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 . Claims included in the prosecution are claims 1-5.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/17/2026 has been entered.
Applicants' arguments, filed 04/17/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 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 1-5 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.
The term “normal” in claim 1 is a relative term which renders the claim indefinite. The term “normal” 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. It is not clear what the normal blood glucose concentration is with respect to. For example, there are fasting and post-meal glucose levels, different glucose levels for diabetics and non-diabetics, and different glucose levels for different ages.
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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Nishiyama et al. (US 2015/0225368, Aug 13, 2015) (hereinafter Nishiyama) in view of Kim et al. (Mitochondrial Complexes I and II are more susceptible to autophagy deficiency in mouse β-cells, 2015) (IDS reference) (hereinafter Kim) and Gonzalez et al. (The emerging role of autophagy in the pathophysiology of diabetes mellitus, Jan. 2011) (hereinafter Gonzalez).
Nishiyama discloses a compound suitable for the detection of mitochondrial complex-I (¶ [0001]). The compound is represented by formula (1-0):
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(¶ [0009]).
Q1 may be 18F or -O11CH3 (¶ [0010]). The compound may be specifically the compound of formula (1-0’):
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(¶ [0029]).
From the viewpoint of binding affinity to mitochondrial complex-1, the compound suitable for detection of mitochondrial complex-1 is preferably a compound represented by formula (1-2):
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(¶ [0031]).
Compound (1) tends to specifically bind to mitochondrial complex-1 when administered to a living body. Therefore, compound (1) is suitable for the detection of mitochondrial complex-1. In a case in which Q1 is 18F or -O11CH3, the compound is enabled to emit positrons. The positrons emit γ-radiation and when this γ-radiation is measured with an apparatus used in a PET method, the biodistribution of the compound (1-0) can be imaged quantitatively over time. Therefore, when the compound (1-0) is used, a site where mitochondrial complex-1 exists in the body of a test subject is detected (¶ [0051]). An experiment for evaluation of the intracerebral activity of mitochondrial complex-1 in a Parkinson's disease model monkey were carried out (¶ [0190]). [18F]BCPP-EF was used as the PET probe. It was found that the amount of the PET probe accumulating in the brain was smaller in the Parkinson’s disease model monkey, compared with the normal monkey. This suggest that there is a correlation between the onset of Parkinson’s disease and the activity of mitochondrial complex-1 (¶ [0197]).
Nishiyama differs from the instant claims insofar as not disclosing using the compound for diagnosing a pancreatic function.
However, Kim discloses wherein damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient β-cells were investigated. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets. Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1). It was concluded that impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy (abstract).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have administered the compound of Nishiyama for diagnosing a pancreatic function motivated by the desire to investigate whether an impairment of autophagy is present without having to isolate pancreatic islets since the compound of Nishiyama detects mitochondrial complex-I and when there is an impairment of autophagy in pancreatic β-cells, mitochondrial complex-1 expression is suppressed as taught by Kim.
The combined teachings of Nishiyama and Kim do not teach wherein the compound is administered to a subject with a normal glucose concentration.
However, Gonzalez discloses wherein a reduced level of β-cell autophagy could be a predisposing factor for type 2 diabetes (page 5).
As discussed above, the compound of Nishiyama detects mitochondrial complex-1 and mitochondrial complex-1 expression is suppressed when there is an impairment of autophagy in pancreatic β-cells. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have administered the compound of Nishiyama to a subject with a normal glucose concentration motivated by the desire to determine whether there is a suppression of mitochondrial complex-1, which would determine whether there is an impairment of autophagy in pancreatic β-cells, and which will then determine whether a subject will be predisposed for type 2 diabetes as taught by Gonzalez.
Response to Arguments
Applicant argues that the present application discloses that the suitability of compound (1-0) as a diagnostic agent for pancreatic function is not predictable without conducting in vivo studies.
The Examiner does not find Applicant’s argument to be persuasive. Obviousness requires a reasonable expectation of success. Obviousness does not require absolute predictability. See MPEP 2143.02. Thus, it is not required for the prior art to show wherein the claimed compound is effective in vivo as a diagnostic agent in order for one of ordinary skill in the art to have used the claimed compound as a diagnostic agent for pancreatic function. As discussed in the rejection, it would have been obvious to one of ordinary skill in the art to have administered the compound of Nishiyama for diagnosing a pancreatic function motivated by the desire to investigate whether an impairment of autophagy is present without having to isolate pancreatic islets since the compound of Nishiyama detects mitochondrial complex-I and when there is an impairment of autophagy in pancreatic β-cells, mitochondrial complex-1 expression is suppressed. Applicant has not explained why based off of these teachings one of ordinary skill in the art would not have had a reasonable expectation of success of using the claimed compound as a diagnostic agent for pancreatic function. As such, Applicant’s argument is unpersuasive.
Applicant argues that the results demonstrate that the present invention enables the detection of a decline in pancreatic function before any abnormal blood glucose levels are detected.
The Examiner does not find Applicant’s argument to be persuasive. One of ordinary skill in the art would have expected that the present invention enables the detection of a decline in pancreatic function before any abnormal blood glucose levels are detected. As discussed in the rejection, the claimed compound detects mitochondrial complex-1. There is an impairment of autophagy in pancreatic β-cells when mitochondrial complex-1 is suppressed. A reduced level of β-cell autophagy could be a predisposing factor for type 2 diabetes. Therefore, since the claimed compound essentially detects impairment of autophagy in pancreatic β-cells and an impairment of autophagy in pancreatic β-cells is a predisposing factor for type 2 diabetes, one of ordinary skill in the art would have expected detection of a decline in pancreatic function before any abnormal blood glucose levels are detected. As such, Applicant’s argument is unpersuasive.
Conclusion
Claims 1-5 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRACY LIU whose telephone number is (571)270-5115. The examiner can normally be reached Mon-Fri 9 am - 5 pm.
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/TRACY LIU/Primary Examiner, Art Unit 1614
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