DETAILED ACTION
This Action is in response to the communication filed on 11/06/2025.
Claims 1-3, 7-14, 18-26 are pending and addressed herein. It is noted that claims 23-26 are new claims.
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 .
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 7-14, 18-26 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 2008/0015158 (hereafter “Ichiro”, of record), in view of Rodriguez-Lebron et al. (Molecular Therapy (2005), of record), US2013/0287736 (hereafter “Passini”), WO 2014117050 A2 (hereafter “Fellman”) and US 20130179999 A1 (hereafter “Hannon”) .
It is noted that independent claims 1 and 12 have been amended to require that the viral vector is an AAV vector comprising a DNA sequence encoding a dsRNA wherein the two strands of the dsRNA are comprised in a pri-miRNA scaffold, and new claims 23-26 further require the pri-miRNA scaffold to be derived from miR-451a or miR-155. The new limitations with respect to the AAV vector address the rejection of claims under 35 USC 112 for lack of antecedent support, and the claims were previously considered as if there was proper support for the AAV vector. Accordingly, the new limitations requiring pri-miRNA scaffold must be addressed.
As previously indicated, Ichiro teaches a method of treating symptoms of Huntington’s disease in a human subject (which encompassed reducing or delaying symptoms of Huntington’s disease) including in a subject that has at least one Huntingtin allele with an abnormal number of CAG repeats, by administering to the subject a viral vector encoding a double stranded RNA comprising a first and second RNA sequence which form an siRNA wherein the first sequence has a sequence length of at least 19 nucleotides that are fully complementary to SEQ ID NO: 1 (e.g., see abstract; paragraphs [0011], [0024], [0050]-[0052]; claims 15-17; Figure 6; sequence alignment provided in a previous Office Action). That is, the dsRNA taught by Ichiro comprises a strand that has 21 nucleotides that includes 19 nucleotides fully complementary to the 19 nucleotide sequence of SEQ ID NO: 1 (see alignment of record). Ichiro teaches that the mutant huntingtin allele can carry 35 or more CAG repeats, including 39 or more repeats (e.g., see [0056], Figure 2, etc.). Ichiro teaches that the delivery can be by, among others, intracerebral injection or intracranial injection, and demonstrates that the intracerebral injection results in suppression of target gene expression in the striatum, indicating that the injection is into the striatum (e.g., see [0022], [0031], [0054], Figs 9-10, etc.).
Ichiro does not teach that the vector is an AAV vector that is a serotype 5 vector or that the sequence encodes the dsRNA strands comprised in a pri-miRNA scaffold. Regarding claims 10 and 21, Ichiro does not teach that a neuron specific promoter, specifically a Neuron Specific Enolase (NSE) promoter, is used in the expression cassette. Regarding claims 23-26, Ichiro does not teach that the pri-miRNA scaffold is derived from miR-451a or miR-155.
Regarding the serotype 5 AAV vector limitations, as previously indicated Rodriguez-Lebron teaches the use of an AAV vector that is a serotype 5 vector (AAV5) to express an RNAi sequence in neuronal cells for the treatment of Huntington’s disease (HD) (e.g., see abstract, page 630 under “rAAV-shRNA plasmid construction”, etc.). Although Rodriguez-Lebron does not teach that the promoter used to express the dsRNA is a neuron-specific promoter, specifically a NSE promoter, using neuron-specific promoters for neuron-specific expression of polypeptides was well known in the prior art. For instance, Passini teaches an AAV5 vector comprising an expression cassette having a neuron-specific promoter, specifically an NSE promoter, for expression in neurons (e.g., see [0108]-[0109] etc.).
Regarding the limitations with respect to the strands of the dsRNA being in a pri-miRNA scaffold, it is noted that incorporating the strands of a dsRNA into a pri-miRNA was taught in the prior art. For instance, Fellman teaches a modified miRNA molecule for producing an artificial siRNA or shRNA molecule that inhibits the expression of a target transcript (e.g., see abstract, paragraph [0007], etc.). Fellman teaches that the miRNA can be a pri-mRNA molecule (e.g., see [0012], etc.), and explicitly teaches, “What is described is engineering of a new backbone of miRNA molecules that leads to better target knockdown through generally improved primary miRNA processing… an engineered backbone for efficient processing of synthetic RNAi triggers, leading to highly improved target knockdown.” (See [0030]). Fellman also teaches a modified miRNA for producing a shRNA inhibitor of luciferase gene expression wherein the modified miRNA is a modified miR-155 (e.g., see [0023], Figure 4).
Although Fellman does not teach that the modified miRNA scaffold is derived from miR-451a, Hannon teaches design and use of miR-451 shRNA mimics (e.g., see abstract, [0013], [0085], Figure 1, etc.). Hannon also teaches an embodiment where the shRNA is modeled on primary miRNA rather than pre-miRNA transcripts wherein a shRNAmir is produced and cleaved into shRNA which is cleaved again to produce siRNA (see [0091]) and explicitly teaches that primary miRNA-451 (pri-miR-451) mimic sequences can be used (see [0012]). It is noted that the instant specification indicates that miR-451 is also referred to as miR-451 (see [0045]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention as made to combine the teachings of Ichiro with and Rodriguez-Lebron and Passini to make and use an AAV vector (that is a serotype 5 vector) comprising a neuron-specific promoter (specifically an NSE promoter) to produce a dsRNA in target neuron cells for the treatment of HD, and to further modify AAV vector that expresses the dsRNA such that the dsRNA is comprised in a pri-mRNA scaffold including a pri-miRNA scaffold derived from miR-155 (as taught by Fellman) or derived from miR-451a (also known as miR-451), as taught by Hannon, with a reasonable expectation of success.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007):
“Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.”
Therefore, the instant claims are prima facie obvious over the prior art.
Response to Arguments
With respect to the rejection of claims under 35 USC 112(b) (for lack of antecedent support), Applicant’s arguments have been fully considered and in view of the amendment to the claims are persuasive. The rejection has been withdrawn.
With respect to the rejection of claims under 35 USC 103 as set forth in the previous office action, Applicant’s arguments have been fully considered and in view of the amendment are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made under 35 USC 103 for the reasons indicated above.
With respect to the non-statutory double patenting rejections, the terminal disclaimer filed on 11/06/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent Nos. 10174321, 10767180, and 11371044 has been reviewed and is accepted. The terminal disclaimer has been recorded. Accordingly, the non-statutory double patenting rejections have been withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637