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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Election filed July 8, 2026.
Claims 1-3 and 5-20 are pending in the instant application.
Election/Restrictions
Applicant’s election (without traverse) of Group I in the reply filed on July 8, 2026 is acknowledged. The further election of the small organic compound, palbociclib as the Pax6 inhibitor species in the reply filed on July 8, 2026 is also acknowledged.
Claims 10-14 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 8, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1-3, 5-9 and 15-19 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed April 17, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
The listing of references in the specification at pages 111-117 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The Drawings filed on November 10, 2023 are acknowledged. However, the Drawings are objected to because some Drawings reference the colors “green” and “red”. See Figure 2C, for example. In the instant application, color drawings have been filed without an accompanying petition. 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.
Color photographs and color drawings are not accepted unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), three sets of color drawings or color photographs, as appropriate, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37CFR 1.84(b)(2). Note that the requirement for three sets of color drawings under 37 CFR 1.84(a)(2)(ii) is not applicable to color drawings submitted via EFS-Web. Therefore, only one set of such color drawings is necessary when filing via EFS-Web.
Nucleotide Sequence Disclosures
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. §1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §1.821-1.825 for the reason(s) set forth below or on the attached Notice To Comply with Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures. The disclosure contains sequences which fall under the purview of 37 CFR 1.821 through 1.825 as requiring SEQ ID NOs., but which are not so identified. For example, see Figure 1C. This is an example and does not indicate that the Examiner has made an exhaustive review of the application. Applicant must fully comply with the sequence rules for any response to this action to be considered fully responsive.
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 1-3, 5-9 and 15-19 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 pre-AIA the applicant regards as the invention.
The claims are indefinite because the term, “Pax6” is not clearly defined. Since abbreviations often have more than one meaning, it is suggested that inserting the full name of the paired box 6 (Pax6) would be appropriate.
Claims 17 and 19 are indefinite because it is unclear whether parts following the term, “optionally” are actually a part of the claims. The term, “optionally” is ambiguous and confusing since the alternatives covered by the claims are not clear. See MPEP 2173.05(h) for further explanation.
Claim 5 is rejected because the claim recites the phrase, “wherein the tauopathy”. The claim is rejected for a lack of antecedent basis because claim 1, from which claim 5 depends never makes reference to tauopathy. Appropriate correction is required.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 1-3, 5-8, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Poster Presentation No. P-H028, Abstract, December 31, 2011) (hereinafter, “Zhang”) (submitted and made of record on the Information Disclosure Statement filed April 17, 2024).
The claims are drawn to a method of reducing Tau phosphorylation or total Tau in neurons of a subject in need thereof comprising administering the subject an effective amount of a direct or indirect inhibitor of Pax6 (Pax6 inhibitor). The claims are also drawn to a method of treating a proteinopathy, amyloidosis, or a tauopathy comprising administering the subject an effective amount of Pax6 inhibitor. Although Applicants elected the small organic compound palbociclib as the Pax6 inhibitor species (see Applicant’s Election filed July 8, 2026), the breadth of the claims read on inhibitory peptides; small organic molecules; or inhibitory nucleic acids, such as siRNA.
The present Specification discloses:
“Effective amount” means a dosage sufficient to alleviate one or more symptoms of a disorder, disease, or condition being treated, or to otherwise provide a desired pharmacologic and/or physiologic effect.
The Examiner will interpret the term, “effect amount” to mean any dosage that causes a physiological effect.
Zhang teach the role of Pax6 in Beta-Amyloid toxicity and Alzheimer’s disease (AD). For example, Zhang teach siRNA-mediated knockdown of Pax6 protects cultured mouse cortical neurons from Ab1-42 induced neuronal death. Zhang teach taken together, Pax6 is required for Ab1-42 induced neuronal apoptosis and play an important role in Alzheimer’s disease pathogenesis. Zhang conclude that their study provides insight into development of therapeutic agents and approaches for AD through inhibition of Pax6 which has lower expression in normal adult brain.
It should be noted that Alzheimer’s disease (AD) is the most frequent type of amyloidosis in humans as evidenced by Ghiso et al. (Advanced Drug Delivery Reviews Vol. 54 (2002), 1539-1551).
While Zhang does not necessarily teach the siRNA Pax6 inhibitor of their studies reduced the Tau phosphorylation or total Tau in neurons of a subject, it is noted that Zhang teach the exact method step as presently claimed. Namely, administration of an effective amount of a siRNA Pax6 inhibitor to a subject. Any underlying mechanism of action would naturally flow and be inherent to administration of the siRNA Pax6 inhibitor to the subject. See MPEP 2112 as it relates to inherency. Also, see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and In re Best, 562 F.2d 1252 (CCPA 1977).
Also, Zhang does not necessarily teach the siRNA Pax6 inhibitor of their studies reduced the formation of amyloid b plaques or the formation of neurofibrillary tangles, however, Zhang teaches the exact method step as presently claimed. As supra, any underlying mechanism of action would naturally flow and be inherent to administration of the siRNA Pax6 inhibitor to the subject. See MPEP 2112; In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990); and In re Best, 562 F.2d 1252 (CCPA 1977).
The Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
Before the effective filing date of the claimed invention, a method of treating Alzheimer’s disease, the method comprising administering a Pax6 inhibitor to a subject in need thereof was known in the prior art of Zhang.
Starting from Zhang, it would have been obvious and a person of ordinary skill in the art would have been motivated to devise the methods of the claimed invention for the purpose of treating Alzheimer’s disease in a subject.
Therefore, the subject matter of claims 1-3, 5-8, 15 and 16 is obvious over Zhang.
******
Claims 1 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Poster Presentation No. P-H028, Abstract, December 31, 2011) (hereinafter, “Zhang”) (submitted and made of record on the Information Disclosure Statement filed April 17, 2024) in view of U.S. Patent No. 8017765 B2.
The claims are as described above.
Zhang is relied upon supra.
Applicant is reminded that Zhang does not necessarily teach the siRNA Pax6 inhibitor of their studies reduced the Tau phosphorylation or total Tau in neurons of a subject, however, Zhang teach the exact method step as presently claimed. Any underlying mechanism of action would naturally flow and be inherent to administration of the siRNA Pax6 inhibitor to the subject. See MPEP 2112; In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990); and In re Best, 562 F.2d 1252 (CCPA 1977).
Zhang does not necessarily teach wherein the Pax6 inhibitor is administered to the subject by an oral, parenteral, transdermal, or transmucosal administration; wherein the Pax6 inhibitor is administered to the subject locally or systemically; or wherein the inhibitor is packaged in a delivery vehicle, such as liposomes.
U.S. Patent No. 8017765 teach rNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA). The patent discloses that siRNA are administered by oral administration or systemically. The patent also teaches that siRNAs are delivered to cells in a delivery vehicle, such as a vector or liposome.
In this rejection, the Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
Before the effective filing date of the claimed invention, a method of treating Alzheimer’s disease, the method comprising administering a Pax6 inhibitor to a subject in need thereof was known in the prior art of Zhang.
It would have been obvious to modify the teachings of Zhang to include the delivery methods of U.S. Patent No. 8017765 for the purpose of targeting the siRNA to specific cells or tissues.
Starting with Zhang, it would have been obvious to devise the methods of the claimed invention for the purpose of treating Alzheimer’s disease in a subject.
A person of ordinary skill in the would have expected reasonable success to administer the siRNA Pax6 inhibitor of Zhang using the delivery methods of U.S. Patent No. 8017765 since the patent teaches successful delivery modes of siRNA for the treatment of Alzheimer’s disease.
Therefore, the subject matter of claims 1 and 17-18 is obvious over Zhang in view of U.S. Patent No. 8017765.
******
Claims 1-3, 5, 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Pallás et al. (Medical Hypotheses (2005) 64, 120-123) or Jorda et al. (Neuropharmacology 45 (2003) 672-683).
The claims are as described above.
Pallás et al. teach flavopiridol as an antitumor drug with potential application in the treatment of neurodegenerative diseases, such as Alzheimer’s disease. For example, Pallás et al. teach that it has been demonstrated that small organic compound, flavopiridol has neuroprotective effects following the administration of MPTP to rats, a model of Parkinson’s disease; and in rat models of stroke, flavopiridol reduces the ischemia-induced damage. Pallás et al. conclude that CDK inhibitors, such as flavopiridol could be used to treat neurodegenerative diseases in humans.
Jorda et al. teach the neuroprotective action of flavopiridol in Alzheimer’s disease. For example, Jorda et al. teach the small organic compound, flavopiridol shows neuroprotective effects in neurons that are independent of the cell cycle but are probably mediated through the inhibition of cdk5. Jorda conclude and suggest that flavopiridol could be a suitable drug in the treatment of neurodegenerative disorders, such as Alzheimer’s disease.
Before the effective filing date of the claimed invention, a method of treating Alzheimer’s disease, the method comprising administering the small molecule inhibitor flavopiridol to a subject in need thereof was known in the prior art of Pallás et al. or Jorda et al.
While neither Pallás et al. nor Jorda et al. necessarily teach the small molecule inhibitor flavopiridol of their studies reduced the Tau phosphorylation or total Tau in neurons of a subject, it is noted that both Pallás et al. and Jorda et al. teach the exact method step as presently claimed. Namely, administration of an effective amount of a Pax6 inhibitor comprising flavopiridol to a subject. Any underlying mechanism of action would naturally flow and be inherent to administration of the inhibitor to the subject. See MPEP 2112 as it relates to inherency. Also, see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and In re Best, 562 F.2d 1252 (CCPA 1977).
In this rejection, the Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
For the reasons discussed above, the subject matter of claims 1-3, 5, 8 and 9 is obvious over either Pallás et al. or Jorda et al.
******
Claims 1-3, 5, 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Venigalla et al. (NEURAL REGENERATION RESEARCH August 2015, Volume 10,Issue 8, pages 1181-1185).
The claims are as described above.
Venigalla et al. teach small organic compound, apigenin as a novel and promising therapeutic against chronic neuroinflammation in Alzheimer’s disease. For example, Venigalla et al. teach based on the results emerging from cell culture, animal and human studies, we conclude that apigenin is an exceptional candidate for an anti-inflammatory therapy against Alzheimer’s disease and other related degenerative disorders, ready to enter clinical trials within a short time frame.
Before the effective filing date of the claimed invention, a method of treating Alzheimer’s disease, the method comprising administering the small molecule inhibitor apigenin to a subject in need thereof was known in the prior art of Venigalla et al.
While Venigalla et al. does not necessarily teach the small molecule inhibitor apigenin of their studies reduced the Tau phosphorylation or total Tau in neurons of a subject, it is noted that Venigalla et al. teach the exact method step as presently claimed. Namely, administration of an effective amount of a Pax6 inhibitor comprising apigenin to a subject. Any underlying mechanism of action would naturally flow and be inherent to administration of the inhibitor to the subject. See MPEP 2112 as it relates to inherency. Also, see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and In re Best, 562 F.2d 1252 (CCPA 1977).
In this rejection, the Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
For the reasons discussed above, the subject matter of claims 1-3, 5, 8 and 9 is obvious over Venigalla et al.
******
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Shaik et al. (Oncotarget, 2018, Vol. 9, (No. 70), pp: 33249-33257) (submitted and made of record on the IDS filed April 17, 2024).
The claim is as described above.
Shaik et al. teach the penetratin-linked peptides, L-Arg PEP Penetratin-HHHRLSH and D-Arg PEP Penetratin-HHH(D)RLSH as drug candidates for targeted molecular therapy of cancers with elevated levels of activated E2F(s).
While Shaik et al. does not necessarily teach the peptide inhibitors of their studies treat a proteinopathy, amyloidosis, or a tauopathy, it is noted that Shaik et al. teach the exact method step as presently claimed. Namely, administration of the peptide inhibitors, L-Arg PEP Penetratin-HHHRLSH and D-Arg PEP Penetratin-HHH(D)RLSH to a subject. It should be noted that any underlying mechanism of action would naturally flow and be inherent to administration of the inhibitor to the subject. See MPEP 2112 as it relates to inherency. Also, see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and In re Best, 562 F.2d 1252 (CCPA 1977).
In this rejection, the Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
For the reasons discussed above, the subject matter of claim 3 is obvious over Shaik et al.
Improper Markush Groups
Claim 9 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Regarding claim 9, the Markush grouping of Pax6 inhibitors is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The groupings do not share a single structural similarity. Between these Pax6 inhibitors, they do not share a single structural similarity as they are structurally different inhibitors (e.g. chemical organic compounds versus nucleic acids).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO's Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO's Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO's PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/TERRA C GIBBS/Primary Examiner, Art Unit 1635
Prosecution Insights