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 .
Election/Restrictions
Applicant’s election of claims 2-12 in the reply filed on 16 April 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 1 has been withdrawn and claims 13-16 have been added.
Claim Objections
Claim 5 is objected to because of the following informalities:
“PaO2 about” in line 1 of claim 5 should read as “PaO2 is about”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 6 is further rejected due to their dependency to claim 5.
The term “about” in claims 5 and 15 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The disclosure fails to provide a clear definition for “about.” It is unclear what it means to be “about 40/50/95 mmHg” as it is unclear what range the term “about” covers. Clarification is requested.
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 2 and 4-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than an abstract idea. A streamlined analysis of claim 2 follows.
STEP 1
Regarding claim 2, the claim recites a series of steps or acts, including administering a deoxyhemoglobin signal using a sequential gas delivery device. Thus, the claim is directed to a process, which is one of the statutory categories of invention.
STEP 2A, PRONG ONE
The claim is then analyzed to determine whether it is directed to any judicial exception. The steps of:
administering a deoxyhemoglobin signal using a sequential gas delivery device;
measuring a magnetic resonance signal in a voxel of the subject’s brain using magnetic resonance imaging (MRI) responsive to the deoxyhemoglobin signal; and
calculating a perfusion metric for the voxel based on the magnetic resonance signal;
wherein the deoxyhemoglobin signal comprises a step change in deoxyhemoglobin implemented by:
targeting a first partial pressure of oxygen in arterial blood (PaO2) in a subject using the sequential gas delivery device for a first duration of time; and
targeting a second PaO2 using the sequential gas delivery device for a second duration of time;
wherein the perfusion metric is calculated based on a rate of change for the magnetic resonance signal and an integral of the rate of change
set forth a judicial exception. These steps describe a concept performed in the human mind (including an observation, evaluation, judgment, opinion). Thus, the claim is drawn to a Mental Process, which is an Abstract Idea. The administering step also describes a concept of managing personal behavior or relationships or interactions between people (including social activities, teaching, and following rules or instructions). Thus, the claim is also drawn to Organizing Human Activity, which is also an Abstract Idea.
STEP 2A, PRONG TWO
Next, the claim as a whole is analyzed to determine whether the claim recites additional elements that integrate the judicial exception into a practical application. The claim fails to recite an additional element or a combination of additional elements to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception. Claim 2 recites calculating a perfusion metric for the voxel based on the magnetic resonance signal, which is merely adding insignificant extra-solution activity to the judicial exception (MPEP 2106.05(g)). The calculating of the perfusion metric does not provide an improvement to the technological field, the method does not effect a particular treatment or effect a particular change based on the calculated perfusion metric, nor does the method use a particular machine to perform the Abstract Idea.
STEP 2B
Next, the claim as a whole is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Besides the Abstract Idea, the claim recites additional step of:
measuring a magnetic resonance signal in a voxel of the subject’s brain using magnetic resonance imaging (MRI) responsive to the deoxyhemoglobin signal; and
The measuring step is a well-understood, routine and conventional activity for those in the field of medical diagnostics. Further, the measuring step is recited at a high level of generality such that it amounts to insignificant presolution activity, e.g., mere data gathering step necessary to perform the Abstract Idea. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional step that distinguishes it from well-understood, routine, and conventional data gathering and comparing activity engaged in by medical professionals prior to Applicant's invention. Furthermore, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and comparing steps do not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int'l, 134 S.Ct. 2347, 2358-59 (2014)).
The device recited in the claim is a generic device comprising generic components configured to perform the abstract idea. The recited sequential gas delivery is configured to perform the Abstract Idea. According to section 2106.05(f) of the MPEP, merely using a computer as a tool to perform an abstract idea does not integrate the Abstract Idea into a practical application.
Consideration of the additional elements as a combination also adds no other meaningful limitations to the exception not already present when the elements are considered separately. Unlike the eligible claim in Diehr in which the elements limiting the exception are individually conventional, but taken together act in concert to improve a technical field, the claim here does not provide an improvement to the technical field. Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claim as a whole does not amount to significantly more than the exception itself. The claim is therefore drawn to non-statutory subject matter.
The dependent claims also fail to add something more to the abstract independent claims. Claims 4, 5, 9, and 13-15 merely provide more details to the first and second PaO2 and perfusion metric, which does not add anything significantly more. Claims 6-8, and 10-12 recite steps that add to the Abstract Idea as these claims recite mental processing steps or mathematical steps. The steps recited in the independent claims maintain a high level of generality even when considered in combination with the dependent claims.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 2, 4-6, 9, 10, and 13-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Poublanc et al. (“Non-invasive brain perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: preliminary data” – cited by Applicant).
Regarding claim 2, Poublanc et al. teaches a method (Page 2, “Methods”) comprising:
administering a deoxyhemoglobin signal using a sequential gas delivery device (Page 2, “Methods”; “A gas blender with a sequential gas delivery breathing circuit and software enabling prospective arterial blood gas targeting was used to implement rapid lung changes in the partial pressure of blood oxygen (PaO2) while maintaining isocapnea.”);
measuring a magnetic resonance signal in a voxel of the subject’s brain using magnetic resonance imaging (MRI) responsive to the deoxyhemoglobin signal (Page 2, “Methods”; “R2* changes were measured using blood oxygenation dependent (BOLD) MRI signal changes); and
calculating a perfusion metric for the voxel based on the magnetic resonance signal (Fig. 4 and Page 11, 2nd paragraph; “Maps displaying CBV, MTT and CBF calculated from the generated data are shown in Fig. 4…Values of perfusion metrics are listed in table 1”);
wherein the deoxyhemoglobin signal comprises a step change in deoxyhemoglobin implemented by:
targeting a first partial pressure of oxygen in arterial blood (PaO2) in a subject using the sequential gas delivery device for a first duration of time (Page 6, “Respiratory protocol”; “End-tidal PO2 (PETO2) was lowered to a baseline of about 55 mmHg (hypoxia baseline)…Hypoxia was maintained for 60 to 90s”); and
targeting a second PaO2 using the sequential gas delivery device for a second duration of time (Pages 3-4; “…we restricted the PO2 range from ~100 mmHg (normoxia) to about ~30 mmHg, corresponding to desaturation.” Page 6, “Respiratory protocol”; “…followed by a gas challenge with the PETO2 target set to 100 mmHg for 10s to transiently saturate hemoglobin with O2 before returning to baseline. This normoxic challenge and return to hypoxic baseline was then repeated 3 to 4 times in one session (Fig. 1).”);
wherein the perfusion metric is calculated based on a rate of change for the magnetic resonance signal and an integral of the rate of change (Fig. 4 and Page 11, 2nd paragraph; “Maps displaying CBV, MTT and CBF calculated from the generated data are shown in Fig. 4…Values of perfusion metrics are listed in table 1”).
Regarding claim 4, Poublanc et al. teaches wherein the first PaO2 corresponds to hypoxia in the subject (Page 6, “Respiratory protocol”; “End-tidal PO2 (PETO2) was lowered to a baseline of about 55 mmHg (hypoxia baseline)…Hypoxia was maintained for 60 to 90s”) and the second PaO2 corresponds to normoxia in the subject (Pages 3-4; “…we restricted the PO2 range from ~100 mmHg (normoxia) to about ~30 mmHg, corresponding to desaturation.” Page 6, “Respiratory protocol”; “…followed by a gas challenge with the PETO2 target set to 100 mmHg for 10s to transiently saturate hemoglobin with O2 before returning to baseline. This normoxic challenge and return to hypoxic baseline was then repeated 3 to 4 times in one session (Fig. 1).”).
Regarding claim 5, Poublanc et al. teaches wherein the first PaO2 is about 40 mmHg (Page 6, “Respiratory protocol”; “about 55 mmHg”) and the second PaO2 is about 95 mmHg (Page 6, “Respiratory protocol”; “100 mmHg”).
Regarding claim 6, Poublanc et al. teaches maintaining normocapnia while targeting the first PaO2 (Page 6, “Respiratory protocol”; “maintaining normocapnia”).
Regarding claim 9, Poublanc et al. teaches wherein the perfusion metric is selected from a group consisting of: contrast arrival time (AT), relative mean transit time (MTT), relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV), absolute CBV, absolute MTT, and absolute CBF (Page 2, “Methods”).
Regarding claim 10, Poublanc et al. teaches wherein the magnetic resonance signal is measured using blood oxygen level dependent (BOLD) MRI (Page 2, “Methods”; “BOLD MRI signal”).
Regarding claim 13, Poublanc et al. teaches wherein the first and second targeted PaO2 are between 20 and 120 mmHg (Page 6, “Respiratory protocol”; “End-tidal PO2 (PETO2) was lowered to a baseline of about 55 mmHg (hypoxia baseline)…Hypoxia was maintained for 60 to 90s…followed by a gas challenge with the PETO2 target set to 100 mmHg for 10s to transiently saturate hemoglobin with O2 before returning to baseline. This normoxic challenge and return to hypoxic baseline was then repeated 3 to 4 times in one session (Fig. 1)”).
Regarding claim 14, Poublanc et al. teaches wherein the first PaO2 is greater than 40 mmHg (Page 6, “Respiratory protocol”; “End-tidal PO2 (PETO2) was lowered to a baseline of about 55 mmHg (hypoxia baseline)…”).
Regarding claim 15, Poublanc et al. teaches wherein the first PaO2 is about 55 mmHg (Page 6, “Respiratory protocol”; “End-tidal PO2 (PETO2) was lowered to a baseline of about 55 mmHg (hypoxia baseline)…”).
Regarding claim 16, Poublanc et al. teaches wherein the steps of administering the deoxyhemoglobin signal and measuring the magnetic resonance signal are repeated and the perfusion metric is further calculated based on the repeated measurement (Page 6, “Respiratory protocol”; “…followed by a gas challenge with the PETO2 target set to 100 mmHg for 10s to transiently saturate hemoglobin with O2 before returning to baseline. This normoxic challenge and return to hypoxic baseline was then repeated 3 to 4 times in one session (Fig. 1).”).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Poublanc et al. in view of Klein et al. ‘481 (US Pub No. 2016/0158481).
Regarding claim 7, Poublanc et al. teaches wherein the sequential gas delivery device is programmed to target the first PaO2 within one or two breaths.
Klein et al. ‘481 teaches that if the goal of the end tidal targeting sequence is to achieve 50 mmHg in one breath, and then maintain 50 mmHg for the ensuing 20 breaths, both FRC (functional residual capacity) and a non-lung related parameter should be tuned. Tuning FRC is important for transitioning accurately between end-tidal values ([0426]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the sequential gas delivery device of Poublanc et al. to include being programmed to target the first PaO2 within one or two breaths as Klein et al. ‘481 teaches that this will aid in turning FRC accurately between end-tidal values.
Regarding claim 8, Poublanc et al. teaches wherein the sequential gas delivery device is programmed to target the second PaO2 within one or two breaths.
Klein et al. ‘481 teaches that if the goal of the end tidal targeting sequence is to achieve 50 mmHg in one breath, and then maintain 50 mmHg for the ensuing 20 breaths, both FRC (functional residual capacity) and a non-lung related parameter should be tuned. Tuning FRC is important for transitioning accurately between end-tidal values ([0426]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the sequential gas delivery device of Poublanc et al. to include being programmed to target the second PaO2 within one or two breaths as Klein et al. ‘481 teaches that this will aid in turning FRC accurately between end-tidal values.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Poublanc et al. in view of Jaspersen et al. ‘320 (US Pub No. 2014/0039320).
Regarding claim 11, Poublanc et al. teaches all of the elements of the current invention as mentioned above except for fitting the rate of change to a gamma variate function, wherein calculating the perfusion metric is based on the gamma variate function.
Jaspersen et al. ‘320 teaches the following equation:
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Jaspersen et al. ‘320 teaches that h is the gamma-variate with parameters α and β, h(y/k)/k corresponds to a gamma-variate with parameters α and kβ. For suitable parameterizations of f, the integral can be carried out analytically, and it is thus easy to computer OEC (oxygen extraction capacity) for any given value of k given a significant advantage upon implantation ([0108]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Poublanc et al. to include fitting the rate of change to a gamma variate function, wherein calculating the perfusion metric is based on the gamma variate function as Jaspersen et al. ‘320 teaches that this will aid in computing oxygen extraction capacity.
Regarding claim 12, Poublanc et al. teaches all of the elements of the current invention as mentioned above except for calculating the integral of the gamma variate function, wherein calculating the perfusion metric is based on the integral of the gamma variate function.
Jaspersen et al. ‘320 teaches the following equation:
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510
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Jaspersen et al. ‘320 teaches that h is the gamma-variate with parameters α and β, h(y/k)/k corresponds to a gamma-variate with parameters α and kβ. For suitable parameterizations of f, the integral can be carried out analytically, and it is thus easy to computer OEC (oxygen extraction capacity) for any given value of k given a significant advantage upon implantation ([0108]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Poublanc et al. to include calculating the integral of the gamma variate function, wherein calculating the perfusion metric is based on the integral of the gamma variate function as Jaspersen et al. ‘320 teaches that this will aid in computing oxygen extraction capacity.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Jiang ‘698 (US Pub No. 2022/0015698) teaches a method of identifying tumor drug resistance during treatment.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AURELIE H TU whose telephone number is (571)272-8465. The examiner can normally be reached [M-F] 7:30-3:30.
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/AURELIE H TU/ Primary Examiner, Art Unit 3791
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