DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim(s) 1-2, 4, 6, and 8-33 are pending.
This action is in response to the amendment, filed 05/27/2026, in which claim(s): (a) 3, 5, and 7 were cancelled; (b) 1, 4, 6, 9, and 18-20 were amended; and (c) 29-33 were newly added.
It is noted that the amendment to the claims filed on 05/27/2026 does not comply with the requirements of 37 CFR 1.121(c) because the status identifier of claim 29 is “(New)”, however, it contains an underlined “(dG)”, signaling that this claim has been amended despite being new. However, in the interest of compact prosecution, the amendment to the claims has been entered.
Applicant’s arguments filed 05/27/2026 have been thoroughly reviewed, but are not persuasive for the reasons that follow. Any rejections and objections not reiterated in this action have been withdrawn. This action is FINAL.
Election/Restrictions
Applicant’s election without traverse of Group I (claim(s) 1-20), drawn A microRNA in the reply filed on 01/06/2026 is acknowledged.
Applicant’s election without traverse of the species of sequences SEQ ID NOs: 1-2 which read on Group I claims 1-9 and 18-20. Election was made without traverse in the reply filed on 01/06/2026.
Claim(s) 10-17 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Claim(s) 21-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as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 01/06/2026.
Newly added claim(s) 29-33 of the current claim set filed 05/27/2026, reads on Group I.
Claim(s) 1-2, 4, 6, 8-9, 18-20, and 29-33 are under consideration.
Priority
Acknowledgement is made of Applicant’s claim for priority based on a provisional application filed as 63/380,520 on 10/21/2022. All claims are given the priority date of 10/21/2022.
Claim Objections
Claim 18 is objected to because of the following informalities: (ii) in line 4 of claim 18 recites, “(ii) one or more pharmaceutical excipients.”, it would be remedial to include “acceptable” after “pharmaceutical” and change “pharmaceutical” to “pharmaceutically” to recites, “(ii) one or more pharmaceutically acceptable excipients.” This wording can be found in para [0084] and [0144] of US 20240132891 A1 (the related publication).
Appropriate correction is required.
Response to Arguments – Claim Objections
The previous objection to claim 4 for lacking an abbreviated form of “deoxyguanosine” has been withdrawn in view of Applicant’s amendments filed 05/27/2026.
Claim Interpretation
Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms (MPEP 2173.01 I paragraph 2).
Claim 19 recites “A vector or viral particle comprising the microRNA, or mimic thereof, of claim 1”. To interpret the breadth of “vector” or “viral particle” one must first look to the specification for any special definition as coined by the Applicant for a “vector” or “viral particle”.
As defined by the specification at paragraph [0045], “As used herein, a "vector" is a composition of matter which can be used to deliver a nucleic acid of interest to the interior of a cell, including a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Thus, the term "vector" includes an autonomously replicating plasmid or a virus. Examples of viral vectors include, but are not limited to, adeno-associated virus (AAV) vectors, retroviral vectors, lentiviral vectors, adenoviral vectors, and the like. An expression construct can be replicated in a living cell, or it can be made synthetically. Vectors capable of directing the expression of genes to which they are operatively linked are often referred to as "expression vectors."
Furthermore, “viral particle” as defined by the specification at paragraph [0090], “A selected nucleic acid sequence can be inserted into a vector (a vector genome) and packaged in viral particles using techniques known in the art (e.g., an rAAV vector packaged in rAAV particles, Vesicular Stomatitis Virus (VSV) G-pseudotyped lentivirus, etc.). The recombinant virus can then be isolated and delivered to cells of the subject.”
Thus, for the purposes of broadest reasonable interpretation “vector” will be interpreted as any composition of matter which can be used to deliver a nucleic acid of interest to the interior of a cell, and a viral particle will be interpreted as a nucleic acid sequence inserted into a vector (defined above as a species of “A vector” wherein a nucleic acid molecule is capable of transporting another nucleic acid to which it has been linked) and packaged into viral particles such as an rAAV.
Claim 20 recites the limitation of “A nanoparticle comprising the microRNA, or mimic thereof, of claim 1.” To interpret the breadth of “nanoparticle” one must first look to the specification for any special definition as coined by the Applicant.
As defined by the specification at paragraph [0098], “In general, nanoparticles contemplated include any compound or substance with a high loading capacity for a nucleic acid (e.g., pre-miR-7) as described herein, including for example and without limitation, a metal, a semiconductor, and an insulator particle composition, and a dendrimer (organic versus inorganic). … Nanoparticles as described herein include those that are available commercially (e.g., Nanohybrids), as well as those that are synthesized, e.g., produced from progressive nucleation in solution (e.g., by colloid reaction) or by various physical and chemical vapor deposition processes.”
Thus, for the purposes of broadest reasonable interpretation, “A nanoparticle” will be interpreted as any compound or substance with high loading capacity for a nucleic acid in nanometer range.
Claim(s) 30 and 33 depend upon themselves, thus, claim(s) 30 and 33 will be interpreted as being dependent upon claim 19.
Response to Arguments – Claim Rejections - 35 USC § 101
The previous rejection of claim(s) 3 and 7 under 35 U.S.C 101, for reciting a product of nature without significantly more, is moot in view of Applicant’s cancellation to the claims filed 05/27/2026.
The previous rejection of claim(s) 1-2, 4, 8-9 and 18-20 under 35 U.S.C 101, for reciting a product of nature without significantly more, has been withdrawn in view of Applicant’s amendments to the claims filed 05/27/2026.
With respect to the rejection of claims 1-2, 4, 8-9 and 18-20 under 35 U.S.C. 101 as being directed to a product of nature without significantly more, Applicant's arguments at page(s) 8-9 of the reply filed 05/27/2026 have been fully considered and are persuasive.
Applicant contends that while not agreeing with the rejection and in order to accelerate examination, the claim(s) 1, 18, 19 and 20 have been amended to include the addition of adding deoxynucleotides to the 3' end of at least one strand. Applicant points to Example 11 of the Subject Matter Eligibility Guidance (2019) as to why the addition of deoxynucleotides to the 3’ end of a microRNA strand contains structural differences that are unique from its closest naturally occurring counterpart.
Examiner agrees with Applicant’s arguments and amendments to the claim(s), thus the rejection under 35 U.S.C. 101 as being directed to a product of nature without significantly more has been withdrawn.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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.
Claim(s) 30 and 33 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. This is a new rejection, necessitated by the amendment to the claims filed 05/27/2026.
Claim 30 recites the limitation ". . . wherein a passenger strand comprises the one or more deoxyribonucleotides at a 3’ end" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 30 depends from itself.
It would be remedial to amend claim 30 to depend from claim 19.
Claim 33 recites the limitation ". . . wherein the microRNA, or mimic thereof, comprises SEQ ID NO: 2." in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 33 depends from itself.
It would be remedial to amend claim 33 to depend from claim 19.
Response to Arguments - Claim Rejections - 35 USC § 112(d) – Improper Claim Dependency
The previous rejection of claim 18 under 35 U.S.C 112(d) for improper claim dependency has been withdrawn in view of Applicant’s amendments of the claim filed 05/27/2026.
Response to Arguments - Claim Rejections - 35 USC § 112(a) – Written Description
The previous rejection of claim(s) 3, 5, and 7 under 35 U.S.C 112(a) for written description is moot in view of Applicant’s cancellation of the claim(s) filed 05/27/2026.
The previous rejection of claim(s) 1-2, 4, 6, 8-9, and 18-20 under 35 U.S.C 112(a) for written description has been withdrawn in view of Applicant’s amendments of the claim filed 05/27/2026.
With respect to the rejection of claim(s) 1-2, 4, 6, 8-9, and 18-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, Applicant's arguments at page(s) 10-12 of the reply filed 05/27/2026 have been fully considered and are persuasive.
Applicant points to paragraphs [0162] to [0175] of US 20240132891 A1 (the applications-related publication) to support the amendments of claim 1, 18, 19, and 20, where applicant amended the claim(s) to recite, “. . . wherein the microRNA, or mimic thereof, is miRNA-7 comprising one or more deoxyribonucleotides added at a 3’ end of one or more of the RNA strands in the microRNA, or mimic thereof.”
Applicant contends that the instant specification describes and/or discloses the following: (1) a set of microRNAs representative of the genus for targeting nervous system dysfunction. Applicant amended the claims to specify miR-7 as the microRNA and points to paras [0162]-[0168] and [0169]-[0175] of the 891 publication (the application’s related publication) to demonstrate (a) protecting neurons in neurodegenerative diseases, e.g., Parkinson’s disease ([0163]) and (b) spinal cord injury. (2) The miRNA of the claimed invention as an identical “guide” strand to the mature miRNA, and that the claims were amended to specify miRNA-7. (3) Which chemical modifications are made to which sugar position or backbone. Applicant cancelled claim 3 and amended claim 4 (the broad recitation of modification) to recite deoxynucleotides added at the 3’ end of miR-7. (4) The miRNA (i.e., miR-7) is associated with spinal cord injury and/or neuro protective effects.
Examiner agrees with the arguments put forth by the Applicant and that through specifying the microRNA to be mir-7, and narrowing the modification(s) to deoxynucleotides at the 3’ end, Applicant has amended the claims to be within the scope of the described disclosure, and that one of skill in the art would reasonably conclude that the inventor had possession of miRNA-7 comprising one or more deoxyribonucleotides added at a 3’end of one or more of the RNA strands in the microRNA, or mimic thereof, capable of treating nervous system dysfunction.
Accordingly, the rejection on 35 U.S.C. 112(a) for lack of written description is withdrawn for claim(s) 1-2, 4, 6, 8-9, and 18-20.
Response to Arguments - Claim Rejections - 35 USC § 112(a) – Enablement
The previous rejection of claim(s) 3, 5, and 7 under 35 U.S.C 112(a) for Enablement is moot in view of Applicant’s cancellation of the claim(s) filed 05/27/2026.
The previous rejection of claim(s) 1-2, 4, 6, 8-9, and 18-20 under 35 U.S.C 112(a) for Enablement has been withdrawn in view of Applicant’s amendments of the claim filed 05/27/2026.
With respect to the rejection of claim(s) 1-2, 4, 6, 8-9, and 18-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the Enablement requirement, Applicant's arguments at page(s) 12-15 of the reply filed 05/27/2026 have been fully considered and are persuasive.
Applicant goes forth and traverses each Wands factor, therefore the following will proceed the same.
Nature of the invention: Without acquiescing to the validity of the current rejection and solely in the interest of expediting prosecution of the instant application, Applicant has amended claims 1, 18, 19 and 20 to specify that the miR is miR-7.
It is of note that Applicant contends that “Accordingly, therapeutic treatment of nervous system dysfunction in a patient by miR-7 is fully enabled.” Applicant is reminded that the independent claim(s) i.e., 1 and 18-20 are composition claims, not method of treating claims. Therefore, the question of whether a therapeutic treatment of nervous system dysfunction in a patient by miR-7 is not one being discussed, argued, and/or rejected by the 35 U.S.C 112(a)- Enablement rejection filed 03/04/2026. The rejection of claim(s) 1-9, and 18-20 for failing to comply with the Enablement requirement in the nonfinal office action filed on 03/04/2026 solely point to whether or not the applicant was enabled for any/all microRNAs capable of therapeutic treatment of nervous system dysfunction in a patient in need thereof. The method of treatment claims were withdrawn in the previous action filed 03/04/2026. Accordingly, capability of a composition versus a method of treating (i.e., a process) are two different inventions and scopes.
Scope of the invention: Applicant points to Example 1 (In vivo validation of the role of specific microRNAs in protecting neurons in the context of neurodegenerative disease; [0162]- [0168]) and Example 2 (SCI; [0169]-[0175]) of the specification for how the amended claims reciting miR-7 is capable of treating nervous system dysfunction.
Guidance of the specification and working examples: Applicant points to the same example(s) as listed above in the scope of the invention for guidance provided by the specification for miR-7. As for working examples, Applicant argues that one of skill in the art would allow one of skill in the art to practice the invention without undue experimentation regarding the use of miR-7.
Predictability of the art: Applicant argues that Applicant’s teachings are clear and on point and that the amended claims correlate with Examples 1 and 2 regarding the teachings of miR-7 and nervous system dysfunction.
Amount of experimentation necessary: Applicant argues that with the amended recitation of miR-7, that the scope of the claimed invention is more than sufficiently enabled and no undue experimentation would be necessary.
Examiner agrees with the arguments put forth by the Applicant and that through specifying the microRNA to be mir-7, Applicant has amended the claims to be within the scope of the enabled disclosure, and that one of skill in the art would reasonably be able to make/use the invention as recited by the claims.
Accordingly, the rejection on 35 U.S.C. 112(a) for Enablement is withdrawn for claim(s) 1-2, 4, 6, 8-9, and 18-20
Response to Arguments - Claim Rejections - 35 USC § 102
The rejection of claim 7 under 35 U.S.C. 102 (a)(1) as being anticipated by ‘266 (US Patent 9,255,266 B2, published 02/09/2016; see PTO 892 filed 03/04/2026, citation A) is moot in view of Applicant’s cancellation of the claims in the reply filed 05/27/2026.
The previous rejection of claim(s) 1, 8-9, and 19-20 under 35 U.S.C. 102 (a)(1) as being anticipated by ‘266 has been withdrawn in view of Applicant’s arguments filed on 05/27/2026.
With respect to the rejection of claim(s) 1, 8-9, and 19-20 under 35 U.S.C. 102 (a)(1) as being anticipated by ‘266, Applicant's arguments at page 16 of the reply filed 05/27/2026 have been fully considered and are persuasive.
Applicant amended the claim to include the limitation of the addition of deoxyribonucleotides at the 3’ end of the miR-7 RNA.
The rejection of claim 7 under 35 U.S.C. 102 (a)(1) as being anticipated Leedman et al (US 9,795,626 B2, publication date October 24th, 2017; see PTO 892 filed 03/04/2026, citation B) is moot in view of Applicant’s cancellation of the claims in the reply filed 05/27/2026.
The previous rejection of claim(s) 1-2, 8-9, and 18-20 under 35 U.S.C. 102 (a)(1) as being anticipated by Leedman et al has been withdrawn in view of Applicant’s arguments filed on 05/27/2026.
With respect to the rejection of claim(s) 1, 8-9, and 19-20 under 35 U.S.C. 102 (a)(1) as being anticipated by Leedman et al, Applicant's arguments at page 16 of the reply filed 05/27/2026 have been fully considered and are persuasive.
Applicant amended the claim to include the limitation of the addition of deoxyribonucleotides at the 3’ end of the miR-7 RNA.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-2, 4, 6, 8, 18-20, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over ‘266 (US Patent 9,255,266 B2, published 02/09/2016; see PTO 892 filed 03/04/2026, citation A) in view of Kadekar et al (Synthetic Design of Asymmetric miRNA with an Engineered 3’ Overhang to Improve Strand Selection, Molecular Therapy: Nucleic Acids, Vol 16, published June 2019; NPL #1 on IDS filed 10/10/2023). A 35 U.S.C. 102(a)(1) rejection was made in the Office action mailed 03/04/2026 over ‘266. This is a new rejection to address the amendment to the claims in the reply filed on 05/27/2026.
Independent claim 1 recites, “for the therapeutic treatment of nervous system dysfunction in a patient in need thereof.” The recitation of the intended use does not result in a structural difference between the claimed invention and prior art. Applicant has elected miRNA-7 and instant SEQ ID NOs: 1 and 2.
Regarding claim 1, ‘266 teaches, “In other embodiments, the present invention is directed to a method for treating a neurodegenerative disease comprising administering an effective amount of a miRNA or a mimic thereof to a patient in need thereof, wherein the miRNA is selected from the group consisting of miRNA-7…”, (see column 1, paragraph (7)).
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Regarding claim 8, ‘266 teaches sequences in Figure 1A and SEQ ID NO: 1 that reads on instant SEQ ID NO: 1.
Regarding claim 18, ‘266 teaches, “The compositions can optionally comprise a suitable amount of a pharmaceutically acceptable excipient so as to provide the form for proper administration to the subject or patient. Such pharmaceutical excipients can be liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic, origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The pharmaceutical excipients can be saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like.”, (col 5, lines 55-61).
Regarding claim 19, “a vector” is being interpreted as any composition of matter which can be used to deliver a nucleic acid of interest to the interior of a cell (see claim interpretation above).
Regarding claim 20, “a nanoparticle” is being interpreted as any compound or substance with a high loading capacity for a nucleic acid in nanometer range.
Regarding claim(s) 19-20, ‘266 teaches, “Transfections were performed using Lipofectamine 2000 reagent (invitrogen) according to the supplier's instructions. For luciferase assay, cells were co-transfected with luciferase reporter constructs and internal control construct pSV-β-galactosidase in the absence or presence of miR-7 or pre-miR-7 at the indicated concentrations. After cell lysis, luciferase activity was measured with Steady-Glo Luciferase Assay System (Promega) using Luminometer (Victor2, Perkin Elmer). β-Galactosidase activity was measured with the D-Galactosidase Enzyme Assay System (Promega) and used to normalize luciferase activity. Experiments were performed in triplicates.”, (see column 9, lines 1-14).
Regarding claim 31, ‘266 teaches sequences in Figure 1A and SEQ ID NO: 1 that reads on instant SEQ ID NO: 1 (see alignment above).
‘266 does not (a) explicitly teach two stands (i.e., a guide and a passenger); (b) teach adding one or more deoxyribonucleotides at a 3’ end of one or more of the RNA strands in the microRNA; or (c) where the modified stand is the passenger strand.
Regarding claim(s) 1, 4, 6, 18-20, and 29-30, Kadekar et al teaches, “To the best of our knowledge, our strand engineering strategy is the first report of improved strand selection of a desired miRNA strand by RISC without using any chemical modifications or mismatches. We believe that such structural modifications of miR34a could mitigate some of the off-target effects of miRNA therapy and would also allow a better understanding of sequence-specific gene regulation. Such a design could also be adapted to other miRNAs to enhance their therapeutic potential.”, (abstract).
More specifically, Kadekar et al teaches, “To design asymmetric miRNAs, we incorporated extra deoxythymine nucleotides (dTs) at the 3’ end of both the miR (5p) and miR* (3p) strands (Figure 1A). Modifying the 3’ end is expected to influence duplex stability because it can destabilize the stacking interaction with the nearest neighbor. To facilitate selective destabilization of the duplex to improve miR strand selection within the RISC complex, we added extra nucleotides at the 3’ end of the miR* strand. To reverse the strand selection and favor miR* strand selection, the extra nucleotides were added to the 3’ end of the miR strand (Figure1A). Because natural miR-34a has a 2-nt overhang at the 3’ end on the miR* strand, we increased the overhang length to 5 and 7 nt by adding 3 and 5 dT nucleotides, respectively. Because the 3’ end of miR strand of miR-34a has a single nucleotide overhang, we increased the overhang length to five and seven by adding four and six dT nucleotides, respectively (Figure 1A).”, (see page 598, column 1, paragraph 3 to column 2, paragraph 1).
Lastly, Kadekar et al teaches, “Of note, our modified miRNA had a better therapeutic effect compared with the commercially available mimics. Because we employed natural nucleotides for modifying miRNA, it would also limit any undesired toxicity that may arise from modified nucleotides generally used in commercial mimics. Such a design could be adapted to other clinically relevant miRNAs, which could address some of the off-target effects associated with the recruitment of undesired strands. We believe that our design strategy will also open new avenues for researchers to study individual strand activity of different miRNAs.”, (page 601, column 1, paragraph 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the miR-7, as taught by ‘266, with the teachings of Kadekar et al, i.e., adding of one or more deoxyribonucleotides to a 3’ end of one or more strands of a microRNA, to yield the predictable results of mir-7 comprising one or more 3’ deoxyribonucleotides on one or more strands. One would have been motivated to make such a modification because Kadekar et al teaches that by employing natural modifications on miRNA, i.e., at the 3’ end of a microRNA, it (1) limits any undesired toxicity that may arise from modified nucleotides generally used in commercial mimics, (2) mitigate some of the off-target effects of miRNA therapy, (3) allow a better understanding of sequence-specific gene regulation, and (4) could also be adapted to other miRNAs to enhance their therapeutic potential.
Accordingly, claim(s) 1-2, 4, 6, 8, 18-20, and 29-31 are rejected as being unpatentable over ‘266 in view of Kadekar et al.
Claim(s) 1-2, 4, 6, 8-9, 18-20, and 29-33 are rejected under 35 U.S.C. 103 as being unpatentable over Leedman et al (US 9,795,626 B2, publication date October 24th, 2017; see PTO 892 filed 03/04/2026, citation B) in view of Kadekar et al (Synthetic Design of Asymmetric miRNA with an Engineered 3’ Overhang to Improve Strand Selection, Molecular Therapy: Nucleic Acids, Vol 16, published June 2019; NPL #1 on IDS filed 10/10/2023). A 35 U.S.C. 102(a)(1) and 103 rejection was made in the Office action mailed 03/04/2026. This is a new rejection to address the amendment to the claims in the reply filed on 05/27/2026.
Independent claim 1 recites, “for the therapeutic treatment of nervous system dysfunction in a patient in need thereof.” The recitation of the intended use does not result in a structural difference between the claimed invention and prior art. Applicant has elected miRNA-7 and instant SEQ ID NOs: 1 and 2.
Regarding claim 1, Leedman et al discloses, “Compositions for the treatment of cancers expressing the type 1 insulin-like growth factor receptor (IGF1R) or a constituent of an IGF1R signaling pathway, in particular melanoma, using the microRNA miR-7-5p.”, (see column 1, lines 12-15).
Leedman et al further teaches, “Embodiments of the invention also contemplate the administration of miRNA variants of miR-7-5p. Variants include nucleotide sequences that are substantially similar to sequences of miRNA disclosed herein. Variants include nucleotide sequences that are substantially similar to sequences of miRNA disclosed herein. In some embodiments, the variant miRNA to be administered comprises a sequence displaying at least 80% sequence identity to the sequence of human miR-7-5p (SEQ ID NO:1). In some embodiments, the miRNA to be administered comprises a sequence displaying at least 90% sequence identity to SEQ ID NO:1. . . Alternatively or in addition variants may comprise modifications, such as non-natural residues at one or more positions with respect to the miR-7-5p sequence.”, (col 10, lines 63-67 to col 11, lines 1-13).
Regarding claim 2, Leedman et al discloses “MicroRNAs (miRNAs) are a class of highly conserved, small (typically 21-25 nucleotides) non-coding RNAs that regulate both mRNA degradation and translation, at least partially through their ability to bind to the 3′-UTR of target genes via a ‘seed region’ of the miRNA. miRNAs are generated from RNA precursors (pri-miRNAs) that usually contain several hundred nucleotides transcribed from regions of non-coding DNA. Pri-miRNAs are processed in the nucleus by RNase III endonuclease to form stem-loop precursors (pre-miRNAs) of approximately 70 nucleotides. Pre-miRNAs are actively transported into the cytoplasm where they are further processed into short RNA duplexes, typically of 21-23 nucleotides. The functional miRNA strand dissociates from its complementary non-functional strand and locates within, the RNA-induced-silencing-complex (RISC). (Alternatively, RISC can directly load pre-miRNA hairpin structures.) miRNAs bind the 3′UTRs of target mRNAs and important in this binding is a ‘seed region’ of approximately 6-7 nucleotides near the 5′ end of the miRNA (typically nucleotide positions 2 to 8). miRNA-induced regulation of gene expression is typically achieved by translational repression, either degrading proteins as they emerge from ribosomes or ‘freezing’ ribosomes, and/or promoting the movement of target mRNAs into sites of RNA destruction.”, (Column 2, lines 1-25). Wherein functional miRNA strand reads on “guide” strand, and non-functional reads on “passenger” strand.
Regarding claim(s) 8 and 9, Leedman et al discloses SEQ ID NO: 2, which comprises both SEQ ID NO: 1 (of claim 8) and SEQ ID NO: 2 (of claim 9) (see alignments below).
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Regarding claim 18, Leedman et al discloses, “The therapeutic agent and the miRNA may be administered in a single composition, formulated together with pharmaceutically acceptable carriers, excipients or adjuvants or may be administered in separate compositions.”, (column 3, lines 13-16).
Regarding claim 19, “a vector” is being interpreted as any composition of matter which can be used to deliver a nucleic acid of interest to the interior of a cell (see claim interpretation above).
Regarding claim 20, “a nanoparticle” is being interpreted as any compound or substance with a high loading capacity for a nucleic acid in nanometer range.
Regarding claim(s) 19 and 20, Leedman et al discloses, “Optimal cell numbers were transfected using Lipofectamine 2000 (Invitrogen) with miR-7-5p (SEQ ID NO: 1; synthesised by Ambion) or miR-NC precursor molecules (hereinafter “miR-NC”; Ambion AM17110) at final concentrations ranging from 1-30 nM. For siRNA transfections, Silencer Select siRNAs (Invitrogen) Negative Control No. 1 (si-NC; 4390843), si-IRS-2 #1 (s16486), si-IRS-2 #2 (s16487) were transfected using Lipofectamine 2000 (Invitrogen) according to the manufacturer's protocol. Cells were harvested 24 hours later for RNA or 2-3 days after transfection for protein extraction.”, (see column 16, lines 49-59).
Regarding claim(s) 31-33, Leedman et al teaches a sequence comprising both instant SEQ ID NO: 1 and 2 (see alignment above).
Despite Leedman et al teaching the potential to modify miR-7-5p with nonnatural residues (reading on nonnatural to RNA), Leedman et al does not teach adding one or more deoxyribonucleotides at a 3’ end of one or more of the RNA strands in the microRNA; or (c) where the modified stand is the passenger strand.
Regarding claim(s) 1, 4, 6, 18-20, and 29-30, Kadekar et al teaches, “To the best of our knowledge, our strand engineering strategy is the first report of improved strand selection of a desired miRNA strand by RISC without using any chemical modifications or mismatches. We believe that such structural modifications of miR34a could mitigate some of the off-target effects of miRNA therapy and would also allow a better understanding of sequence-specific gene regulation. Such a design could also be adapted to other miRNAs to enhance their therapeutic potential.”, (abstract).
More specifically, Kadekar et al teaches, “To design asymmetric miRNAs, we incorporated extra deoxythymine nucleotides (dTs) at the 3’ end of both the miR (5p) and miR* (3p) strands (Figure 1A). Modifying the 3’ end is expected to influence duplex stability because it can destabilize the stacking interaction with the nearest neighbor. To facilitate selective destabilization of the duplex to improve miR strand selection within the RISC complex, we added extra nucleotides at the 3’ end of the miR* strand. To reverse the strand selection and favor miR* strand selection, the extra nucleotides were added to the 3’ end of the miR strand (Figure1A). Because natural miR-34a has a 2-nt overhang at the 3’ end on the miR* strand, we increased the overhang length to 5 and 7 nt by adding 3 and 5 dT nucleotides, respectively. Because the 3’ end of miR strand of miR-34a has a single nucleotide overhang, we increased the overhang length to five and seven by adding four and six dT nucleotides, respectively (Figure 1A).”, (see page 598, column 1, paragraph 3 to column 2, paragraph 1).
Lastly, Kadekar et al teaches, “Of note, our modified miRNA had a better therapeutic effect compared with the commercially available mimics. Because we employed natural nucleotides for modifying miRNA, it would also limit any undesired toxicity that may arise from modified nucleotides generally used in commercial mimics. Such a design could be adapted to other clinically relevant miRNAs, which could address some of the off-target effects associated with the recruitment of undesired strands. We believe that our design strategy will also open new avenues for researchers to study individual strand activity of different miRNAs.”, (page 601, column 1, paragraph 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the miR-7-5p, as taught by Leedman et al, with the teachings of Kadekar et al, i.e., adding of one or more deoxyribonucleotides to a 3’ end of one or more strands of a microRNA, to yield the predictable results of mir-7-5p comprising one or more 3’ deoxyribonucleotides on one or more strands. One would have been motivated to make such a modification because Kadekar et al teaches that by employing natural modifications on miRNA, i.e., at the 3’ end of a microRNA, it (1) limits any undesired toxicity that may arise from modified nucleotides generally used in commercial mimics, (2) mitigate some of the off-target effects of miRNA therapy, (3) allow a better understanding of sequence-specific gene regulation, and (4) could also be adapted to other miRNAs to enhance their therapeutic potential.
Accordingly, claim(s) 1-2, 4, 6, 8-9, 18-20, and 29-33 are rejected as being unpatentable over Leedman et al in view of Kadekar et al.
Response to Arguments - Claim Rejections - 35 USC § 103
The previous rejection of claim 3 and 5 under 35 U.S.C 103 for obviousness is moot in view of Applicant’s cancellation of the claim filed 05/27/2026.
The previous rejection of claim 4 and 6 under 35 U.S.C 103 for obviousness has been maintained in view of Applicant’s amendments of the claim filed 05/27/2026.
With respect to the rejection of claim(s) 4 and 6 under 35 U.S.C. 103 as being unpatentable over Leedman et al (supra) in view of Kadekar et al (supra), Applicant's arguments at page 16-18 of the reply filed 05/27/2026 have been fully considered and are not persuasive for at least the following reasons.
Applicant contends that there is no teaching, disclosure or suggestion by Leedman et al to guide one of skill in the art to select Applicant’s sequences from the 110 nucleic acid sequence of Leedman et al (SEQ ID NO: 2) that anticipates both instant SEQ ID NOs: 1 and 2. Also that nothing in Leedman et al provides a hint to select Applicant’s sequences.
Examiner would respectfully disagree and would like to point to the original 35 U.S.C 101 rejection in Office action filed 03/04/2026 for support.
Gajda et al (The Role of miRNA-7 in the Biology of Cancer and Modulation of Drug Resistance, Pharmaceuticals (Basel), Vol 12, Issue 2, Pages 1-23, Published February 12th, 2021; see PTO 892 filed 03/04/2026, citation W) teaches, “MiRNA-7 (miR-7, hsa-miRNA-7) was first reported in Drosophila melanogaster, nevertheless, the sequence of the guide strand is strongly conserved across different species, which highlights its importance. In humans, miR-7 originates from three precursors: pri-miR-7-1, pri-miR-7-2, and pri-miR-7-3 (Figure 2). They are encoded by the MIR7-1, MIR7-2, and MIR7-3 genes located on three chromosomes: 9q21, 15q26, and 19q13, respectively. Pri-miR-7-1 and pri-miR-7-3 lie within introns of the heterogeneous nuclear ribonucleoprotein K-encoding gene (HNRNPK) and pituitary specific factor 1 gene (PIT1), respectively. The pri-miR-7-2-encoding gene is placed in the intergenic region of chromosome 15. Originally, miR-7 referred to miR-7-5p, since it seemed to be the only mature miRNA from all three precursors that affects cellular pathways. However, other biologically significant miRNAs, miR-7-1-3p and miRNA-7-2-3p, have also been reported. There are slight changes within the sequence of nucleotides between the miRNAs.”, (page 3, paragraph 3). Gajda et al discloses miR-7 and both SEQ ID NOs: 1 and 2, in Figure 2C. Figure 2C is expanded below. Wherein SEQ ID NO: 1 of Leedman et al is miR-7-5p, the precursor sequence that comprises both instant SEQ ID NO: 1 and 2.
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Thus, one of skill in the art would know how to construct mature miR-7 from precursor miR-7-5p (of Leedman et al) because Gajda et al teaches that this is what occurs in nature.
Applicant contends that one of skill in the art would still not arrive at the instant invention since Leedman et al does not provide any teachings as to which microRNA sequences would be selected and still retain activity when the microRNA is modified by the teachings of Kadekar et al, i.e., adding dexoynucleotides at the 3’ end of the microRNA.
Examiner respectfully disagrees. As provided above, Leedman et al does teach the instant claimed sequences through divulging the precursor microRNA of miR-7, since mature RNA is the only miRNA that affects cellular pathways, as taught by Gajda et al. Kadekar et al teaches that the additions limit undesired toxicity and off-target effects and one of skill in the art would be able to identify the mature microRNA sequence provided by Leedman et al, and modify said sequence(s) to limit undesired toxicity and off-target effects.
Applicant contends that in addition, there is no further motiviation to combine and no reasonable expectation of success since Kadekar et al discusses that the dT additions to assymetric miRNAs in generally for strand-selection in cancer applications, and that nothing in the combination of Leedman et al. and Kadekar et al. or would lead the skilled artisan to apply that modification specifically to miR-7 for treatment of nervous system dysfunction.
Examiner respectfully disagrees with the Applicant’s argument. Since claim 1 is a composition-based claim, i.e., a microRNA or a mimic thereof, the recitation of “for the therapeutic treatment of nervous system dysfunction in a patient in need thereof” is an intended use and does not hold patentable weight when determining art-based rejections, i.e., 35 USC 102 or 103 rejections. The intended use does not impart a structural modification to the body of the claim. Thus, it does not matter what the use of the composition is for.
Accordingly, the rejection of claims 4 and 6 are maintained for being unpatentable over Leedman et al in view of Kadekar et al.
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.
Claim(s) 1-2, 4, 6, 8-9, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 9,255,266 B2 in view of Kadekar et al (Synthetic Design of Asymmetric miRNA with an Engineered 3’ Overhang to Improve Strand Selection, Molecular Therapy: Nucleic Acids, Vol 16, published June 2019; NPL #1 on IDS filed 10/10/2023). An Anticipation-Type Nonstatuatory Double Patenting rejection was made in the Office action mailed 03/04/2026 over claim 8 of ‘266. This is a new rejection to address the amendment to the claims in the reply filed on 05/27/2026.
Claim 8 of the ‘266 patent is drawn to “The method for “treating Parkinson's disease in a patient in need thereof comprising administering to said patient an effective amount of a composition comprising miRNA-7 (SEQ ID NOs. 1-2)”, wherein the composition comprising miRNA-7 is administered through a delivery system, and wherein the delivery system comprises at least one of a viral vector, a liposome, a microparticle, capsules, and combinations thereof.”
Claim 8 does not require wherein one or more deoxyribonucleotides are added at the 3’ end of one or more of the RNA strands in the microRNA.
Kadekar et al teaches, “To the best of our knowledge, our strand engineering strategy is the first report of improved strand selection of a desired miRNA strand by RISC without using any chemical modifications or mismatches. We believe that such structural modifications of miR34a could mitigate some of the off-target effects of miRNA therapy and would also allow a better understanding of sequence-specific gene regulation. Such a design could also be adapted to other miRNAs to enhance their therapeutic potential.”, (abstract).
More specifically, Kadekar et al teaches, “To design asymmetric miRNAs, we incorporated extra deoxythymine nucleotides (dTs) at the 3’ end of both the miR (5p) and miR* (3p) strands (Figure 1A). Modifying the 3’ end is expected to influence duplex stability because it can destabilize the stacking interaction with the nearest neighbor. To facilitate selective destabilization of the duplex to improve miR strand selection within the RISC complex, we added extra nucleotides at the 3’ end of the miR* strand. To reverse the strand selection and favor miR* strand selection, the extra nucleotides were added to the 3’ end of the miR strand (Figure1A). Because natural miR-34a has a 2-nt overhang at the 3’ end on the miR* strand, we increased the overhang length to 5 and 7 nt by adding 3 and 5 dT nucleotides, respectively. Because the 3’ end of miR strand of miR-34a has a single nucleotide overhang, we increased the overhang length to five and seven by adding four and six dT nucleotides, respectively (Figure 1A).”, (see page 598, column 1, paragraph 3 to column 2, paragraph 1).
Lastly, Kadekar et al teaches, “Of note, our modified miRNA had a better therapeutic effect compared with the commercially available mimics. Because we employed natural nucleotides for modifying miRNA, it would also limit any undesired toxicity that may arise from modified nucleotides generally used in commercial mimics. Such a design could be adapted to other clinically relevant miRNAs, which could address some of the off-target effects associated with the recruitment of undesired strands. We believe that our design strategy will also open new avenues for researchers to study individual strand activity of different miRNAs.”, (page 601, column 1, paragraph 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the miR-7, as taught by ‘266, with the teachings of Kadekar et al, i.e., adding of one or more deoxyribonucleotides to a 3’ end of one or more strands of a microRNA, to yield the predictable results of mir-7 comprising one or more 3’ deoxyribonucleotides on one or more strands. One would have been motivated to make such a modification because Kadekar et al teaches that by employing natural modifications on miRNA, i.e., at the 3’ end of a microRNA, it (1) limits any undesired toxicity that may arise from modified nucleotides generally used in commercial mimics, (2) mitigate some of the off-target effects of miRNA therapy, (3) allow a better understanding of sequence-specific gene regulation, and (4) could also be adapted to other miRNAs to enhance their therapeutic potential.
Accordingly, instant claim(s) 1-2, 4, 6, 8-9, and 19-20 are rejected for obvious-type Nonstatuatory double patenting over claim 8 of ‘266 in view of Kadekar et al.
Response to Arguments – Double Patenting
The previous rejection of claim 7 for Anticipatory-Type Nonstatutory Double Patenting in view of claim 8 of US 9,255,266 B2 is moot in view of Applicant’s cancellation of the claim filed 05/27/2026.
The previous rejection of claim(s) 1, 8-9, and 19-20 for Anticipatory-Type Nonstatutory Double Patenting in view of claim 8 of US 9,255,266 B2 has been withdrawn in view of Applicant’s amendments of the claim filed 05/27/2026.
The previous rejection of claim(s) 3 and 5 for Obviousness-Type Nonstatutory Double Patenting in view of claim 8 of US 9,255,266 B2 in further view of Kadekar et al (supra) is moot in view of Applicant’s cancellation of the claim filed 05/27/2026.
The previous rejection of claim(s) 2, 4, and 6 for Obviousness-Type Nonstatutory Double Patenting in view of claim 8 of US 9,255,266 B2 in further view of Kadekar et al (supra)is maintained. Applicant's arguments at page 19 of the reply filed 05/27/2026 have been fully considered and are not persuasive for at least the following reasons.
Applicant contends that the ‘266 patent in view of Kadekar et al do note teach, discloses, or otherwise suggest SEQ ID NOs: 1 and 2 [as discussed above], nor that the miR-7 comprises one or more deoxyribonucleotides added at the 3’ end of one or more of the RNA strands, and that claim 8 of ‘266 depends upon claim 1 and therefore includes all the claim limitations of independent claim 1.
Applicant is reminded the instant SEQ ID NOs: 1 and 2 are not required of instant claim(s) 2, 4, or 6, thus, the argument above is unsubstantiated.
Accordingly, the rejection for obviousness-type nonstatuatory double patenting of claims 2, 4, and 6 are maintained over claim 8 of ‘266 in view of Kadekar et al.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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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/L.M.T./Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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