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 .
Claim Status
1. Claims 1-10 are pending and under examination on the merits.
Claims 11-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on November 20, 2024.
Nucleotide and/or Amino Acid Sequence Disclosures
2. Applicant’s remarks and amendments filed 05/28/2025 have overcome the objections of record.
Response to Arguments – Objections to the Specification
3. Applicant’s remarks and amendments filed 05/28/2025 have overcome the objections of record.
Response to Arguments – Objections to the Drawings
4. Applicant’s remarks and amendments filed 05/28/2025 have overcome the objections of record.
Response to Arguments – Claim Objections
5. Applicant’s remarks and amendments filed 05/28/2025 have overcome the objections of record.
Response to Arguments – Claim Rejections - 35 USC § 112(b)
6. Applicant’s remarks and amendments filed 05/28/2025 have overcome the rejections of record.
Response to Arguments – Claim Rejections - 35 USC § 112(a)
7. Applicant’s remarks and amendments filed 05/28/2025 have been carefully considered but do not overcome all of the rejections of record.
In the previous Office Action dated 01/28/2025, claims 1-10 were rejected under the Written Description requirement of 35 U.S.C. 112(a) for failing to disclose and/or describe alleles of ms10 and aa commensurate in scope with the claims. In particular, the claims were rejected due to Applicant’s lack of disclosure of dominant negative alleles ms10 or aa or alleles that result in the reduced expression of the wildtype alleles of MS10 or AA despite said alleles being within the scope of the claims. Applicant’s remarks do not specifically address or refute this deficiency but instead appear to traverse the deficiency regarding the lack of disclosure of plants comprising an inversion and/or deletion in the genomic region between mutant ms10 and aa alleles. While the Office appreciates the specification’s description of “tomato plants comprising three desirable traits at the same time[169],” said description does not address the lack of disclosure dominant negative alleles. Similarly, Applicant’s Examples 1 and 2 also do not disclose or describe dominant negative alleles of ms10 or aa.
Furthermore, in traversing the rejection of the claims under 35 U.S.C. 102(a)(1) as being anticipated by Martinez et al. (Euphytica. 2011; 178:215–228 (previously cited)) in light of Jeong et al. (Journal of Experimental Botany. 2014; 65(22):6693-6709 (Applicant’s IDS)), Applicant indicates that the claimed tomato plant comprising a mutant ms10 allele, a mutant aa allele, and a reduced frequency of recombination between cannot be yielded from simply any combination of mutant ms10 and mutant aa alleles. Accordingly, it appears the claimed reduced recombination frequency between said alleles requires some unknown but specific feature, phenomenon, event, and/or combination of alleles not disclosed in the prior art (see excerpt below from p. 13 of Applicant’s Remarks). However, Applicant has not disclosed said feature,
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phenomenon, event, and/or combination of alleles.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Applicant has not described a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics. Therefore, this rejection is maintained.
Regarding the rejection of claim 6, Applicant appears to argue that the specification’s description of “tomato plants comprising three desirable traits at the same time” and the disclosure of Examples 1 and 2 conveys a reasonable of possession of plants comprising an inversion and/or deletion in the genomic region between mutant ms10 and aa alleles (p. 12). Additionally, Applicant appears to have misunderstood the Examiner’s acknowledgement of the specification’s disclosure regarding transformed protoplasts and plants. On p. 12 of the reply dated 01/28/2025, the Examiner states “Applicant discloses the induction of targeted CRISPR/Cas9-mediated deletions in the MS10 and AA genes of tomato protoplasts (p. 35, “Protoplast transfection”) and plants (p. 36, “Plant transformation”), and the presence of induced inversions between the deleted ms10 and aa genes in protoplasts expressing the CRISPR/Cas9 construct (p. 35, “Checking the presence of induced inversions”; p. 38, [161]).” Thus, the Examiner acknowledged the disclosure of only protoplasts comprising inversions between the deleted ms10 and aa genes, not plants. The specification does not disclose plants comprising inversions between the deleted ms10 and aa genes. Furthermore, as previously stated, Applicant suggests a need to regenerate at least 1900 shoots from transgenic protoplasts to successfully find even one plant comprising an inversion and/or deletion in the region between ms10 and aa (p. 39, [167]). Given the low frequency of inversion/deletion event(s) reported by the Applicant and the lack of disclosure of a regenerated plant comprising said event(s), it is highly unlikely that Applicant generated a plant comprising an inversion and/or deletion in the region between ms10 and aa. Furthermore, Applicant indicates that it cannot be concluded from simply the presence of a mutant ms10 allele and a mutant aa allele that said alleles would exhibit a reduced recombination frequency (see excerpt below from p. 13 of Applicant’s Remarks).
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Thus, Applicant has not disclosed sufficient relevant identifying characteristics to allow one skilled in the art to predictably determine which, if any, of the disclosed plants comprise an inversion and/or deletion in the genomic region between ms10 and aa. Accordingly, this rejection is maintained.
Claim Rejections - 35 USC § 112(a)
8. 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.
Written Description Rejections
9. Claims 1-10 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.
Issue #1: Applicant has not disclosed dominant negative alleles of ms10 or aa or alleles that result in the reduced expression of the wildtype alleles of MS10 or AA.
Claim 1 is drawn to a tomato plant comprising a reduced frequency of recombination (relative to the wildtype genes) between at least one mutant allele of ms10 and at least one mutant allele of aa and wherein the mutant allele of ms10 and the mutant allele of aa encode proteins with reduced function and/or result in reduced expression of their corresponding wildtype genes. Thus, the claim is broad and encompasses tomato plants comprising a dominant negative allele of ms10 and a dominant negative allele of aa. The limitations encompassing dominant negative alleles of ms10 and aa lack adequate written description for the following reasons.
Applicant discloses the induction of targeted CRISPR/Cas9-mediated deletions in the MS10 and AA genes of tomato protoplasts (p. 35, “Protoplast transfection”) and plants (p. 36, “Plant transformation”), and the presence of induced inversions between the deleted ms10 and aa genes in protoplasts expressing the CRISPR/Cas9 construct (p. 35, “Checking the presence of induced inversions”; p. 38, [161]).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Applicant has not described a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics.
For example, applicant does not disclose mutant alleles of ms10 or mutant alleles of aa that reduce the expression of the wildtype alleles of MS10 or AA. While one skilled in the art can transform virtually any mutant allele into virtually any plant, one skilled in the art cannot predict which mutations will result in a dominant negative allele or reduce the expression of the wildtype allele. The state of the art at the time of filing teaches the role of the tomato MS10 male-sterility gene in pollen development and meiosis and the close chromosomal proximity and genetic linkage of MS10 and AA (Jeong et al., Molecular Breeding. 2016; 36(8):1-10 (Applicant’s IDS)). The state of the prior art does not teach dominant negative alleles of ms10 or aa or mutant alleles of ms10 or aa that result in the reduced expression of the corresponding wildtype genes. Thus, Applicant has not disclosed sufficient relevant identifying characteristics to allow one skilled in the art to predictably determine which mutations will result in a dominant negative allele of ms10 or aa. Because dependent claims 3-10 do not address the recitations regarding mutant alleles that result in reduced expression of the wildtype allele, they also lack adequate written description. Accordingly, there is lack of adequate written description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing.
Issue #2: Applicant has not described plants comprising an inversion and/or deletion in the genomic region between mutant ms10 and aa alleles.
Claim 6 is drawn to a tomato plant comprising an inversion and/or deletion mutation in the genomic region between a mutant ms10 allele and a mutant aa allele. The claim is narrow and only encompasses inversions and deletions induced in plants.
Applicant’s disclosure is as set forth above.
Applicant does not describe a plant comprising an inversion and/or deletion in the region between ms10 and aa. Applicant only describes protoplasts comprising an inversion and/or deletion in the region between ms10 and aa (p. 38, [160]). Though Applicant describes plants comprising mutations in the ms10 and aa genes (p.36, [153]), Applicant does not disclose whether those plants comprise inversion and/or deletions in the genomic region between ms10 and aa. The state of the art, at the time of filing, does not teach a plant comprising an inversion and/or deletion in the genomic region between a mutant ms10 allele and a mutant aa allele. Furthermore, Applicant discloses the low frequency (~1/1890) of the induction of inversion/deletion events (p. 38, [161]) and suggests it would require the regeneration of more than 1900 shoots from transgenic protoplasts to successfully find even one plant comprising an inversion and/or deletion in the region between ms10 and aa (p. 39, [167]). Given the low frequency of inversion/deletion invents reported by the Applicant, it is highly unlikely that Applicant generated a plant comprising an inversion and/or deletion in the region between ms10 and aa. Thus, Applicant has not disclosed sufficient relevant identifying characteristics to allow one skilled in the art to predictably determine which, if any, of the disclosed plants comprise an inversion and/or deletion in the genomic region between ms10 and aa. Accordingly, there is lack of adequate written description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing.
Response to Arguments – Claim Rejections - 35 USC § 102
10. Applicant’s remarks and amendments filed 05/28/2025 have overcome the rejections of record. In particular, Applicant’s argument that the basis the rejection relies of Jeong et al. cited on p. 15 of the previous Office Action, that Jeong is silent regarding the recombination frequency between the disclosed MS10 gene and adjacent genes, and that it ultimately cannot be derived from Jeong that the tomato plants described by Martinez would have a reduced meiotic recombination frequency between a mutant MS10 allele and a mutant AA allele is persuasive. The Office acknowledges that a particular combination of mutant alleles and/or mutation events are required to produce plants comprising both the mutant ms10 and aa alleles, wherein the alleles display a reduced frequency of recombination in comparison to the wildtype alleles.
Response to Arguments – Claim Rejections - 35 USC § 103
11. Applicant’s remarks and amendments filed 05/28/2025 have overcome the rejections of record.
Conclusion
12. No claim is allowed. 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.
13. The closest prior art, Martinez discloses the genetic linkage of S. lycopersicum MS10 and AA genes with a recombination frequency of 1.7%-4.1%, the presence of the mutant aa phenotype (lack of anthocyanin) as an indicator of the mutant ms10 phenotype (male sterility/lack of pollen; p. 216, right column, second full paragraph, lines 25-35), and the production of hybrid plants comprising a wildtype allele of MS10, a mutant allele of ms10, a wildtype allele of AA, and a mutant allele of aa (p. 217, left column, “Plant material”). Martinez teaches a S. lycopersicum plant. Applicant discloses SEQ ID NO:1 (p. 07, [33]) and SEQ ID NO:3 (p. 08, [34]) as obtained from the genome of a S. lycopersicum plant. Therefore, S. lycopersicum plants inherently comprise genes encoding proteins with at least 95% sequence identity to SEQ ID NO:1 and SEQ ID NO:3, which comprise a mutant allele of ms10 and a mutant allele of aa, respectively (p. 217, left column, “Plant material”). The state of the prior art teaches that plants comprising mutant alleles of ms10 demonstrate dysfunctional meiosis when compared to wildtype plants (Jeong et al., Journal of Experimental Botany. 2014; 65(22):6693-6709 (Applicant’s IDS)). However, the plant taught by Martinez does not appear to comprise a reduced recombination frequency between the mutant alleles of ms10 and aa in comparison to the wildtype alleles.
Examiner’s Contact Information
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEQUANTARIUS J 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/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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