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 50-55, 57-70, 72 and 74 are pending and examined. Claims 1-49, 56, 71 and 73 have been cancelled.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 25 June 2026 has been entered.
Claim Objections
Claim 54 is objected to for using “a” as opposed to the definitive article --the-- to refer back to a previous claims. It is suggested the claim be amended to the limitations of claim 66.
Appropriate action is advised.
Claim Rejections - 35 USC § 112
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 50-55, 57-70, 72 and 74 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.
Claim 50 is drawn to a vector system for modifying genetic material in a plant cell without introducing exogenous DNA into the plant cell.
The metes and bounds of the claim are indefinite because it is not clear how one modifies genetic material in a cell without introducing polynucleotides into the cell to modify the genetic material in said cell.
Claim 50 also recites the limitation the second polynucleotide sequence is inserted into the TSWV genome segment. The metes and bounds of the claim are indefinite because it is not clear what genome segment the polynucleotide is introduced into.
Claim 60 presents the same issue and is therefore rejected for the same reason as provided for claim 50.
Claims 51-55, 57-59, 61-70, 72 and 74 are rejected for depending upon a rejected base claim and for failing to remedy the issues of indefiniteness.
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 50-55, 57-70, 72 and 74 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being arguably enabling for a vector system comprising SEQ ID NO: 1, 2 and 5 wherein CRISPR/Cas9 effector protein is inserted into SEQ ID NO: 2 and a guide RNA is inserted into SEQ ID NO: 1, does not reasonably provide enablement for the vector system as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In In re Wands (8 USPQ2d 1400 (CAFC 1988)), the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation". These factors include: (a) the quantity of experimentation; (b) the amount of guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the predictability of the prior art; (g) the breadth of the claims; and (h) the relative skill in the art. The factors are analyzed in turn for the instant case as follows:
Here, the claims are broadly drawn to a recombinant virus vector system comprising TSWV genome segments having as little as 90% sequence identity to SEQ ID NO: 1, 2 and 3, respectively wherein the M segment comprises a sequence coding for a glycoprotein precursor (GP) and at least a first heterologous sequence encoding a CRISPR/Cas effector protein inserted into the M genome segment to replace the all or part of the GP and at least a second heterologous nucleotide sequence encoding a CRISPR guide RNA inserted into the TSWV genome segment, wherein the system further comprises at least one RNA silencing suppressor, wherein the first sequence is linked to a viral mRNA transcription cis-element and wherein the S segment comprises the second sequence operably linked to a viral mRNA transcription cis-element and the L segment is codon optimized and comprises SEQ ID NO: 5, wherein the second sequence in the S segment replaces the non-structural protein (NSs), wherein the segments are in molar ratios of 1~2(L):2~10(M):1~2(S), plants produced from said system, a method for modifying the genetic material of a plant cell by using said system, and a kit comprising said system.
Meanwhile, the specification teaches that all three TSWV S, M and L genome segments are needed for expression of recombinant genes in plant cells (e.g., see Example 2 and p. 49). However, the specification also teaches that the M genomic segment is not suitable for rescue of recombinantly expressed Cas12a-crRNA (p. 52, last ¶). Moreover, the specification teaches that it is a specific ratio of S, M and L genome segments that is required for functional TSWV-Cas12a-crRNA (p. 52, last ¶).
In the instant matter, the claims encompass a vast genus of viral vectors yet the specification only teaches a single embodiment of the invention: a TSWV vector designed using the nucleic acid sequences of SEQ ID NO: 1, 2 and 3 as opposed to nucleic acid sequences having as little as 90% sequence identity to SEQ ID NO: 1, 2 and 3.
Here, and for example, because claim 50 encompasses nucleic acid sequences having as little as 90% sequence identity to SEQ ID NO: 1, the vector of claim 50 encompasses a polynucleotide sequence having 296 nucleic acid substitutions relative to SEQ ID NO: 1 and would encompass 3296 distinct gene variants.
However, without teaching where in the sequence of SEQ ID NO: 1 such variations can be sustained (or in SEQ ID NO: 2 and 3), one would be unable to predictably make and/or use the genus of polynucleotide sequences that retain TSWV functional activity to express the effector and guide proteins to target or modify genomic sequences in a plant cell.
These teachings are critical in light of the state of the art which teaches that that reconstitution of NSVs in planta is particularly difficult as all constructs need to be delivered in to the same plant cell, because the RdRp of TSWV is exceptionally large making it difficult to express, and because achieving the proper ratios of all three genome segments is not easy or consistent (Feng et al, 2020, PNAS, 117:1181-1190; see p. 1182, col. 1, ¶ 3; see also p. 1187, col. 2, ¶ 1).
Feng et al further teach that S antigenomic, M genomic and L antigenomic DNA of TSWV wherein the M genomic DNA is codon optimized results in systemic infection and viral rescue whereas the nonstructural protein of the S segment (NS) interfered with rescue of genomic RNA (see Abstract; see also p. 1184, col. 1, ¶ 2 bridging p. 1185; see also p. 1188, col. 2, last ¶).
Moreover, Feng et al teach that particular promoters should be used in order to successfully express the aforementioned minireplicon system (e.g., see p. 1182, col. 2, penultimate ¶; see also p. 1186, col. 2, last ¶). Here, the specification suggests that any promoter may be used but only teaches, in fact, the use of a double 35S promoter (e.g., see Figure 3).
Thus, the art makes clear that it is not any promoter or polynucleotide sequence of TSWV permits expression of a sequence of interest. Rather, it is a specific promoter or specific sequences of polynucleotides of TSWV that permits expression of a sequence of interest in a plant cell.
Here, the instant specification has merely taught that a particular set of TSWV polynucleotide sequence may introduce a sequence specific nucleic acid modifying enzyme, and has failed to teach any other polynucleotide sequence to allow one to predictably make and use the genus of virus vector systems, methods of using said system and kits comprising said system as broadly claimed.
Therefore, in light of the extreme breadth of the claims, the failure of the specification to teach a structure-function correlation for the TSWV segments as claimed, the lack of working examples and the state of the art which teaches that specific TSWV polynucleotide sequences are required to express a polynucleotide of interest, the skilled artisan would be required to engage in impermissible and excessive trial and error experimentation.
Claims 50-55, 57-70 and 72 REMAIN rejected, and 74 is NOW 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.
Instant claims 50-55, 57-70, 72 and 74 are broadly drawn to a recombinant virus vector system comprising TSWV genome segments having as little as 90% sequence identity to SEQ ID NO: 1, 2 and 3, respectively wherein the M segment comprises a sequence coding for a glycoprotein precursor (GP) and at least a first heterologous sequence encoding a CRISPR/Cas effector protein inserted into the M genome segment to replace the all or part of the GP and at least a second heterologous nucleotide sequence encoding a CRISPR guide RNA inserted into the TSWV genome segment, wherein the system further comprises at least one RNA silencing suppressor, wherein the first sequence is linked to a viral mRNA transcription cis-element and wherein the S segment comprises the second sequence operably linked to a viral mRNA transcription cis-element and the L segment is codon optimized and comprises SEQ ID NO: 5, wherein the second sequence in the S segment replaces the non-structural protein (NSs), wherein the segments are in molar ratios of 1~2(L):2~10(M):1~2(S), plants produced from said system, a method for modifying the genetic material of a plant cell by using said system, and a kit comprising said system.
The specification describes that all three TSWV S, M and L genome segments are needed for expression of recombinant genes in plant cells (e.g., see Example 2 and p. 49). However, the specification also describes that the M genomic segment is not suitable for rescue of recombinantly expressed Cas12a-crRNA (p. 52, last ¶). Moreover, the specification describes that it is a specific ratio of S, M and L genome segments that is required for functional TSWV-Cas12a-crRNA (p. 52, last ¶).
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.
In the instant matter, the claims encompass a vast genus of viral vectors not limited to those derived from TSWV yet the specification only describes a single embodiment of the invention: a TSWV vector designed using the nucleic acid sequences of SEQ ID NO: 1, 2 and 3 as opposed to nucleic acid sequences having as little as 90% sequence identity to SEQ ID NO: 1, 2 and 3.
Here, and for example, because claim 52 encompasses nucleic acid sequences having as little as 90% sequence identity to SEQ ID NO: 1, the tospovirus vector of claim 50 encompasses a polynucleotide sequence having 296 nucleic acid substitutions relative to SEQ ID NO: 1 and would encompass 3296 distinct gene variants.
However, without describing where in the sequence of SEQ ID NO: 1 such variations can be sustained (or in SEQ ID NO: 2 and 3), one would not be led to believe that Applicant was in possession of the genus of polynucleotide sequences that retain TSWV functional activity to express the effector and guide proteins to target or modify genomic sequences in a plant cell.
This description is paramount in light of the state of the art which describes that that reconstitution of NSVs in planta is particularly difficult as all constructs need to be delivered in to the same plant cell, because the RdRp of TSWV is exceptionally large making it difficult to express, and because achieving the proper ratios of all three genome segments is not easy or consistent (Feng et al, 2020, PNAS, 117:1181-1190; see p. 1182, col. 1, ¶ 3; see also p. 1187, col. 2, ¶ 1).
Feng et al further describe that S antigenomic, M genomic and L antigenomic DNA of TSWV wherein the M genomic DNA is codon optimized results in systemic infection and viral rescue whereas the nonstructural protein of the S segment (NS) interfered with rescue of genomic RNA (see Abstract; see also p. 1184, col. 1, ¶ 2 bridging p. 1185; see also p. 1188, col. 2, last ¶).
Moreover, Feng et al describe that particular promoters should be used in order to successfully express the aforementioned minireplicon system (e.g., see p. 1182, col. 2, penultimate ¶; see also p. 1186, col. 2, last ¶). Here, the specification suggests that any promoter may be used but only describes, in fact, the use of a double 35S promoter (e.g., see Figure 3).
Thus, the art makes clear that it is not any promoter or polynucleotide sequence of TSWV permits expression of a sequence of interest. Rather, it is a specific promoter or specific sequences of polynucleotides of TSWV that permits expression of a sequence of interest in a plant cell.
The Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material." Id.
Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus." Id. See MPEP 2163.
Applicant should note that the written description requirement serves to warn an innocent purchaser of the infringement of a patent, and conversely requires the patentee to distinguish the invention in the disclosure, and thus prevents the inventor from practicing upon the credulity or fears of other persons or from pretending that the invention is more than what it is. see Vas-Cath Inc. v. Mahurkar 1991 (CA FC) 19 USPQ2d 1111, 1115.
Here, the instant specification has merely described that a particular set of TSWV polynucleotide sequence may introduce a sequence specific nucleic acid modifying enzyme, and has failed to describe any other polynucleotide sequence of a tospovirus that would persuade a skilled artisan that Applicant was in possession of the genus of virus vector systems, methods of using said system and kits comprising said system as broadly claimed.
As such, these claims are “reach through” claims in which Applicant has only described a starting material and at least one method step, but has not described the resulting product such that the genus of products that can be produced by the recited method steps and materials is so large that one of skill in the art would not readily envision the members of the claimed genus. (See Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004)).
Therefore, in light of the extreme breadth of the claims, the failure of the specification to describe a representative number of species from the broad genus of tospovirus polynucleotide sequences, the lack of working examples and the state of the art which describes that specific TSWV polynucleotide sequences are required to express a polynucleotide of interest, the skilled artisan would not be of the opinion that Applicant was in possession of the invention as broadly claimed.
Response to Arguments
Applicant traverses the rejection of the claims because the claims recite 90% identity which is consistent with the official species demarcation criterion for the family TospoviridaeI to which TSWV belong (Applicant reply dated 26 May 2026, p. 1, ¶ 4).
This argument is not persuasive for the reasons as set forth above. First, the specification fails to describe, in fact, a representative number of species of TSWV genome segments as claimed that retain functional activity (e.g., see sequence search results dated 03 June and 04 June 2026). Second, the specification has failed to describe any of the domains or motifs that are required to confer functional activity.
This description is critical because in light of the art as noted above, and because Applicant even admits on page 2 in the Declaration filed under 37 C.F.R. section 1.132 submitted on 07 August 2026 that:
experimental data further demonstrates critical unpredictable differences in vector compatibility. When attempting to rescue TSWV vectors carrying the CRISPR/Cas12a inserts using the only functional combination taught by Feng et al. S(+) + M(₊) + L(+)opt, no viable recombinant virus could be recovered, or the rescued viruses suffered massive deletion of exogenous Cas sequences. In sharp contrast, the S(+) + M(₊) + L(+)opt configuration established in the claimed invention enables stable rescue and systemic infection of TSWV vectors carrying diverse large nuclease cargos.
Thus, it is clear that specific structures are required to predictably possess a functional vector system as claimed rather than a genus of TSWV genomic segments as claimed.
Claim Rejections - 35 USC § 103
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.
Claim(s) 50-55, 57-70 and 72 REMAIN rejected, and 74 is NOW rejected, under 35 U.S.C. 103 as being unpatentable over Harling et al (Patent No. US 11,492,630 B2) and Cody et al (2017, Plant Physiology, 175:23-35) and Ali et al (2015, Molecular Plant 8, 1288-1291) and Gao (2019, New Phytologist, 223:2120-2133) in view of Feng et al (2020, PNAS, 117:1181-1190) and Hu et al (2011, Arch Virol., 156(10)1905-1908) and in further view of Fazio et al (1980, Archives of Virology, 63:305-309).
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.
Claims 50-55 and 57-70, 72 and 74 are broadly drawn to a recombinant virus vector system comprising TSWV genome segments having as little as 90% sequence identity to SEQ ID NO: 1, 2 and 3, respectively wherein the M segment comprises a sequence coding for a glycoprotein precursor (GP) and at least a first heterologous sequence encoding a CRISPR/Cas effector protein inserted into the M genome segment to replace the all or part of the GP and at least a second heterologous nucleotide sequence encoding a CRISPR guide RNA inserted into the TSWV genome segment, wherein the system further comprises at least one RNA silencing suppressor, wherein the first sequence is linked to a viral mRNA transcription cis-element and wherein the S segment comprises the second sequence operably linked to a viral mRNA transcription cis-element and the L segment is codon optimized and comprises SEQ ID NO: 5, wherein the second sequence in the S segment replaces the non-structural protein (NSs), wherein the segments are in molar ratios of 1~2(L):2~10(M):1~2(S), plants produced from said system, a method for modifying the genetic material of a plant cell by using said system, and a kit comprising said system
Harling et al teach methods for the targeted modification of nucleic acid regions in plant using the CRISPR/Cas system and wherein the CRISPR/Cas system is introduced using a vector system comprising single-strand RNA viruses having various advantages (see Abstract; see also col. 15 bridging col. 16; see col. 66, Examples 2, 5 and 10). Harling et al teach that TMV is a suitable virus for the claimed methodology (col. 76, ¶ 1).
Similarly, Cody et al teach multiplexed gene editing and protein overexpression using a TMV viral vector which obviates the prior art problems of using CRISPR based editing processes in plants (see Abstract; see also p. 23, col. 2, ¶ 1; see also p. 24, col. 1, ¶ through col. 2). The use of Streptococcus pyogenes CRISPR/Cas9 was known in the art (e.g., see p. 23, col. 1).
Cody et al teach that CP deletion prevents the virus from systematically moving throughout the plant while still allowing localized cell to cell movement through the movement protein (p. 24, col. 1, ¶ 1).
Cody et al specifically teach and suggest viral vectors may be used to co-deliver Cas9 and sgRNA to host plants and that there are a limited number of viral vectors that will tolerate an insertion the size of Cas9 ORF (p. 31, col. 1, ¶ 2).
Still more, Ali et al teach the predictable use of a viral vector for introducing the CRISPR/Cas9 system to target a desired polynucleotide sequence (p. 1288, col. 2, ¶ 1). Ali et al teach that the virus mediated genome editing platform is not limited to vectors derived from TRV but that other RNA viruses could also be used to deliver gRNA molecule to various plant species (p. 1290, col. 2, ¶ 1).
Or see Gao et al, which teaches the predictable introduction of large effector proteins using negative-stranded RNA viruses for modifying genetic material without introducing exogenous DNA into the host genome (e.g., see Abstract; see also p. 2125, col. 2, last ¶).
Thus, while Harling et al and Cody et al and Ali et al and Gao et al teach that it was known in the art to use different viral vectors for introducing a sequence specific nucleic acid modifying enzyme to target and cleave a specific genomic sequence in a plant cell, the issue is whether one would have modified the teachings of Harling et al and Cody et al and Ali et al and Gao et al by using a TSWV viral vector as opposed to a TMV or TRV or BYSMV viral vector.
To this point, Feng et al teach that reconstitution of NSVs in plana is particularly difficult as all constructs need to be delivered into the same plant cell, and because the RdRp of TSWV is exceptionally large making it difficult to express, and because achieving the proper ratios of all three genome segments is not easy or consistent (p. 1182, col. 1, ¶ 3; see also p. 1187, col. 2, ¶ 1).
In particular, Feng et al teach that S antigenomic, M genomic and L antigenomic DNA of TSWV wherein the M genomic DNA is codon optimized resulted in systemic infection and viral rescue with the addition of various RNAi suppressors including P19, HcPro and γb whereas the nonstructural protein of the S segment (NS) interfered with rescue of genomic RNA (see Abstract; see also p. 1184, col. 1, ¶ 2 bridging p. 1185; see also p. 1188, col. 2, last ¶). These constructs included or excluded reported genes (e.g., see p. 1186, col. 1).
Feng et al teach that the choice of plant promoter is one of the major and critical factors for the construction of a reverse genetics system for TSWV, and that the 35S/Pol II promoter may be successfully used (p. 1186, col. 2, last ¶ par.). VSRs such as P19 increased expression, and the GP of the segment may be replaced with a heterologous polynucleotide (p. 1183, col. 2, ¶ 1 and last ¶).
Feng et al teach that TSWV has a very broad host range infecting more than 1,000 plant species over 80 families (p. 1181, col. 1, ¶ 1).
Hu et al teach that the S, M and L genomic segments as claimed were known and available in the art (see Attachment A in the Office action dated 26 February 2026).
Fazio et al teach that it was known in the art the Ribavirin may be used to control TSWV systemic infection (e.g., see Abstract).
Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Harling et al and Cody et al and Ali et al and Gao et al by instead using TSWV as a viral vector as taught by Feng et al because the viral vectors are functionally equivalent and could be used in a wide array of different plant hosts.
Applicant should note that the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958). See MPEP 2144.06
Factors that will support a conclusion that the prior art element is an equivalent are: (1) the prior art element performs the identical function specified in the claim in substantially the same way, and produces substantially the same results as the corresponding element disclosed in the specification. Kemco Sales, Inc. v. Control Papers Co. , 208 F.3d 1352, 54 USPQ2d 1308 (Fed. Cir. 2000); or (2) a person of ordinary skill in the art would have recognized the interchangeability of the element shown in the prior art for the corresponding element disclosed in the specification. Caterpillar Inc. v. Deere & Co. , 224 F.3d 1374, 56 USPQ2d 1305 (Fed. Cir. 2000); or (3) there are insubstantial differences between the prior art element and the corresponding element disclosed in the specification. IMS Technology, Inc. v. Haas Automation, Inc., 206 F.3d 1422, 1436, 54 USPQ2d 1129, 1138 (Fed. Cir. 2000). See MPEP 2183.
Here, the conclusion that TSWV and other viral vectors are equivalent is based on the fact (1) that one appreciates that viral vectors function in the same way in order to introduce sequence specific nucleic acid modifying enzymes; (2) virus mediated genome editing platforms are not limited to vectors derived from TRV and that other RNA viruses could also be used to deliver gRNA molecule to various plant species (e.g., see Ali et al); and (3) there are insubstantial differences between the disclosure of the instant specification and that of Feng et al and Hu et al which teach all of the necessary elements in order to produce a recombinant TSWV viral vector system for introducing a nucleic acid modifying enzyme.
One would have a reasonable expectation of success in arriving at the viral vector because each of Harling et al and Cody et al and Ali et al and Gao et al teach the successful use of viral vector systems to introduce the CRISPR system for genome editing in plants.
One would have found it obvious, and with a reasonable expectation of success in arriving at the ratios as recited in instant claims 58 and 69 because differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 (II)(A).
Here, Feng et al clearly teach the general conditions needed in order to produce a recombinant viral vector system as claimed with a reasonable expectation of success (e.g., see p. 1182, col. 2, last ¶).
Finally, one would have found it obvious to, and with a reasonable expectation of success, to add ribavirin to the culture medium comprising cells having the viral vector system as set forth above to ensure that there is no TSWV present to infect cells or regenerated plants produced therefrom or to prevent spread of TSWV to cells or plants that have not been treated with the viral vector system.
Response to Arguments
Applicant traverses the rejection of the claims because the art indicates that CRISPR/Cas9 proteins cannot be expressed in plant cells using RNA viral vectors due to limitation in cargo capacity and that there is no expectation of success for genome editing without using stable transformation. Applicant cites various review articles and citations to background section non-patent literature to support this position (Applicant reply dated 26 May 2026, section 1).
First, it should be noted that because Applicant has not rebutted the position of the Office that it would have been prima facie obvious to modify the teachings of Harling et al and Cody et al and Ali et al and Gao et al by instead using TSWV as a viral vector as taught by Feng et al it is assumed that Applicant accepts the argument there are teachings, suggestions and motivation to do so.
Instead, Applicant primarily relies on the argument that one would not have a reasonable expectation of success in inserting larger proteins such as CRISPR/Cas9 effector proteins into TSWV genomic segments based on the teaching of Feng and post-filling art.
However, this argument is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Here, the Office has presented numerous examples of why one would be motivated to arrive at the instantly claimed invention, and that one would have a reasonable expectation of success in doing so.
This argument is also not persuasive because it is not commensurate in scope with what is claimed. Namely, the claims are not limited to any particular size for the effector protein, the claims are not drawn to exemplified TSWV sequences in the specification that are functional (e.g., the claim does not require the codon-optimized sequence of SEQ ID NO: 5 but rather variants), and the claims fail to recite any particular location into which the first and second polynucleotide sequences are inserted and that are distinguishable from the teachings of Feng.
Furthermore, all cited references post-date Applicant’s filing and thus do not speak to whether one would have found the instant invention obvious at the time of the effective filling date.
Moreover, Applicant’s use of the art as evidence of unexpected results or solving a long-felt need in the art are misleading and unpersuasive. For example, Applicant cites to Ellison as proof that RNA viral vector have limited cargo capacity yet Ellison clearly teaches that negative-sense RNA viruses could provide a larger carrying capacity than the positive-sense RNA viruses demonstrating expression of both sgRNA and Cas9 (p. 17, last ¶). In any event, Gao speaks to one’s reasonable expectation of success as it teaches expression of large effector proteins using negative-stranded RNA virus.
Thus, there is clearly motivation in the art to use a fully transient expression system with a reasonable expectation of success as opposed to a stable one not only in view of Elison but also in view of Cody which specifically teaches and suggests viral vectors may be used to co-deliver Cas9 and sgRNA to host plants and that there are a limited number of viral vectors that will tolerate an insertion the size of Cas9 ORF (p. 31, col. 1, ¶ 2).
Applicant generally argues there are fundamental structural differences between the cited art and the claimed invention and that the instant invention provides an unexpected technical advantage (Applicant reply dated 07 August 2026, p. 11).
This argument is not persuasive because (1) it is immaterial whether there are structural differences so long as the Office provides a rationale for arriving at the instant claims with a reasonable expectation of success and (2) the instant claims can hardly be deemed to provide an unexpected advantage in so far as CRISPR/Cas9 technology is explicitly concerned with genome editing a plant without permanent exogenous DNA integrating into the plant cell genome (e.g., see Harling and Cody and Ali and Gao).
Applicant argues that Feng only teaches expressing small proteins and does not provide a reasonable basis to support that TSWV can accommodate large Cas nucleases (Applicant reply dated 26 May 2026, p. 13, last ¶).
This argument is not persuasive as one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Here, the Office has presented numerous examples of why one would be motivated to arrive at the instantly claimed invention, and why one would have a reasonable expectation of success in doing so.
Applicant argues that even if the cited references are combined the instantly claimed vector system cannot be obtained (Applicant reply dated 26 May 2026, section 2).
This argument is not persuasive because arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). See MPEP 716.01(c)(II). Here, Applicant has merely argued that arriving at the instant invention is not possible when the art clearly teaches and suggests the opposite is true.
Moreover, Applicant appear to insinuate that one must predictably arrive at the claims. However, the issue is not whether one may predictably arrive at the invention. Rather, the issue is whether one reasonably expects to arrive at the instant invention.
Applicant argues the instant invention eliminates the need to use hammerhead ribozymes (Applicant reply dated 26 May 2026, p. 14, last ¶). This argument is not persuasive as it is not commensurate in scope with what is claimed: the instant claims do not preclude the use of hammerhead ribozymes.
Applicant argues the instant invention provides unpredictable differences in vector compatibility (Applicant reply dated 26 May 2026, p. 15, ¶ 1; see also Declaration filed under 37 C.F.R. section 1.132 submitted on 07 August 2026, p. 2, section 2).
This argument is not persuasive because it is not commensurate in scope with what is claimed. The instant claims are drawn to a genus of TSWV genome segments yet the instant application provides a single functional and exemplary species from a genus of vector systems. In fact, Applicant’s claims as currently constructed encompass embodiments that are non-enabled and/or described (see also Declaration filed under 37 C.F.R. section 1.132 submitted on 07 August 2026, p. 2, section 2).
Applicant argues that the results of Feng cannot be extrapolated to large CRISPR nucleases (Applicant reply dated 26 May 2026, p. 15, ¶ 2; see also Declaration filed under 37 C.F.R. section 1.132 submitted on 07 August 2026, p. 2, section 2).
Again, Applicant’s arguments are unpersuasive because they are not commensurate in scope with what is claimed. Namely, the claims are not drawn to exemplified TSWV sequences in the art that are functional (e.g., the claim does not require the codon-optimized sequence of SEQ ID NO: 5 but rather encompass variants), and the claims fail to recite any particular location into which the first and second polynucleotide sequences are inserted and that are distinguishable from the teachings of Feng.
Here, the fact that Feng’s construct comprising CRISPR/Cas9 effector protein does not allegedly work fails to preclude the fact that other iterations of inserting said effector into the M genome segment as taught by Feng would be functional (see Declaration filed under 37 C.F.R. section 1.132 submitted on 07 August 2026, p. 2, section 3). Thus, Applicant’s arguments are not commensurate in scope with what is claimed.
Additionally, Applicant has not provided any data to this effect but rather proffers data demonstrating that when the effector protein is inserted into the S genomic segment that functionality is not obtained (e.g., see Declaration filed under 37 C.F.R. section 1.132 submitted on 07 August 2026, p. 2, section 3). Thus, Applicant’s arguments are not commensurate in scope with what is claimed.
Moreover, Applicant’s data supports the position of the Office that the claims are not enabled and/or described: if the construct of Feng did not work when inserting the effector protein into the M genomic segment then the instant claims lack any features that distinguish the construct of Feng from the construct of the instant invention.
Applicant asserts that none of the references disclose beneficial features of the system of claim 50 (Applicant reply dated 26 May 2026, p. 18, section 4). This argument is not persuasive as the references need not individually disclose the feature of the claims as the rejection is not anticipatory. Rather, the combination of the references as evidenced above need to only suggest arriving at inserting CRISPR/Cas9 into the M genomic segment to produce functional protein with a reasonable expectation of success.
Conclusion
No claim is allowed.
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/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
