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 .
Priority
This application claims priority to three foreign applications. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 for PCT/EP2021/086348 (12/16/2021) and EP21209719.0 (11/22/2021). However, there are no certified documents presented for EP2021469.5 (12/16/2020).
Further, regarding claim 5, support was not found in the specification of EP21209719.0 (11/22/2021), to claim that one or more mutations do not consist of R372A, K375A and D450N. Re: claim 6, support was not found in EP21209719.0 (11/22/2021), for increased excision at sites any T560 modification, any S564 modification, any S573 mutation, any S592 mutation, any F594 mutation corresponding to the position number corresponding to the amino acid number of SEQID NO: 9.
Re: claim 8, support was not found in EP21209719.0 (11/22/2021), for decreased DNA binding activity at R275, R277, R347, K375, or in claim 9 for K375.
Therefore, the effective filing date for these claims is based upon PCT/EP2021/086348 and is 12/16/2021.
Election/Restriction & Claim Status
Applicants’ Invention Group election was made without traverse in the reply filed 2/17/2026 and is acknowledged. The election of Invention Group I, claims 1-18 and 20 will be examined. Invention Group II, claim 21, is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group.
Applicant's election with traverse of the species election in the reply filed on 2/17/2026 is acknowledged. The traversal is on the ground(s) that no prior art document was cited and therefore there is no search burden; further when a single mutation is elected (D450N), there is no search burden of searching for variants of the protein that comprise multiple mutations including the elected mutation. This is not found persuasive because while breaking Unity with art may be relevant, it is not the only method possible. In the restriction (12/18/2025) an explanation was provided regarding Markush groupings and the chemical compounds that share a common structure in that they are mutations to PiggyBac sequence but that this is not a significant structural element/structurally distinct (reasons were provided in that Office action), and these groups are not a recognized class of compounds. Further, search burden is not a consideration for 371 applications. The requirement is still deemed proper and is therefore made FINAL.
Applicants’ species elections include: Claims 6-10: D450N, Claim 11: N347A/D450N, Claim 14: RNA-guided nuclease, Claim 15: SpCas9 of SEQIDNO:31.
Note: This application has been transferred to a new examiner. The amended Claims of 2/17/2026, specifically claims 1-18 and 20 are under consideration in this Office action.
Information Disclosure Statement
The information disclosure statements (IDS’s) submitted on 6/27/2023 and 8/7/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. It is noted that there was no “publication date” recited for Fu (NPL Ref 9 of 8/7/2023 IDS), a dissertation submitted in 2018, so this date has been added to the IDS.
Specification
The disclosure is objected to because of the following informalities: reference to color in drawings is found in the Figure Legends (see below), but the drawings are not in color, which results in a lack of clarity:
Pg 6 “LEGENDS OF THE FIGURES” discusses color in drawings:
FIG 1. Programmable transposase technology: cas9 (in red)… PB transposase domain (in pink).
FIG 2. Addresses green, orange and blue in drawing.
FIG 3. Addresses gray triangles.
FIG 6. PAM is highlighted in red.
The disclosure is objected to because of the following informalities: Trademarks (see below):
The use of the term PIGGYBAC (throughout Specification) is a trade name or mark used in commerce, that has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 17, and Pg 87).
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.
Appropriate corrections are required.
Claim Objections
Claim 11 is objected to because of the following informalities: “one of the following amino acid substitution”, where for proper grammar, “substitution” should be replaced with “substitutions”.
Claim 12 is objected to because of the following informalities: “an hyperactive PiggyBac with SEQ ID NO:9, or a modified hyperactive PiggyBac with comprising one or more amino acid mutations as compared to the hyperactive PiggyBac with SEQ ID NO: 9”.
First, “an hyperactive PiggyBac” should be replaced with “a hyperactive PiggyBac”, since hyperactive does not start with a vowel, nor is the “h” silent.
Second, the claim continues, “or a modified hyperactive PiggyBac with comprising one or more amino acid mutations as compared to the hyperactive PiggyBac with SEQ ID NO:9”. The “with” before comprising should be removed for clarity. Third, for clarity and consistency across claims, “with SEQ ID NO: 9” should be replaced with “of SEQ ID NO: 9”.
Claim 15 is objected to for the use of “at least 100%”, since more than 100% is not possible. Removing “at least” prior to 100% obviates the issue.
Appropriate correction is required.
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 1-18, 20 and 21 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 pre-AIA the applicant, regards as the invention.
Claim 1 is rejected as indefinite in the recitation of “said transposase is a modified hyperactive PiggyBac, comprising one or more amino acid mutations as compared to hyperactive PiggyBac of SEQ ID NO: 9” because it is unclear whether “modified hyperactive PiggyBac” means that the hyperactivity is modified relative to SEQ ID NO: 9, in addition to at least one amino acid, or whether the only change required to be a transposase that is a modified hyperactive PiggyBac is the amino acid(s) mutation. Claims 2-18, 20 and 21 depend from claim 1 and are indefinite for the same reason.
Claims 1, 4, 6-12 contain the trademark/trade name PiggyBac. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an engineered transposase and, accordingly, the identification/description is indefinite. Claims 2, 3, 5, 13-18, 20 and 21 depend from claim 1 and are indefinite for the same reason.
Claim 5 is indefinite in the recitation of “one or more mutations do not consist of R372A, K375A and D450N” since it is unclear how these site positions are identified when the mutant may have, for example, additional amino acids (“one or more amino acid mutations”; see below regarding definition from the Specification, of “mutation”) relative to SEQIDNO: 9.
Claim 11 is indefinite in the recitation of “typically said modified transposase has an amino acid sequence selected among any of the SEQ ID NO:” recited. The use of “typically”, or exemplary language, makes unclear the requirements of the claim, including whether the modified transposase must be limited to one of SEQ ID NO: 2-8, 10-18 and 135-149, or not.
Claims 18 and 20 are also indefinite in the recitation of “typically”, since its use makes unclear whether a size outside of the range recited does or does not meet the claim limitation for claim 18, or whether something other than a mRNA does or does not, for claim 20. Further, claim 18 is also indefinite in the recitation of a “large” DNA fragment. Large DNA fragment is not found in the specification definitions (nor is large) and establishing the metes and bounds of the claim inclusive of the term “large” DNA fragment, is not possible.
Claim Rejections - 35 USC § 112(a)
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 1-5, 8-9, 11-18, 20 and 21 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by 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 claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Nature of the Invention:
The claims are broadly directed to the composition of claim 1 that comprises a DNA binding protein and transposase that is a modified hyperactive PiggyBac, with a generic mutation, namely any mutation, relative to SEQ ID NO: 9. The included dependent claims that, while further limiting to the invention, largely do not further limit the breadth of the modified PiggyBac to a substantive degree, which therefore does not suffice as sufficient breadth limitation.
The claims are drawn to a very large genus of any mutation or number of mutations to SEQID NO: 9, which is 594 amino acids long. As an example of the scope of the mutated piggyBac sequences possible, if as few as any two amino acid sites were mutated of the 594 amino acid protein, then there are (594 positions pick 2), or ((594*593)/2) = 176,121 combinations that exist just for the two mutant positions. There are 19 AA options per site for each of the two mutants, or 192 = 361 amino acid options. Thus, the total number of combinations of just mutated two amino acid positions in a 594 amino acid protein are (176,121 * 361 =63,580,681), or more than 63 million combinations. Many additional mutational combinations fall within the claimed genus.
Since the claims require a modified hyperactive function and a large genera of possible mutations, the Specification must sufficiently demonstrate possession of a representative number of these mutations with the desired mutated hyperactive function, that results from the relationship, or correlation between structure and function, allowing for predictability of mutant behavior, sufficient to allow one of skill in the art to identify possession of the full scope of the invention.
While claim 8 (and others) may appear to narrow the hyperactive piggyBac genus by claiming one or more mutations from up to 8 positions, this is still a very large genus. Just considering the combination of 19 possible amino acids for eight sites would result in 198 = 16,983,563,041 possible options.
State of the Art:
After first articulating, “little is known” “about the structure-function relationships of the different domains of PB” (piggyBac), Morellet (Morrellet et al., 2018, Nucleic Acids Res 46, 260-2677; cited on IDS) disclosed the first structural insight into a singular functional piggybac (PB) binding domain (Abstract; Pg 2673, left col, end para to right col, first para). Morellet obtained unexpected results, including identifying a surprising site of interaction (Pg 2674, left col, first full para), indicative of both a general lack of knowledge in the art regarding piggybac structure-function relationships, and unpredictability in functional aspects of PBs in general.
Morellet further disclosed PB structure conservation, including a conserved RNase catalytic core with a conserved trio of amino acids (D268, D346 and D447) required for transposition, and a highly conserved C-terminus CRD (Pg 2661, left col, para 2), the latter essential for DNA breakage, joining and transposition (Pg 2661, left col, para 3). The CRD binds to DNA end sequences (of 19bp), but also to the additional “unexpectedly” internal site at the left end (Abstract; Pg 2661, left col, para 3), thus CRD mutations could alter binding, not hyperactivity.
Morellet noted, transposition frequency could be increased with longer ends, though particular protected ends, or internal end regions, existed that varied between a full-length PB and a truncated PB (Pg 2665, right col, 3rd full para- Pg 2666 left col para 1-3), thus precisely how that would work was unclear. The CRD, conserved among PB families, has a distinct common motif (Pg 2665, right col, first full para).
Morellet commented upon the possible value of mutants with increased or altered activity as useful for further dissection of structure-function relationships and for genome engineering (Pg 2675 right col, para 3), indicating the results of such work were not known. They recited mutants they previously reported as hyperactive (S509G/N571S and more) with particular C-terminal tail modifications, S564 and N571 as directly implicated in DNA binding and possibly hyperactive phenotype based upon their structural model (Pg 2674, right col, para 3). They noted that the structure of PB would likely be useful for design of mutants (Pg 2674 right col, final para).
Li (Li et al., 2013, PNAS, 110 E2279-2287; Cited on IDS) mutated piggyBac transposase (to avoid genome modification by reintegration following piggyBac excision), creating an “excision competent/integration defective” transposase (Abstract). Introduction of the mutant into hyperactive PB yielded a 5-6X higher excision frequency than a wt PB (Pg E2279, right col, para 1). Speculation that the mutated positions were likely positions of interaction between the transposase and target DNA was as far as the structure-function relationship for this hyperactive mutant was determined (Pg. E 2279, right col, para 2), meaning this mutant or relationship did not suggest predictable functional changes for other hyperactive mutations across the entire sequence. In fact, Li stated “modifications of nonviral vector systems to alternative integration pattens in a predictable manner would provide molecular biological tools with relevance to diverse applications…” (Pg E2279, right col, para 2), indicative we are not yet to this point.
Li, like Morellet pointed to the catalytic domain of PBS, with a required conserved trio of amino acids (D268, D346 and D447) (Pg E2280, left col, para 1), and near this, 15 required arginines and lysines, highly conserved among piggyBac proteins, suggestive that mutation would likely be deleterious, but some of these, hypothesized to be involved in transposition (Pg E2280, left col, para 3), so mutagenesis was conducted (Pg 2280, left col, para 3). The catalytic domain functions in excision and integration of DNA and it was hypothesized alanine substitutions may alter excision or integration, both or neither (Pg E2290, left col, para 4). The results were unpredictable: some mutants were excision positive, others were not, and of those that were (+), some were integration positive, others were not or had low activity (Pg. E2280 left col, end to top right).
Keith (2008, BMC Mol Biol., 73: 1-20) had identified important effects of mutation, through use of directed mutagenesis, that did not induce hyperactive piggyBac. Keith had evaluated three piggyBac residues (D268, D346, D447; possible catalytic core), plus D450, where all mutations at these sites decreased excision frequency in cell culture relative to wt transposase (Abstract; Pg 10 right col final para). Keith determined all of these aspartates were therefore necessary for excision to occur (Abstract). Thus, these mutations are known to not induce hyperactivity of this piggyBac, counter to the goals of the instant claims. In GenBank alignments with a wt piggyBac, additional sites were found (D32, D38, E45, D49) to be aspartate or glutamate, even within families, without consequence (Pg 3 left col, para 3).
Teachings in the Specification:
There appear to be a very limited number of PiggyBac mutations tested as related to SEQ ID NO: 9 and the independent claim, which discloses a composition comprising a modified hyperactive PiggyBac with one more mutations, compared to hyperactive PiggyBac of SEQ ID NO: 9. Those mutants tested appear to pale in number by orders of magnitude (see below), relative to the possible number of mutations for the genus of all possible mutations to SEQ ID NO: 9.
The working examples relay efforts to combine CRISPR and piggyBac variants that “exhibit enhanced insertion and excision activity and lower target DNA binding activity”, where SpCas9 was fused with a piggyBac transposase (Fig 1), followed by construction of a diverse library of piggyBac and SpCas9 variants and linkers (FIG 2a, b,c), thus appearing to mean combinations from the mutations in FIG.1 (Pg 76). FIG. 1 depicts five categories of mutants (10 total mutants), Fig. 2A depicts efficiency for different Cas_PBs (cas9_PB, nCas9_PB, dCas9_PB)…not obviously disclosing additional piggyBac mutants, Fig 2B depicts on target efficiency for Cas9, Cas9_PB, and 9 particular mutants/mutant combinations that would arise from those mutations recited in Fig 1 (except that Fig 2B recites and S573A mutation which is S563A in FIG 1). Different mutant combinations, again from the individual mutations recited in FIG1, are presented in FIG 4A, 4B, 4C.
After mentioning catalytic core domain formed by 3 residues, surrounded by 15 arginine/lysines, in addition to hyperactive variants explored in the past, it is disclosed “we diversified additional residues that may influence PB excision and integration activities (SEQ 1-N), (where it is unclear what exactly N references), and to isolate best performers a reporter system was developed for targeted gene insertion. Thus, a number of mutations were generated and tested, though the relationship, if any, between structure (mutants across SEQID NO:9) and hyperactive function, is not apparent.
The Specification discloses that high excision piggyBac mutants appear to contribute to higher programmable insertion (D450N, M194V; FIG 2B, 4A, 4B). Regarding results of Cas9-hyPB mutant variants, to identify mutant combinations that displayed “better efficiencies”, selection using the reporter system was conducted, and combinations were observed that out performed Cas9-hyPB R372A-K375A-D450N, including variants “worth mention” (SEQ ID NO: 2 and 3). However, this is testing of variants and obtaining a result, absent prediction across SEQID NO 9 regarding mutant performance.
Results of Cas9-hyPB mutant variants section, it is stated a PiggyBac library was produced…cloned in fusion with Cas9 into vector, used with reporter cell line where ultimately PB was amplified, and best performers were selected, again absent apparent predicted results or structure-function relationships, or clear demonstration of hyperactivity due to mutation across SEQID NO:9. In the section on co-expression of Cas9-hyPB and hyPB variants, site directed mutagenesis is disclosed to introduce “different mutations”, 10 mutations are recited and reference to SEQ ID NO:90-99, but nothing further regarding knowledge on other modified hyperactive PiggyBac mutations that extends beyond this directed mutagenesis (Pg 84).
Conclusion regarding possession:
Applicant does not have sufficient breadth of disclosure, namely a representative number of species and/or with the structure: function relationship (mutated hyperactive PiggyBac) necessary to effectively demonstrate possession of the invention, for the exceptionally large genus of modified hyperactive PiggyBac mutants disclosed in claim 1. To demonstrate this, the generic structure of a protein with mutations to SEQ ID NO: 9 must be modified in a manner to have the claimed function of modified hyperactivity. The disclosed libraries/tested mutants are insufficient to make predictable the hyperactive function that might be associated with mutations, one or more of which can occur, across the 594 amino acids comprising SEQ ID NO:9. Instead, unpredictability exists regarding the function of all possible mutations of one or more amino acids to SEQ ID NO: 9 with respect to hyperactivity, with the art demonstrating that some mutants were hyperactive, with others hypoactive.
The species described are insufficient to serve as representative of the entire genus. The nature of experimentation necessary to identify the mutants with the desired function would be unusually high and the motivation to test all mutants would therefore be very low. Taking into consideration the factors outlined above, including the nature of the
invention, the state of the art, the guidance provided by the Specification, it is concluded that the specification does not demonstrate sufficient written description to indicate possession of the invention as recited in the claims.
Claim interpretation
The claims shall be given their broadest reasonable interpretation in light of the specification (MPEP 2111). Regarding the said transposase in claim 1 that is a modified hyperactive PiggyBac, comprising one or more amino acid mutations compared to SEQ ID NO: 9, this would therefore be inclusive of any modified hyperactive PiggyBac that does not have the identical sequence to SEQ ID NO: 9.
The definition of mutation disclosed in the Specification (Pg 19) is recited: “mutation” refers to a substitution of a residue within a sequence, a nucleic acid or amino acid sequence, with another residue; and/or to a deletion or insertion of one or more residues within a nucleic acid or amino acid sequence.
Claim Rejections - 35 USC § 103
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.
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) 1-2, 4 and 5, 14,16,17 are rejected under 35 U.S.C. 103 as being unpatentable over Shrock (WO2018175872A1, published 27 Sept 2018; cited on the IDS) in view of Yusa (Yusa, K. et al., 2011, PNAS, 108, 1531-1536; cited on IDS)
‘039 Claim 1. A Composition comprising
(i) a first protein comprising or consisting of a site-specific DNA binding protein capable of binding and cleaving a target nucleic acid sequence; or a nucleic acid construct encoding said first protein; and
(ii) a second protein comprising or consisting of a transposase; or a nucleic acid construct encoding said second protein;
wherein said transposase is a modified hyperactive PiggyBac, comprising one or more amino acid mutations as compared to hyperactive PiggyBac of SEQ ID NO: 9.
‘039 Claim 2. The composition according to claim 1, wherein the first protein and the second protein are fused together to form a fusion protein.
Re: claims 1-2, 4 and 5, 14,16,17 Shrock disclosed a Cas9 transposase fusion protein (meeting instant claim 2) that cleaved target nucleic acid (Abstract; Pg 24). The transposase could be a hyperactive piggyBac (Pg 3) selected from Yusa’s mutants, thus meeting the claimed modified hyperactive PiggyBac, comprising one or more mutations compared to SEQ ID NO: 9, based upon the broadest reasonable interpretation discussed in the claim interpretation.
Shrock did not explicitly recite the mutants of Yusa.
Yusa generated 18 mutants in yeast, five that were hyperactive (increase excision activity) in mammalian cells (meeting instant claims 1 and 4) (Abstract).
Yusa also combined all mutations to generate a unique hyperactive piggyBac transposase with increased excision and integration (Abstract) where mutants with high activity in excision were identified as I30V/G165S, S310P, M282V, S509G/N570S and N538K (Pg 1532 left col end, to right col top; Pg 1533 left col, para 1). The mutations did not comprise R372A, K375A or D450N as disclosed (see Fig 1B, C; meeting instant claim 5). The engineered system used can be RNA-guided nuclease (Pg 6; meeting instant claim 14). The donor nucleic acid is a sequence to be inserted into genomic DNA, and is exogenous to the cell, and the Cas9-gRNA system enables RNA guided DNA regulation by tethering transcriptional activation/repressor domains, or regulatory proteins, to guide RNAs (Pg 18; meeting instant claim 16). In one aspect there may be a Cas9 protein fused with functional proteins, such as transcriptional regulators like Fok 1, an aptamer, a binding protein PP7, MS2 (Pg16, meeting instant claim 17). The donor nucleic acid may be a transposon sequence, even a piggyBac (Pg 18), however no disclosure related to this being of large size.
Prior to effective filing date it would have been prima facie obvious to one or ordinary skill in the art to have incorporated a hyperactive piggyBac mutant from Yusa into the invention of Shrock to generate the construct of interest to Schrock. One would have been motivated to do so, particularly since that was the direction provided by Schrock, so it would have been obvious to try this combination from the few articulated in Shrock. There would have been a reasonable expectation of success when combining Yusa’s known functional piggyBac mutant with the Cas9 of Shrock since that combination was the foundation of Shrock’s invention.
Conclusion
All claims are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lisa Horth whose telephone number is (703)756-4557. The examiner can normally be reached Monday-Friday 8-4 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LISA HORTH/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights