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 of Group I drawn to claims 32-36 and to the species of SEQ ID NO: 3 and SEQ ID NO:4 in the reply filed on 02/23/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
Claims 32-48 are pending.
Claims 37-48 are withdrawn as being drawn to a non-elected invention.
Claims 32-36 including the sequences of SEQ ID NOs: 3-4 are examined on the merits.
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 32-36 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has recently 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". See 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 a description of that material". Further, the court held that to adequately describe a claimed genus, a 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".
These claims include at least three areas which add breadth. First the claims are drawn to the broad genera of target sequences, specifically Ms1 polynucleotides and polynucleotides which encode Ms1 polypeptides which have at least 85% sequence identity to the sequences of SEQ ID NO: 3 and SEQ ID NO: 4, respectively. Second, the claims are drawn to any modification whatsoever in the target sequence. Third, the claims are drawn to a broad genus of target plants which includes nearly any wheat plant whatsoever, regardless of whether it is bread wheat or another wheat plant.
However, these same claims which have such breadth also have a narrower limitation, requiring the wheat plants comprising the modifications to have the specific phenotype of male sterility.
With respect to MS1 polynucleotide and MS1 polypeptide sequences, the claims require the broad genus of MS1 sequences, while these genes are required to have 85% sequence identity to SEQ ID NO: 3 or to encode sequences having at least 85% sequence identity to SEQ ID NO: 4, this additional limitation fails to limit the scope of the claim to subject matter having adequate written description. Given that these limitations refer to a diverse genus of sequences and further given that the specific regions of the sequences and/or specific motifs or features that must be conserved in order for a sequence to be a Ms1 gene and to have the requisite function of producing a male-sterile wheat plant when any genetic modification is made to it are not adequately described.
Specifically, SEQ ID NO: 3 is a polynucleotide sequence and without the specific nucleotides that must be conserved there are many different sequences that have at least 85% identity to SEQ ID NO: 3, which is 669 nucleotides in length. This means that it is possible for a sequence to be 85% identical to SEQ ID NO: 3 and differ by 100 nucleotides. This is complicated because polypeptides are encoded for by nucleotide triplets, additionally there are multiple triplets which encode for the same amino acid which allows for silent mutations where the nucleotide sequence changes but the translated protein has the original sequence. This means that a sequence having 100 single nucleotide polymorphisms (SNPs) and which is otherwise identical to SEQ ID NO: 3 falls within the scope of the claimed Ms1 sequences. Importantly, if each of the SNPs was found in a different nucleotide triplet, it is possible to have a polypeptide sequence that is produced by transcribing and translating this sequence that differs by 100 amino acids as compared to a polypeptide produced by transcribing and translating the reference sequence, this sequence would share only 55 percent sequence identity with the reference polypeptide sequence.
Second, the claim is drawn to introducing any genetic modification into at least one endogenous Ms1 gene. This scope includes single nucleotide polymorphisms, longer substitutions, small and large in frame deletions as well as nonsense and missense mutations. Additionally, these modifications can be found in introns, exons, the promoter, the terminator or even cis regulatory elements. Given that different modifications would have different effects depending on their location with the Ms1 gene and the breadth of the different modifications included within the scope of the claim it is clear that applicants use of the phrase “introducing a genetic modification into at least one or more endogenous MS1 polynucleotide sequences in a wheat plant cell” adds significant claim breadth.
Third, the claims are drawn to methods of modifying any wheat plant whatsoever. This includes the well-studied bread wheat, but also includes other polyploid wheat varieties, wild type wheat varieties and extensively modified wheat plants, including those having undergone extensive mutagenesis using techniques including EMS mutagenesis or plants which have undergone extensive transformation and harbor numerous transgenes. As such even the genus of wheat plants which can be targeted using this method is more broad than it appears at first glance.
As illustrated above, the claims are drawn to a broad and diverse genus of methods of introducing any genetic modification into any Ms1 gene in any wheat plant which produces the narrow and specific phenotype of male sterility.
Despite the breadth of the claims, with enough description, specifically, the relationship between the structure of any modification in any wheat Ms1 polynucleotide and the function of male sterility, the ordinary artisan would be able to identify if they were in possession of the claimed invention.
However, given the limited description provided by the applicant this relationship is not clear.
Rather than providing description of the broadly claimed methods, Applicant has provided a single example of using gene editing methods to target a single specific fertility gene from the B genome in wheat, see example 3 in paragraphs 0187-0188 on pages 55-56 of the instant specification.
There are at least two aspects of this example that are of note given the claimed invention. First, while the claims are drawn to any modification whatsoever in a MS1 gene applicant only provides description of two modifications in a single MS1 gene in wheat. These mutations are a 1 base pair insertion and a 3 base pair deletion. Importantly, while the allele with the single base pair insertion conferred male sterility when present in a homozygous state when present in a heterozygous state this allele did not produce the male sterility phenotype. The example was silent on whether the 3 base pair deletion allele conferred sterility.
The second aspect which is of note is that applicant’s lone example targeted the Ms1 gene in the wheat B genome, while applicant’s remarks dated 02/23/2026 in response to the restriction requirement make clear the currently examined Ms1 sequence (SEQ ID NO: 3) is the Ms1 gene from the wheat A genome. As such applicant has not provided description of a single example of a mutation in the claimed sequence which produces male sterility in wheat. In combination with the fact that the only described mutation in a wheat Ms1 gene in applicant’s specification does not produce male sterility unless present in a homozygous state it appears that applicant has not provided any example of a single genetic modification in a Ms1 gene in wheat that produces a male-sterile wheat plant.
While it was known in the art that Ms1 plays a role in male sterility in wheat plants, the allele from the A genome in wheat, applicant’s elected SEQ ID NO: 3, is known to be epigenetically silenced in wild type plants and therefore the relationship between this specific allele and male-sterility and more importantly, the relationship between any modification in sequences having at least 85% sequence to instant SEQ ID NO: 3 and male sterility is unclear (Wang, Proceedings of the National Academy of Sciences 114.47 (2017): 12614-12619)(Wang, Page 12614, Abstract).
In fact applicant does not even make clear what the exact sequence of Ms1 is.
As demonstrated above the gap between the broadly claimed invention and the description provided by applicant is broad.
Therefore, Applicants have not sufficiently described the necessary structural features linked to the broadly claimed modified genus of methods of introducing an genetic modification to any Ms1 gene in any wheat plant to produce male-sterile plants. Applicants have not adequately linked modifications in Ms1 to male-sterility such that the ordinary artisan would be able to determine if any plant having any modification in any Ms1 gene in any wheat plant would have male-sterility.
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 methods is very large in size. Even the limitations on Ms1 sequences only require these sequences to have 85% identity to SEQ ID NOs: 3-4 which have inherent breadth as discussed above. Further, claimed methods are not limited to any specific modifications to these Ms1 sequences or to any specific wheat plants. Given the lack of a causal relationship between modifications in Ms1 and male-sterility, even if the claims were significantly narrowed, they would still appear to lack written description because without this relationship the ordinary artisan would not be able to determine if a modified plant would have male-sterility due to a modification in a Ms1 sequence.
Moreover, Applicants have broadly claimed Ms1 sequences without any description of motifs, sequences, or positions which must be conserved in order to provide male-sterility upon the introduction of any modification to these sequences. Therefore, the ordinary artisan would understand that the broadly claimed genus of Ms1 sequences is large and diverse and the introduction of any modification into this broad and diverse genus of sequences is required to produce male-sterility in any wheat plant.
Given the breadth of the structural variable associated with these embodiments, the claims read on an extremely broad and highly diverse genus.
Thus, in view of the analysis presented above, a skilled artisan would appreciate that the claims are directed to extremely broad and highly diverged genus of modifications to endogenous wheat Ms1 sequences which are required to have the function of producing male-sterile plants. In contrast, Applicants do not appear to describe and reduce to practice any Ms1A sequences (SEQ ID NO: 3) which have an introduced genetic modification which confers male-sterility to wheat plants.
Given the large size and structural diversity associated with the claimed genus, Applicant’s disclosure is not representative of the claimed genus as a whole.
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.
All pending claims are rejected as lacking written description.
While it was known in the art that Ms1 plays a role in male sterility in wheat plants, the allele from the A genome in wheat, applicant’s elected SEQ ID NO: 3, is known to be epigenetically silenced in wild type plants and therefore the relationship between this allele and male-sterility and more importantly, the relationship between any modification in sequences having at least 85% sequence to instant SEQ ID NO: 3 and male sterility is unclear (Wang, Proceedings of the National Academy of Sciences 114.47 (2017): 12614-12619)(Wang, Page 12614, Abstract).
Claim Rejections - 35 USC § 102
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 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 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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 32 and 34-36 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Darvey, US 11,697,822 B2, patented July 11, 2023 with the earliest effective filing date of August 29, 2017.
Claim 32 is drawn to a method for producing a male-sterile wheat plant comprising:
introducing a genetic modification, including whole gene deletions (See page 37, Paragraph 0110 of the specification) into an endogenous MS1 polynucleotide sequence in a wheat plant.
Where the MS1 polynucleotide is selected from a group of sequences including those having at least 85% sequence identity to instant SEQ ID NO: 3.
obtaining the male-sterile wheat plant.
With respect to claim 32, Darvey discloses methods for generating male-sterile wheat plants, comprising introducing a whole gene deletion (genetic modification) into at least one Ms1 gene in a wheat plant (Darvey, Column 1, Lines 36-42). Further, Darvey discloses obtaining male sterile cereal plants by mutation of an endogenous gene that results in the suppression of the gene and then obtaining homozygous versions of these plants through crossing experiments after mutating the target genes (Darvey, Column 40, Lines 18-36). Darvey also discloses a Ms1 gene having SEQ ID NO: 14 of Darvey (MS1 from a wild diploid wheat Triticum boeticum) which shares 97.6% sequence identity with instant SEQ ID NO: 3, see figure 3, below (Darvey, Column 129, Claim 7).
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Figure 3: Description of sequence alignment of instant SEQ ID NO: 3 and SEQ ID NO: 14 of Darvey.
With respect to claim 34, Darvey discloses all the limitations of claim 32, see above. Further, Darvey discloses that the genetic modifications are deletions (Darvey, Column 1, Lines 36-42; Darvey, Column 40, Lines 18-36).
With respect to claim 35, Darvey discloses all of the limitations of claim 32, see above. Further, Darvey discloses obtaining male-sterile wheat plants which includes an implicit selecting step in which those plants that are homozygous for the modification are obtained by crossing steps during which the desired plant would be selected in order to produce plants having mutations in both alleles (Darvey, Column 40, Lines 31-36).
With respect to claim 36, Darvey discloses all of the limitations of claim 32, see above. Further, Darvey discloses crossing Ms1 deletion lines with another wheat line to obtain hybrid wheat seed (Darvey, Figure 16B, Step g)
Claims 32 and 34-36 are rejected as anticipated by Darvey.
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 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 33 is rejected under 35 U.S.C. 103 as being unpatentable over Darvey, US 11,697,822 B2, patented July 11, 2023 with the earliest effective filing date of August 29, 2017.
With respect to claim 33, Darvey teaches all of the limitations of claim 32, See 35 USC 102 rejection above.
With respect to claim 33, Darvey does not explicitly teach a single embodiment in which the genetic modification which produces the male-sterile plant is introduced by a TALEN, a meganuclease, a zinc finger nuclease, or a CRISPR-associated nuclease.
With respect to claim 33, Darvey does teach that male sterility genes can arise from mutations in male fertility genes and that these mutations can include deletions or insertions of one or a few nucleotides (Darvey, Column 40, Lines 18-28). Darvey also teaches that CRISPR nucleases can be used as site-specific nucleases to make a double-strand break a target site in a target cereal plant line (Darvey, Column 53, lines 57-66). Finally, Darvey teaches that CRIPSR-associated nucleases can be used to generate knock-out cells (Darvey, Sentence Spanning Columns 59-60).
At the time of filing it would have been obvious to modify the method of Darvey to use CRISPR-Associated nucleases to generate the modifications in the MS1 gene, given that Darvey teaches the use of CRISPR nucleases as site-specific nucleases capable of generating knock outs. This would have been obvious because Darvey in one embodiment teaches methods of generating male-sterile wheat plants by introducing mutations into a Ms1 gene and in another section of the disclosure teaches the use and benefits of CRISPR-associated nucleases for generating targeted, specific mutations including those that produce knock outs. The ordinary artisan would have been motivated to combine these teachings because of the accuracy, flexibility and efficiency of CRISPR nucleases and the ease with which they would allow for the generation of Ms1 mutations. Therefore, claim 33 is rejected as obvious given the teachings of Darvey.
Conclusion
All examined claims are rejected.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN JAMES SULLIVAN whose telephone number is (571)272-0561. The examiner can normally be reached 7:30 to 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on (571)270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN JAMES SULLIVAN/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663