Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-12 remain pending.
Claims 2-4, 6-7 and 9-12 are newly amended.
Claims 1-12 remain rejected.
Response to Applicant Arguments – Specification
Applicant’s arguments and amendments to the specification dated 03/18/2026 overcomes the objection to the specification of record and it is withdrawn.
Response to Applicant Arguments - Claim Objections
Applicant’s arguments and amendments to the claims dated 03/18/2026 overcome the claim objections of record and they are withdrawn.
Response to Applicant Arguments - Indefiniteness
Applicant’s arguments and amendments to the claims dated 03/18/2026 have been fully considered. With respect to the indefiniteness rejections due to the recitation of “MON89788” applicant’s arguments are found to be persuasive and the rejections of record are withdrawn. With respect to the indefiniteness rejections due to the recitations of “transgenic locus” and “junction polynucleotide” applicant’s arguments have been fully considered but are not found to be persuasive.
Applicant’s arguments are drawn to the following:
The Examiner’s assertion that the specification allegedly provides two in consistent meanings of the term “transgenic locus” ignores the broader context of the specification including the explicit definition of “transgenic locus” in paragraph 0030 of the specification. Given this definition “transgenic locus” refers to the genomic insertion site of a transgene and the genomic DNA containing that insertion (Applicant Remarks Dated 03/18/2026, Pages 9-10).
The defining structural characteristics of the “junction polynucleotide” – the boundary between endogenous DNA and inserted transgenic DNA- remains clearly identifiable regardless of the precise fragment length analyzed and therefore, a person of ordinary skill in the art would readily understand the structure and boundaries of such sequences (Applicant Remarks Dated 03/18/2026, Pages 12-14).
These arguments related to one another and will be addressed together. While applicant provides definitions of both “transgenic locus” and “junction polynucleotide” which include features which describe these terms, applicant’s definitions do not make clear the scope imparted on the claim by these recitations.
Specifically, applicant’s definition of “transgenic locus” states that this term refers “to an insertion of one or more transgenes at a unique site in the genome of a plant as well as to DNA fragments, plant cells, plants, and plant parts (e.g. seeds) comprising genomic DNA containing the transgene insertion”. While applicant urges that this definition makes clear the meaning of this term, the scope imparted to the claim by the recitation of “transgenic locus” is not clear because the bounds of the “transgenic locus” are not clear.
Claim 1 is drawn to “a transgenic soybean plant cell comprising a modification of a MON89788 transgenic soybean locus”, while applicants urge that this locus comprises the transgene and surrounding genomic DNA the bounds of the genomic DNA included in the “transgenic locus” are not clear and therefore the scope of “transgenic locus” is not clear.
The term “junction polynucleotide” and Applicant’s definition of this term share the same issue. While, the specification in paragraph 0025 makes clear that the junction polynucleotide comprises both endogenous chromosomal DNA from the plant and heterologous transgenic DNA and includes the feature of the junction between these two sequences the bounds of this structure are not clear. As noted in the rejection of record given the definition provided in paragraph 0025 the length of the endogenous DNA and the length of the heterologous transgenic DNA appear to be arbitrary how does a person of ordinary skill in the art identify the end point of the junction polynucleotide in the endogenous DNA?
This is particularly important to the claimed invention which is drawn to transgenic soybean plants which comprise modifications of a MON89788 transgenic soybean locus where the modification is a DNA deletion in a junction polynucleotide and/or an insertion and/or substitution of DNA in the junction polynucleotide. Without knowing the bounds of the “transgenic locus” and “junction polynucleotide” when presented with a transgenic soybean plant cell comprising mutations in the endogenous DNA, given the definitions in the specification it is not clear at what point these modifications fall into the MON89788 transgenic locus and junction polynucleotide and therefore due to the recitations of “transgenic locus” and “junction polynucleotide” the scope of the claims are not clear.
Therefore, while applicant has provided definitions with structures for “transgenic locus” and “junction polynucleotide” because the metes and bounds conferred by the recitations of these terms in the claims are not clear Applicant’s arguments are not found to be persuasive and the rejections of record are maintained.
Claim Rejections - 35 USC § 112 (Indefiniteness)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 remain rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In claims 1 and 7 the recitations of “MON89788 transgenic soybean locus” and in claims 1-6 and 9-12 the recitations of “MON89788 transgenic locus” render the claims indefinite because the scope of the phrases introduce more than one scope of the claims.
These recitations are indefinite because the specific structure or genus of structures conferred unto the claim invention by these terms is unclear. Specifically, while the general concept of a transgenic locus is clear the specific bounds of this term are not clear. In particular, it is not clear how much of the endogenous DNA is considered part of the transgenic event. and further applicant appears to use this term in a loose fashion in the specification such that it appears that at times no endogenous DNA is included by the use of the term transgenic event.
Even applicant’s definition in paragraph 0030 of the specification does not clarify the scope of “transgenic locus”. This definition includes the concept that the transgenic locus includes transgenes at a unique site in the genome of a plant such that they comprise genomic DNA containing the transgene insertion, however, the boundaries on how much endogenous DNA is included in the transgenic locus are not clear and further, this definition appears to indicate that “transgenic locus” also refers to plants, plant parts and plant cells which comprise genomic DNA containing the transgene.
Therefore, given the analysis above, the scope of “transgenic locus” is not clear and claims 1-7 and 9-12 remain rejected as indefinite. Claim 8 remains rejected as depending on an indefinite claim and failing to limit the scope of the claim to definite subject matter.
In claims 1-6 and 12 the recitation of “junction polynucleotide” renders the claims indefinite because these phrases introduce more than one scope of the claims.
The scope imparted on the claims by the use of the term junction polynucleotide is unclear because the bounds of the specific structure represented by a junction polynucleotide is not clear. In paragraph 25, the specification defines “junction polynucleotide” as follows:
“As used herein, the phrases “DNA junction polynucleotide” and “junction polynucleotide” refers to a polynucleotide of about 18 to about 500 base pairs in length comprised of both endogenous chromosomal DNA of the plant genome and heterologous transgenic DNA which is inserted in the plant genome. A junction polynucleotide can thus comprise about 8, 10, 20, 50, 100, 200, 250, 500 or 1000 base pairs of endogenous chromosomal DNA of the plant and about 8, 10, 20, 50, 100, 200, 250, 500, or 1000 base pairs of heterologous transgenic DNA which pan the one end of the transgene insertion site in the plant chromosomal DNA. Transgene insertion sites in chromosomes will typically contain both a 5’ junction polynucleotide and a 3’ junction polynucleotide”
This definition in the specification raises at least the following two questions:
The junction polynucleotide must include heterologous transgenic DNA and endogenous chromosomal DNA but beyond this is the junction polynucleotide required to have any other specific structures? The definition quoted above, indicates that the junction polynucleotide comprises about 1000 nucleotides or less of endogenous DNA, so is any sequence which has both heterologous DNA and endogenous DNA and considered a junction polynucleotide.
Given that the length of the endogenous portion of the DNA junction polynucleotide appears to be arbitrary how does a person of ordinary skill in the art identify the end point of the junction polynucleotide in the endogenous DNA?
Given the definition provided by applicant, the specific metes and bounds of the structure and therefore scope imparted by the use of the term “junction polynucleotide” is not clear and as such claims 1-6 and 12 remain rejected as indefinite. Claims 7-11 remain rejected as depending on indefinite claims and failing to limit the scope to definite subject matter.
Response to Applicant Arguments – Written Description
Applicant’s arguments and amendments to the claims dated 03/18/2026 have been fully considered however they are not found to be persuasive and the rejections of record are maintained.
Applicant’s arguments are drawn to the following:
A person of ordinary skill in the art would be able to identify the boundaries of the MON89788 transgenic locus because the specification provides multiple structural identifiers including the reference sequence of SEQ ID NO: 1, the sequence present in the deposited seed under ATCC Accession No. PTA-6708 and the MON89788 even described in US Patent 9,944,945, which is incorporated by reference in the instant application (Applicant Remarks Dated 03/18/2026, Pages 15-16).
Applicant’s arguments summarized in A. above have been fully considered but are not found to be persuasive because while applicant has provided the structural identifiers described above, applicant’s description relating to SEQ ID NO: 1 and the MON89788 transgenic locus in the specification is non-limiting.
The specification on page 3 in paragraph 0010 which describes Figures 1A-B states that “Figure 1A-B shows a sequence (SEQ ID NO: 1) of the MON89788 event transgenic locus”. That the specification states “shows a sequence” makes clear that this is just one sequence of the MON89788 transgenic locus and as such this description does not limit the MON89788 transgenic locus to this exact sequence. This does not appear to have been an artifact of the specific language of that paragraph because later on page 8 of the specification, in paragraph 0027, Applicant states that “MON89788 transgenic loci include loci having the sequence of SEQ ID NO: 1, the sequence of the MON89788 locus in the deposited seed of Accession No. PTA-6708 and any progeny thereof, as well as allelic variants and other variants of SEQ ID NO: 1.” This description does provide information on the characteristics of the MON89788 transgenic locus, but because the locus is made up of a transgenic DNA insertion and the surrounding genomic DNA and the non-limiting nature of the description provided in the specification the bounds of the transgenic locus (how much endogenous DNA is included) is not clear, see indefiniteness rejection above.
Therefore, given that the claims are not limited to a specific transgenic locus sequence and that the specification does not provide description on how much genomic DNA is included in the transgenic locus the bounds of the MON89788 transgenic locus are not clear and Applicant’s arguments summarized in A. above are not found to be persuasive.
The structure of the junction polynucleotide is characterized by the boundary between the endogenous genomic DNA and inserted transgenic DNA and as such the position of the junction polynucleotide relative to the endogenous genome can be determined by comparing a non-transgenic genomic sequence to the non-transgenic DNA portion of the junction polynucleotide. Therefore the specification provides clear structural guidance for identifying the claimed junction sequences (Applicant Remarks Dated 03/18/2026, Pages 16-17).
Applicant’s arguments summarized in B. above have been fully considered but are not found to be persuasive because while applicant urges that there is sufficient description to find the junction. Applicant’s method of comparing non-transgenic genomic DNA to genomic portion of the transgenic event allows for the junction between the transgene and genomic DNA to be located. This method does not clarify any other features which the junction polynucleotide must possess nor how to determine the far bounds of the junction polynucleotide, the point in the genomic DNA of the transgenic event where the sequence ceases to be part of the junction polynucleotide. As such the bounds of the structure of the junction polynucleotide have not been adequately described and Applicant’s arguments summarized in B. above are not found to be persuasive.
The specification in example 1 and 3 describes Cas12a-mediated gene editing of the junction regions flanking the MON89788 transgene insertion and the insertion of a cognate guide RNA recognition site (CgRRS) at the 3’ end of the MON89788 event and therefore, the disclosure clearly conveys possession of modifications within the junction regions of the MON89788 event (Applicant Remarks Dated 03/18/2026, Page 17).
Applicant’s arguments summarized in C. above have been fully considered but are not found to be persuasive because as noted in the response to Applicant’s Arguments summarized in B. above, while applicant describes how to identify the junction between the transgene and the endogenous DNA and while applicant provides description of insertions into regions flanking the transgene the bounds of the junction polynucleotide have not been adequately described, see indefiniteness rejection above. Without knowing where the bounds of this structure are Applicant’s examples do not demonstrate possession of the full scope of the claimed genus which includes transgenic soybean plant cells comprising deletions, insertion or substitutions in any portion of the junction polynucleotide.
The written description requirement does not require that every species within a claimed genus be expressly described, rather the disclosure must provide a representative example or structural feature sufficient to demonstrate possession of the genus. In this case the specification provides the sequence of the MON89788 locus, the genomic insertion boundaries of the event and representative modifications within the those junction regions, which provide a clear structural framework for modifications occurring within the defined insertion locus and therefore, the claims are not directed to an undefined genus of soybean sequences, but rather to modifications occurring within a specific, well-characterized genomic locus (Applicant Remarks Dated 03/18/2026, Pages 17-18).
Applicant’s arguments summarized in D. above have been fully considered but are not found to be persuasive because the specification provides a non-limiting example of the MON89788 transgenic locus and describes the locus as comprising a genomic insertion of a transgene and flanking regions including the junction site. As noted in the indefiniteness rejections above, the scope imparted by the use of the term “transgenic locus” is not clear and Applicant’s non-limiting description of the sequence of SEQ ID NO: 1 does not limit the scope of this term, especially given that the transgenic locus and junction polynucleotide each comprise genomic DNA.
Without knowing where the genomic DNA that is part of the transgenic locus and junction polynucleotide ends and regular genomic DNA that is not part of these structures begins the bounds of the genomic locus are not clear.
To illustrate, Applicant urges in the arguments on page 10 of the remarks dated 03/18/2026 in the second to last paragraph that “the term “transgenic locus” refers to the genomic insertion site of a transgene and the genomic DNA containing that insertion”. Given this definition wouldn’t the whole chromosome where the transgene was inserted be considered the MON89788 transgenic locus? While the Examiner believes that the MON89788 genomic locus does not comprise an entire chromosome the bounds of the structure conferred by this term are not clear and therefore Applicant’s arguments drawn to D. above are not persuasive because the genomic locus where the modifications are to be made is not specific.
The description provided in the specification includes both structural guidance and representative examples demonstrating possession of the claimed invention (Applicant remarks dated 03/18/2026, Pages 18-21).
Applicant’s arguments summarized in E. above have been fully considered but are not found to be persuasive because given the indefinite nature of the MON89788 transgenic locus and the junction polynucleotide and the corresponding unclear scope of these structures, the structural guidance provided in the specification does not clarify these structures and therefore Applicant’s description of examples does not demonstrate possession of the full scope of the claimed genus of modified soybean plants.
As such the written description rejections of record are maintained.
Claim Rejections - 35 USC § 112 (Written Description)
Claims 1-12 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id.
The claims are broad in the following aspects:
Claims 1-9 are drawn to soybean plant cells and soybean plants comprising those cells, wherein the plants and cells comprise a modification of a junction polynucleotide of a MON89788 transgenic locus. (Attention directed to this aspect)
Claims 10-11 are drawn to methods of obtaining bulked population of inbred seed having the modified MON89788 transgenic locus and of obtaining hybrid soybean seed comprising the modified MON89788 transgenic locus.
Finally, claim 12 is drawn to a processed transgenic soybean plant product comprising the modified MON89788 transgenic locus.
As discussed above in the indefiniteness rejections, the terms “MON89788 transgenic soybean locus”, “MON89788 transgenic locus” and “junction polynucleotide” are indefinite because the bounds of the structures claimed by the use of these terms is not clear. This indefiniteness leads to written description issues, particularly the use of the term “junction polynucleotide”.
This is because while the ordinary artisan would be able to identify a transgenic soybean plant cell comprising a MON89788 transgene and further would be able to identify if that MON89788 transgene had been modified or further if regions around that MON89788 transgene had been modified, given the description provided in the instant disclosure and the state of the art the ordinary artisan would not be able to identify the bounds of the MON89788 transgenic locus nor would the ordinary artisan be able to identify the bounds of the MON89788 junction polynucleotide.
As such while the ordinary artisan would be able to identify modifications to the soybean genome including both endogenous sequences and exogenous transgene sequences the ordinary artisan would not be able to determine if a modification was in the MON89788 transgenic locus or the junction polynucleotide of the MON89788 transgenic locus and as such the ordinary artisan would not be able to determine if they were in possession of the instantly claimed invention at the time of filing (Emphasis added by Examiner).
Similarly, it does not appear that applicant had possession of the full scope of the claimed invention because even though applicant has provided examples of modified sequences near the MON89788 transgene it is not clear that these modifications are found within the MON89788 transgenic locus nor that these modifications are found within the MON89788 junction polynucleotides.
Therefore, Applicants have not adequately described the structural features that are required to be retained by members of the claimed genus of MON89788 transgenic locus sequences or junction polynucleotide sequences as to establish a structure-function relationship, or the structural features required to distinguish members of the claimed genus from other chemical structures.
The analysis will now turn to the second element of the court’s decision in Eli Lilly; namely, the description of a representative number of species. The broadly claimed genus of MON89788 transgenic locus and junction polynucleotide sequences is large and appear to include any soybean sequence whatsoever as long as it includes the MON89788 transgene.
Given the virtually infinite structural variable associated with these embodiments, the claims read on a broad and diverse genus of structures. In contrast, Applicant has only described one example of a modified junction polynucleotide sequence.
Specifically, applicant has provided the descriptions of MON89788 transgenic loci and junction polynucleotides quoted above in the indefiniteness rejections (see indefiniteness rejections above). Applicant also describes methods of using the Cas12a gene editing system to modify the 5’ and 3’ ends of the MON89788 event in examples 1 and 2 on pages 56 of the instant specification.
Of particular interest is example 3 which provides description of a method of inserting a cognate guide RNA recognition site (CgRRS)element at the 3’ end of the MON89788 event. This method uses the Cas12a system and a donor repair template in order to insert a sequence which is identical to a Cas12a recognition site located at the 5’ end of the MON89788 event into the 3’ end of the MON89788. These two Cas12a recognition sites are referred to as the OgRRS (5’) and CgRRS (3’) (Specification, Paragraphs 0124-0126).
Importantly, the specification states that other gRNAs can be used to introduce double stranded breaks in the MON89788 junction polynucleotide for insertion of a CgRRS making clear that there is no specific set of guide RNAs or specific target sequences associated with this technique. Finally the specification notes that the modified soybean plants comprising both the OgRRS and the CgRRS are advantageous because a gene editing system with a single guide RNA which targets the OgRRS or CgRRS can be used to efficiently excise the transgenic locus.
This guidance is insufficient to provide description such that the ordinary artisan would be able to identify if a sequence was a MON89788 junction polynucleotide or if an endogenous soybean DNA sequence was a part of the MON89788 transgenic locus or if it was located too far away from the MON89788 transgene to be considered part of that locus.
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Response to Applicant Arguments – Obviousness
Applicant’s arguments and amendments to the claims dated 03/18/2026 have been fully considered however they are not found to be persuasive and the rejections of record are maintained.
Applicant’s arguments are drawn to the following:
Claim 1 and its dependent claims require the following:
A MON89788 transgenic soybean locus.
Modification of a junction polynucleotide of the MON89788 locus.
Introduction of recognition sites flanking the locus.
The ability to excise the transgenic locus using the modified flanking sites.
Neither Srivastava, Corbin nor Malven teach or suggest this claimed configuration (Applicant Remarks dated 03/18/2026, Pages 21-24).
Applicant’s arguments summarized in A. above have been fully considered but are not found to be persuasive because in this portion of Applicant’s remarks the analysis considers the features required of the claims and the features taught by the references individually (Applicant’s arguments drawn to the lack of motivation to combine the references to arrive at the claimed invention is addressed in C below).
First, Applicant urges on page 22 that the claimed invention requires the features described in a.-c. above and that the ability to excise the transgenic locus is a resulting ability from these features. Importantly, this ability is not recited anywhere in the claims. Similarly, applicant urges that the claims require “introduction of recognition sites flanking the locus”, this does not appear anywhere in the claims. While claims 2, 5-6 and 12 recite the insertion of a CgRRS into the locus none of these claims talk about any other recognition site on the other side of the locus and claims 1, 3-4 and 7-11 the claims do not require an insertion, rather they only require a deletion of DNA in a 5’ or 3’ DNA junction polynucleotide of a MON89788 transgenic locus.
While, applicant urges that the references do not teach the above features the references teach the following:
A MON89788 transgenic soybean locus (Malven, Column 2, Third Full Paragraph; Malven, Column 33, Claims 1 and 5).
Modification of the regions flanking a transgene (Corbin, Page 4, Paragraph 0033).
Inserting nuclease target sites on the regions flanking a transgenic insertion including those that match a sequence on the other side of the insertion (Corbin, Page 4, Paragraph 0033).
Excising the transgene through the use of the CRISPR system in order to generate double stranded breaks on either side of the transgene which can then be spliced together, neatly excising the transgene (Srivastava, Page 154, Paragraph spanning columns 1-2; Srivastava, Figure 1a).
While these teachings may use slightly different language from that of the instant application the references do teach all of the limitations of the claims and therefore Applicant’s arguments summarized in A. above are not found to be persuasive.
The claims are distinct from the art in the following ways:
The present claims require specific recognition sites flanking the MON89788 transgenic locus. Specifically, the OgRRS and CgRRS sequences are identical recognition sites enabling excision using a single guide RNA while Srivastava does not disclose or suggest identical recognition sites, nor does Srivastava disclose modification of a junction polynucleotide of a specific soybean transgenic event.
The claims require modification of the junction polynucleotide of a known transgenic event in order to introduce matching nuclease sites while Corbin teaches construct design and insertion of nuclease recognition sites during the generation of transgenic events (Applicant Remarks dated 03.18/2026, Pages 22-24).
Applicant’s arguments summarized in B. above have been fully considered but are not found to be persuasive because Applicants urging that the claimed invention differs from the prior art is not found to be persuasive in light of the teachings of the art.
Applicant argues that the claims require specific recognition sites flanking the MON89788 transgenic locus. Specifically, OgRRS and CgRRS sequences which are identical recognition sites enabling excision using a single guide RNA and further urges that Srivastava does not disclose or suggest identical recognition sites, nor does Srivastava disclose modification of a junction polynucleotide of a specific soybean transgenic event. This is not persuasive because the OgRRS is not found anywhere in the claims. To the extent to which the implicit function of the CgRRS is that it hybridizes to the same nuclease as a corresponding site on the other flank of the target (the OgRRS) Corbin teaches that it is advantageous to use the same target site on either side of the target because it allows for the use of the same site specific nuclease and allows for target genes to be excised with a single nuclease and therefore this argument is not found to be persuasive (Corbin, Page 4, Paragraph 0034; Corbin, Page 14, Paragraph 0129; Corbin, Page 30, Description of SEQ ID NO: 17).
Additionally, Applicant’s urging that Srivastava does not teach the excision of transgene from soybean attacks that reference individually and fails to consider the teachings of the references as a whole.
With respect to Applicant’s arguments drawn to the timing of the introduction of the target sites, this argument is not found to be persuasive. Applicant states that the claims require modification of the flanking regions of a known transgenic locus which Applicant implies must occur after the generation of transgenic events and urges that Corbin is drawn to construct design and insertion of nuclease recognition sites during the generation of transgenic events and therefore the teachings of Corbin differ from the claimed invention.
Claim 1 recites “A transgenic soybean plant cell comprising a modification of a MON89788 transgenic soybean locus”. This does not require that a soybean plant having that locus undergo further modification to produce the claimed invention only that the MON89788 transgenic locus be modified. Rather it only requires that the MON89788 transgenic locus be modified. Therefore, this locus could be cloned, additional target sites added as taught in Corbin and then the modified locus could be introduced into either an existing MON89788 containing plant cell or into a wild type plant cell at the appropriate target site using homology directed repair.
Further, the argument that because the teachings of Corbin were primarily drawn to construct design and the insertion of target sites during the generation of transgenic events the ordinary artisan would not have found it obvious to applying the concept taught by Corbin, namely the introduction of nuclease recognition sites flanking a transgene of interest in order to efficiently excise that gene from plants, to other scenarios in the art of molecular biology and transgenic plants is not persuasive because “the test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA].” and given the teachings of Srivastava, Corbin and Malven the ordinary artisan would have found it obvious to modify the existing MON89788 transgenic locus of Malven (MPEP 2145 IV).
The Office Action asserts that the skilled artisan would have been motivated to excise the MON89788 locus to alleviate biosafety concerns or facilitate retransformation, however this reasoning does not explain why the artisan would specifically modify the junction polynucleotide of the MON89788 locus to introduce identical recognition sequences flanking the locus, as required by the claims and therefore arriving at the instantly claimed invention would require impermissible hindsight (Applicant Remarks dated 03/18/2026, Pages 24-25).
Applicant’s arguments summarized in C. above have been fully considered but are not found to be persuasive because the claimed invention does not require identical recognition sequences flanking the locus. Instead claims 2, 5-6 and 12 require the insertion of a CgRRS which may have the implicit function of hybridizing to the same nuclease as a corresponding site on the other flank of the target (the OgRRS).
However, Corbin provides reasoning to use identical target sequences, stating that it is advantageous to use the same target site on either side of the target because it allows for the use of the same site specific nuclease (ZFN) to excise the marker gene and gene of interest and therefore this argument is not found to be persuasive (Corbin, Page 4, Paragraph 0034; Corbin, Page 14, Paragraph 0129; Corbin, Page 30, Description of SEQ ID NO: 17).
In conclusion, Applicant’s arguments have been fully considered but are not found to be persuasive and therefore the rejections of record are maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-12 remain rejected under 35 U.S.C. 103 as being unpatentable over Srivastava, Plant Cell, Tissue and Organ Culture (PCTOC) 129.1 (2017), in view of Corbin, US Patent Publication US 2018/0163218 A1, June 14, 2018 and Malven, 7,632,985 B2, Dec. 15, 2009.
With respect to claim 1, Srivastava teaches that certain genes including selection marker genes can be used in the plant transformation process but may have limited use after this process while raising biosafety concerns and act as a barrier in the retransformation of the transgenic line (Srivastava, Page 154, Column 2, First Full Paragraph). As such, Srivastava provides motivation to excise transgenes from crop plants (rice plants).
In order to do this, Srivastava teaches the use of the CRISPR system in order to generate double stranded breaks on either side of the transgene which can then be spliced together, neatly excising the transgene (Srivastava, Page 154, Paragraph spanning columns 1-2; Srivastava, Figure 1a).
Srivastava does not explicitly recite OgRRS or CgRRS sequences however Srivastava does teach Cas recognition and binding sequences on either side of the transgene to be targeted, the only difference between the Cas recognition sites of Srivastava and the OgRRS and the CgRRS sequences of the claims appears to be that the OgRRS and CgRRS sequences are identical where the Cas recognition sites of Srivastava are not identical.
With respect to claim 1, Srivastava does not explicitly teach modifying a junction polynucleotide of a MON89788 locus nor does Srivastava explicitly teach the excision of transgenes in soybean.
However, with respect to claim 1, Corbin teaches a method of excising a transgene wherein the method comprises the use of a plant comprising a first copy of a site specific nuclease binding site, a transgene then a second copy of the site specific nuclease binding site (Corbin, Page 3, Paragraph 0016).
Corbin further teaches the treatment of this plant with a site specific nuclease which can target both the first and the second site specific nuclease binding sites and cleave the DNA at those sites, thus excising the transgene (Corbin, Page 3, Paragraph 0016), although Corbin teaches that the site specific nuclease can be introduced into the target cell by crossing the second plant with a first plant comprising a sequence encoding the site specific nuclease (Corbin, Page 3, Paragraph 0016).
Importantly, Corbin teaches that the site to be targeted is important and should be constructed to have specific features, specifically Corbin teaches that a sequence comprising target sites for the nucleases should be inserted into the target region of the genome (This includes CgRRS sequences which match the OgRRS sequence on the other side of the transgene)(Corbin, Page 4, Paragraph 0033).
Corbin, also teaches that it is advantageous to use the same target site on either side of the target because it allows for the use of the same site specific nuclease and allows for target genes to be excised or for additional genes to be stacked at a target site efficiently (Corbin, Page 4, Paragraph 0034; Corbin, Page 14, Paragraph 0129; Corbin, Page 30, Description of SEQ ID NO: 17). Therefore, Corbin provides motivation to make a modification on one side of a transgene which matches a target on the other side of the transgene, stated differently Corbin provides motivation to introduce a CgRRS site into the region flanking a target gene.
Finally, Corbin teaches that these methods are applicable in many different crop plants including soybean (Corbin, Page 4, Paragraph 0026; Corbin Page 8, Paragraph 0075
In addition, with respect to claim 1, Malven teaches and claims a transgenic plant cell comprising the MON89788 transgenic event which is set forth in instant SEQ ID NO: 14 (Malven, Column 2, Third Full Paragraph; Malven, Column 33, Claims 1 and 5).
At the time of filing it would have been obvious to modify the plants and methods of Srivastava to use the identical target approach of Corbin to excise the MON89788 transgenic soybean locus of Malven.
This would have been obvious because the teachings are drawn to generating modified plants having altered characteristics. Specifically, Srivastava teaches motivation to excise transgenes from crop plants and Srivastava and Corbin teach methods of excising transgenes from crops including soybean, with the method of Corbin including introducing sequences which appear to be the CgRRS sequences of the instant claims to the region flanking the target gene and Malven teaches agronomically important soybean plants comprising the MON89788 transgene.
Given the teachings described above, the ordinary artisan would have been motivated to excise the MON89788 transgene from transgenic soybean plants. This is because the MON89788 even confers herbicide tolerance which can be used in research to select for plants which have been transformed with this construct or other breeding methods which may rely on the presence of this marker to identify certain germplasm or use this transgene to enrich a population of seeds with certain traits linked to the transgene. As stated in Srivastava the presence of selection marker genes, as the MON89788 is in the hypothetical breeding schemes described above, is pointless after the transgenic clones have been recovered. Therefore, the ordinary artisan would have had motivation to excise the MON89788 transgene in order to alleviate biosafety concerns and to eliminate a potential barrier for the retransformation of those soybean plants in order to introduce new genes.
The ordinary artisan would further have been motivated to modify the region around the MON89788 transgene in order to produce two identical binding sites for site directed nucleases as taught in Corbin. This would have been motivating because it increases efficiency by requiring only a single gRNA to be developed and optimized and the target plants need only be transformed with a single gRNA rather than the coupled gRNAs described in Srivastava. The use of a single gRNA also enriches for uniform cleavage at each target site and allows for the efficient excision of transgenes but also the efficient stacking of traits at that specific genomic location. It is clear that Corbin provides motivation for the use of identical target sites on either side of the target transgene and that this method is an improvement on the method of Srivastava which relies on paired gRNAs.
With these teachings and the motivation from both Srivastava and Corbin it is clear that it would have been obvious at the time of filing to modify the plants of Srivastava in order to generate an identical site at the 3; end of the target gene which matched that at the 5’ end of the target gene.
Further, it would have been obvious for this target plant of the combined method of Srivastava and Corbin to be the transgenic soybean plant of Malven. This would have been obvious because the MON89788 transgene is an effective herbicide which allows for the rapid selection of plants which possess this transgene.
Given the evidence provided above, the ordinary artisan would have found it obvious to modify the transgenic soybean plant of Malven by inserting a second site specific nuclease binding site at the 3’ end of the transgene that is identical to a target site at the 5’ end of the target gene of interest (MON89788 transgene) as taught in Corbin for use in methods of excising the transgene as taught in Srivastava. Therefore, claim 1 remains rejected as obvious.
With respect to claims 2-6, Srivastava in view of Corbin and Malven collectively teach all of the limitations of claim 1, see above.
Further, the additional limitations in these claims drawn to specific deletions or insertions to produce target sites represent simple design choices and given that Corbin provides motivation to modify sequences flanking a target gene and teaches that this modification could produce an identical target site to a target site flanking the other end of the target gene the ordinary artisan would have been motivated to make insertions, deletions or substitutions depending on which target site on opposite flanking region they were trying to match.
With respect to claims 7-9, Srivastava in view of Corbin and Malven collectively teach all of the limitations of claim 1, see above.
Further, Srivastava, Corbin and Malven all teach modified plants and Malven also teaches modified plant parts including seeds (Srivastava, Page 154, Abstract; Corbin, Page 37, Claim 18; Malven, Column 33, Claims 1-2).
With respect to claims 10-11, Srivastava in view of Corbin and Malven collectively teach all of the limitations of claim 1, see above.
Further, Malven teaches methods of producing a soybean plant comprising crossing the soybean plant of Malven with a genetically distinct soybean plant to product progeny plants and also teaches a method of self-fertilizing a plant comprising the modification (MON89788 locus) to produce a progeny plant and selecting for a plant that is homozygous for the genomic modification (Malven, Column 34, Claim 12; Malven Column 35, Claim 13).
With respect to claim 12, Srivastava in view of Corbin and Malven collectively teach all of the limitations of claim 1, see above.
Further, Malven teaches commodity plant products produced from the modified soybean plant (Malven, Column 33, Claim 3).
While the references do not explicitly teach the exact modifications described in claims 2-6 nor do they explicitly recite that methods of obtaining inbred seed produce a “bulked” population, these claimed features are intrinsic characteristics of the combined methods and plants of Srivastava in view of Corbin and Malven. This is because the additional limitations in these claims drawn to specific deletions or insertions to produce target sites represent simple design choices and given that Corbin provides motivation to modify sequences flanking a target gene and teaches that this modification could produce an identical target site to a target site flanking the other end of the target gene, the ordinary artisan would have been motivated to make insertions, deletions or substitutions depending on which target site on opposite flanking region they were trying to match.
As such the additional limitations in these claims do not add any additional elements that require a different obviousness analysis than that provided with respect to claim 1 above. Therefore, that analysis is applied to claims 2-12 and presented below.
At the time of filing it would have been obvious to modify the plants and methods of Srivastava to use the identical target approach of Corbin to excise the MON89788 transgenic soybean locus of Malven.
This would have been obvious because the teachings are drawn to generating modified plants having altered characteristics. Specifically, Srivastava teaches motivation to excise transgenes from crop plants and Srivastava and Corbin teach methods of excising transgenes from crops including soybean and Malven teaches agronomically important soybean plants comprising the MON89788 transgene.
Given the teachings described above, the ordinary artisan would have been motivated to excise the MON89788 transgene from transgenic soybean plants. This is because the MON89788 even confers herbicide tolerance which can be used in research to select for plants which have been transformed with this construct or other breeding methods which may rely on the presence of this marker to identify certain germplasm or use this transgene to enrich a population of seeds with certain traits linked to the transgene. As stated in Srivastava the presence of selection marker genes, as the MON89788 is in the hypothetical breeding schemes described above, is pointless after the transgenic clones have been recovered. Therefore, the ordinary artisan would have had motivation to excise the MON89788 transgene in order to alleviate biosafety concerns and to eliminate a potential barrier for the retransformation of those soybean plants in order to introduce new genes.
The ordinary artisan would further have been motivated to modify the region around the MON89788 transgene in order to produce two identical binding sites for site directed nucleases as taught in Corbin. This would have been motivating because it increases efficiency by requiring only a single gRNA to be developed and optimized and the target plants need only be transformed with a single gRNA rather than the coupled gRNAs described in Srivastava. The use of a single gRNA also enriches for uniform cleavage at each target site and allows for the efficient excision of transgenes but also the efficient stacking of traits at that specific genomic location. It is clear that Corbin provides motivation for the use of identical target sites on either side of the target transgene and that this method is an improvement on the method of Srivastava which relies on paired gRNAs.
With these teachings and the motivation from both Srivastava and Corbin it is clear that it would have been obvious at the time of filing to modify the plants of Srivastava in order to generate an identical site at the 3; end of the target gene which matched that at the 5’ end of the target gene.
Further, it would have been obvious for this target plant of the combined method of Srivastava and Corbin to be the transgenic soybean plant of Malven. This would have been obvious because the MON89788 transgene has been for years known in the art as an effective herbicide which allows for the rapid selection of plants which possess this transgene.
Given the evidence provided above, the ordinary artisan would have found it obvious to modify the transgenic soybean plant of Malven by inserting a second site specific nuclease binding site at the 3’ end of the transgene that is identical to a target site at the 5’ end of the target gene of interest (MON89788 transgene) as taught in Corbin for use in methods of excising the transgene as taught in Srivastava. Therefore, claims 2-12 remain rejected as obvious.
Conclusion
All claims are rejected.
Finality
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.
Examiner’s Contact Information
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/BRIAN JAMES SULLIVAN/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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