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 .
Claim Status
Claims 35-54 are pending. Claims 1-34 are canceled. Claims 39 and 52 are withdrawn. Claims 35-38, 40-51, and 53-54 are examined only to the extent of the elected sequences SEQ ID NO: 16 and 28 in the instant application.
Claim Objections
Claims 35-38, 40-51, and 53-54 are objected to because of the following informalities:
In claim 36 needs a colon or period between “NO” and “11”.
In claims 37, 38, 49, 50 and 54 should have “Nos.” or “NOs:” or “NOs.”.
In claim 42, “RanGAP1 ortholog” should be amended to “ortholog RanGAP1 protein” for language consistency.
In claim 44, it is suggested “expressing” be amended to “comprising an expressed”, because claim 44 is a product claim.
Dependent claims are included.
Correction is required.
Claim Rejections - 35 USC § 112(b) (Indefinite)(Amended)
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.
4. Claims 35-38, 40-51 and 53-54, are 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 claim 35, it is unclear whether the recitation within the parentheses is intended to be a claim limitation or a nonlimiting example. It is suggested the parentheses be deleted.
In claims 35 and 45, the LRR domain, the N-terminal WPP motif and the pfam PF13943 domain of a protein of undisclosed structure (ortholog) cannot be determined. The domains and motifs are not structurally defined. Does WPP motif refers to three amino acids only?
In claim 35, it is unclear whether the limitation of “mutation, truncation or deletion” also applies to the pfam PF13943 domain.
In claims 35 and 45, it is unclear how the modified RanGAP1 protein comprises a deleted N-terminal WPP motif and/or pfamPF13943 domain. If these are deleted, they are not present in the modified RanGAP1 protein.
In claims 35 and 45, it is unclear which region of the wild type RanGAP1 ortholog protein constitutes the N-terminal. Where does the N terminal of the ortholog begin and end?
In claims 35 and 45, it is unclear what sequence structure constitutes “pfam PF13943”. The specification does not define this recitation as having a particular structure.
In claim 35, 40 and 45, the metes and bounds of “similar conditions” are unclear. It is not known what conditions are encompassed by the “similar” recitation.
In claim 36, it is unclear how the modified RanGAP1 protein comprises a deleted LRR domain. If the LRR domain is deleted, it is not present in the modified RanGAP1 protein.
In claim 36, “corresponding residues of plant RanGAP1 orthologs” are unclear because undisclosed residues and positions of undisclosed sequence structures cannot be determined.
In claim 36, the recitation of “one or more positions corresponding to Arg190 and/or Asn219” is unclear. It is unclear what positions correspond to Arg190 and what positions correspond to Asn219 in SEQ ID NO:11. Moreover, it is unclear how Arg190 and Asn219 are truncated. How does one truncate a single amino acid?
In claim 36, the metes and bounds of the LRR domain are unclear. What positions of SEQ ID NO:11 constitute the LRR domain?
In claim 40, “increased agricultural productivity” should be amended to “increased biomass”. Otherwise, claim 40 does not further limit claim 35.
In claim 41, the metes and bounds of “an ortholog RanGAP1 protein of an ortholog plant” are unclear. An undisclosed protein of an undisclosed plant cannot be determined. Further, it is not known what plant is “an ortholog plant” of the generic plant of claim 35.
In claims 42 and 47, the recitation “derived” is unclear because it is not known what is retained in the derived product. It is suggested “derived” be amended to “obtained”. It is noted that claims 42 and 47 were inadvertently omitted in the previous Office action with regard to the recitation of “derived”.
In claim 43, it is unclear whether “the RanGAP1 protein” refers to the modified RanGAP1 protein as amended or an unmodified RanGAP1 protein.
In claim 44, “an SRF-TF-binding domain” suggests there are multiple SRF-TF-binding domains in the SRF-TF-domain-containing protein. If there is only one domain, “an” should be amended to “the”.
In claim 45, the recitation “normal” is unclear because it is not known what is considered normal. For example, what is considered normal for one plant it is not normal for another. It is suggested “normal” be deleted.
In claim 45, the recitation of “agricultural productivity” is unclear. Applicant’s definition on page 31 is inadequate, because the “amount of a crop grown” indicates the quantity of plants being sown and grown, and does not indicate what is being produced from said grown plants. It is suggested “agricultural productivity” be amended to “biomass”. The method claims were examined with the product claims because they were related as product and method of using said product. If the method claims are no longer a method of using the claimed product, the method claims would be excluded from allowable product claims, as permitted under In re Ochiai. Additionally, as amended, the product claims recite the SEQ ID NOs. of the modified RanGAP1 protein. The method claims recite the SEQ ID NOs. of the unmodified RanGAP1 protein. Thus, the method claims are not a method of using the claimed product.
In claim 45, it is unclear whether the WPP motif refers to three amino acids only, or encompasses a sequence that contains WPP amino acids. It is further unclear where in SEQ ID NO:11 the WPP domain is located. Additionally, it is unclear whether “corresponding to pfam PF13943” refers to the WPP motif or the WPP domain. It is unclear where in SEQ ID NO:11 pfam PF13943 is located. Is the WPP domain the same as pfam PF13943? It is also unclear whether the 90% sequence identity refers to SEQ ID NO:11 or the modified RanGAP1 protein.
In claim 46, “the exogenous nucleic acid sequence” lacks antecedence.
In claim 47, “the RanGAP1 ortholog” should be amended to “the wild-type RanGAP1 ortholog” for proper antecedence.
In claim 48, “a nucleic acid sequence of a RanGAP1 protein” suggests there are multiple nucleic acid sequences encoding multiple RanGAP1 proteins in a plant. If there is only one, “a” should be amended to “the”.
In claim 48, line 3, “a modified” should be amended to “the modified” for proper antecedence. Also “a mutated” should be amended to “the mutated” for proper antecedence.
In claim 53, it is unclear whether the “putative SRF-TF-domain” of line 3 is the same as the “SRF-TF DNA binding domain” in line 5.
In claim 54, it is unclear whether “having” refers to the WPP domain or the RanGAP1 protein.
In claim 54, it is unclear whether “any one of the foregoing” refers to the SEQ ID NOs. recited in claim 54, the sequences having 90% sequence identity the SEQ ID NOs. recited in claim 54, both, or any of the sequences in the preceding claims.
In claim 54, the recitation “at least 90% sequence homology…” is unclear. It is unclear whether the percent sequence identity is based on sequence comparison or evolutionary relatedness. It is suggested that “90% sequence homology” is amended to “90% sequence identity”.
In claim 54, the recitation of “at least 90% sequence homology to RanGAP1 protein having a mutated, truncated or deleted WPP domain, having an amino acid sequence selected from SEQ ID NOs 14, 16- 19, 39-42, 49-52, 59-63, or 71-75, or a sequence having at least 90% sequence identity to any one of the foregoing.“ is unclear. It is unclear what the 90% homology to the 90% sequence identity is intended to encompass. Is Applicant claiming 90% of 90%, which is 81%, of SEQ ID NO: 16? Applicant is suggested to amend claim appropriately.
Correction and/or clarification is required.
Since the rejections have been modified to reflect the amendment to the claims, only the arguments that are relevant to the current rejections are addressed below.
Applicant argues that they have provided variants retaining the conserved LRR domain while comprising the mutation, secondly argues the pfam PF13943 is well understood in the art, thirdly that “agricultural productivity” is understood in the art as “harvestable yield/output (standard agronomy), and not plant density”.
(Remarks, December 30, 2025, page 10).
This argument has been fully considered but not found persuasive.
Regarding Applicants 1st argument the 90% sequence identity requirement is unclear because it fails to establish a consistent baseline. If the WPP motif is deleted or truncated, the total length of the protein changes. Without a defined alignment to determine the 90% sequence identity, a person skilled in the art cannot determine if a modified sequence meets the threshold.
Regarding Applicants 2nd argument the LRR domain remains poorly defined. Relying on figure 12, a structural illustration, does not provide the specific amino acid location and therefore unclear. Identifying two isolated residues (Arg190 and Asn219) is insufficient to define the boundaries of an entire functional domain across diverse plant species.
Regarding Applicants 3rd argument the term “agricultural productivity” lacks a comparable and measurable standard. The Applicant’s definition includes 12 distinct, often competing traits (i.e. leaf area vs. seed yield). Because a modification could increase one trait (biomass) while decreasing another (fruit weight), the claim fails to provide a clear boundary for what constitutes “improved productivity”, leaving one skilled in the art to guess which trait to measure.
At least for these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 112(a) (Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 35-38, 40-51 and 53-54 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.
Applicant’s disclosure is as follows.
Soybean, Arabidopsis, and tobacco were transformed with an SRF-TF-domain-containing protein (SEQ ID NO: 1), which resulted in the stay-green phenotype and increased seed, shoot, and fruit (see examples 1-4). Soybean, Arabidopsis, and tobacco were transformed with RanGAP1 proteins having SEQ ID NO: 2 and 3 (see examples 2, 5, and 9), which resulted in increased seed, biomass, and shoot. SEQ ID NO:1 (SRF-TF-domain-containing protein), SEQ ID NO:2 (RanGAP1) and SEQ ID NO:3 (RanGAP1) are obtained from Trichoderma harzianum, as identified in Applicant’s Provisional Application No. 63/178171. RanGAP1 proteins from fungi and plants have a common LRR domain, but only plants have the additional WPP domain (example 10, figure 12). RanGAP1 native protein from potato (SEQ ID NO:11) was modified to produce variants having SEQ ID NO:12-17 (substitutions and/or deletions of the WPP motif/domain, or substitutions and/or deletions of the WPP motif/domain in addition to substitutions and/or deletions in the LRR domain) resulted in significantly increased shoot weight or average total weight compared to the native protein SEQ ID NO: 11 (p. 9, example 10). Furthermore, Applicant discloses that RanGAP1 proteins from plants (soy, rice, potato, Arabidopsis) that do not contain the WPP motif resulted in increased total weight in Arabidopsis (see pages 48-49, figure 16, example 11).
The claimed invention lacks adequate written description for the following reasons.
Applicant fails to adequately describe the structure and Increased biomass phenotype for the modified protein. Claim 35 the genus of wildtype RanGAP1 genes contains allelic variants that do not alter its function, and the WPP domain contains amino acids outside of the three amino-acid WPP sequence that may be mutated, truncated or deleted without affecting its functional activity. Applicant substituted a Trp11 with an Ala in SEQ ID NO:11 (p. 9). One skilled in the art cannot predict the structure or function of a RanGAP1 protein when it contains both a 90% sequence identity threshold and a mutated, truncated, or deleted WPP motif.
Specifically, when the Applicant has not described what are the structural locations for the LRR, WPP, Pfam regions in the wild-type RanGAP1. For example, how would one skilled in the art predictably identify these structures if one doesn’t know where it begins or ends, especially looking at a truncated version. Accordingly, a RanGAP1 sequence having 90% sequence identity to SEQ ID NO: 16 and a mutated, truncated or deleted WPP motif and/or domain is not adequately described.
Furthermore, while one skilled in the art can generate a population of sequences having 90% sequence identity to SEQ ID NOs:16 and 28, it is unpredictable which species within the population would also have increased biomass activity. The disclosure of SEQ ID NOs: 16 and 28 is not representative of sequences having 90% sequence identity to SEQ ID NOs: 16 and 28 and having increased biomass activity. No common structure or motif is disclosed.
Applicant has only disclosed other amino acid sequences (SEQ ID NO: 12-15 and 18) having at least 99% sequence identity to SEQ ID NO: 16, and SEQ ID NO: 17 having at least 94% sequence identity to SEQ ID NO: 16. Additionally, Applicant has only disclosed one other nucleotide sequence (SEQ ID NO: 29) having at least 94% sequence identity to SEQ ID NO: 28. Therefore, Applicant has not provided a representative number of sequences to show possession of sequences with as little as 90% sequence identity to SEQ ID NOs: 16 and 28, or allow one skilled in the art to identify sequences having at least 90% sequence identity that would produce increase biomass phenotype. See also Claims 37 and 38.
Additionally, in claim 36, there is no disclosure of the location of the LRR domain in the RanGAP1 protein, the mutation, truncation or deletion to be made in the LRR domain, and the resulting plant phenotype with increased biomass. The Arg190 and Asn219 of the wildtype RanGAP1 protein (SEQ ID NO:11) were substituted with Ala (p. 9), but it is unpredictable whether substitutions with other amino acids or at other positions, or other mutations, truncations or deletions in the LRR domain, would produce the plant traits in the working examples, without known the exact LRR sequence. Additionally, Applicant has not described the corresponding position to Arg190 and Asn219 of SEQ ID NO: 11. Moreover the lack of the residues that correspond to one or more position corresponding to Arg190 and Asn219 of a plant RanGAP1 ortholog of an undisclosed structure.
Claim 40 recites the phenotypes of the plant of claim 35. Dependent claim 40 does not address the structure of the wildtype RanGAP1 protein having 90% sequence identity to modified variant, the location of the WPP motif and/or domain, and the mutation, truncation or deletion to be made in the WPP motif and/or domain. See also claim 45.
With regard to claims 41 and 42, because the structure of the wild type RanGAP1 protein in claim 35 is not disclosed, the structures of the orthologs of said wild type RanGAP1 protein cannot be determined. Rendering unpredictable whether all sequences within the 90% sequence identity genus to SEQ ID NO:1 have the same functional activity. Applicant has not described the specific species that qualifies as an “ortholog plant” under claims 35. Additionally, the Applicant is referring to a wild-type RanGAP1 protein from an ortholog plant; rather the claim specifically recites an ortholog RanGAP1 protein derived from an ortholog plant (a twice removed relationship). Therefore, it is unpredictable what structures the genus of ortholog RanGAP1 proteins of ortholog plants would have the same functional activity. See also claims 46 and 47.
Claim 43 merely states that the RanGAP1 protein is “a gene edited version” of the endogenous RanGAP1 protein. However, absent a disclosure of the structure of the endogenous RanGAP1 protein, the structure of the gene edited RanGAP1 protein cannot be predictably determined. See also claim 48.
Claim 44 does not address any of the issues discussed above with regard to claim 35. Applicant failed to identify the positions of the SRF-TF-binding domain(s) of SEQ ID NO:1. From a population of sequences having 90% sequence identity to SEQ ID NO:1, one skilled in the art cannot predictably determine which sequences within said population retains at least one undisclosed SRF-TF-binding domain. Additionally, it is unpredictable whether all sequences within the 90% sequence identity to a protein having 90% sequence identity to SEQ ID NO:1 have the same functional activity. If not, there is inadequate disclosure with regard to which sequences within the 90% sequence identity scope would have the desired functional activity or produce a plant having a desired phenotype. See also claim 53 with regard to a sequence having 90% sequence identity to SEQ ID NO:1 Additionally, how would one skilled in the art distinguish or confirm sequences that are not putative.
Claims 49-51 lack adequate written description because the Applicant has not disclosed the regions where the mutations, truncations, or deletions need to occur to SEQ ID NO: 11 to arrive to SEQ ID NO: 16. Such as the positions where the mutations would occur on the LRR, WPP, pfam PF13943. Let alone 90% sequence identity to SEQ ID NO: 16. The Applicant does not address the mutations (additions, deletions, substitutions, and any combination thereof) within the 90% sequence identity to SEQ ID NO:16, or 90% sequence identity to SEQ ID NO:28, scope that would produce a plant having increased “agricultural productivity”. There is no evidence in the prior art and Applicant’s working examples that all sequences within said 90% sequence identity of these sequences would increase “agricultural productivity”. It is unpredictable which sequence(s) within the claimed 90% scope would produce a plant having “increased agricultural productivity”. Accordingly, sequences having 90% sequence identity to SEQ ID NO:16 and 90% sequence identity to SEQ ID NO:28 for increasing “agricultural productivity” are not adequately described.
Claim 54 lacks adequate written description because while one skilled in the art can produce a population of sequences having 90% sequence identity to a particular SEQ ID NO., 90% sequence identity to SEQ ID NOs: 16 having a mutated, truncated or deleted WPP domain at an undisclosed position of an undisclosed sequence cannot be determined or predicted.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111
Since the rejections have been modified to reflect the amendment to the claims, only the arguments that are relevant to the current rejections are addressed below.
Applicant argues that 90% sequence identity to the variants SEQ ID NOs: 16. Secondly, that Applicant claims that they have clearly defined on page 9 and figure 12 the structure of the LRR, WPP and Acidic domains and the pattern of modifications that anyone can follow.
(Remarks, December 30, 2025, page 12-14).
This argument has been fully considered but not found persuasive.
MPEP says," An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention. See, e.g., Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1323, 56 USPQ2d 1481, 1483 (Fed. Cir. 2000)." (MPEP, 2163/II,A,3, (a)).
In regard to Applicant’s 1st argument, the Applicant’s specification on shows >99% sequence identity to SEQ ID NO: 16. Claiming a 90% identity genus allows for 1924 distinct protein variants comprising mutations, truncations, or deletions. There is zero evidence that a protein with 1924 random mutations remains functional or stable. The Applicant has failed to provide a “representative species” at the lower end of the claimed range (i.e. 90-93%), making the claim an overreach. Additionally, Applicant has not proven that every 90% identical sequence to the truncated variants will function. A single amino acid change is the remaining LRR domain could potentially abolish the proteins core function “RanGTP/RanGDP gradient [is] critical for nuclear transport.”, leading to plant death rather than “increased biomass”.
In regard to Applicants 2nd argument, page 9 and figure 12 provided conceptual “cartoons” of domains (LRR, WPP and Acidic) domains, not precise molecular blueprints. A diagram of a “box” labeled WPP does not pinpoint which specific residues in cocoa, switchgrass, or coffee must be modifies. Because protein folding is unpredictable, a general “type” description for 20+ different crops is a research plant, not a disclosed invention. It unpredictable to know if the Applicant was in possession of the invention and sequences with as little as 90% sequence identity without identifying the regions/borders. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
At least for these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 112(a) (Enablement)
Claims 35-38, 40-51, and 53-54 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
Applicant’s disclosure is as set forth in the written description rejection above. Applicant has not fully enabled the claimed invention for the following reasons.
With regard to claim 35, the location of the WPP motif and/or domain of SEQ ID NO: 16 is not identified because it is deleted so how would one identify a non-present structure. It would require undue experimentation to determine the location of the WPP motif and/or domain to be targeted in of SEQ ID NO: 16 without further guidance. Specifically, the Applicant has not provided clear guidance where to mutate, truncate or delete on the LRR, WPP, Pfam regions. For example, how would one skilled in the art cannot predictably make these structures if one doesn’t know where it begins or ends, especially looking at a truncated version. Accordingly, a RanGAP1 sequence having 90% sequence identity to SEQ ID NO: 16 and a mutated, truncated or deleted WPP motif and/or domain is not adequately enabled.
Additionally, even if the structure of the sequence and the WPP motif and/or domain are recited in the claim, the number of possible mutations, truncations and additions to the WPP motif and/or domain is virtually ad infinitum. The breadth of "mutated" encompasses additions, deletions, substitutions and any combination thereof within the WPP motif and/or domain, aside from other mutations outside of the WPP motif and/or domain of the sequence. From this virtually ad infinitum population of sequences, no guidance is provided as to how one skilled in the art can readily make the desired or operable embodiments or readily eliminate inoperable embodiments without resorting to random trial and error requiring undue experimentation without proper instructions of where to modify and how much?
The state of the art teaches that some mutations will retain sequence functional activity while others do not. Thus, absent a disclosure of (1) the structure of the mutated sequence, such as SEQ ID NO:16 or 28, or (2) a disclosure of the structure of the RanGAP1 protein, the location of the WPP motif and/or domain within said protein, the position(s) of the WPP motif and/or domain to be targeted, the mutation, truncation or deletion at said position(s), and the phenotype resulting from said mutation, truncation or deletion of the WPP motif and/or domain, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without undue experimentation.
While one skilled in the art can readily produce a population of sequences having 90% sequence identity to SEQ ID NO:16 or SEQ ID NO:28, one skilled in the art cannot readily determine which of the 90% genetically modified structure(s) has the desired activity or produces a desired phenotype. No guidance is provided with regard to which region(s) of SEQ ID NO:16 or SEQ ID NO:28 can be altered, and which region(s) must be conserved. The state of the art teaches that some mutations will retain sequence functional activity while others do not. The claims do not indicate whether the sequence(s) having the 90% sequence identity is required to have a particular functional activity or produce a plant having a particular phenotype. Thus, for these reasons, one skilled in the art cannot make and use a sequence having 90% sequence identity to SEQ ID NO:16 or SEQ ID NO:28 as commensurate in scope with the claims without undue experimentation. See also claims 37 and 38.
Similarly, with regard to claim 36, while one skilled in the art can readily mutate, truncate or delete a LRR domain of a RanGAP1 protein, one skilled in the art cannot readily mutate, truncate or delete a domain without undue experimentation and location of desired modification. It would require undue experimentation to determine the location of the LRR domain to be targeted in SEQ ID NO: 16 since the LRR domain is deleted, without further guidance. Additionally, even if the structure of the RanGAP1 protein having a mutated, truncated or deleted WPP motif and/or domain and the LRR domain are recited in the claim, the number of possible mutations, truncations and additions to the LRR domain is virtually ad infinitum. The breadth of "mutated" encompasses additions, deletions, substitutions and any combination thereof within the LRR domain, aside from other mutations outside of the LRR domain of the sequence. From this virtually ad infinitum population of sequences, no guidance is provided as to how one skilled in the art can readily identify the desired or operable embodiments or readily eliminate inoperable embodiments without resorting to random trial and error requiring undue experimentation. In claim 35, there is no modified LRR domain, while in claim 36 there is a modified LRR domain. The phenotype of the plant of claim 35 is likely different from the phenotype of the plant of claim 36, because they recite different embodiments.
Additionally, the claim does not remedy the issue of a plant having a mutated, truncated or deleted WPP motif and/or domain of a RanGAP1 protein. The state of the art teaches that some mutations will retain sequence functional activity while others do not. Thus, absent a disclosure of (1) the structure of the mutated sequence, such as SEQ ID NO:16 or 28, or (2) a disclosure of the structure of the RanGAP1 protein, the location of the WPP motif and/or domain within said protein, the position(s) of the WPP motif and/or domain to be targeted, the mutation, truncation or deletion at said position(s), the phenotype resulting from said mutation, truncation or deletion of the WPP motif and/or domain, the location of the LRR domain within said protein, the position(s) of the LRR domain to be targeted, the mutation, truncation or deletion at said position(s), and the phenotype resulting from said mutation, truncation or deletion of the LRR domain, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without undue experimentation.
Even though claim 40 recites the phenotype of “increased agricultural productivity”, how would one skilled in the art distinguish between a genetically modified plant or other abiotic factors influencing increased agricultural productivity without undue experimentation.
With regard to claims 41-42, because the RanGAP1 protein having at least 90% sequence identity is not adequately enabled, one skilled in the art cannot readily mutate, truncate or delete an ortholog sequence without undue experimentation. See also claim 47.
Claim 44 does not address any of the issues discussed above with regard to claim 35. Additionally, there is no disclosure as to what phenotype is obtained from expressing the genus of sequences having 90% sequence identity to SEQ ID NO:1. It is unlikely that all sequences within the 90% sequence identity to SEQ ID NO:1 have the same functional activity. The phenotype of the plant of claim 35 is likely different from the phenotype of the plant of claim 44, because they recite different embodiments. However, no phenotype is recited for the plant of claim 44 to allow one skilled in the art to determine which combination(s) of mutated, truncated or deleted WPP motif and/or domain and 90% sequence identity to a putative non-plant SRF-TF-domain-containing SEQ ID NO:1 would produce the undisclosed desirable phenotype if the domain is not identified in the claim. See also claim 53 with regard to a sequence having 90% sequence identity to SEQ ID NO: 1. Absent of a disclosure of the embodiments discussed in claim 35 and further guidance as to how to determine which sequence(s) within the 90% sequence identity to SEQ ID NO:1 have the desired functional activity or produce a plant having a desired phenotype, one skilled in the art cannot make and use a plant having a modified RanGAP1 protein as set forth in claim 35 and a putative non-plant SRF-TF-domain-containing protein as commensurate in scope with the claims without undue experimentation.
With regard to claim 45, the phenotype of “increased agricultural productivity”, this phenotype is not fully enabled because the breadth of “agricultural productivity” encompasses all plant products, including oil content, protein content, genetic material, seed size, seed number, leaf size, number of leaves, number of lateral shoots, fresh/dry weight of leaves, flowers, stems, roots, etc., as well as all plant morphological and physiological characteristics. Because all plant proteins directly or indirectly affect “agricultural productivity”, one skilled in the art cannot determine the phenotype of “increased agricultural productivity” of a plant having a mutated, truncated or deleted WPP motif and/or domain of a RanGAP1 protein without excessive burden. Absent a recitation of a phenotype that can be readily identified and correlated with a plant comprising a RanGAP1 protein having a mutated, truncated or deleted WPP motif and/or domain, one skilled in the art cannot make and use a plant having the phenotype of “increased agricultural productivity” as commensurate in scope with the claims without undue experimentation. Lastly, how would one skilled in the art distinguish between a genetically modified plant or other abiotic factors influencing increased agricultural productivity?
With regard to claims 46 and 47, because of the reasons above, one skilled in the art cannot readily determine the structures of RanGAP1 orthologs (plant or non-plant sources) and mutate, truncate or delete their undisclosed WPP motif and/or domain without undue experimentation.
Claim 48 merely states that the RanGAP1 protein is endogenous and is gene edited to produce a RanGAP1 protein having a mutated, truncated or deleted WPP motif and/or domain. Claim 48 does not address any of the issues set forth above for claim 45.
With regard to claims 49-51, it should be noted that the 90% sequence identity is over the entire sequence and not limited to any particular region of SEQ ID NO:16 or SEQ ID NO:28. The phenotype of “increased agricultural productivity” is not enabled as discussed for claim 45. While one skilled in the art can readily produce a population of sequences having 90% sequence identity to SEQ ID NO:16 or SEQ ID NO:28, one skilled in the art cannot readily determine which of the 90% genetically modified structures would produce a plant having “increased agricultural productivity”. The phenotype of “increased agricultural productivity” is not correlated with any particular sequence structure. No guidance is provided with regard to which region(s) of SEQ ID NO:16 or SEQ ID NO:28 can be altered, and which region(s) must be conserved. The state of the art teaches that some mutations will retain sequence functional activity while others do not. The claims do not indicate whether the sequence(s) having the 90% sequence identity is required to have a particular functional activity to produce the “increased agricultural productivity” phenotype. Thus, for these reasons, one skilled in the art cannot make and use a sequence having 90% sequence identity to SEQ ID NO:16 or SEQ ID NO:28 to produce a plant having “increased agricultural productivity” phenotype as commensurate in scope with the claims without undue experimentation.
Claim 53 is not enabled for the reasons set forth in claim 44. The phenotype of “increased agricultural productivity” is also not enabled for the reasons set forth in claim 45.
Claim 54 is not enabled for the same reasons set forth in claim 35. Additionally, one skilled in the art cannot produce a population of sequences having 90% sequence identity to SEQ ID NO: 16 and 28 without further guidance and undue experimentation.
The nature of the invention is a plant and method of increasing agricultural productivity by expressing a RanGAP1 protein having a mutated, truncated or deleted WPP motif and/or domain in a plant. The breadth of the claims encompasses RanGAP1 proteins of any structure, or RanGAP1 protein structures whereby the region for mutation, truncation or deletion of the WPP motif and/or domain and the particular mutation, truncation or deleted WPP motif and/or domain are not identified. The state of the prior art does not teach a particular structure that can be correlated with a functional activity or the increased agricultural productivity plant phenotype. It is unpredictable which mutation, truncation or deletion of the WPP motif and/or domain would increase agricultural productivity. Applicant’s working examples are amino acid truncations or substitutions at specific positions of RanGAP1 proteins having particular SEQ ID Nos. Applicant provides no guidance as to how mutations, truncations and deletions of the WPP motif and/or domain of an undisclosed RanGAP1 protein, or of a sequence having 90% sequence identity to SEQ ID NO:16 or 28, can be determined from Applicant’s specific working examples. Given these difficulties, notwithstanding a relatively high level of ordinary skill of those in the art, the amount of experimentation would likely be extensive and undue.
Weighing all the Wands factors based on the totality of the record as discussed above, the Office determines that it would require undue experimentation for a person of ordinary skill in the art to make and use the invention as claimed.
Since the rejections have been modified to reflect the amendment to the claims, only the arguments that are relevant to the current rejections are addressed below.
Applicant argues that cloning and gene editing are “well within the level of ordinary skill,” so making the variants is feasible. Secondly, The Applicant claims the “structure-function” relationship (WPP disruption=increased biomass) is so predictable that any modification in that domain will work. Thirdly, Applicant argues that just because a claim is broad does not mean it is invalid, as long as they provided “representative” examples. Lastly, the Applicant claims a skilled artisan can “readily identify” which 90% identical sequences will work based on the provided “types” (1-9).
(Remarks, December 30, 2025, page 15-16).
This argument has been fully considered but not found persuasive.
MPEP states, "The Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id." (MPEP, 2164.01).
In regard to Applicant’s arguments, while the methods of genetically modifying are routine, the functional outcomes of a 10% sequence divergence in RanGAP1 is highly unpredictable. The Applicant provides no data for any variant at the 90% identity threshold, only for those nearly identical to SEQ ID NO: 16 and 28. Consequently, a skilled artisan would be required to engage in undue experimentation to screen which of millions of potential 90% identity permutations actually retain the “increased biomass” phenotype without compromising essential cellular transport functions.
As for the disclosed “Types 1-9” represent a narrow set of specific structural permutations, namely targeted mutations of the WPP domain, but these discrete functional modifications do not provide a representative sequence space or enabling guidance for the millions of random amino acid substitution permitted under the broader 90% sequence identity claim.
Just as Amgen’s “conservative substitutions” roadmap was insufficient, the Applicant’s “90% sequence identity” claim is more of a research plan than clear guidance. Applicant has not enabled the millions of permutations possible within that 10% variance especially since the Applicant has only provided data for 94%+ sequence identical variants. Specifically, needs to provide where and how to mutate in sequence with as little as 90% sequence identity.
At least for these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 112(d)(New)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 35-38, 40-51 and 53-54, are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In claim 35, there is no modified LRR domain, while in claim 36 there is a modified LRR domain. The phenotype of the plant of claim 35 is likely different from the phenotype of the plant of claim 36, because they recite different embodiments, thus not further limiting the claims invention. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/C.J.O./Examiner, Art Unit 1663
/PHUONG T BUI/Primary Examiner, Art Unit 1663