Detailed Action
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 41-43 and 46-60 are pending.
Claims 50-60 are withdrawn.
Claims 41-43 and 46-49 are examined on the merits in the present Office action.
Withdrawn objections
The objection to the Specification is withdrawn in light of amendments made by Applicant.
Withdrawn rejections
The rejection of claim 42 under 35 USC 112(b) is withdrawn in light of amendments made by Applicant.
Claim Objections
Claim 42 is objected to because of the following informalities: in part (b), “1079-109” appears to be a typographical error, which should instead recite, “1079-1094” based on Table 1. Appropriate correction is required.
Written description
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 41-43 and 46-49 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.
Due to Applicant's amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 4/24/2025, as applied to claims 41-43 and 46-49.
Claim 41 requires a wheat plant comprising a heterologous polynucleotide segment conferring leaf and stripe rust resistance ranging from marker 2-3HS2 to 2-3HS3 wherein 2-3HS2 is amplified by forward and reverse primers SEQ ID NO: 32 and 33, respectively and 2-3HS3 is amplified by forward and reverse primers SEQ ID NO: 37 and 38, respectively. The 2-3HS2 marker comprises a nucleic acid sequence with at least 98% identity to SEQ ID NO: 34. The 2-3HS3 marker comprises at least 98% identity to SEQ ID NO: 39. The heterologous polynucleotide segment comprises a scaffold having at least 97% identity to SEQ ID NO: 23 and is devoid of SEQ ID NO: 35, SEQ ID NO: 36 or a combination thereof. It is noted that the limitation of the heterologous polynucleotide segment being devoid of SEQ ID NO: 35, SEQ ID NO: 36 or a combination thereof is drawn to the exclusion of both SEQ ID NO: 35 and SEQ ID NO: 36 or a single sequence of SEQ ID NO: 35 or SEQ ID NO: 36, i.e., the claim is inclusive of either SEQ ID NO: 35 or SEQ ID NO: 36 but not both.
Claim 42 requires all of the limitations of claim 41 and further requires at least 97% identity to one of (a)-(d) which each includes all of the specified segments of either SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 31 or SEQ ID NO: 2, respectively.
Claim 43 limits the wheat plant of claim 41 by requiring that the Aegilops sharonensis from which the heterologous polynucleotide segment is derived is Accession TH548, which has been deposited with NCIMB under Accession no. 43567.
Claim 46 limits the wheat plant of claim 41 by requiring that the heterologous polynucleotide segment is located within chromosome 6B of said wheat plant.
Claim 47 limits the wheat plant of claim 41 by requiring the heterologous polynucleotide segment is a construct comprising at least one regulatory element.
Claim 48 limits the wheat plant of claim 46 by requiring that the plant is either homozygous or heterozygous for the heterologous polynucleotide segment on chromosome 6B.
Claim 49 requires that the wheat plant of claim 41 shows a phenotype of enhanced resistance to leaf and stripe rust compared to a plant not comprising the heterologous polynucleotide segment.
Applicant has described secondary recombinant “SR” lines having leaf rust resistance (Table 4, pages 50-51). The applicant describes that all recombinant lines were also highly resistant to stripe rust with the exception of R-4, which segregated for resistance (Example 4, page 50). Applicant describes that markers 2-3HS2 and 2-3HS3 are present in all resistant lines and absent in all susceptible lines, citing Fig. 4 (page 48, paragraph 1). Applicant describes in the Brief Description of the Figures (page 18) regarding Fig. 4, that the wheat lines presented include 12 secondary recombinant lines (designated R-[No.]), one tertiary recombinant line “P-37”, a line derived from a cross between R-10 and R-18 “R-1018-8” and a line derived from a cross between R-10 and R-16 “R-1016-10”. Applicant describes that Fig. 4 indicates which regions from A. sharonensis are present in each line. However, the “Wheat lines ID” column of Fig. 4 does not appear to correspond to the described entries on page 18. For example, one row with the entry “R1/11” may be interpreted as indicating that two of the 12 secondary recombinant lines R1 and R11, described by Applicant as being designated “R-[No.]”, have the same regions from A. sharonensis, however, it is then unclear what “R8/18”, for example, is referring to. Alternatively, if the number after the “/” is referring to an individual from one of the 12 secondary recombinant lines, it is not clear why there are only 9 of the 12 secondary recombinant lines presented in Figure 4. Additionally, it is noted that it is not clear how these entries correspond to the resistance data provided in Table 4. Applicant describes that R-1-2-103 and R-1-2-104 were very resistant in addition to all recombinant lines, citing figure 6 (page 51), however it is not clear which segments are present. In Example 5, Applicant describes conducting EMS on resistant parent lines 42 and 34 to identify loss of resistance mutations (Table 5); however, it is not clear whether these lines were screened for resistance (or loss thereof) or screened for similarity to A. sharonensis as Applicant appears to describe was conducted in the last paragraph of page 54 and the first paragraph of page 55. The applicant describes that the scaffolds contain SNPs in, or close to, potential resistance genes (Example 5, page 55). The applicant describes scaffolds in Table 6 which are associated with marker 2-3HS2 located in the genomic region 34-62 Mbp on 6Ssh of A. sharonensis (page 55, paragraph 1). The Applicant describes Sanger sequencing performed to compare resistant and susceptible lines to validate presence of SNPs in scaffolds 19799, 00757, 1934717, 1549600 and 20860; however, it is not clear that applicant validated results by screening for resistance to a stripe rust isolate, for example, or screened for similarity to parent lines. (Example 6). The Applicant refers to introducing the sequence of potential resistance gene(s); however, the Applicant does not appear to have reduced this to practice (Example 6).
It is noted that Wheat cultivar Galil comprises leaf rust resistance Lr26 and stripe rust resistance Yr19 gene, but is susceptible to the leaf and stripe rust isolates that were used in the present disclosure (page 39, paragraph 3).
Applicant has not described a representative number of species demonstrating increased leaf and stripe rust resistance across the claimed genus of plants comprising nucleic acid sequences with 98% identity to marker 2-3HS2, i.e., SEQ ID NO: 34, 98% identity to marker 2-3HS3, i.e., SEQ ID NO: 39 and a scaffold comprising at least 97% identity to SEQ ID NO: 23 nor a nucleic acid sequence with at least 97% identity to all of the specified segments of either SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 31 or SEQ ID NO: 2. Applicant has not described a structure-function relationship other than plant which comprise not only the entire segments of 2-3HS2 and 2-3HS3 but additional flanking regions, as provided in Fig. 4.
Applicant has not described a representative number of species nor a structure function relationship across all stripe and leaf rust isolates, nor those specific to the isolates which Galil are susceptible to. It is noted that it is not clear which regions are present and absent in the lines found to be resistant in Tables 4 which may provide additional resolution, however, Applicant has not described recovery of loss-of-resistance or other support for a causal mutation or allele but only regions containing SNPs in, or close to, potential resistance genes. Applicant has not described increased leaf and stripe rust resistance in any wheat plant background other than Galil other than PHIb induction of homoeologous pairing between cultivar Chinese Spring and A. sharonensis (page 39). Furthermore, the applicant has not provided a structural-functional correlation presented for 2-3HS2, 2-3HS3 or the protein which is responsible for leaf and stripe rust in the specification. For example, while Applicant has not clearly provided that the region of 2-3HS2, 2-3HS3 alone confers improved resistance to leaf and stripe rust in wheat (see for example, Figure 4), it is not clear what SNP must be present in SEQ ID NO: 34, SEQ ID NO: 39 and SEQ ID NO: 23 in order for one of ordinary skill in the art to recognize possession of the claimed resistance traits. Given that Applicant claims these sequences with 97-98% identity, it is not clear how one would determine, among all potential differences, which would include SNPs found to be associated with resistance.
Given that Applicant has provided only provided evidence that the region of 2-3HS2 to 2-3HS3 comprising SEQ ID NO: 23 and at least some additional flanking region from sequences that are linked to unspecified loci that confer the claimed function in a very large chromosomal interval spanning the region 34-62 Mbp on 6Ssh of A. sharonensis, it remains unclear which embodiments of the claimed invention comprise the claimed function. The specification fails to provide an adequate written description to support the breadth of the claims. Therefore, one skilled in the art would not have recognized Applicants to be in possession of the claimed invention at the time the application was filed.
Response to Applicant’s arguments regarding rejection under 35 USC 112(a) for failing to comply with the written description requirement
Applicant's arguments filed 9/8/2025 have been fully considered but they are not persuasive.
The Declaration under 37 CFR 1.132 filed 9/8/2025 is insufficient to overcome the rejection of claims 41-43 and 46-49 based upon 35 USC 112(a) as set forth in the last Office action.
Applicant argues that claims 41 and 42 have been amended to characterize the claimed nucleic acid segment as ranging from 2-3HS2 to 2-3HS3, comprising a 5Mb region rather than a 34-62Mb region. Applicant argues that this segment comprises the claimed function of conferring or enhancing resistance of wheat to leaf and stripe rust. Applicant argues that the Declaration indicates the recited sequences would not be lost due to crossover events. Applicant argues that section 7 of the Declaration indicates that mapping the causal allele to the claimed segment was performed by analysis of frequency of recombination events. SNPs were used to develop PCR probes which distinguish between the alien segment and the wheat chromatin. Crosses of plants comprising the resistance-associated SNPs enabled the identification of the shortest segment. Both 2-3HS2 and 2-3HS3 were present in all secondary recombinant lines that retained rust resistance, whereas other flanking markers showed some degree of variation or absence. Additionally, these markers (note: Examiner presumes Applicant is referring to 2-3HS2 and 2-3HS3) were absent in susceptible lines. Applicant argues that Section 8 of the Declaration provides that all crosses between a resistant plant of the invention and a susceptible plant showed resistance to leaf rust and that all resistant secondary recombinant plants of the invention necessarily comprise the A. sharonensis segment spanning from 2-3HS2 to 2-3HS3. Applicant argues that further analyses of the segment defined by markers 2-3HS2 and 2-3HS3 located several candidate scaffolds found to be associated with marker 2-3HS2 and resistance to the rust diseases. Having a well-defined sequence of SEQ ID NO: 23 and being located within the segment boundaries, scaffold 1549600 has been selected as an additional marker or resistance conferring segment. Applicant argues that claim 41 clearly requires the presence of the sequence between 2-3HS2 and 2-3HS3, and that SEQ ID NO: 23 is within the segment.
This argument has been fully considered but it is not persuasive. Applicant has not provided a structure other than the full length of the sequence between 2-3HS2 to 2-3HS3 comprising SEQ ID NO: 23 and at least some additional flanking region from sequences that are linked to unspecified loci that confer the claimed function in a very large chromosomal interval spanning the region 34-62 Mbp on 6Ssh of A. sharonensis resulting in the claimed function. While Applicant has provided support that the 5 Mb region of 2-3HS2 to 2-3HS3 comprising SEQ ID NO: 23 confers the claimed function, Applicant has claimed each of these three sequences with variability, without having disclosed the specific SNP used to identify the resistant allele.
Enablement
Claims 41-43 and 46-49 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 enablement requirement. The claim(s) contains 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.
Due to Applicant's amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 9/23/2024, as applied to claims 41-43 and 46-49.
Due to Applicant's amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 4/24/2025, as applied to claims 41-43 and 46-49.
Claim 41 requires a wheat plant comprising a heterologous polynucleotide segment conferring leaf and stripe rust resistance ranging from marker 2-3HS2 to 2-3HS3 wherein 2-3HS2 is amplified by forward and reverse primers SEQ ID NO: 32 and 33, respectively and 2-3HS3 is amplified by forward and reverse primers SEQ ID NO: 37 and 38, respectively. The 2-3HS2 marker comprises a nucleic acid sequence with at least 98% identity to SEQ ID NO: 34. The 2-3HS3 marker comprises at least 98% identity to SEQ ID NO: 39. The heterologous polynucleotide segment comprises a scaffold having at least 97% identity to SEQ ID NO: 23 and is devoid of SEQ ID NO: 35, SEQ ID NO: 36 or a combination thereof. It is noted that the limitation of the heterologous polynucleotide segment being devoid of SEQ ID NO: 35, SEQ ID NO: 36 or a combination thereof is drawn to the exclusion of both SEQ ID NO: 35 and SEQ ID NO: 36 or a single sequence of SEQ ID NO: 35 or SEQ ID NO: 36, i.e., the claim is inclusive of either SEQ ID NO: 35 or SEQ ID NO: 36 but not both.
Claim 42 requires all of the limitations of claim 41 and further requires at least 97% identity to one of (a)-(d) which each includes all of the specified segments of either SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 31 or SEQ ID NO: 2, respectively.
Claim 43 limits the wheat plant of claim 41 by requiring that the Aegilops sharonensis from which the heterologous polynucleotide segment is derived is Accession TH548, which has been deposited with NCIMB under Accession no. 43567.
Claim 46 limits the wheat plant of claim 41 by requiring that the heterologous polynucleotide segment is located within chromosome 6B of said wheat plant.
Claim 47 limits the wheat plant of claim 41 by requiring the heterologous polynucleotide segment is a construct comprising at least one regulatory element.
Claim 48 limits the wheat plant of claim 46 by requiring that the plant is either homozygous or heterozygous for the heterologous polynucleotide segment on chromosome 6B.
Claim 49 requires that the wheat plant of claim 41 shows a phenotype of enhanced resistance to leaf and stripe rust compared to a plant not comprising the heterologous polynucleotide segment.
The Applicant has taught identifying a plant with the full length of 2-3HS2 to 2-3HS3 comprising SEQ ID NO: 23 in addition to scaffolds which in the genomic region 34-62 Mbp on 6Ssh of A. sharonensis (Table 6) which is associated with leaf and stripe rust resistance.
The Applicant has not taught how to practice the claimed invention. Applicant has not taught increased leaf and stripe rust resistance across the claimed genus of plants comprising nucleic acid sequences with 98% identity to marker 2-3HS2, i.e., SEQ ID NO: 34, 98% identity to marker 2-3HS3, i.e., SEQ ID NO: 39 and a scaffold comprising at least 97% identity to SEQ ID NO: 23 nor a nucleic acid sequence with at least 97% identity to all of the specified segments of either SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 31 or SEQ ID NO: 2. The Applicant has not taught a plant comprising a heterologous polynucleotide conferring resistance to leaf or stripe rust as the Applicant has only prophetically described transformation of a plant (page 57).
The markers claimed only seem to be used for mapping purposes. As such, the markers cannot be considered polymorphic or part of the allele associated with male sterility. As such, the markers only serve to describe a specific location from a specific source material that comprises the locus. However, outside of the specific population exemplified in the specification, it would be unpredictable that these markers would be predictive. To support this position, reference is made to the teaching of Mauricio (Mauricio, R. Nature Reviews, Genetics. 2:370-381, 2001). In this review, Mauricio summarizes the results of several QTL mapping experiments on yield and height of maize, including replicate studies of the same crosses. Although the same QTLs were detected across studies, some of those detected were unique to each cross. Even the replicate studies did not detect the same QTLs. See page 378, right column, second paragraph. As such, in view of Mauricio, the broad population contemplated by Applicant raises issues of unpredictability with respect to QTLs being repeatable in a genetically divergent cross.
Because the polymorphism associated with the phenotype is not specified, and the location where said polymorphism occurs is not recited other than vague and broad genetic linkage to a locus, wherein the locus is not defined by structure, size or location, one skilled in the art cannot make and use the claimed methods as commensurate in scope with the claims without excessive burden and undue experimentation.
Moreover, there would be unpredictability with using markers as the basis to define the genetic material from other backgrounds as the source of the introgressed traits. In other words, the markers only seem enabled for an introgressed genomic region wherein the source comprises the specific wheat lines described in the specification.
Therefore, given the breadth of the claims, the lack of guidance and working examples showing how to use the claimed markers to make the broad genus of plants having the male sterility phenotype, and the state-of-the art as discussed above, it is clear that undue trial and error experimentation would have been required to practice the claimed invention. Therefore, the invention is not enabled throughout the broad scope of the claims.
Claim 43 is rejected under 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.
Claim 43 recites that the Aegilops sharonensis referred to in claim 41 is Accession TH548, seed of which has been deposited with NCIMB under the Accession No. NCIMB 43567.
Since the Aegilops sharonensis plant is essential to the claimed invention, it must be obtainable by a repeatable method set forth in the specification or otherwise be 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. 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. It is noted that Applicant has disclosed having deposited seeds of TH548 on January 31, 2020 at the NCIMB but there is no indication that the deposit has been made and accepted under the Budapest Treaty, and thus it is unclear whether proof of viability testing is required.
If the deposit of these seeds is made 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 or a statement that all requirements under 37 CFR 1.801-1.809 will be complied with would satisfy the deposit requirement made herein.
Currently, there are seven Budapest Treaty International Depositary Authorities (IDAs) that accept seeds for deposit. Of those seven, the American Type Culture Collection (ATCC), which is one of the largest IDAs, has in the past, required 2,500 seeds for deposit. Effective January 1, 2019, ATCC reduced the number of seeds required for patent seed deposits to 25 packets of 25 seeds for deposit, for a total of 625 seeds. It should be noted, however, that although a deposit of 625 seeds is compliant for submission to ATCC, other IDAs may have different minimum requirements. Accordingly, any depositor should confirm that the number submitted to a specific IDA complies with that IDA’s requirements for seed deposits.
If the deposit has not been made 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 removedupon granting of the patent for the enforceable life of the patent in accordance with 37 CFR § 1.808(a)(2);(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, if not already present. See 37 CFR 1.801 - 1.809 (MPEP §§ 2401 -2411) for additional explanation of these requirements.
Response to Applicant’s arguments regarding rejection under 35 USC 112(a) for failing to comply with the enablement requirement
Applicant's arguments filed 9/8/2025 have been fully considered but they are not persuasive.
Applicant argues on page 13 of the remarks that the claims have been amended to require a higher percentage of identity with the markers and sequences associated with resistance.
This argument has been fully considered but it is not persuasive. Applicant has claimed a plant comprising enhanced resistance of a wheat plant to leaf and stripe rust diseases. The teaching of characterizing mutations that differ between a resistant and a susceptible plant may be informative, but Applicant has not provided evidence that one can predictably make and use the claimed plant with the loci which have only been associated with an unknown proximity to an unknown causal locus or loci of disease resistance. Applicant has not disclosed specific polymorphism in the claimed sequences and variations of SNPs, presumably including those which do not possess the resistant allele, would be expected to be encompassed by the claimed variation of sequences. It would require undue experimentation to determine the causal SNP or SNPs.
Closest Prior Art
Claims 41-43 and 46-49 are free of the prior art. The closest prior art is Millet (Millet et al. Genome (57)6:309-316. 2014), as applied to claims 41-49 under 35 USC 103 in the Non-Final Rejection filed 3/7/2024. Millet discloses inducing homoeologous recombination to obtain recombinant leaf and stripe rust resistant wheat lines from Aegilops sharonensis accession TH548. Millet does not make any teachings or suggestions which make obvious a wheat plant comprising a scaffold comprising at least 95% identity to SEQ ID NO: 23.
Conclusion
Claims 41-43 and 46-49 remain rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID R BYRNES whose telephone number is (571)270-3935. The examiner can normally be reached 9:00 - 5:00 M-F.
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/DAVID R BYRNES/Examiner, Art Unit 1662
/MYKOLA V. KOVALENKO/Primary Examiner, Art Unit 1662