DETAILED ACTION
Applicants’ arguments, filed 10 February 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
Claim 1 recites a diffusivity contrast agent. The specification discloses the following on page 14 regarding the diffusivity contrast agent.
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For the purposes of examination under prior art, the examiner understands the above-indicated contrast agents to be diffusivity contrast agents. As such, a prior art reference teaching at least one of the above-indicated contrast agent is understood to meet the claim requirement that the contrast agent be a diffusivity contrast agent. This is understood to be the case regardless of whether the prior art identifies these contrast agents as diffusivity contrast agents. Something which is old does not become patentable upon the discovery of a new property, and this feature need not have been recognized at the time of filing. See MPEP 2112(I & II).
Additionally, as best understood by the examiner, the terms “gadopentate meglumine” and “gadopentetate meglumine” are understood to refer to the same substance and are understood to be alternate spellings.
Additionally, the examiner understands the blood-brain barrier to be within the scope of the required biological barrier of the 4th line of claim 1.
Applicant does not appear to have explicitly addressed the issues set forth in the section entitled “Claim Interpretation” in applicant’s response on 10 February 2026.
Claim Rejections - 35 USC § 103 – Obviousness
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.
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.
Claim(s) 1-7, 14, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. (Journal of Neurooncology, Vol. 112, 2013, pages 257-266) in view of Gillies et al. (US 2017/0071496 A1).
Harris et al. (hereafter referred to as Harris) is drawn to pre-contrast and post-contrast MRI images in human glioblastoma, as of Harris, page 257, title and abstract. See also Harris, page 259, figure 1, reproduced below.
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As to claim 1, first step, the claim requires a diffusivity contrast agent. Harris teaches obtaining gadopentetate dimeglumine, apparently from Magnevist; Berlex, Wayne, NJ, as of Harris, page 258, right column, top paragraph, reproduced below with annotation by the examiner.
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The skilled artisan would have understood gadopentate dimeglumine to have been a diffusivity contrast agent even though Harris did not specifically teach that gadopentetate dimeglumine is a diffusivity contrast agent because gadopentetate dimeglumine is the same contrast agent used in the instant application. Something which is old (e.g. gadopentate dimeglumine) does not become patentable upon the discovery of a new property (that this contrast agent is a diffusivity contrast agent), and this feature need not have been recognized at the time of filing. See MPEP 2112(I & II). See the section above entitled “Claim Interpretation” in which this issue is described in greater detail.
As to claim 1, second step, Harris teaches administering a detectable dose of MRI contrast agent. Harris teaches administering a bolus of 0.075 mmol/kg of gadopentetate dimeglumine, as of Harris, page 258, top paragraph as of the right column.
As to claim 1, third step, Harris teaches acquiring post-contrast images, as of the above-reproduced figure 1.
For the purposes of this rejection, the examiner understands that Harris is deficient because Harris does not measure the diffusivity of the region of interest.
Gillies et al. (hereafter referred to as Gillies) is drawn to tumor imaging to determine different heterogeneous habitats inside a tumor, as of Gillies, title and abstract. Gillies concentrates on imaging glioblastoma, as of Gillies, page 17, right column, claim 2. One mode of imaging conducted by Gillies is the apparent diffusion coefficient of water, which is abbreviated as ADC, as of Gillies, page 17, paragraphs 0187 and 0188. Gillies uses change in apparent diffusion coefficient of water to aid in diagnosis, as of Gillies, paragraphs 0027-0028.
The examiner has not rejected the instant claims over Gillies by itself because it is unclear whether the contrast agent in Gillies would read on the required diffusivity contrast agent. This is because, while Gillies teaches that the contrast agent comprises gadolinium (e.g. as of paragraph 0075 of Gillies – gadolinium is a common ingredient in MRI contrast agents), it does not appear that Gillies provides the full chemical name of the contrast agent.
It would have been prima facie obvious for one of ordinary skill in the art to have used the ADC imaging protocol in Gillies to have imaged the patients in Harris. Harris teaches acquiring pre-contrast and post-contrast images of patients suffering from glioblastoma. Gillies indicates that ADC imaging protocols could be used to help diagnose tumors including glioblastoma. As such, the skilled artisan would have been motivated to have used the ADC imaging protocol of Gillies to have imaged the patients of Harris in order to have predictably investigated and diagnosed microenvironments in glioblastoma patients with a reasonable expectation of success.
As to claim 2, the teachings of Harris indicate that the contrast agent crosses the blood brain barrier because the contrast agent clearly influences the images taken of the brain.
As to claim 3, Harris teaches selecting gadopentetate dimeglumine, as of Harris, page 258, right column, top paragraph, reproduced above. While Harris does not appear to provide reasons why this contrast agent is selected, it is nevertheless the case that the contrast agent selected by Harris appears to be within the scope of the required contrast agents. See the section above entitled “Claim Interpretation.”
As to claim 4, the apparent diffusion of water method of Harris would appear to indicate that the diffusion of water is modulated depending upon where in the brain the water is located. The skilled artisan would have expected that this difference in apparent diffusion would have been applicable to solutes dissolved in the water, including but not limited to the contrast agent.
As to claim 5, the skilled artisan would have expected that the diffusivity contrast agent would have been synthesized as per Magnevist; Berlex, Wayne, NJ, as of Harris, page 258, right column, top paragraph, reproduced above.
As to claim 6, the skilled artisan would have expected that the gadopentate dimeglumine of Harris would have read on the required metal ions, ligands, and chelates, as it comprises a chelated gadolinium ion.
As to claim 7, the skilled artisan would have expected that the gadopentate dimeglumine of Harris would have read on the required compound.
As to claim 14, the skilled artisan would have understood gadopentate dimeglumine to have had a molecular weight about 547 Daltons.
As to claim 22, both Harris and Gillies teach diagnosing glioblastoma.
Claim(s) 8-13, 15, 21, and 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. (Journal of Neurooncology, Vol. 112, 2013, pages 257-266) in view of Gillies et al. (US 2017/0071496 A1), the combination further in view of Wahsner et al. (Chemical Reviews, Vol. 119, 2019, pages 957-1057).
Harris is drawn to MRI imaging of glioblastoma with contrast agent. Gillies is drawn to the use of diffusion MRI imaging for imaging of the brain, including for diagnosis of glioblastoma. See the rejection above over Harris in view of Gillies.
For the purposes of this rejection, the examiner understands that neither Harris nor Gillies teaches modulating properties such as solubility and mass weight of the contrast agent.
Wahsner et al. (hereafter referred to as Wahsner) is drawn to the chemistry of MRI contrast agents, as of Wahnser, page 957, title and abstract. Wahnser teaches a variety of commercially approved T1 (longitudinal relaxation time) contrast agents on page 961, as well as other contrast agents in development elsewhere in the reference. Wahnser teaches imaging of a patient with glioblastoma, as of Wahnser, page 964, right column, figure 7, reproduced below.
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It would have been prima facie obvious for one of ordinary skill in the art to have modified the contrast agent taught by Harris and/or Gillies in view of the teachings of Wahnser. Harris and Gillies teach the use of gadolinium contrast agents to image the brain, including for glioblastoma. Wahnser teaches a variety of contrast agents for MRI. As such, the skilled artisan would have been motivated to have used the contrast agents of Wahnser to have predictably imaged the brain with a reasonable expectation of success.
As to claim 8, Wahnser teaches increasing the solubility of contrast agents, as of at least page 965, right column, paragraph below figure 11, as well as page 979, right column, first full paragraph.
As to claim 9, Wahnser teaches increasing the solubility of contrast agents, as of at least page 965, right column, paragraph below figure 11, as well as page 979, right column, first full paragraph. Wahnser also teaches synthesis of said contrast agents as of at least page 981, left column, bottom paragraph.
As to claim 10, Wahnser teaches chemical modification of a contrast agent, as of at least Wahnser, page 986, left column.
As to claim 11, Wahnser teaches adjusting the molecular weight of the paramagnetic compound (i.e. gadolinium contrast agent), as of Wahnser, page 969, left column, third to last paragraph.
As to claim 12, Wahnser teaches hyperpolarized C-13 contrast agents such as hyperpolarized pyruvate, as of Wahnser, page 959, left column, second paragraph. The examiner understands these to be non-paramagnetic and non superparamagnetic substances because paramagnetism is determined by unpaired electrons whereas hyperpolarization acts upon the atomic nucleus rather than upon electrons.
As to claim 13, Wahnser teaches hyperpolarized pyruvate, as of Wahnser, page 959, left column, second paragraph. Pyruvate has a molecular weight of about 87 Daltons, which is within the claim scope.
As to claim 15, Wahnser teaches high molecular weight contrast agents; one example would be the tetramer on page 985, figure 33(e). Also, Wahnser teaches targeted contrast agents such as that described on Wahnser, page 998, figure 52. These appear to have molecular weights in the claimed range.
As to claim 21, Wahnser teaches intravenous administration of contrast agent as of page 960, section 3.1 of Wahnser.
As to claim 23, Wahnser reviews iron oxide contrast agent and teaches that superparamagnetic iron oxide is used as a therapeutic drug for iron replacement therapy, as of Wahnser, page 995, right column, top paragraph.
As to claim 24, the skilled artisan would have identified the administered agent prior to administering said agent.
Claim(s) 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. (Journal of Neurooncology, Vol. 112, 2013, pages 257-266) in view of Gillies et al. (US 2017/0071496 A1) and Wahsner et al. (Chemical Reviews, Vol. 119, 2019, pages 957-1057), the combination further in view of Orcutt et al. (US 2015/0297160 A1).
Harris is drawn to MRI imaging of glioblastoma with contrast agent. Gillies is drawn to the use of diffusion MRI imaging for imaging of the brain, including for diagnosis of glioblastoma. See the rejection above over Harris in view of Gillies. Wahnser teaches a wide variety of contrast agents, and indicates that these contrast agents can have different molecular weights. See the rejection above over Harris in view of Gillies and Wahnser by themselves.
None of the above references teach the diffusivity of the contrast agent.
Orcutt et al. (hereafter referred to as Orcutt) is drawn to determination of pharmacokinetic parameters, as of Orcutt, title and abstract. Orcutt teaches the following, as of paragraph 0031, reproduced in part below.
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The above-reproduced text would appear to indicate that diffusivity can be determined from molecular weight.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the diffusivity of the contrast agent in Harris, Gillies, and Wahnser. Wahnser teaches a variety of MRI contrast agents, and teaches that molecular weight impacts the effects of the contrast agent, as of e.g. Wahnser page 964, left column, portion of document above figure 6. As such, the skilled artisan would have been motivated to have optimized molecular weight in order to have predictably optimized the effect of the contrast agent with a reasonable expectation of success. The skilled artisan would have expected that optimization of molecular weight would have resulted in optimization of diffusivity.
As to claims 16-18, the examiner notes that the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. See MPEP 2144.05(II)(B), last paragraph in section. In this case, the skilled artisan would have understood that molecular weight would have been a result-effective variable, for the reasons set forth in the above paragraph. As diffusivity correlates with molecular weight, the skilled artisan would have also understood diffusivity to have been a result-effective variable.
Claim(s) 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. (Journal of Neurooncology, Vol. 112, 2013, pages 257-266) in view of Gillies et al. (US 2017/0071496 A1) and Wahsner et al. (Chemical Reviews, Vol. 119, 2019, pages 957-1057), the combination further in view of Hao et al. (Journal of Magnetic Resonance Imaging, Vol. 36, 2012, pages 1060-1071).
Harris is drawn to MRI imaging of glioblastoma with contrast agent. Gillies is drawn to the use of diffusion MRI imaging for imaging of the brain, including for diagnosis of glioblastoma. See the rejection above over Harris in view of Gillies. Wahnser teaches a wide variety of contrast agents, and indicates that these contrast agents can have different molecular weights. See the rejection above over Harris in view of Gillies and Wahnser by themselves.
None of the above references teach the viscosity of the contrast agent.
Hao et al. (hereafter referred to as Hao) is drawn to the chemistry and safety of MRI contrast agents, as of Hao, pages 1060-1061, title and abstract. Hao teaches viscosity of various MRI contrast agents, as of page 1063, Table, reproduced below with annotation by the examiner.
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The minimum viscosity measured here is 1.3 mPa.s or 0.0013 Pa.S, and the maximum viscosity is about 0.0053 Pa.S.
It would have been prima facie obvious for one of ordinary skill in the art to have formulated the viscosity of the contrast agents taught by Harris, Gillies, and Wahnser. Harris, Gillies, and Wahnser teach the use of various MRI contrast agents, including a wide variety of said contrast agents. These references are silent regarding viscosity; nevertheless, Hao teaches viscosity, as of the above-reproduced table. As such, the skilled artisan would have been motivated to have formulated the viscosity of the contrast agents in the amount taught by Hao in order to have predictably provided MRI contrast with a reasonable expectation of success.
As to claim 20, the viscosity taught by Hao would appear to be within the claimed range. The examiner notes that, e.g. 1.3 mPa.s, as taught by Hao, is the same as 1.3 X 10-3 Pa.S, which is within the claimed range.
As to claim 19, the viscosities taught by Hao appear to be slightly higher than those recited by claim 19. Nevertheless, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). In this case, the general conditions of administering an MRI contrast agent with a viscosity have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have determined the optimum or workable ranges of viscosity by routine experimentation.
Response to Arguments Regarding Prior Art Rejections
Applicant has provided arguments regarding the previously presented prior art rejections, as of applicant’s response on 10 February 2026 (hereafter referred to as applicant’s response). These arguments are addressed below.
In the prior office action mailed on 10 February 2026, the examiner took the position that Harris is deficient because Harris does not measure the diffusivity of the region of interest, and took the position that this deficiency is cured by Gillies. Applicant appears to dispute the examiner’s position that this deficiency in Harris is cured by Gillies, as of applicant’s response, bottom half of page 14 of applicant’s response. Applicant presents the following arguments, as of the first paragraph on page 15 of applicant’s response, which is reproduced below.
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The examiner notes that the acronym “ADC” refers to “apparent diffusion coefficient.”
As an initial matter, applicant’s response is somewhat unclear as to what applicant believes to be the endogenous agent in Gillies; however, the last sentence of the paragraph appears to be a statement that the endogenous agents referred to by the first sentence of the above paragraph is water. This argument does not appear to be persuasive for at least the following reasons:
As best understood by the examiner, the following is the case regarding MRI. First, in MRI, (as well as in nuclear magnetic resonance (NMR)), a sample (which in the case of MRI, is the body of a patient) is placed in a strong, stable magnetic field. This causes nuclei with non-zero spins to align such that the majority of spins are with the magnetic field, and the minority of spins are against the magnetic field. A radiofrequency pulse is then applied, which flips the spins such that the majority of spins are against the magnetic field, at least for a certain period of time. This causes a signal to be produced for a temporary period of time that contributes to the MRI image. In the case of almost all MRI imaging procedures conducted on human medical patients, the nucleus with the non-zero spin measured is hydrogen, and the majority of the hydrogen atoms in the body are part of water molecules. As such, the examiner’s best understanding is that MRI measures the presence of water, which is an endogenous agent; this is the case for the procedure of the instant application as well as that of all of the prior art references cited by the examiner in the office action. Water is an endogenous agent in all of these MRI procedures.
The examiner notes that the issues in the above-reproduced paragraph are discussed in Plewes et al. (“Physics of MRI: A Primer” Journal of Magnetic Resonance Imaging, Vol. 35, 2012, pages 1038-1054). Relevant text from Plewes has been reproduced below, such as that from Plewes, page 1041, left column.
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The examiner clarifies that Plewes is not part of the statement of rejection, and was cited by the examiner to explain issues surrounding the physics of MRI that would have been well-known to the skilled artisan at the time of filing.
As such, applicant’s argument that Gillies differs from the claimed invention because Gillies teaches an endogenous agent whereas the claims require an exogenous agent is not persuasive because in both the claimed invention and the MRI method of Gillies, the MRI signal is coming from endogenous hydrogen, with the majority of that signal coming from endogenous water (and the minority of that signal coming from other endogenous molecules containing hydrogen).
With that being said, the examiner notes that the instant claims do recite administration of an exogenous agent, wherein the exogenous agent is referred to as a diffusivity contrast agent as of claim 1, 3rd through 6th lines. The instant specification indicates that this agent may be a gadolinium containing contrast agent such as gadopentetate dimeglumine, as of page 14 of the instant specification. The examiner notes here that all of Harris, Gillies, and Wahnser teach an exogenous gadolinium contrast agent, with Harris teaching gadopentetate dimeglumine on page 258, right column, top of page. As such, all of the cited prior art references teach the same class of exogenous references as disclosed in the instant application.
The examiner further notes here that the use of an exogenous gadolinium containing contrast agent in both the claimed invention and prior art does not mean that the exogenous gadolinium itself is being measured by the MRI. In contrast, the mode of operation of gadolinium contrast agents is that administration of said agents, in combination with the use of particular pulse sequences, results in either enhancement or loss of MRI signal in the location in the body where the contrast agents are located. This is explained as of Wahnser, page 959, left column, relevant paragraph reproduced below.
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As such, it is the endogenous bulk water molecules that are being measured; however, their signal intensity changes due to the presence of contrast agents. As such, to the extent that applicant is arguing that either the claimed method or the method of the prior art directly measures the presence of an exogenous contrast agent, this argument is not persuasive.
Applicant then makes the following argument on page 15, relevant text reproduced below.
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Regarding item 1, the examiner notes that the claims recite administering a contrast agent that reads on the required diffusivity contrast agent to a subject. This phrase is defined on page 11, first full paragraph, reproduced below.
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Nothing in the claim, or in the above-reproduced definition of the phrase “diffusivity contrast agent” is drawn to an agent that is configured to alter apparent diffusion. As such, to the extent that applicant argues that the claims are drawn to administration of an agent to alter apparent diffusion, this is an argument relating to subject matter not actually recited by the claims. Such an argument is not persuasive. See MPEP 2145(VI).
Regarding item #2, applicant argues that the claims are drawn to acquisition of images that capture agent-induced changes in water mobility. The examiner takes the position that that this feature is taught by the prior art. Specifically, Gillies teaches apparent diffusion coefficient of water maps as of paragraph 0009 of Gillies. Also see Gillies, paragraphs 0023-0024, 0027-0028, as well as elsewhere in the reference. The examiner notes that Gillies uses acronym “ADC” to refer to “apparent diffusion coefficient”, as of paragraph 0009 of Gillies, and this acronym appears in the Gillies reference sixty-one times.
Applicant then presents the following arguments, as of the table on the bottom of page 15 of applicant’s response, which is reproduced below with annotation by the examiner in order to best address applicant’s response.
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These arguments are addressed below by the examiner.
A1 - Contrast Mechanism – Part 1: First, the examiner disagrees that the prior art fails to teach contrast as it relates to apparent diffusion coefficient (ADC). Gillies, paragraph 0009, defines the acronym “ADC” to refer to apparent diffusion coefficient of water, and the acronym “ADC” appears sixty-one times in the Gillies reference. Gillies teaches ADC measurements as of at least 0027-0028 and 0032-0033, as well as multiple other locations in the reference. As such, applicant’s arguments that the prior art fails to teach measurement of ADC change does not appear to be persuasive as this feature is taught multiple times by Gillies.
A2 – Contrast Mechanism Part 2: Applicant also appears to argue that the prior art operates by T1/T2 relaxivity, whereas the claimed method does not operate in this manner. The examiner disagrees that this is an appropriate description of the invention as described by the instant specification. The instant specification discloses that the MRI contrast agents may be one of various agents containing gadolinium, as of page 14 of the instant specification, including gadopentetate dimeglumine, Gadobutrol, Gadoterate meglumine, and others. The skilled artisan would have been aware that gadolinium containing MRI agents are T1/T2 relaxivity agents, as of Wahnser, page 963, relevant text reproduced below.
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As such, the skilled artisan would have expected that the method described by the instant application would have operated by T1/T2 relaxivity to the extent that a gadolinium contrast agent was used, even if applicant insists in the arguments that the claimed invention operates in a different manner.
B – Imaging Sequence (i.e. Pulse Sequence): Applicant appears to argue that the claims require diffusion weighted imaging, which is not taught by the prior art. This is not persuasive. As an initial matter, it is not clear that claim 1 actually requires diffusion weighted imaging, as the phrase “diffusion weighted imaging” is not recited by claim 1. Nevertheless, even if, purely en arguendo, claim 1 was understood to require diffusion weighted imaging, this argument remains unpersuasive. This is because diffusion weighted imaging was taught by Gillies. See Gillies, paragraphs 0044, 0126, 0134, 0142, 0181, and 0183.
C – Measured Phenomenon: As an initial matter, the examiner argues that the assertion that the measured phenomenon in the prior art is proton relaxation is not technically accurate. This is because the measured phenomenon in all proton MRI scans (which are the vast majority of MRI scans conducted clinically) is the endogenous presence of hydrogen atoms. This is applicable both to the claimed invention and the prior art. The examiner notes that prior art methods using gadolinium as a contrast agent conduct a pre-contrast scan and a post-contrast scan, and the differences between the pre-contrast scan and the post-contrast scan provides details regarding proton relaxation. However, these details are obtained by comparing the post-contrast scan and pre-contrast scan, and are not directly measured by a single MRI scan.
Secondly, the examiner notes that the phrase “water mobility modulation” is not actually recited by the instant claims. As such, it is unclear if the argument in item C actually relates to subject matter recited by the claims. See MPEP 2145(VI).
Third, the contrast agents taught by the prior art are gadolinium contrast agents, which appear to be the same as the gadolinium contrast agents disclosed on page 14 of the instant specification. For example, Harris teaches gadopentetate dimeglumine on page 258, right column, and this is the same contrast agent disclosed on page 14 of the instant specification as a diffusivity contrast agent. As such, because the contrast agent in the prior art is the same as what is disclosed by the instant application, there would have been a reasonable expectation that the measured phenomenon in the prior art would have been the same as that in the instant invention.
D - Diagnostic Target: To the extent that applicant is arguing that the prior art fails to teach barrier transport function, this is not persuasive. See Gillies, paragraph 0131, paragraph reproduced in part below.
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As such, Gillies teaches diffusion MRI of ADCs, as well as interpolating the information of diffusion barriers, as of the above-reproduced text. As such, contra to applicant’s arguments, Gillies does appear to teach targeting barrier transport function.
Secondly, the examiner notes that although claim 1 recites that the diffusivity contrast agent is configured to pass a biological barrier of a subject, this requirement does not appear to be the same as requiring that the diagnostic target be barrier transport function. As such, it is unclear as to what extent the “barrier transport function” discussed in the table on page 15 of applicant’s response is actually recited by the claim. Arguments related to unclaimed limitations are not persuasive; see MPEP 2145(VI).
Applicant argues the following on page 16, top paragraph.
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This is not persuasive. Claim 1 requires that the contrast agent be a diffusivity contrast agent. The instant specification on page 14 indicates that said contrast agent may be gadopentetate dimeglumine. This indicates that gadopentetate dimeglumine is within the scope of the required diffusivity contrast agent. Both Harris and Wahnser teach gadopentetate dimeglumine, as of Harris, page 258, right column and Wahnser, page 961. As such, there would have been a reasonable expectation that the contrast agents of the prior art would have operated by the same mechanism as the contrast agents of the instantly claimed invention.
As such, at most, it appears that applicant may have discovered a new scientific explanation for the method by which the contrast agents of the prior art function (though the inclusion of this sentence in the office action should not be construed as an admission that applicant has discovered a new scientific explanation for the method by which the contrast agents of the prior art function). This would not be sufficient to overcome the applied rejection. The discovery of a scientific explanation for the prior art’s functioning does not render the old composition patentable to the discoverer. See MPEP 2112(I). The examiner understands that this rationale applies to known methods along with known compositions; see MPEP 2112.02(I).
Applicant then makes the following argument, as of page 16 of applicant’s response.
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This is not persuasive. The claims do not require that the exogenous agent alters diffusion behavior. In contrast, the claims recite a diffusivity contrast agent which is defined in the following manner on the first full paragraph of page 11 of the specification.
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Nothing in the above-definition indicates that the diffusivity contrast agent itself is required to alter diffusion behavior. In contrast, the claims require that the diffusivity contrast agent be used to characterize diffusivity, not to alter diffusivity. It is the examiner’s position that the methods of Gillies, which entail administering a contrast agent as well as conducting an MRI scan, would have characterized diffusivity, which is what is required by the instant claims. Applicant appears to be arguing subject matter not actually recited by the claims; see MPEP 2145(VI).
Claim Rejections - 35 USC § 101 – Subject Matter Eligibility
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 1-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of an abstract idea without significantly more.
As an initial matter, the examiner notes the following process for determining eligibility under 35 U.S.C. 101, as of MPEP 2106(III).
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Regarding step 1, this claim is drawn to a process.
Regarding step 2A, this analysis has two prongs, as of MPEP 2106.04(II)(A), relevant figure reproduced below.
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Regarding Step 2A, Prong 1, the claim recites an abstract idea, which is a judicial exception. Claim 1 recites comparing the images obtained in the presence of the contrast agent to those obtained in the absence of the contrast agent, and thereby forming a mental characterization of the transport of the contrast agent.
Regarding Step 2A Prong Two, the examiner notes that MPEP 2106.05(g) states that consideration when determining whether a claim integrates the judicial exception into a practical application in Step 2A Prong Two or recites significantly more in Step 2B is whether the additional elements add more than insignificant extra-solution activity to the judicial exception. The term "extra-solution activity" can be understood as activities incidental to the primary process or product that are merely a nominal or tangential addition to the claim. MPEP 2106.05(g)(3) indicates that an example of insignificant extra-solution activity is whether the limitation amounts to necessary data gathering and outputting, (i.e., all uses of the recited judicial exception require such data gathering or data output). An example of this under (i) is performing clinical texts on individuals to obtain input for an equation.
In this case, claim 1 recites obtaining the diffusivity contrast agent, administering this to the subject, and acquiring both pre-contrast and post-contrast images. However, the examiner understands this to be insignificant extra-solution activity as the purposes of these steps is to obtain clinical data for the purposes of comparing the post-contrast image with the pre-contrast image.
Regarding Step 2B, the examiner notes that the analysis for extra-solution activity also applies to Step 2B along with Step 2A prong two; see MPEP 2106.05(g). Nevertheless, the issue of whether the extra-solution activity is routine and conventional is to be analyzed for Step 2B. In this case, the general idea of obtaining pre-contrast MRI and post-contrast MRI and comparing these has been taught as of Harris et al. (Journal of Neurooncology, Vol. 112, 2013, pages 257-266), Gillies et al. (US 2017/0071496 A1) and Wahsner et al. (Chemical Reviews, Vol. 119, 2019, pages 957-1057), which were relied upon in the above prior art rejection. See e.g. Wahnser, page 964, right column, figure 7, reproduced below.
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As such, the general idea of comparing pre-contrast and post-contrast images would appear to be routine and conventional, and not add significantly more than the judicial exception.
Response to Arguments Regarding Patent Eligibility Issues
Applicant has presented arguments regarding the previously applied rejection for lack of patent eligibility, as of applicant’s response on 10 February 2026 (hereafter referred to as applicant’s response), pages 7-12. These arguments are addressed below.
Regarding Revised Step 2A Prong One of the eligibility analysis, applicant argues that the claimed subject matter is not directed to mathematical concepts, certain methods of organizing human activity, or mental processes, as of applicant’s response, page 8 and the top of page 9.
This is not persuasive. First, prong one of the revised Step 2A of the eligibility of analysis is the following:
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The above-reproduced text indicates that a claim which recites an abstract idea is drawn to the judicial exception of an abstract idea, and must be further analyzed under Step 2A prong 2 and Step 2B. In contrast, the above-reproduced text does not indicate that the claim must be entirely drawn to a judicial exception in order to be patent ineligible. Therefore, a method claim which includes steps drawn to abstract ideas and steps not drawn to abstract ideas would have been understood to have been drawn to the judicial exception of abstract ideas.
The last two steps of claim 1 recite the following.
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It is the examiner’s position that these steps can be performed in the human mind.
The examiner further notes that claim 1 also requires the following steps:
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The examiner takes the position that the administering step and the acquiring step cannot be entirely performed within the human mind. Nevertheless, it is the examiner’s position that these steps are insignificant extra-solution activity because these steps are being conducted to obtain data that will be analyzed in the human mind. See MPEP 2106.05(d)(II).
Applicant then argues the following, as of page 10, top of page.
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The examiner does not dispute that acquiring data by an MRI apparatus cannot be performed entirely in the human mind. However, the examiner takes the position that acquiring data by MRI is extra-solution activity in this case. The issue of extra-solution activity does not appear to have been addressed anywhere in applicant’s response.
Regarding Revised Step 2A Prong Two and Step 2B of the eligibility analysis, the examiner notes that applicant makes the following arguments on page regarding step 2A Prong Two:
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Similar arguments are made regarding Step 2B, relevant text reproduced below from page 12 of applicant’s response.
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These arguments are not persuasive. First, the examiner notes that a “mechanism” is not one of the four statutory categories set forth in Step 1 of the eligibility analysis. As best understood by the examiner, a “mechanism” is neither a process, a machine, a manufacture, nor a composition of matter. With that being said, the examiner does not take the position that instant claim 1 is not drawn to one of the four statutory categories because instant claim 1 is not drawn to a mechanism. With that being said, a new mechanism would not appear to be one of the four statutory categories and would consequently not appear to be patent eligible.
Additionally, the examiner disagrees that a new contrast mechanism or method has been invented, at least because the contrast agents taught by the prior art appear to be the same as the contrast agents disclosed on page 14 of the instant specification. The claims also do not recite any difference in e.g. the MRI apparatus, the pulse sequence, or the method of administering the contrast agent. In view of this, the examiner disputes applicant’s position that a new contrast mechanism has been discovered.
Applicant then provides additional arguments related to the Berkheimer memo, as of applicant’s arguments, page 12. Relevant text from applicant’s response has been reproduced below.
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The examiner understands this argument to be the following: First, the examiner understands that applicant does not appear to dispute the position that the first three steps of obtaining the diffusivity contrast agent, administering to the subject the diffusivity contrast agent, and acquiring post-contrast images by an MRI apparatus are routine and conventional. In contrast, applicant’s argument only appears to be that the “determining” and the “characterizing” steps of claim 1, which are the last two steps, are not routine and conventional. To the extent that this is applicant’s argument, it is not persuasive to overcome the applied rejection even if applicant’s position is correct. This is because the “determining” and “characterizing” steps of claim 1, even if not routine and conventional, are performed entirely in the human mind and therefore do not confer patent eligibility to the instant claims. The examiner has provided the following annotated version of claim 1 to best explain this position.
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As such, in view of this, the examiner maintains the position that the instant claims are not patent eligible.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571)272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612