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 with traverse of Group I claims 1-12, and the species of PsbS, ZEP, and VDE in the reply filed on March 04, 2026 is acknowledged. Upon further consideration claims 1-15 are examined in the instant application, thus the group restriction is withdrawn. However, the species election remains and is made FINAL.
Claim Status
Claims 1-15, are pending and examined in the instant application. Claims 16-25, are cancelled.
Priority
This application is claiming the benefit of Provisional Application No.
63500518 filed May 05, 2023.
Information Disclosure Statement (IDS)
The IDS submitted on 10/14/2024 and 03/04/2026 have been considered. Signed copies are attached.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Pg. 60 para. [0117], (https://doi.org/10.l 186/gb-2007-8-2-rl9)
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-15, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. US 11572569 B2 (A) in view of Si et al. “Manipulating gene translation in plants by CRISPR–Cas9-mediated genome editing of upstream open reading frames”, 2020, Nat. Protoc. 15, 338–363 (U). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions encompass increasing expression of photosystem II subunit S (PsbS), zeaxanthin epoxidase (ZEP), and violaxanthin de-epoxidase (VDE).
In regard to claims 1-15, Long et al. teaches on a genetically modified plant comprising a “transfected” (i.e. transformed) nucleotide sequences encoding PsbS, ZEP, and VDE, operably linked to at least one expression control sequence (i.e. promoter), wherein the transcript levels of PsbS, ZEP and VDE are all increased as compared to a control plant lacking the transfected nucleotide sequences grown under the same conditions and the plant has improved growth under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions (claim 1). Additionally, Long et al. teaches many of the plant species found in claim 10 (claim 5).
Long et al. does not teach on specifically targeting the upstream reading frame (uORFs) in a transcript leader sequence (TLS).
In regard to claims 1-15, Si et al. teaches a method of using CRIPSR Cas 9 editing systems to target and disrupt the uORFs, specifically “the putative start codon of the uORF is mutated to AAA to prevent translation of the putative uORF” (i.e. TLS region) (pg. 6 second paragraph). Si et al. teaches that “uorfAtBRI mutants that enabled us to upregulate expression, resulting in different amounts of pORF protein [i.e. mORF]” (pg. 24 and Fig. 5) in Arabidopsis, iceberg lettuce, and tomato (pg. 7). Since, Applicant did not specify the location or positions of the uORF or TLS Si et al. reads on the claims. Lastly, Si et al. teaches that this method “achieves fine-tuning of gene translation in transgene-free derivatives, which accelerates the analysis of gene function and the improvement of crop traits” (Abstract).
Therefore, prior to the effective filing date, it would have been prima facie
obvious to one of ordinary skill in the art to substitute the method of using a promoter to increase expression of PsbS, ZEP, and VDE of Long et al. with the method of using CRISPR–Cas9-mediated genome editing of upstream open reading frames of Si et al. to increase expression of the endogenous PsbS, ZEP, and VDE gene in plants. The increased PsbS, ZEP, and VDE gene expression would improve plant growth, as taught by Long et al. The choice of using a promoter or CRISPR to increase expression is an experimental design choice well within the means of one skilled in the art without any surprising or unexpected results and with a reasonable expectation of success.
MPEP 2143 (b) states that “Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious." Id. at 301, 213 USPQ at 536” and “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007)”
Claim Rejections - 35 USC § 112(b)
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 1-15, 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 1, it is unclear how one skilled in the art can distinguish an endogenous PsbS, ZEP, or VDE polypeptide. No function or structure is recited for the mutated sequence. Does Applicant intend for the mutated sequence to be any sequence having the gene name. See also claims 2, 4 and 13-14.
In claim 1, uORFs and TLS are unclear. Applicant does not disclose the structure or location of these regions, or how is one supposed to edit these uORFs and TLS? What positions need to be edited?
In claim 1 the recitation of “edited nucleotide sequences are edited” is unclear. Is the plant already edited and further modifications are added? If so then what does the wild-type sequence look like? What is the structure?
In claim 2, the recitation “and/or wherein the edited endogenous” further broadens the claim, because it implies that the edits can be anywhere in the uORFs and not specifically in the TLS as claimed in claim 1. Applicant is advised to appropriately amend the claim.
In claims 2, 4-8 and 13-14, the recitation of “the endogenous PsbS, ZEP, or VDE gene/polypeptide” is unclear to which endogenous gene/polypeptide is Applicant referring to since in claim 1 which it depends from is open to many PsbS, ZEP, VDE genes.
In claim 2, the recitation of “a TLS” should be amended to “the TLS” for proper antecedent basis.
In claims 2, 4-7, “increase expression” lacks a comparative basis.
In claim 3, “efficiency” lacks a comparative basis.
In claim 3, (i) and (iii) are unclear how they differ? It seems like they are the same just rewritten differently. Therefore, not further limiting the claim.
Claims 3, 6 and 13-14 the recitation of “an endogenous” or “an uORF” implies at least two embodiments. However, only one is claimed and no structure has been disclosed.
In claim 5, the recitation ”further genetic modifications” are unclear. Applicant does not define what these modification look like? The location? The function? Or structure? And how do they differ from naturally occurring mutations?
In claims 8 and 11, the metes and bounds of “fluctuating light conditions” is unclear. The term “fluctuating” is not clearly defined in Applicant’s disclosure. For example, does that include 1 hour of light and 23 hours of darkness? Or 23 hours of light and 1 hour of darkness? Or intervals of light?
In claims 10 and 14, it is unclear whether the “optionally” clause is intended to be a claim limitation. Optional embodiments are not considered by the Office to be claim limitations.
In claim 10, 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 claim 11 the recitation of “an increase” is unclear. Applicant does not define how much does the rate need to increase to be considered “an increased rate”? is there different types of increased rates?
Claim 13 the recitation of “an endogenous” implies at least two embodiments. However, only one is claimed and no structure has been disclosed.
Clarification and/or correction is required.
Claim Rejections - 35 USC § 112(d)
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.
Claim 3, is 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. Claim 3 depend from claim 1 which specifies the edits are found in the TLS region. However, claim 3 broadens the scope to the entire uORF region which is a bigger region than just the TLS region. 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.
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 1-15, 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.
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant’s disclosure is as follows.
Applicant describes genetically modifying Nicotiana benthamiana plant by mutating the uORF in GmPsbS atg1 (SEQ ID NO:2) and ttg6 (SEQ ID NO:3), VuPsbS atg4 (SEQ ID NO:13) and ttg4 (SEQ ID NO:15), GmVDE atg1 (SEQ ID NO: 5), GmZEP ttg1 (SEQ ID NO: 11) resulting in increased expression of the respective gene (fig. 3b).
Claims encompass polypeptides having any structure, undescribed function and at undescribed location in the TLS.
The claimed invention lacks adequate written description for the following reasons. While one skilled in the art can generate a population of sequences and target the endogenous PsbS, ZEP, and VDE having a mutated TLS region, one skilled in the art cannot predictably determine which endogenous sequences PsbS, ZEP, and VDE with the mutated TLS result in increased expression. The claims do not recite a structure / function for the endogenous PsbS, ZEP, and VDE genes with the mutated TLS, or a structure / function for the mutated PsbS, ZEP, and VDE sequences with the mutated TLS, to distinguish one from the other. Additionally, “gene edits” encompass deletions, additions, substitutions, etc. yet Applicant has only described substitutions of 3 nucleotides, so it is unclear if these other variations would produce the claimed phenotype.
The instant claims recite endogenous N. benthamiana PsbS, ZEP, and VDE sequences based on only the name of the gene. However, the Applicant fails to disclose the specific structures of the naturally occurring mutants and allelic variants claims to encompass, specifically the location and regions of the uORF, TLS, and mORF, or the region that needs to be mutated to see increase of expression of PsbS, ZEP, and VDE. Because the disclosure of a single N. benthamiana sequence is not representative of the diverse sequences PsbS, ZEP, and VDE with the TLS region mutated across the entire species of plant, there are insufficient identifying characteristics to identify these variants without undue experimentation. Consequently, the Applicant has failed to provide either a representative number of species or common structural features necessary to support the claimed genus.
Additionally, claim 1 only recites the endogenous PsbS, ZEP, and VDE gene having the TLS region mutated. There are virtually an ad infinitum number of possible mutations to the recited sequences of the endogenous PsbS, ZEP, and VDE genes having a mutated TLS region. It is highly unpredictable from said ad infinitum number of possible mutations predict which mutation or combination of mutations would produce the claimed phenotypes. The undisclosed mutations does not allow one skilled in the art to predictably determine other mutations for producing the claimed phenotypes.
In regard to claim 5, the specification fails to describe the additional modifications that increase expression of one or more of the PsbS, ZEP, or VDE polypeptide. While these modifications may encompass the entire PsbS, ZEP, or VDE genes, the specification lacks the necessary details regarding edit locations, target regions or conserved sequences required to ensure the resulting polypeptide retain their functional activity.
In regard to claim 11, are directed to the phenotype. However, the specification fails to provide enough representative number of species with the claimed traits in claim 11. Therefore, it is unpredictable how one skilled in the art can appreciate that the Applicant was in possession of the invention as claimed.
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
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1-15, 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 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.
“The first paragraph of 35 U.S.C. § 112 requires, inter alia, that the specification of a patent enable any person skilled in the art to which it pertains to make and use the claimed invention. Although the statute does not say so, enablement requires that the specification teach those in the art to make and use the invention without ‘undue experimentation.’ In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is ‘undue.’” In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original); see also In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’”) “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” Wands, supra.
Some experimentation, even a considerable amount, is not “undue” if, e.g., it is merely routine, or if the specification provides a reasonable amount of guidance as to the direction in which the experimentation should proceed. Factors to consider 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. Id.
Applicant’s disclosure is as set forth above. The claimed invention is not enabled for the following reasons. To comply with 35 USC 112(a) enablement, one skilled in the art must be able to make and use the claimed invention.
(A) The breadth of the claims
The breadth of the claims encompasses any plant comprising at least one edit in an endogenous PsbS, ZEP, or VDE genes having any structure, wherein the mutation is in the TLS region.
(B) The nature of the invention.
The nature of the invention is a N. benthamiana plant comprising at least one mutation in an endogenous PsbS, ZEP, or VDE genes having any structure, wherein the mutation is in the TLS region resulting improved non-photochemical quenching relaxation.
(C) The state of the prior art
The state of the prior art does not teach particular structures or mutations that can be correlated with a functional activity, nor does it disclose the mutations in the TLS region conferring claimed function.
(D) The level of one of ordinary skill
The level of one of ordinary skill in the art is high.
(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.
The claimed invention lacks adequate enabling guidance for the following reasons. With regard to claim 1, it should be noted that the mutations are located in the TLS region having any structure. Again, no functional activity is recited for population of sequences having said edit. No resulting objective is recited for the sequence having said mutated PsbS, ZEP, and/or VDE genes having a mutated TLS region. While one skilled in the art can readily produce a population of sequences having a mutation in the TLS region of PsbS, ZEP, and/or VDE polypeptides, one skilled in the art cannot readily determine which of the structures are endogenous PsbS, ZEP, and/or VDE genes having an undisclosed function, as seen in claim 1. No guidance or working examples are provided to allow one skilled in the art predict which identity genus are endogenous PsbS, ZEP, and/or VDE sequences or which region(s) of TLS, uORF, mORF, or the entire gene can be altered, and which region(s) must be conserved. Additionally, “gene edits” encompass deletions, additions, substitutions, etc. yet Applicant has only taught substitutions of 3 nucleotides, so it is unclear if these other variations would produce the claimed phenotype. No structure and function is recited for the endogenous PsbS, ZEP, and/or VDE genes or for the mutated PsbS, ZEP, and/or VDE sequences. 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 mutation 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 a mutation in the TLS region of PsbS, ZEP, and/or VDE polypeptides as commensurate in scope with the claims without undue experimentation. See also claim 3, the claim is direct to mutations to the entire uORF and not limited to the TLS region. The same reasons above the Applicant has not taught the structures, enough working examples, or how to make and use said invention without undue experimentation.
With regard to claims 5, while one skilled in the art can readily construct polypeptides with said mutations in said uORF, TLS, or mORF, one skilled in the art cannot construct the polypeptide without the location, and conserved regions to maintain, without undue experimentation. Specifically, the additional gene modifications that increase expression of one or more PsbS, ZEP, or VDE genes, which include up to the entire gene. Additionally, as mentioned above there is a lack of disclosed functional activity which makes it highly unpredictable to determine the unknown function without undue experimentation. Furthermore, the lack of clear guidance on the resulting objective of said polypeptide one skilled in the art would find it impossible to know what to do with the polypeptide, or what is the purpose of the mutations? Therefore, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without undue experimentation.
In regards to claim 10, even though Applicant further clarifies what species of plant to use the nucleotide sequence that encodes a polypeptide having a mutated PsbS, ZEP, and/or VDE genes having a mutated TLS region, it is still lacking guidance on the phenotype that is required for one skilled in the art should produce. For example, Kromdijk et al. “Relaxing non-photochemical quenching (NPQ) to improve photosynthesis in crops”, 2022, BURLEIGH DODDS SERIES IN AGRICULTURAL SCIENCE, Understanding and improving crop photosynthesis, pp. 113–130 (V) teaches that “when the same approach was used in Arabidopsis, productivity was negatively affected (Garcia-Molina and Leister, 2020). Thus, similar to the effects of overexpression of PsbS, the effects of VPZ overexpression on photosynthetic efficiency and productivity seem to be specific to species and growth conditions” (p 14). Suggesting that overexpression PsbS, VDE, and ZEP is plant specific and unpredictable if one skilled in the art would predictably produce a plant with said function. Therefore, the lack of phenotype makes it unpredictable for one skilled in the art to produce a plant or part of a plant with a particular unknown phenotype without undue experimentation.
With regard to claim 11, the nature of the invention is a mutation in a N. benthamiana PsbS, ZEP, and/or VDE genes resulting the plant has improved growth under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions; the plant has increased lutein under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions; the plant has increased photosynthetic efficiency under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions; the plant has improved photoprotection efficiency under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions; the plant has an increased rate of relaxation of non-photochemical quenching (NPQ) under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions; and/or the plant has improved quantum yield and CO2 fixation under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions. The scope of the claims encompasses deletions, insertions, substitutions, and any combination thereof in any region of the endogenous PsbS, ZEP, and/or VDE genes having a mutated TLS region. Applicant’s working examples are 3 nucleotide substitutions in the uORF in GmPsbS atg1 (SEQ ID NO:2) and ttg6 (SEQ ID NO:3), VuPsbS atg4 (SEQ ID NO:13) and ttg4 (SEQ ID NO:15), GmVDE atg1 (SEQ ID NO: 5), GmZEP ttg1 (SEQ ID NO: 11) to produce the increased expression. Applicant has no working example of a mutation of any other plants and additional modification as claimed in claim 5 having the claimed phenotype. It is unpredictable whether a mutation in endogenous PsbS, ZEP, and/or VDE genes would produce the claimed phenotypes, and if so, it is not known which mutation(s) in what location(s) of PsbS, ZEP, and/or VDE genes would do so.
It is unpredictable which variant would control the claimed phenotype. Applicant’s working examples are working examples are 3 nucleotide substitutions in the uORF of uORF in GmPsbS atg1 (SEQ ID NO:2) and ttg6 (SEQ ID NO:3), VuPsbS atg4 (SEQ ID NO:13) and ttg4 (SEQ ID NO:15), GmVDE atg1 (SEQ ID NO: 5), GmZEP ttg1 (SEQ ID NO: 11) to produce the increased expression. Applicant has no working example of a mutation of all PsbS, ZEP, or VDE for producing claimed phenotype of claim 11. Only producing less than 2 mutants of each is not sufficient working examples to provide enough guidance for one skilled in the art. It is unpredictable whether a mutation in TLS region alone would produce the claimed phenotypes, and if so, it is not known which mutation(s) in what location(s) of PsbS, ZEP, and/or VDE genes would do so. The gene edits recited in claim 1 indicates there are many naturally occurring wildtype PsbS, ZEP, and/or VDE genes having mutations that do not produce the claimed phenotypes. Other than the 3 nucleotide substitutions in the uORF of uORF in GmPsbS atg1 (SEQ ID NO:2) and ttg6 (SEQ ID NO:3), VuPsbS atg4 (SEQ ID NO:13) and ttg4 (SEQ ID NO:15), GmVDE atg1 (SEQ ID NO: 5), GmZEP ttg1 (SEQ ID NO: 11), no guidance is provided for one skilled in the art to predictably determine other combinations of mutations to produce the claimed phenotypes without resorting to random trial and error requiring undue experimentation. 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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-15, are rejected under 35 U.S.C. 103 as being obvious over Kromdijk, et al. “Improving photosynthesis and crop productivity by accelerating recovery from photoprotection”, 2016, Science. 354:857-861, (V) in view of Si et al. “Manipulating gene translation in plants by CRISPR–Cas9-mediated genome editing of upstream open reading frames”, 2020, Nat. Protoc. 15, 338–363 (U). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions encompass increasing expression of photosystem II subunit S (PsbS), zeaxanthin epoxidase (ZEP), and violaxanthin de-epoxidase (VDE).
In regard to claims 1-15, Kromdijk et al. teach that PsbS, ZEP, and VDE polypeptides are natural polypeptides in native (wild-type) plants (p.858, fig 2). Kromdijk et al. further teach that PsbS, ZEP, and VDE expression increase in plants when plant leaves are exposed to fluctuated light conditions (a natural condition) as compared to that are not exposed to fluctuated light condition (p. 858, fig 1). Kromdijk et al. teach on “Nicotiana tabacum was transformed with the coding sequences of Arabidopsis VDE, ZEP, and PsbS under the control of different promoters for expression in leaves” and “All three VPZ lines showed increases in total (transgenic plus native) transcript levels of VDE (10-fold), PsbS (threefold), and ZEP (sixfold) relative to those of the wild type (WT)” (pg. 859 Fig. 2, A, C, and E). The plant line expressing all three VDE, PsbS, and ZEP (VPZ) polypeptides resulted in an increase in growth (Fig.5.), photosynthetic efficiency (Fig. 4D), CO2 assimilation (Fig. 4B), and “[u]nder fluctuating light, the VPZ lines showed faster and greater decreases in NPQ after transitions from high to low light, relative to that of WT (Fig. 4F and fig. S5H), which increased the quantum yield of CO2 assimilation by 14% (Fig. 4B), providing proof that on transition from high to low light, NPQ does indeed limit photosynthetic efficiency” (p.860). Overall, Kromdijk et al. teach how increasing expression of PsbS, ZEP, and VDE results in improved plant performance in N. tabacum.
Kromdijk et al. does not teach on specifically targeting the upstream reading frame (uORFs) in a transcript leader sequence (TLS) to increase expression of PsbS, ZEP, and VDE.
In regard to claims 1-15, Si et al. teaches a method of using CRIPSR Cas 9 editing systems to target and disrupt the uORFs, specifically “the putative start codon of the uORF is mutated to AAA to prevent translation of the putative uORF” (i.e. TLS region) (pg. 6 second paragraph). Si et al. teaches that “uorfAtBRI mutants that enabled us to upregulate expression, resulting in different amounts of pORF protein [i.e. mORF]” (pg. 24 and Fig. 5) in Arabidopsis, iceberg lettuce, and tomato (pg. 7). Since, Applicant did not specify the location or positions of the uORF or TLS Si et al. reads on the claims. Lastly, Si et al. teaches that this method “achieves fine-tuning of gene translation in transgene-free derivatives, which accelerates the analysis of gene function and the improvement of crop traits” (Abstract). Overall, Si et al. teach on the motivation to use CRISPR editing systems to target the uORF to increase expression of desired genes.
Therefore, prior to the effective filing date, it would have been prima facie
obvious to one of ordinary skill in the art to substitute the method of using a promoter to increase expression of PsbS, ZEP, and VDE of Kromdijk et al. (A) with the method of using CRISPR–Cas9-mediated genome editing of upstream open reading frames of Si et al. to increase expression of the endogenous PsbS, ZEP, and VDE gene in plants. The increased PsbS, ZEP, and VDE gene expression would improve plant growth, as taught by Kromdijk et al (A). The choice of using a promoter or CRISPR to increase expression is an experimental design choice well within the means of one skilled in the art without any surprising or unexpected results and with a reasonable expectation of success.
MPEP 2143 (b) states that “Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious." Id. at 301, 213 USPQ at 536” and “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007)”
Accordingly, the claimed invention is prima facie obvious in view of the prior art.
Claims 1-15, are rejected under 35 U.S.C. 103 as being obvious over Long et al. US 11572569 B2 (A) in view of Si et al. “Manipulating gene translation in plants by CRISPR–Cas9-mediated genome editing of upstream open reading frames”, 2020, Nat. Protoc. 15, 338–363 (U). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions encompass increasing expression of photosystem II subunit S (PsbS), zeaxanthin epoxidase (ZEP), and violaxanthin de-epoxidase (VDE).
In regard to claims 1-15, Long et al. teaches on a genetically modified plant comprising a “transfected” (i.e. transformed) nucleotide sequences encoding PsbS, ZEP, and VDE, operably linked to at least one expression control sequence (i.e. promoter), wherein the transcript levels of PsbS, ZEP and VDE are all increased as compared to a control plant lacking the transfected nucleotide sequences grown under the same conditions and the plant has improved growth under fluctuating light conditions as compared to the control plant grown under the same fluctuating light conditions (claim 1). Additionally, Long et al. teaches many of the plant species found in claim 10 (claim 5).
Long et al. does not teach on specifically targeting the upstream reading frame (uORFs) in a transcript leader sequence (TLS).
In regard to claims 1-15, Si et al. teaches a method of using CRIPSR Cas 9 editing systems to target and disrupt the uORFs, specifically “the putative start codon of the uORF is mutated to AAA to prevent translation of the putative uORF” (i.e. TLS region) (pg. 6 second paragraph). Si et al. teaches that “uorfAtBRI mutants that enabled us to upregulate expression, resulting in different amounts of pORF protein [i.e. mORF]” (pg. 24 and Fig. 5) in Arabidopsis, iceberg lettuce, and tomato (pg. 7). Since, Applicant did not specify the location or positions of the uORF or TLS Si et al. reads on the claims. Lastly, Si et al teaches that this method “achieves fine-tuning of gene translation in transgene-free derivatives, which accelerates the analysis of gene function and the improvement of crop traits” (Abstract). Overall, Si et al. teach on the motivation to use CRISPR editing systems to target the uORF to increase expression of desired genes.
Therefore, prior to the effective filing date, it would have been prima facie
obvious to one of ordinary skill in the art to substitute the method of using a promoter to increase expression of PsbS, ZEP, and VDE of Long et al. with the method of using CRISPR–Cas9-mediated genome editing of upstream open reading frames of Si et al. to increase expression of the endogenous PsbS, ZEP, and VDE gene in plants. The increased PsbS, ZEP, and VDE gene expression would improve plant growth, as taught by Long et al. The choice of using a promoter or CRISPR to increase expression is an experimental design choice well within the means of one skilled in the art without any surprising or unexpected results and with a reasonable expectation of success.
MPEP 2143 (b) states that “Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious." Id. at 301, 213 USPQ at 536” and “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007)”
Accordingly, the claimed invention is prima facie obvious in view of the prior art.
Conclusion
No claims are allowed.
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/C.J.O./Examiner, Art Unit 1663 /Amjad Abraham/SPE, Art Unit 1663
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