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 .
Election/Restrictions
Applicant’s election without traverse of Group I, species marker allele M1 in the reply filed on 7/3/2025 is acknowledged.
Information Disclosure Statement
The information disclosure statement filed 5/23/23 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the data given on the 1449 does not accurately reflect the reference. The IDS states:
PNG
media_image1.png
107
786
media_image1.png
Greyscale
But the actual reference provided only provides data regarding Chr1:34400..530000 of the Maize B73 RefGen. The reference is not titled “MaizeGDB Genome Center” nor does the URL at the bottom of the document match the URL in the IDS citation:
PNG
media_image2.png
62
813
media_image2.png
Greyscale
. Furthermore, the document provided is two pages, not 1 page is indicated on the 1449.
The reference provided has been placed in the application file, but the information lined through has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
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, 3-4 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-9 of copending Application No. 18/569441 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims, including teaching detection of instant M1.
The copending claims teach obtaining a nucleic acid sample from a maize plant or plant part, detecting the presence of a QTL by detecting marker M1 and selecting the maize plant. The copending claims do not state that the plant part has increased resistance to NCLB, however, this is an inherent property associated with the presence of the allele and does not distinguish the action of the instantly claimed method from that set forth in the copending application.
The copending claims in claim 5 teach selecting a plant or plant part comprising marker allele M1 which is identical to the elected M1 herein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
In the response filed 11/25/25 applicant argued that the amendments overcame the rejection of record but did not explain further. The examiner does not agree and the rejection is maintained for the reasons stated in the rejection.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-4 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental process and/or a natural phenomenon without significantly more.
The claim(s) recite(s) “identifying a maize plant or plant part” and “selecting the maize plant or plant part” which are a mental process judicial exception.
Furthermore, claim 1 recites that the plant or plant part an association between the qTL alelle and increased resistance to a pathogen causing NCLB. This sets forth a relationship between genomic content and a phenotype, which is a naturally occurring correlation that has been recognized by the courts as a law of nature.
This judicial exception is not integrated into a practical application because the only steps in addition to the judicial exceptions are obtaining a sample and detecting the presence of a QTL allele, which is presolution data gathering that does not apply or use the judicial exception in any way. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because steps in addition to the judicial exceptions are obtaining a sample and detecting the presence of a QTL allele in a chromosomal interval. This extra-solution data gathering step is recited at such a high level of that it encompasses any possible method for determining if a QTL allele is present in a maize plant or plant part, including many well-known molecular biology techniques like sequencing or hybridization analysis with allele-specific probes. See specification p. 54, lines 10-11.
The response filed 11/25/25 traverses the rejection stating the method requires concrete, physical steps of obtaining a sample and subjecting it to “a specific molecular analysis.” No “specific” analysis is required; the claims are sufficiently broad so as to encompass any possible analysis that could determine the presence of the QTL. The reasons why the additional steps neither integrate the judicial exceptions nor amount to significantly more than the judicial exceptions are given previously in the rejection. The rejection is modified and maintained.
Claims 1 and 9 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
Applicant has elected the marker M1.
The claims at issue are methods for identifying and selecting maize plants that display increased resistance to a pathogen causing Northern Corn Leaf Blight (NCLB). Claim 9 recites that the plant or plant part has increased resistance to Exserohilum turcicum.
The claims are of varying breadth, with claim 1 encompassing for detecting “the presence” of a QTL allele on chromosome 4 in a maize plant or plant part, wherein said QTL allele is flanked by marker alleles A and B. The claims do not require that the “detecting” detect marker A or B, nor even necessarily genomic content between A and B. The list of markers in the final clause of claim 1 sets forth features of the QTL allele, but does not require assaying any one of those recited SNP. The claims further set forth that the plant or plant part is identified as having increased resistance to a pathogen if said QTL or one or more of said marker alleles are present.
The disclosure teaches that the QTL allele recited in the instant claims is associated with resistance to the pathogen Exserohilum turcicum. No rejected claim specifically recites that particular genotypic content is in fact associated E. turcicum resistance.
Since the allele is being used to determine the presence of a QTL associated with increased resistance to blight caused by E. turcicum, it also follows that the allele must be associated with increased or decreased mechanical strength.
Thus, there are a variety of properties any allele that is detected that would be used in a method within the scope of the claims must possess:
(i) The marker has to be a naturally occurring variant in a maize plant
(ii) The marker must be “within" or otherwise indicative of the content (i.e. in linkage with) of a chromosomal interval comprising and flanked by marker alleles A and B
(iii) The allele must be able to “identify” the plant, and in some embodiments identify the plant as being resistant to a pathogen
(iv) The allele must be indicative of a QTL if it is to function in the method for “screening for the presence of a QTL allele.”
The nature of the invention is that a reliable association between the allele of the marker whose presence or absence is being detected and these features is required in order for the claimed methods to be meaningfully practiced.
The claims are sufficiently broad so as to encompass detecting an SNP or other polymorphic marker that is “linked” to any of the alleles disclosed in the specification and/or recited in claim 1. The term linkage refers to the preferential segregation of a particular polymorphic form with another polymorphic form at a different chromosomal location more frequently than expected by chance. Therefore, the claims encompass detecting a potentially large genus of nucleic acids. The polymorphisms that are in linkage with any of the markers specifically disclosed herein have not been identified. Furthermore, although 57 SNP within the QTL have been identified, the region identified is 2,363,181 nucleotides. The 57 SNP identified are between two specific strains of maize, and do not represent every possible SNP within the over two million base pair region of the maize genome.
Furthermore, the claims are inclusive of detecting a QTL or SNP that are associated with any possible pathogen, and that come from a plant of any parental origin.
The specification teaches analysis to determine regions of the maize genome that are quantitative trait loci for resistance to E. turcicum in plants with maize line H102 as parent. The specification discloses a QTL on chromosome 4 and sets forth genes within the QTL (Table 2) SNP within the QTL that “might be used” for the development of molecular makers for the detection of NCLB resistant corn plants (Table 4). However, there is no analysis showing that any one of these SNP alone is sufficient to predict the presence of resistance to “pathogens” in general (as set forth in claim 6) or E. turcicum in particular.
Example 1 supports the finding that a portion of chromosome 3 is associated with resistance to E. turcicum, but provides no further written description of particular alleles within the identified region that are useful for practicing the claimed methods.
The specification invites one skilled in the art to identify markers that would function for meaningfully selecting plants that exhibit a “QTL” and in particular that are likely to have increased resistance to northern corn leaf blight caused by E. turcicum.
Of all of the possible polymorphic positions in the region bound by and including Marker allele A and Marker allele B, the specification discloses only a very limited set of actual polymorphisms that could be used in the practice of the claimed invention, and even then, fails to show that any marker alone is sufficient to identify resistance in a plant or plant part.
The specification does not provide any guidance as to the physical structure of the region that may be between the two markers (i.e. the sequence is not given) other than to disclose that the region is approximately 2,363,181 nucleotides. The claims broadly encompass determining the presence or absence of any polymorphic marker in linkage with the QTL, provided it is within the physical region given in the claim. The claim does not define the structure of the linked polymorphisms or make any particular physical identification of alleles to be used within the claimed methods.
While the state of the art and level of skill in the art with regard to detection of a previously identified polymorphism in a known gene sequence is high, the level of unpredictability in associating any particular polymorphism with a phenotype is even higher. Whether or not a particular allele is associated with a phenotype must be determined empirically.
There are expected to be numerous markers that meet the functional requirements set forth in the claims. However, the specification does not teach a predictable means for distinguishing between markers that meet these functional requirements and are associated with resistance to E. turcicum and markers that are on chromosome 4 that are not associated. Practice of the claimed invention using a marker in linkage any of the particularly disclosed markers requires knowledge that the linked marker exists, knowledge that the marker is associated with the phenotype, and which allele is indicative of risk for the phenotype. While it may have been known at the time of the invention how to identify markers in linkage disequilibrium with one another it was also known in the art that not every marker at any level of linkage disequilibrium with one another will be associated with the same phenotype.
Wall (Nature Reviews Genetics (2003) volume 4, pages 587-597) teaches that linkage disequilibrium (LD) refers to the fact that particular alleles at nearby sites can co-occur on the same haplotype more often than is expected by chance (page 587, 1st column, 1st paragraph). Wall teaches that patterns of LD are known to be noisy and unpredictable as pairs of sites tens of kilo bases apart might be in complete LD, whereas nearby sites from the same region can be in weak LD (page 587, 2nd column, last paragraph). Wall teaches that population history, population size, and population structure lead to differences in LD (page 588, 1st column, top). Wall teaches, “Measuring LD across a region is not straightforward" (box 1, last paragraph, page 588). Wall teaches it is difficult to compare results from different LD studies directly because of the variation in study design and methods of analyzing the data (page 591, 2nd column, 1st full paragraph). Wall teaches there are clear differences in LD between African’s and non-Africans (page 593, 1st column). Thus, Wall teaches that LD is not predictable.
It is expected that there are thousands of SNP and other polymorphisms or alterations throughout the region bound by Marker Allele A and Marker Allele B, but applicant has provided no guidance as to which of these will be associated with resistance to E. turcicum, and which allele of those that are associated will be predictive, other than by identifying the alleles of the particular polymorphisms identified in the specification. Practice of the claimed invention using a particular polymorphic marker requires knowledge that the marker exists, that it is associated with the phenotype, and which allele is indicative of risk for the phenotype. Thus, to practice the claimed invention commensurate in scope with the currently written claims every possible position of the region will have to be tested and analyzed to determine if there is an association between the genomic location and the phenotype. Such analysis will have to include replicated, case-controlled studies, as at the time the invention was made, it was known that SNP association studies typically are not easily replicated.
Having carefully considered the scope of the claims, the guidance in the specification, the disclosed working examples and the unpredictability in the technology area, it is concluded that it would require undue experimentation to practice the claimed invention commensurate in scope with the claims.
Claims 1, 3, 4 and 9 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 screening for the presence of a QTL allele located on chromosome 4 in a maize or maize plant by identifying at least the nucleotide present at M1 (consonant with the election), does not reasonably provide enablement for screening for the presence of the QTL allele via the detection of any possible marker linked with or within the allele. Furthermore, the specification is not enabling for predicting the resistance to any pathogen, and is not enabling for predicting resistance or detecting the QTL in plants that are not derived from the H102 line. 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 use the invention commensurate in scope with these claims.
The specification teaches that the term “quantitative trait locus” or “QTL” may refer to a region of DNA that is associated with the differential expression of a quantitative phenotypic trait in at least one genetic background. The region of the QTL encompasses or is closely linked to the gene or genes that affect the trait in question. An “allele of a QTL” can comprise multiple genes or other genetic factors within a contiguous genomic region or linkage group (p. 35).
Thus, the scope of “screening for the presence of a QTL allele” is quite broad and can encompass methods which detect any marker that is associated with the quantitative phenotypic trait, whether it is within the bounds of marker A and marker B or not. The specification has provided very little guidance as to what nucleotide content is sufficient to identify the QTL in any plant that does not originate from the H102 parental line.
The examples in the instant specification teach crossing maize H102 (an E. turcicum resistant maize) mapping populations and identifying a region on Chromosome 4 of the H102 progeny plants that is associated with increased resistance to E. turcicum in four different F2 populations (p. 120). The specification reports whole genome sequencing and assembly of the donor line H102 (p. 120). Instantly elected M1 is reported to be in gene Zm00001d049121. At the cDNA level, the resistant H102 genotype shares 98.3% identity with susceptible B73 genotype, and at protein level 97.7%. An alignment of the cDNA sequences is provided in Fig 1A-1D. The H102 cDNA sequences is given in SEQ ID NO: 1 (Table 2, p. 122). The specification demonstrates that by expressing the H102 Zm00001d049121 gene in the susceptible maize genotype A199 increased resistance was achieved in two transgenic lines (p. 124; figures 13 and 14). Table 4 provides a list of differences between SEQ ID NO: 1 and SEQ ID NO: 11, the former alleles representing the H102 resistant donor alleles. Of these, M1, which is the nucleotide present at position 1071 of SEQ ID NO: 1 was elected for prosecution.
The claimed invention is asserted be for "identifying a maize plant or plant part,” which read in light of the specification is identification of a maize plant or plant part that display or is likely to display increased resistance to a pathogen, more specifically leaf blight caused by E. turcicum by screening for the presence of a QTL.
While the specification demonstrates that the H101 cDNA represented in SEQ ID NO: 1 itself, when expressed in its entirety, is sufficient to increase resistance in plants engineered to express the gene, the specification does not, demonstrate that the presence of any one SNP alone of those recited, or M1 in particular is sufficient to identify the QTL or resistance to any pathogen, or even resistance to blight caused by E. turcicum.
The practice of the claimed invention requires the knowledge of particular alleles at particular polymorphic positions in order to identify the QTL. There are tens of thousands of possible positions of DNA included in the chromosomal region bound by and marker A and marker B. There is very limited disclosure of particular markers or alleles that would function in the claimed methods.
QTL are not expected to be the same in every population of plants tested. For example, Ding et al. (IDS; 2015) and Wang et al. (IDS; 2018) both disclose mapping experiments to identify genomic regions associated with northern corn leaf blight. The two references used mapping populations different from each other and different from the instant specification. They identified QTL in different portions of the genome. None of the regions of interest identified in their study overlap with those disclosed here, and the obtained different results in each of the populations they tested. This is relevant because it demonstrates that it would be highly unpredictable as to whether or not one attempting to elucidate the actual alleles of markers that would function in the claimed method would even be successful, depending on the plant populations they used in order to attempt to make the determination.
It would require a prohibitively large and unpredictable amount of experimentation in order to practice the invention commensurate in scope with the claims. The common set of markers is essential to the practice of the invention and must be selected from hundreds of thousands of possible polymorphic positions with minimal guidance. Further, although the specification discloses a limited set of markers that may function in the claimed invention, the disclosure does not provide any guidance for using M1 alone or with any other markers to determine the presence of the QTL in plants that do not have SEQ ID NO: 1 originating from H102. The disclosure contains an invitation to anyone attempting to practice the claimed invention to undertake experimentation that would involve case-controlled comparisons of susceptible and resistant maize plants, identification of polymorphic sites and then testing alleles to determine which particular alleles are associated with the phenotype. Since a QTL may be present in one population but not another, the experimentation may or may not successfully identify markers in linkage with the disclosed markers or with the trait itself.
Thus, having carefully considered all of these factors, it is concluded that it would require undue experimentation to practice the claimed invention commensurate in scope with the instant claims.
The response filed 11/25/25 traverses the rejections under 112a set forth in the previous office action.
Applicant argues that claim 1 is no longer directed to an open-ended group of unknown markers, instead it is directed to a specific genus of 56 markers. However, even though the claim defines these markers as features of the QTL, the claim does not require the detection of any one of the recited markers to identify the QTL, it still encompasses detecting the recited QTL by detecting any content within or linked to the QTL.
Conclusion
The claims are not rejected over the prior art because, with regard to the elected M1, no reference teaches identifying a T at the recited position 1071 within SEQ ID NO: 11.
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 Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682