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 action is in response to the papers filed February 4, 2026.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/04/2026 has been entered.
Claim Listing
The claim listing filed on 02/04/2026 is acknowledged. No amendments have been made relative to the immediate prior version of the claims filed on 09/19/2025.
Claims 1, 7, 9-10, 13-19, 22-28 are pending.
Claims 1, 7, 9-10, 13-16, and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 17-19, 23-28 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See the Requirement for Restriction/Election mailed 05/01/2025.
Applicant elected without traverse the invention of Group 2, drawn to a method of promoting functional recovery in a subject following SCI. See, applicant’s reply filed 05/13/2025.
Applicant further elected without traverse a rAAV, as the species of gene transfer vehicle for the gene therapy. See, the interview summary mailed 06/20/2025.
Accordingly, claims 1, 7, 9-10, 13-16, and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. In particular, claims 1, 7, 9-10, 13-14 are drawn to nonelected Group 1 (products), and claims 15-16 and 22 are drawn to a nonelected species of gene transfer vehicle. Election was made without traverse in the reply filed on 05/13/2025.
Priority
The instant application 17/759,832 was filed on 07/29/2022. This application is a national stage of international application PCT/US21/16044 filed 02/01/2021, claiming priority based on U.S. Provisional Application 62/969,338 filed 02/03/2020.
Prior Rejections Maintained
No amendments have been made relative to the immediate prior version of the claims filed on 09/19/2025, and claims 17-19, 23-28 were fully examined and rejected in the previous Office action mailed 11/07/2025. The same grounds of rejection are maintained in this action and reiterated below. A response to applicant’s traversal follows the reiterated rejections.
Claim Interpretation
As stated in a previous Office action, the claims recite “a recombinant viral vector comprising a polynucleotide sequence comprising a nucleic acid sequence encoding pre-miR-7” (claim 17).
Li et al. (2016) “miR-7a/b attenuates post-myocardial infarction remodeling and protects H9c2 cardiomyoblast against hypoxia-induced apoptosis involving Sp1 and PARP-1” Sci Rep 6, 29082, 11 pages, discloses miR-7 is an evolutionarily conserved mRNA in mammals and miR-7a/b (miR-7a and miR-7b) are the two subtype of miR-7, which differs by a single nucleotide in the mice.
Zhao et al. (2015) "MicroRNA-7: a promising new target in cancer therapy" Cancer cell international, 15:103, 8 pages, discloses that the primary transcripts of miRNA (pri-miRNA) are cleaved into precursor miRNA (pre-miRNA) by nuclear RNase III Drosha, and further processed to mature miRNAs by cytoplasmic RNase III Dicer. See also Figure 1:
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Paragraph 15 of applicant’s specification discloses that pre-microRNA-7 (pre-miR-7) refers to native human or mouse RNA sequence having the sequence according to SEQ ID NO: 1, which is processed into the mature form, miR-7, when in the cytosol of a cell.
Accordingly, the limitation “a recombinant viral vector comprising a polynucleotide sequence comprising a nucleic acid sequence encoding pre-miR-7” (claim 17) is interpreted to be consistent with the meaning provided by the specification and prior art. A DNA sequence encoding pri-miR-7 is a DNA sequence encoding pre-miR-7 and a DNA sequence expressing miR-7 because the coding DNA is transcribed into the pri-miRNA, which is processed into the pre-miRNA in the nucleus of a cell, which is further processed into miRNAs in the cytosol of a cell. In addition, miR-7a and miR-7b are subtypes of miR-7, and the terms miR-7, miRNA-7 and microRNA-7 are used interchangeably.
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 17-19, 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over Sakai et al. (2013) “miR-7a alleviates the maintenance of neuropathic pain through regulation of neuronal excitability” Brain, 136(9), 2738-2750; in view of Jan et al. (2019) “Gene transfer in rodent nervous tissue following hindlimb intramuscular delivery of recombinant adeno-associated virus serotypes AAV2/6, AAV2/8, and AAV2/9” Neuroscience Insights, Volume 14, 12 pages; as evidenced by Hu et al. (2019) “Silencing of lncRNA PKIA-AS1 attenuates spinal nerve ligation-induced neuropathic pain through epigenetic downregulation of CDK6 expression” Frontiers in cellular neuroscience, Volume 13, Article 50, 12 pages.
This rejection is repeated for the same reasons provided in the previous Office action. A response to applicant’s traversal follows this rejection.
Sakai discloses that miR-7a is downregulated in the late phase of neuropathic pain, and local induction of miR-7a, using an adeno-associated virus (AAV) vector, suppressed established neuropathic pain (Abstract). To create a neuropathic pain model, the lumbar fifth (L5) spinal nerve in rat was exposed and tightly ligated (pg. 2739, Animal Models). To express mature miR-7a, a sequence including the miR-7a coding sequence was amplified from the rat genome and cloned onto an AAV vector (pg. 2740, Plasmids and Adeno-associated virus vector production). The miR-7a AAV vector was directly injected into L5 dorsal root ganglion (DRG) neurons, resulting in alleviation of both mechanical allodynia and thermal hyperalgesia in the late phase of neuropathic pain (pg. 2742, miR-7a overexpression alleviates the late phase of neuropathic pain). Sakai concludes that miR-7a specifically suppresses neuropathic pain, suggesting a “clinical utility” for treatment of established neuropathic pain (pg. 2748, first full paragraph). The Abstract also states: “miR-7a replenishment offers a novel therapeutic strategy for chronic neuropathic pain.”
"[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). See MPEP 2144.01.
Sakai’s rAAV vector comprises the genome coding sequence for expressing mature miR-7a (pg. 2740, Plasmids). Since pre-miR-7 is produced from the primary transcripts of the genome coding sequence, and subsequently processed into mature miR-7a in the cytosol, the genome coding sequence expressing mature miR-7a, as found in Sakai, encodes for pre-miR-7, as claimed. For these reasons, Sakai’s rAAV vector is found to read on “a recombinant viral vector comprising a polynucleotide sequence comprising a nucleic acid sequence encoding pre-miR-7,” as instantly claimed in claim 17.
Sakai administers the rAAV vector to a rat model subjected to L5 spinal nerve ligation (pg. 2739, Animal Models). Spinal cord injury (SCI) is damage to the spinal cord, including damage to the nerves within the bony protection due to trauma (see, e.g., paragraphs 5 and 82 of applicant’s specification). In addition, the Hu disclosure [evidentiary reference] describes spinal nerve ligation (SNL) as a model for studying spinal cord injury. See, e.g., Abstract and page 4, last paragraph. For these reasons, ligation of the L5 spinal nerve, as described in Sakai, is therefore found to read on spinal cord injury, as instantly claimed in claim 17.
To the extent the claims require translation of Sakai’s method to humans, as recited in claim 19, Sakai performed AAV administration in model rats for neuropathic pain (pg. 2742, miR-7a overexpression alleviates the late phase of neuropathic pain) and fairly suggests clinical translation for alleviating chronic neuropathic pain (pg. 2748, first full paragraph; Abstract, last sentence). Therefore, Sakai fairly suggests translation to humans, and one of ordinary skill in the art would have been motivated to do so in order to alleviate chronic neuropathic pain in human subjects.
For these reasons, Sakai is found to teach or fairly suggest a method of promoting functional recovery in a subject following SCI, the method comprising administering to the subject having a SCI an effective amount of a recombinant virus comprising a recombinant viral vector comprising a polynucleotide sequence comprising a nucleic acid sequence encoding pre-miR-7, or an effective amount of a composition comprising the recombinant virus comprising a recombinant viral vector comprising a polynucleotide sequence comprising a nucleic acid sequence encoding pre-miR-7, wherein the recombinant virus vector is a rAAV (claim 17), wherein the subject is a mammal (claim 18), wherein the mammal is a human (claim 19).
Sakai does not teach that the rAAV comprises serotype 1 or 9 capsid proteins and a serotype 2 rAAV vector, as claimed in claim 17.
Jan is relevant prior art for disclosing gene transfer in rodent nervous tissue via adeno-associated virus (AAV) serotype 2/9. The rAAV2/9 contains a recombinant genome containing AAV2-inverted terminal repeats packaged into capsid proteins derived from AAV9. Jan teaches that the rAAV2/9 has been shown to transduce neurons in dorsal root ganglia (DRG) and spinal cord. See, e.g., Abstract and Introduction on pages 1-2, and Figures 1-2.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Sakai by using a rAAV2/9 vector (i.e., a rAAV comprising serotype 9 capsid proteins and a serotype 2 rAAV vector), as taught by Jan, with a reasonable expectation of success because the rAAV2/9 vector effectively transduces the lumbar DRG and spinal cord, which is the target of Sakai’s gene transfer of miR-7a.
The claims further recite that the recombinant virus promotes functional recovery in a subject following SCI (claim 17), increases neuronal survival and axon regeneration in the subject (claim 23) and improves at least one of: locomotor function, bladder function, bowel function, numbness and tingling in the subject (claim 24). MPEP 2111.04 instructs that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In this case, the limitations “promoting functional recovery” (claim 17), “increases neuronal survival and axon regeneration” (claim 23) and “improves at least one of: locomotor function, bladder function, bowel function, numbness and tingling” (claim 24) describe functional properties or intended results which naturally flow from the administration step performed in claim 17, which is an administration step suggested by the prior art, Sakai and Jan combined. For these reasons, the recited functional properties or intended results are not found to result in a structural or manipulative difference that patentably distinguishes the instantly claimed invention from the combined teachings of the cited references.
For these reasons, claims 17-19, 23-24 would have been prima facie obvious over the prior art.
Regarding dependent claims 25 and 27, Sakai injected the AAV vectors directly into L5 DRG of the spinal cord.
Regarding dependent claim 26, Sakai administered the AAV vectors seven days after spinal nerve ligation. See, e.g., Figure 2B.
Response to arguments
Applicant’s remarks filed on 02/04/2026 have been carefully considered, but are not found persuasive for the following reasons:
Applicant argues that Sakai does not teach a “method of promoting functional motor recovery after spinal cord injury (SCI),” as recited in the preamble of claim 17. See, pg. 6 of applicant’s reply.
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See, MPEP 2111.02.
In this case, Sakai administers the rAAV vector to a rat model subjected to L5 spinal nerve ligation (pg. 2739, Animal Models), which is found to read on a subject having spinal cord injury (SCI), as claimed. This claim interpretation is consistent with both applicant’s specification (see, paragraphs 5 and 82, describing SCI as damage to the spinal cord, including damage to the nerves within the bony protection due to trauma), and the teachings of the prior art (see, Hu, Abstract and page 4, last paragraph, describing spinal nerve ligation (SNL) as a model for studying spinal cord injury).
Applicant argues that the specification of the present application describes mice transduced with AAV1-miR-7, and provides evidence of enhanced axonal regeneration following SCI. See, pg. 6 of applicant’s reply.
Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In this case, the broadest claim 17 is not limited to AAV serotype 1 (AAV1) vector or a particular route of administration. Rather, claim 17 broadly embraces use of an AAV serotype 9 (AAV9) vector instead (as found in Jan) and any route of administration, e.g., intramuscular injection (as found in Jan) or direct injection into the spinal cord (as found in Sakai).
Applicant argues that Jan is directed to retrograde transduction properties of rAAV2/6, 2/8 and 2/9, and further utilizes a reporter gene, eGFP, instead of an miR-7 therapeutic, as claimed. Applicant further argues that Jan would rend Sakai “inoperable” because Jan allegedly reports little to no expression in distant tissues such as the DRG, spinal cord, or brain after local nerve injection. See, pg. 6 of applicant’s reply.
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In this case, the rejection of record relies on Sakai to provide a rAAV encoding the miR-7 therapeutic and treatment of SCI by administration thereof, as claimed. Jan is cited to modify Sakai by using the rAAV2/9 vector, as claimed. The rejection of claim 17 does not suggest modifying the route of administration, and the claim is not limited to a particular route of administration. The claim broadly embraces both intramuscular injection, as found in Jan, and direct injection into the spinal cord, as found in Sakai. Further, Jan acknowledges that efficient rAAV delivery to select neuroanatomical areas is “most commonly achieved by direct parenchymal (ie, intracerebral or intrathecal) injection” and “results in the highest gene expression at the site of injection,” but there is interest in exploring less invasive approaches for rAAV-mediated gene delivery to the nervous system, e.g., intramuscular injection. See, pg. 1-2, joining paragraph, of Jan. Thus, one of ordinary skill in the art would have recognized a variety of administration routes, all of which are broadly embraced by claim 17, and selected one particular route by weighing of the advantages and disadvantages.
The examiner further disagrees with applicant’s understanding of the Jan disclosure. Jan teaches that the rAAV2/9 transduces neurons in dorsal root ganglia (DRG) and spinal cord. See, e.g., Abstract, “Our data show that the select recombinant adeno-associated virus serotypes transduce sciatic nerve and groups of neurons in the dorsal root ganglia on the injected side, indicating that the intramuscular recombinant adeno-associated virus delivery is useful for achieving gene transfer in local neuroanatomical tracts;” pg. 2, “Among the commonly used rAAV serotypes, rAAV2/6, 2/8, and 2/9 have been shown to transduce neurons in dorsal root ganglia (DRG) and spinal cord following peripheral routes of delivery, purportedly via retrograde transduction;” pg. 10, “In conclusion, we compared 3 common rAAV serotypes (rAAV2/6, 2/8, and 2/9 - CMV or hSyn promoter), which have been shown to transduce nerve structures following peripheral routes of delivery, and confirm their utility in achieving gene transfer in local neuroanatomical tracts following hindlimb [intramuscular] inoculation;” and Figures 1-2, and 5, showing (C) viral transduction of the L4-L5 dorsal root ganglia (DRG). The target site of Sakai’s miR-7a gene transfer is not “distant tissues” like the brain, but rather the local DRG. See, e.g., Abstract, “local induction of miR-7a, using an adeno-associated virus vector, in sensory neurons of injured dorsal root ganglion, suppressed established neuropathic pain;” pg. 2742, “To assess the direct contribution of miR-7a to neuropathic pain, we induced miR-7a expression specifically in L5 DRG neurons using a recombinant serotype 6 AAV vector.” Accordingly, the teachings of Jan regarding the rAAV2/9 vector are compatible with Sakai’s method.
For these reasons, Jan’s teachings would not render Sakai “inoperable,” as alleged by applicant.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Sakai et al. (2013) “miR-7a alleviates the maintenance of neuropathic pain through regulation of neuronal excitability” Brain, 136(9), 2738-2750; Jan et al. (2019) “Gene transfer in rodent nervous tissue following hindlimb intramuscular delivery of recombinant adeno-associated virus serotypes AAV2/6, AAV2/8, and AAV2/9” Neuroscience Insights, Volume 14, 12 pages; and Hu et al. (2019) “Silencing of lncRNA PKIA-AS1 attenuates spinal nerve ligation-induced neuropathic pain through epigenetic downregulation of CDK6 expression” Frontiers in cellular neuroscience, Volume 13, Article 50, 12 pages [evidentiary reference], as applied to claims 17-19, 23-27 above; in further view of Ding et al. (13-Jan-2020) “MiR-7a ameliorates spinal cord injury by inhibiting neuronal apoptosis and oxidative stress” European Review for Medical & Pharmacological Sciences, 24(1), pages 11-17.
This rejection is repeated for the same reasons provided in the previous Office action. A response to applicant’s traversal follows this rejection.
Sakai and Jan do not teach a step of conducting assays for measuring improvement of at least one of locomotor function, bladder function, bowel function, numbness and tingling in the subject at a time point subsequent to administration of the recombinant virus or the composition comprising the recombinant virus, as claimed in claim 28.
Ding is relevant prior art for teaching the administration of microRNA-7a (miR-7a) mimics for treating spinal cord injury (SCI) in a subject, resulting in improved locomotor recovery, neuronal survival and axon regeneration. See, e.g., Abstract; Results on page 15; Figures 1 and 4. Ding further describes means of measuring and evaluating locomotor function at a time point after administration of the miR-7a mimic. See, e.g., Methods and Results on page 13, and Figure 1.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Sakai and Jan combined to further include a step of conducting assays for measuring improvement of locomotor function, as taught by Ding, with a reasonable expectation of success because improved locomotor function is an expected functional outcome of miR-7a therapy following SCI, and thus measuring and evaluating locomotor function at a time point after administration of the miR-7a therapeutic would be conducted to observe, monitor and/or validate the effectiveness of treatment.
Response to arguments
Applicant’s remarks filed on 02/04/2026 have been carefully considered, but are not found persuasive for the following reasons:
Regarding dependent claim 28, applicant argues that Hu is directed to PKIA-AS1/CDK6 epigenetic silencing in neuropathic pain, and Ding does not add anything that would motivate one of skill in the art to utilize an AAV1-pre-miR7 composition to treat SCI. See, pages 7-8 of applicant’s reply.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, Hu is not combined with the other references, but rather Hu is an evidentiary reference describing spinal nerve ligation (SNL) as a model for studying spinal cord injury (SCI). Dong is combined with Sakai and Jan to provide a step of conducting assays for measuring improvement of locomotor function, as recited by dependent claim 28. Sakai and Jan are relied upon for providing the remaining claim limitations, i.e., those of claims 17-19, 23-27.
The remainder of applicant’s traversal is for the same reasons addressed above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 17-19, 23-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 18/484,001 (reference to claim listing filed 10/10/2023); in view of U.S. Patent No. 9,255,266 B2 to Mouradian et al. (issued: 09-Feb-2016); and Challagundla et al. (2015) “AAV‐mediated expression of BAG1 and ROCK2‐shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury” Journal of Neurochemistry, 134(2), 261-275; as evidenced by Koprich et al. (2010) “Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease” Molecular neurodegeneration, 5, 1-12.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the copending claims and secondary references. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection is repeated for the same reasons provided in the previous Office action.
The copending claims recite a process for treating nervous system dysfunction in a patient in need thereof by administration of a microRNA to the patient (claim 21), wherein the nervous system dysfunction is caused by spinal cord injury (claim 25), and wherein the microRNA is miRNA-7 (claim 7). The copending claims further recite a vector or viral particle comprising the microRNA (claim 19), and administration of the therapeutic by direct injection or intra-spinal cord (claim 22).
The copending claims do not recite that the viral vector comprises a nucleic acid sequence encoding pre-miR-7, as claimed in claim 17.
Prior to the effective filing date of the instantly claimed invention, Mouradian teaches a method of decreasing the expression of α-synuclein in a patient in need thereof comprising administering to said patient an effective amount of a composition comprising miRNA-7 (claim 1), and wherein the miRNA-7 is delivered by a viral vector (claims 4-5). For the viral vector delivery system, Mouradian further teaches a recombinant virus comprising a recombinant viral vector comprising a sequence encoding pri-miR-7 operably linked to a promoter sequence, thereby expressing the miR-7 when delivered to a cell. See, e.g., col 7, ll. 20-22; col. 11-12.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of the copending claims by having the viral vector comprise a nucleic acid sequence encoding pre-miR-7, as taught by Mouradian, the with a reasonable expectation of success because a nucleic acid sequence encoding pri-miR-7 is a nucleic acid sequence encoding pre-miR-7, and such a nucleic acid sequence expresses the mature miR-7 when processed in the cytosol of a cell, miR-7 being the therapeutic of the copending claims.
The copending claims do not recite, and Mouradian does not disclose, that the rAAV comprises serotype 1 or 9 capsid proteins and a serotype 2 rAAV vector, as claimed in instant claim 17.
Prior to the effective filing date of the instantly claimed invention, Challagundla discloses injection of a recombinant AAV1/2 virus for delivering shRNA to the spinal cord following spinal cord injury (SCI) in order to promote neuronal survival and axonal regeneration. The virus transduced the red nucleus (RN) and rubrospinal tract (RST). See Abstract; Results on pages 265-267; Materials and methods on pages 262-263; and Figures 1-2.
The recombinant AAV1/2 virus, as found in Challagundla, is a chimeric vector comprising a capsid comprising AAV1 and AAV2 serotype proteins and a genome comprising AAV2 serotype inverted terminal repeats (ITRs), as evidenced by Koprich (pg. 10, right column). Accordingly, a recombinant AAV1/2 virus, as found in Challagundla, reads on a rAAV comprising serotype 1 capsid proteins and a serotype 2 rAAV vector, as claimed in claim 17.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the copending invention by using a recombinant AAV1/2 virus for gene delivery to the spinal cord, as found in Challagundla, with a reasonable expectation of success because the copending claims recite that the viral delivery system (claim 19), and the AAV1/2 viral vector has previously been shown to effectively delivery genes to the spinal cord for the promotion of neuronal survival and axonal regeneration following SCI.
The instant claims further recite that the method “promot[es] functional recovery” (claim 17), “increases neuronal survival and axon regeneration” (claim 23) and “improves at least one of: locomotor function, bladder function, bowel function, numbness and tingling” (claim 24). MPEP 2111.04 instructs that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In this case, the limitations “promoting functional recovery” (claim 17), “increases neuronal survival and axon regeneration” (claim 23) and “improves at least one of: locomotor function, bladder function, bowel function, numbness and tingling” (claim 24) describe functional properties or intended results which naturally flow from the administration step performed by instant claim 17, which is an administration step taught or fairly suggested by the copending claims and secondary references combined. Therefore, the recited functional properties or intended results are not found to result in a structural or manipulative difference that patentably distinguishes the instantly claimed invention from the invention of the copending claims and secondary references.
For these reasons, instant claims 17, 23-24 would have been prima facie obvious over the copending claims and secondary references.
Regarding instant claims 18-19, Mouradian discloses that the patient is a mammal or human (see, e.g., col. 2, ll. 26-27).
Regarding instant claims 25 and 27, the copending claims recite intra-spinal cord administration and direct injection (claim 22).
Regarding instant claim 26, Challagundla discloses AAV injection immediately after SCI. See, e.g., Figure 1 on page 264; Materials and methods on page 263, left column.
Regarding instant claims 28, Challagundla discloses measuring and evaluating locomotor function in the subject at a time point after administration. See, e.g., Results on page 269; Discussion on page 273, left column; and Figure 7.
Claims 17-19, 23-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,255,266 B2; in view of the specification of U.S. Patent No. 9,255,266 B2 (issued: 09-Feb-2016); Zeng et al. (2019) “Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with spinal cord injury” Journal of neuroinflammation, 16, 1-19; Ding et al. (13-Jan-2020) “MiR-7a ameliorates spinal cord injury by inhibiting neuronal apoptosis and oxidative stress” European Review for Medical & Pharmacological Sciences, 24(1), pages 11-17; and Challagundla et al. (2015) “AAV‐mediated expression of BAG1 and ROCK2‐shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury” Journal of Neurochemistry, 134(2), 261-275; as evidenced by Koprich et al. (2010) “Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease” Molecular neurodegeneration, 5, 1-12. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the patent claims and secondary references.
This rejection is repeated for the same reasons provided in the previous Office action.
Claim 1 of over U.S. Patent No. 9,255,266 B2 recites a method of decreasing the expression of α-synuclein in a patient in need thereof comprising administering to said patient an effective amount of a composition comprising miRNA-7, and claims 4-5 recite that the miRNA-7 is delivered by a viral vector.
The patent claims do not recite treatment of a patient having spinal cord injury (SCI), as instantly claimed.
U.S. Patent No. 9,255,266 B2 issued on February 9, 2016, which is more than one year before to the effective filing date of the instantly claimed invention. The specification discloses that increased levels of α-synuclein is deleterious to neurons, and the invention is related to treatments of neurodegenerative diseases associated with excess α-synuclein via miRNAs or mimics thereof, which suppress α-synuclein expression and/or inhibit α-synuclein-mediated cell death. See, e.g., col. 1-2. For the viral vector delivery system, the specification discloses a recombinant virus comprising a recombinant viral vector comprising a sequence encoding pri-miR-7 operably linked to a promoter sequence, thereby expressing the miR-7 when delivered to a cell. See, e.g., col 7, ll. 20-22; col. 11-12.
In addition, prior to the effective filing date of the instantly claimed invention, Zeng discloses that α-synuclein (SCNA) aggregates after SCI, and inhibition of α-synuclein aggregation improves the survival of neurons after SCI. Zeng found that a shRNA-carrying lentivirus mediated down-regulation of α-synuclein in rats with SCI, thereby reducing neuroinflammation and promoting functional recovery. See, e.g., Abstract; see Conclusion and Figure 11 on page 17.
In addition, Ding teaches that administration of microRNA-7a (miR-7a) mimics treated spinal cord injury (SCI) in a subject, resulting in improved locomotor recovery, neuronal survival and axon regeneration. See, e.g., Abstract; Results on page 15; Figures 1 and 4.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of decreasing α-synuclein expression in a patient in need thereof, as recited by the patent claims, by administering the miR-7 therapeutic to a patient suffering from spinal cord injury (SCI), in view of the patent specification, Zeng and Ding, with a reasonable expectation of success because decreasing α-synuclein expression after SCI improves neuron survival and promotes functional recovery (see Zeng, above), and administration of miR-7 mimics have been previously shown to treat SCI, resulting in improved locomotor recovery and neuron survival (see Ding, above).
The patent claims do not recite, and the patent specification, Zeng and Ding do not disclose, that the rAAV comprises serotype 1 or 9 capsid proteins and a serotype 2 rAAV vector, as claimed in instant claim 17.
Prior to the effective filing date of the instantly claimed invention, Challagundla discloses injection of a recombinant AAV1/2 virus for delivering shRNA to the spinal cord following spinal cord injury (SCI) in order to promote neuronal survival and axonal regeneration. The virus transduced the red nucleus (RN) and rubrospinal tract (RST). See Abstract; Results on pages 265-267; Materials and methods on pages 262-263; and Figures 1-2.
The recombinant AAV1/2 virus, as found in Challagundla, is a chimeric vector comprising a capsid comprising AAV1 and AAV2 serotype proteins and a genome comprising AAV2 serotype inverted terminal repeats (ITRs), as evidenced by Koprich (pg. 10, right column). Accordingly, a recombinant AAV1/2 virus, as found in Challagundla, reads on a rAAV comprising serotype 1 capsid proteins and a serotype 2 rAAV vector, as claimed in claim 17.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the patented invention by using a recombinant AAV1/2 virus for gene delivery to the spinal cord, as found in Challagundla, with a reasonable expectation of success because the patent discloses that the viral delivery system is a rAAV (see col. 11-12), and the AAV1/2 viral vector has previously been shown to effectively delivery genes to the spinal cord for the promotion of neuronal survival and axonal regeneration following SCI (see Challagundla, above).
The instant claims further recite that the method “promot[es] functional recovery” (claim 17), “increases neuronal survival and axon regeneration” (claim 23) and “improves at least one of: locomotor function, bladder function, bowel function, numbness and tingling” (claim 24). The patent specification discloses that the therapeutic inhibits α-synuclein-mediated cell death (see, e.g., col. 1-2). Zeng discloses that the recombinant viral vector, which inhibits α-synuclein expression, promoted functional recovery, improved neuronal survival and improved locomotor function (see, e.g., Title, Abstract, and Figure 3). Ding discloses that the miR-7a mimic increased neuronal survival and axon regeneration (e.g., Abstract, Results on page 15, and Figure 4) and improved locomotor function (see, e.g., Abstract and Figure 1).
Moreover, MPEP 2111.04 instructs that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In this case, the limitations “promoting functional recovery” (claim 17), “increases neuronal survival and axon regeneration” (claim 23) and “improves at least one of: locomotor function, bladder function, bowel function, numbness and tingling” (claim 24) describe functional properties or intended results which naturally flow from the administration step performed in claim 17, which is an administration step taught or fairly suggested by the patent claims and secondary references combined. Therefore, the recited functional properties or intended results are not found to result in a structural or manipulative difference that patentably distinguishes the instantly claimed invention from the invention of the patent claims and cited references. Moreover, as shown above in the preceding paragraph, the cited references disclose the same or similar functional properties or intended results as instantly claimed in claims 17, 23-24.
For these reasons, instant claims 17, 23-24 would have been prima facie obvious over the patent claims and secondary references.
Regarding instant claims 18-19, the patent specification discloses that the patient is a mammal or human (see, e.g., col. 2, ll. 26-27). Zeng and Ding both treat SCI in a rat model (see, e.g., Abstracts of Zeng and Ding).
Regarding instant claims 25 and 27, the patent specification discloses administration of the rAAV by injection (see, e.g., col. 12). Zeng teaches direct injection of the recombinant virus to the spinal cord (see, e.g., Abstract; Methods on page 3; and Figure 11). Ding discloses intrathecal injection of the miR-7a mimic (see, e.g., Abstract; Methods on page 12).
Regarding instant claim 26, Zeng injects the recombinant virus on the same day as the SCI (i.e., at least “within 24 hours of SCI injury”). See, e.g., Figure 1 and Methods on page 3. Ding discloses injection of the miR-7a mimic on the same day as the SCI (i.e., at least “within 24 hours of SCI injury”). See e.g., Figure 1 and Methods on page 12.
Regarding instant claim 28, Zeng discloses measuring and evaluating locomotor function at a time point after administration of the therapeutic (see, e.g., Abstract and Methods on page 4, left column; Results on page 3; and Figure 3). Ding discloses measuring and evaluating locomotor function at a time point after administration of the therapeutic (see, e.g., Methods and Results on page 13, and Figure 1).
Noncompliance with 37 CFR 1.111(b):
Applicant’s remarks filed 02/04/2026 are acknowledged. Applicant requests that the nonstatutory double patenting (NSDP) rejections be held in abeyance until allowable subject matter is identified. As stated in the previous Office action, MPEP 804 instructs that a complete response to a NSDP rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims or the filing of a terminal disclaimer in accordance with 37 CFR 1.321. Such a response is required even when the nonstatutory double patenting rejection is provisional. Accordingly, applicant’s reply filed 02/04/2026 is not in compliance with 37 CFR 1.111(b), which requires a complete reply to every ground of objection and rejection set forth in the prior Office action. Applicant is respectfully reminded to provide a complete reply to every ground of objection and rejection, as required by 37 CFR 1.111(b), in order to avoid delays prosecution.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631