DETAILED ACTION
This Office action details a non-final action on the merits for the above referenced application No. Claims 1, and 7-13 are pending in this application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 15 Dec. 2025 has been entered.
Response to Amendment
The amendments filed on 15 Dec. 2025 have been entered.
Response to Arguments
In view of the approved terminal disclaimer, the rejection of claims 1-2 and 7-13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of US patent No. 11,512,305 B2, in view of Rowbotham et al. (Nat. Comm.; published 2020), Ascue Avalos et al. (ChemBioChem; published 2019) and Klymbys et al. (Green Chem.; published 2018) is withdrawn.
Claim Rejections - 35 USC § 103
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 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, 7, and 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Medintz et al. (US 2018/0171325 A1; published 21 Jan. 2018), in view of Ascue Avalos et al. (ChemBioChem; published 2019) and Rowbotham et al. (Nat. Comm.; published 2020) the reasons cited in the Office action filed on 14 Aug. 2025.
Claim(s) 1, 8, and 12-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Medintz et al. (US 2018/0171325 A1; published 21 Jan. 2018), in view of Rowbotham et al. (Nat. Comm.; published 2020) and Klumbys et al. (Green Chem.; published 2018) the reasons cited in the Office action filed on 14 Aug. 2025.
Applicants Arguments
Applicants assert that a response which overcomes the double patenting rejection should also overcome the substantive rejections. Overcoming the double patenting rejection should also overcome the obviousness rejection because they are based on the very same references.
Applicant's arguments filed 15 Dec. 2025 have been fully considered but they are not persuasive. First, it should be emphasized that a terminal disclaimer cannot be used to overcome a prior art rejection under 35 USC 103. MPEP 804.02.II. Second, Medintz, Acue Avalos, and Rowbotham/Klymbus provide adequate reason and motivation to arrive at the instant method of incorporating a radioisotope into a product molecule. Medintz teaches a method that provides for a nanoparticle attached to a plurality of enzymes configured as an enzymatic cascade such that a product of the first enzyme is a substrate of a second enzyme and so forth and allows the enzyme to act on at least one source substrate thereby forming a product molecule. The method and nanoparticles of Medintz are not limited to a particular enzyme or enzyme cascade. At [0029], Medintz teaches that the overall kinetics of an enzymatic cascade that includes a nanoparticle bound enzyme can be enhanced. A bound enzyme appears unaffected by the presence of additional enzymes suggesting that the method is resistant to fouling. Multiple enzymes that comprise a sequential enzymatic cascade can be immobilized onto a NP surface with a net result of a significant increase in the rate of catalysis as well as product yield. The NPs enable binding of several enzymes simultaneously and has allowed observation of catalytic enhancement of enzyme cascades that include 7 different enzymes. Rowbotham teaches and motivates a method that allows for enzymatic incorporation of deuterium into a product molecule. The method combines a clean reductant (H2) with a cheap source of 2H-atoms (2H2O) to generate and recycle [4-2H]NADH. By coupling [4-2H]NADH recycling to an array of C=O, C=N, and C=C reductases, Rowbotham demonstrates asymmetric deuteration across a range of organic molecules. Ascue Avalose teaches and motivates NADPH dependent C=C reduction of (R)-carvone using PETNR to (2R,5R)-dihydrocarvone with high yields and diastereoselectivity wherein the method uses an enzyme triple variant (F249A/F280A/F35A, CMO3M; cyclohexanone monooxygenase, CHMO). Klumbys teaches and motivates an enzymatic cascade that produces cinnamyl alcohol, the enzymatic cascade uses PAL and two reduction enzymes that use NADPH or NADH: CAR and AHD. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Medintz so that the method comprises (i) providing a nanoparticle attached to a plurality of enzymes comprising PETNR and CMO3M or comprising PAL, CAR and AHD; (ii) provides at least one deuterium source (2H2O, NADP-2H and/or NADH-2H) and a source substrate to the enzymatic cascade; and (iii) allows the enzyme cascade to act on the deuterium source and the source substrate to produce a deuterated product molecule (dihydrocarvide or cinnamyl alcohol) as taught by Rowbotham, Acue Avalos, and Klumbys because the providing and allowing would have been expected to advantageously enable the enzymatic production of deuterated dihydrocarvide or deuterated cinnamyl alcohol at an enhanced rate.
New Grounds of Rejection
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, 7-9, and 11-13 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. In this case, the preamble of instant claim 1 is directed to a method of incorporating a radioisotope into a product molecule; however, the body of the claim merely allows for transferring deuterium from at least one deuterium source into a product molecule. Since deuterium is not a radioisotope, the reference to incorporating a radioisotope is unclear and indefinite. Claims 7-8 depend to claim 1 and fall therewith. The Examiner suggest replacing “radioisotope” with “deuterium”. In claims 1, 9, and 11-13, the recitations of “(NADP-2H)” and/or “(NADH-2H)” are indefinite because it is not clear if recitations are examples of a deuterated nicotinamide adenine dinucleotide phosphate or a deuterated reduced nicotinamide adenine dinucleotide or abbreviations or required limitations. Claims 7-8, and 10 depend to one of those claims and fall therewith. In claim 10, the recitation of “(CHMO3M)” is indefinite because it is not clear if the recitation is an example, an abbreviation or a required limitation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618