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
Claims 1-7 and 11-19 are pending and examined. Claims 8-10 have been cancelled. All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Amendments
Status of Objections
In regard to the claim objection is withdrawn.
Status of Rejections from action:
The rejection of claims 1-19 on the basis of 101 is withdrawn in light of Applicant’s argument that the “resistance genes recited in claims 1-10 are not naturally present in the claimed Spinacia oleracea spinach plants”.
The rejection of claims 1-7 and 11-19 on the basis that it contains written description issues under 112(a) is modified in view of the amendments.
The rejection of claims 1-7 and 11-19 on the basis that it contains enablement issues under 112(a) is modified in view of the amendments.
The rejection of claims 1-19 on the basis that it contains deposit enablement issues under 112(a) is withdrawn until allowance.
Response to Declaration
The Applicant mainly argues that the “resistance genes recited in claims 1-10 are not naturally present in the claimed Spinacia oleracea spinach plants” is considered and found persuasive. Therefore, the 101 rejection is withdrawn.
Claim Rejections - 35 USC § 112(a) (Written Description)
Claims 1-7 and 11-19 REMAIN 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.
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing 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 invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant’s disclosure is as follows.
Applicant has described the gene originating from S. tetrandra but not something with 95% to SEQ ID NO: 2 from lettuce. Furthermore, the specification describes the resistance that was only seen with marker 2 (SEQ ID NO: 4) and marker 4 (SEQ ID NO: 6), (pg. 6 lines 32-33). Lastly, the specification validated that said gene specifically confers resistance to Peronospora farinose races Pfs6 to Pfs8, Pfs10, and Pfs14 to Pfs18 (pg. 11 table 3).
(1) Applicant has not described the structures found with the protein and coding sequence of SEQ ID NOs: 2 and 1, respectively, that confer functionality and (2) has not described a representative number of structures from the genus of structures having at least 95% sequence identity to SEQ ID NOs: 2 and 1 from lettuce (e.g., see sequence search results).
The specification does not describe the features, motifs, and conserved regions of sequences having as little as 95% sequence identity to SEQ ID NO: 2 and a coding sequence of at least 95% sequence identity to SEQ ID NO: 1 from lettuce which confers resistance to Pfs.
The specification does not describe any common structures or motifs found within the Pfs resistance gene (also referred as L6 resistance gene) which confers resistance to the broad genus of Pfs as encompassed by the claims. Therefore, one skilled in the art would appreciate that Applicant does not possess the genus of structures as claimed and which retain functionality.
Additionally, the specification describes that SEQ ID NO: 2 is a “novel candidate dominant Pfs resistance gene is a so called NBS-LLR type of gene” (spec. pg. 3 lines 8-9). However, the NBS-LRR family are very large gene family with diverse functions thus there are many different structures that confer function in the gene family.
The specification does not describe any information about the structure of this gene family so one could make a protein having a completely different function than that of conferring resistance.
For example, McHale et al. (“Plant NBS-LRR proteins: adaptable guards” Genome biology vol. 7,4: 212, 2006 (previously cited)) describes that “[t]he majority of disease resistance genes in plants encode nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins. This large family is encoded by hundreds of diverse genes per genome and can be subdivided into the functionally distinct TIR-domain-containing (TNL) and CC-domain-containing (CNL) subfamilies. Their precise role in recognition is unknown; however, they are thought to monitor the status of plant proteins that are targeted by pathogen effectors” (pg. 212.1).
Thus, one skilled in the art would be unable to identify the claimed resistance gene when there are so many genes to look through. Compounding this issue is one has to identify a resistance gene with as little as 95% sequence identity that will retain functional activity and confer resistance to the genus of claimed races.
The specification fails to describe that variants with at least 95% sequence identity will confer resistance against Pfs across all varieties of spinach rendering it unknown if the variants will retain functional activity and confer resistance to the claimed races.
Here, it is not described whether variants of SEQ ID NOs: 1-2 (i.e., sequences with as little as 95% identity to SEQ ID NOs: 2 and 1 from lettuce) will retain functional activity because the specification does not describe functional domains or motifs such that one would have no idea if the variants possess the necessary structures to be functionally active and confer resistance.
Furthermore, claims 1-7 and 11-19 encompass a protein sequence having at least 95% identity to SEQ ID NO: 2, or coding sequence having at least 95% identity to SEQ ID NO: 1 from lettuce. This requires the specification to describe nucleic acid sequences encoding such proteins.
However, the specification does not describe a coding sequence having at least 95% identity to SEQ ID NO: 1, or a polypeptide with at least 95% identity to SEQ ID NO: 2 from lettuce, which leads to a functional L6 resistance gene.
A nucleic acid sequence having at least 95% identity to SEQ ID NO: 1 would have 170 nucleic acid substitutions relative to SEQ ID NO:1, while a polypeptide with at least 95% identity to SEQ ID NO: 2 would have 57 amino acid substitutions relative to SEQ ID NO: 2.
These polynucleotide and polypeptides would encompass 3170 and 1957 distinct gene and protein variants, respectively. In the absence of describing where in the sequence of SEQ ID NO: 1 such variations can be sustained, one of skill in the art would not be led to believe that Applicant possesses this vast genus of nucleic and amino acid sequences that retain functional activity, or to the make the polypeptide which would retain the activity of SEQ ID NO: 2, and lead to resistance to Pfs.
Therefore, while the examples describe that a specific L6 resistance gene can confer resistance with spinach, the specification fails to provide adequate description on the motifs, catalytic domains, etc. in these sequences having as little as 95% sequence identity to SEQ ID NO: 2 from lettuce that confers the specifically claimed function of Pfs resistance.
The specification has described one structure/sequence which is not deemed to be a representative number of structures/sequences from the genus of sequences having 95% sequence identity to SEQ ID NO: 1-2 from lettuce, respectively, that retain function and thus confer Pfs resistance.
Furthermore, the specification has not described if the SEQ ID NO:2 or sequence with at least 95% sequence identity to SEQ ID NO: 2 from lettuce will confer Pfs resistance in spinach cultivars.
For example, a blast search of the top ten results shows proteins as unnamed, predicted, and hypothetical genes.
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These alignments (1) do not have high sequence similarity and (2) do not describe structures that confer resistance as claimed. Therefore, based on the state of the art the skilled artisan would not know the structures found within sequence having as little as 95% sequence identity to SEQ ID NO: 2 that confer resistance to the genus of races as claimed.
This description is also critical because Table 3 shows that the gene DOES NOT confer resistance against Pfs 4, 9 and 11 which further suggests that the genus of sequences as encompassed by the claims would not have functionality.
Also note claims encompass more than just 19 Pfs as described in the specification. In other words, claims encompass a large genus of sequences that confer resistance to known and yet to be found Pfs.
The lack of a description of a representative number of structures/sequences, the absence of information in the art on conserved regions required for activity, or the impact of 5% variation of the sequence, one skilled in the art would not know the structures conferring claimed resistance. The examples are specific examples tied to a specific starting material, and not reasonably reproducible description to predictably produce downy mildew resistant spinach plants.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111.
Response to Arguments
Applicants’ arguments filed 06/12/2026 have been fully considered but they are
not persuasive. Applicant argues “Plants comprising marker 2 (SEQ ID No. 4) and 4 (SEQ ID No. 6) comprised the resistance locus 6 comprising the resistance gene in contrast to the susceptible plant comprising marker 1 and 3." and that these molecular markers provide structural characteristics that identify the resistance gene and demonstrate possession of the claimed invention”, disclosing the “deposit number NCIMB 43935” and that one skilled in the art would preserve the NBS-LRR regions.
The Applicant has described the gene originating from S. tetrandra but not structures having as little as 95% to SEQ ID NO: 2 from lettuce. The specification does not show a representative number of structures having at least 95% sequence identity to SEQ ID NOs: 1 and 2 from lettuce and conferring said phenotype.
The Applicant incorrectly conflates finding a gene using markers with predicting whether sequence variants will retain function. Identifying markers provides no structure-function relationship for the Pfs resistance gene, nor does it describe a representative number of species across the claimed genus.
Additionally, even though the Applicant discloses the deposit number, one skilled in the art would find it hard to believe that the Applicant was in possession of sequences having at least 95% sequence identity to SEQ ID NOs: 1 and 2 from lettuce. Thus, Applicant’s arguments are not commensurate in scope with what is claimed, because claim 1 is not directed to the deposited plant of NCIMB 43935. Plus, the deposited plant doesn’t have a polynucleotide with at least 95% identity to SEQ ID NO:2, it has SEQ ID NO:2. Therefore, the specification fails to adequately describe and show possession of sequences with at least 95% sequence identity of the invention as broadly claimed.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1-7 and 11-19 REMAIN 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 the spinach plant comprising a Pfs resistance gene (SEQ ID NO: 2), specifically to races Pfs6 to Pfs8, Pfs10, and Pfs14 to Pfs18 (pg. 11 table 3), does not reasonably provide enablement for any spinach plant comprising a protein having as little as 95% sequence identity to SEQ ID NO: 2 or a coding sequence having as little as 95% sequence identity to SEQ ID NO: 1, or methods of using said protein. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
“The first paragraph of 35 U.S.C. § 112 requires, inter alia, that the specification of a patent enable any person skilled in the art to which it pertains to make and use the claimed invention. Although the statute does not say so, enablement requires that the specification teach those in the art to make and use the invention without ‘undue experimentation.’ In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is ‘undue.’” In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original); see also In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’”) “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” Wands, supra.
Some experimentation, even a considerable amount, is not “undue” if, e.g., it is merely routine, or if the specification provides a reasonable amount of guidance as to the direction in which the experimentation should proceed. Factors to consider include “(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.” Id.
Applicant’s disclosure is as set forth above. The claimed invention is not enabled for the following reasons. To comply with 35 USC 112(a) enablement, one skilled in the art must be able to make and use the claimed invention.
(A) The breadth of the claims
The claims encompass any spinach plant comprising a resistance gene having any structure within 95% sequence identity to SEQ ID NOs: 2 providing resistance against a broad genus of Pfs.
(B) The nature of the invention.
The nature of the claimed invention is directed to any spinach plant comprising a L6 resistance gene having at least 95% sequence identity to SEQ ID NO: 2 from lettuce and which confers resistance against any Pf.
(C) The state of the prior art
The state of the prior art does not teach structures having at least 95% sequence identity to SEQ ID NOs: 2 and 1 from lettuce, respectively, that have functional activity and confer Pfs resistance.
(D) The level of one of ordinary skill
The level of one of ordinary skill in the art is high.
(E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The specification does not provide the adequate amount of direction or guidance regarding the features, motifs, and conserved regions of sequences having as little as 95% sequence identity to SEQ ID NO: 2 and a coding sequence of at least 95% sequence identity to SEQ ID NO: 1 from lettuce which confers resistance to Pfs.
The specification does not teach common structures or motifs for the Pfs resistance gene or that confer resistance to the genus of Pfs as encompassed by the claims. Therefore, one skilled in the art would appreciate that Applicant does not possess or showing enough working examples of the genus of structures as claimed and which retain functionality.
The specification has failed to teach (1) the structures found with the protein and coding sequence of SEQ ID NOs: 2 and 1, respectively, that confer functionality or (2) provided enough working examples for the genus of structures having at least 95% and 95% sequence identity to SEQ ID NOs: 2 and 1 from lettuce, respectively.
Additionally, the specification teaches that SEQ ID NO: 2 is a “novel candidate dominant Pfs resistance gene is a so called NBS-LLR type of gene” (spec. pg. 3 lines 8-9). However, the NBS-LRR family are very large gene family with diverse functions thus there are many different structures that confer function in the gene family.
Moreover, the specification does not teach any information about the structure so one could make a protein having a completely different function. For example, McHale et al. (“Plant NBS-LRR proteins: adaptable guards” Genome biology vol. 7,4: 212, 2006 (U) teaches that “[t]he majority of disease resistance genes in plants encode nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins. This large family is encoded by hundreds of diverse genes per genome and can be subdivided into the functionally distinct TIR-domain-containing (TNL) and CC-domain-containing (CNL) subfamilies. Their precise role in recognition is unknown; however, they are thought to monitor the status of plant proteins that are targeted by pathogen effectors” (pg. 212.1).
Thus, one skilled in the art would find it be unable to predictably identify and make the claimed resistance gene when there are so many sequences to screen. Adding another layer of unpredictability is one must identify a resistance gene with as little as 95% sequence identity that will retain functional activity and confer resistance to the genus of claimed races.
The specification fails to teach that variants with at least 95% sequence identity will retain function and confer resistance against the genus of Pfs across different spinach varieties. Additionally, the specification has not provided any working example that sequence with at least 95% sequence identity would result in Pfs resistance phenotype.
The resistance observed is tied to this singular, isolated genetic material in a specific plant, and the specification has failed to teach that variants of SEQ ID NOs: 1-2 from lettuce (i.e., sequences with as little as 95% identity to SEQ ID NOs: 2 and 1 from lettuce, respectively) will predictably confer resistance which is important because the specification does not teach functional domains or motifs that confer functional activity and will confer resistance. This teaching is also critical because Table 3 shows that the gene DOES NOT confer resistance against Pfs 4, 9 and 11 which further suggests that the genus of sequences as encompassed by the claims would not have the intended functionality as broadly claimed in claim 1.
Also note claims encompass more than just 19 pfs as described in the specification. In other words, claims encompass a large genus of sequences that confer resistance to known and yet to be found Pfs.
Furthermore, claims 1-7 and 11-19 encompass a protein sequence having at least 95% identity to SEQ ID NO: 2, or coding sequence having at least 95% identity to SEQ ID NO: 1 from lettuce. This requires the specification to teach nucleic acid sequences encoding such proteins.
However, the specification does not teach or provide guidance for making a coding sequence having at least 95% identity to SEQ ID NO: 1, or a polypeptide with at least 95% identity to SEQ ID NO: 2 from lettuce, which leads to a functional L6 resistance gene.
A nucleic acid sequence having at least 95% identity to SEQ ID NO: 1 would have 170 nucleic acid substitutions relative to SEQ ID NO:1, while a polypeptide with at least 95% identity to SEQ ID NO: 2 would have 57 amino acid substitutions relative to SEQ ID NO: 2.
These polynucleotide and polypeptides would encompass 3170 and 1957 distinct gene and protein variants, respectively. In the absence of guidance indicating where in the sequence of SEQ ID NO: 1 such variations can be sustained, undue trial and error experimentation would be required to make the claimed coding of SEQ ID NO: 1, or to the make the polypeptide which would retain the activity of SEQ ID NO: 2 from lettuce, and lead to resistance to Pfs.
Therefore, while the examples teach that certain specific L6 resistance gene SEQ ID NO: 2 from lettuce can confer resistance with spinach, the specification fails to teach motifs, catalytic domains, etc. in these sequences that confer the specifically claimed function of resistance. Applicant has not taught the genus of structure/sequence having 95% sequence identity retain function and thus confer resistance.
For example, a blast search of the top ten results shows proteins as unnamed, predicted, and hypothetical lacking adequate enabling guidance of other resistance genes.
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Therefore, because the art fails to teach the structures required for L6 resistance gene functional activity, a person skilled in the art would be unable to predictably make, and thus use, the claimed amino and nucleic acid sequences as the specification fails to teach the critical domains and motifs that are required for functional activity.
The lack of representative sequences, information on conserved regions required for activity, or the impact of 5% variation of the sequence, shows there is not enough guidance to predictably make and/or use the claimed sequences. The examples are specific examples tied to a specific starting material, and not reasonably reproducible teachings to predictably produce downy mildew resistant spinach plants.
The claimed invention lacks adequate enabling guidance with regard to the genus of spinach plants that comprise L6 resistance gene whereby the plant confers resistance to downy mildew races Pfs 6, 8 and 18.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples regarding the structure of L6 resistance gene having at least 95% sequence identity to SEQ ID NO: 2 from lettuce which confer functional activity in spinach, the state of the prior art, and unpredictability in the art, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without excessive burden and undue experimentation.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Response to Arguments
Applicants’ arguments filed 06/12/2026 have been fully considered but they are not persuasive. Applicants argues (1) “the specification discloses that seeds of Spinacia oleracea plant according to the present invention "were deposited on 17 January 2022 at NCIMB Ltd, Ferguson Building, Craibstone Estate Bucksburn, AB21 9YA Aberdeen, United Kingdom."14 This biological deposit (NCIMB 43935) provides the skilled artisan with direct access to the exact genetic material comprising the resistance gene, eliminating any need for undue experimentation to obtain the starting material”; (2) “the specification provides clear guidance on methods for introducing the resistance gene into susceptible spinach plants. As disclosed, the method comprises "introducing or providing of a resistance gene in the genome of a susceptible spinach plant thereby providing the downy mildew resistant spinach plant."15 The specification further teaches that "[t]he resistance gene can be introduced or provided to the susceptible spinach plant via one or more mutations in the on locus 6 on chromosome 3 in spinach (Spinachbase.org), wherein the one or more mutations comprise deletions, insertions or substitutions resulting in the coding sequence of SEQ ID No. 1 thereby providing Pfs resistance”; (3) “the specification describes a crossing method for providing resistant spinach plants, comprising the steps of "a) providing a spinach plant comprising the resistance gene of present invention, b) crossing the spinach plant of step a) with a susceptible spinach plant, c) optionally, selfing the plant obtained in step b) for at least one time, d) selecting the plants that are resistant to downy mildew”; (4) “The specification further explains that "[r]esistant spinach plants were transient transformed with a L6 gene silencing construct (L6 VIGS) and infected with Peronospora farinose (Pfs 17) causing downy mildew in spinach.” Through these experiments, "it was demonstrated that the L6 gene was associated with downy mildew resistance, i.e. resistant spinach lines were made susceptible via virus induced gene silencing thereby silencing the L6 resistance gene”; and (5) the specification provides molecular markers for identifying plants comprising the resistance gene.
In regard to argument (1) Applicant’s arguments are not commensurate in scope with what is claimed, because claim 1 is not directed to the deposited plant of NCIMB 43935. Plus, the deposited plant doesn’t have a polynucleotide with at least 95% identity to SEQ ID NO:2, it has SEQ ID NO:2.
In regard to arguments (2) and (3) Applicant has not provided guidance or working examples on structures having at least 95% sequence identity to SEQ ID NO: 2 from lettuce and that confer functional activity. Thus, the scope as it is claimed is not enabled.
In regard to argument (4), the specification does not enable sequences having at least 95% sequence identity to SEQ ID NOs: 1 and 2 and conferring resistance the genus of Pfs. As seen in table 3 SEQ ID NOs:1 and 2 do not confer resistance to all the races listed such as races 1-5, 9 and 11-13, let alone all the undisclosed species of Pfs. Thus, Applicant’s arguments are not commensurate in scope with what is claimed, and the specification fails to adequately enable sequences with at least 95% sequence identity and provide enough working examples of the invention as broadly claimed.
In regard to argument (5), Applicant has taught the gene originating from S. tetrandra but not structures having as little as 95% to SEQ ID NO: 2 from lettuce. The specification does not teach working examples or clear guidance on structures having at least 95% sequence identity to SEQ ID NOs: 1 and 2 from lettuce and conferring said phenotype.
The Applicant incorrectly conflates finding a gene using markers with predicting whether sequence variants will retain function. Identifying markers provides no structure-function relationship for the Pf resistance gen, nor does it enable working examples of species across the claimed genus.
Therefore, the rejection is maintained.
Conclusion
No claims are 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.
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/C.J.O./Examiner, Art Unit 1663 /JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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