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 .
Claims 1-16 are pending and have been considered on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 6 is objected to because of the following informalities: the term “VPR” in claim 6 would be more appropriate with a full name followed by the abbreviation in the parenthesis. 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 1-16 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.
Claims 1 and its dependent claims disclose “primordial germ cell like cell (PGCLC)”. The term “like” renders this term “primordial germ cell like cell (PGCLC)” indefinite as it is not clearly defined what the scope of the term is. Thus, it cannot be clearly determined what kind of cells would be included or excluded for the claimed cell type.
Claims 2-7 disclose “a CRISPRa fusion protein”. It is not clear what subject matter this term “CRISPRa” intends to point out. If this is for “activating” CRIPSR, applicant is advised to amend the claim language to disclose the meaning.
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 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to the method of producing PGCLC from a PSC upon the overexpression of GATA5. Throughout the instant specification, the experimental evidence provided by the specification is that the overexpression of GATA5 in PSCs, particularly iPSCs, is the expression of PGC markers including EOMES, SOX17, PRDM1 and TFAP2C.
The scope of overexpression is broad. The specification fails to provide what level of GATA5 overexpression is minimally required for the differentiation of PGCLC from the PSCs. It is noted that the specification as well as the dependent claims of claim 1 disclose the use of CRISPRa fusion protein operably linked to an inducible promoter. However, it is not fully described whether any inducible promoter is sufficiently overexpress GATA5 and thus produce PGCLC from PSCs.
The instant specification and claims discloses that the increased expression of EOMES, SOX17, PRDM1 or TFAP2C, the markers for PGC, in PSCs would qualify the cells as PGCLC. However, the specification does not provide any evidence that the GATA5 overexpressing PSCs that express PGC markers are indeed differentiated into functional PGCLC. It is known in the art that functional PGCLC can be derived from PSCs according to Oikawa et al. (2022, Science). However, it is also known in the art that overexpression of GATA5 in ESCs would promote cardiac differentiation of the ESCs according to Turbendian et al. (2013, Development).
In the absence of any showing that the overexpression of GATA5 in ESCs would produce PGCLC as claimed, and the most relevant evidence provided by the instant specification being the expression of PGCLC markers in GATA5 overexpressing ESCs, it is considered that the inventors had no possession on the method of producing PGCLC from PSCs by overexpressing GATA-5.
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
M.P.E.P. § 2163 also recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention… one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.” and further, “The description needed to satisfy the requirements of 35 U.S.C. 112 "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.< Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art. In most technologies which are mature, and wherein the knowledge and level of skill in the art is high, a written description question should not be raised for claims >present in the application when originally filed,< even if the specification discloses only a method of making the invention and the function of the invention. See, e.g., In re Hayes Microcomputer Products, Inc. Patent Litigation, 982 F.2d 1527, 1534-35, 25 USPQ2d 1241, 1246 (Fed. Cir. 1992) ("One skilled in the art would know how to program a microprocessor to perform the necessary steps described in the specification. Thus, an inventor is not required to describe every detail of his invention. An applicant's disclosure obligation varies according to the art to which the invention pertains. Disclosing a microprocessor capable of performing certain functions is sufficient to satisfy the requirement of section 112, first paragraph, when one skilled in the relevant art would understand what is intended and know how to carry it out."). In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5, 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lustig et al. (2022, BioRxiv; IDS ref.; published 8/3/2022).
The claimed method is interpreted as a method of overexpressing GATA5 in a pluripotent stem cell (PSC) as the active step of the method is “overexpressing GATA5 in a PSC”.
Lustig et al. teach a method of screening Xist activators or repressors by expressing CRISPRa system with a custom sgRNA library targeting X-chromosomal genes (Fig. 1). The screening system utilizes mouse ESC (Fig. 1). Lustig et al. teach the CRISPRa system is utilized to overexpress GATA factors 1-6 (Fig. 2), and all GATA factors can induce Xist expression (Fig. 2). The expression of GATA factor 5 expressed by the CRISPRa system in mESCs taught by Lustig et al. in Figure 2 would meet the claimed method step of overexpressing GATA5 in a PSC, and thus anticipate the claimed method.
Regarding the intended purpose of producing a PGCLC, the preamble does not require any additional active step to be carried out other than overexpressing GATA5 in a PSC. As the method of Lustig et al. anticipates the claimed active step, the results obtainable from the method are expected the same.
Regarding claim 2, a CRISPRa fusion protein stimulates expression of GATA5 in the presence of a guide RNA, the system of CRISPRa constitutes two components of dCas9 and the VPR activating domain are fused to ABI and PYL1 proteins respectively (p.20, Methods).
Regarding claim 3, while Lustig et al. do not particularly teach the expression of GATA5 is stimulated from its endogenous locus, the CRISPRa system utilized by Lustig et al. is understood to activate the endogenous GATA5 in their genetic locus.
Regarding claim 4, Lustig et al. teach that the CRISPRa system utilizes doxycycline-inducible promoter (p.21, 1st col.).
Regarding claim 5, Lustig et al. teach the mESC line stably integrated doxycycline-inducible CRISPRa SunTag system and the CRISPRa system utilizes dCas9 fused to VP64 (Fig. 1 and 2).
Regarding claim 7 directed to the method introducing the guide RNA or a nucleic acid encoding the gRNA into the PSC, Lustig et al. teach the mESCs are transduced with CRISPRaX sgRNA library (Fig. 1), and this teaching would meet the limitation.
Thus, the reference anticipates the claimed invention.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lustig et al. (supra) as applied to claims 1-5 above, and further in view of Guo et al. (2017, Protein Cell; IDS ref.).
Lustig et al. anticipate the subject matter of claims 1-5 and 7, and thus, render them obvious.
Regarding claim 6, Lustig et al. teach the mESC line stably integrated doxycycline-inducible CRISPRa SunTag system and the CRISPRa system utilizes dCas9 fused to VP64 (Fig. 1 and 2). However, Lustig et al. do not teach VPR fused to dCas9.
Guo et al. teach an inducible CRISPR-ON system comprising a dox inducible dCas9-VP64-p65-Rta (dCas9-VPR) transcription activator that is knocked in the human PSCs (Abstract).
It would have been obvious to a person skilled in the art to use the CRISPR-ON system taught by Guo et al. for the method of Lustig et al.
A person of ordinary skilled in the art would have been motivated to do so because the CRISPR-ON system taught by Guo et al. is well known alternative to CRISPRa system of Lustig et al. for activating endogenous gene expression.
Regarding claims 8-11 directed to the GATA5 overexpression being carried out by introducing a nucleic acid encoding GATA5 to a PSC in a recombinant expression vector or a virus comprising a nucleic acid encoding GATA5, Lustig et al. do not particularly teach the limitations.
However, it is extremely well known in the art that one protein can be overexpressed by introducing exogenous nucleic acid encoding the protein such as a virus vector. It would have been obvious to a person skilled in the art to overexpress GATA5 using exogenously introduced expression vector in place of the endogenous GATA5 activation taught by Lustig et al. with a reasonable expectation of success.
Furthermore, one skilled in the art would try to use human ESCs or hiPSCs to determine if the GATA TF including GATA5 identified as Xist would also have the same results in human cells. Thus, it would have been obvious to try human ESCs or iPSCs in the method of Lustig et al.
Regarding claims 14-16 directed to the PSCs being human cell, derived from a human patient or induced PSC, Lustig et al. do not teach the limitation as they teach mouse ESCs. However, it would have been obvious to a person skilled in the art to use PSCs from other sources including hPSCs or iPSCs from human cells as they are well known in the art. A person of ordinary skilled in the art would have been motivated to do so because the method taught by Lustig et al. is also applicable to human cells including hiPSCs.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631
