DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-14, 32-36, and 39-54 are pending.
Election/Restrictions
Applicant previously elected the invention of Group II. However, they have now amended the claims to include part of Invention Group I. Since the claims now recite some of the same subject matter, it would not be in the interest of the American public to allow separate patents to Inventions I and II. So the new claims will be examined for that reason.
Claim 1(a), previously withdrawn from consideration as a result of a restriction requirement, and new Claims 39-46, which fit into non-elected Invention I, are rejoined. The restriction requirement between the pending claims, as set forth in the Office action mailed on 01 April 2025, is hereby withdrawn and claims 1(a) and 39-46 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
NOTE: No claims are currently allowable. This withdrawal is made merely in view of Applicant’s claim amendments.
Status of the Application
Applicant’s response and amendment filed 25 November 2025 are acknowledged and entered.
Applicant has amended Claims 1, 32-33. Applicant has added Claims 39-54. Applicant has cancelled claims 15-31.
Response to Amendment
Applicant has amended the Spec. and Drawings to overcome Objections; the previous objections are withdrawn.
Applicant has amended the Claims to overcome Objections; the objections to Claims 1 and 33 are withdrawn but one of the objections to Claim 32 wasn’t addressed so it is maintained.
Applicant has amended Claims 1 and 32-33 to overcome the 112(a) written description and enablement rejections; the 112(a) rejections are maintained.
Applicant has amended the claims to overcome the 112(b) rejections; the previous rejections are withdrawn.
Claims 1-14, 32-36, and 39-54 are examined.
Arguments applicable to newly applied rejections to amended or newly presented claims are addressed below. Arguments that are no longer relevant are not addressed.
Rejections not reiterated here are withdrawn.
Specification
The disclosure is objected to because of the following informalities: the Spec. is missing ¶99.
Appropriate correction is required.
Claim Interpretation
The claims recite neuronal cell. A “neuronal cell” is interpreted as any kind of neuron.
The GARS gene of Claim 1 is interpreted as a GARS gene encoding a functional GARS protein. The claim is interpreted that way because the claims recite a knock down and replace strategy, as discussed in the Spec. and indicated by Applicant’s remarks in response to the restriction requirement.
In Claim 5, the rep gene is interpreted as an AAV Replication gene and cap is interpreted as an AAV capsid gene.
Claim Objections
Claims 1 and 32 are objected to because of the following informalities:
Claim 1 shows the “l” in at least in part (b)(i) is crossed out but that “l” shouldn’t be crossed out.
Claim 32 recites …a method of delivering to a neuronal cell comprising a mutant GARS gene… but does not specify an object of delivering (i.e., the claim needs to say what is delivered)..
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-14, 32-36, and 39-54 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection. This rejection is maintained and updated in response to the claim amendments.
Claims 1, 39, and 47 recite a nucleic acid comprising either (a) a nucleic acid encoding a GARS miRNA comprising at least 90%... 100% identity to any one of SEQ ID NOs 1-25 or (b) a nucleic acid encoding a GARS miRNA comprising at least 90%... 100% identity to any one of SEQ ID NOs 1-25 and a nucleic acid comprising an RNAi-resistant GARS gene comprising at least 90% … 100% identity to any one of SEQ ID NOs 51-57. Claim 39 recites only (a) and Claim 47 recites only (b). The broad claims encompass one or two of the following large genera of nucleic acids that are comprised by the claimed nucleic acids:
Nucleic acids encoding a GARS miRNA which comprises at least 90% identity to any polynt sequence set forth in any one of SEQ ID NOs 1-25 and
Nucleic acids encoding an RNAi-resistant GARS gene which comprises at least 90% identity to any polynt sequence set forth in any one of SEQ ID NOs 51-57.
Any sequence that encodes either a GARS miRNA or a GARS miRNA and an RNAi-resistant GARS gene and is at least 90% identical to the recited SEQ ID NOs would be encompassed by the claims as instantly presented. However, Applicant has not disclosed what portion of the miRNA SEQ ID NOs is responsible for miRNA function or what portion of the RNAi-resistant GARS gene SEQ ID NOs is responsible for the RNAi resistance and GARS encoding functions.
An original claim may lack written description support when a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163.
Nucleic acids encoding a GARS miRNA that comprises at least 90% identity to any polynt sequence set forth in SEQ ID NOs 1-25 and nucleic acids encoding an RNAi-resistant GARS gene that comprises at least 90% identity to any polynt sequence set forth in SEQ ID NOs 51-57 encompass large genera of nt sequences that may be ≤10% different from SEQ ID NOs 1-25 and 51-57. A nt sequence could be or have:
up to 10% of the nts removed from SEQ ID NOs 1-25 and 51-57;
a single chunk comprising ≤10% of the nts different from SEQ ID NOs 1-25 and 51-57;
up to 10% additional nt added to SEQ ID NOs 1-25 and 51-57;
one out of every 10 nt (starting at any position) different from SEQ ID NOs 1-25 and 51-57;
one out of every 10 nt (starting at any position) removed from SEQ ID NOs 1-25 and 51-57;
any other combination of nts mutated, removed, or added from SEQ ID NOs 1-25 and 51-57, as long as the sequence retains up to ≤10% identity to the parent sequence.
Each of those categories comprises a broad subgenus with diverse members and different structures that affect their functions. Some of those structures may have altered miRNA activity, altered RNAi-resistance, altered GARS gene function and/or other altered function(s).
SEQ ID NOs 1-25 are all 86-mers so they could comprise as many as 8 nt different (86*0.9=77.4 but nt cannot be portions so ≈ 78; 86-78=8 nt). SEQ ID NOs 51-57 are 2220- or 2246-mers so they could have as many as 222-224 nt different (2220*0.9=1998; 2220-1998=222 nt; 2246*0.9=2021.4 but nt cannot be portions so ≈ 2022; 2246-2022=224 nt). A person of ordinary skill in the art would easily determine that sequences with those numbers of different nt could encode very different products from what the parent sequence encodes.
While Applicant provides the miRNA SEQ ID NOs 1-25 and the RNAi-resistant GARS gene SEQ ID NOs 51-57, Applicant never indicates what portion(s) of each sequence must be preserved for it to function as claimed. Yet, each sequence is permitted to be altered to a point where it retains as little as 90% identity to the parent SEQ ID NO. Applicant has not defined what portion(s) of SEQ ID NOs 1-25 must be preserved for the sequences to be processed into the processed strand. Applicant has not defined what portion(s) of SEQ ID NOs 51-57 must be preserved for the sequences to retain RNAi-resistance or to encode a functional GARS protein.
Example 8 (¶132-135; Figs. 13-14) is a prophetic example that describes administering an AAV9 vector that uses RNAi to knock down mutant GARS and also expresses an RNAi-resistant GARS gene. The example describes (¶133) that the miRNAs avoi[d] any sequences containing known GARS mutations associated with CMT2D [emphasis added]. But an artisan would know that there are many GARS mutations that exist or will exist but are not yet known; the Spec. itself discusses a de novo mutation that they only recently identified (see Example 1, ¶92). Example 8 briefly discusses cDNA sequences (shown in Fig. 15) that are resistant to the miRNAs but which still encode wildtype GARS protein. However, the text does not clearly define what portion(s) of the miRNA can be changed up to 10% wherein the miRNA will still target the GARS mRNA, and the claim recites that any portion may be changed. The text does not clearly define what portion(s) of the cDNA/mRNA (i.e., the RNAi-resistant GARS gene) can be changed up to 10% wherein it will still be resistant to any GARS-targeting miRNA comprising SEQ ID NOs 1-25 (which can also be changed up to 10%, further exacerbating the written description issues) and still be a GARS gene (i.e., encode GARS protein).
Although the Spec. discloses SEQ ID NOs 1-25 and 51-57, it does not teach any core structure that is responsible for the functions encoding a GARS miRNA or comprising an RNAi-resistant GARS gene. It does not teach which 10% of nts may or may not be altered for the sequences to function. It does not teach which 90% of nts must be present or must not be altered for the sequences to function. It does not teach the portion of the sequences necessary to carry out the claimed functions. Although the claims recite functional characteristics (i.e., encoding a GARS miRNA or comprising an RNAi-resistant GARS gene), the functional characteristics are not coupled with known structures.
Although the Specification teaches the sequences discussed above, it does not identify a core structure necessary for performing the claimed function(s) of encoding a GARS miRNA or comprising an RNAi-resistant GARS gene. The Spec. does not disclose any core structure, partial structure, physical or chemical property, or functional characteristic coupled with a known or disclosed structure/function relationship responsible for encoding a GARS miRNA or comprising an RNAi-resistant GARS gene in such a way to demonstrate possession of the full invention as claimed at time of filing. The recited SEQ ID NOs do not share a core structure and the SEQ ID NOs altered up to 10% do not share any core structure.
The specification teaches only a limited number species within the claimed genus/genera, namely the specific sequences of exactly SEQ ID NOs 1-25 and 51-57. However, those are only a paltry number compared with the breadth of what is claimed. Altogether, the number of species disclosed by complete structure is not sufficient to provide the written description support for the huge genera and subgenera that are encompassed by the claims: (1) nucleic acid sequences encoding a GARS miRNA and comprising at least about 90% identity to SEQ ID NOs 1-25 and (2) nucleic acid sequences comprising an RNAi-resistant GARS gene and comprising at least about 90% identity to SEQ ID NOs 51-57.
While none of these elements is specifically required to demonstrate possession, in combination their absence means that one skilled in the art at the time of filing would conclude that the inventors lacked possession of the full breadth of the invention claimed. Claims 1, 39, and 47 are rejected for failing to demonstrate possession of the claimed invention. Claims 2-14, 32-36, and 39-54 are rejected because they depend from Claim(s) 1 and do not remedy the issues.
Claims 1-14, 32-36, and 39-54 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This is an enablement rejection. This rejection is maintained and updated in response to the claim amendments.
The factors to be considered in determining whether a disclosure would require undue experimentation include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the specification; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims and the nature of the invention: With respect to claim breadth, the standard under 35 U.S.C. §112(a) entails determining what the claims recite and what the claims mean as a whole.
Claim 1 recites: A nucleic acid comprising
a polynucleotide sequence encoding a GARS miRNA, the polynucleotide sequence encoding a GARS miRNA comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25; or
a polynucleotide sequence comprising
a first polynucleotide sequence encoding a GARS miRNA, the first polynucleotide sequence comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25; and
a second polynucleotide sequence comprising an RNAi-resistant GARS gene, comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 51-57.
Claim 39 recites: The nucleic acid of claim 1 comprising a polynucleotide sequence encoding a GARS miRNA, the polynucleotide sequence encoding a GARS miRNA comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25.
Claim 47 recites: The nucleic acid of claim 1 comprising
a first polynucleotide sequence encoding a GARS miRNA, the first polynucleotide sequence comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25 to any one of SEQ ID NOs: 1-25; and
a second polynucleotide sequence comprising an RNAi-resistant GARS gene, comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 51-57.
[text contributing to the enablement problem is emphasized for Claim 1 above.]
The broadest reasonable interpretation (BRI) of Claim 1 is that it can encompass either (a) a nucleic acid that encodes a GARS miRNA and comprises at least 90% identity to any one of the polynt sequences of SEQ ID NOs 1-25 or (b) two nucleic acid components comprised on a single nucleic acid: (1) a nucleic acid that encodes a GARS miRNA and comprises at least 90% identity to any one of the polynt sequences of SEQ ID NOs 1-25 and (2) a nucleic acid that comprises an RNAi-resistant GARS gene and whose sequence comprises at least 90% identity to any one of the polynt sequences of SEQ ID NOs 51-57. As discussed in the written description rejection, both of those nucleic acids possess specific functions: the first (i.e., [a] and [b][i]) encodes a miRNA that targets GARS mRNA; implied in that function is that all the claimed miRNAs (including those with as little as 90% identity to the claimed SEQ ID NOs) inhibit GARS mRNA function, thereby inhibiting translation of GARS mRNA [Wingdings font/0xE0]GARS protein. The second nucleic acid has two functions: it is resistant to any RNAi and it encodes GARS protein. An artisan would readily interpret that the two nucleic acid components are intended for use in a “suppress and replace” or “knock down and replace” gene therapy strategy wherein the miRNA is used to suppress expression of endogenous mutant GARS protein and the nucleic acid comprising an RNAi-resistant GARS gene provides a functional copy of GARS that cannot be suppressed by the miRNA.
The BRI of Claim 39 is the same as for Claim 1(a) and the BRI of Claim 47 is the same as for Claim 1(b).
Claim 33 recites: A method of treating a subject suffering from a mutant Glycyl-tRNA Synthetase (GARS) gene, the method comprising administering to the subject an effective amount of the nucleic acid of claim 1 and wherein the subject is a human subject (Claim 36). The BRI of Claims 33 and 36 is that the method of administering the nucleic acids of claim 1 will treat any subject suffering from any mutation in their GARS gene, and that the subject of the treatment method can be a human subject. Since Claim 1 now recites (a) which is just a nucleic acid comprising a polynt sequence encoding a GARS miRNA, the BRI of Claims 33 and 36 is that any of the miRNA of Claim 1(a) can be used to treat a subject or human subject suffering from a mutant GARS gene.
Claim 34 recites: The method of claim 33 wherein the subject suffers from Charcot-Marie-Tooth Disease Type 2D (CMT2D) or Distal Hereditary Motor Neuropathy. The BRI of Claim 34 is that the treatment method will work on any subject suffering from distal hereditary motor neuropathy (dHMN) or CMT, specifically type 2D (CMT2D). Any subject suffering from CMT2D or dHMN can be treated by the claimed method, as long as they have a mutation in their GARS gene.
The nature of the invention is a method of treating any condition caused by any mutation in a GARS gene (or the specific conditions CMT2D or dHMN) using either (a) a suppress/knockdown strategy or (b) a suppress and replace strategy that comprises administering a nucleic acid comprising the nucleic acid component(s) recited in Claims 1, 39, and 47: an miRNA for suppressing or an miRNA for suppressing and an RNAi-resistant nucleic acid for expressing an mRNA that is resistant to RNAi and which encodes a functional GARS protein.
A skilled artisan would not be able to use the method as claimed with a reasonable expectation of success based on guidance provided in the specification and art at the time of the filing of the application.
The state of the art and prior art, the level of one of ordinary skill, and the level of predictability in the art: A review of the art and prior art shows:
MiRNA must be specific for its target.
Applicant has not determined that their purportedly RNAi-resistant GARS sequences are resistant to any GARS-targeting miRNA.
MiRNA used in inhibition or suppress and replace gene therapy should be mutation-agnostic.
Components of an RNAi or suppress/replace strategy must be validated to ensure they work as intended.
Mutations in multiple genes can cause dHMN.
Regarding point 1, the art of Christopher (et al. 2016. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect. Clinic. Res. 7[2]:68-74, “Christopher”, of record) teaches (§Introduction ¶1) miRNAs regulate expression of target genes through sequence specific hybridization. Christopher teaches (same §) the miRNAs block translation or cause direct degradation of target mRNA. Christopher teaches (same § ¶2) an ideal design for an active synthetic miRNA is that it should bind to its respective target with high affinity and specificity.
Christopher indicates a miRNA should be specific for its target. Yet, the claimed invention recites miRNA and RNAi-resistant GARS sequences that can share as little as 90% identity to the parent sequence. As discussed in the written description rejection, Applicant has not identified any portions of the sequences that must be preserved for function to be preserved. Add to that the fact that the claims allow altering both the miRNA and the RNAi-resistant GARS sequences. A person of ordinary skill in the art would determine that, without provision of more guidance:
Modifying the miRNA sequences could result in a miRNA that (1) does not target a mutant GARS sequence or (2) actually targets the purportedly RNAi-resistant GARS sequences.
Modifying the purportedly RNAi-resistant GARS sequences could result in a sequence that:
No longer encodes GARS and/or
Is no longer RNAi-resistant.
Therefore an artisan would determine that without evidence demonstrating otherwise, using the full breadth of what is recited in Claims 1, 39, and 47 would produce unpredictable results.
Regarding point 2, teachings in the Spec. (¶3) identify GARS as a known target of interest for down-regulation. That means there are many GARS-targeting RNAis out in the world, as well as more being developed (e.g., Creative Biolabs siRNA, Anti-Human GARS, Backbone-modified. Cat. No. SIRGT07669WQ-BB. Available at creative-biolabs.com, of record). Applicant has not verified that their purportedly RNAi-resistant GARS sequences are resistant to their own claimed miRNAs, let alone the breadth of GARS-targeting RNAis that exist or can exist.
Regarding point 3, the art of Millette (et al. 2022. A Single Transcript Knockdown-Replacement Strategy Employing 5’ UTR Secondary Structures to Precisely Titrate Rescue Protein Translation. Frontier. Genom. Edit. 4:803375, “Millette”, of record) and Millington (et al. 2011. Suppression and Replacement Gene Therapy for Autosomal Dominant Disease in a Murine Model of Dominant Retinitis Pigmentosa. Molec. Ther. 19[4]:642-649, “Millington”, of record), both directed to suppress and replace gene therapy approach for a dominantly inherited disorder for genes other than GARS, teach (Millette, §Introduction ¶1; Millington, §Introduction ¶2) such disorders can be caused by heterogenous mutations within a gene. Regarding mutations in specifically GARS, the instant Spec. teaches (¶3) diverse mutations in GARS cause CMT2D, including (¶52) de novo mutations, and (¶3) disease-associated mutations are distributed across the protein as well as (Fig. 13A) distributed across the cDNA/mRNA. Millette also teaches §Introduction ¶4) clinical trials targeting the central nervous system are commonly unsuccessful.
Regarding point 3 as it pertains to the amended claims, namely RNAi strategies, Ding (et al. 2003. Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis. Aging Cell 2:209-217, “Ding”) teaches that (§Abstract) RNAi can be a promising strategy for treating diseases caused by gain-of-function mutations but proper validation is required. Ding teaches (§Introduction ¶3) design of RNAi that targets mutations that result in single amino acid changes is not straightforward and that siRNAs that differ from the sequence of their target RNA at one or more [nt] retain efficacy in some cases and lose activity in others. Ding discusses the importance of validating their RNAi, including for individual mutant alleles. Grice (et al. 2015. Dominant, toxic gain-of-function mutations in gars lead to non-cell autonomous neuropathology. Hum. Molec. Genet. 24[15]:4397-4406, “Grice”) teaches (§Abstract) CMT2D is caused by toxic gain of function mutations in GARS and that (§Introduction ¶2) GARS can be caused by single amino acid substitutions and that overexpression of wildtype GARS doesn’t rescue CMT2D mice indicating that gain of function mutations are responsible for the disease. Grice teaches (§Abstract; §Discussion, penultimate ¶) certain protein domains within GARS protein are responsible for disease symptoms. Together, the teachings of Ding and Grice indicate that RNAi must be specific for its target and must possess specificity for treating gain-of-function mutations caused by single amino acid changes. Those teachings indicate that such RNAi must be thoughtfully designed and validated in vitro and in vivo. Therefore an artisan would understand that the miRNA comprising SEQ ID NOs 1-25, altered up to 10%, would have unpredictable effects on treating any condition caused by a mutant GARS gene or the specific condition CMT2D.
Regarding point 4, which is related to points 1-3, the art indicates that miRNA nucleotide sequences must be validated to ensure they downregulate their target and RNAi-resistant protein encoding sequences must be validated to ensure they are RNAi resistant and encode a functional protein. Li (et al. 2011. Combination therapy utilizing shRNA knockdown and an optimized resistant transgene for rescue of diseases caused by misfolded proteins. PNAS 108[34]:14258-14263, “Li”, of record) teaches (§Optimized AAT Transcript Is Resistant to Wild-Type AAT shRNA) they validated their shRNA–cDNA pairs—in vitro and in mice—before determining their optimized cDNA could escape targeting by their shRNAs. Similarly, Jones (et al. 2024. Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy. Molec. Ther. 32[10]:3318-3330, “Jones”, of record) teaches (§Bivalent adeno-associated virus vector to deliver RNAi and cDNA gene therapy; Fig. 2B) out of the five miRNAs targeting their gene of interest, one also silenced their codon-optimized target (which had been designed to be RNAi resistant). That indicates that although Jones designed their cDNA to encode an RNAi-resistant gene—so it should be resistant to their own miRNAs—when they validated system performance, either the miRNA or the purportedly RNAi-resistant gene did not perform as anticipated. The findings of Jones indicate to an artisan that even if a specific miRNA–RNAi-resistant gene pair are mindfully designed, their actual function must be validated. Similarly, the art of Dotzler (et al. 2021. Suppression-Replacement KCNQ1 Gene Therapy for Type 1 Long QT Syndrome. Circulation 143:1411–1425, “Dotzler”, of record) teaches (§Generation of a KCNQ1-SupRep Gene Therapy Construct) at least one of their shRNAs did not downregulate its target. Once again, that finding points to the need to validate the performance of any nucleic acids, as well as the fact that such validation is standard in the art. The teachings of Ding, discussed in the preceding ¶, make the same point: validation is necessary.
Furthermore, administration of either component alone does not guarantee treatment. The art of Millington (cited above) teaches that (§Discussion ¶5) while administering their entire suppress and replace strategy (i.e., components of both suppression and replacement) successfully treated mice with retinitis pigmentosa, neither suppression alone nor replacement alone resulted in treatment. Grice makes the same point about CMT2D (cited above). That would indicate to an artisan that without demonstration of in vivo validation, the ability of the suppress and replace strategy to treat a condition is unpredictable. Although both nucleic acid components are comprised on a single nucleic acid, the claims allow for substantial modification of either component, so without validation, there is no guarantee that both components—or either—will perform as claimed.
As discussed, Christopher and Ding teach miRNAs must be specific for their target. Between the modified miRNAs and modified RNAi-resistant GARS sequences and variation in GARS mutations, an artisan would determine that there is too much variation within the claimed sequences to predictably suppress expression of GARS comprising any mutation. Furthermore, Applicant has not validated the ability of any of their miRNAs (i.e., even those with the exact sequences claimed) to downregulate mutant GARS while not interfering with expression of functional GARS protein encoded by their RNAi-resistant GARS genes; that validation is particularly notable given that the claim encompasses not only the exact sequences recited but variations of up to 10%. Similarly, Applicant has not validated the ability of any of their purportedly RNAi-resistant GARS gene sequences to resist any RNAi.
Finally, regarding point 5, although Morelli (cited on IDS) teaches that the type of CMT specified in Claim 34, CMT2D, is caused by mutations in GARS, the art teaches mutations in other genes can cause dHMN. For example, Dierick (et al. 2008. Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype–phenotype correlation study. Brain 131:1217-1227, “Dierick”, of record) teaches (§Abstract) dHMN is a clinically and genetically heterogeneous group of disorders caused by dominant mutations in GARS and several other genes. The recent art of Panzo (et al. 2025. Distal Hereditary Motor Neuropathies: A Rare Familial Case Caused by a Mutation in the VWA1 Gene. J. African Clin. Case. Rev. 9[2]:321-327, “Panzo”, of record) teaches (§Introduction ¶1) 38 genes have been implicated. The Spec. describes (¶108) silent single nt differences between mouse and human GARS. That demonstrates that silent mutations in GARS occur. In theory, a patient could comprise both a silent mutation in GARS and could suffer from dHMN caused by a mutation or mutations in other gene(s). Alternatively a patient could have mutations in both GARS and another gene that causes dHMN. It is therefore not clear that the methods of treatment recited in Claims 33-34 or 36 could in fact treat any subject or human subject suffering from a mutant GARS gene or any subject or human subject suffering from dHMN.
Altogether, the art indicates that successfully using the claimed compounds (which require either functional miRNAs or both functional miRNAs and RNAi-resistant GARS genes) and methods of treating a subject or human subject suffering from a mutant GARS gene (and the specific diseases CMT2D and dHMN) would be unpredictable because the compounds and variants of them haven’t been validated, mutations underlying a genetic condition are heterogeneous, and no actual treatment from any of the claimed sequences has been demonstrated. Therefore, although the skill level of an artisan is high, successfully using the full breadth of the claimed compounds (which haven’t been validated) and the art of using the claimed suppress and replace strategy to treat diseases, neurological diseases, and specifically CMT2D or dHMN, is unpredictable as evidenced by the state of the art discussed above.
The amount of direction provided by the specification and the existence of working examples: What is enabled by the working examples does not enable the claimed invention. The Spec. teaches certain examples; only Example 8, a prophetic example, is directly relevant to the claimed invention:
Example 1 (¶92-94) discusses mutation analysis of a CMT2D patient who has a ΔETAQ GARS mutation.
Example 2 (¶95-100; Fig. 1) investigated the effect of the ΔETAQ GARS mutation and found the mutation has no observable effect on GARS mRNA transcription or GARS protein production.
Example 3 (101-112) describe three mouse models of CMT2D, including production of a mouse model comprising the newly identified ΔETAQ GARS mutation which was found (Fig. 2) to reproduce CMT2D symptoms. All three models comprise a mutation in GARS.
Example 4 (¶113-116; Figs. 4-5) identified miRNAs that silence the ΔETAQ GARS mutation. This example discusses (¶116) slight differences in mouse ΔETAQ GARS mRNA vs. human ΔETAQ GARS mRNA result in their lead miRNA being unable to knockdown the mouse ΔETAQ GARS mutant allele. The Spec. describes that those miRNAs are shown in Fig. 5; that Fig. shows the miRNA used in the example have SEQ ID NOs that are different from the claimed SEQ ID NOs.
Example 5 (¶117-119) describes producing an scAAV9 vector that carries the miRNA that targets the ΔETAQ GARS mutation. The Spec. describes that mi.ΔETAQ is shown in Fig. 4B; that Fig. shows the miRNA used in the example has a sequence that is different from any of the claimed SEQ ID NOs.
Example 6 (¶120-122; Fig. 4) discusses delivering to mice (who carry the ΔETAQ mutation but before disease onset) the AAV vector carrying the ΔETAQ-targeting miRNA, and shows that the miRNA improves outcomes in the ΔETAQ GARS mouse.
Example 7 (¶123-131; Fig. 6) discusses administering the gene therapy to mice after disease onset and found the ΔETAQ mice were better off by some measures than mice receiving no treatment. An AAV carrying an miRNA targeting another mutation, P278KY, (Fig. 7) was also tested and (Figs. 8-12) improvements were observed
Example 8 (¶132-135; Figs. 13-14) is a prophetic example that describes administering an AAV9 vector that uses RNAi to knock down mutant GARS and also expresses an RNAi-resistant GARS gene. The example describes that (¶133) the miRNAs avoid targeting any sequences containing known GARS mutations associated with CMT2D. Inherent in the statement about known GARS mutations is the fact that there exist unknown GARS mutations. The example briefly discusses cDNA sequences (shown in Fig. 15) that are resistant to the miRNAs but which still encode wildtype GARS protein. However, the text does not clearly define what portion(s) of the miRNA can be changed up to 10% wherein the miRNA will still target the GARS mRNA. The text does not clearly define what portion(s) of the cDNA/mRNA can be changed up to 10% wherein it will still be resistant to any GARS-targeting miRNA comprising SEQ ID NOs 1-25 (also changed up to 10%) and still encode GARS protein (assuming that SEQ ID NOs 51-57 are resistant to any RNAi, which has not been demonstrated). Nor does the Spec. provide information about how to make that determination. Although Fig. 17 aligns human and mouse GARS mRNAs, neither that figure nor the Spec. disclose what parts of the mRNA can be altered or must be preserved for the mRNA to both encode GARS protein and be resistant to GARS miRNAs. It is reiterated that the claimed sequences have not been validated for their claimed functions.
Example 9 (¶136-140; Fig. 16) discusses defining how much GARS gene expression is required for normal function which is ≈30% of wildtype levels.
Example 10 (¶141-144) discusses experiments that sought to understand how ΔETAQ GARS affects enzyme function; those experiments indicated that ΔETAQ GARS retained less than 0.01% of its aminoacylation activity and ΔETAQ GARS could not complement growth in yeast with a deleted ortholog.
Example 11 (¶145-148) discusses how ΔETAQ GARS interacts with NRP1, which is unrelated to the claimed invention.
Altogether, the examples don’t enable the invention because:
The claims recite the invention comprises a nucleic acid comprising an RNAi-resistant GARS gene comprising at least 90% identity to any one of the sequences set forth in SEQ ID NOs 51-57.
But Applicant has not demonstrated that those RNAi-resistant GARS genes are actually resistant to either their own claimed miRNA or other GARS-targeting RNAis that exist out in the world. Nor has Applicant demonstrated that sequences possessing only 90% identity to the claimed SEQ ID NOs would function as claimed, exhibiting resistance to RNAi and encoding a functional GARS gene.
The claims recite the invention comprises a nucleic acid encoding a GARS miRNA comprising at least 90% identity to the polynt sequence of SEQ ID NOs 1-25.
However, Applicant has not demonstrated that sequences possessing only 90% identity to the claimed SEQ ID NOs would function as claimed, miRNAs that target GARS.
Applicant has not validated their claimed miRNAs, RNAi-resistant GARS genes, or methods of treating a subject.
Applicant has not validated that even just the claimed sequences (and not their up-to-90% variants) function as claimed. The art described above (Dotzler, Ding) indicates that even mindfully designed miRNAs/RNAi do not necessarily suppress expression of an endogenous allele. The art (Jones) describes even a mindfully designed mRNA that was codon-optimized for resistance to a paired miRNA was subject to knockdown by a miRNA. Millington showed that in their system, both components were required for successful treatment. But Applicant’s examples do not show using any of the claimed sequences to treat any condition, let alone in a human.
dHMN is not necessarily caused by a mutation in GARS.
As discussed above, an individual could very well comprise a silent mutation in GARS but also have a pathogenic mutation in a gene that causes dHMN. Such individual would meet the terms of Claims 33-34 and 36 but would not be treated by the claimed methods; at least nothing in the Spec. provides evidence of treatment.
In summary, the guidance present in the specification does not provide any guidance in addressing the enablement issues raised in view of the state of art discussion presented above.
The quantity of experimentation needed to make or use the invention: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given the teachings described above, an artisan of ordinary skill would not be able to use the invention as claimed with a reasonable expectation of success. The amount of experimentation required for enabling guidance commensurate in scope with what is claimed goes beyond what is considered “routine” within the art and constitutes undue further experimentation in order to successfully use the nucleic acid comprising a nucleic acid encoding a GARS miRNA comprising at least 90% identity to the polynt sequence set forth in any of SEQ ID NOs 1-25 and a nucleic acid comprising an RNAi-resistant GARS gene comprising at least 90% identity to the polynt sequence set forth in any of SEQ ID NOs 51-57. Successfully using the claimed methods of treating recited conditions or conditions encompassed by recited characteristics is also determined to be unpredictable.
Claims 1, 33-34, 36, 39, and 47 are rejected for lack of enablement. Claims 2-14, 32-36, and 39-54 are rejected because they depend from Claims 1, 33-34, 39 and/or 47 and don’t remedy the issues.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14, 32-36, and 39-54 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 rejection is necessitated by the claim amendments.
Claims 1, 39, and 47 recite the limitation "a polynucleotide sequence" and "the polynucleotide sequence" in L2-3, 7-9, 13-14, and 16 (Claim 1); L1-2, 4 (Claim 39); and L2, 4-7 (Claim 47). There is insufficient antecedent basis for this limitation in the claim because each claim recites or depends from a claim that recites more than one polynucleotide sequence. The claim language does not clarify which polynucleotide (polynt) sequence is being referenced.
Claims 1, 39, and 47 are rejected for those reasons. Claims 2-14, 32-36, 39-54 are rejected because they depend from Claims 1, 39, and 47 and don’t remedy the issues.
In the interest of compact prosecution, the claims are interpreted as follows:
Claim 1. A nucleic acid comprising
a polynucleotide sequence encoding a GARS miRNA, the polynucleotide sequence encoding a GARS miRNA comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25; or
a polynucleotide sequence comprising
a first polynucleotide sequence encoding a GARS miRNA, the first polynucleotide sequence comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25; and
a second polynucleotide sequence comprising an RNAi-resistant GARS gene, comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 51-57.
Claim 39. The nucleic acid of claim 1 comprising a polynucleotide sequence encoding a GARS miRNA, the polynucleotide sequence encoding a GARS miRNA comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25.
Claim 47. The nucleic acid of claim 1 comprising
a first polynucleotide sequence encoding a GARS miRNA, the first polynucleotide sequence comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 1-25 to any one of SEQ ID NOs: 1-25; and
a second polynucleotide sequence comprising an RNAi-resistant GARS gene, comprising at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 51-57.
Sequences Free of or Nonobvious Over Prior Art of Record
The following sequences were searched and found free of the prior art of record:
SEQ ID NOs 1-25 and 51-57.
Response to Arguments
Applicant's arguments filed 25 November 2025 have been fully considered but they are not persuasive. Arguments that are no longer relevant are not addressed. References ¶ number count the first full ¶ on each page of Remarks as ¶1.
Objection
The previous Office action described that there is no object indicating what is delivered in Claim 32. A method of delivering [__?__] to a neuronal cell comprising a mutant Glycyl-tRNA Synthetase (GARS) gene, the method comprising administering to the neuronal cell an effective amount of any of the nucleic acids of claim 1. Although Remarks (p. 10 ¶4-5) state that this objection was addressed, there is no indication that is the case.
Claim 1 is objected to because a typographical error results in L in “least” being struck-through.
112(a) written description
Applicant argues (p. 11 ¶3) that since the claims recite at least 90% identity to SEQ ID NOs, the claims encompass only minimal substitutions with respect to the reference sequences. Applicant argues (same p., ¶4) a person of ordinary skill would know how to make such minimal substitutions and determine that the nucleotide sequence works for its intended purpose and therefore the person or ordinary skill would understand that the inventors were in possession of the full scope of the claimed invention at time of filing.
That is not persuasive because the claims encompass sequences defined in terms of their function and percent shared identity to recited SEQ ID NOs but the Spec. doesn’t describe what portions of each SEQ ID NO are responsible for the function(s) the claims recite.
Regarding SEQ ID NOs 1-25, 8 out of 86 nt isn’t a huge number but what matters is which 8 nt are changed/added/removed. Applicant hasn’t said which nt can be changed/added/removed, nor have they presented any evidence demonstrating that miRNA sequences with any nt alterations perform as miRNA as claimed. Yet, their claim recites that all of those sequences comprising at least 90% identity to SEQ ID NOs 1-25 would possess the function of being a miRNA for GARs. The current claims do not meet the burden of demonstrating possession of the full breadth of the claims.
Regarding SEQ ID NOs 51-57, 222-224 nt is a much larger number of nt that can be changed/added/removed. Applicant hasn’t said which nt can be changed/added/removed, nor have they presented any evidence demonstrating that any sequences with that many alterations would be miRNA/RNAi-resistant or encode GARS which are required functions of the claims. Yet, their claims recite that all of those sequences comprising at least 90% identity to SEQ ID NOs 51-57 would possess the functions of being both miRNA/RNAi-resistant and encoding GARS. The current claims do not meet the burden of demonstrating possession of the full breadth of the claims.
Applicant should either narrow their claims, present evidence that a representative number of altered sequences function as claimed, and/or disclose what portions of SEQ ID NOs 1-25 and 51-57 are responsible for the claimed functions of being either (a) a miRNA or (b) miRNA/RNAi-resistant and encoding GARS. Since there is currently no evidence that Applicant was in possession of the full breadth of their claims so the rejection is maintained.
112(a) enablement
Applicant argues (p. 12 ¶8) as long as the specification discloses at least one method for making and using the claimed invention that bears a reasonable correlation to the entire scope of the claim, then the enablement requirement of 35 U.S.C. §112 is satisfied and that a considerable amount of routine experimentation is permissible. Applicant argues that 8 out of 86 nt substitutions aren’t too many and 222-224 out of 2220 or 2246 aren’t too many.
That is not found persuasive for several reasons.
First, the claims are broad but they also recite specific functions of compounds and outcomes of treatment. The full scope of the claims must be enabled. The fact pattern here is similar to the following:
The breadth of the claims was a factor considered in Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991), cert. denied, 502 U.S. 856 (1991). In Amgen, the patent claims were directed to a purified DNA sequence encoding polypeptide analogs of the protein erythropoietin (EPO). The court stated that:
Amgen has not enabled preparation of DNA sequences sufficient to support its all-encompassing claims. . . . [D]espite extensive statements in the specification concerning all the analogs of the EPO gene that can be made, there is little enabling disclosure of particular analogs and how to make them. Details for preparing only a few EPO analog genes are disclosed. . . . This disclosure might well justify a generic claim encompassing these and similar analogs, but it represents inadequate support for Amgen’s desire to claim all EPO gene analogs. There may be many other genetic sequences that code for EPO-type products. Amgen has told how to make and use only a few of them and is therefore not entitled to claim all of them.
927 F.2d at 1213-14, 18 USPQ2d at 1027. However, when claims are directed to any purified and isolated DNA sequence encoding a specifically named protein where the protein has a specifically identified sequence, a rejection of the claims as broader than the enabling disclosure is generally not appropriate because one skilled in the art could readily determine any one of the claimed embodiments.
MPEP §2164.08
Here, the claims encompass a vast number of analogs to the claimed miRNAs and mRNAs—analogs which are all purported to possess specific functions—instructions on how to make and use only a few of them, namely the specific SEQ ID NOs. Although the mRNA and protein sequences of GARS are known, the mRNA protein sequences of GARS that possesses the specific function of being RNAi-resistant is not known. Furthermore, the state of the art discussion explains how the art teaches the full breadth of the claims is unpredictable.
Regarding the number of substitutions being “minimal”, the arguments aren’t persuasive because it matters which 8 or 222-224 nt are changed. As discussed in the rejection, Ding teaches RNAi that targets mutations that alter a single amino acid in the protein (the kinds of mutations Grice teaches underlie CMT2D) require mindfully designed and validated RNAi sequences. An artisan would understand that such mindfulness considers the target sequence and the RNAi sequence. Applicant hasn’t identified which bases of their claimed miRNA and RNA sequences are responsible for claimed functions, so it would not be possible for an artisan to undertake mindful design without also undertaking undue experimentation. Applicant’s Spec. doesn’t identify which nt may and may not be changed. The fact that Applicant hasn’t pointed to any place in the Spec. or any references substantiating their assertion (i.e., that making such vast changes to a sequence is routine) indicates that there isn’t enough known about GARS and mutations in it, their claimed miRNAs and mutations in them, or their claimed GARS-encoding mRNA and mutations in them to determine that making such alterations is as routine as they assert. Applicant asserts that 10% alterations—even 222 to 224 nt!—are “minimal” amounts of alterations but they have presented absolutely zero evidence substantiating that. Meanwhile the teachings of Ding and the other cited references conflict with Applicant’s assertion.
ATTORNEY ARGUMENTS CANNOT TAKE THE PLACE OF EVIDENCE
The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
See MPEP § 2145 generally for case law pertinent to the consideration of applicant’s rebuttal arguments.
MPEP §716.01(c)
The art of Grice was discussed above and is pertinent to Claim 1(b) (the suppress and replace strategy) because Grice indicates (§Abstract, § GlyRS toxicity and synapse binding, but not secretion, are dependent on the WHEP domain, §Discussion) that CMT2D symptoms can be caused by a mutation in a single GARS domain. In addition to the other cited art, that specific teaching indicates that an mRNA encoding GARS, if altered by as much as 10%, would have unpredictable effects on treating any condition caused by a mutant GARS gene or the specific condition CMT2D. Similarly, the enablement rejection cites Ding and other references that teach RNAi must be specific to its target and validated before it can be ascertained to have its predicted effect. The references teach that is the case particularly for conditions caused by gain-of-function mutations. The claims recite treating any condition caused by any mutation in GARS but mutations vary, and that affects how an artisan would design miRNA sequences. Since Applicant hasn’t disclosed any GARS mutation or a representative number of them, and since the art doesn’t teach any GARS mutations underlying such conditions, Applicant should disclose what portions of their claimed sequences may not be changed for their invention to work.
Furthermore, there are issues with the claims that were explained in the enablement rejection and Applicant’s remarks don’t address those issues. Those issues include:
The BRI of Claims 33 and 36 is that the method of administering the nucleic acids of claim 1 will treat any subject suffering from any mutation in their GARS gene. That hasn’t been demonstrated, particularly in view of the wide range of mutations in GARS and teachings that miRNAs must be specific for their target.
The fact that Applicant has not validated the ability of any of their miRNAs (i.e., even those with the exact sequences claimed) to downregulate mutant GARS while not interfering with expression of functional GARS protein encoded by their RNAi-resistant GARS genes
The fact that Applicant has not validated the ability of any of their purportedly RNAi-resistant GARS gene sequences to resist any RNAi. The claims recite resistance to any RNAi, not only the miRNAs claimed.
The rejection discusses that the instant Spec. teaches (¶3) diverse mutations in GARS cause CMT2D, including (¶52) de novo mutations, and (¶3) disease-associated mutations are distributed across the protein as well as (Fig. 13A) distributed across the cDNA/mRNA. Applicant has not demonstrated that their miRNAs inhibiting a representative number of mutations in a GARS gene.
Because those issues weren’t addressed, and because of the other reasons as discussed, the enablement rejection is maintained. To overcome this rejection Applicant can either (1) disclose specific motifs that are required for miRNA and mRNA/RNAi-resistance function, (2) show a representative number of modified miRNAs and RNAi-resistant mRNAs that function as claimed, or (3) narrow their claims.
112(b)
The claims are indefinite due to unclear antecedent bases.
112(d)
This rejection is necessitated by the claim amendments. Claim 1 recites a nucleic acid that comprises (a) or (b) wherein (b) encompasses two parts, (i) and (ii). Part (b)(i) is simply (a). Therefore either (a) or (b) encompasses (a). Claim 39 depends from Claim 1 and recites a nucleic acid comprising (a). Claim 39 does not further limit Claim 1 because Claim 39 recites a nucleic acid comprising (a) and Claim 1 recites a nucleic acid that always comprises (a).
Conclusion
Claims 1-14, 32-36, and 39-54 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUTHIE S ARIETI whose telephone number is (571)272-1293. The examiner can normally be reached M-Th 8:30AM-4PM, alternate Fridays 8:30AM-4PM (ET).
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RUTHIE S ARIETI
Examiner (Ruth.Arieti@uspto.gov)
Art Unit 1635
/RUTH SOPHIA ARIETI/Examiner, Art Unit 1635
/NANCY J LEITH/Primary Examiner, Art Unit 1636