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 .
Election/Restrictions
Claims 65, 70-73 and 91 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/11/2026.
Drawings
The drawings are objected to because Figures 1, 4 and 5 appear to be unreadable. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 1, 2, 6-8, 10, 11, 13-15, 21, 30, 32 and 35 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 base claim provides for a system that comprises a polypeptide and nucleic acid sequence. The sequence comprises a 900 amino acid, or less, sequence that codes for a nuclease functionality, and a nucleic acid guide sequence that is capable of binding D4Z4; the claim further provides for functional characteristics of this compound, wherein biding and modifications of genes is described.
When looking at the instant specification, the only discussion of “nuclease” is drawn to Un1Cas12f1 and SEQ ID NO 43 and 44; there is, additionally, brief mention of other CRISPR-nucleases, like Cas9. There is no mention of any other nucleases. The claimed D4Z4 binding is only described to be achieved by (unclaimed) SEQ ID NO 1-14, wherein they are described as targeting the Dux4 gene. There are no other sequences described as being capable of targeting D4Z4 motifs, and there is no explicit mention of other sequences capable of targeting the Dux4 gene. When taking all of this information together, the Applicant clearly shows possession of very specific sequences, and variants, but does not show a reasonable cross-section of other variants that could fulfil the claimed limitations. Furthermore, the independent claim requires highly specific functionalities that would necessitate the skilled artisan to perform an immense number of experiments to make the claimed system, as claimed.
This is further underscored by the requirement that the invention provide for a nuclease that has about 900, or less, amino acids. This means that the inventor is requiring the skilled artisan to find a functional nuclease that is at most 900 amino acids, then ensure this functional nuclease can be functionally attached to the guide nucleic acid, wherein the system provides for the claimed functionalities.
Based upon the instant specification, and the broadly claimed invention, the Applicant has claimed significantly more than what they had possession of, and has only shown possession of a very narrow number of functional variants. This lack of possession is underscored because the claims require a specific functionality for them to read upon the claimed invention. This specific functionality, without describing any sequences, would require a skilled artisan an immense amount of work to reproduce. This analysis is consistent with the most recent 35 USC 112(a) Written Description examples provided by the Office on the USPTO website.
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, 2, 6-8, 10, 13-15, 21, 30, 32 and 35 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.
The term “about” in claims 1, 8 and 35 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Since there is no definition for the “term” about, it is unclear how much variability in the claimed 900 amino acids is within the scope of the claims. When considering the explicitly claimed SEQ ID NO 43 and 44, which are claimed to describe this limitation, both possess 529 amino acids, which fulfill the limitation, but do not shed light on what the upper end of “about 900 amino acids” could include. This rejection will be withdrawn if “about” is removed from the claim.
Claims 2, 6, 7, 10, 11, 13-15, 21, 30, and 32 are rejected insofar as they claim dependence on claim 1, but do not clarify the scope of “about.”
Claim 2 is further indefinite because it is unclear if the claimed function is directed by a particular ingredient provided in the composition, or if this is an inherent behavior of the claimed composition. Based upon the instant specification, this behavior appears to be inherent to the function of the claimed system, and if any art provides for the claimed system, that art would also inherently provide for this functionality.
Claim 6 is further unclear because the parent claim is drawn to targeting the D4Z4 repeat array; it is unclear how a particular diagnosis or suspected diagnosis would affect this targeting. If this limitation is drawn to targeting a specific mutation, this should be claimed; however, it does not appear as any specific mutations are described in the instant specification. For the sake of examining the claim on its merits, it will be assumed that the targeting of claim 6 is drawn to targeting the Dux4 gene.
Claim 10 is further indefinite because it is unclear what the scope of “modified variant” is. It is unclear if the claim is drawn to any modified Un1Cas12f1, or if the claim is also drawn to “variants” of Un1Cas12f1, wherein a “variant” is merely a nuclease that possesses overlapping functionalities.
Claim Rejections - 35 USC § 103
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 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.
Claims 1, 2, 6-8, 10, 11, 13, 21, 30, 32 and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jones, et al (PGPub 2020/0017842) and Seamon, et al (US Pat. 11,807,877). Jones teaches a system that comprises a recombinant gene editing protein, like the nuclease Cas9, and a nucleic acid sequence that is designed to specifically target D4Z4. See paragraph [0005] [0028] [0041]. Jones teaches that the system is capable in inhibiting aberrant Dux4 expression, which is consistent with the claimed functional characteristics of effecting expression level and/or methylation of the target gene. Jones differs from the claimed invention because Jones describes unmodified Cas9, which has nearly 1400 amino acids. However, Jones does not state that the composition can only function with Cas9, and suggests other functionally similar nucleases could be exchanged. See paragraph [0041].
Seamon provides for nuclease sequences that describe Cas-like activity. Following a sequence search the claimed SEQ ID NO 43 is identical to SEQ ID NO 1177 of Seamon, wherein Seamon explicitly states that this sequence possesses Cas-like nuclease activity. See column 4, lines 1-5.
Although Jones does not teach the claimed 900 or less amino acids in the nuclease, Jones explicitly states that any amino acid with Cas-like nuclease functionality should predictably work for the claimed system to perform. As such, the substitution of any of the Cas-like nucleases of Seamon would provide for highly predictable results, because the substitution of one Cas sequence, with another, would provide for nearly identical results.
With respect to claim 1, Jones teaches all of the claimed limitations, except for a nuclease that is, about, 900 amino acids or less. Seamon provides for functional nucleases that fall within the same class as those described by Seamon: CRISPR-Cas9. As such, it would be obvious to substitute one nuclease with another functionally identical nuclease, found within the same subgroup of nucleases, particularly Cas nucleases.
With respect to claim 2, this behavior should be inherent to the composition provided by Jones. If Jones is modified by Seamon, it would continue to be inherent, because Seamon provides for functionally identical nucleases as those disclosed in Jones.
With respect to claims 6 and 7, Jones is specifically drawn to treating FSHD by targeting the Dux4 gene. See paragraph [0005].
With respect to claims 8, 10, and 11, Jones describes that any Cas-like nuclease can predictably be used. Seamon describes Cas variants that are consistent with claims 8 and 11.
With respect to claims 13 and 21, Jones teaches KRAB domain. See paragraph [0010].
With respect to claim 32, Jones describes the composition in the form of a viral vector. See paragraph [0011].
With respect to claim 30, Jones describes using Cas sequences that “lack nuclease activity.” See paragraph [0041].
With respect to claim 34, Jones teaches the claimed method.
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Jones, et al (PGPub 2020/0017842) Seamon, et al (US Pat. 11,807,877) and McDonald, et al (Biology Open, 5, 866-874, 2016). Although Jones does teach a transcriptional regulator, specifically teaching the KRAB limitation, Jones does not teach the DNA methyltransferase limitation. However, based upon McDonald, if the ordinary artisan wants a functionally similar manner of silencing a gene when using a CRISPR/Cas9-based system, they would use a DNA methyltransferase to predictable results. See page 866, “Abstract” section. This would be obvious because there are a limited number of means for gene silencing, when using a CRISPR/Cas-system, wherein those known methods would provide for predictable gene silencing.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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