstract idea. Therefore, the claims recite elements that constitute a judicial exception in the form of an abstract ideas. (Step 2A, Prong One: Yes.)
Step 2A, Prong Two:
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs). Here at Step 2A, Prong Two, any remaining steps and/or elements not identified as JEs are therefore in addition to the identified JE(s), and are considered additional elements. Because the claims have been interpreted as being directed to judicial exceptions (abstract ideas in this instance) then Step 2A, Prong Two provides that the claims be examined further to determine whether the judicial exception is integrated into a practical application [see MPEP § 2106.04(d)]. A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
MPEP § 2106.04(d)(I) lists the following five example considerations for evaluating whether a judicial exception is integrated into a practical application:
(1) An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a).
(2) Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2).
(3) Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
(4) Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c).
(5) Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
The claims recite additional elements as follows:
Additional elements of data gathering, inputting, and/or outputting steps are recited in: obtaining ADC maps by DW-MRI (claim 3); collecting serum PSA values (claim 4). Data gathering steps are additional elements which perform functions of inputting, collecting, and outputting the data needed to carry out the abstract idea. These steps are considered insignificant extra-solution activity, and are not sufficient to integrate an abstract idea into a practical application as they do not impose any meaningful limitation on the abstract idea or how it is performed, nor do they provide an improvement to technology (see MPEP § 2106.04(d)(I)).
Additional elements of computers are recited in: a computer system (claims 1 and 6). The claims require only a generic computer, which does not improve computer technology, and does not integrate the recited judicial exception into a practical application (see MPEP § 2106.04(d)(1) and MPEP § 2106.05(f)).
Step 2A Prong Two summary: The claims have been further analyzed with respect to Step 2A, Prong Two, and no additional elements have been found, alone or in combination, that would integrate the judicial exception into a practical application. At this point in examination, it is not yet the case that any of the Step 2A Prong Two considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of: (1) an improvement, (2) a treatment, (3) a particular machine, or (4) a transformation is clear in the record. For example, regarding the first consideration for improvement at MPEP 2106.04(d)(1), the record, including the Specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field, and the claims do not yet clearly result in such an improvement. (Step 2A, Prong Two: No).
Step 2B:
Because the additional claim elements do not integrate the abstract idea into a practical application, the claims are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept. An inventive concept is furnished by an element or combination of elements that is recited in the claim in addition to the judicial exception, and is sufficient to ensure that the claim, as a whole, amounts to significantly more than the judicial exception itself (see MPEP § 2106.05).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are well-understood, routine, and conventional. Those additional elements are as follows:
Additional elements of data gathering, inputting, and/or outputting steps: The additional elements of obtaining ADC maps by DW-MRI (claim 3), and collecting serum PSA values (claim 4), do not cause the claims to rise to the level of significantly more than the judicial exception. The courts have recognized receiving or transmitting data over a network; storing and retrieving information in memory; and determining the level of a biomarker in blood by any means, [see MPEP§2106.05(d)(II)], as well-understood, routine, conventional activity when they are claimed in a merely generic manner (e.g., at a high level of generality) or as extra-solution activity.
Additionally, the data gathering by obtaining ADC maps by DW-MRI is shown to be conventional by the following reference(s):
Turkbey (Current opinion in urology, vol. 22(4), p.310-315 (2012); cited on the attached form PTO-892) presents a review on multiparametric MRI in prostate cancer diagnosis and risk stratification. Turkbey shows ADC values derived from DW-MRI (p.311-314) and serum PSA (p.312-314).
All limitations of claims 1-20 have been analyzed with respect to Step 2B, and none provides a specific inventive concept, as they all fail to rise to the level of significantly more than the identified judicial exception, and thus do not transform the judicial exception into a patent eligible application of the exceptions. Step2B: NO.
Therefore, the claims, when the limitations are considered individually and as a whole, are rejected under 35 U.S.C. § 101 as being directed to non patent-eligible subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Note: The two Lorenzo references used in the 103 rejections below are referred to as Lorenzo-2020 and Lorenzo-2019 to distinguish the references and avoid confusion. (Full citations are included below.)
Bold emphasis throughout the rejection below has been added by the examiner.
103-1 (of 4):
Claims 1-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Lorenzo-2020 (Computer Methods in Applied Mechanics and Engineering, vol. 362:112843, p.1-21 (2020); cited on the 12/13/2024 IDS), in view of Jarrett (Physics in Medicine & Biology, vol. 63(10):105015, p.1-16 (2018); cited on the attached form PTO-892).
Regarding claim 1, the recited performing operations on a computer to generate a tumor growth model for a prostate gland of the subject reads on "a simulation study based on our mechanically-coupled model of prostate cancer (PCa) growth." (Lorenzo-2020, p.3, ¶ 3.)
Regarding claim 1, the recited performing operations to generate a tumor growth model for a prostate gland of the subject reads on "a simulation study based on our mechanically-coupled model of prostate cancer (PCa) growth." (Lorenzo-2020, p.3, ¶ 3.)
Regarding claim 1, the recited simulating evolution of a tumor in the prostate gland based on a coupled system of reaction-diffusion equations and a patient-specific geometric model of the prostate gland reads on "we use the phase-field method to describe the coupled evolution of healthy and cancerous tissue," "the generic nutrient s follows the reaction–diffusion dynamics described in Eq. (2)," (Lorenzo-2020, p.4, ¶ 3); "the use of a patient-specific geometric model of the tumor and harboring organ contributes to accurately predict tumor growth," (Lorenzo-2020, p.3, ¶ 3).
Regarding claim 1, the recited reaction-diffusion equation including dynamics of a nutrient field reads on "...the generic nutrient s follows the reaction–diffusion dynamics described in Eq. (2), where the reactive terms respectively represent nutrient supply, nutrient consumption by the tumor, and a natural decay" (Lorenzo-2020, p.4, ¶ 3).
Regarding claim 5, the recited tumor growth models are implemented to determine prostate cancer progression; extracapsular extension; a personalized monitoring plan; the Gleason score; a spatial map of the Gleason score; a decision to prescribe treatment; and/or to being implemented to plan biopsies and design optimal treatment, reads on " The computational technology used in this study can offer a unique approach to monitor patients using 5α-reductase inhibitors (5ARIs)." (Lorenzo-2020, p.17, ¶ 1).
Lorenzo-2020 does not show the recited reaction-diffusion equations is an equation representing dynamics of tumor cell density field N(x,t) of claim 1 (shown by Jarrett).
Lorenzo-2020 does not show the recited reaction-diffusion equations include an equation representing the dynamics of the tumor cell density field for each tumor present in the prostate gland of claim 2 (shown by Jarrett).
Lorenzo-2020 does not show the recited the tumor cell density field is initialized from ADC maps obtained by DW-MR of claim 3 (shown by Jarrett).
Lorenzo-2020 does not show the recited patient-specific parameters being obtained by solving an inverse problem using ADC maps of claim 3 (shown by Jarrett).
Regarding claim 1, the recited one of the reaction-diffusion equations is an equation representing dynamics of tumor cell density field N(x,t)... reads on "Equation (2) describes the spatiotemporal change in voxel tumor cell density due to the combined effects of tumor cell diffusion...and logistic growth..." (Jarrett, p. 4, ¶ 1).
Regarding claim 2, the recited reaction-diffusion equations include an equation representing the dynamics of the tumor cell density field for each tumor present in the prostate gland reads on "Equation (2) describes the spatiotemporal change in voxel tumor cell density." (Jarrett, p. 4, ¶ 1).
Regarding claim 3, the recited the tumor cell density field is initialized from ADC maps obtained by DW-MRI reads on "Tumor cell densities are calculated using the DW-MRI data, where ADC values are converted to the number of tumor cells per voxel within the defined tumor ROI" (Jarrett, p. 6, Fig. 1, panel (f)).
Regarding claim 3, the recited patient-specific parameters being obtained by solving an inverse problem using ADC maps read on "there is abundant literature on the inverse relationship between the measured ADC and tumor cellularity." (Jarrett, p. 13, ¶ 5).
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 method for generating tumor growth models of Lorenzo-2020 to include the tumor cell density field from ADC maps and the tumor cell density equation of Jarrett, because Jarrett shows preliminary results show substantial reductions in the errors of the model, and the total predicted cellularity versus the calculated cellularity improved. One of ordinary skill would have had a reasonable expectation of success in modifying, because although Jarrett is directed to breast cancer, a phosita would have understood how to apply the teaching of Jarrett to the related teachings of Lorenzo-2020, and as such, the combination would have been obvious.
103-2 (of 4):
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Lorenzo-2020 in view of Jarrett as applied to claims 1-3 and 5 above, and further in view of Lorenzo-2019 (Proceedings of the National Academy of Sciences, vol. 116(4), pp.1152-1161; cited on the 12/13/2024 IDS).
While Lorenzo-2020 in view of Jarrett shows reaction diffusion equations as taught above (in 103-1(of 4)), Lorenzo-2020 alone or with Jarrett does not show the recited reaction diffusion equations include an equation representing dynamics of PSA, where the tissue PSA is initialized from serum PSA values of claim 4 (shown by Lorenzo-2019).
While Lorenzo-2020 in view of Jarrett shows reaction diffusion equations as taught above (in 103-1(of 4)), Lorenzo-2020 alone or with Jarrett does not show the recited reaction diffusion equations include an equation representing dynamics of PSA, where the tissue PSA is initialized from serum PSA values of claim 4 (shown by Lorenzo-2019).
Regarding claim 4, the recited reaction diffusion equations include an equation representing dynamics of PSA, where the tissue PSA is initialized from serum PSA values reads on "Eq. 3 describes the reaction–diffusion dynamics of tissue PSA p, defined as the serum PSA concentration leaked to the bloodstream per unit volume of prostatic tissue." (Lorenzo-2019, p.1158, ¶ 3).
Regarding claim 4, the patient-specific parameters are obtained by solving an inverse problem using serum PSA values reads on "Eq. 3 describes the reaction–diffusion dynamics of tissue PSA p, defined as the serum PSA concentration leaked to the bloodstream per unit volume of prostatic tissue." (Lorenzo-2019, p.1158, ¶ 3)
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 method for generating tumor growth models using tumor cell density of Lorenzo-2020 and Jarrett, with the reaction–diffusion dynamics of tissue PSA using serum PSA of Lorenzo-2019. This is because Lorenzo-2020 provides motivation to modify by stating the effects of 5ARIs on PSA dynamics deserves further research, and the computational model used in this study could be extended to include an equation for PSA dynamics. As such, a phosita would have been motivated to apply the teachings of Lorenzo-2019 to the related teachings of Lorenzo-2020 and Jarrett, and as such, the combination would have been obvious.
103-3 (of 4):
Claims 6 and 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lorenzo-2020 (Computer Methods in Applied Mechanics and Engineering, vol. 362:112843, p.1-21 (2020); cited on the 12/13/2024 IDS) in view of Lorenzo-2019 (Proceedings of the National Academy of Sciences, vol. 116(4), pp.1152-1161; cited on the 12/13/2024 IDS).
Regarding claim 6, the recited performing operations to generate a tumor growth model for a prostate gland of the subject reads on "a simulation study based on our mechanically-coupled model of prostate cancer (PCa) growth." (Lorenzo-2020, p.3, ¶ 3.)
Regarding claim 6, the recited simulating evolution of a tumor in the prostate gland based a coupled system of reaction-diffusion equations and a patient-specific geometric model of the prostate gland reads on "We use the phase-field method to describe the coupled evolution of healthy and cancerous tissue," "the generic nutrient s follows the reaction–diffusion dynamics described in Eq. (2)," (Lorenzo-2020, p.4, ¶ 3); "the use of a patient-specific geometric model of the tumor and harboring organ contributes to accurately predict tumor growth," (Lorenzo-2020, p.3, ¶ 3).
Regarding claim 6, the recited the reaction-diffusion equations include equations representing the dynamics of the tumor,...the mechanical equilibrium, and the mechanotransductive function reads on "Eq. (1) governs tumor dynamics" (Lorenzo-2020, p.7 , ¶ 4); "... resolved the quasistatic mechanical equilibrium every two time steps," (Lorenzo-2020, p.7 , ¶ 4); and parameters, tumor dynamics, and mechanotransductive constants 1 and 2 (Lorenzo-2020, p.10, Table 2).
Regarding claim 8, the recited equation of mechanical equilibrium implemented to account for the mechanical deformation of the prostate gland reads on "...we first computed tumor growth by solving Eqs. (16) and (17), and then we updated the displacements by solving Eq. (18). Because the deformation of the prostate in this study was slow overall, we only resolved the quasistatic mechanical equilibrium every two time steps..." (Lorenzo-2020, p.7, ¶ 4).
Regarding claim 9, the recited mechanical deformation of the prostate gland is due to coexisting prostate cancer and benign prostatic hyperplasia reads on "we developed a mechanically-coupled model to describe the growth of localized PCa in a patient’s prostate deformed by the tumor mass effect and BPH.." (Lorenzo-2020, p.4, ¶ 2).
Regarding claim 10, the recited equation for the mechanotransductive function is implemented to account for mechanical stresses on the evolution of the tumor reads on "...we are only interested in obtaining an acceptable estimation of the mechanical stress fields in the prostate to compute the mechanotransductive factor M(σ) and hence adjust tumor dynamics in Eq. (1)." (Lorenzo-2020, p.16, ¶ 4.)
Regarding claim 11, the recited equation for the mechanotransductive function implements at least one scalar metric that summarizes mechanical stress across the prostate gland reads on "The function M (σ) in Eq. (1) models the inhibitory effect of mechanical stress on tumor growth with a coefficient... we define M (σ) with a combination of σv and σh following a similar approach to multiaxial stress-based criteria..." (Lorenzo-2020, p.5, ¶ 1.)
Regarding claim 12, the recited equation of mechanical equilibrium includes a term that represents stresses induced by the evolution of the tumor, wherein the term is a function of a variable representing position of tumor tissue reads on "where σ is the stress tensor,...and x is the position vector." (Lorenzo-2020, p.6, ¶ 3.)
Regarding claim 13, the recited equation of mechanical equilibrium includes a term that represents stresses induced by benign prostatic hyperplasia reads on "the rate of BPH-induced CG volumetric enlargement gBPH," (Lorenzo-2020, p.6, ¶ 3.), and " The function vBPH (t) describes the volumetric deformation induced by BPH." (Lorenzo-2020, p.5, ¶ 5 and Eqn.(9).)
Regarding claim 14, the recited assessing effects of a 5-alpha reductase inhibitor (5ARIs) on the evolution of the tumor reads on "We ran ...simulations in this study, as follows: ...Simulations of tumor growth exclusively under the mechanical effects of 5ARIs." (Lorenzo-2020, bridging p.9-10.)
Regarding claim 15, the recited assessing effects of the 5-alpha reductase inhibitor includes determining whether the tumor...exhibits faster dynamics reads on "we focus on the mechanic and apoptotic effects of these drugs on PCa growth" and "The last two terms in Eq. (1) represent tumor growth driven by a generic nutrient s and apoptosis (i.e. programmed cell death), respectively" (Lorenzo-2020, p.4, ¶ 2- 3.)
Regarding claim 16, the recited assessing effects of the 5-alpha reductase inhibitor includes implementing a factor representing a drug-induced increase in tumor cell death in the equation representing tumor dynamics reads on "we focus on the mechanic and apoptotic effects of these drugs on PCa growth" (these drugs are 5ARIs) and "The last two terms in Eq. (1) represent tumor growth driven by a generic nutrient s and apoptosis (i.e. programmed cell death), respectively" (Lorenzo-2020, p.4, ¶ 2- 3.)
Regarding claim 17, the recited assessing effects of the 5-alpha reductase inhibitor includes implementing a term representing inhibition of benign prostatic hyperplasia and drug induced shrinkage of the prostate gland reads on "we used available data in the literature from two landmark clinical trials of finasteride and dutasteride for the treatment of BPH symptoms" (Lorenzo-2020, p.8, ¶ 6) and "we used an equation like Eq. (11) to describe the empirical 5ARI-induced prostate volume shrinkage." (Lorenzo-2020, p.8, ¶ 7.)
Regarding claim 18, the recited developing a therapeutic plan for treatment of the subject using a 5-alpha reductase inhibitor reads on "The computational technology used in this study can offer a unique approach to monitor patients using 5ARIs." (Lorenzo-2020, p.17, ¶ 1.)
Regarding claim 19, the recited implementing model simulations to determine a personalized monitoring plan, to plan treatment of prostate cancer or benign prostatic hyperplasia, and/or to plan prostate biopsies reads on "The computational technology used in this study can offer a unique approach to monitor patients using 5ARIs." (Lorenzo-2020, p.17, ¶ 1.)
Regarding claim 20, the recited performing longitudinal, non-rigid registration of imaging data of the prostate of the subject based on the tumor growth model, which with personalized model simulations are used in assessing disease progression, determining personalized treatment plans, planning treatments and biopsies, and/or detecting undiagnosed prostate cancer reads on "inverse or machine learning methods could be used to extract personalized parameter values based on each patient’s longitudinal dataset... these simulations would assist physicians to define a personalized monitoring strategy by determining the best time to obtain new medical images and perform clinical tests." (Lorenzo-2020, p.17, ¶ 1.)
Lorenzo-2020 does not show the recited the reaction-diffusion equations include equations representing ...the dynamics of tissue PSA... of claim 6 (shown by Lorenzo-2019).
Lorenzo-2020 does not show the recited assessing effects...includes determining whether...the serum PSA exhibits faster dynamics of claim 15 (shown by Lorenzo-2019).
Regarding claim 6, the recited the reaction-diffusion equations include equations representing ...the dynamics of tissue PSA... reads on "Eq. 3 describes the reaction–diffusion dynamics of tissue PSA p, defined as the serum PSA concentration leaked to the bloodstream per unit volume of prostatic tissue." (Lorenzo-2019, p.1158, col.2, ¶ 3)
Regarding claim 15, the recited assessing effects...includes determining whether...the serum PSA exhibits faster dynamics reads on "Our model also estimates PSA dynamics at tissue level by computing the serum concentrations of this biomarker produced at healthy and cancerous regions per unit volume of prostatic tissue." (Lorenzo-2019, p.1153, col.2, ¶ 1.)
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 method for generating tumor growth models of Lorenzo-2020 to include the tissue PSA dynamics of Lorenzo-2019. This is because Lorenzo-2020 provides motivation to modify by stating the effects of 5ARIs on PSA dynamics deserves further research, and the computational model used in this study could be extended to include an equation for PSA dynamics. As such, a phosita would have been motivated to apply the teachings of Lorenzo-2019 to the related teachings of Lorenzo-2020, and as such, the combination would have been obvious.
103-4 (of 4):
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Lorenzo-2020 in view of Lorenzo-2019 as applied to claims 6 and 8-20 above, and further in view of Jarrett (Physics in Medicine & Biology, vol. 63(10):105015, p.1-16 (2018); cited on the attached form PTO-892).
Regarding claim 7, the recited equation representing the dynamics of the tumor is an equation representing dynamics of an evolution of a tumor phase field...reads on "We use the phase-field method to describe the coupled evolution of healthy and cancerous tissue," (Lorenzo-2020, p.4, ¶ 3).
Lorenzo-2020 alone or with Lorenzo-2019 does not show the recited equation representing the dynamics of the tumor... is an equation representing dynamics of tumor cell density field of claim 7 (shown by Jarrett).
Regarding claim 7, the recited equation representing the dynamics of the tumor... is an equation representing dynamics of tumor cell density field reads on "Equation (2) describes the spatiotemporal change in voxel tumor cell density due to the combined effects of tumor cell diffusion...and logistic growth..." (Jarrett, p. 4, ¶ 1).
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 method for generating tumor growth models to include the tissue PSA dynamics of Lorenzo-2020 and Lorenzo-2019, to include the tumor cell density field from ADC maps and the tumor cell density equation of Jarrett, because Jarrett shows preliminary results show substantial reductions in the errors of the model, and the total predicted cellularity versus the calculated cellularity improved. One of ordinary skill would have had a reasonable expectation of success in modifying, because although Jarrett is directed to breast cancer, a phosita would have understood how to apply the teaching of Jarrett to the related teachings of Lorenzo-2020 and Lorenzo-2019, and as such, the combination would have been obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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NSDP Rejection:
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over one or more claims of U.S. Patent No. 11,631,502 (the '502 patent; from application 16/327,875) in view of Lorenzo-2020 (Computer Methods in Applied Mechanics and Engineering, vol. 362:112843, p.1-21 (2020); cited on the 12/13/2024 IDS), in view of Jarrett (Physics in Medicine & Biology, vol. 63(10):105015, p.1-16 (2018); cited on the attached form PTO-892), in view of Lorenzo-2019 (Proceedings of the National Academy of Sciences, vol. 116(4), pp.1152-1161; cited on the 12/13/2024 IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because the '502 patent as well as the instant application recites claims which involve methods of modeling progression of prostate cancer using a coupled system of reaction-diffusion equations and a patient specific geometric model.
While the instant application recites limitations for a tumor cell density field (Jarrett, p. 4, ¶ 1; and p. 6, Fig. 1, panel (f)); the tissue PSA is initialized from serum PSA values (shown by Lorenzo-2019, p.1158, ¶ 3); assessing effects of the 5-alpha reductase inhibitor (Lorenzo-2020, p.4, ¶ 2- 3; p.8, ¶ 7; and bridging p.9-10); and using the model to in monitoring and determining disease, risk, progression, and treatments (Lorenzo-2020, p.17, ¶ 1); this narrowing versus the '502 patent claims is now interpreted as obvious, such that the instant invention would have been prima facie obvious in view of the cited art.
Conclusion
No claims are allowed.
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/M.A.V./Examiner, Art Unit 1687
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686
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