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 .
Applicants' arguments, filed August 15, 2025, 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.
Response to Amendment
The declaration under 37 CFR 1.132 filed August 15, 2025 is insufficient to overcome the rejection of claim 1 based upon Jain et al. (US 2015/0250906) as set forth in the last Office action because: the conclusion set forth as to the alleged unexpected results is not supported by the reasoning that led to such a conclusion, which does not appear to align with the enzymatic reaction being discussed so additional explanation is required, and there is no data presented for any another compounds for comparison with the results obtained from the claimed compound.
The declaration states that use of PABA compounds with the 11C labeled at positions other than the carbon atom of the carboxylic acid as claimed “may not allow for incorporation the label into DHP [dihydropteroate] via the metabolic pathway described above” (section 6), providing unexpected results. In that pathway, the enzyme dihydropteroate synthase reacts PABA and DHPPP to form a compound with 11C as shown on p 3 of the declaration. The incorporation of the labeled PABA into DHP has important implications for in vivo use, including distinguishing M. abscessus pulmonary infection from sterile inflammation and permitted monitoring of treatment with antibiotic in a mouse model as shown in the declaration.
These statements are unpersuasive. The figure showing the reaction catalyzed by the enzyme is blurry in the copy declaration in the file wrapper so the reaction scheme is also shown below and hopefully will be of higher clarity in the record.
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The question is whether labeling of the carbon of the carboxylic acid group with 11C rather than one of the ring carbon atoms of PABA produces unexpected results. In this reaction, the primary amine of the PABA, located para to the carboxylic acid group, reacts with the DHPP to liberate pyrophosphate from the DHPPP and form a secondary amine in the resulting conjugate product but otherwise no atoms of the PABA are lost in the reaction. Therefore it is not understood how any labeled carbon atom in the PABA would not be present in the enzymatic reaction product and therefore visualizable in the manner described in the declaration. The reaction does not involve any of the carbon atoms in the PABA so it would seem unlikely that the presence of a carbon isotope in the ring would alter the reactivity of this substrate to such an extent that one of ordinary skill in the art would not expect a 11C PABA labeled within the ring to be a substrate for dihydropteroate synthase. The declaration provides no comparative evidence such as a greater signal observed when the claimed PABA product is used compared to one in which a ring carbon atom was labeled with 11C. Therefore only showing that the compound claimed can undergo a reaction that produces an in vivo product useful for diagnosis is not evidence of unexpected results but rather than in one application, the claimed compound can react to form an imaging agent. The evidence of record in support of the alleged unexpected results does not outweigh the prima facie case of obviousness and therefore the rejection is maintained.
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 was rejected under 35 U.S.C. 103 as being unpatentable over Jain et al. (US 2015/0250906). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed May 16, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that the declaration demonstrates unexpected results regarding the carbon atom placement and the compound performed unexpectedly well in in vivo PET imaging in both mice and humans based on the figures in the declaration, establishing the non-obviousness of the claimed compound. When the claimed compound is analyzed as a whole, that the claimed compound is metabolizable into 11C-DHP so that it may be used to visualize infectious lesions via PET scan must be given proper consideration.
These arguments are unpersuasive. The declaration established that a metabolite of the claimed compound can be used in the manner claimed but that compound is not the compound being claimed. Unlabeled PABA is the natural substrate for the reaction and that the presence of 11C within the ring would be expected to alter the compound to such an extent that it would not reasonably be expected by one of ordinary skill in the art when the reaction occurs at the primary amine has not been established. This is might not always be the case if an atom such as fluorine not found in the natural substrate is added to generate the imaging agent but that is not the fact pattern for the instant rejection. The declaration provides no comparison with any other 11C labeled compound so how the observed results are unexpected better cannot be determined. In the absence of actual comparisons with other 11C labeled PABA compounds, the evidence of record at best shows that the claimed PABA labeled with 11C can be used in vivo but provides no information as to how other species labeled within the ring would behave to establish that the observed results for the claimed compound are in fact unexpected. Therefore the evidence of record in support of alleged unexpected results does not outweigh the prima facie case of obviousness and the rejection is maintained.
Conclusion
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.
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