DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Amendment filed on July 7, 2026, has been received and entered.
Claim Disposition
3. Claims 3 and 18 have been cancelled. Claims 1-2, 4-17 and 19 are pending and are under examination.
Claim objection
4. Claims 1-2, 4-17 and 19 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to recite the GC rich microorganism especially since it’s the first step in the method. It is suggested that claim 2 is incorporated into claim 1. The dependent claims hereto are also included.
For clarity it is suggested that claim 1 is amended to read,
“iv) [[optionally,]] selecting a transformed cell…..microorganism; and
v) obtaining ………”.
For clarity and precision of claim language it is suggested that claim 5 is amended to read, “….claim 1, wherein said at least one…..single-guide RNA…..., [[and]] wherein said at least one……guided RNA, and wherein a sequence…..”.
For clarity and precision of claim language it is suggested that claims 12 and 15-16 are amended to recite “….wherein……and, wherein…..”.
For clarity it is suggested that claims 13-14 are amended to recite, “selected from the group consisting of”. The dependent claims hereto are also included.
For clarity it is suggested that claims 14 and 15 are amended to delete the dash lines in front of the claim limitations. The dependent claims hereto are also included.
For clarity it is suggested that 15 is amended to recite proper sequence notation, “SEQ ID NOs:” in lieu of “SEQ ID Nos:”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
5. Claims 1-2, 4-13, 16-17 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), 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 claimed invention is directed to “a method of genetically modifying a GC rich microorganism, a genetically modified GC rich oleaginous microorganism, and method of preparing a target. The claimed invention in claim 1 is not adequately described because there is no clear description of the organism to be modified and it is also not clearly described the mechanism (i.e., specific products utilized). The claimed invention provides a laundry list in claim 2 of genus of organisms and claim 13 recites that it is an oleaginous microorganism (which includes yeasts, microalgae, fungi and molds), none of which limits claim 1 and 13 which needs to stand on its own. The invention encompasses a large variable genus. The claimed invention also encompasses a plasmid or plasmid collection and the claim is devoid of structural limitations. The method of claims 16 is also directed to a large genus with respect to microorganisms and genes. Therefore the invention as claimed is not adequately described.
The claimed invention is not commensurate in scope with the disclosure and no correlation is made between structure and function. The specification fails to provide a representative number of species for the claimed genus to show that applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described, are representative of the entire genus.
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
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.
6. 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.
7. Claim(s) 1-2, 4-17 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable Jiao Xiang (2019, of record in the application) as evidenced by Wen Zhiqiang et al. (2020, of record in the application), in view of Yip Bon et al. (2020, of record in the application), Kawai Shigeyuki et al. (2010, of record in the application), Gorner Christian et al. (2016 of record in the application) and Telford (US Patent No. 7,939,087, 2011).
Jiao Xiang discloses a method of genetically modifying the yeast Rhodosporidium toruloides, comprising integrating a Cas9 cassette into the R. toruloides genome, and transforming a sgRNA plasmid including donor DNA flanked by
two homologous arms of the gene CRTI for homologous recombination (HR) of
a HYG cassette into the CRTI locus of the Cas9 expressing strain. Mutants
were generated wherein the donor DNA was integrated by HR into the CRTI
locus. Selection of genetically modified yeasts is done with hygromycin (Jiao Xiang,
abstract, experimental section, 2.6, 3.2 and 3.4; Fig. 3A; page 6, last par.).
Rhodosporidium toruloides is well known in the art as an oleaginous yeast with
a high GC content of >60% (as evidenced by Wen Zhiqiang et al., see abstract; page 2 col. 1 par. 1 and col. 2 par. 3). Jiao Xiang thus discloses all the features of the method according to any of claims 1-2, 4-7, 12, 13 (with regard to optional features, please see Item VIII below). Jiao Xiang is also considered to disclose, in the broadest sense, a "plasmid collection" comprising a mRNA encoding Cas9 and at least one gRNA.
Jiao Xiang disclose all the method steps of claim 1, and the additional steps of applying the endonuclease in the form of an mRNA encoding it (claim 8), of pretreating the microorganism (claims 9, 10), and of transforming the yeast using one of the methods recited in claim 11 are not explicitly disclosed in Jiao Xiang.
Yip Bon et al. which reviews Cas9 delivery strategies, reports that the CRISPR/Cas9 system can be delivered in the format of DNA ("all-in-one" plasmid), mRNA (Cas9 and sgRNA), or protein (RNP), for example, in the form of lipid-based nanoparticles (LNPs), which can be formed with Lipofectamine. Yip Bon et al. describes the successful delivery of the CRISPR/Cas9 system with Lipofectamine
transfection in vitro and in vivo for gene editing. Yip Bon et al. is therefore considered to
anticipate the subject-matter of claim 14 relating to a composition or
plasmid(s) comprising Cas and gRNA (see Yip Bon et al., abstract; Fig. 1A; page 8, 3.3.).
The additional steps of claims 8-11 are well known in the art and do not per se
account for an inventive step of said claims over the method of Jiao Xiang. It is
generally known that Cas9 can be delivered in the forms of DNA, mRNA (claim
8), or protein, see for example, Yip Bon et al., Fig. 1A. The transformation of yeast spheroplasts, which are prepared, for example, by enzymatic digestion, is also well known in the art, see for example, Kawai Shigeyuki et al. (page 395, last par.-page 396, col. 2 par. 1; Table 1; pages 401-402, Conclusion). The transformation methods of claim 11 are well known in the art, as mentioned for example, in Jiao Xiang (Introduction, col. 1-col. 2 bridging sentence) and are merely considered obvious variations which a skilled person would consider in accordance with the circumstances, without the exercise of inventive skill. Jiao Xiang demonstrates the feasibility of engineering R. torulosis’s with CRISPR/Cas by using a selection marker as donor DNA. Jiao Xiang is prior art for claim 16. Claim 16 differs from Jiao Xiang in that the donor DNA comprises a gene involved in
the production of a target compound and/or specific fatty acid by the GC rich
microorganism. It is clearly stated in Jiao Xiang that R. torulosis’s is a promising host for the production of lipids and carotenoids, and that the findings of Jiao Xiang establish CRISPR/Cas9 as a tool to facilitate efficient genetic engineering to generate advanced cell factories (abstract). Consequently, using a gene involved in lipid production as
the donor DNA is obviously one option envisaged in Jiao Xiang, and cannot per se
account for an inventive step. Thus, claim 16 is obvious over Jiao Xiang. Beyond Jiao Xiang, Gorner Christian et al. relates to genetic engineering of T. oleaginosus ATCC 20509 by Agrobacterium mediated transformation, but suggests developing a CRISPR
Cas based technique to address the challenge of homologous recombination in
T. oleaginosus (Gorner Christian et al., abstract; page 2038, col. 2, second full par.; page 2039, col.1, par.2 and col. 2 par. 2; Fig. 2; page 2045, col. 1 last par.). Further, the structures of the RNA-guided endonuclease are known in the art and one such reference is Telford that discloses SEQ ID NO: 1 with 100% sequence identity and its usage (see the entire reference).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious. The references are considered to be analogous art, thus motivation to combine exists.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Response to Arguments
8. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that the rejections of record remain for the reasons stated above and herein., but have been altered to reflect amendments made to the claims. Applicant traverses the rejection under 112, first paragraph by stating that claim 1 especially has been amended. This argument is not persuasive, because the amendments obviated some of the issues raised, however, some remains. The claimed invention remains directed to a broad variable genus of organisms. It is suggested that the organisms in claim 2 are imported for example into claim 1.
The art rejection remains and applicant states that the primary reference does not teach the GC content of at least 50%. This argument is not persuasive because this is a resulting effect of using the organism which is the same as disclosed in the art. Moreover, applicant state that the art does not teach genetically modifying the organism with is also not persuasive since the reference also transformed the organism as is done in the invention, thus the GC rich organism utilized would necessarily produce the same content, absent evidence to the contrary. The examiner would welcome an opportunity to discuss the remaining issues with applicant to place the application in better form.
Conclusion
9. No claims are presently allowable.
10. Applicant’s amendment necessitated the new/modified 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
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