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 .
Claims 1-25 are pending in this application. The Examiner notes that Claim 22 is duplicated. The second Claim 22 should be designated as Claim 23 and subsequent Original Claims 23-25 should be renumbered as Claims 24-26. This numbering will be used in the action subsequently.
Election/Restrictions
Applicant’s election of Group IV (Claims 16-23) in the reply filed on 08/04/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 1-15 and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/04/2026.
Claims 16-23 were examined on their merits.
Claim Objections
Claim 22 is objected to because of the following informalities: Claim 22 is duplicated. The second Claim 22 should be designated as Claim 23. Original Claims 23-25 should be renumbered as Claims 24-26. Appropriate correction is required.
Information Disclosure Statement
The listing of references in the specification 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
Color photographs and color drawings are not accepted in utility applications 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), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, 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:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Alternatively, Applicant may delete references to arrow color in the descriptions of Figures 3-4.
Specification
The use of the terms HALOTAG™, VECTASHIELD™, LSRFORTESSA™, FLOWJO™, NANODROP™, NUCRED™ and NEUROBASAL™, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
The preamble of Claim 16 recites, “A method to inhibit formation of Tau bundles/inclusions…”. This is an intended use or purpose which will be examined to determine if it results in a manipulative difference between the claimed invention and the prior art. See the MPEP at 2111.02, II.
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.
Claim 23 is rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting formation of tau bundles/inclusion comprising contacting a neuronal cell with an inhibitor of an UFMylation pathway protein with an shRNA having the sequence of SEQ ID Nos: 4-6 and 8-10, does not reasonably provide enablement for inhibition of an UFMylation pathway protein with an shRNA having the sequence of SEQ ID No. 4:. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The published Specification at Pg. 18, Table 1 indicates that SEQ ID Nos. 7 and 11 are a control shRNA sequence and control shRNA primer sequence which would not be expected to be effective in inhibiting any UFMylation pathway protein.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 16, 17, 20 and 21 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Endo et al. (03/14/2023), Article and Supplement, as evidenced by Wang et al. (10/29/2023).
Endo et al. teaches production of pSIH1-copGFP-UFM1 RNAi (Supplement, Pg. 2, Lines 20-23 and Pg. 3, Lines 1-16) and infection of primary cortical neurons with the lentivirus for knockdown (inhibition) of UFM1 protein (Supplement, Pg. 6, Lines 19-21 and Pg. 7, Lines 1-8 and Article, Pg. 4, Fig. 2E), and reading on Claims 16, 20 and 21.
With regard to Claim 17, Wang et al. evidences that UFM1 is a required substrate for the UFMylation enzyme cascade wherein mature UFM1 is transferred to UBA5, then to UFC1, then to UFL1/CDK5RAP3 (Pg. 3, Fig. 1). Thus, it would be inherent in the method of Endo et al. that the lentiviral-RNAi-UFM1 knockdown would also inhibit UBA5, UFC1, and UFL1/CDK5RAP3.
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.
Claims 16, 17, 18, 19, 20 and 21 are rejected under 35 U.S.C. § 103 as being unpatentable over Endo et al. (03/14/2023), Article and Supplement, as evidenced by Wang et al. (10/29/2023), as applied to Claims 16, 17, 20 and 21, and further in view of Fang et al. (2021).
The teachings of Endo et al. were discussed above.
Endo et al. did not teach a method wherein the inhibitor of an UFMylation pathway is the small molecule inhibitor Usenamine A, as required by Claims 18 and 19.
Fang et al. teaches that based on molecular docking, usenamine A has the potential to occupy the binding interfaces between UBA5 and UFM1 (Pg. 11, Lines 2-18 and Fig. 7) and that usenamine A exhibits UBA5 inhibitory activity in breast cancer cells (Pg. 13, Lines 45-46).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Endo et al. of inhibiting UFMylation pathway proteins in neurons by lentiviral knockdown of UFM1 to use usenamine A as the inhibitor of UFMylation pathway proteins, as taught by Fang et al.
because this would provide a potential alternative chemical means of inhibiting UFMylation pathway proteins. Those of ordinary skill in the art would have been motivated to make this modification in order to inhibit UFMylation pathway proteins without having to construct or use a lentiviral RNAi vector. There would have been a reasonable expectation of success in making this modification because both references are drawn to inhibitors of UFMylation pathway proteins.
Claims 16, 17, 20, 21 and 22 are rejected under 35 U.S.C. § 103 as being unpatentable over Endo et al. (03/14/2023), Article and Supplement, as evidenced by Wang et al. (10/29/2023), as applied to Claims 16, 17, 20 and 21, and further in view of Kumari et al. (2022) in view of Rao et al. (2009).
The teachings of Endo et al. were discussed above.
Endo et al. did not teach a method wherein the inhibitor is a shRNA inhibitory sequence which knocks down UBA5, as required by Claim 22.
Kumari et al. teaches generating UBA5 knockdown cells by infecting HEK293T cells with lentivirus containing shRNA-UBA5 or shRNA-UFC1 (Pg. 8, Paragraph 4.3).
Rao et al. teaches that RNA interference (RNAi) is a natural process through which expression of a targeted gene can be knocked down with high specificity and selectivity and methods for mediating the RNAi effect involve small interfering RNA (siRNA) (as taught by Endo) or short hairpin RNA (shRNA) (as taught by Kumari) wherein the simplicity of siRNA manufacturing and transient nature of the effect per dose are optimally suited for certain medical disorders, however using the endogenous processing machinery, optimized shRNA constructs allow for high potency and sustainable effects using low copy numbers resulting in less off -target effects (Pg. 746, Abstract).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Endo et al. of inhibiting UFMylation pathway proteins in neurons by lentiviral siRNA knockdown of UFM1 to use lentivirus containing shRNA-UBA5 or shRNA-UFC1, as taught by Kumari et al. because both methods will result in the inhibition of UFMylation pathway proteins. Those of ordinary skill in the art would have been motivated to make this modification because Rao et al. teaches that both siRNA and shRNA are known processes through which expression of a targeted gene can be knocked down with high specificity and selectivity. The reference further teaches that advantageously, optimized shRNA constructs allow for high potency and sustainable effects using low copy numbers resulting in less off-target effects. There would have been a reasonable expectation of success in making this modification because both the Endo and Kumari references are drawn to lentiviral RNA mediated inhibitors of UFMylation pathway proteins.
Claims 16, 17, 20, 21, 22 and 23 are rejected under 35 U.S.C. § 103 as being unpatentable over Endo et al. (03/14/2023), Article and Supplement, as evidenced by Wang et al. (10/29/2023), in view of Kumari et al. (2022) and Rao et al. (2009), as applied to Claims 16, 17, 20, 21 and 22, and further in view of Lou et al. (US 2019/0330638 A1).
The teachings of Endo et al., Kumari et al. and Rao et al. were discussed above.
None of the above references taught a method wherein the shRNA inhibitor has the sequence of SEQ ID NO: 5, as required by Claim 23.
Lou et al. teaches inhibitors of UFM1 activity include molecules containing the peptide sequence include nucleic acids designed to promote RNA interference of the UFM1 polypeptide including shRNA having SEQ ID NO. 16 (corresponding to instant SEQ ID No. 5).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Endo et al. and Kumari et al. of inhibiting UFMylation pathway proteins in neurons by using lentivirus containing shRNA-UBA5 or shRNA-UFC1, to use the shRNA-UFM1 of Lou et al. because both methods will result in the inhibition of UFMylation pathway proteins, and thus the UFMylation pathway. Those of ordinary skill in the art would have been motivated to make this modification because Rao et al. teaches that shRNA is a known processes through which expression of a targeted gene can be knocked down with high specificity and selectivity. The Rao reference further teaches that advantageously, optimized shRNA constructs allow for high potency and sustainable effects using low copy numbers resulting in less off-target effects. There would have been a reasonable expectation of success in making this modification because the Endo, Kumari and Lou references are drawn to RNA mediated inhibitors of UFMylation pathway proteins.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 08/24/2026
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