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 .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 08, 2026 has been entered.
Claim Status
2. Claims 1, 5-6, 8-12, 14-15, and 21-27 are pending and under examination on the merits.
Claims 2-4, 7, 13, and 16-20 are cancelled.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on July 08, 2026 and July 14, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS are being considered by the examiner.
Response to Arguments – Claim Objections
4. Applicant’s amendments filed July 08, 2026 have overcome the objections of record. However, said amendments have introduced new grounds for objection.
Claim Objections
5. Claims 1, 5-6, 8-12, 14-15, and 21-27 are objected to because of the following:
The amendments to claim 1 were not properly entered as required by 37 CFR 1.121. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. For example, the recitation “thereby reducing or eliminating the expression of, amount of, and/or activity of the two or more modified KTI genes and/or gene products as compared to a wild-type or conventionally cultivated soybean plant and/or soybean therefrom” from lns. 2-3 of claim 1 as filed on 03/03/2026 should be shown by strike-through in the presently amended claim 1 from which it has been deleted (e.g., “
In claims 1, 5-6, 8-10, 21-24, and 27, “KTI” “KTI1” and “KTI3” should be italicized in all such cases where said term refers to a gene name. It is standard in the biological arts to italicize the names of genes to distinguish them from their protein products.
Dependent claims are included.
Appropriate correction is required.
Response to Arguments – Claim Rejections - 35 USC § 112(a)
6. Applicant’s arguments and amendments filed July 08, 2026 have necessitated new grounds of rejection.
Claim Rejections - 35 USC § 112(a)
7. 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.
8. Claims 1, 5-6, 8-12, 14-15 and 21-27 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 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.
Issue #1: Applicant has not disclosed a representative number of KTI1 and KTI3 gene sequences and/or structures, features, or sequences required therein to convey possession of the claimed invention commensurate with the scope of encompassed KTI genes.
Issue #2: Applicant has not disclosed a representative number of soybean plants modified to overexpress KTI1 and/or KTI3 gene sequences and/or increase activity of KTI1 and/or KTI3 polypeptides to convey possession of the claimed invention commensurate with the scope of encompassed modifications.
The claims all require a soybean plant comprising a modified KTI1 gene and a modified KTI3 gene. The specification indicates that modifications resulting in a reduction of trypsin inhibitor activity are essential to the operation of the claimed invention[0227], [0245], [0257].
Claim 1 is drawn to soybean plants comprising modifications to a genus of Kunitz-type trypsin inhibitor genes denoted “KTI1” and “KTI3”. With respect to claim 1, no structure is provided for the unmodified KTI1 and KTI3 sequences from which the modified sequences were obtained. Though the engineered plant is limited to soybean, the modified KTI genes and the KTI gene sequences which were modified to yield said modified KTI gene sequences are not limited to soybean genes. Therefore, claim 1 is broad and encompasses any and all KTI1 and KTI3 genes. The claims also encompass any and all modifications to said sequences wherein the modification results in a qualitative or quantitative change[0065]; this encompasses modifications that result in increased KTI gene and/or protein activity. The limitations encompassing any and all KTI1 and KTI3 genes and any and all modifications to said genes lack adequate written description for the following reasons.
Claim 1 places no limitations on the original structure/sequence of the modified KTI genes prior to modification and does not recite any function or effect resulting from the modified KTI1 and KTI3 genes; therefore, claim 1 encompasses all KTI1 and KTI3 genes encoding Kunitz-type trypsin inhibitors from any organism. KTI genes are well-known and the state of the art teaches the presence of thousands of KTI genes identified across various animal and plant species (p. 935, “3.1 Kunitz inhibitors in various protein databases”; Bendre et al., Int J Biol Macromol. 2018;113:933-943 (U)).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). When there is substantial variation within a genus, as here in which the genus comprises 1000s of distinct KTI1 and/or KTI3 genes from various species, one must describe a sufficient variety of species to reflect the variation within the genus.
However, Applicant describes modifications to only two sequences obtained from a single plant species. Applicant describes the transformation[0227] and cloning of modified KTI1 and KTI3 genes from transgenic soybean[0231] and the development of gene-edited soybean plants comprising loss-of-function mutations in both KTI1 and KTI3[0245-0256]. Applicant discloses only one modified KTI1 gene sequence of SEQ ID NO:5[0251] encoding a modified KTI1 polypeptide comprising a deletion of 22 amino acids which abolishes the trypsin inhibitor activity of the polypeptide[0258]. Regarding the modified KTI3 gene sequence, Applicant discloses only five modified KTI3 gene sequences of SEQ ID NOs:6-9 and SEQ ID NO:49[0252-0256] encoding modified KTI3 polypeptides comprising various deletions and/or truncations. Both the KTI1 and KTI3 gene sequences disclosed by Applicant were obtained from soybean. The specification indicates that the desired phenotype of reduced trypsin inhibitor activity resulted from a loss of trypsin inhibitor function in the gene products of SEQ ID NOs:5-9 and/or 49[0006],[0009],[0227],[0237],[0245],[0257-0258]. Applicant’s examples do not describe modifications resulting in the increased expression, amount, or activity of any of SEQ ID NOs:5-9 or 49, any wild-type KTI gene sequences, or any of the polypeptides encoded therein. The art also teaches that KTI genes are not predictably functional when expressed heterologously as demonstrated in the failure of the soybean KTI3 gene to enhance pest resistance when expressed in transgenic poplars, tobacco, and sugarcane (p. 482, first paragraph; Li et al., Mol. Plant. 2008; 1(3):482-495 (V)). Accordingly, one of ordinary skill in the art cannot reasonably predict the effects or results of expressing an undisclosed but modified KTI1 and/or KTI3 gene in soybean without knowing both the desired goal of said expression and the structures/sequences required in the modified KTI1 and KTI3 sequences to yield said goal. Neither the claims nor specification describe any structures/sequences required to yield any required phenotypes in the claimed soybean beyond a deletion in the modified KTI1 gene sequence which results in a truncated polypeptide. Accordingly, two modified KTI genes resulting in reduced trypsin inhibitor activity are not representative of the entire genus of 1000s of distinct KTI1 and/or KTI3 genes and modifications as encompassed. Applicant has not disclosed sufficient relevant identifying characteristics to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, had possession of the claimed invention at the time the application was filed. Thus, claim 1 lacks adequate written description.
Though claim 5 limits the scope of the modified KTI1 gene to SEQ ID NO:5, which encodes a loss-of-function allele of KTI1, the claim encompasses any and all KTI3 gene sequences, of which Applicant has not provided sufficient relevant identifying characteristics to convey possession commensurate in scope with the claim. The claim also fails to limit the scope of the modifications to the KTI3 gene sequence to those that reduce gene/protein activity, amount, or expression. Accordingly, claim 5 also lacks adequate written description.
Though claim 6 limits the scope of the modified KTI3 gene to SEQ ID NO:6-9 and 49, which encode loss-of-function alleles of KTI3, the claim encompasses any and all KTI1 gene sequences, of which Applicant has not provided sufficient relevant identifying characteristics to convey possession commensurate in scope with the claim. The claim also fails to limit the scope of the modifications to the KTI1 gene sequence to those that reduce gene/protein activity, amount, or expression. Accordingly, claim 6 also lacks adequate written description.
Similar to claim 1, claims 22-26 encompass any and all KTI1 gene sequences, of which Applicant has not provided sufficient relevant identifying characteristics to convey possession commensurate in scope with the claim. The claims also fail to limit the scope of the modifications to the KTI1 gene sequence to those that reduce gene/protein activity, amount, or expression. Accordingly, claims 22-26 also lack adequate written description.
Though claims 8-12, 14-15, and 27 appear to limit the scope of the encompassed modifications to those resulting in reduced gene and/or polypeptide expression, activity, and/or amount, the claims do not limit the scope of the KTI1 and KTI3 genes encompassed. Accordingly, claims 8-12, 14-15, and 27 also lack adequate written description.
Response to Arguments – Claim Rejections under 35 USC § 102 and 35 USC § 103
9. Applicant’s amendments filed July 08, 2026 have been carefully considered, but they are not persuasive and do not overcome the rejections of record. However, said amendments have necessitated new grounds of rejection under 35 U.S.C. 102.
In traversing the rejection, Applicant argues that: A) claim 1 is not disclosed, taught, or suggested by the cited references; B) Gillman et al. (Journal of Agricultural and Food Chemistry. 2015; 63(5):1352-1359 (previously cited)) does not teach the claimed in-frame translated truncation; C) “Obvious to try” is insufficient to support a conclusion of obviousness absent a finite number of predictable solutions; D) neither cited NCBI reference supplies the missing features and guidance of Gillman; E) reliance on Applicant’s own disclosure is impermissible hindsight reasoning; G) MPEP 2183 does not govern; H) the dependent claims are allegedly separately allowable; and I) claims 21-26 are allegedly nonobvious over the cited art.
With regard to A) and B), Applicant argues primarily that the rejection rests on an unreasonably broad interpretation of the claims (p. 07), that claim 1 has been amended to specify that the modified KTI1 gene comprises an in-frame deletion of at least 60 base pairs within a region encoding a C-terminal portion of a KTI1 polypeptide such that the modified KTI1 gene encodes a truncated KTI1 polypeptide that retains an N-terminal portion of the KTI1 polypeptide (p. 08), and that Gillman fails to teach an in-frame truncation as claimed (pp. 08-09). This is not persuasive for several reasons. First, the amended claim 1 is not limited to any specific KTI1 or KTI3 gene or polypeptide sequences. Second, the claims are not limited to a deletion within the C-terminus because the recitation of “at least 60bp” encompasses deletions of the entire C-terminus. Applicant argues that “the claimed structure” is distinct from the sequence taught by Gillman because the instant modified KTI1 polypeptide retains the N-terminal portion of the protein (pp. 08-09). However, the recited KTI genes, as currently amended, are not limited to any specific sequences and do not recite any specific functions; the recited genes encompass a genus of sequences which may be obtained from any origin, wherein the only limitation on the modified sequences is that the modified KTI1 gene sequence encodes a truncated protein wherein at least 60 bases have been deleted from the C-terminus. Therefore, Gillman’s modified KTI1 gene sequence, which encodes a truncated sequence wherein at least 60 bases have been deleted from the C-terminus (Figure 2) anticipates the instant modified KTI1. Third, alleged Gillman’s failure to detect a truncated KTI1 polypeptide does not mean the truncated polypeptide was not encoded by the modified sequence taught by Gillman, only that Gillman allegedly failed to detect said polypeptide. Additionally, Gillman does not report that the KTI1 protein was abolished, only that the protein levels were reduced (p. 1354, “Identification of a Germplasm Line with Reduced Kunitz Trypsin Inhibitor Content.”; p. 1354, Figure 1). Furthermore, Park et al. (Agriculture. 2023; 13:2070 (W)) report that the KTI1 and KTI3 alleles disclosed by Gillman are null/loss-of-function mutations that result in truncated KTI1 and KTI3 polypeptides (p. 02, third full paragraph; p. 11, second full paragraph). Therefore, despite Applicant’s assertion that Gillman’s modified KTI1 gene does not produce a truncated polypeptide, the state of the art indicates that Gillman’s modified KTI1 gene produces a truncated polypeptide. Finally, the claims do not require that the encoded truncated polypeptide be expressed, produced, or detected, only that the polypeptide be encoded in the modified KTI1 sequence. Even if an encoded polypeptide fails to express or fails to accumulate to detectable levels, the polypeptide is still encoded in the sequence encoding said polypeptide. Therefore, Gillman, which teaches a soybean plant comprising modified KTI1 and KTI3 genes wherein the modified KTI1 gene encodes a truncated polypeptide which retains a portion of the N-terminus anticipates the amended claim 1.
Applicant argument that the Examiner’s interpretation of the claims in view of the cited art is unreasonable and/or unsound is not persuasive (pp. 07-08). The loss-of-function mutation taught by Gillman performs the identical function specified in the claim (i.e., production of an engineered soybean plant) in substantially the same way (i.e., modification of KTI1 wherein at least 60bp have been deleted from the C-terminus) and produces substantially the same results (i.e., reduction in trypsin inhibitor activity) as the corresponding element disclosed in the specification. Loss-of-function mutations result in a loss-of-function regardless of the specific sequence of the mutation reducing function and are functionally equivalent absent some evidence to the contrary. More importantly, the amended claim 1 is anticipated by the teachings of Gillman rendering the present argument moot.
With regard to C), the Office does not make the argument that any specific KTI1 and/or KTI3 gene sequence is “obvious to try” but that Gillman teaches that plants comprising loss-of-function mutations in KTI1 and KTI3 display reduced trypsin inhibitor activity and that loss-of-function mutations are functionally equivalent absent some reasonable evidence or assertion to the contrary. The mutagenesis of crop plants and the selection of plants comprising mutations in target genes is routine in the biological arts. The selection of plants comprising loss-of-function mutations in target genes is routine in the biological arts. Gillman teaches and provides motivation to reduce the expression and/or activity of KTI1 and/or KTI3. Regardless of the structure/sequence of a loss-of-function allele of a gene, the end result, absent some assertion or evidence of surprising results, is the same: a loss of protein activity. Applicant argues that paragraph [0259] of the instant specification confirms that a truncated KTI1 may still possess trypsin inhibitor activity (p. 12). The Examiner respectfully disagrees with this interpretation of paragraph [0259] of the instant specification. The specification discloses that Applicant’s only working examples comprise loss-of-function alleles and gene knockouts[0227], [0245], and [0258-0259]. Though paragraph [0259] suggests that a truncated protein may retain some activity, the same paragraph along with Figures 8A and 8B of the Drawings filed 04/10/2023 disclose that the sole modified KTI1 gene sequence described by Applicant encodes a truncated protein that fails to inhibit trypsin activity and lacks trypsin inhibitor function. Accordingly, there is no evidence that the modified KTI1 polypeptide described in instant paragraph [0259] retains any of the function of the unmodified KTI1 sequence. Applicant also argues that Gillman performs no structure-function analysis of the KTI1 polypeptide, identifies no functional domains, and ascribes no role to the C-terminal portion of the polypeptide and, ultimately, does not render it obvious to try a specific structural solution (p. 09). This not persuasive because the recited KTI genes, as amended, are not limited to any specific sequences and do not recite any specific functions. The claims are not directed to a “specific structural solution” but to a genus of sequences which may be obtained from any origin, wherein the only limitation on the modified sequences is that the KTI1 gene sequence be modified such that the modified KTI1 gene sequence comprises an in-frame deletion of at least 60 bases from the C-terminus and encodes a truncated protein. Because the claims are not limited to any specific structure and do not describe any function associated with any specific structure, Applicant appears to be arguing limitations that are not present in the claims. The modified KTI1 gene, as currently amended, is anticipated by the KTI1 gene disclosed by Gillman.
With regard to D), the Examiner concedes that NM_001250776.3 is the wild-type KTI1 sequence corresponding to Applicant’s SEQ ID NO:1 and that NM_001251682.2 is the wild-type KTI3 sequence corresponding to Applicant’s SEQ ID NO:3. However, Applicant’s arguments that the cited prior art sequences do not supply the missing features and guidance of Gillman is not persuasive because the teachings of Gillman anticipate loss-of-function mutations in KTI1 and KTI3 and the cited prior art sequences teach wild-type KTI1 and KTI3. The mutagenesis of crop plants and the selection of plants comprising mutations in target genes is routine in the biological arts. The selection of plants comprising loss-of-function mutations in target genes is routine in the biological arts. One of ordinary skill in the art would have been motivated by Gillman and reasonably capable of doing of introducing loss-of-function mutations into SEQ ID NO:1 and SEQ ID NO:3 to produce soybean plants with increased digestibility. Furthermore, amended claim 1 does not recite specific KTI1 or KTI3 gene sequences and is anticipated by Gillman alone.
With regard to E), the Examiner’s analysis does not rely on hindsight but on the broadest reasonable interpretation of the claims in view of the prior art. Applicant’s argument regarding the production of a “truncated, N-terminus-retaining KTI1 polypeptide” (p. 13) is not persuasive because the claimed invention does not require such a polypeptide be produced. The claims only require that such a polypeptide be encoded in the modified KTI1 sequence, not that said polypeptide be expressed or produced. Therefore, Applicant is arguing limitations that are not present in the claims.
With regard to G), Applicant’s argument is not persuasive. Though claims 1, 5-6, 8-12, 14-15 do not recite any function and therefore lack any mean-plus-function limitation, the amended claim 1 is anticipated by the teachings of Gillman. Furthermore, the function or activity or a gene or polypeptide is inherent to its sequence. Therefore, in reciting a soybean plant comprising a sequence, the claims inherently recite a soybean plant comprising the function of that sequence. Additionally, claims 21-27 do recite a means-plus-function limitation in the recitations wherein the recited modified genes reduced the expression, activity, and/or amount of the modified genes.
With regarding to H) and I), these arguments are not persuasive because the amended claim 1 is anticipated by the teachings of Gillman. Furthermore, the Examiner respectfully disagrees with Applicant’s interpretation that paragraph [0259] of the instant specification suggests that the described modified KTI1 gene sequence may retain some function. As stated above, the specification discloses that Applicant’s only working examples comprise loss-of-function alleles and gene knockouts[0227], [0245], [0258-0259] and disclose that the sole modified KTI1 gene sequence described by Applicant encodes a truncated protein that fails to inhibit trypsin activity and lacks trypsin inhibitor function (Figures 8A and 8B). Accordingly, there is no evidence that the modified KTI1 polypeptide described in instant paragraph [0259] retains any of the activity of the unmodified KTI1 sequence. Though Gillman may be silent to SEQ ID NOs:5-9 and 49, Gillman teaches that plants comprising loss-of-function mutations in KTI1 and KTI3 display reduced trypsin inhibitor activity. Regardless of the structure/sequence of a loss-of-function allele of a gene, the end result, absent some assertion or evidence of surprising results, is the same: a loss of protein activity. Therefore, loss-of-function mutations are prima facie equivalent absent some reasonable evidence or assertion to the contrary.
Accordingly, the rejection of claims 5-6 and 21-26 under 35 U.S.C. 103 as being unpatentable over Gillman et al. (Journal of Agricultural and Food Chemistry. 2015; 63(5):1352-1359 (previously cited)), in view of NCBI Reference Sequence: NM_001250776.3 (NCBI. 2017 (previously cited)), and further in view of NCBI Reference Sequence: NM_001251682.2 (NCBI. 12 Mar 2022 (previously cited)) is maintained. However, the amendments to claim 1 have necessitated new grounds of rejection of claims 1, 8-12, 14-15, and 27.
Claim Rejections - 35 USC § 102
10. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
11. Claims 1, 8-12, 14-15 and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gillman et al. (Journal of Agricultural and Food Chemistry. 2015; 63(5):1352-1359 (previously cited)) as evidenced by Park et al. (Agriculture. 2023; 13:2070 (W)).
Regarding claim 1, Gillman teaches an engineered soybean plant comprising two modified KTI genes, wherein the two or more mutant KTI genes comprises a modified KTI1 gene and a modified KTI3 gene, and wherein the modified KTI1 gene comprises an in-frame deletion of at least 60 base pairs with a region encoding the C-terminal portion of a KTI1 polypeptide such that the modified KTI1 gene encodes a truncated KTI1 polypeptide that retains an N-terminal portion of the KTI1 polypeptide (Abstract; p. 1353, left column, first full paragraph; p. 1353, left column, “Population Development”; p. 1354, left column, “Determination of Molecular Genetic Basis for Reduced KTi Levels in PI 68679.”; p. 1354, Figure 1 and Figure 2). Claim 1 is not limited to any specific KTI1 or KTI3 gene or polypeptide sequences and the recitation of “at least 60bp” encompasses deletions of the entire C-terminus. Furthermore, the state of the art teaches that Gillman’s modified KTI1 allele encodes a truncated polypeptide (p. 11, second full paragraph; Park et al., Agriculture. 2023; 13:2070 (W)). Therefore, Gillman’s modified KTI1 gene sequence, which encodes a truncated sequence wherein at least 60 bases have been deleted from the C-terminus (Figure 2) anticipates the instant modified KTI1.
Regarding claim 8, in addition to the teachings discussed above, Gillman teaches crossing KTI1- soybean lines with KTI3- soybean lines (p. 1353, left column, “Population Development”). Because the F1 offspring of the above crossings will comprise a copy of each KTI allele inherited from either parent, Gillman teaches an engineered soybean/soybean plant wherein the soybean/soybean plant is heterozygous for two or more mutant KTI genes.
Regarding claim 9, in addition to the teachings discussed above, Gillman teaches an engineered soybean/soybean plant wherein the soybean/soybean plant is homozygous for two or more mutant KTI genes (p. 1354, right column, “Proteomic Investigations of Mutant Lines Bearing KTi- Mutations.”).
Regarding claim 10, in addition to the teachings discussed above, Gillman teaches a soybean/soybean plant wherein the plant lacks any KTI protein (p. 1354, right column, “Proteomic Investigations of Mutant Lines Bearing KTi- Mutations.”; p. 1355, Figure 4). Therefore, Gillman teaches a soybean/soybean plant wherein the expression of, amount of, and/or activity of the one or more modified KTI genes and/or gene products is reduced 0.1-1000-fold or more.
Regarding claim 11, in addition to the teachings discussed above, Gillman teaches a soybean/soybean plant wherein the plant has reduced trypsin inhibitor amount and/or activity as compared to a control (Abstract; p. 1354, right column, “Proteomic Investigations of Mutant Lines Bearing KTi- Mutations.; p. 1355, Figure 4).
Regarding claim 12, in addition to the teachings discussed above, Gillman teaches a method of growing, harvesting, or otherwise cultivating an engineered soybean/soybean plant (p. 133, left column, “Population Development”).
Regarding claim 14, in addition to the teachings discussed above, Gillman suggests a feed/food product comprising a soybean/soybean plant comprising reduced trypsin inhibitor activity (Abstract; p. 1352, left column, first and second full paragraphs; p. 1358, left column, first full paragraph).
Regarding claim 15, in addition to the teachings discussed above, Gillman suggests feeding a feed/food product comprising a soybean/soybean plant comprising reduced trypsin inhibitor activity to a human or non-human animal (Abstract; p. 1352, left column, first and second full paragraphs; p. 1358, left column, first full paragraph).
Accordingly, the claimed invention is anticipated by the prior art.
Claim Rejections - 35 USC § 103
14. 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
15. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Gillman et al. (Journal of Agricultural and Food Chemistry. 2015; 63(5):1352-1359 (previously cited)), as evidenced by Park et al. (Agriculture. 2023; 13:2070 (W)), as applied above to claims 1, 8-12, 14-15, and 27, in view of NCBI Reference Sequence: NM_001250776.3 (NCBI. 2017 (previously cited)), and further in view of NCBI Reference Sequence: NM_001251682.2 (NCBI. 12 Mar 2022 (previously cited)).
The teachings of Gillman are as discussed above in the rejection of the claims under 35 U.S.C. 102(a)(1).
Regarding claim 5, in addition to the teachings discussed above, Gillman teaches the role of trypsin inhibitors in limiting the digestibility of raw soybeans (Abstract); that heating the soybean inactivates the inhibitors, is costly, and reduces the nutritional value of the soybeans (Abstract); and an engineered soybean plant comprising a mutant KTI1 gene and a mutant KTI3 gene each comprising a frameshift mutation which truncates and lowers protein amount and/or activity of the genes and/or products encoded therein (Abstract; p. 1353, left column, first full paragraph; p. 1353, left column, “Population Development”; p. 1354, left column, “Determination of Molecular Genetic Basis for Reduced KTi Levels in PI 68679.”; p. 1354, Figure 1 and Figure 2).
Gillman does not teach SEQ ID NO:5.
However, NCBI Reference Sequence: NM_001250776.3 teaches a KTI1 gene comprising an upstream in-frame stop codon (p. 01, “misc_feature”).
The combination of Gillman and NCBI Reference Sequence: NM_001250776.3 renders obvious an engineered soybean plant, soybean, or both comprising two or more modified KTI1 genes, wherein the two or more modified KTI genes comprises a modified KTI1 gene and a modified KTI3 gene, and wherein the modified KTI1 gene comprises an in-frame deletion of at least 60 base pairs within a region encoding a C-terminal portion of a KTI1 polypeptide such that the modified KTI1 gene encodes a truncated KTI1 polypeptide that retains an N-terminal portion of the KTI1 polypeptide.
The level of ordinary skill in the plant biotechnology arts is high as evidenced by Gillman. In view of the teachings of Gillman, NCBI Reference Sequence: NM_001250776.3, and NCBI Reference Sequence: NM_001251682.2 it would have been prima facie obvious for one of ordinary skill in the art to engineer a soybean plant comprising loss-of-function mutations in the KTI1 and KTI3 gene sequences. One of ordinary skill in the art would have been motivated to do so because Gillman teaches that soybean accession PI 68679 comprises a frameshift mutation in its KTI1 gene and demonstrates a reduction in trypsin inhibitor activity (p. 1354, left column, second full paragraph; p. 1354, Figure 1 and Figure 2; p. 1355, “Trypsin and Chymotrypsin Activities in Seed of Mutant Lines.”). Though Gillman does not teach SEQ ID NO:5, SEQ ID NO:5 provides no surprising or unexpected effect or result in comparison to the kti1 loss-of-function allele taught by Gillman. Applicant’s SEQ ID NO:5 comprises a kti1 loss-of-function allele resulting in a truncated KTI1 polypeptide that lacks trypsin inhibitor activity[0258]. Applicant has provided no evidence supporting any surprising or unexpected function, activity, or benefit of such a truncated polypeptide; furthermore, Applicant indicates the allele encoding the truncated polypeptide is simply a loss-of-function mutation[0245-0246]. The mutation in the KTI1 gene in Gillman resulted in a truncated transcript being expressed and a reduced trypsin inhibitor activity in the plant. It would, therefore, be obvious to those of ordinary skill in the prior art that abolishing KTI1 protein activity by causing deletions in the KTI1 gene coding region, including in the region encoding the C-terminal portion, would also result in expression of a truncated transcript and reduced trypsin inhibitor activity in the plant as well. Absent any evidence and assertion to the contrary, the claimed kti1 loss-of-function alleles are prima facie equivalent to the kti1 loss-of-function allele taught by Gillman. Furthermore, methods for introducing mutations into a targeted gene are both routine and well-known in the art as discussed by Applicant[0153]. Accordingly, a kti1 loss-of-function allele comprising SEQ ID NO:5 would provide no surprising or unexpected results when compared to the teachings of Gillman in view of NCBI Reference Sequence: NM_001250776.3. Given the global economic importance of soybeans, one of ordinary skill in the art would be motivated to develop soybean with increased raw digestibility to reduce the production costs and increase the nutritional value of food and feed products made from soybean.
Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention with a reasonable expectation of success and without any surprising results.
16. Claims 6 and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Gillman et al. (Journal of Agricultural and Food Chemistry. 2015; 63(5):1352-1359 (previously cited)), as evidenced by Park et al. (Agriculture. 2023; 13:2070 (W)), as applied above to claims 1, 8-12, 14-15, and 27, in view of NCBI Reference Sequence: NM_001250776.3 (NCBI. 2017 (previously cited)), and further in view of NCBI Reference Sequence: NM_001251682.2 (NCBI. 12 Mar 2022 (previously cited)).
The teachings of Gillman are as discussed above in the rejection of the claims under 35 U.S.C. 102(a)(1).
Regarding claims 6 and 21, in addition to the teachings discussed above, Gillman teaches the role of trypsin inhibitors in limiting the digestibility of raw soybeans (Abstract); that heating the soybean inactivates the inhibitors, is costly, and reduces the nutritional value of the soybeans (Abstract); and engineered soybean plants comprising a modified KTI1 gene, a modified KTI3 gene, or a modified KTI1 gene and a modified KTI3 gene wherein each of the KTI1 and KTI3 genes comprise a frameshift mutation which reduces or eliminates the expression of, amount of, and/or activity of the modified KTI1/KTI3 gene and/or gene product (Abstract; p. 1353, left column, first full paragraph; p. 1353, left column, “Population Development”; p. 1354, left column, “Determination of Molecular Genetic Basis for Reduced KTi Levels in PI 68679.”; p. 1354, Figure 1 and Figure 2).
Gillman does not teach SEQ ID NOs:6-9 or 49.
However, NCBI Reference Sequence: NM_001251682.2 teaches a soybean KTI3 sequence identical to Applicant’s SEQ ID NO:3, from which Applicant’s SEQ ID NOs:6-9 and 49 are obtained[0250].
The level of ordinary skill in the plant biotechnology arts is high as evidenced by Gillman. In view of the teachings of Gillman and NCBI Reference Sequence: NM_001251682.2 it would have been prima facie obvious for one of ordinary skill in the art to engineer a soybean plant comprising loss-of-function mutations in the KTI1 and KTI3 gene sequences. One of ordinary skill in the art would have been motivated to do so because Gillman teaches that soybean accession PI 157740 comprises a frameshift mutation in its KTI3 gene and demonstrates a 40% reduction in trypsin inhibitor activity and an increase in raw digestibility (p. 1353, left column, first full paragraph; p. 1354, left column, second full paragraph; p. 1354, Figure 1 and Figure 2; p. 1355, “Trypsin and Chymotrypsin Activities in Seed of Mutant Lines.”). The mutation in the KTI3 gene in Gillman resulted in reduced trypsin inhibitor activity in the plant. It would, therefore, be obvious to those of ordinary skill in the prior art that abolishing KTI3 protein activity by causing deletions in the KTI3 gene coding region, would also result in reduced trypsin inhibitor activity in the plant as well. The specification indicates Applicant’s sequences are simply loss-of-function mutations[0245-0247] and Applicant has provided no evidence supporting any surprising or unexpected function, activity, or benefit of such alleles. Though Gillman does not teach SEQ ID NOs:6-9 or 49, SEQ ID NOs:6-9 and 49 provide no surprising or unexpected effect or result in comparison to the kti3 loss-of-function allele taught by Gillman. Absent any evidence and assertion to the contrary, the claimed kt31 loss-of-function alleles are prima facie equivalent to the kti3 loss-of-function allele taught by Gillman. Furthermore, methods for introducing mutations into a targeted gene are both routine and well-known in the art as discussed by Applicant[0153]. Accordingly, a kti3 loss-of-function allele comprising SEQ ID NOs:6-9 or 49 would provide no surprising or unexpected results when compared to the teachings of Gillman in view of NCBI Reference Sequence: NM_001251682.2. Given the global economic importance of soybeans, one of ordinary skill in the art would be motivated to develop soybean with increased raw digestibility to reduce the production costs and increase the nutritional value of food and feed products made from soybean. Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention with a reasonable expectation of success and without any surprising results.
Regarding claim 22, in addition to the teachings discussed above, Gillman also teaches soybean plant comprising a mutant KTI1 gene and a mutant KTI3 gene (Abstract; p. 1353, left column, first full paragraph; p. 1353, left column, “Population Development”; p. 1354, left column, “Determination of Molecular Genetic Basis for Reduced KTi Levels in PI 68679.”; p. 1354, Figure 1 and Figure 2).
Regarding claim 23, as discussed above in the rejection of claim 8 under 35 U.S.C. 103, Gillman teaches an engineered soybean/soybean plant wherein the soybean/soybean plant is heterozygous for a mutant KTI3 gene (p. 1353, left column, “Population Development”).
Regarding claim 24, in addition to the teachings discussed above, Gillman teaches a soybean/soybean plant comprising a frameshift mutation in KTI3 that results in a 40% reduction in trypsin inhibitor activity and a soybean/soybean plant wherein the plant lacks any KTI protein (p. 1353, left column, first full paragraph; p. 1354, right column, “Proteomic Investigations of Mutant Lines Bearing KTi- Mutations.”; p. 1355, Figure 4). Therefore, Gillman teaches a soybean/soybean plant wherein the expression of, amount of, and/or activity of KTI3 and/or its gene products is reduced 0.1-1000-fold or more.
Regarding claim 25, in addition to the teachings discussed above, Gillman teaches a soybean/soybean plant wherein the plant has reduced trypsin inhibitor amount and/or activity as compared to a control (Abstract; p. 1354, right column, “Proteomic Investigations of Mutant Lines Bearing KTi- Mutations.; p. 1355, Figure 4).
Regarding claim 26, in addition to the teachings discussed above, Gillman suggests a feed/food product comprising a soybean/soybean plant comprising reduced trypsin inhibitor activity (Abstract; p. 1352, left column, first and second full paragraphs; p. 1358, left column, first full paragraph).
Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention with a reasonable expectation of success and without any surprising results.
Conclusion
17. No claim is allowed.
Examiner’s Contact Information
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEQUANTARIUS J SPEED whose telephone number is (703)756-4779. The examiner can normally be reached M-F; 9AM-5PM ET.
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/DEQUANTARIUS JAVON SPEED/Junior Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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