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 .
Claim Status
1. Claims 13, 16, 27-28, 31-33, and 44 are pending and examined to the extent of the elected species.
Claims 1, 6, 8, 19-20, 23-24, 35, 38-39, 41, and 46 are withdrawn.
Restrictions/Elections
2. The Office acknowledges receipt of Applicant’s restriction election filed December 01, 2025. Applicant elects Group I, claims 27, 13, 16, 28, and 31-33, without traverse. Applicant further elects the species of SEQ ID NO:326, SEQ ID NO:204, SEQ ID NO:289, SEQ ID NO:178, SEQ ID NO:324, SEQ ID NO:214, SEQ ID NO:293, SEQ ID NO:224, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:126, SEQ ID NO:168, SEQ ID NO:250, SEQ ID NO:252, SEQ ID NO:315, and SEQ ID NO:316, without traverse. Upon further consideration, the Office has decided to examine claim 44 with the elected Group I.
Claims 1, 6, 8, 19, 20, 23, 24, 35, 38, 39, 41, and 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on June 05, 2024, January 17, 2025, May 19, 2025, July 22, 2025, August 29, 2025, and February 05, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
4. The drawings are objected to because the shading in Figures 4, 7, 12, 15, 22, 24-26, and 59 make it impossible to distinguish between the different datasets. For example, the shadings for 11-Oxomogroside II-E, Mogroside II-A, and 11-Oxomogroside IV in Figure 4 are indistinguishable to the Examiner. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered, and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
5. The specification is objected to because of the following informalities:
In [0710], ln.2, there is a punctation error; a period is missing after “expression cassette SP1463”.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
6. Claims 27, 13, 16, 28, and 31-33 are objected to because of the following:
Claim 16, ln. 1 contains a typographical error. The semicolon after “comprising” should be replaced with a colon.
In claim 16, lns. 4 and 13 contain the same typographical error; “phosphorylase dependent” should be amended to “phosphorylase-dependent”. See also claim 27, lns. 10 and 12.
Claim 27, ln. 17 contains a typographical error; the period after “SEQ ID NO:11” should be replaced with a comma.
In claim 27, ln. 29, it is suggested Applicant amend “seventh or eighth polynucleotide” to “seventh and/or eighth polynucleotide” unless Applicant intends to imply that only one of the recited polypeptides is expressed from the recited recombinant DNA molecule. See also: claim 28.
Dependent claims are included.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
7. 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.
Enablement
8. Claims 27, 13, 16, 28, 31-33, and 44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for recombinant DNA molecules comprising SEQ ID NOs:124, 279, 281, 283, 285, 287, 289, 291, 303, 305, 320, 322, 324, and any other sequences comprised within the expression cassettes described in Figure 2 (i.e., SP0336, SP3798, SP0315, SP0545, SP1202, SP4870, SP3190, SP0265, SP2916, SP3095, SP1603, SP3015, SP1908, SP0565, SP0769, SP2355, SP4762, SP3029, SP2057, SP3088, SP2152, SP4156, SP1463, SP4406, SP0796, SP3488, SP3139), Figures 4-6 and 12-14 (i.e., SP2031, SP0951, SP2571, SP3201, SP4263, SP5024, SP5025, SP5027, SP5028, SP5030, SP5032, SP5033, SP5034, SP5035, SP5037, SP5038, SP5039, SP5040, SP5041, SP5043, SP5044, SP5045, SP5046, SP5047, SP5048, SP5049, SP5050, SP5051, and SP5091), Figures 7-8 and 15-16 (i.e., SP2015, SP4332, SP5029, SP5030, SP5031, SP5032, and SP5033), and Figures 10[0030] and 17[0037] (i.e., SP1463) of the drawings filed on 03/18/2024 and Figures 22, 25, and 26 (i.e., SP05655, SP0641, SP1463, SP1908, SP3015, SP3016, SP3029, SP3190, SP3308, SP3488, and SP3684) of the drawings filed on 06/05/2024, does not reasonably provide enablement for SEQ ID NO:178, SEQ ID NO:204, SEQ ID NO:214, SEQ ID NO:224, SEQ ID NO:326 and/or sequences having at least 90% sequence identity thereto. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to produce the invention commensurate in scope with these claims.
Applicant describes the construction of 94 expression cassettes comprising varying combinations of nucleotide sequences encoding mogroside pathway enzymes and regulatory elements (Example 1, pp. 91-134), the transient expression of some undisclosed number of said expression cassettes in whole tomato, zucchini, or cucumber fruit, leaves of Nicotiana benthamiana, lettuce, or sugar beet, slices of sugar beet taproot, or cores of watermelon fruit[0695-0696]; the detection of mogrosides and siamenoside accumulation in said watermelon fruit cores[0699-0701], N. benthamiana leaves[0698], and lettuce leaves[0702-0704] (Example 3, pp. 137-140); and the detection of mogrosides and siamenoside accumulation in transgenic watermelon[0710-0714], tomato[0719], potato[0722-0723], sugar beet[0732],[0796], and lettuce[0796-0797]. Figures 2, 4-8, 10, 12-17, 22, and 25-26 describe the accumulation of mogrosides in plants and/or plant parts comprising the expression constructs designated SP0265, SP0315, SP0336, SP0545, SP0565, SP0641, SP0769, SP0796, SP0951, SP1202, SP1463, SP1603, SP1908, SP2015 (comprises SEQ ID NO:279), SP2031, SP2057, SP2152, SP2355, SP2571, SP2916, SP3015, SP3016, SP3029, SP3088, SP3095, SP3139, SP3190, SP3201, SP3308, SP3488, SP3684, SP3798, SP4156, SP4263 (comprises SEQ ID NOs:281, 303, and 320), SP4332 (comprises SEQ ID NO:283, 305, and 324), SP4406, SP4762, SP4870, SP5024, SP5025, SP5027, SP5028, SP5029 (comprises SEQ ID NO:285), SP5030 (comprises SEQ ID NO:287 and 322), SP5031 (comprises SEQ ID NO:289), SP5032 (comprises SEQ ID NO:291), SP5033, SP5034 (comprises SEQ ID NO:124), SP5035, SP5037, SP5038, SP5039, SP5040, SP5041, SP5043, SP5044, SP5045, SP5046, SP5047, SP5048, SP5049, SP5050, SP5051, and SP5091.
Applicant provides no guidance as to how to identify which, if any, of SEQ ID NO:178, SEQ ID NO:204, SEQ ID NO:214, SEQ ID NO:224, or SEQ ID NO:326 are comprised within the expression cassettes described in Figures 2, 4-8, 10, 12-17, 22, and 25-26.
The state of the art teaches the native biosynthesis of mogrosides in monk fruit (Itkin et al., PNAS. 2016; 113:E7619-E7628 (Applicant’s IDS)). The state of the art also teaches the bioengineering of mogroside synthesis in watermelon and other species. Chambers et al. (WO-2021/126960-A1, published 06/24/2021 (N)) discloses a heterologous enzyme pathway catalyzing the synthesis of mogrosides (p. 02, lns. 15-20) comprising a polynucleotide sequence encoding a cytochrome P450 polypeptide (SEQ ID NO:221) having at least 91% sequence identity to instant SEQ ID NO:2 (claim 29); a polynucleotide sequence encoding a cucurbitadienol synthase polypeptide (SEQ ID NO:40) having at least 90% sequence identity to instant SEQ ID NO:5 (claim 20); a polynucleotide sequence encoding a uridine phosphorylase-dependent glycosyltransferase (SEQ ID NO:116) polypeptide having at least 90% sequence identity to instant SEQ ID NO:9 (p. 06, lns. 5-7); a polynucleotide sequence encoding a uridine phosphorylase-dependent glycosyltransferase polypeptide (SEQ ID NO:122) having at least 90% sequence identity to instant SEQ ID NO:11 (p. 06, lns. 5-7); a polynucleotide sequence encoding a squalene epoxidase polypeptide (SEQ ID NO:17) having at least 90% sequence identity to SEQ ID NO:13 (claim 2); and a polynucleotide sequence encoding an epoxy hydrolase polypeptide (SEQ ID NO:58) having at least 90% sequence identity to SEQ ID NO:15 (claim 31). The state of the art does not teach the production of mogrosides in plants or plant parts expressing just any polynucleotide sequence.
Accordingly, one of ordinary skill in the art could not reliably predict the functionality of these sequences in producing mogrosides in any plant or plant part without engaging in extensive and undue experimentation to discover which sequences hold sufficient functionality when paired with other sequences encoding mogroside pathway enzymes.
In making this determination, the Office has weighed each of the Wands factors. The breadth of the claims is found in claim 27 drawn to a recombinant DNA molecule comprising nucleotide sequences encoding 8 mogroside pathway enzymes. The nature of the invention comprises increasing the accumulation of mogrosides in crop plants. The level of skill one in this art is high. The specification teaches functional sequences comprising SEQ ID NOs:124, 279, 281, 283, 285, 287, 289, 291, 303, 305, 320, 322, 324 and the expression cassettes designated SP0265, SP0315, SP0336, SP0545, SP0565, SP0641, SP0769, SP0796, SP0951, SP1202, SP1463, SP1603, SP1908, SP2015, SP2031, SP2057, SP2152, SP2355, SP2571, SP2916, SP3015, SP3016, SP3029, SP3088, SP3095, SP3139, SP3190, SP3201, SP3308, SP3488, SP3684, SP3798, SP4156, SP4263, SP4332, SP4406, SP4762, SP4870, SP5024, SP5025, SP5027, SP5028, SP5029, SP5030, SP5031, SP5032, SP5033, SP5034, SP5035, SP5037, SP5038, SP5039, SP5040, SP5041, SP5043, SP5044, SP5045, SP5046, SP5047, SP5048, SP5049, SP5050, SP5051, and SP5091. The state of the prior art does not teach the production of mogrosides in plants or plant parts expressing just any generic cytochrome protein, any generic cucurbitadienol synthase, any generic squalene synthase, any generic uridine phosphorylase-dependent glycosyltransferase polypeptide, any generic epoxy hydrolase, or any generic truncated 3-hydroxy-3-methylglutaryl-CoA reductase. Applicant discloses no working examples of mogroside production in plants or plant parts comprising SEQ ID NOs: 2, 5, 7, 9, 11, 13, 15, 17, 25, 27, 29, 31, 33, 86, 100, 102, 110, 112, 174, 176, 178, 180, 182, 184, 200, 202, 204, 206, 214, 216, 218, 220, 222, 224, 273, 275, 277, 295, 297, 299, 301, 318, or 326. Weighing all of the Wands factors based on the totality of the record as discussed above, the Office determines that it would require undue experimentation for a person of ordinary skill in the art to make and use the invention as claimed.
Claim Rejections - 35 USC § 103
9. 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.
10. Claims 27, 13, 16, 28, 31-33, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Houghton-Larsen et al. (US-10633685-B2, published 04/28/2020 (Applicant’s IDS)).
Regarding claims 27 and 44, Houghton-Larsen discloses a recombinant host cell capable of producing a mogrol precursor, a mogroside precursor, and/or a mogroside compound comprising: a) a first polynucleotide encoding a polypeptide comprising a cytochrome P450 protein having at least 98% sequence identity to SEQ ID NO:326 (i.e., SEQ ID NO:74); b) a second polynucleotide encoding a polypeptide comprising a cucurbitadienol synthase polypeptide having at least 90% sequence identity to SEQ ID NO:204 (i.e., SEQ ID NO:43); c) a third polynucleotide encoding a polypeptide comprising a cytochrome P450 polypeptide having at least 99% sequence identity to SEQ ID NO:289 (i.e., SEQ ID NO:44); d) a fourth polynucleotide encoding a uridine phosphorylase-dependent glycosyltransferase polypeptide having at least 91% sequence identity to SEQ ID NO:178 (i.e., SEQ ID NO:62); e) a fifth polynucleotide encoding a uridine phosphorylase-dependent glycosyltransferase polypeptide having at least 99% sequence identity to SEQ ID NO:324 (i.e., SEQ ID NO:53); f) a sixth polynucleotide encoding a squalene epoxidase polypeptide; g) a seventh polynucleotide sequence encoding an epoxy hydrolase polypeptide having at least 99% sequence identity to SEQ ID NO:293 (i.e., SEQ ID NO:40); and h) an eight polynucleotide sequence encoding a truncated 3-hydroxy-3-methyl-glutaryl-CoA reductase polypeptide; wherein the first, second, third, fourth, fifth, sixth, seventh, or eighth polynucleotide is operably linked to a heterologous promoter (claim 1; col. 16, lns. 49-65).
Houghton-Larsen is silent to sequences having at least 90 sequence identity to SEQ ID NO:214 or 224 and to a recombinant DNA molecule comprising each of the above elements a)-h).
However, the level of ordinary skill in the plant biotechnology art is high. It would have been prima facie obvious for one of ordinary skill in the art to design a recombinant DNA molecule comprising: a) a first polynucleotide encoding a polypeptide comprising a cytochrome P450 protein having 100% sequence identity to SEQ ID NO:326; b) a second polynucleotide encoding a polypeptide comprising a cucurbitadienol synthase polypeptide having at least 90% sequence identity to SEQ ID NO:204; c) a third polynucleotide encoding a polypeptide comprising a cytochrome P450 polypeptide having at least 99% sequence identity to SEQ ID NO:289; d) a fourth polynucleotide encoding a uridine phosphorylase-dependent glycosyltransferase polypeptide having at least 91% sequence identity to SEQ ID NO:178; e) a fifth polynucleotide encoding a uridine phosphorylase-dependent glycosyltransferase polypeptide having at least 99% sequence identity to SEQ ID NO:324; f) a sixth polynucleotide encoding a squalene epoxidase polypeptide; g) a seventh polynucleotide sequence encoding an epoxy hydrolase polypeptide having at least 99% sequence identity to SEQ ID NO:293; and h) an eighth polynucleotide sequence encoding a truncated 3-hydroxy-3-methyl-glutaryl-CoA reductase polypeptide given the teachings of Houghton-Larsen as described above. Though Houghton Larsen is silent to SEQ ID NO:214 and SEQ ID NO:224, the squalene epoxidase and 3-hydroxy-3-methyl-glutaryl-CoA reductase taught by Houghton-Larsen function have the same functions as the polypeptides comprising SEQ ID NO:214 and SEQ ID NO:224, respectively. Applicant has made no assertion and provided no evidence of surprising or unexpected results that would distinguish the instant invention from the prior art (see MPEP 716.02 and MPEP 2183). Additionally, the construction of recombinant DNA molecules and the introduction of said molecules into a host plant is routine in the art and a recombinant host cell comprising the polynucleotides described above inherently requires a recombinant DNA molecule(s) comprising said polynucleotides. Both the instant invention and the recombinant DNA molecule(s) taught by Houghton-Larsen are used in processes for the production of mogrol and mogrosides. Therefore, the instant invention is prima facie obvious in view of the teachings of Houghton-Larsen. Given the economic importance of sugar substitutes such as mogrols, one of ordinary skill in the art would have been motivated by the teachings of Houghton-Larsen to design an expression vector comprising the recited sequences and/or sequences encoding polypeptides that are functionally equivalent thereto to produce recombinant organisms capable of producing mogrols and mogrosides. Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention without any surprising or unexpected results.
Regarding claim 13, in addition to the teachings discussed above, Houghton-Larsen teaches a selectable marker sequence (col. 32, lns. 30-47).
Regarding claim 16, in addition to the teachings discussed above, Houghton-Larsen teaches a polypeptide having at least 90% sequence identity to in SEQ ID NO:104 (claim 1). Houghton-Larsen is silent to SEQ ID NO:108, SEQ ID NO:126, SEQ ID NO:168, SEQ ID NO:250, SEQ ID NO:252, SEQ ID NO:315, and SEQ ID NO:316. However, the further inclusion of these constructs does not produce any surprising and/or unexpected result when compared to the teachings of Houghton-Larsen. Accordingly, the claimed invention is obvious in view of Houghton-Larsen.
Regarding claim 28, in addition to the teachings discussed above, Houghton-Larsen teaches multiple copies of the sixth polynucleotide (col. 16, lns. 24-31).
Regarding claim 31, Houghton-Larsen is silent to the sequences of the heterologous promoters from which the claimed polypeptides are expressed. However, the design of expression vectors and the selection of promoters is a routine design choice for one of ordinary skill in the art. Because Applicant has provided no evidence of surprising or unexpected results due to the recited promoter sequences, these claim limitations are obvious in view of the teachings of Houghton-Larsen.
Regarding claims 32-34, Houghton-Larsen is silent to terminator sequences. However, the design of expression vectors and the selection of terminator sequences is a routine design choice for one of ordinary skill in the art. Because Applicant has provided no evidence of surprising or unexpected results due to the recited terminator sequences, these claim limitations are obvious in view of the teachings of Houghton-Larsen.
Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention without any surprising or unexpected results.
Conclusion
11. No claim is allowed.
Examiner’s Contact Information
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEQUANTARIUS JAVON SPEED whose telephone number is (703)756-4779. The examiner can normally be reached M-F; 9AM-5PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on (571)-270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DEQUANTARIUS JAVON SPEED/Junior Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663