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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 January 29, 2026 has been entered.
Applicants' arguments, filed January 29, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Claim Interpretation
Independent claim 1, from which all other claims depend and dependent claims 2 and 5 all contain wherein clauses.
A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.") MPEP 2111.04
The wherein clauses merely characterize the results of those steps so the "wherein" clause is not entitled to weight in construing the claim.
Claim Rejections - 35 USC § 112 – 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 – 3, 5, 12, 18, 20 and 21 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. This is a new matter rejection.
The claims were previously rejected as containing new matter and the claims as currently presented still contain new matter as detailed below.
For the wherein clauses of claim 1, 2 and 5, new language has been added discussing a comparison with tissue that does not have an injury or pathology (claim 1), tissue that does not have cancer (claim 2) or tissue that does not have the increment or decrement of metabolic activity (claim 5). No citation for support for this claim language has been provided and the closest support the Examiner could locate in the disclosure as filed is ¶ [0031] of the PGPub of the instant application which states “[i]n some embodiments, the method involves a single imaging step that detects elevated HDO in a tissue, e.g. by comparing it to other tissues” but particulars of those other tissues like “does not have an injury or pathology” or “does not have the increment or decrement of metabolic activity” are not disclosed. This embodiment is limited to elevated HDO and not a decrease, as would be encompassed by the “impaired glucose utilization and/or fatty acid oxidation” in claim 1 or the “decrement in metabolic activity” portion of claim 5. Therefore each of these claims contained new matter as the basis for the comparison and conclusion being drawn are not supported by the disclosure as originally filed.
The dependent claims fall therewith.
If Applicant is in disagreement with the Examiner regarding support for the amended claims, Applicant is respectfully requested to point to page and line number wherein support may be found for the instant invention and/or explain where and how inherent or implicit support is present for all of the claim limitations.
Claim Rejections - 35 USC § 112 – Indefiniteness
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.
Claim 5 is 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. This rejection is MAINTAINED for the reasons set forth herein.
Claim 5 was previously rejected as indefinite and remains indefinite for the reasons set forth below.
Neither the amendments nor the arguments provide any clarification as to the scope of “increment” based on the definition of “a usually small amount or degree by which something is made larger or greater” from the Britannica Dictionary that accompanied the December 10, 2025 Office Action. How large the change must be to qualify as an increment of metabolic activity remains unclear as there appears to be a size threshold such that any change in metabolic activity does not qualify as an increment. But what that threshold is has not been clarified and therefore remains unclear.
Claim 5 initially indicates that detection of elevated glucose utilization (emphasis added) in an indication of an increment of metabolic activity in the tissue. This is line with the definition of increment from the Britannica Dictionary that accompanied the December 10, 2025 Office Action and also definition 2 of increment from Merriam-Webster (accessed June 9, 2026). Claim 5 then goes on to recite “wherein elevated glucose utilization and/or fatty oxidation in the tissue having the increment of decrement of metabolic activity. There is insufficient antecedent basis for the limitation “the tissue having the increment of decrement of metabolic activity” in the claim. While this antecedent basis issue adds to the confusion, based on the physical parameter being measured, it would seem that an increment only referring to an increase would align with elevated glucose utilization and/or fatty acid oxidation phrasing of these claims. Definition 1 of increment from Merriam-Webster indicates that increment can mean “the amount of degree by which something changes” and those changes in value can be positive or negative change. But as decrement is then added which is associated with a decrease, it does not appear that the interpretation of increment being positive or negative is being used in the context of elevated glucose utilization and/or fatty acid oxidation. This renders the claim unclear as can any increase or decrease, of some undefined magnitude, be an indication of elevated glucose utilization and/or fatty acid oxidation? Claim 1 says impaired utilization indicates injury or pathology and claim 2 indicates that elevated glucose utilization indicates the specific pathology of cancer so increases and decreases can indicate the same type of issue. Does the recitation “increment or decrement of metabolic activity” indicate that the standalone recitation of “increment of metabolic activity” includes positive or negative changes in the metabolic activity?
The basis of this comparison is “a tissue that does not have an increment or decrement of metabolic activity”. Unless a tissue is dead, all tissues have some level of metabolic activity. Does this mean that “a tissue that does not have an increment or decrement of metabolic activity” is one whose metabolic activity is relatively constant such that any variation is less than the threshold to be considered an increment and/or decrement? Even if this is what is meant, without a clear definition as to the magnitude of change required to be an increment and/or decrement, the claim remains unclear. Or is this comparison made with dead tissue that does not have metabolic activity, but then the level of metabolic activity cannot have negative values.
Please clarify.
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.
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, 2, 5, 18, 20 and 21 were rejected under 35 U.S.C. 103 as being unpatentable over De Feyter et al. (Sci Adv, 2018) in view of Mateescu et al. (Adv Exp Med Bio, 2011). This rejection is MAINTAINED for the reasons of record set forth herein.
De Feyter et al. discloses the administration of [6,6’-2H2]glucose to either rats or humans (p 8, col 1, ¶¶ 3 and 4) followed for 2H MR signal acquisition (p 9, col 1, ¶ 1), reading on 2-NMR magnetic imaging required of the instant claims. The title indicates that the studies are for 3D mapping of metabolism in vivo and as glucose was the deuterated substrate administered, this indicates that the studies would provide information as to glucose utilization in the subject. As shown in figures 1 – 4, imaging of the brain of the subject was carried out. As evidenced by Mateescu et al. (Adv Exp Med Bio, 2011), the peak for HDO occurs at 4.8 ppm (legend of figure 26.2), and therefore the signal from HDO was collected in the experiments of De Feyter et al. (e.g., Figures 2D and 3B). [6,6’-2H2]glucose was preferred over the perdeuterated glucose (also known as [1,2,3,4,5,6,6-2H7]glucose or [2H7]glucose) for cost reasons and to minimize 2H NMR spectra complexity (p 8, col 1, ¶ 3).
The use of [2H7]glucose and explicit analysis of the DHO signal are not disclosed by De Feyter et al.
Mateescu et al. discloses the measurement of the rate of formation of nascent deuterated mitochondrial water using deuterium magnetic resonance (DMR) after intravenous administration of deuterated glucose (whole document, e.g., abstract). DMR has been used to elucidate the metabolic pathways of gluconeogenesis and in fermentation (p 194, ¶ 2). The left panel of figure 1 shows glucose metabolism and HDO water formation in mitochondria. The hydroxyl protons of glucose are rapidly exchanging and employing glucose deuterated at all carbon atoms results in high intensity deuterium signals (p 197, ¶ 2). Baseline spectra were recorded at the beginning of the process and then[2H7]glucose was administered (p 195, ¶ 1). As shown in time course of figures 3 and 4, the simultaneous in vivo, noninvasive determination of glucose and oxygen consumption could be determined as initial HDO signals originate overwhelmingly in mitochondria (p 197, ¶ 1). The peak for HDO occurs at 4.8 ppm (legend of Figure 2).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the perdeuterated [2H7]glucose for deuterium magnetic resonance studies such as those involving measurement of the HDO signal to monitor the conversion of [2H7]glucose into HDO as disclosed by De Feyter et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because various compounds can be administrated and localization of specific isotopes such as deuterium measured. The protons found in glucose can become present in HDO whose signal can be measured and tracked over time. Therefore, the use of perdeuterated glucose is preferred for such studies as when not all protons present are deuterium, as in the preferred substrate of De Feyter et al., not all of the resulting water would not be trackable via DMR and more atoms of deuterium will result in a larger signal. As to the time course of signal acquisition, short time frames as in Mateescu et al. allow for determination of water generated in the mitochondria before it can diffuse elsewhere in the cell. However, such spatial resolution is not important for all applications and after baseline spectral acquisition, longer time frames can permit a broader view of glucose metabolism and HDO generation at longer time scales such as to make determinations as to a decreased or increased metabolic rate for a particular tissue, which given the conditions under which the DMR data was collected can inform the person of ordinary skill in the art as to the state of the tissue such as the brain being observed. While healing tissue or rapidly growing tissue can be more metabolically active, lack of metabolic activity compared to an expected metabolic level would also indicate issues such as injury that one of ordinary skill in the art could investigate further. The collection of multiple scans at various time points such as shown in figure 3 of Mateescu et al. allows for information as to the kinetics of HDO formation to be investigated. The implications of the imaging, e.g., detection of elevated or impaired glucose utilization as recited in the wherein clauses, necessarily arises from the imaging of the subject and claimed method of imaging a tissue in a subject is carried out even without explicit recitation as to the elevated/impaired nature of glucose utilization by the applied prior art and is also the result of a mental step of evaluation of the data generated and does not patentably distinguish the instant claims over the prior art.
Applicants traverse this rejection on the grounds that claim 4 was not rejected over this combination of prior art and respectfully requests withdrawal of the rejection.
Claim 4 was inadvertently omitted from the prior art rejections in the Final Officer Action mailed December 10, 2025 and as discussed above, the wherein clauses merely describe the outcome of the positively recited method steps and do not patentably distinguish over the applied prior art.
Claim(s) 20 and 21 were rejected under 35 U.S.C. 103 as being unpatentable over De Feyter et al. and Mateescu et al. as applied to claims 1, 2, 5, 18, 20 and 21 above, and further in view of Fan et al. (US 2012/0237937).
De Feyter et al. and Mateescu et al. are discussed above.
Neither reference explicitly discloses scan acquisition within 8 – 24 minutes of step (a), the administration of the labeled substrate step.
Fan et al. discloses methods of detecting the presence of cancer in animal tissue by administration of a labeled molecule and in some embodiments, the methods comprising obtaining an NMR spectra (whole document, e.g., abstract). The administered molecules can be glucose and can contain 13C and/or 2H (¶ [0030]). For a 13C labeled glucose, the signal strongly increased immediately after injection and decreased with an apparent half-life of 16 – 22 minutes in the mice used in these experiments, and the rate of appearance of 13C lactate was approximately equal to the initial rate of glucose consumption, but then decayed after about 20 minutes (¶ [0136]). The time courses were also dependent on the tissue being studied (e.g., figure 9 and ¶ [0138] onward).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to vary the time scale of data acquisition depending on factors such as the compound(s) being monitored and the tissue(s) of interest in the method of De Feyter et al. that can use the perdeuterated substate disclosed by Mateescu et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the labeled compounds undergo various reactions in the body and part of the method is to monitor such products. Depending on the compound(s) being monitored, the compounds can appear or disappear at different rates and the data analysis should be optimized based on the expected time scales of the process being investigated. Fan et al. discloses a half-life of 13C glucose of about 20 minutes, and when looking for a product produced from glucose metabolism, a time frame of approximately 1 half-life should result in sufficient glucose degradation compounds being generated to be observable. The collection of multiple images at different time can generate information about the rate of the process being observed. It would have been customary for an artisan of ordinary skill to determine the optimal time for each image in order to best achieve the desired results and there is no evidence of record as to the criticality of the claimed time frame.
Applicants argues that these claims depend from claim 1 and Fan does not rectify the deficiencies between De Feyter et al. and Mateescu.
As discussed in greater detail above, De Feyter et al. and Mateescu are not deficient as alleged by Applicants so Fan is not required to cure the alleged deficiencies and provides explicit disclosure of the acquisition of multiple images within the time frame required by the rejected claims and there is no evidence of record as to the criticality of the claimed time frame.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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