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 reply to the Restriction Requirement, dated April 26, 2026, has been received. By way of this submission, Applicant has elected, without traverse, the species of a guide RNA and inhibition of BMPR1A.
Claims 1-13 are pending in the application. Claims 5, 7-8, and 10-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 26, 2026.
Claims 1-4, 6, 9, and 13 are therefore under examination before the Office.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at paragraph 0102. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 6 is objected to because of the following informalities: the claim refers to “the” nucleic acid. Appropriate correction is required.
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.
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.
Claims 1-4, 6, 9, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Chen ("Inhibiting The Bmp Pathway Rescues Neural Stem Cell Defects In Alzheimer's Disease" ProQuest Dissertations, November 20, 2019, cited in IDS) in view of Park (Nat Neurosci. 2019 Apr;22(4):524-528).
Chen teaches that BMP signaling is increased in a model of Alzheimer's Disease, and that self-renewal defects seen in Alzheimer's Disease neural stem cells can be rescued by employing a small molecule inhibitor of BMP (page 64, last paragraph). Chen also teaches that increased BMP signaling may be the cause of increased astrogliosis seen in Alzheimer's Disease (page 68, last paragraph). Chen also teaches that use of a BMP receptor inhibitor rescues self-renewal deficits in Alzheimer's Disease, suggesting that this may treat the disease (page vi, also see page x: "A BMPR Inhibitor Rescues Neural Stem Cell Deficits in Human Alzheimer's Model").
Chen further teaches that inhibition of BMP signaling by administration of LDN-193189 increases self-renewal of cells (Figure 31), which is pertinent to claims 2-3. According to Applicant's specification at paragraph 0061, LDN-193189 is a small molecule inhibitor of BMPR-1A ("In some embodiments, the small molecule inhibitor is LDN193189 (or DM3189; CAS No. 1062368-24-4). See e.g., WO Patent Publications WO2009/114180, WO2012/100229, all of which are incorporated herein by reference for teaching of the LDN193189 small molecule inhibitor.").
However, Chen does not teach a guide RNA.
Park teaches that gene editing with CRISPR-Cas9 is a useful method to inhibit activity of a protein for the purpose of treating Alzheimer's disease (Figure 2). Park also teaches that this method is more efficient than chemical inhibition (page 527, left column).
Park also teaches that this method replies upon a guide RNA that targets Cas9 to the appropriate location (page 524, left column, last paragraph: "In the present study, we tested whether Cas9 and single-guide RNAs (sgRNAs) loaded into an amphiphilic nanocomplex could lead to efficient gene targeting in post-mitotic neurons in vivo.").
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Chen and Park to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Chen and Park are concerned with treatments for Alzheimer's disease. Inhibition of BMPR-1A was known to be useful in treating Alzheimer's disease by increasing self-renewal of neural stem cells, according to the teachings of Chen. Park teaches that gene editing with CRISPR-Cas9 guide RNAs are one such method to achieve inhibition of genes known to be relevant for Alzheimer's disease. One of ordinary skill could apply the guide RNA and Cas9 complex of Park to inhibit BMPR-1A according to Chen, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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