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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/20/2021 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Acknowledgment is made of applicant’s claim for priority. Application claims benefit of Provisional Application No. 62/864,308. As such, the effective filing date of claims 1-15 is 6/20/2019
Claim Status
Claims 1-15 are pending.
Claims 1-15 are rejected.
Withdrawn Rejections/Objections
The office action filed 8/10/2026 was improperly filed as Final as new grounds of rejection were made under 35 U.S.C. 103. As such the previous finality of the prosecution is withdrawn, and this non-final office action is to replace the office action mailed on 8/10/2026.
The objection to the specification in the Office Action mailed 11/17/2025 is withdrawn in view of the amendments filed 5/18/2026.
The rejection of claims 4, 8-9, 23, 27-28, and 41 under 35 U.S.C. §102 in the Office action mailed 11/17/2025 is withdrawn in view of the amendments filed 5/18/2026.
Specification
Response to Amendment
In view of applicant’s amendments to the specification, previous objections to the specification over use of trade names/marks is withdrawn.
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 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claims recite a method, system and CRM for determining a treatment for a tumor. The judicial exception is not integrated into a practical application because while claims 1-15 attempt to integrate the exception into a practical application, said application is either generically recited computer elements that do not add a meaningful limitation to the abstract idea, or it is insignificant extra solution activity and simply implementing the abstract idea on a computer. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the computer elements only store and retrieve information in memory as well as perform basic calculations that are known to be well-understood, routine and conventional computer functions as recognized by the decisions listed in MPEP § 2106.05(d).
Framework with which 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]
Claims are directed to stator subject matter, specifically methods (claims 1-11), a system (claims 12-14), and a CRM (claim 15).
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)]
The claims herein recite abstract ideas, mental processes and mathematical concepts.
With respect to the Step 2A Prong One evaluation, the instant claims are found herein to recite abstract ideas that fall into the grouping of mental processes and mathematical concepts.
Claim 1: Processing the 3D image, and determining a number of treatment sites, locations and dosages are processes of comparing/contrasting, optimizing, and calculating data that can be done with pen and paper or in the human mind are therefore abstract ideas, specifically mental processes.
Claim 2: Generating the model and conducting one or more simulations of treatment are processes of optimizing, fine-tuning, and calculating data that can be done with pen and paper or in the human mind are therefore abstract ideas, specifically mental processes.
Claim 3: Each volume being a cuboid is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claim 4: The volumes being of equal size is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claim 5: The volumes including one or more of the spaces provided in the specified group is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claim 6: Obtaining tumor density, texture, and vascularity for use in the model is a process of calculating data that can be done with pen and paper or in the human mind are therefore abstract ideas, specifically mental processes.
Claim 7: The model describing intratumoral thermal dynamics is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claim 8: The model describing pharmacodynamics is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claim 9: Segmenting the tumor from background information is a process of refining information that can be done with pen and paper or in the human mind and is therefore an abstract idea, specifically a mental process.
Claim 10: Adjusting the determined dosage by a pre-determined safety margin is a process of refining information that can be done with pen and paper or in the human mind and is therefore an abstract idea, specifically a mental process.
Claim 12: Processing the 3D image, and determining a number of treatment sites, locations and dosages are processes of comparing/contrasting, optimizing, and calculating data that can be done with pen and paper or in the human mind are therefore abstract ideas, specifically mental processes. Providing a treatment plan of the tumor with the treatment dosage to a user is a method of organizing human activity, specifically in regards the interaction between a doctor and a patient, and is therefore an abstract idea.
Claim 15: Processing the 3D image, and determining a number of treatment sites, locations and dosages are processes of comparing/contrasting, optimizing, and calculating data that can be done with pen and paper or in the human mind are therefore abstract ideas, specifically mental processes. Providing a treatment plan of the tumor with the treatment dosage to a user is a method of organizing human activity, specifically in regards the interaction between a doctor and a patient, and is therefore an abstract idea.
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) and MPEP § 2106.05(a)-(c) & (e)-(h)]
Because the claims do recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application.
The following claims recite the following additional elements in the form of non-abstract elements:
Claim 1: Obtaining a 3D image of a tumor is an insignificant extra solution activity specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. Treating the tumor with the treatment dosage is merely a nonspecific treatment claim as it does not expand what the treatment is nor the dosage required and is equal to “treat the disease with a treatment and a dosage” which is generic and nonspecific [See MPEP § 2106.04(d)(2)].
Claim 7: The treatment being a thermal treatment is merely a nonspecific treatment claim as it does not expand on a type of treatment nor a dosage, it is merely a broad treatment using heat/cold [See MPEP § 2106.04(d)(2)].
Claim 8: The treatment being a drug treatment is merely a nonspecific treatment claim as it does not expand on a type of treatment nor a dosage, it is merely a broad treatment using any drug [See MPEP § 2106.04(d)(2)].
Claim 11: Retrieving an image from an electronic storage device is merely retrieving information from memory (See Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(d)(II)].
Claim 12: A system, communication device, and processor are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. Obtaining a 3D image of a tumor is an insignificant extra solution activity specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)].
Claim 13: A storage device in communication with the communication interface are generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 14: Providing treatment instructions to an output interface is an insignificant extra solution activity, specifically necessary data outputting (See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968, and OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015)) [See MPEP § 2106.05(g)].
Claim 15: A non-transitory computer-readable medium, computer program, and a computer are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. Obtaining a 3D image of a tumor is an insignificant extra solution activity specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)].
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? [see MPEP § 2106.05]
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.
The claims do not recite additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are generic, conventional, nonspecific, or insignificant extra solution activity. These additional elements include:
The additional elements of s non-transitory computer-readable medium, computer program, a computer, storage device in communication with the communication interface, a system, communication device, and a processor are all generic and nonspecific elements of a computer that are well- understood, routine and conventional within the art and therefore do not improve the functioning of any computer or technology described therein (Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(d)(II)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional elements of obtaining a 3D image of a tumor (Conventional: Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)), providing treatment instructions to an output interface (Conventional: Mayo, 566 U.S. at 79, 101 USPQ2d at 1968), and retrieving an image from an electronic storage device (Conventional: Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) are all insignificant extra solution activities, specifically mere data gathering and necessary data outputting (See Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), TLI Communications LLC v. AV Auto. LLC, 823 F.3d 607, 610, 118 USPQ2d 1744, 1745 (Fed. Cir. 2016) (using a telephone for image transmission), OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015) (sending messages over a network), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(g)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional elements of treating the tumor with the treatment dosage (Conventional: Tannock et al. 1998), the treatment being a thermal treatment (Conventional: Tannock et al. 1998), and the treatment being a drug treatment (Conventional: Tannock et al. 1998) are conventional within the art. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
Therefore, claims 1-15, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 5/18/2026 have been fully considered but they are not persuasive.
Applicant asserts on page 7 of the Remarks filed 5/18/2026 that the use of model equations and simulations for treatment dynamics require computation processing beyond human capabilities. However, examiner reminds applicant that the use of copious information or various models does not preclude the process from being an abstract idea, as MPEP 2106.04(a)(III) states - The courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972))…The courts do not distinguish between mental processes that are performed entirely in the slide rule) to perform the claim limitation…Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. As the Federal Circuit has explained, "[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent-ineligible invention could be performed via pen and paper or in a person’s mind." Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681, 1702 (Fed. Cir. 2015). Determining treatment sites using an intratumoral treatment dynamics model is a mental process here, which stands in contrast to methods not performable within the human mind such as those in Example 39 of the Subject Matter Eligibility guide which examined facial detection technology that used computer vision to analyze image data, a process which cannot be performed by humans in any context.
Applicant asserts on page 7 of the Remarks filed 5/18/2026 that the claims integrate any abstract ideas into a practical application, that of determining treatment sites and dosage. However, examiner reminds applicant that an argument for treatment according to MPEP 2106.04(d)(2) - Examiners should keep in mind that in order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of such a limitation is a step of "administering amazonic acid to a patient" or a step of "administering a course of plasmapheresis to a patient." If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. In this case the treatment for the tumor is actively recited, however the treatment is not specific, but rather is a general treatment and so therefore cannot serve as a specific treatment for a particular disease, and thus a practical application.
Finally, applicant asserts on page 8 of the Remarks filed 5/18/2026 that the office action filed 11/17/2025 did not identify the ordered combination of claim limitations as being well understood, routine, and conventional, specifically the determining treatment sites using an intratumoral model. However, examiner reminds applicant that the identification of well understood, routine, and conventional elements within the claim is limited to the additional elements, whereas the determination of treatment sites was determined to be part of the judicial exception (See MPEP 2106.05(d) - Another consideration when determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry).
Claim Rejections - 35 USC § 102
Response to Arguments
Applicant’s arguments, see pages 8-10 of the Remarks, filed 5/18/2026, with respect to the rejection of claims 1-2, 4-6, 8-13, and 15 under 35 U.S.C. 102 for anticipation have been fully considered and are persuasive. The rejection of claims 1-2, 4-6, 8-13, and 15 has been withdrawn.
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.
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 1-2, 4-6, 8-13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Orcutt et al. (US 20140321723 A1) and Gerlowski et al. (Journal of pharmaceutical sciences (1983) 1103-1127).
Claim 1 is directed to a method of tumor treatment using 3D imaging to determine tumor morphology and treatment sites, locations, and dosages.
Claim 12 is directed to a system for treatment of a tumor using 3D imaging to determine tumor morphology and treatment sites, locations, and dosages.
Claim 15 is directed to a CRM for treatment of a tumor using 3D imaging to determine tumor morphology and treatment sites, locations, and dosages.
Orcutt et al. teaches in paragraph [0002] “The present invention relates to molecular imaging and mathematical modeling and more particularly to methods that use these techniques in concert to assess various physiological parameters relevant to drug development and patient treatment. For example, the present methods can be used to estimate tumor vascularity, contrast agent internalization rate, contrast agent binding affinity, and binding site concentration from molecular imaging data”, and in claim 1 “providing one or more images of a tissue in a subject to whom a dose of a contrast agent (CA) has been administered; and (b) determining, using a computer equipped with image processing software, the concentration or relative concentration of the agent in a region or regions of interest in the tissue… describing the time-based behavior of concentrations of CA within the tissue using a pharmacokinetic model that is based on a set of pharmacokinetic model parameters; and (d) fitting, using computer code, the pharmacokinetic model to the concentration data, varying one or more parameters, wherein the best fit estimates a parameter of physiological significance”, paragraph [0025] “we describe a method using a pharmacokinetic model… to quantitatively estimate an array of physiological parameters including the aforementioned number of binding sites in the tumor, the internalization rate of the imaging agent and the tumor vascularity to name a few”, and paragraph [0043] “the present methods include those in which the analyses described herein are carried out before a patient begins treatment and during the course of treatment to determine efficacy”, reading on obtaining 3D imaging of the tumor; processing the 3D imaging of the tumor to obtain tumor morphology.
Gerlowski et al. teaches in the abstract “For medicinal purposes, pharmacokinetics can be used to estimate optimal drug scheduling and dosage regimens. For industrial toxins, pharmacokinetics can be used to aid in determining safe working environments. The modeling procedure is useful in animal and clinical applications, and for obtaining fundamental knowledge of the transport and metabolism of a substance in vivo”, and on page 1104, column 2, paragraph 1 “Still other agents are desired to be toxic to a specific tissue (e.g., anticancer agents to tumors) or are desired to accumulate in a target organ (e.g., general anesthetics in the nervous system). This information is applied with physiological (tissue volumes and blood flow rates), physicochemical (binding, lipid solubility, ionization, etc.), and pharmacological (mechanism of transport, sites of action, etc.) knowledge of the substance in the body to simplify the model”, on page 1118, column 1, paragraph 4 “Procaine2 is a local anesthetic used primarily in dental surgery. The drug blocks the function of the nerves near an injection site by attaching to and preventing sodium transfer across the nerve cell membrane, thus hindering the formation and propagation of the action potential on the membrane. The process is reversible, so the effects on the cell are only temporary (19). A nine compartment flow-limited model was developed by Smith et al. (67) to describe procaine pharmacokinetics in humans. Independently determined nonlinear binding and nonlinear metabolism terms were incorporated into the model. Model simulations showed good agreement with human data in the arterial plasma, brain, muscle, adipose tissue, and viscera regions. The model was also applied to lidocaine in humans and compared well with the human plasma data”, and page 1122, column 1, paragraph 1 “The model included transport to the site of metabolism, inhibition of the transformation of butanone to 3-hydroxy-2-butanone, reabsorption of the latter in the liver, and elimination of all four compounds from the animal”, which in view of the teachings of Orcutt et al. reads on determining a number of treatment sites, the locations of such sites, and the treatment dosage using a model of intratumoral treatment dynamics between vascular, intracellular, and extracellular space in order for the tumor to receive a therapeutic dosage at every location of the tumor; and treating the tumor at each of the determined treatment sites and with the determined treatment dosage.
It would have been obvious at the time of first filing to have modified the teachings of Orcutt et al. for the mathematical modeling of patient treatment with the teachings of Gerlowski et al. for the determination of site specific activity using pharmacokinetic models as both metho methods are employing similar modeling approaches and the latter is a review of methods. One would have had a reasonable expectation of success given that the latter presents “a unified theoretical framework for physiologically based pharmacokinetics” and an “extensive compilation of the literature on all substances modeled to date with this technique and discuss formulation of the equations, limitations of the modeling process, and areas of future applications”. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 2 is directed to the method of claim 1 but further specifies generating a model with a plurality of interconnected volumes with each volume having adjacent volumes with a shared boundary and conducting one or more simulations of treatment overtime using the model.
Orcutt et al. teaches in claim 8 “The method of claim 1, wherein the pharmacokinetic model for performing the analysis is a distributed model”, in claim 9 “The method of claim 8, wherein the distributed model is based on the Krogh cylinder”, and in paragraph [0002] “The present invention relates to molecular imaging and mathematical modeling and more particularly to methods that use these techniques in concert to assess various physiological parameters relevant to drug development and patient treatment. For example, the present methods can be used to estimate tumor vascularity, contrast agent internalization rate, contrast agent binding affinity, and binding site concentration from molecular imaging data”, paragraph [0025] “we describe a method using a pharmacokinetic model… to quantitatively estimate an array of physiological parameters including the aforementioned number of binding sites in the tumor, the internalization rate of the imaging agent and the tumor vascularity to name a few”, and paragraph [0043] “the present methods include those in which the analyses described herein are carried out before a patient begins treatment and during the course of treatment to determine efficacy”, reading on wherein determining a number of treatment sites, the locations of such sites, and the treatment dosage further comprises: generating the model to include a plurality of interconnected volumes wherein each volume has one or more adjacent volumes with a shared boundary; and conducting one or more simulations of treatment over time using the model, each simulation having a set of one or more initial parameters.
Claim 4 is directed to the method of claim 2 and thus claim 1, but further specifies that the volumes are of equal size.
Orcutt et al. teaches in claim 8 “The method of claim 1, wherein the pharmacokinetic model for performing the analysis is a distributed model”, in claim 9 “The method of claim 8, wherein the distributed model is based on the Krogh cylinder”, it is inherent to the Krogh Cylinder model that the radius r be constant and each cylinder be of equal length thereby reading on wherein the plurality of volumes are of equal size.
Claim 5 is directed to the method of claim 2 and thus claim 1, but further specifies that the volumes include one or more the spaces provided in the specified in group.
Orcutt et al. teaches in paragraph [0002] “The present invention relates to molecular imaging and mathematical modeling and more particularly to methods that use these techniques in concert to assess various physiological parameters relevant to drug development and patient treatment. For example, the present methods can be used to estimate tumor vascularity, contrast agent internalization rate, contrast agent binding affinity, and binding site concentration from molecular imaging data”, reading on wherein each of the volumes includes one or more of intracellular space, extracellular space, and vascular space.
Claim 6 is directed to the method of claim 1 but further specifies that the processing of the 3D image include obtaining one of the specified metrics and one of the specified metrics be used in the model.
Orcutt et al. teaches in paragraph [0002] “The present invention relates to molecular imaging and mathematical modeling and more particularly to methods that use these techniques in concert to assess various physiological parameters relevant to drug development and patient treatment. For example, the present methods can be used to estimate tumor vascularity, contrast agent internalization rate, contrast agent binding affinity, and binding site concentration from molecular imaging data”, in paragraph [0006] “More specifically, the methods allow in vivo molecular imaging to be used to quantitatively estimate physiological parameters such as antigen expression levels, contrast agent internalization rate, tumor vascularity…”, and in paragraph [0007] “The SUV-time data is then fit to the model varying antigen density and tumor vascularity…”, reading on wherein processing the 3D imaging additionally includes obtaining one or more of tumor density, texture, and vascularity, and the model of intratumoral treatment dynamics is further based on the obtained tumor density, texture, and/or vasculature.
Claim 8 is directed to the method of claim 1 but further specifies that the treatment be a drug and the model be a pharmacodynamics model.
Orcutt et al. teaches in paragraph [0002] “The present invention relates to molecular imaging and mathematical modeling and more particularly to methods that use these techniques in concert to assess various physiological parameters relevant to drug development and patient treatment. For example, the present methods can be used to estimate tumor vascularity, contrast agent internalization rate, contrast agent binding affinity, and binding site concentration from molecular imaging data”, and in paragraph [0017] “The uptake of a given compound (e.g., a radiolabeled compound that can be imaged) by a tissue (e.g., a tumor) and the distribution of the compound in the tissue depends on a variety of parameters including, but not limited to, binding affinity, the concentration of binding sites within the tissue, and the extent to which the tissue is vascularized… An array of qualitative metrics for the distribution of radiopharmaceuticals are employed in nuclear medicine, most commonly some weighted form of the percent injected dose…”, paragraph [0026] “The pharmacokinetic model may be a distributed model… For tumor targeting compounds, significant spatial heterogeneity is prevalent and incorporating this spatial heterogeneity into mathematical models describing tumor uptake allows insight into drug microdistribution.”, and paragraph [0044] “For a patient with more than one tumor, the antigen expression level in each tumor may be quantified and the patient may be selected to receive targeted therapy if a predetermined metric, that is a function of the antigen expression estimates and the number of tumors, is greater than a predetermined cut point”, reading on wherein the treatment is a drug treatment and the model describes pharmacodynamics.
Claim 9 is directed to the method of claim 1 but further specifies the segmentation of the tumor from background information.
Orcutt et al. teaches in paragraph [0017] “Image analysis techniques are applied to composite images in order to quantify the uptake or concentration of an imaging agent. For example, a radiologist can classify a tumor within a PET image and a region of interest can be created to segment said tumor within the image”, reading on wherein processing the 3D imaging of the tumor comprises segmenting the tumor from background information.
Claim 10 is directed to the method of claim 1 but further specifies the adjusting of the determined treatment dosage by a pre-determined safety margin.
It would be inherent to any therapy given that an adjustment of the dosage would be required for a safety margin as any drug or treatment inherently has an LC50 or dosage at which said chemical or treatment is poisonous/lethal.
Claim 11 is directed to the method of claim 1 but further specifies that the image is retrieved from an electronic storage device.
Orcutt et al. teaches in the abstract “One or more images are provided of a tissue in a subject to whom a dose of a contrast agent (CA) has been administered, using a computer equipped with image processing software…”, it would then be inherent that any image input to the image processing software would come from an electronic storage device, thereby reading on wherein the image is obtained by retrieval from an electronic storage device.
Claim 13 is directed to the system of claim 12 but further specifies that a storage device be in communication with the communication interface.
Orcutt et al. teaches in the abstract “One or more images are provided of a tissue in a subject to whom a dose of a contrast agent (CA) has been administered, using a computer equipped with image processing software…”, it would then be inherent that any image input to the image processing software would come from an electronic storage device and that it would be communicatively coupled to an communication interface such as a keyboard, thereby reading on further comprising a storage device in communication with the communication interface.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Orcutt et al. (US 20140321723 A1) and Gerlowski et al. (Journal of pharmaceutical sciences (1983) 1103-1127) as applied to claims 1-2, 4-6, 8-13, and 15 above.
Claim 14 is directed to the system of claim 12 but further specifies the providing of treatment instructions to an output interface.
Orcutt et al. teaches in paragraph [0006] “The present methods can be used to estimate tumor and contrast agent properties from molecular imaging data, parameters which may be used in accelerating the development of cancer therapeutics, improving patient selection and stratification for clinical trials and treatment regimes, and monitoring patient responses to treatment”, it would be obvious to any method that improves treatment regimes via computer that it would necessitate the outputting of such regimes to personnel who would provide such treatment, thereby reading on wherein the processor is further programmed to provide treatment instructions to an output interface.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Orcutt et al. (US 20140321723 A1) and Gerlowski et al. (Journal of pharmaceutical sciences (1983) 1103-1127) as applied to claims 1-2, 4-6, 8-13, and 15 above, and further in view of Mellal et al. (Appl. Sci. Res. Rev (2017) 1-11).
Claim 7 is directed to the method of claim 1 but further specifies that the treatment be a thermal treatment and that the model describe intratumoral thermal dynamics.
Orcutt et al. teaches in paragraph [0017] “The uptake of a given compound (e.g., a radiolabeled compound that can be imaged) by a tissue (e.g., a tumor) and the distribution of the compound in the tissue depends on a variety of parameters including, but not limited to, binding affinity, the concentration of binding sites within the tissue, and the extent to which the tissue is vascularized… An array of qualitative metrics for the distribution of radiopharmaceuticals are employed in nuclear medicine, most commonly some weighted form of the percent injected dose…”.
Mellal et al. teaches on page 2 through equations 1-7 the mathematical models for thermal transfer in living tissue and in the abstract teaches “Thermal therapy is a promising treatment for many patients particularly those with surgery intolerance…We exposed the recent advances and the limitations of these modalities. However, to improve the quality of the treatment and increase the rate of survival, the research is still investigating these modalities. We discussed the future challenges and perspectives of the thermal therapies. Propositions to overpass the limitations of some techniques were introduced”, reading on wherein the treatment is a thermal treatment and the model describes intratumoral thermal dynamics.
It would have been obvious at the time of filing to combine the teachings of Orcutt et al. and Gerlowski et al. for the method of claim 1 with the teachings of Mellal et al. for using mathematical models of thermal therapy as both focus on the same field of cancer treatment and treatment modeling with Mellal et al. being an overall review of current methods within the field, providing slight adjustments to mathematical models used this would merely be a simple substitution of one known element, the model within Orcutt et al., with another known element, the model within Mellal et al., to obtain a predictable result, the use of thermal models and therapies. As they both focus on intratumoral treatment dynamics one would have had a reasonable expectation of success in combining them given that Mellal et al. provides an overview of how to use various models. Therefore, it would have been obvious at the time of filing to combine the teachings of each and to be successful.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Orcutt et al. (US 20140321723 A1) and Gerlowski et al. (Journal of pharmaceutical sciences (1983) 1103-1127) as applied to claims 1-2, 4-6, 8-13 and 15 above, and further in view of Popilski et al. (Expert opinion on drug metabolism & toxicology (2015) 767-84).
Claim 3 is directed to the method of claim 2 but further specifies that each volume is a cuboid.
Orcutt et al. and Gerlowski et al. teach the method of claim 1 as previously described.
Orcutt et al. and Gerlowski et al. do not teach that each volume is a cuboid.
Popilski et al. teaches on page 771, column 1, paragraph 3-4 “Different types of mathematical models can be applied to describe the processes of intratumoral drug/DDS disposition…Krogh cylinder (Figure 2A) assumes that the tissue is composed of cylinders with the blood vessel in their center that is surrounded by tissue. The local blood concentration is determined by the intercapillary distance (i.e., the diameter of the cylinders), blood velocity, permeability of the vessel wall and additional parameters, such as extent of drug protein binding in the blood/plasma. Other types of models assume spherical shape of the tumor (Figure 2B) and radial (two- or three-dimensional) gradient of drug/DDS concentrations in it due to the diffusion and degradation of the drug molecules. In some cases, effects of additional processes are incorporated in the model (such as drug internalization by the cells, rate of tumor cells divisions, tumor porosity, etc.), or multilayer nature of spheroids is assumed… Compartmental models can also be applied for analyzing intratumoral drug/DDS disposition (Figure 2E and F). Such models assume existence of kinetically homogeneous compartments in the tumor tissue”, it would have been obvious to a person skilled in the art that homogeneous compartments of various shapes would include cubes, thereby reading on wherein each volume of the plurality of volumes is cuboid.
It would have been obvious at the time of filing to combine the teachings of Orcutt et al. and Gerlowski et al. for the method of claim 1 with the teachings of Popilski et al. for using mathematical models of intratumoral drug/DDS disposition (intratumoral treatment dynamics) as both focus on the same field of cancer treatment and treatment modeling with Popilski et al. being an overall review of current methods within the field, providing slight adjustments to mathematical models used this would merely be a simple substitution of one known element, the model within Orcutt et al., with another known element, the model within Popilski et al. to obtain a predictable result, the modeling of volumes as cuboid instead of rectangular. As they both focus on intratumoral treatment dynamics one would have had a reasonable expectation of success in combining them given that Popilski et al. provides an overview of how to use various models including those that are used within Orcutt et al. for tumor- and pharmacodynamics. Therefore, it would have been obvious at the time of filing to combine the teachings of each and to be successful.
Response to Arguments
Applicant’s arguments, see pages 10-11 of the Remarks, filed 5/18/2026, with respect to the rejections of claims 3, 7, and 14 under 35 U.S.C. 103 for obviousness have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Gerlowski et al. (Journal of pharmaceutical sciences (1983) 1103-1127).
Conclusion
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/K.N.A./ Examiner, Art Unit 1687
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686
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