Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-15 are pending. Claims 11-15 are withdrawn due to species election and not examined on its merits. Claim 16 is canceled. Claims 1-10 are examined in the instant application. All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Amendments
Status of Rejections from action:
In regard to Claims 1-10 under 112(b) is modified in view of amendments.
In regard to Claims 1-10 under 112(a) written description is modified in view of amendment.
In regard to Claims 1-10 under 112(a) enablement is modified in view of amendment.
In regard to Claim 16 under 112(d) it is withdrawn due to Applicant canceling the claim.
In regard to Claims 1-10 under 103 is modified in view of amendment.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No EP21306460.3, filed on October 19, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 12, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)(Indefinite)
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 1-10 REMAIN rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation wherein the left ubiquitin-like region and the right ubiquitin-like region comprise between 50 and 1900 nucleotides with at least 90% sequence identity with a region in 5' and in 3', respectively, of the polyubiquitin gene.
The metes and bounds of the claim are indefinite because it seems as if the left ubiquitin-like region and the right ubiquitin-like region comprising between 50 and 1900 nucleotides with at least 90% sequence identity with a region in 5' and in 3', respectively will cause the entire polyubiquitin gene to be replaced as these regions encompass the entire gene as opposed to only encompassing insertion in only the 5’ or 3’ of the polyubiquitin gene, which contradicts the claim’s requirement for targeted insertion into just the 5’ or 3’ end.
Claim 1 recites the limitation “ubiquitin-like region comprise between 50 and 1900 nucleotides with at least 90% sequence identity with a region in 5' and in 3” is unclear. Because no specific reference sequence or SEQ ID NOs are recited, the exact structure to which the ubiquitin-like regions (UBL) has 90% sequence identity to is not clear. One skilled in the art would not be able to determine the structure.
Claims 6 and 8 recite the same limitation and are therefore rejected for the same reason as provided for claim 1.
Claims 2-5, 7 and 9-10 are rejected for depending upon a rejected base claim and for failing to remedy the issues of indefiniteness.
Correction and/or clarification is required
Response to Arguments
Applicant's arguments filed 06/05/2026 have been fully considered but they are
not persuasive. The Applicant argues that they have amended the claims to define the structure of the UBL and that the UBL is defined in the specification. However Applicant does not actually put any structure in the claim (i.e., no SEQ ID), and the specification does not define UBL but provides exemplary embodiments. Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)(Written description)
Claims 1-10 REMAIN rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for 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 disclosure is as follows.
The specification describes targeting a polyubiquitin gene on Chr7DL of Chinese Spring (TraesCS7D01G443100) and identifies specific polyubiquitin target sequences for wheat (SEQ ID NOs: 3-5), in maize line B73 (SEQ ID NOs: 43-46), and Brassica napus (SEQ ID NOs: 57-59). The Applicant describes transforming wheat, maize, and B. napus with vectors comprising 1st gRNA target, a corresponding plant-specific left ubiquitin-like region, at least one gene of interest (GOI) such as (BAR, RFL29 or RFL79, ACCase, or ALS), a corresponding plant-specific right ubiquitin-like region, and 2nd gRNA target (examples 1-6).
Applicant describes increasing herbicide resistance using the BAR gene in wheat (p. 30 table 1) and the ALS gene (p.35 and fig. 9) as well as the restoration of fertility in wheat using RFL29 and RFL79 genes (p.32 line 19-21 and table 2).
The specification fails to describe a representative number of species or nucleic acid structures from the genus of ubiquitin-like region as broadly claimed.
The claims require a repair DNA comprising a “left ubiquitin-like region” and a “right ubiquitin-like region” defined broadly structurally only as comprising between 50 and 1900 nucleotides with at least 90% sequence identity to a 5’ or 3’ region of a “polyubiquitin gene”. However, the specification fails to describe specific nucleic acid structures or defining characteristics for these left and right regions across the broad genus of UBL’s with at least 90% sequence identity encompassed by the claims.
These ubiquitin-like regions encompass sequences homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene obtained from sources other than a plant, with structures and identities that are not disclosed. Because the specification does not adequately describe structures for ubiquitin like regions one would appreciate that Applicant doesn’t possess the genus of structures encompassed by the limitation “ubiquitin like region”.
From the disclosure of ubiquitin-like regions in the instant specification one skilled in the art cannot predict the structures of other ubiquitin-like regions genes or fragments from other sources and their allelic variants with ubiquitin-like regions that can effectively bind to an unknown polyubiquitin gene. Ubiquitin-like regions is a broad genus of structures/nucleic acid sequences which both the art and specification fail to define and are thus not described.
The ubiquitin-like regions encompass a broad genus of structures because the specification fails to define a ubiquitin-like region and only provides examples of ubiquitin-like regions as a sequence homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene (spec. p. 10 lines 1-14, image below).
The limited description of a few species of these polyubiquitin genes and ubiquitin-like regions are not representative of the ENTIRE and broad genus of polyubiquitin genes and ubiquitin-like regions as encompassed by the claims. Thus, there are insufficient relevant identifying characteristics to allow one skilled in the art to predictably determine the structures necessary to target the polyubiquitin genes for integration of a GOI or to determine the structures ubiquitin-like regions which retain functional activity for targeted integration in the broad genus of all plants as claimed.
Moreover, while one skilled in the art can generate sequences having at least the same structures of the polyubiquitin genes and ubiquitin-like regions as described in the specification, it is unpredictable which species within the genus of ubiquitin genes and ubiquitin-like regions as broadly claimed would also yield a functional vector for targeted integration of a gene of interest.
Here, “ubiquitin-like region” as claimed includes an exhaustive genus of sequences, homologs, fragments, or sequences having at least 90% sequence identity to any sequence found within the ubiquitin like region. This region is defined as being homologous to a sequence comprising the end of the polyubiquitin coding region and at least a portion of the 5’ and /or 3’ UTR.
However, the only ubiquitin-like region sequences that the specification discloses are SEQ ID NOs: 66-69 (p.25) yet the claims are not limited to said sequences. Because there is no definition for “ubiquitin-like region” in the specification, the limitation remains defined by a function rather than a structure.
For example, Han et al. (“Regulation of polyubiquitin genes to meet cellular ubiquitin requirement.” BMB reports vol. 54,4 (2021): 189-195. doi:10.5483/BMBRep.2021.54.4.005 (previously cited)) describes the different roles for polyubiquitin genes such as “Monoubiquitination is known to regulate histone modification, receptor endocytosis, etc. (3). Polyubiquitination plays different roles depending on the type of Ub chains (4). It is involved in a variety of cellular processes, such as proteasomal degradation, stress response, signal transduction, and membrane protein trafficking.” (p. 189 Introduction). This suggests that depending on the cellular processes the expression pattern of the gene will fluctuate.
This variability in function would not allow one skilled in the art to predictably produce ubiquitin-like regions that would target the integration of a gene of interest into a polyubiquitin gene as the art describes polyubiquitin gene function differs. Therefore, the specification has not described a representative number of species from the genus of ubiquitin-like regions necessary to target all polyubiquitin genes.
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.
Response to Arguments
Applicant argued that there is enough written description of the genus of ubiquitin-like regions necessary to target all polyubiquitin genes; (2) the specification provides the specific polyubiquitin target sites for 3 wheat genomes Ubi7DL (SEQ ID NO: 3), Ubi7BL (SEQ ID NO: 4), and Ubi7AL (SEQ ID NO:5) along with their respective gRNA (SEQ ID NOs: 6-8), and very specific homology repair arms: left homology arm (680bp) and right homology arm (740bp) flanking the Ubi7DL target site; and (3) the specification demonstrates specific polyubiquitin landing pads, wheat, maize, and rapeseed (Exs. 1-6).
(Remarks, 06/05/2026, pages 11-15).
Applicant's arguments filed 04/23/2026 have been fully considered but they are
not persuasive. While Applicants argue very specific target sites and SEQ ID NOs. have been described, the specification does not describe sequences to UBL’s having at least 90% sequence identity to a 5’ or 3’ region of an undisclosed sequence.
Thus, Applicant’s argument are not commensurate in scope with what is claimed, and the specification fails to adequately describe sequences of UBL’s comprising 50-1,900 nucleotides having at least 90% sequence identity to any polyubiquitin gene and provide a representative number of species of UBL’s having at least 90% sequence identity to any polyubiquitin gene and having specific functional targeting of the invention as broadly claimed.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1-10 REMAIN rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for targeting a polyubiquitin gene on Chr7DL of Chinese Spring (TraesCS7D01G443100) and identifies specific target sequences for wheat (SEQ ID NOs: 3-5), in maize line B73 (SEQ ID NOs: 43-46), and Brassica napus (SEQ ID NOs: 57-59), 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 use the invention commensurate in scope with these claims.
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.
(A) The breadth of the claims
The breadth of the claims encompasses any plant being genetically modified in the endogenous polyubiquitin gene with a vector comprising 1st gRNA target, left ubiquitin-like region, at least one any gene of interest (GOI), right ubiquitin-like region, and 2nd gRNA target, wherein the polyubiquitin gene and ubiquitin-like region have any structure and function. Wherein the left/right ubiquitin-like region comprises between 50 and 1900 nucleotides with at least 90% sequence identity with a region in 5’ and 3” of the undisclosed polyubiquitin gene.
(B) The nature of the invention.
The nature of the claimed invention is directed to a vector comprising 1st gRNA target, left ubiquitin-like region, at least one any gene of interest (GOI), right ubiquitin-like region, and 2nd gRNA target, wherein the polyubiquitin gene and ubiquitin-like region have any structure and function. Wherein the left/right ubiquitin-like region comprises between 50 and 1900 nucleotides with at least 90% sequence identity with a region in 5’ and 3” of the polyubiquitin gene (SEQ ID NO: 3-5).
(C) The state of the prior art
The state of the prior art has taught that various polyubiquitin genes have various roles see Han et al. 2021 above. Additionally, many of these polyubiquitin genes vary in structure and 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 claims require a repair DNA comprising a “left ubiquitin-like region” and a “right ubiquitin-like region” defined broadly structurally only as comprising between 50 and 1900 nucleotides with at least 90% sequence identity to a 5’ or 3’ region of a “polyubiquitin gene”. However, the specification fails to teach specific nucleic acid structures or defining characteristics for these left and right regions across the broad genus of UBL’s with at least 90% sequence identity encompassed by the claims.
These ubiquitin-like regions encompass sequences from non-plant sources with structures and functions that are not taught. The specification does not enable one skilled in the art to predict which ubiquitin-like regions will be functionally active. Consequently, producing a functional vector would require undue experimentation to test near-infinite combinations of these unknown structures to produce a functional vector.
The ubiquitin-like regions as claimed encompass a broad genus of structures because the specification teaches the ubiquitin-like region may be a sequence homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene (spec. p. 10 lines 1-14, image below).
The limited guidance regarding the structures of polyubiquitin genes and ubiquitin-like regions does not allow one skilled in the art to predictably determine the structures required to target a gene of interest into a polyubiquitin gene in the broad genus of all plant as claimed without undue experimentation.
Moreover, while one skilled in the art can generate sequences having at least the same polyubiquitin genes and ubiquitin-like regions as taught in the specification, it is unpredictable which structures would predictably insert a gene of interest into the genus of polyubiquitin genes as claimed without undue experimentation.
Additionally, the limitation “ubiquitin-like region” includes other sequences or homologs, fragments, or variants having at least 90% sequence identity to structures within a polyubiquitin gene. The only ubiquitin-like region sequences that the specification teaches are SEQ ID NOs: 66-69 (p.25) yet however the claims are not limited to said sequences. Because there is no definition for “ubiquitin-like region” in the specification, the limitation has been defined by a function rather than a structure.
For example, Han et al. (“Regulation of polyubiquitin genes to meet cellular ubiquitin requirement.” BMB reports vol. 54,4 (2021): 189-195. doi:10.5483/BMBRep.2021.54.4.005 (previously cited)) teaches the different roles such as “Monoubiquitination is known to regulate histone modification, receptor endocytosis, etc. (3). Polyubiquitination plays different roles depending on the type of Ub chains (4). It is involved in a variety of cellular processes, such as proteasomal degradation, stress response, signal transduction, and membrane protein trafficking.” (p. 189 Introduction).
This variability would not allow one skilled in the art to predictably produce ubiquitin-like regions for targeted integration of a gene of interest into polyubiquitin genes as broadly claimed. Therefore, the specification has not provided adequate working examples to practice the claimed invention.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples regarding the structure of ubiquitin-like regions which target all polyubiquitin genes, the state of the prior art, and unpredictability in the art, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without excessive burden and undue experimentation.
For at least this reason, the specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Response to Arguments
Applicant argues there is enough enabling guidance and working examples of the genus of ubiquitin-like regions necessary to target all polyubiquitin genes; (2) the specification provides the specific polyubiquitin target sites for 3 wheat genomes Ubi7DL (SEQ ID NO: 3), Ubi7BL (SEQ ID NO: 4), and Ubi7AL (SEQ ID NO:5) along with their respective gRNA (SEQ ID NOs: 6-8), and very specific homology repair arms: left homology arm (680bp) and right homology arm (740bp) flanking the Ubi7DL target site; and (3) the specification demonstrates specific polyubiquitin landing pads, wheat, maize, and rapeseed (Exs. 1-6).
(Remarks, 06/05/2026, page 11-15).
Applicant's arguments filed 04/23/2026 have been fully considered but they are
not persuasive. While Applicants argue very specific target sites and SEQ ID NOs. have been taught, the specification does not teach sequences or provide working examples to UBL’s having at least 90% sequence identity to a 5’ or 3’ region of an undisclosed sequence.
Thus, Applicant’s argument are not commensurate in scope with what is claimed, and the specification fails to enable sequences of UBL’s comprising 50-1,900 nucleotides having at least 90% sequence identity to any polyubiquitin gene or provide working examples of species of UBL’s having at least 90% sequence identity to any polyubiquitin gene and having specific functional targeting of the invention as broadly claimed without undue experimentation.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-10 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over Baltes (WO 2018/005589 (previously cited)) in view of Do et al. (BMC Plant Biology (2019) 19:311 https://doi.org/10.1186/s12870-019-1906-8 (previously cited)), and Gilchrist et al. (The Journal of biological chemistry, vol. 272, issue 51, 1997, pgs. 32280-32285, doi:10.1074/jbc.272.51.32280, (U)).
Claim interpretation:
The Applicant does not define “left” and “right” “ubiquitin-like region” leaving room for interpretation. The Office interprets the terms as any sequence from a ubiquitin gene fused to both ends of the gene of interest, making a “ubiquitin sandwich” with the GOI in the middle.
In regard to claims 1-5, 7 and 9-10, Baltes teaches using a vector to target insertion of GmEPSPS, BAR or YFP genes downstream of GmUbi3 in soybean protoplast (claim 13 p. 42-44 ex. 2-4). Additionally, Baltes teaches having a left and right ubiquitin TALEN target DNA sequence (which the right/left ubiquitin-like region is being interpreted as a gene being inserted into the ubiquitin gene) (p.42 table 1, ex. 2 and Figs. 6-7). In regard to claims 6 and 8, Baltes teaches transforming plants with said vector and editing systems (p. 43 ex. 3).
Baltes teaches that “molecules designed to knockin GmEPSPS, Bar, or YFP into the GmUbi3 gene (3' insertion)” (i.e. at least one gene of interest in the 3’ of a polyubiquitin gene) (claim 4, p. 7 lines 10-11, ex. 2 and Figs. 6-7). Furthermore, when knocking in EPSPS gene it enhances herbicide tolerance (p.46-47 ex. 8). Lastly, Baltes teaches that CRISPR Cas9 systems can be used with said vector (p. 21 lines 17-32).
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Overall, Baltes teaches on a blueprint on how to target at least one gene of interest in the 5’ or 3’ of an endogenous polyubiquitin gene.
In regard to claims 1-5, 7 and 9-10, while Baltes teaches using one gRNA, Baltes does not teach using two CRISPR gRNAs, utilizing a sequence encoding a site cleavable by a ubiquitin protease, or left/right ubiquitin-like regions comprising between 50-1900 nucleotides with at least 90% sequence identity with a region in the 5’ and 3’ of the polyubiquitin gene.
In regard to claims 1-5, 7 and 9-10, Do et al. teach using “dual gRNA CRISPR/Cas9 system offers a rapid and highly efficient method to simultaneously edit” (pg.1 Abstract and Figs. 1 and 4). Do et al. teach knocking in mutations to the GmFAD gene resulting in 80% increase in oleic acid (Fig. 4). Lastly, Do et al. teach on specifically using “Cas9 expression construct for targeted mutagenesis, pSK-AtU6–26- gRNA1 was cut with BamHI-SpeI, pSK-AtU6–26- gRNA2 was cut with BamHI-EcoRI, and 35S-Cas9-SK was digested with HindIII-SpeI. These 3 fragments were assembled into pFGC5941 by HindIII-EcoRI restriction digestion followed by ligation to give the pFGC-GmFAD2-CRISPR construct.” (p.11). In regard to claims 6 and 8, Do et al. teach transforming plants with said vector and editing systems (p. 11 col. 2).
Overall, Do et al. demonstrates how a dual gRNA system can be used to effectively and efficiently genetically modify plants to improve crop performance, because previous methods using one gRNA to deliver multiple constructs simultaneously results in low transformation frequency (p.2, col.2).
In regard to claims 1-5, 7 and 9-10, Gilchrist et al. teach ubiquitin-specific proteases for cleaving ubiquitin-fusion proteins in biotechnology, that they are able to “efficiently and precisely cleave the ubiquitin-proline bond either in vitro or in vivo” (pg. 32284, col.1, discussion section), and they are beneficial because “uncleaved ubiquitin fusions are recognized as abnormal proteins and rapidly degraded” (p. 32280, col.2). Gilchrist et al. teach that using ubiquitin-specific proteases for cleaving “improves the versatility of the ubiquitin fusion technique” (pg. 32284, col.1, discussion section).
Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious for one of skill in the art to modify the teachings of Baltes using a vector system for targeted integration of a GOI into the endogenous polyubiquitin gene of Glycine max (claim 13 p. 42-44 ex. 2-4) by instead using the dual gRNA system as taught by Do et al. because using one gRNA to deliver multiple constructs simultaneously results in low transformation frequency (p.2, col.2) while using a first and second gRNA target offers a rapid and highly efficient method to simultaneously edit (pg.1 Abstract and Figs. 1 and 4).
Moreover, prior to the effective filing date of the instant invention it would have been prima facie obvious to modify the method of Baltes in view of Do et al. by also including a sequence encoding a site cleavable by a ubiquitin protease, for example as taught by Gilchrist et al., because doing so improves the versatility of the ubiquitin fusion technique as taught by Baltes and prevents abnormal proteins production or rapid protein degradation.
As for the left and right ubiquitin-like region having at least 90% sequence identity it would have been obvious for one skilled in the art to because one understands that regions with 100% identity results in efficient homologous recombination.
One would have a reasonable expectation of success in doing so because of Baltes successfully expresses a GOI when inserted into native polyubiquitin gene (claim 4, p. 7 lines 10-11, ex. 2 and Figs. 6-7) and because Do et al. successfully teaches the predictable use of two gRNA’s to improve crop performance.
Response to arguments
Applicant argues that (1) Baltes does not specifically teach on using CRISPR; (2) Baltes inserts sequences at the 3’ end downstream of the GmUbi3 sequence or using GmUbi3 homology arms fused to an in-frame 2A sequence; (3) does not teach utilizing endogenous ubiquitin protease that flanks a GOI and releases it.
Regarding (1) Applicant is reminded that this is a 103 rejection and not a 102 rejection, and that the rejections is based on the combination of references. In this case, Applicant argues that Baltes does not specifically teach using CRISPR. Baltes is not required to teach the use of CRIPSR but suggests doing do so while Do et al. provides motivation for using two gRNA targets and that the use of CRISPR provides a high expectation of success.
Regarding (2) Baltes does in fact claim gene insertion in the 5’ or 3’ region (claims 4-5). As for the homology arms fused to an in frame 2A sequence, the claims do not exclude using such sequence.
Regarding (3) Gilchrist et al’s. teaches and provides motivation for utilizing ubiquitin protease to cleave the ubiquitin-proline bond and improve the ubiquitin fusion technique resulting in normal protein production and decreased degradation (pg. 32284, col.1, discussion section).
Moreover, Applicant’s arguments are not commensurate in scope with what is claimed because the claims do not require a sequence encoding two site cleavable by a ubiquitin protease that “flank” a gene of interest or “release” the protein encoded by the gene of interest.
Therefore, the rejection is maintained.
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
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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