DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 26 May 2026 has been entered, and the arguments presented therein 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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
The instant claims have been amended to require acquisition of diffusion weighted MRI images. The examiner presents the following regarding how this phrase will be interpreted.
As relevant art which the examiner cites in order to clarify how the phrase “diffusion weighted MRI” interpreted, the examiner cites MRIQuestions (https://mriquestions.com/making-a-dw-image.html accessed 25 June 2026, 3 printed pages). MRIQuestions teaches the following on page 1, relevant text and figure reproduced below.
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The caption at the bottom right of the above-reproduced figure indicates that stationary spins (corresponding to stationary molecules) have a signal unaffected by the gradients, but diffusing spins (corresponding to diffusing molecules) are affected by the gradients. This would appear to indicate that signal from either stationary or diffusing molecules is lost in the diffusion weighted imaging. The diffusion weighted image, when compared to MRI completed with a “regular” pulse sequence, indicates what components of the MRI signal are diffusing and what components of the MRI signal are not diffusing.
MRIQuestions provides a more modern diffusion weighted imaging pulse sequence on the bottom of page 1, which is reproduced below.
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The examiner clarifies that the claims are not understood to be limited to the exact pulse sequence described above. Nevertheless, the phrase “diffusion weighted” is understood to refer to pulse sequences that have the same general features as those described by MRIQuestions. A simple 90° radiofrequency pulse with no magnetic field gradients would not appear to be diffusion weighted imaging.
Claim Rejections - 35 USC § 112(a) – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-11 and 13-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 has been amended to recite the following:
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The above-indicated claim amendment indicates that the modulated diffusivity contrast agent is administered to the subject. This appears to lack adequate support in the original application as filed. In contrast, the original application as filed appears to disclose administering the diffusivity contrast agent to the subject rather than administering the modulated diffusivity contrast agent to the subject. In support of this position, the examiner has reproduced an annotated version of figure 1 below.
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As such, it is the examiner’s position that the instant application fails to disclose administration of the modulated diffusivity contrast agent to the subject. Therefore, claim amendments drawn to this appear to be drawn to new matter unsupported by the original application as filed.
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 1-11 and 13-24 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 tests 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 prior art rejection set forth in the office action mailed on 26 May 2026. 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. Even though the above-cited reference teaches a contrast agent that is outside the scope of the currently claimed contrast agents, the above-cited reference still teaches that comparing pre-contrast and post-contrast images would have been routine and conventional.
Response to Arguments Regarding Subject Matter Eligibility Issues
Applicant has presented arguments regarding the previously applied rejection for lack of patent eligibility, as of applicant’s response on 26 May 2026. These arguments are discussed below.
Applicant argues that the instant claims are not drawn to judicial exceptions. See applicant’s response, page 8, relevant text reproduced below.
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Applicant makes further arguments regarding this as of the bottom of page 9, relevant text reproduced below.
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The examiner does not dispute that administration of a contrast agent and acquisition of an MRI image cannot practically be performed in the human mind. Nevertheless, applicant’s arguments are not persuasive because the examiner understands these steps to be extra-solution activity. To further explain this position, the examiner cites MPEP 2106.04(d)(2)(c), which states the following:
For example, consider a claim that recites (a) administering rabies and feline leukemia vaccines to a first group of domestic cats in accordance with different vaccination schedules, and (b) analyzing information about the vaccination schedules and whether the cats later developed chronic immune-mediated disorders to determine a lowest-risk vaccination schedule. Step (b) falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). While step (a) administers vaccines to the cats, this administration is performed in order to gather data for the mental analysis step, and is a necessary precursor for all uses of the recited exception. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.
The examiner notes that in the above-indicated example, the claimed step of administering vaccination to cats clearly cannot be performed in the human mind. Nevertheless, the MPEP appears to indicate that the above-indicated claim is patent ineligible. As such, the presence of a single step in a method claim reciting a process that is not a mental process would be insufficient in and of itself to render the instant claims to be patent eligible.
Applicant then makes the following argument, as of the top of page 10 of applicant’s response.
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Even if, purely en arguendo, it is true that the claimed invention uses a contrast approach not used in conventional gadolinium-enhanced MRI, this still does not address the issue of extra-solution activity and is therefore not persuasive for that reason. This argument similarly applies to applicant’s arguments on pages 12-13 of applicant’s response.
Applicant makes the following argument on page 11, which is reproduced below.
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This is not persuasive because the description of the MRI apparatus and image acquisition as “post-solution activity” does not represent an accurate summary of the examiner’s position. In contrast, the examiner takes the position that the MRI apparatus and image acquisition are pre-solution activity rather than post-solution activity. This is because the MRI apparatus and image acquisition occur prior to the steps of determining changes and characterizing a transport of the diffusivity contrast agent. The MRI apparatus and image acquisition are used to gather data for the “determining” and “characterizing” step. Such data gathering is taught by the MPEP to be pre-solution activity as per MPEP 2106.05(g), first paragraph in section.
Applicant argues on page 11 that the claimed subject matter does not simply automate known technology. This is not persuasive as it appears to address a position not actually taken by the examiner. At no point did the examiner argue that the claimed invention simply automates known technology.
Applicant makes the following argument on page 13.
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The examiner disagrees that the instant claims can be characterized as reciting a specific diffusivity. The term “specific” is generally interpreted as being drawn to a numerical value. However, the instant claims do not recite a numerical value of diffusivity. As such, contrary to applicant’s arguments, the instant claims do not recite a specific diffusivity.
Suggestion on How to Overcome the Subject-Matter Eligibility Rejection:
The examiner takes the position that in order to overcome the applied rejection, applicant may cancel the following two steps from claim 1 to overcome the applied rejection under 35 U.S.C. 101.
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Applicant should also cancel claims 22 and 24 as these claims appear to further limit steps performed in the human mind.
Cancelling the above-indicated subject matter would appear to overcome the patent-ineligibility rejection because upon doing so, the steps of administering the contrast agent and acquiring an image with an MRI apparatus would no longer be pre-solution activity for the “determining” and “characterizing” steps.
With that being said, the examiner notes that
cancellation of these steps from claim 1 does not overcome the applied rejection over 35 U.S.C. 112, and
cancellation of the above-indicated steps from claim 1 will necessitate the examiner to conduct a new prior art search because such an would cause claim 1 to be broader than prior to this amendment.
As such, applicant should not expect that amending the claims to cancel the above two indicated steps and to cancel claims 22 and 24 would necessarily and/or immediately result in allowable subject matter.
Withdrawn Prior Art Rejections
Previously in the prosecution history, the examiner rejected the instant claims as obvious over Harris et al. (Journal of Neurooncology, Vol. 112, 2013, pages 257-266) in view of Gillies et al. (US 2017/0071496 A1), and further in view of Wahsner et al. (Chemical Reviews, Vol. 119, 2019, pages 957-1057). Previously presented prior art rejections relying upon these references have been withdrawn. This is because all of the above references are drawn to gadolinium contrast agents. Gadolinium contrast agents are understood by the examiner to be paramagnetic; see Wahnser, page 963, right column, section 3.2.1, reproduced below with annotation by the examiner.
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As such, in view of the newly added claim limitation excluding paramagnetic or super-paramagnetic contrast agents, the previously applied prior art rejections over Harris, Gillies, and Wahnser have been withdrawn.
Applicant presented arguments in applicant’s response on 26 May 2026. The examiner has not substantively addressed the arguments on pages 14-18 of applicant’s response regarding the previously applied prior art rejections, as these arguments appear to be moot in view of the withdrawal of previously applied prior art rejections.
Relevant Prior Art – No Rejection – T2 Magnetic Contrast Agents
The examiner additionally notes that another common form of MRI contrast agents are iron containing nanoparticles, usually iron oxide nanoparticles. As best understood by the examiner, these are often used as T2 contrast agents. See e.g. Hyeon et al. (US 2015/0079006 A1), with Hyeon teaching that these contrast agents are superparamagnetic in paragraphs 0008 and 0011. These contrast agents are also understood to be excluded by the newly amended instant claims because they are superparamagnetic.
Relevant Prior Art – No Rejection – Hyperpolarized MRI Imaging Agents
The examiner further notes that there is prior art relating to the use of hyperpolarized xenon as an MRI imaging agent to evaluation diffusion and barrier function. Such work has been performed by the inventor Bastiaan Driehuys, and Driehuys et al. (US 2008/0089846 A1) is representative. Driehuys et al. (hereafter referred to as Driehuys) is drawn to the use of hyperpolarized 129Xe to evaluate barrier function in a patient, as of Driehuys ‘846, title and abstract. This method evaluates hyperpolarized xenon diffusion, as of Driehuys, at least paragraph 0018.
As best understood by the examiner, hyperpolarized xenon is neither paramagnetic nor superparamagnetic.
With that being said, it appears to the examiner that hyperpolarized xenon cannot meet the requirement of being a modulated contrast agent, and Driehuys does not teach the requirement of modulating one or more of the molecular weight, solubility, and viscosity of the contrast agent. This is at least because xenon is a noble gas, and as such is always in gaseous form and does not engage in covalent bonding under the conditions taught by Driehuys. As such, the molecular weight, solubility, and viscosity of xenon is not modulated by Driehuys. The process of hyperpolarization of xenon, which is taught by Driehuys, does not meet the claimed requirements because it does not affect the molecular weight, solubility, or viscosity of the xenon. The examiner notes that the process of hyperpolarization does involve cooling to near absolute zero, which would have resulted in a decrease in viscosity. However, the administered xenon would appear to be in a gaseous state, indicating that the viscosity of the pre-hyperpolarized xenon and post-hyperpolarized xenon is the same, indicating no net change in viscosity.
Additionally, although Driehuys is drawn to measuring diffusion, the method of Driehuys cannot be considered to be diffusion weighted imaging. See the above section entitled “Claim Interpretation” for more information as to how the examiner is interpreting the phrase “diffusion weighted MRI.” In contrast, the pulse sequence appears to be a single radiofrequency pulse, as of Driehuys, paragraph 0009, which would not appear to be diffusion weighted imaging. Driehuys appears to use differences in chemical shift of xenon to detect diffusion rather than diffusion weighted imaging. This is discussed in paragraph 0075. As best understood by the examiner, xenon at 0 ppm refers to gaseous xenon, xenon at 197 ppm refers to xenon in the barrier, and xenon at 211 ppm refers to xenon in the blood. As such, while Driehuys measures xenon diffusion, Driehuys does not use diffusion weighted imaging to do so and there would have been no motivation for the skilled artisan to have used diffusion weighted imaging for this purpose.
In order to promote compact prosecution, the examiner has set forth an explanation of what would be likely to cause the examiner to reconsider the decision not to reject the claims over Driehuys. The examiner takes the position that if applicant were to amend the claims to recite that
(a) the diffusivity contrast agent, rather than the modulated diffusivity contrast agent is administered to the subject and
(b) if applicant were to amend the claims to remove the requirement of diffusion weighted MRI,
then the examiner would likely reconsider the decision not to rejection the claims as obvious over Driehuys.
Conclusion
No claim is allowed.
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.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
Prosecution Insights