DETAILED ACTION
Examiner’s Comment
Applicant’s response to the previous 105 request is not fully responsive. See MPEP 704.12(c). The exact information needed by the Office is the source of Accession 42785, that is the parental material of Accession 42786 and its seed origin, as the original source of the claimed L. virosa germplasm Accession 42786. Applicant’s deposit material inherently has parents from which it was derived, and the previous 105 request is directed to clarifying the identity of those parents and the source of the original L. virosa seed stock of Applicant’s Accession 42785 (i.e. the original source of SEQ ID NO.1-2), if obtained from a seedbank or elsewhere.
Examiner and Examiner’s supervisor are requesting a phone interview at Applicant’s earliest convenience to address this issue and respond to the previous interrogatories.
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 1-3, 5-6, 12-14 & 18-21 are under examination on the merits.
Claims 4, 7-11 & 15-17 are canceled.
Priority
Claims 1-3, 5-6, 12-14 & 18-21 receive the U.S. effective filing date of 3 June 2022.
Previous objection to the specification is withdrawn in view of Applicant’s amendment to the claims.
Previous objection to claims 16-17 is withdrawn due to Applicant’s cancelation of the claims.
Previous rejection of claims 1-6, 10-11, 14-15 & 18-20 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendment to the claims.
Previous rejection of claims 1-9 & 14-17 under 35 U.S.C. 101 as directed to a product of nature is withdrawn in view of Applicant’s amendment to the claims.
Previous rejection of claims 10-12 & 18-20 under 35 U.S.C. 101 as directed to a natural phenomenon is withdrawn in view of Applicant’s amendment to the claims.
Claim Rejections - 35 USC § 112
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, 5-6, 12-14 & 18-21 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 claims contain 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 invention.
Due to Applicant’s amendment of the claims, the rejection is modified from that set forth in the Office action mailed 11 May 2026 as applied to claims 1-20. Applicant’s arguments 5 Aug 2026 have been considered but are not persuasive.
Claims 1 & 12-13 are drawn to a protein which confers Bremia resistance in lettuce but has only 98% sequence identity to SEQ ID NO.2. All other claims depend from claim 1 or 12.
Further, Applicant has indicated that the V10 resistance gene is an allele which is not present in all Lactuca virosa, and is a specific allele contributed by a singular individual, L. virosa NCIMB 42786 [Response to 105 Request, expunged]. This represents one breeding line, naturally limited by alleles, QTL, and chromosomes it contains. Referring to the specification, we see that the V10 resistance is contributed by this one genotype from the many thousands of Lactuca lines used in lettuce breeding. Applicant does not specify in the claims that the particular germplasm being claimed is limited to or constrained by this narrow pool of breeding material (i.e. NCIMB 42786) which they have described.
A review of sequence search information reveals that there appear to be no reports of polypeptides conferring Bremia resistance of less than 100% identity to the claimed polypeptide SEQ ID NO.2 identified in the single line ‘NCIMB 42786’ reported by Applicant. Thus, prior art does not provide structural description of proteins conferring Bremia resistance having less than 100% identity to SEQ ID NO.2.
Proteins with 98% identity to the 980-residue long SEQ ID NO.2 encompass polypeptides with approximately 19 random amino acid substitutions. Describing a genus of polypeptides with all possible single amino acid substitutions relative to the 980-amino-acids-long polypeptide of SEQ ID NO.2 would require describing 1920 polypeptide sequences; a representative number of which were not described by the Applicant at the time of filing. Similarly, dependent claims recite a nucleotide with only 98% identity to the 2,943bp long SEQ ID NO.1 presented as encoding the protein of SEQ ID NO.2, which encompasses nucleic acids with ~58 nucleotide substitutions, of which a representative number were not described by the Applicant at the time of filing.
Applicant is claiming a broad range of structurally variable proteins by requiring only 98% identity to SEQ ID NO.2, and a broad range of nucleic acids by requiring only 98% identity to SEQ ID NO.1. No further structural information is provided identifying functional variants and without further guidance in the written description, such structural modification would amount to making random mutational changes in the V10 resistance gene. Making random changes in proteins is unpredictable, and thus one would not be enabled to isolate or derive such proteins as V10 conferring disease resistance with less than 100% identity to SEQ ID NO.2 with any reasonable certainty that it would function properly or reduce disease due to Bremia infection.
It has been shown within the art that highly homologous resistance genes can have different functionality owing to even small sequence changes. It has been demonstrated that mutation of a single SNP within a disease resistance gene/locus can lead to gain or loss of resistance to mildews or Oomycete pathogens [see p.423, col.1, ¶2—col.2, ¶2 in Wang; New Phytologist (2019) 221: 415–430; Published 13 June 2018].
Because of this, claims 1 & 12-13 and their dependents are rejected as not having been fully enabled, as such variable proteins conferring Bremia resistance are not described in the specification, nor taught by the existing art. Even with numerous Bremia resistance genes known and extensive study of resistance to the pathogen in lettuce no variants of V10 have been described with less than 100% identity to SEQ ID NO.2 [See Parra 2016; Euphytica (2016) 210:309–326; Published 2 May 2016].
Therefore, without guidance from the specification as to which proteins of 98% identity to SEQ ID NO.2 confer resistance to Bremia infections, it would require undue experimentation to find these proteins and their encoding sequences, if it is even possible to do so.
Applicant is advised to amend and limit claims to sequences of 100% identity and to the specific source accession(s) or germplasm reflective of the written description.
Response to Arguments
Applicant urges that rejection under U.S.C. 112(a) is improper because claims have been amended from sequence similarity of 95% to a required sequence similarity of 98%, thus narrowing the claimed genus [Remarks, p.6, par.6-p.7, par.1].
This is not convincing because Applicant has shown use of one distinctive V10 allele, from one source germplasm. Applicant does not describe or provide any examples of alternate proteins variants of <100% identity to singular natural allelic source provided. It is unclear how much, or if any variation in the V10 protein sequence would affect its function in conferring disease resistance.
Applicant argues that a resistance gene possessing a TIR domain and no NBS represents distinctive domain architecture that satisfies structural description [Remarks, p.7, par.1, l.1-4]. However, this indicates that the known conserved structural features of typical NBS-LRR resistance genes/proteins are distinct from the V10 allele now described. This emphasizes the lack of structural similarities between V10 and known resistance genes.
Applicant further argues that gene silencing experiments utilizing the disclosed sequences resulted in disease susceptibility, thus supporting claim to sequences of less than 100% similarity [Remarks, p.7, par.1, l.4-6], and that mapping of V10 in a single source germplasm (i.e. identifying the single allele associated with claimed sequences) supports claim to a narrow band of similar, but not described, V10 variants [Remarks, p.7, par.1, l.7-12].
However, the art has demonstrated even single nucleotide changes can dramatically alter the function of disease-resistance proteins [see p.423, col.1, ¶2—col.2, ¶2 in Wang; New Phytologist (2019) 221: 415–430; Published 13 June 2018], and no attempt has been made to alter V10 sequence and validate variant forms. Applicant’s functional validation relied solely on gene-silencing, or total knockdown of expression, rather than testing effects of protein sequence mutations or variations directly [Specification, p.9, par.3—p.11, par.2]. It is clear that presence/absence of functional V10 impacts disease resistance, but there is no description of how sequence modification(s) impact functionality.
Claims 1-3, 5-6, 12-14 & 18-21 are rejected 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims 1-3, 5-6, 12-14 & 18-21 require seeds of the Lactuca virosa line corresponding to NCIMB Accession Number 42786.
Applicant has stated that not all Lactuca virosa contain the V10 resistance gene and that only one specific line described in their specification, NCIMB42786, has been identified as a source of the claimed resistance [Response to 105 Request, expunged]. Since this seed claimed is essential to one being able to reproduce the claimed invention, it must be obtainable by a repeatable method set forth in the specification or otherwise be readily available to the public.
The specification does not disclose a repeatable process to obtain the exact same seed in each occurrence, and it is not apparent if such a seed is readily available to the public.
If a seed is not so obtainable or available, a deposit thereof may satisfy the requirements of 35 U.S.C. 112(a). So long as the number of seeds deposited complies with the requirements of the IDA where the deposit is made, the USPTO considers such a compliant submission as satisfying the rules under 37 CFR 1.801 through 1.809.
It is noted that Applicant has made deposit of the required Lactuca virosa germplasm at the NCIMB [Specification, p.11, par.3]. However, there is no affirmative statement in the specification that all restrictions upon availability to the public will be irrevocably removed upon granting of the patent.
If the deposit of these seeds is made and accepted under the terms of the Budapest Treaty, then an affidavit or declaration by the Applicant, or a statement by an attorney of record over his or her signature and registration number, stating that the seeds will be irrevocably and without restriction or condition released to the public upon the issuance of a patent would satisfy the deposit requirement made herein.
If the deposit has not been made and accepted under the Budapest Treaty, then in order to certify that the deposit meets the requirements set forth in 37 CFR 1.801-1.809, Applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number showing that:
(a) during the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the enforceable life of the patent, whichever is longer; and
(d) the viability of the biological material at the time of deposit will be tested (see 37 CFR 1.807).
In addition, the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. See 37 CFR 1.801 - 1.809 [MPEP 2401-2411.05] for additional explanation of these requirements.
Accordingly, there is lack of adequate description to enable a skilled artisan to recreate the claimed inventive method, because there is no clear way for them to obtain the critical V10 resistance allele contributed by the singular germplasm NCIMB 42786.
Applicant is advised to (a) provide affidavit of necessary deposit requirements, and, (b) amend and limit claims to the specific accession or germplasm reflective of the written description.
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.
For the purposes of examination, claims are currently being interpreted in view of the previous 105 request seeking clarification on the nature of the source of the V10 gene. Until Applicant can clarify, the Office’s assumption is that MRC1, and all L. virosa germplasm generally, inherently comprises the V10 gene of the instant invention as a form of non-host resistance.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lambalk [U.S. Patent 7,501,555; Published 5 Jan 2006] in view of Scheurwater [U.S. Patent Application Publication US 2020/0029523; Published 30 Jan 2020] and Parra [Theoretical and Applied Genetics (2021) 134:519–528; Published 31 Oct 2020].
Due to Applicant’s amendment of the claims, the rejection is modified from that set forth in the Office action mailed 11 May 2026 as applied to claims 1-20. Applicant’s arguments 5 Aug 2026 have been considered but are not persuasive.
The claims are drawn to methods of introduction of a downy mildew resistance gene in lettuce plants via cross-breeding and/or transgenic methods (i.e. uses of a gene construct or plasmid) which is operably linked to ‘expression providing sequences’. Claims are drawn to resulting Bremia resistant lettuce plants and seeds.
Lambalk teaches the introduction of downy mildew resistance genes in lettuce plants, specifically the transfer or introduction of genes from wild lettuce relatives including Lactuca virosa [col.2, l.49—col.3, l.43; col.4, l.56—col.5, l.12]. Lambalk teaches that alleles from wild lettuce relatives can have broad-spectrum resistance to Bremia infections [col.2, l.4-14]. Lambalk emphasizes that transfer of disease resistance alleles from wild lettuces such as L. virosa can confer qualitative, broad-spectrum resistance to Bremia lactucae (i.e. resistance to all races of Bremia) [col.5, l.14-20 & l.53-63].
Lambalk does not teach the introduction of said disease resistance alleles using biotechnological methods, including use of gene constructs and/or plasmids. Lambalk does not teach sequences linked to Applicant’s V10 gene, or the specific use of the associated major resistance cluster 1 (MRC1) in lettuce.
Scheurwater teaches the use of biotechnological approaches, specifically the use of nucleic acid fragments, constructs, and plasmids to introduce Bremia resistance genes in lettuce [¶201, 237, 239]. They teach that Bremia resistance genes can be utilized in transformation or conversion of susceptible plants to resistant forms via Agrobacterium transformation utilizing plasmid constructs with wild Bremia resistance alleles [¶246-249].
Parra teaches sources of such alleles in the identification of new genes for resistance to downy mildew in lettuce, specifically a cluster of numerous disease resistant genes in MRC1, and the use of linked markers (i.e. expression providing sequences) to characterize this cluster of disease resistance genes [p.520, col.1, ¶3—p.522, col.1, ¶1; p.523, col.1, ¶2—col.2, ¶2; Figure2; Figure 3; p.525, col.2, ¶2—p.526, col.1, ¶1].
The specification establishes that the V10 gene, and sequences comprising it, are part of the known MRC1 disease resistance cluster [Specification, p.2, l.31-32].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to modify the transfer of wild disease resistance alleles via biotechnology as taught by Lambalk to biotech methods of transferring alleles, as in Schuerwater, to the MRC1 locus, and genes contained within it, as described in Parra.
One of ordinary skill in the art would have been motivated to do so because it is simply the use of a known technique (i.e. introduction of wild disease resistance-alleles within the MRC1) to improve a similar method (i.e. introduction of wild disease-resistance alleles from Lactuca virosa) in the same way (i.e. ‘plugging in’ a new resistance locus and/or allele). The use of wild relatives as sources of disease resistance alleles to generate improved cultivars as newly described loci are reported is common and obvious to a plant breeder.
Regarding claims 1-3, 7-9, 16-17 the claims recite methods of using, or plants containing, the V10 gene and/or protein with 95-100% identity to SEQ ID NO.2 that confers Bremia resistance. Because V10 is comprises the MRC1 cluster, this limitation is met by Lambalk who teaches use of wild disease resistance alleles [col.2, l.49—col.3, l.43; col.2, l.4-14] and by Parra who teaches the MRC1 as a site harboring such alleles for conferring Bremia resistance [p.520, col.1, ¶3—p.522, col.1, ¶1; p.523, col.1, ¶2—col.2, ¶2; Figure2; Figure 3; p.525, col.2, ¶2—p.526, col.1, ¶1].
Regarding claims 4-6, 14 the claims recite the limitation that V10 is to be used in lettuce plants or seeds (i.e. embryonic or immature plants). This limitation is met again by both Lambalk and Parra whose teachings are specific to lettuce, including L. virosa [Lambalk, [col.2, l.49—col.3, l.43; Parra, p.520, col.1, ¶3—p.522, col.1, ¶1; p.523, col.1, ¶2—col.2, ¶2; Figure2; Figure 3; p.525, col.2, ¶2—p.526, col.1, ¶1].
Regarding claims 10-12, 18-20, the claims recite limitation of identifying disease resistant plants by ‘establishing presence of V10’. This limitation is broad, since ‘establishing presence’ can be achieved simply by looking at plants to see if they show symptoms of disese (i.e. mycelia on leaves) or using more complex methods such as screening molecular markers. The limitation is met by Parra (2020), who clearly teaches the identification of the MRC1 cluster by phenotyping plants (i.e. visually determining resistance) [p.520, col.2, ¶2] and also via identification with genetic markers (i.e. genotyping for resistance) [p.520, col.2, ¶3—p.522, col.1, ¶1].
Regarding claim 13, the claim recites use of gene constructs or plasmids to transfer the V10 disease resistance in lettuce (i.e. transgenic methods of using). This limitation is met by Scheurwater, who teaches methods of making transgenic Bremia resistant lettuce plants using sequences from wild relatives [¶201, 237, 239, 246-249]. The method of Scheurwater could be applied to any sequence conferring Bremia resistance, including transfer or the MRC1 cluster using associated markers and sequences described by Parra.
Because of the limitations of all claims are met by prior art describing use of wild alleles in breeding, biotech methods of their manipulation, and the identity and sequences of the MRC1 cluster containing the V10 resistance sequence(s), claims 1-20 are obvious and rejected.
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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEITH R WILLIAMS whose telephone number is (571)272-3911. The examiner can normally be reached Mon - Fri, 9:30 - 5:30 EST.
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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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/KEITH R. WILLIAMS/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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