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.
Applicants' arguments, filed 11/03/2025, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 § 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).
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.
Response to Arguments
Applicant argues that a person of ordinary skill in the art could not have predicted that the accumulation of compound (1-0) in the pancreas would vary in proportion to MC-I activity as a function of pancreatic organ damage.
The Examiner does not find Applicant’s argument to be persuasive. As discussed in the rejection, as taught by Kim, when there is an impairment of autophagy in pancreatic β-cells, mitochondrial complex-1 expression is suppressed. The compound of Nishiyama (i.e., claimed compound (1-0)) detects mitochondrial complex-1. Therefore, since the compound of Nishiyama (i.e., claimed compound (1-0)) detects MC-1 and MC-1 expression is suppressed when there is impairment of pancreatic β-cells, one of ordinary skill in the art would have predicted that the accumulation of the compound of Nishiyama (i.e., claimed compound (1-0)) in the pancreas would vary in proportion to MC-I activity as a function of pancreatic organ damage. As such, Applicant’s argument is unpersuasive.
Applicant argues that there is no teaching or motivation in Kim that its in vitro results would correlate with the behavior of MC-I in vivo. A person of ordinary skill in the art cannot assume that MC-I activity or expression can be detected in vivo in the same manner as an in vitro assay, nor can a person of ordinary skill in the art predict actual in vivo behavior of MC-I based solely on the disclosure of Kim.
The Examiner does not find Applicant’s argument to be persuasive. The rejection uses the combined teachings of Nishiyama and Kim. Nishiyama discloses in paragraph [0051] that when the compound (1-0) is used, a site where mitochondrial complex-1 exists in the body of a test subject is detected. Thus, Nishiyama teaches wherein MC-1 activity or expression can be detected in vivo. Furthermore, obviousness does not require absolute predictability. See MPEP 2143.02(II). Therefore, although Nishiyama does not disclose detecting MC-1 in the pancreas specifically, because Nishiyama discloses wherein MC-1 can be detected in the body, one of ordinary skill in the art would have been motivated to detect MC-1 in the pancreas. As such, Applicant’s argument is unpersuasive.
Applicant argues that Kim does not disclose or reasonably suggest the compound disclosed in Nishiyama. Therefore, a person of ordinary skill in the art, upon reviewing the disclosure of Kim, would have no reason to select the specific compound disclosed in Nishiyama and expect it to work as a diagnostic agent for pancreatic function in vivo.
The Examiner does not find Applicant’s argument to be persuasive. As this is a 103 obviousness rejection, no one piece of prior art is required to teach each and every claim limitation. If Kim taught the compound of Nishiyama, the teachings of Nishiyama would not have been necessary. One of ordinary skill in the art would have been motivated to select the specific compound disclosed in Nishiyama since Kim discloses the correlation between expression of MC-1 and impairment of autophagy in pancreatic β-cells and Nishiyama discloses a compound that can detect MC-1. As such, Applicant’s argument is unpersuasive.
Applicant argues that the behavior of Nishiyama’s compound in vivo is not predictable based on the disclosure of Kim.
The Examiner does not find Applicant’s argument to be persuasive. As discussed above, obviousness does not require absolute predictability. See MPEP 2143.02(II). Therefore, although Nishiyama does not disclose detecting MC-1 in the pancreas specifically, because Nishiyama discloses wherein MC-1 can be detected in the body, one of ordinary skill in the art would have been motivated to detect MC-1 in the pancreas. As such, Applicant’s argument is unpersuasive.
Applicant argues that there is no sufficient rationale to the person of ordinary skill in the art to select the specific compound of Nishiyama in view of all the compounds that are known in the art to detect MC-I. The compound of Nishiyama is not indicated as being preferred in any way.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not shown wherein there are other compounds that detect MC-I. Even if there is, choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success supports a conclusion of obviousness. See MPEP 2143(I). Thus, it would have been obvious to one of ordinary skill in the art to choose from known compounds that detect MC-I. Furthermore, a reference that “discloses a multitude of effective combinations does not render any particular formulation less obvious.” Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). Thus, having multiple compounds to choose from does not make any one compound less obvious. Moreover, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See MPEP 2123(I). Thus, one of ordinary skill in the art may select a non-preferred compound. As such, Applicant’s argument is unpersuasive.
Conclusion
Claims 1-5 are rejected.
No claims are 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.
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/TRACY LIU/Primary Examiner, Art Unit 1614