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
Applicant’s election without traverse Group II and election of TSS 2a, DNA binding recognition sequences: SEQ ID NO: 122,123,72,75,124 and 125 which corresponds to SEQ ID NO: 121 for the binding sequence (claim 28) and SEQ ID NO: 199 (full amino acid sequence) in the reply filed on 3/25/26 is acknowledged.
Claims 1-10, 12, 14-15, 18-25, 28-35 are pending.
Claims 18-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1-10, 14-15 and 28-35 read on the elected Group II and species and are under consideration.
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 1-10, 12, 14-15, 28, 30, 31, and 34 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, 30 and 31 are indefinite because the limitation “…and the “^” indicates that the arginine (R ) residue at the 4th position upstream of the 1st amino acid in the indicated helix is changed to a glutamine (Q)” is unclear. The claim recites only the indicated peptide sequences and does not identify any upstream amino acid sequence from which the “4th position upstream” can be determined. Accordingly, it is unclear which residue is modified by the symbol. It is impossible to determine the metes and bounds of the claim.
Claim 1 is also indefinite because it is unclear if the peptides can be picked from any row in the F1 to F6 order or if the sequences are meant to be in a single row. For example, can any peptide be chosen from column F1, F2, F3, F4, F5 and F6 or if the sequences are confined to a single row. It is impossible to determine the metes and bounds of the claim.
Claim 5 is indefinite because the limitation “at least about” is unclear. The limitation “about” is broad but not indefinite. Similarly, the limitation “at least” is broad but not indefinite. However, “at least about” is indefinite because the metes and bounds cannot be determine. “About” indicates values below 40%, which necessarily fails to meet the limitation of “at least”.
The term “minimal” in claim 5 is a relative term which renders the claim indefinite. The term “minimal” 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. The limitation “minimal” denotes some off target binding or activity, however it is unclear what amount is considered “minimal” as opposed to not-minimal.
Claims 2-10, 12, 14-15, 28, 30-31 and 34 are rejected for depending from claim 1.
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 1-9, 12, 14-15, 28 and 34 are rejected under 35 U.S.C. 103 as being obvious over Miller et al. (US2020/0109406, published 4/9/2020).
The applied reference has a common inventor (Zeitler) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Miller et al. teach a composition comprising two or more artificial transcription factors for use in specific and active modulation of gene expression (Abstract). Miller et al. teach fusion proteins and nucleic acids encoding them [0118]. Miller et al. teach the fusion proteins contain a function component, such as a transcriptional repressor [0121]. In particular, Miller et al. teach the DNA binding domains of the artificial transcription factors of the genetic modulator comprise a ZFP to from a ZFP-TF. Any of the zinc finger proteins described herein may include 1,2,3,4,5,6 or more zinc fingers, each zinc finger having a recognition helix that binds to a target subsite in the selected target sequence. Miller et al. teach repression of the human alpha-synuclein gene (SNCA) [0045-0046]. Miller et al. teach exemplary designs of the fusion protein with ZFP domains F1 to F6 [0179, Table 1]. Table 1 discloses ZFP domains. Miller et al. teach the ZFP domains can be in any order or combination [0015].
Miller et al. teach the effects of 132 combinations of ZFP-TF’s targeting the alpha-synuclein gene at various spacing between repression domains [0046]. With respect to the limitation “in F1 to F6 order, a DNA-binding recognition sequence as shown in the table below”, Miller et al. teach ZFP domains that meet the limitation of the instantly claimed domains. For example, Miller et al. teach SEQ ID NO: 36, which is identical to instantly claimed SEQ ID NO: 124 (Table 1, p. 25). Miller et al. teach SEQ ID NO: 19, which is identical to instant SEQ ID NO: 48 (Table 1, p. 25). Miller et al. teach SEQ ID NO: 20 that meets the limitation of instant SEQ ID NO: 49 (Table 1, p. 25). Miller et al. teach SEQ ID NO: 42 that meets the limitation of instant SEQ ID NO: 22(Table 1, p. 25).
Miller et al. teach SEQ ID NO: 20 that meets the limitation of instant SEQ ID NO: 49 (Table 1, p. 25). Miller et al. teach SEQ ID NO: 19 that meets the limitation of instant SEQ ID NO: 48 (Table 1, p. 25). Therefore, Table 1 of Miller et al. comprises peptides that meet the limitations of F1 through F6.
Miller et al. does not teach the order of the peptides is F1 to F6. However, Miller is suggestive of the limitation as indicated in claim 1.
It would have been obvious to a person of ordinary skill in the art to optimize the order of the ZFP domain peptides in order to optimize repression of alpha-synuclein. A person of ordinary skill in the art would look to the teachings of Miller et al. and have a motivation to optimize the order of the ZFP domain peptides because Miller et al. teach the ZFP domains can be in any order and combination. There is a reasonable expectation of success given that Miller et al. teach each of the peptides claimed and also teach methods of making and testing the fusion proteins.
With respect to claim 2, Miller et al. teach the target region is within 0 to 600 bp of the TSS [0007,0022]. 0-600 bp meets the limitation of “within 1 Kb”. Miller et al. teach repression of the human alpha-synuclein gene (SNCA) [0045-0046].
With respect to claims 3-4, it would have been obvious to a person of ordinary skill in the art to target a region 500 bp upstream of TSS1, within 500 bp downstream of TSS1, within 500bps upstream of TSS 2a and/or within 500 bp downstream of TSS 2b of the SNCA gene using the disclosed ZFP domains because the prior art teaches the identical peptides having the same recognition properties. There is a reasonable expectation of success given that the same peptides disclosed would bind the same target sequences located within the claimed region of the TSS.
With respect to claim 5, it would be obvious to a person of ordinary skill in the art to repress the SNCA gene by at least 40%. The amount of SNCA gene repression is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, Miller et al. teach using the methods described in the application, the methods can yield about 50% or greater…or about 95% or greater repression of target alleles (e.g. SNCA gene). It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the repression of SNCA, to arrive at the ranges of claim 5.
With respect to claim 6, Miller et al. teach transcription repressor domain comprises the KRAB domain of Kox1 [0035,0038,0042,0044,0046,0081,0116].
With respect to claim 7, Miller et al. teach the ZFPs can be linked to one or more transcriptional regulatory (e.g. repressor domains) to form a ZFP-TF (e.g. repressor) [0089]. Miller et al. teach that the ZFP domains can be linked via linkers of 5 or more amino acids [0088]. It would have been obvious to optimize the fusion protein including peptide linkers to create a fusion protein capable of binding to SNCA gene.
With respect to claims 8 and 9, Miller et al. teach the promoter is a human synapsin 1 promoter [0026, 0039,0040,0211,0213]. As evidenced by claim 9, hSyn1 promoter is constitutively active or inducible in a brain cell.
With respect to claims 12, 14,15 and 34. Miller et al. teach methods for delivering the nucleic acids and proteins including viral vectors [0135-0137]. Miller et al. teach host cells comprising viral particles, such as 293 cells [0151]. Miller et al. teach the fusion proteins formulated with a pharmaceutically acceptable carrier [0120].
With respect to claim 28, Miller et al. does not teach the ZFP domain binds to the genomic target sequence of claim 28. However, as indicated above, the fusion protein of claim 1 was made obvious my Miller et al. Therefore, the same fusion protein would necessarily bind the same target sequence. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (US2020/0109406) as applied to claims 1-9, 12, 14-15,28 and 34 above, and further in view of GenBank AAS00545.1 (04/05/2004).
Miller et al. does not teach the sequence of the KRAB domain. However, the teachings of GenBank cure this deficiency.
GenBank teaches the sequence the transcription repressor KRAB domain is identical to SEQ ID NO: 12.
It would have been obvious to a person of ordinary skill in the art to use sequence of KRAB from Genbank because it is the known sequence for the repressor domain. There is a reasonable expectation of success given that the sequence is well known in the art.
Allowable Subject Matter
Claims 29, 32,33 and 35 are objected to as being dependent upon a rejected base claim, but would be allow, able if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The peptides of claims 29, 32, 33 and 35 are free of the art. The closest art is Miller et al. (presented above). However, Miller et al. does not teach or suggest SEQ ID NO: 199-225. SEQ ID NO: 199-225 contain specific F1-F6 ZFP’s in a specific order with intramodule and intermodule linkers that is neither taught or suggested by the prior art.
Conclusion
Claims 1-10, 12, 14-15, 28, 30, 31 and 34 are rejected.
Claims 29, 32, 33 and 35 are objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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