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 .
Applicant's cancellation of claims 7, amendment of claims 1, 5, in the paper of 4/23/2026, is acknowledged. Applicants' arguments filed on 4/23/2026, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1, 5, 6, 8, 9, 11, 13, 14, 16-18, 21-25, 28, 32-33 are still at issue and are present for examination.
Election/Restrictions
Applicant's election without traverse of the invention of Group 1, claims 1, 5-7, to cytochrome P450 monooxygerase, in the paper of 11/14/2025, is acknowledged. Applicant's election without traverse of the following species:
Species Group 1: CPt 10-hydrosylase (CPT10H).
Species Group 2: Camptotheca acuminata.
Species Group 3: SEQ ID NO:3.
Species Group 4: camptothecine.
Species Group 5: 10-hydroxycamptothesin.
Species Group 6: 9-[(dimethylamino)methyl]-10-hydroxycamptothecin (topotecan).
Species Group 7: 12-[(dimethylamino)methyl]-11-hydroxycamptothecin (topotecan- 11).
in the paper of 11/14/2025, is acknowledged.
Claims 8, 9, 11, 13, 14, 16-18, 21-25, 28, 32-33 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1 and 5-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
This rejection was stated in the previous office action as it applied to previous claims 1 and 5-7. In response to the rejection applicants have amended claims 1 and 5, cancelled claim 7 and argue the rejection as it applies to newly amended claims 1 and 5-6.
Applicants submit that claim 1 is amended to recite "A purified recombinant cytochrome P450 monooxygenase..." Applicant submits that a purified recombinant cytochrome P450 monooxygenase as recited in amended claim 1 is not naturally occurring as any naturally occurring enzyme from Nothapodytes nimmoniana is found in a complex cellular plant environment. Applicants further submit that as discussed at paragraph [0063] of the application as filed, a purified cytochrome P450 monooxygenase is substantially or essentially free from components that normally accompany or interact with the protein as found in its naturally occurring environment. Applicants submit that an isolated or purified protein or nucleic acid molecule is substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized.
Applicants submit that furthermore, naturally occurring plant enzymes typically exhibit plant-specific post-translational modifications, including distinctive glycosylation profiles, which are absent when the enzymes are recombinantly expressed in yeast or other heterologous hosts. Applicant further submits that the recited sequences are also not naturally occurring in Nothapodytes nimmoniana. Applicants submit that the current claims are narrowly drawn to defined nucleic acid and amino acid sequences encoding enzymes that have been experimentally demonstrated to possess a specific and non-obvious catalytic function: the oxidation of monoterpenoid indole alkaloid (MIA) substrates bearing indole or quinoline moieties. Applicants submit that the claims do not encompass cytochrome P450 enzymes as a broad class, but rather recite particular sequences whose catalytic activity has been individually characterized and confirmed.
Applicants submit that the claimed enzymes were identified and validated through targeted experimental work that established their capacity to carry out defined oxidative transformations on MIA substrates-a functional result that is not predictable from enzyme class membership alone, given that substrate specificity among related enzymes can vary. Applicants submit that the inventive contribution therefore lies not in the recognition of an enzyme family, but in the identification and functional characterization of particular sequences conferring a distinct and experimentally verified biochemical activity.
Applicant further submits that the claims do not pre-empt any natural phenomenon or product of nature. Applicant further submits that the claims are directed to structurally defined sequences and their established, non- generic utility in carrying out targeted oxidative transformations of defined MIA substrates. Applicant further submits that the claimed sequences and their demonstrated catalytic function together integrate any recited natural elements into a practical application that is specific, substantial, and credible-namely, the enzymatic conversion of MIA substrates through a catalytic mechanism that a skilled artisan would not have predicted from sequence data alone. Applicant further submits that this practical application satisfies the requirement that the claims recite significantly more than a judicial exception, and places them squarely within the realm of patent-eligible subject matter.
Applicants amendment of the claims and applicants complete argument is acknowledged and has been carefully considered, however, is found non-persuasive for the reasons previously made of record and for those reasons repeated herein.
In response to applicants submission that claim 1 is amended to recite "A purified recombinant cytochrome P450 monooxygenase..." and that as recited is not naturally occurring as any naturally occurring enzyme is found in a complex cellular plant environment is not found persuasive, on the basis that the cytochrome P450 monooxygenase capable of oxidizing a monoterpenoid indole alkaloid (MIA) substrate, wherein the MIA substrate comprises a quinoline moiety or an indole moiety, wherein the purified recombinant cytochrome P450 comprises a sequence selected from SEQ ID NO: 3 is a naturally occurring enzyme. This is evidenced by Nguyen et al. (Commun. Chem. Vol 4, (1), 1-7, 2021 and Genbank UUY85546, Aug 2022) who teach that the cytochrome P450 monooxygenase comprising SEQ ID NO:3 is a naturally occurring enzyme found in Camptotheca acuminata. In response to applicants submission that a purified cytochrome P450 monooxygenase is substantially or essentially free from components that normally accompany or interact with the protein as found in its naturally occurring environment, while this may be true, this is insufficient alter the claimed naturally occurring cytochrome p450 monooxygenase such that it has markedly different characteristics from what occurs in nature. As such applicants claims read on that cytochrome p450 monooxygenase that is structurally and functionally identical to that which occurs naturally in Camptotheca acuminata.
In response to applicants submission that naturally occurring plant enzymes typically exhibit plant-specific post-translational modifications, including distinctive glycosylation profiles, which are absent when the enzymes are recombinantly expressed in yeast or other heterologous hosts, this is not found persuasive as applicants claims do not read on that enzyme with specific post-translational modifications or distinctive glycosylation profiles.
In response to applicants submission that the claims do not encompass cytochrome P450 enzymes as a broad class, but rather recite particular sequences whose catalytic activity has been individually characterized and confirmed, this is not found persuasive because regardless of applicants stated breadth of cytochrome P450 enzymes as a class, the claims continue to read on the naturally occurring cytochrome P450 monooxygenase comprising SEQ ID NO:3 found in Camptotheca acuminata.
Regardless of how the enzymes were identified and validated through targeted experimental work that established their capacity to carry out defined oxidative transformations on MIA substrates-a functional result that is not predictable from enzyme class membership alone, given that substrate specificity among related enzymes can vary, the claims continue to read on the naturally occurring cytochrome P450 monooxygenase comprising SEQ ID NO:3 found in Camptotheca acuminata.
In response to applicants submission that the inventive contribution therefore lies not in the recognition of an enzyme family, but in the identification and functional characterization of particular sequences conferring a distinct and experimentally verified biochemical activity, this is not found persuasive on the basis that, as stated previously and repeated herein the claims continue to read on the naturally occurring cytochrome P450 monooxygenase comprising SEQ ID NO:3 found in Camptotheca acuminata.
In response to applicants submission that the claims are directed to structurally defined sequences and their established, non- generic utility in carrying out targeted oxidative transformations of defined MIA substrates, this is not found persuasive on the basis that, as stated previously and repeated herein the claims continue to read on the naturally occurring cytochrome P450 monooxygenase comprising SEQ ID NO:3 found in Camptotheca acuminata.
Claims 1 and 5-6 remain directed to a cytochrome P450 monooxygenase capable of oxidizing a monoterpenoid indole alkaloid (MIA) substrate, wherein the MIA substrate comprises a quinoline moiety or an indole moiety, that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., 106 USPQ2d 1972 (June 13, 2013 Nguyen et al. (Commun. Chem. Vol 4, (1), 1-7, 2021 and Genbank UUY85546, Aug 2022), evidence that a cytochrome P450 monooxygenase comprising SEQ ID NO:3, capable of oxidizing a monoterpenoid indole alkaloid (MIA) substrate, wherein the MIA substrate comprises a quinoline moiety or an indole moiety, which naturally occurs in Camptotheca acuminata and is thus not patent eligible.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 1 and 7 under 35 U.S.C. 102(a)(1) as being anticipated by Godbole et al. (Genome, Vol 64, pages 1-14, ISSN: 0831-2796; Sept. 2020) is hereby withdrawn based upon applicants amendment of the claims in the paper of 4/23/2026.
The rejection of claim(s) 1 and 7 under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al. (Uniprot Accession No. A0A5J5ABU3, 12/11/2019) ) is hereby withdrawn based upon applicants amendment of the claims in the paper of 4/23/2026.
Remarks
No claim is allowed.
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 RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
6/10/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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