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 of Group III, claims 17-26 in the reply filed on 22 May 2025 and Applicant’s election without traverse of SEQ ID NO: 280 in the reply filed on 03 October 2025 are acknowledged. The amendments to the claims on 22 May 2025 necessitated the election of species.
Claims 1-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 22 May 2025.
Claim Status
Claims 1, 7-8, and 17 have been amended, claims 22 and 27-28 are canceled, claims 1-16 are withdrawn, and claims 17-21 and 23-26 have been considered on their merits.
Drawings
The drawings are objected to because in the drawings submitted on 01 April 2022, the figures at pp. 20 and 39-41 do not have a label indicating the figure number.
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 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 17-21 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.
Regarding claim 17, drawn to the recitation in the third and fourth line of the claim, “…as shown in a single row in a table shown in FIG. 8A…”. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP 2173.05(q).
Claims 18-21 depend from claim 17 and do not resolve the issue, therefore, they are included in the rejection.
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 17-21 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Zeitler et al. (Molecular Therapy, 2017, IDS ref.) in view of Hossain et al. (Journal of Cellular Biochemistry, 2015) and Maccecchini (US 2012/0225922, published 06 September 2012).
Regarding claim 17, Zeitler et al. teach zinc finger protein (ZFP)-transcription factors (TF) can be engineered to regulate any gene and ZFP-TF (a fusion protein) are derived from human proteins and do not edit or cut the DNA (slide 6). Zeitler et al. teach a single AAV-ZFP-TF blocked production of tau at the DNA level, demonstrating the ability of the fusion proteins ability to reach the brain of the subject and effectively block transcription (slide 7).
Zeitler et al. is silent to where the fusion protein binds to the specific binding sequence as shown in a table shown in Fig. 8A, wherein the binding sequence is SEQ ID NO: 280, thereby inhibiting the expression of PrP in the cell.
However, designing ZFP DNA binding domains to a specific sequence is known in the art.
Hossain et al. teach there are several widely used tools that can predict the optimal target DNA sequence for recognition by tailored zinc finger DNA binding domains (ZFDBDs) (p. 2436, Design and Generation of Artificial ZF-DNA Binding Proteins). Hossain et al. teach to target a unique site in the human genome ZFDBDs need to contain at least 6 ZFs and the reason for this is a DNA sequence larger than 18 bps is predicted to be present only once in the human genome (p. 2437, 1st column). Hossain et al. teach several platforms are available that assist in the design and generation of ZFDBDs (p. 2437, 2nd column). Hossain et al. teach ZFDBDs can be fused to transcriptional activation or repression domains to alter expression of specific genes (p. 2439, Application of ZFDBDS). Hossain et al. teach ZFDBDs have the advantage of being relatively small and of being able to penetrate cell membranes (p. 2442, Conclusions and Future Directions).
Zeitler et al. in view of Hossain et al. are silent to the binding sequence is SEQ ID NO: 280.
Maccecchini teaches the sequence of the human prion gene 5’ UTR, SEQ ID NO: 21, which comprises instant SEQ ID NO: 280, as shown in the sequence search results, file us-17-766-083-280.rng result 4. See alignment below:
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156
620
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Greyscale
Maccecchini is silent to a fusion protein which binds said sequence, however, the teachings of Maccecchini highlight the relationship between tauopathies, such as Alzheimer’s disease, and prion diseases, such as transmissible spongiform encephalopathies. Maccecchini teaches methods of inhibiting production of a neurotoxic aggregating protein in a subject (para. [0022]). Maccecchini teaches various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), transmissible spongiform encephalopathies (TSEs), and amyotrophic lateral sclerosis (ALS), have been shown to share a common cause and pathological mechanism-the misfolding, aggregation and accumulation of proteins in the brain, resulting in neuronal apoptosis (para. [0001]). Maccecchini teaches unlike other kinds of infectious disease by microbes, the infectious agent in TSEs is thought to be a specific protein called prion protein (para. [0008]). Maccecchini teaches non-limiting examples of transmissible spongiform encephalopathies (TSE) prions are Creutzfeldt-Jakob disease (CJD) or Variant Creutzfeldt-Jakob disease (vCJD, nvCJD) prion (para. [0073]).
Therefore, it would have been obvious to one of ordinary skill in the art to apply the teachings of Hossain et al. and Maccecchini to the ZFP-TF of Zeitler et al. with a reasonable expectation of success because designing specific ZFP binding motifs and the sequence of the prion protein are well known in the art. One would be motivated to apply the teachings of Hossain et al. and Maccecchini to the ZFP-TF of Zeitler et al. because Hossain et al. suggest future ZFDBDs may be used without a DNA intermediate, which not only reduces concerns about DNA integration mediated mutagenesis, but also may allow precise dosing of these proteins for experimental or therapeutic purposes (p. 2442, Conclusions and Future Directions) and because Zeitler et al. teach ZFP-TF can be engineered to regulate any gene (slide 6).
Regarding claims 18-20, Zeitler et al. suggest a therapy wherein a single AAV-ZFP-TF is administered to a human patient (claim 18), wherein the AAV traffics to neurons (claim 19), ZFP-TF is expressed, and represses tau (slide 7). Said in vivo therapy reads as wherein the cell is in the brain of a patient suffering from or at risk of developing prion disease (claim 20). Zeitler et al. teach their methods can be applied to any neurodegenerative disease and neurodegenerative diseases affect neurons, but also glial cells. Maccecchini teach neurodegenerative diseases include prion disease. Neurons are well-known to express prions. Therefore, the combined teachings of Zeitler et al. in view of Hossain et al. and Maccecchini teach the limitations of the claims.
Regarding claim 21, Maccecchini teaches non-limiting examples of transmissible spongiform encephalopathies (TSE) (acquired prion disease) prions are Creutzfeldt-Jakob disease (CJD) or Variant Creutzfeldt-Jakob disease (vCJD, nvCJD) prion (para. [0073]).
Regarding claim 23, Zeitler et al. teach the AAV-ZFP-TF serotype is AAV9 (slides 9-11). Additionally, AAV9 is a well-known serotype for transfecting cells of the CNS because of the ability to cross the blood-brain barrier.
Regarding claims 24 and 26, Maccecchini teaches non-limiting examples of transmissible spongiform encephalopathies (TSE) (acquired prion disease) prions are Creutzfeldt-Jakob disease (CJD) or Variant Creutzfeldt-Jakob disease (vCJD, nvCJD) prion (para. [0073]).
Regarding claim 25, Zeitler et al. teach three options for administration, to include intrathecal, intravenous, or intracranial (slide 7).
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.
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Haigh et al. (International Journal of Biomedical Science, 2006)
Haigh et al. teach Transmissible Spongiform Encephalopathies (TSEs) are a group of rare neurodegenerative diseases, which can be transmitted between members of the same species and possibly across different species. Haigh et al. teach the link between the emergence of Bovine Spongiform Encephalopathy (BSE) and the new variant form of Creutzfedlt Jakob Disease (vCJD). Haigh et al. teach the agent responsible for these diseases is a conformationally altered form of a normal cell surface glycoprotein, called the prion protein (PrP). Haigh et al. teach the control of PrPc expression is complex which involves not only the promoter and regulatory regions preceding the promoter, but also intron 1. Haigh et al. suggest a new approach, such as gene regulation, could increase the possibility of finding the appropriate target for a via therapeutic strategy for TSEs. Encephalopathies (TSEs)
Conclusion
No claims are allowed.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631