DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II and the species of a decrease in expression level in the reply filed on 8/6/2026 is acknowledged.
Claims 1-5 & 13-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group or Species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/6/2026.
The election is made FINAL.
Status of Claims
Claims 6-12 are under examination on the merits.
Claims 1-5 & 13-14 are withdrawn.
Claim Interpretation
Claims 6-12 require modifying soybean gene Glyma.13G252100. Claims 8-12 further require that modifying refers to a decrease in an expression level, and claim 9 explicitly encompasses RNA interference. Based on the language of the claims and because the specification does not provide a more specific definition of “modifying”, claims 6-12 have been examined under the interpretation that “modifying” encompasses post-transcriptional regulation.
Nucleotide and/or Amino Acid Sequence Disclosures
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834.
Sequence identifiers are missing from Figure 3. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.832(a)), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers in the Brief Description is clear. See MPEP 2412.04. The sequences for the wildtype and A-H1 mutant depicted in Figure 3 must be added to the Sequence Listing File, if not already present, and the sequence ID numbers must be added to the figure or to the brief description in paragraph [0019]).
Full compliance with the sequence rules is required in response to this Office action. A complete response to this Office action must include both compliance with the sequence rules and a response to the issues set forth herein. Failure to fully comply with both of these requirements in the time period set forth in this Office action will be held to be non-responsive.
Claim Objections
Claims 6 & 10-12 are objected to because of the following informalities:
Claim 6 (line 1): --a-- should be inserted before “soybean”.
Claim 10 (line 2): The acronyms “TALEN” and “ZFN” should be written out in full in their first use in the claims.
Claim 11 (line 2): --the-- should be inserted before “nucleotide”.
Claim 12 (line 1): “an” should be replaced with --a--.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Scope of Enablement
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 6-12 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 a method of enhancing the resistance of a soybean to Phytophthora by generating a loss of function mutant, does not reasonably provide enablement for modulating the resistance of a soybean to any Phytophthora by any decrease in expression level including by any deletion, substitution, insertion, inversion, or translocation of at least a portion of the sequence of the gene Glyma13G252100. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant claims require modifying soybean gene Glyma.13G252100, wherein the sequence of soybean gene Glyma.13G252100 is set forth in SEQ ID NO: 1. Claim 7 further requires that the modifying is achieved by deletion, substitution, insertion, inversion, or translocation of at least a portion of the nucleotide sequence or a chemical modification of a portion of the nucleotide sequence. Claims 8-12 require that modifying refers to a decrease in an expression level and an enhancing of resistance of the soybean to Phytophthora.
The instant specification teaches an example of targeting Glyma.13G252100 with gRNA to generate mutants with large fragment deletions, one example is provided with a 189 bp deletion (paragraphs [0079-0088]). The instant specification teaches that this mutant has significantly enhanced resistance to Phytophthora root rot compared to a wild-type soybean (table 2). No other examples of modifications such as substitution, insertion, inversion, translocation, or chemical modification are provided.
Soybean genes comprising 100% sequence identity to instant SEQ ID NO: 1 are known in the art. NCBI Reference Sequence NC_041012.1 (bases 43478172 to 43479090) (available 3/12/2019) teaches a sequence with 100% sequence identity to instant SEQ ID NO: 1 annotated as Gene ID LOC114373320 and encoding a protein annotated to be a “probably inactive leucine-rich repeat receptor-like protein kinase At5g48380”. See alignment below.
Score
Expect
Identities
Gaps
Strand
1631 bits(883)
0.0
883/883(100%)
0/883(0%)
Plus/Plus
Query 1 ATGGTCTACTATGCCCCTTGGACAGAATTCAAAAAGAGGAGGAGTAACGCTATTCATCCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 37 ATGGTCTACTATGCCCCTTGGACAGAATTCAAAAAGAGGAGGAGTAACGCTATTCATCCC 96
Query 61 TTAATGAAGAAGCAGAACCATCAAAAGAACACTAGACAAGAAGCTGAATTGCTACCACTA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 97 TTAATGAAGAAGCAGAACCATCAAAAGAACACTAGACAAGAAGCTGAATTGCTACCACTA 156
Query 121 GCCATGCAAGAGCAAGGAAGCAAAGAGGTActctctctctctctctctctctctctctct 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 157 GCCATGCAAGAGCAAGGAAGCAAAGAGGTACTCTCTCTCTCTCTCTCTCTCTCTCTCTCT 216
Query 181 GTTTCTCTATTGATCAGTTGTGAGCACATGATATTTGAGATCAAACACTGATGTCATTAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 217 GTTTCTCTATTGATCAGTTGTGAGCACATGATATTTGAGATCAAACACTGATGTCATTAC 276
Query 241 TTTAAGGTCACGTCACGTATTTATTTTCAAATTTTTATGTCCATGATATATCAAGATTGT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 277 TTTAAGGTCACGTCACGTATTTATTTTCAAATTTTTATGTCCATGATATATCAAGATTGT 336
Query 301 GACATATATTTCATCTAAGCTATCAAGATTGTTGGAGAGATTGATTCCTAGAATGAGCTT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 337 GACATATATTTCATCTAAGCTATCAAGATTGTTGGAGAGATTGATTCCTAGAATGAGCTT 396
Query 361 CAAGGAATTATGCAAGGCAACCGATTACTTTAGCACAGATAACGTTTTAGGGATAGGAAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 397 CAAGGAATTATGCAAGGCAACCGATTACTTTAGCACAGATAACGTTTTAGGGATAGGAAC 456
Query 421 GACAGGGATTATGTACAAGGCAAAGGTACCAAATAACTGTTTTCTAGCAGTTAAGAGACT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 457 GACAGGGATTATGTACAAGGCAAAGGTACCAAATAACTGTTTTCTAGCAGTTAAGAGACT 516
Query 481 ATATGGCGCTGATGAATACAAGAGGGAATTCTTGCTTGAAACAATGATTCTGGGGAGACA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 517 ATATGGCGCTGATGAATACAAGAGGGAATTCTTGCTTGAAACAATGATTCTGGGGAGACA 576
Query 541 CAGGCACAGAAACATAGCTCCATTGGTAGGATTCTGCATAGAAAAAAGAGAAAGGATTTT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 577 CAGGCACAGAAACATAGCTCCATTGGTAGGATTCTGCATAGAAAAAAGAGAAAGGATTTT 636
Query 601 GGTGTATAAGTACATGTCTAATGGAAGACTCAGTGATTGGTTCCATTCTGATGAAGGAGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 637 GGTGTATAAGTACATGTCTAATGGAAGACTCAGTGATTGGTTCCATTCTGATGAAGGAGA 696
Query 661 TCAAAAAATAAAACTAGAATGGCCAGAGAGAATTCACATTGCACTTGGGATTGCAAGAGG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 697 TCAAAAAATAAAACTAGAATGGCCAGAGAGAATTCACATTGCACTTGGGATTGCAAGAGG 756
Query 721 TTTATCTTGGCTCCACAAAAGGTGCAAGATATTCCATCTTAATTTAGATTCAGAGTGTGT 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 757 TTTATCTTGGCTCCACAAAAGGTGCAAGATATTCCATCTTAATTTAGATTCAGAGTGTGT 816
Query 781 CTTGCTAGACAGGTATTTTGAGCCAAAAATATCCAATTTTGAGAAGGCAAAATTTCTAAA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 817 CTTGCTAGACAGGTATTTTGAGCCAAAAATATCCAATTTTGAGAAGGCAAAATTTCTAAA 876
Query 841 CCATACAGTTGAAGATCATGTGAGGATGAATGTTATGAATTAG 883
|||||||||||||||||||||||||||||||||||||||||||
Sbjct 877 CCATACAGTTGAAGATCATGTGAGGATGAATGTTATGAATTAG 919
Soybean genes encoding BAK1-interacting receptor-like kinases (BIR), which are homologs of the Arabidopsis BIR1 of At5g48380, are known in the art. Hawk et al (2023) New Phytologist. 239: 2335–2352. (published 6/20/2023, hereafter Hawk) teaches a Glycine max BAK1-INTERACTING RECEPTOR LIKE KINASE1 (BIR1), Glyma16G079200 (page 2336, right column, paragraph 1). Hawk teaches that BIR1 is a LRR-RLK that negatively regulates immune responses and cell death and that BIR1 interacts with BAK1 and might inhibit the function of BAK1 in the absence of infection (page 2336, left column, paragraph 2). However, Hawk teaches that the underlying mechanism of BIR1 in plant immunity is poorly understood (page 2336, left column, paragraph 3).
Hawk teaches that receptor-like kinases (RLKs) contain an intracellular kinase domain, a membrane-spanning region, and a ligand-binding extracellular domain, and most members involved in immunity and disease resistance are in the leucine-rich repeat subclass (page 2336, left column, paragraph 1). Hawk teaches that coreceptors and regulatory proteins are most likely crucial for signaling initiation by RLKs (page 2336, left column, paragraph 1).
Hawk teaches that GmBIR1 is one such critical RLK that impacts phosphorylation of several proteins with potential roles in the interaction between soybean and soybean cyst nematode and regulation of alternative mRNA splicing (page 2348, left column, paragraph 2). Hawk teaches that a kinase-inactive variant of GmBIR1 enhanced resistance to soybean cyst nematode (page 2338, right column, paragraph 4-page 2339, left column, paragraph 1; figure 2), and that the response could be due to phytohormone biosynthesis impacting syncytium formation (page 2340, left column, paragraph 3-right column, paragraph 1). Hawk also teaches that GmBIR1 induces phosphorylation changes that are soybean cyst nematode dependent (page 2347, left column, paragraph 2).
Liu et al (2022) International Journal of Molecular Sciences. 23. 7450. (published 7/5/2022, hereafter Liu) teaches another GmBIR1 as a negative regulator of defense responses in soybean (abstract; page 2, paragraph 5). Liu teaches that silencing of Glyma.18g246400 induces expression of the PR1 gene and teaches another gene, Glyma.09g246600, which shares 95% identity with Glyma.18g246400; these genes were labeled GmBIR1a and GmBIR1b (page 3, paragraph 1). GmBIR1-silenced plants have enhanced disease resistance against Soybean Mosaic Virus and Pseudomonas syringae pv. glycinea (page 4, paragraph 3-page 5, paragraph 2). The autoimmune phenotype of the silenced plants is a result of co-silencing both GmBIR1a and GmBIR1b (page 7, paragraph 2). Liu teaches based on these findings that the function of BIR1 homologs is conserved across plant species (page 2, paragraph 5; page 7 paragraph 1). BIR1 is an active kinase and kinase activity is at least partially required for function (page 2, paragraph 4), but BIR1 may not function in the perception of pathogen-associated molecular patterns (page 7, paragraph 1).
Although the role of BIR1 in susceptibility to a broad range of pathogens is taught in the art, and the kinase domain is known to be important in BIR1 function, the instant claims encompass more than just methods of silencing or loss of function mutations.
In genomes of the soybean G. soja, inversions and translocations are known to be present, but semisterility is a characteristic of plants heterozygous for these chromosomal aberrations (Wang et al (2021) New Phytologist. 232: 1765-1777; published 8/7/2021; page 1770, left column, paragraph 2). In transgenic plants, some differences in gene expression attributable to genomic location have been described and are likely caused by interaction with nearby genes (Betts et al (2019) Frontiers in Plant Science. 10. 1209. published 10/24/2019, hereafter Betts; page 2, left column, paragraph 2). For transgenes, chromosomal location is thought to have a significant influence on expression in plants; approximately 30% of insertion sites experienced silencing or impaired transgene expression (page 2, right column, paragraph 2). Betts teaches that the effect of genomic location on expression is real, if minor (page 11, right column, paragraph 2).
Given the unpredictability of expression after inversion and translocation in plant genomes, the effect of a translocation or inversion of the full Glyma.13G252100 gene, which is encompassed by the claims, would not have been predictable to one of ordinary skill in the art. One of ordinary skill in the art would have been required to conduct undue experimentation to determine which inversions or translocations, if any, lead to a decrease in expression and enhanced resistance to Phytophthora.
Hence, while the instant specification enables one of skill in the art to perform a method of enhancing the resistance of a soybean to Phytophthora by generating a loss of function mutant in the gene Glyma13G252100 with the sequence of instant SEQ ID NO: 1 or by a gene editing system or RNA interference, does not reasonably provide enablement for modulating the resistance of a soybean to any Phytophthora by any decrease in expression level including by any deletion, substitution, insertion, inversion, or translocation of at least a portion of the sequence of the gene Glyma13G252100 over the full scope of the claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Victoria L DeLeo whose telephone number is (703)756-5998. The examiner can normally be reached M-F 8:00am-4pm EDT.
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/VICTORIA L DELEO/Examiner, Art Unit 1662
/Anne Kubelik/Primary Examiner, Art Unit 1663
