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 .
DETAILED ACTION
Claims 1-17 and 24-31 are pending. Claims 18-23 are canceled. Claims 14-17 and 24-26 are withdrawn. Claims 1-3, 11-13, and 27-31 are examined herein.
Response to Arguments
Applicant's arguments filed 8/20/2026 have been fully considered but they are not persuasive.
Applicant argues against the written description rejection of claims under 35 U.S.C. 112(a) on the grounds that the specification discloses the functions of the enzymes recited in the claims and methods of determining activity and function of variants of the enzymes (Arguments, Table A, pages 13-14).
In response, this argument is unpersuasive because a representative number of species of the claimed genera of enzymes is not disclosed in the specification or the prior art and neither the specification nor the prior art teach the structure-function relationship of the claimed genera of enzymes. For example, Table A lists page 40, lines 5-10 and lines 23-29 of the specification as support for the claimed genus of THAS variants. However, these lines do not disclose which regions of the THAS enzyme are subject to variation and what are acceptable amino acid substitutions to retain the claimed activity. These lines also do not exemplify any species of variants of THAS that retain activity.
Applicant argues against the rejection of claims 1-3 under 35 U.S.C. 103 over Geerlings 2001 in view of Gerasimenko on the grounds that SGD from Catharathus roseus is not functional in S. cerevisiae, thus, one skilled in the art would be discouraged from employing such modified yeast as an in vivo production platform of strictosidine aglycone and MIAs because such a modification would render the CroSGD disclosed in Geerlings 2001 inoperable (Arguments, page 16, paragraph 3).
In response, this argument is unpersuasive. First, SGD from Catharathus roseus is functional in S. cerevisiae. Geerlings 2001 teaches that SGD is not excreted into the medium, so only trace amounts of cathenamine are detected in the medium (Geerlings 2001; paragraph bridging pages 422-423). SGD hydrolyzes strictosidine to an unstable aglycone that converts spontaneously to cathenamine. Thus, SGD from Catharathus roseus is functional S. cerevisiae and produces strictosidine aglycone. Otherwise, trace amounts of cathenamine would not have been detected. Furthermore, there is no part of the obviousness rationale that requires the modification of the CroSGD disclosed in Geerlings 2001. Rather, the rationale relies on replacing CroSGD with the SGD from R. serpentina.
Applicant argues against the rejection of claim 11 under 35 U.S.C. 103 on the grounds that Stavrinides fails to teach, suggest, or disclose combining CroTHAS with any of the SGDs recited in claim 1 in a yeast (Arguments, paragraph 3 on page 17).
This argument is not persuasive because Geerlings 2001 is relied on to teach yeast comprising an SGD. Stavrinides teaches tetrahydroalstonine synthase from Catharanthus roseus is an enzyme that converts strictosidine aglycone to tetrahydroalstonine (Summary and page 336, right column, Results and Discussion, bottom paragraph). Stavrinides also teaches that strictosidine aglycone rearranges into several isomers (Figure 1B), including the dominant isomer cathenamine (page 338, left column, bottom paragraph). Geerlings 2001 teaches a recombinant yeast that produces the cathenamine (Abstract and page 423, right column, top paragraph). Thus, the person of ordinary skill in the art would have been motivated to modify the yeast of Geerlings 2001 with tetrahydroalstonine synthase from Stavrinides to produce tetrahydroalstonine and the person of ordinary skill in the art would have had a reasonable expectation of success in doing so.
Applicant argues against the obviousness-type nonstatutory double patenting rejections of record on the grounds that copending Application No. 18/860,052 is later-filed and has a later priority date than the present application (Arguments, paragraph 5 on page 17).
However, this argument is not persuasive because the obviousness-type nonstatutory double patenting rejection is not the final outstanding issue in this action.
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.
Claim 28 is 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.
Claim 28 is indefinite because it recites that wherein said THAS is CroTHAS and/or HYS is CroHYS or variants thereof, having at least 90% identity to SEQ ID NO: 28 and/or SEQ ID NO: 46. There are at least two different reasonable interpretations of the claim, rendering the claim indefinite. In one interpretation, the claim scope encompasses variants of CroHYS only. In a second interpretation, the claim scope encompasses variants of CroTHAS as well as variants of CroHYS. It is further unclear whether the limitation “variants having at least 90% identity to SEQ ID NO: 28 and/or SEQ ID NO: 46” applies to the CroTHAS, the CroHYS, or both the CroTHAS and the CroHYS. It is also unclear which sequence limitation applies to the CroTHAS (SEQ ID NO: 28 or SEQ ID NO: 46) and which sequence limitation applies to the CroHYS (SEQ ID NO: 28 or SEQ ID NO: 46) or whether both sequence limitations apply to both CroTHAS and CroHYS.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 11-13, and 27-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a genus of strictosidine-beta-glucosidase (SGD) variants with at least 90% identity to any one of SEQ ID NO: 24-27 and SEQ ID NO: 47-67. In an alternative embodiment, claim 1 recites a mosaic SGD comprising an amino acid sequence having the formula D1-D2-D3-D4, wherein D3 is SEQ ID NO: 91 or a variant having at least 90% identity to SEQ ID NO: 91 and D4 is SEQ ID NO: 92 or a variant having at least 90% identity to SEQ ID NO: 92.
The person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genus of SGD variants or mosaic SGD variants.
The specification describes in Example 7 the alignment of 28 different SGD homologs and illustrates the alignment in Figure 12. However, among the 28 selected sequences, only RseSGD2 and IpeSGD are known to have low SGD activity in vitro (lines 6-7 on page 101). Thus, the alignment is insufficient to establish a structure-function correlation between the enzyme and its function. Seven are putative beta-glucosidases or hypothetical proteins from monoterpenoid indole alkaloid (MIA) producing plants, one (OeuSGD) is an oleuropein beta-glucosidase from Olea europaea, and 12 are putative beta-glucosidases with various putative activities from plants that do not produce MIAs but a range of different glycosylated natural products (page 101, lines 6-12). Six of the selected sequences are putative beta-glucosidases and hypothetical proteins from fungi (lines 14-15 on page 101). Yeast strains expressing VmiSGD1, AhuSGD, HimSGD2, SinSGD, TelSGD, VunSGD, NsiSGD1, LprSGD, AchSGD1, HsuSGD, MroSGD, RseSGD2, PgrSGD, OpuSGD, HpiSGD, HanSGD1, AchSGD2, HimSGD1, lpeSGD, LsaSGD1, and CarSGD were able to produce tetrahydroalstonine and hereby also strictosidine aglycone (specification page 105 lines 21-25Figure 8). However, no variants of these enzymes are disclosed that retain activity.
Although the specification establishes the structure-function correlation between four different SGD domains and the function of producing tetrahydroalstonine (see Figure 9, Table 6, page 108, lines 5-14), the specification does not provide the structure-function correlation within each protein domain. For example, the specification states that “all functional SGD variants have RseSGD domain 3” (line 8 on page 108). RseSGD domain 3 is SEQ ID NO: 91. However, the specification does not disclose variants of SEQ ID NO: 91 that retain activity. The specification also discloses that of the functional SGD variants, the four sequences with RseSGD domain 3 and domain 4 are able to produce the highest amount of tetrahydroalstonine (page 108, lines 9-12). SEQ ID NO: 92 is domain 4 of RseSGD from Rauvolfia serpentina. However, the specification does not disclose any variants of SEQ ID NO: 92 that retain activity.
Claim 1 recites variants of 25 different SGD sequences. Even for the more widely studied SGD enzymes, such as RseSGD, there is a limited amount of information taught by the art regarding the structure-function correlation of the enzyme. Barleben et al. (The Plant Cell 19.9 (2007): 2886-2897; cited in the Non-Final Action mailed on 3/20/2026) teaches the three-dimensional structure of both native R. serpentina SGD and the complex of its inactive mutant Glu207Gln with the substrate strictosidine (Abstract). Barleben teaches a limited amount of structure-function information is known in the art about SGD: Sequence alignment of SG with glucosidases of various origins indicates complete conservation of amino acid residues Glu-207, Glu-416, and His-161, and that both Glu-207 and Glu-416 catalyze the concerted hydrolysis of the glucoside bond (page 2888, right column, bottom paragraph). Barleben also infers that His-161 is also likely to play a critical role in the reaction catalyzed by SG (page 2888, right column, bottom two lines). Barleben also teaches a small number of species of SGD mutants (Table 1), of which only a few retain activity. Each mutant contains a single point mutation and no combinations of mutations are tested.
Claim 27 recites a genus of variants of CroSTR having at least 90% identity to SEQ ID NO: 30. Claim 28 recites a genus of variants of CroTHAS or CroHYS having at least 90% identity to SEQ ID NO: 28 or 46, respectively. Claim 30 recites a genus of variants of GseSBE having at least 90% identity to SEQ ID NO: 29. Claim 31 recites a genus of variants of SEQ ID NO: 31-41.
The specification does not disclose any variants of any of the above enzymes.
SEQ ID NO: 28, 31-41, and 46 are each different enzymes from Catharanthus roseus (plant). SEQ ID NO; 29 is from Gelsemium sempervirens. Each of these enzymes ranges in size from 134 amino acids to 714 amino acids. Thus, variants with at least 90% sequence identity range from 13 amino acid substitutions to 71 amino acid substitutions.
Regarding the enzymes tabersonine synthase (TS) and a catharanthine synthase (CS), these enzymes have only recently been identified in Catharanthus roseus: see Abstract and Figure 2 of Caputi et al. ("Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle." Science 360.6394 (2018): 1235-1239; cited in the Non-Final Action mailed on 3/20/2026), which is published in the year prior to the effective filing date of the claimed invention. Caputi does not teach any variants of either enzyme.
Qu et al. (Planta 247.3 (2018): 625-634; cited in the Non-Final Action mailed on 3/20/2026) only recently identified geissoschizine synthase from Catharanthus roseus (paragraph bridging pages 629-630) in 2018, which is the year prior to the effective filing date of the claimed invention, and no variants of the geissoschizine synthase were generated.
Stavrinides et al. (Nature communications 7.1 (2016): 12116; cited in the Non-Final Action mailed on 3/20/2026) performs site-directed mutagenesis of THAS1 and HYS (page 9, left column, “site-directed mutagenesis of THAS1 and HYS). However, Stavrinides teaches a small number of species of THAS1 and HYS mutants: see paragraph bridging left and right columns on page 9.
Dang et al. (Nature chemical biology 14.8 (2018): 760-763; cited in the Non-Final Action mailed on 3/20/2026) teaches an SBE enzyme from C. roseus called CrAS (page 762, left column, bottom paragraph). Dang produces a small number of variants of the enzyme with six point mutations (page 762, right column, top paragraph).
Given the lack of variants disclosed by the specification and the limited number of variants disclosed in the prior art, as well as the lack of a structure-function correlation in the specification and the prior art, the person of ordinary skill in the art would have been unable to reasonably predict and visualize the structures of all the species within the claimed genera of variants of each of the enzymes.
Claim 12 recites that the microorganism is capable of producing strictosidine aglycone with a titre of at least 1 μM or more. Claim 13 recites the microorganism according to claim 11, capable of producing tetrahydroalstonine with a titre of at least 1 μM or more, and/or tabersonine with a titre of at least 0.01 μM.
Figures 1, 3, 9-10, and 11B of the specification illustrate production of tetrahydroalstonine. Figure 6B and 7-8 of the specification illustrate tabersonine titer.
The specification discloses that since strictosidine aglycone is chemically unstable, the yield is estimated from the equimolar conversion to tetrahydroalstonine (lines 8-10 and 18-19 on page 111).
The maximum yield of tetrahydroalstonine exemplified within the specification is approximately 15 µM (Figure 3). The maximum yield of tabersonine exemplified within the specification is 0.095 µM (Fig. 7).
The prior art does not teach any microorganisms capable of producing tetrahydroalstonine or strictosidine aglycone with yields greater than 15 µM, or tabersonine with yields greater than 0.095 µM.
Neither the prior art nor the specification teach the structure-function correlation between the structure of the microorganism and the ability to produce more than 15 µM tetrahydroalstonine, more than 15 µM strictosidine aglycone, or more than 0.095 µM tabersonine.
Therefore, the person of ordinary skill in the art would also not have recognized that the inventors had possession of the claimed genus of microorganisms capable of producing more than 15 µM tetrahydroalstonine or strictosidine aglycone or more than 0.01 µM tabersonine.
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.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Geerlings et al. (Appl Microbiol Biotechnol (2001) 56:420–424; hereafter Geerlings2001) in view of Gerasymenko (Eur. J. Biochem. 269, 2204–2213 (2002)) as evidenced by Geerlings et al. (Journal of Biological Chemistry 275.5 (2000): 3051-3056; hereafter Geerlings2000) and by AJ302044 (2005 website).
Geerlings2001 teaches a transgenic Saccharomyces cerevisiae comprising strictosidine beta-glucosidase (SGD) and strictosidine synthase (STR) from Catharanthus roseus (Abstract). STR converts tryptamine and secologanin into strictosidine (Abstract). SGD hydrolyzes strictosidine to an unstable aglycone
that converts spontaneously to cathenamine as evidenced by Geerlings2000 (page 3055, right column, Discussion, paragraph 1).
Geerlings2001 does not teach that the SGD is SEQ ID NO: 24. (SGD from R. serpentina).
Gerasymenko teaches the heterologous expression of R. serpentina strictosidine glucosidase in E. coli (Abstract). Although Gerasymenko calls the enzyme strictosidine glucosidase rather than strictosidine-beta-glucosidase, the in vitro deglucosylation of strictosidine by R. serpentina SG proceeds by the same mechanism as has been shown for C. roseus enzyme preparation (Abstract), so the enzymes have the same activity. Gerasymenko teaches the accession number of the SG from R. serpentina is AJ302044 (footnotes page 2204). The amino acid sequence of the enzyme is identical to instant SEQ ID NO: 24 (OA Appendix B of the Non-Final Action mailed on 3/20/2026) and is called strictosidine-beta-glucosidase as evidenced by AJ302044 (see Title and “Translation”).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the SGD from Catharanthus roseus with the SGD taught by Gerasymenko in order to screen for enzymes with the highest SGD activity in S. cerevisiae. The person of ordinary skill in the art would have had a reasonable expectation of success in the replacement given that Gerasymenko already expressed the plant (R. serpentina) SGD in E. coli and Geerlings 2001 was already successful in expressing a plant (C. roseus) SGD in S. cerevisiae.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over of Geerlings et al. (Appl Microbiol Biotechnol (2001) 56:420–424; Geerlings 2001) in view of Gerasymenko (Eur. J. Biochem. 269, 2204–2213 (2002)) and as evidenced by Geerlings et al. (Journal of Biological Chemistry 275.5 (2000): 3051-3056; hereafter Geerlings 2000) and by AJ302044 (2005 website), as applied to claims 1-3 above, further in view of Stavrinides et al. (Chemistry & biology 22.3 (2015): 336-341).
This rejection applies to the embodiment in which the microorganism further comprises a tetrahydroalstonine synthase (embodiment (i)).
Regarding claim 11, Geerlings 2001 does not teach that the S. cerevisiae further comprises tetrahydroalstonine synthase.
Stavrinides teaches the heterologous expression of tetrahydroalstonine synthase (THAS) from Catharanthus roseus in E. coli, which is an enzyme that converts strictosidine aglycone to tetrahydroalstonine (Summary and page 336, right column, Results and Discussion, bottom paragraph). Stavrinides teaches that strictosidine aglycone rearranges into several isomers (Figure 1B), including the dominant isomer cathenamine (page 338, left column, bottom paragraph).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further engineer the Saccharomyces cerevisiae of Geerlings 2001 modified by Gerasymenko by introducing a gene encoding tetrahydroalstonine synthase from Catharanthus roseus in order to produce tetrahydroalstonine. The person of ordinary skill in the art would have had a reasonable expectation of success given that Stavrinides teaches the heterologous expression of tetrahydroalstonine synthase from Catharanthus roseus in E. coli.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over of Geerlings et al. (Appl Microbiol Biotechnol (2001) 56:420–424; Geerlings 2001) in view of Gerasymenko (Eur. J. Biochem. 269, 2204–2213 (2002)) and Stavrinides et al. (Chemistry & biology 22.3 (2015): 336-341) and as evidenced by Geerlings et al. (Journal of Biological Chemistry 275.5 (2000): 3051-3056; hereafter Geerlings 2000) and by AJ302044 (2005 website), as applied to claim 11 above, further evidenced by AKF02528.1 (2015 website).
See discussion of Geerlings 2001, Gerasymenko, and Stavrinides above, which is incorporated into this rejection as well.
Regarding claim 28, Stavrinides teaches THAS with accession number KM524258 (page 340, left column, Experimental Procedures line 1). This gene encodes a THAS protein that is identical to the instant SEQ ID NO: 28 as evidenced by AKF02528.1 (OA Appendix D).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 11, and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55-56 and 58-62 of copending Application No. 18/860,052 (reference application; hereafter ‘052). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 1 is obvious over claim 59 of ‘052 and claims 2-3, 11, and 28 are obvious over claims 55-56 and 58-62 of ‘052.
Claim 55 of ‘052 recites a microorganism producing halogenated strictosidine aglycone or derivatives thereof, said microorganism expressing strictosidine-O-beta-D-glucosidase, wherein the SGD is capable of converting halogenated strictosidine to halogenated strictosidine aglycone.
Claim 56 of ‘052 recites that the microorganism expresses a tetrahydroalstonine synthase (THAS).
Claim 58 of ‘052 recites that the microorganism further expresses an NADPH-cytochrome P450 reductase.
Claim 59 of ‘052 recites that SGD is RseSGD as set forth in SEQ ID NO: 82.
Claim 60 of ‘052 recites that the THAS is CroTHAS1 and has SEQ ID NO: 83.
Claim 61 of ‘052 recites that the microorganism further comprises a cytochrome b5 or strictosidine synthase.
Claim 62 of ‘052 recites that the microorganism is a bacterium or a yeast of the genus Saccharomyces.
Instant claim 1 of ‘052 is obvious over claim 59 of ‘052 for the embodiment of instant claim 1 in which the SGD is SEQ ID NO: 24. SEQ ID NO: 82 of ‘052 is identical to the instant SEQ ID NO; 24 (OA Appendix C of the Non-Final Action mailed on 3/20/2026). Although claim 59 of ‘052 does not limit the microorganism to yeast, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to express the specific SGD according to SEQ ID NO:82 in yeast, since claim 62 of ‘052 is drawn to a yeast comprising an SGD.
Instant claim 3 is obvious over claims 59 and 61 of ‘052. Although claim 61 of ‘052 does not recite that the SGD is RseSGD (SEQ ID NO: 82), it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to express the SGD according to SEQ ID NO: 82 in the microorganism comprising the strictosidine synthase in order to provide the precursor for the SGD.
Instant claim 11 is obvious over claims 56 and 58-60 of ‘052. Claims 56 and 59-60 of ‘052 each depend from claim 55 of ‘052, which recites that the microorganism comprises an SGD but does not recite that the SGD is RseSGD (SEQ ID NO: 82). Claim 59 recites a specific SGD (RseSGD). Thus, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to apply the SGD of claim 59 of ‘052 to any of the microorganisms in claims 56 or 60 of ‘052.
Instant claim 28 is likewise obvious over claims 56 and 58-60 of ‘052 because SEQ ID NO: 83 recited in claim 60 of ‘052 is identical to the instant SEQ ID NO: 28 (OA Appendix E).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at (571)272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
