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 Preliminary Amendments filed on December 16, 2024 and February 27, 2025, have been received and entered.
Claim Disposition
3. Claims 1-40 are canceled. Claims 41-60 have been added. Claims 41-60 are pending and are under examination.
Information Disclosure Statement
4. The Information Disclosure Statements filed on February 27, 2025, July 2, 2025, October 28, 2025, December 23, 2025, April 15, 2026, June 2, 2026, June 25, 2026 and July 29, 2026, have been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action. Note that a reference has been lined through based on an improper citation of the date.
Drawing
5. The Drawings filed on December 16, 2024, are accepted by the examiner.
Specification Objection
6. The specification is objected to for the following informalities:
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: "An epigenetic editing system and methods of using the same".
Appropriate correction is required.
Claim objection
7. Claims 41-60 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 41 is amended to spell out acronym ‘DNMT3L’ (see also claims 47-48, 51 and 57, for example). The dependent claims hereto are also included.
For clarity it is suggested that claims 42, 44, 50, 52 and 59 are amended to delete ‘homologous’ and instead recite “sequence identity’ for example, “…at least 90% sequence identity to ……”, because homology speaks to evolutionary ties and sequence identity is comparing the sequence structures.
For clarity it is suggested that claims 48-49 are amended to delete ‘derived’ and instead recite ‘obtained’.
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.
8. Claims 41-60 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 “an epigenetic editing system comprising a fusion protein with two domains from a species selected from several organisms…or a nucleic acid molecule encoding the fusion protein”, however the claim language is devoid of any structural limitations, thus not adequately described. The invention as claimed in claim 41 does not provide the structure of the domains, or the structure of the fusion protein or the structure of the nucleic acid that encodes the fusion protein. It is noted that dependent claims provide structures, however, the independent claim needs to stand on its own.
The claimed invention encompasses a large variable genus of structures with the recitation of “at least 90% homologous” to the list of sequences recited in the claims. The claimed invention is overly broad and not commensurate in scope with the disclosure in the specification because the invention includes analogs, derivatives, fragments etc. with the recitation of the afore-mentioned percentages and no alignment is made with a specific structure that is 90% with retention of activity. The claimed invention does not inform the ordinary skilled worker of the specific product, as no correlation is made between structure and function.
The claimed invention encompasses a large variable genus of structures for the protein and nucleic acid, that is not adequately described. The art recognizes that a single change in the protein structure can be detrimental for functioning, which would produce a different structure and which makes the instant claim language overly broad. The structural difference could render the protein as non-functional. The claimed invention is not adequately described because the claims far exceed the scope of the disclosure in the specification and the art. The claimed invention also encompasses additional domains with no assertion of where they are positioned in the fusion protein.
Thus the claimed invention is not adequately described because there is no demonstration of applicant being in possession of the vast genus encompassed in the claims. 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:
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.
9. 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.
10. Claim(s) 41, 54, 56 and 58 is/are rejected under 35 U.S.C. 103 as being unpatentable over by Naldini et al., (WO 2016/063264, 2016, of record in the application) in view of Zoch et al. (Edinburgh Research Explorer, 2020).
The claimed invention is directed to an epigenetic editing system comprising a fusion protein structure….or a nucleic acid molecule encoding the fusion protein. Based on the breath of claim 41 the below reference is being applied.
Naldini et al. teach a product comprising two or more artificial transcription repressors (ATRs), or polynucleotides encoding therefor, selected from groups (a), (b), (c) or (d): (a) an ATR comprising a DNA-binding domain operably linked to a KRAB domain or homologue thereof; (b) an ATR comprising a DNA-binding domain operably linked to a DNMT3A, DNMT3B or DNMT1 domain or homologue thereof; (c) an ATR comprising a DNA-binding domain operably linked to a DNMT3L domain or homologue thereof; and (d) an ATR comprising a DNA-binding domain operably linked to a SETDB1 domain or homologue thereof, wherein at least two of the ATRs are selected from different groups (a), (b), (c) or (d), (see Abstract). The structure of the reference has NLS structure (see SEQ ID NO:1). The reference teaches methods and uses of the present invention, for example methods of gene therapy or silencing a target gene, may also include a step of inactivating an endogenous gene that may counteract the activity of the ATRs or separate effector proteins of the invention. For example, the DNMT3B gene may be inactivated. The inactivation of this method step may, for example, be transient or permanent. The inactivation may, for example, be accomplished by genetic deletion, for example by using CRISPR/Cas9-based approaches, or by post- transcriptional downregulation, for example by using sh/siRNAs, or by transcriptional downregulation, for example by using an individual KRAB-based ATR targeted to the regulatory sequences of the gene of interest. Inactivating DNMT3B may be particularly preferred when three ATRs individually comprising KRAB, DNMT3A and DNMT3L domains are used. The primary reference does not teach the organisms found in claim 41, however, they are known in the field, one such reference is Zoch et al. which teaches Ailuropoda melanoleuca (see pages 1-3 of the reference).
Zoch et al. discloses acquisition of the germline from the soma provides the germline with male germline RNA-directed DNA methylation silences young active transposable elements (TEs)2-4. The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) instruct TE DNA methylation3,5. PiRNAs are proposed to tether MIWI2 to nascent TE transcripts, however the mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery…..(see pages 1-4 and figures (specifically FIG 0.4)).
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 render the claimed invention as obvious. Motivation exists to combine the references because they are analogous art.
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.
Conclusion
11. No claims are presently allowable.
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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