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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copies have been filed in parent Application No. 17/334,345, filed on May 28, 2021.
Application Status
This Application is a Divisional of US Application No. 17/334,345 filed
05/28/2021. After Restriction Requirement of Inventions claimed in Application No. 17/334,345, dated 02/03/2023, Applicant responded with the election of Group I, encompassing claims 1-9 for further examination without traverse on 03/04/2023.
However, Applicant amended the claims in instant application in such a way that the claims no longer have “consonance” with the original application.
MPEP 804.01 states “The following are situations where the prohibition against nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply:” , “(B) The claims of the application under examination and claims of the other application/patent are not consonant with the restriction requirement made by the examiner, since the claims have been changed in materials respects from the claims at the time the requirement was made.”
Therefore, the instant claimed subject matters do not benefit from protection under 35 U.S.C. §121 against a Non Statutory Double Patenting rejection given to divisional applications.
Amendments to claims filed 01/12/2026 were presented without strike-
throughs and/or underlines. This is an error in claim presentation according to MPEP § 714 (II)(C) and rule 37 C.F.R. 1.121 “Manner of making amendments in application”, section (c ). However, the error did not preclude examination.
Amendments to claims filed 01/12/2026 are hereby acknowledged. Claim 1 is amended. Claims 2-7 are cancelled.
Therefore, claim 1 is currently pending and under consideration in this office action.
Any objection or rejection not reiterated herein has been overcome by amendments. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Specification
Applicant states that a Substitute Specification was filed on 01/12/2026 and was provided with corrections. However, no such file was found. Therefore, the objections to the Specification are maintained.
The use of the terms “EndoFectin” (page 27, line 24), “Secrete-Pair” (page 27, line 28), “Synergy HTX” (page 27, line 30), “SuperSignal West Pico” (page 29, line 21), “ImageQuant” (page 29, line 22), “TaqMan” (page 26, lines 21, 24; page 30, lines, 3, 6; page 31, lines 9, 11; page 33, line 16, 19; page 36, lines 10, 13), “CFX Connect” (page 26, line 25; page 30, line 7; page 31, line 12; page 33, line 20; page 36, line 14) , which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “thereby increasing expression of the SYNCRIP in a brain striatum”. The claim should read “ thereby increasing expression of the SYNCRIP gene in a brain striatum”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1 is 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.
Regarding claim 1, the claim recites “thereby increasing expression of the SYNCRIP in a brain striatum and restoring serum microRNA-137 levels”. The meaning of “restoring serum microRNA-137 levels” is not clear. There is no specific standard recited for the level of microRNA-137 to return to.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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.
Nature of the Invention:
Claim 1 recites “A method for treating methamphetamine addiction in a subject,
comprising: administering to the subject an effective amount of a vector comprising a nucleic acid encoding synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) having the sequence set forth in SEQ ID NO: 1, thereby increasing expression of the SYNCRIP in a brain striatum and restoring serum microRNA-137 levels.”
It is therefore expected, in the instant application a disclosure of a method, adaptable to any subject, human subjects, and especially a method that is feasible on a significant sample size population for establishing level ranges. It is expected in the disclosure the demonstration of a connection between high levels of SYNCRIP in subject’s samples and a lack of addictive behavior.
It is expected a measure of levels in samples in different populations of subjects to be able to compare and establish a “normal control range” to be able to “restore” the levels to normal range.
It is expected in the disclosure a method for treating methamphetamine addiction, including examples of compounds or mixtures of compounds with specific structures, e.g., delivery vehicle, liposome and the like, capable of decreasing substance abuse, and capable of targeting the brain.
It is expected in the disclosure the “naming” of such compounds as part of a specific pharmaceutical composition capable of increasing SYNCRIP protein or mRNA levels, as well as serum miR-137 levels.
It is therefore expected in the disclosure a reduction to practice of the method of analysis of brain striatum for monitoring efficiency of delivery to the brain in a human subject or in a population sample.
It is expected a non-invasive method of visualizing the brain of subjects before and after treatment for assessing the increase of SYNCRIP expression, as well as serum miR-137 levels.
The State of the Art:
Methamphetamine use disorder (MUD) and treatment:
Khan (Khan, R. et al. “Genes, cognition, and their interplay in methamphetamine use disorder”. Biomolecules, Vol. 15 (2025), p: 306; previously cited) teaches that sensitivity/predisposition or protection against MUD is associated with genetic polymorphism in BDNF, FAAH, SLC18A1, and SLC18A2 (see abstract). Khan teaches that the drug induces dopamine release, with secondary effects on dopamine transporters leading to a cascade of downstream events that can explain modifications in levels of proteins in the brain (see Figure 2). Khan also teaches that methamphetamine induces neuroinflammation with lasting changes in microglia, and damage to nerve terminals, even after abstinence (see page 3). Khan teachings therefore suggest individual differences according to genetic polymorphisms, depending on cognition, and a need for personalized medicine.
Ezard (Ezard, N. et al. “Lisdexamfetamine in the treatment of methamphetamine dependence: A randomized, placebo-controlled trial”. Addiction, Vol. 120 (2025), pp: 1345-1359; previously cited) teaches a recent Randomized placebo-Controlled Trial conducted in six specialist outpatient clinics in Australia with 164 participants (see title and abstract). Ezard teaches a specific compound, Lisdexamfetamine, that reduces the methamphetamine abuse over a 12-week treatment period (see abstract). However, the efficiency of the treatment was self-reported using a questionnaire (see page 1347, “Primary outcome” section). The self-reported abstinence was confirmed using urine test (see page 1347, “Secondary outcome” section).
Possible methods for follow-up:
Li (Li, F. et al. “Recent trends and future perspectives of emergent analytical techniques for methamphetamine sensing”. Analytical Methods, Vol. 17 (2025), pp: 6944-6959; previously cited) teaches the most recent methods for diagnosing drug abuse, especially methamphetamine abuse (see title). Li teaches methods for sensing methamphetamines more broadly, encompassing detection in food/beverage samples (see Figure 6), involving electrochemical sensors (see Table 4). Li teaches that recent developments includes detection using hand-held, wearable/portable sensor systems, with fast analysis involving smartphone and artificial intelligence and remote monitoring (see section 3, page 6956). The samples used in these analytics are body fluids such as urine, vapor, plasma, blood, saliva and sweat, and hair (see Table 2). These types of analysis and diagnostic methods are non-invasive and allow for instant diagnosis of drug usage. However, they do not teach about the addiction itself, only the recent use.
Jang (Jang, W-J. et al. “Identification of potential biomarkers for diagnosis of patients with methamphetamine use disorder”. International Journal of Molecular Sciences, Vol. 24 (2023), p: 8672; previously cited) teaches one of the effort made to identify specific biomarkers for diagnosing methamphetamine use disorder (MUD) (see title and abstract). Jang teaches that currently diagnosis relies mainly on self-reports of patients who are seeking treatment, as well as their psychological and physical symptoms, and screening instruments such as NIDA-ASSIST (National Institution of Drug Abuse-alcohol, smoking and substance involvement screening test), DUDIT (Drug Use Disorder identification test) and DAST (drug abuse screening test) (see page 2, second paragraph; and page 12, section 3, first paragraph).
Therefore, there is a need for accurate markers to assess disease severity. Jang teaches case control studies, comparing healthy controls, non-recovered patients and almost-recovered patients, using hair follicles collections for high-throughput analysis using RNAseq and computer-aided data analysis (see Figure 1). Jang teaches a set of hundreds of transcripts with significantly changed levels, none of them identified clearly as SYNCRIP or miR-137 (see Figures 2-4).
SYNCRIP, miR-137 and Drug Addiction:
Mizutani (Mizutani, A. et al. “SYNCRIP, a cytoplasmic counterpart of Heterogeneous Nuclear Ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms”. The Journal of Biological Chemistry, Vol. 275, No. 13 (2000), pp: 9823-9831; previously cited) teaches the isolation of SYNCRIP and its activity as binding partner to synaptotagmins (see abstract). Mizutani provides evidence that SYNCRIP binds to mRNAs of its targets and stabilizes them, therefore, SYNCRIP is likely to be involved in editing, sorting, degradation, transportation and translation of targeted RNAs.
He (He, E. et al. “MIR137 schizophrenia-associated locus controls synaptic function by regulating synaptogenesis, synapse maturation and synaptic transmission”. Human Molecular Genetics, Vol. 27, No. 11 (2018), pp: 1879-1891; previously cited) teaches that miR-137 is a genetic risk factor for schizophrenia (see title and abstract). MiR-137 is well expressed in the brain and is involved in neurogenesis, being embryonic lethal if knock-out in mouse (see “Introduction” section, page 1880, left column, second paragraph).
He teaches that miR-137 roles encompass synaptogenesis, synapse maturation and synaptic transmission (see title).
He also teaches that miR-137 regulates other genes’ expression involved in synapse development and neurogenesis, among which SYNCRIP (see page 1883, left column).
Most (Most, D. et al. “Synaptic microRNAs coordinately regulate synaptic mRNAs: perturbation by chronic alcohol consumption”. Neuropsychopharmacology, Vol. 41 (2016), pp: 538-548; previously cited) performs transcriptome analysis on RNAs isolated from mice after chronic alcohol consumption, a model for alcohol abuse (see abstract). Most shows that synaptic microRNA-mRNA interactions are regulated by alcohol (see page 543, left column). Most shows the microarray analysis results of RNAs in synaptoneurosomes. Table 5 shows co-expressed alcohol-responsive microRNAs and their mRNA targets, among them miR-137 with SYNCRIP as an overlapping targets (see page 546).
Compounds/Factors that upregulate SYNCRIP or miR-137:
Martin (Martin, R.A. et al. “Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a posttranscriptional influence”. American Journal of Physiology Cell Physiology, Vol. 329 (2025), pp: C953-C971; previously cited) teaches a surprising effect of acute exercise on the proteome of nuclei isolated from muscle cells (see title and abstract). Although one can argue that Exercise is not a compound, it is certainly a factor that influence greatly the accumulation of SYNCRIP proteins in cell nuclei 1hour post-exercise. One of ordinary skills in the art can appreciate that the gene expression post-exercise is influenced by factors released/modified such as ATP, glucose, stress hormones and other hormones, heat shock proteins, neurotransmitters and other transcription factors acting upstream in diverse metabolic pathways. Martin teaches that SYNCRIP is one of the protein that responds to acute exercise and is upregulated (see page C962, right column). Therefore, Martin teaches that SYNCRIP is highly responsive to environmental factors/cues.
Chen ( Chen, S. et al. “SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation”. Veterinary Research, Vol. 52 (2021), p: 73; previously cited) reminds that abnormal SYNCRIP expression is associated with immune response disorders and neuro-degenerative disorders (see page 2, left column). Chen teaches that SYNCRIP binds to viral mRNA and influences its alternative splicing (see page 5, “Results” section, left column, and Figure 2). Chen also teaches that the viral infection increases significantly SYNCRIP mRNA 12 hours post-infection (see page 5, right column, last paragraph). Therefore, viral titer increases the expression of SYNCRIP, confirming that environmental cues and factors influence SYNCRIP’s expression.
Du (Du, Y. et al. “Inputs and outputs of insulin receptor” Protein & Cell, Vol. 5 No. 3 (2014), pp: 203-213; previously cited) teaches that insulin and IGF1/2 activate SYNCRIP and increase the level of its tyrosine phosphorylated isoform that cannot bind RNAs (see page 208, left column, “SYNCRIP and Sam68” section and Figure 1). Therefore, insulin and IGF1/2 can increase the protein level of SYNCRIP phosphorylated form and affect its activity.
Wang ( Wang, X. et al. “Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate”. BMC Genomics, Vol. 11 (2010), p: 360; previously cited) teaches that one the major excitatory neurotransmitter in the mammalian brain, glutamate is capable of upregulating SYNCRIP gene expression (see title and abstract; see page 4, Table 1).
Guo (Guo, X. et al. “ISO, via upregulating MiR-137 transcription, inhibits GSK3B-HSP70-MMP-2 axis, resulting in attenuating urothelial cancer invasion”. Molecular Therapy: Nucleic Acids, Vol. 12 (2018), pp: 337-349; previously cited) teaches that miR-137’s expression can be upregulated by naturally occurring antineoplastic agents such as Isorhapontigenin (ISO) (see page 343, left column, second paragraph). ISO is a stilbene derivative (see page 337, right column, second paragraph). Therefore, it is likely that other antineoplastic agents or chemicals that are structurally related would have the same effect on upregulating miR-137’s expression.
What the Specification does and does not teach:
The Specification states in “Background of the Invention”, “Drug addicts cannot live their normal life without using addictive drugs. For example, drug addicts show a tendency to pay more attention to certain things and suffer from symptoms such as paranoid schizophrenia, cardiac disorder…” (page 2, lines 11-15).
In “Summary of the Invention”, Applicant discloses the use of a drug addiction animal model (see page 5, lines 21-30).
In “Brief description of the Drawings”, Applicant discloses the main embodiments
as an animal model, drug addiction model and transgenic animal, or cells in culture.
Applicant discloses that the treatment constitute overexpression of SYNCRIP, either in the cells in culture or in the transgenic animal model (see page 6-7).
However, in the “Detailed description of the Invention”, Applicant defines the terms “Drug addiction” as a substance-induced disorder and symptoms that are caused when a highly addictive drug is administered or taken. Applicant further adds “Drug addiction is considered a type of drug dependence and can be defined as a state in which a person has lost the power of self-control to continuously seek or take drugs despite an emotional state such as physical or mental impairment”. Applicant also uses terms such as “without medical supervision” and “interpersonal problems” (see page 8, lines 17-25).
Therefore, it seems that the invention is also intended to be practiced with/for subjects that are “persons”, i.e. humans.
Applicant further states that when expression of SYNCRIP in the brain striatum of drug addiction animal model is increase, the expression of serum miR-137, a biomarker for drug addiction, is restored to a normal level. Therefore, Applicant states the availability of the biomarker composition for the diagnosis of drug addiction (see page 5, lines 18-26).
These statements are for drug addiction in generally, not specifically for Methamphetamine use disorder (MUD), the Specification stating that the drug is not particularly limited as long as it is classified as a narcotic in the art, illegal or legal drugs such as tranquilizers without medical supervision (see page 8, lines 17-30).
The disclosure states that the drug is more preferably methamphetamine (see page 9, line 1).
The Drawings present results of analysis of expression levels of miR-137 or SYNCRIP proteins and mRNAs in serum and brain striatum samples from a control group and a drug addiction animal model (see Figures 1, 3-4). Figures 2 and 6 present results using transfection in cell lines. Figures 7-8 shows results in transgenic animal overexpressing SYNCRIP in the brain, and expression levels of miR-137 levels used as a biomarker for drug addiction. The results are supposed to present a comparison between a “mild drug addicted” and a “drug-addicted” transgenic animal models. Figures 9-13 presents spatial learning behavior tools and results using a water cross maze. Applicant states that Figure 13 shows hyperactivity of a drug addiction animal model with SYNCRIP overexpression when methamphetamine is administered.
The disclosure does not teach a range of what would be normal concentrations of miR-137 in serum, nor a correlation with different amount of drug use. There is no other embodiment and experiment with a compound, natural or synthetic as part of a pharmaceutical composition used to target the brain, to be administered to subjects. The Specification only states that “the subject is diagnosed as having addiction if the expression level of the biomarker in the subject sample is lower than that in the normal control sample” (see page 16, lines 12-18). There is no reference range taught.
The Specification does not teach a method to measure the SYNCRIP gene expression in the brain of a Human subject. There is no method of imaging designed for human subjects.
The disclosure only teaches the overexpression of SYNCRIP gene as a method to treat drug addiction, and the measure of only one gene miR-137 as a method to monitor treatment, while the state of the art informs that panels of genes might be required, given the polymorphisms that exist in populations.
The state of the art also shows that many factors and compounds can affect the expression levels of miR-137 and SYNCRIP. Environmental factors such as exercise, i.e. swimming in a water maze, can also affect the expression of SYNCRIP.
Conclusion:
Taking into consideration the factors outlined above, including the nature of the
invention, the state of the art, the guidance provided by the applicant and the specific example, it is the conclusion that Applicant does not possess the invention. There is no specific written example of compounds in a pharmaceutical composition designed to reach the brain, besides SYNCRIP nucleic acid itself, nor a method to visualize striatum expression levels of SYNCRIP in a human brain and evaluate compared to pre-treatment levels, within the Specification that would lead one with ordinary skills in the art to a different conclusion.
Response to Arguments
Applicant's arguments filed 01/12/2026 have been fully considered but they are not persuasive.
Applicant argues on page 5 of Remarks filed 01/12/2026 that “all limitations of amended claim 1 are expressly described in the Specification, and the requirements of 35 U.S.C. § 112(a) are satisfied”.
In response, the new rejection of claim 1 under 35 U.S.C. § 112(a) are specific to the fact that there are no human subject presented in the Disclosure, although the claim is broad enough to encompass all subjects. There are no specific range for a normal expression of SYNCRIP or miR-137 presented. There is no other compound described to ensure targeted brain tissue delivery of the nucleic acid in a human subject.
Claim 1 only states one step of administering a nucleic acid to a subject, with a recitation of end result, i.e., “thereby increasing expression of SYNCRIP in a brain striatum and restoring serum microRNA-137 levels”. There are no reference standards established for humans in the Specification, no normal ranges to return to, no concrete step for monitoring. The methods described in the disclosure are adapted to cell culture or to an animal model. Adapting these methods to a Human would be unethical, thus special adaptation steps, compositions and methods need to be considered and addressed. Therefore, Written Description is lacking in this method for treating methamphetamine addiction in a subject.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The following rejection is new as necessitated by Applicant’s amendments filed 01/12/2026:
Claim 1 is rejected under 35 U.S.C. §103 as being unpatentable over Mikoshiba (Mikoshiba, K. et al. US Patent No. 6,794,500 B2, published September 21, 2004; previously cited), Deng (Deng, X. et al. “Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method”. Molecular Brain Research, Vol. 93 (2001), pp: 64-69), Most (Most, D. et al. “Synaptic microRNAs coordinately regulate synaptic mRNAs: perturbation by chronic alcohol consumption”. Neuropsychopharmacology, Vol. 41 (2016), pp: 538-548; previously cited), NCBI- NM_019666 (Mus Musculus Synaptotagmin binding, cytoplasmic RNA interacting protein (SYNCRIP), transcript variant 1, mRNA; NM_019666.2, version updated September 07, 2006), Cheng (Cheng, Y. et al. “Partial loss of psychiatric risk gene Mir137 in mice causes repetitive behavior and impairs sociability and learning via increased Pde10a”. Nature Neuroscience, Vol. 21 (2018), pp: 1689-1703; previously cited), and Smith (Smith, A.C.W. et al. "MicroRNAs regulate synaptic plasticity underlying drug addiction". Genes, Brain and Behavior, Vol. 17 (2018), pp: 1-11; previously cited).
Regarding claim 1, the claim recites: “A method for treating methamphetamine addiction in a subject, comprising: administering to the subject an effective amount of a vector comprising a nucleic acid encoding synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) having the sequence set forth in SEQ ID NO: 1, thereby increasing expression of the SYNCRIP in a brain striatum and restoring serum microRNA-137 levels”.
Regarding claim 1, Mikoshiba teaches the use of SYNCRIP gene and protein (see abstract). Mikoshiba teaches that the gene or the protein of the invention is useful as an activator for neurons or an agent for gene therapy for neurological diseases and that SYNCRIP gene or protein can be administered orally or parenterally, systemically or locally (see column 10, lines 26-32). Mikoshiba further teaches that when the gene, i.e., SYNCRIP gene, is used as an agent for gene therapy to treat neurological diseases, the gene can be directly administered by injection, or a vector incorporating the gene of the invention may be administered (see column 11, lines 19-23).
Mikoshiba teaches the use of SYNCRIP as a therapeutic agent for neurological diseases, such as Parkinson’s disease and Alzheimer’s disease, which are neurodegenerative diseases, or an independent disease that may be complicated with a neurological disorder (see column 10, lines 33-44).
Mikoshiba also teaches that SYNCRIP gene or protein may be used as a regulator for allowing the expression of neurotransmitters at the nerve terminal, i.e. as a pharmaceutical for regulating neuronal functions (see column 10, lines 20-26).
Mikoshiba does not specifically teach a substance abuse disorder, nor a methamphetamine addiction.
However, Deng teaches that methamphetamine causes widespread apoptosis in the mouse brain (see title). This teaching indicates that methamphetamine provokes neuronal cell death (see abstract). Therefore, methamphetamine addiction can be considered a neurodegenerative disorder, which is a neurological disorder and encompassed in the diseases listed by Mikoshiba.
Mikoshiba does not teach specifically SEQ ID NO: 1, nor microRNA-137 (MiR-137) levels.
However, NCBI-NM_019666 teaches the sequence claimed.
The instant Specification refers to SEQ ID NO: 1 as NM_019666. The sequence of mouse SYNCRIP has been described and available in the public domain before 2006, updated and republished.
Most teaches an animal model of addiction (see page 539, “Materials and Methods” section). Most teaches an Alcohol addiction mouse model, with the motivation of researching neuronal networks leading to addiction, for a better understanding of the regulatory systems in synapses and to better target them for treatment solutions (see page 538, left column, “Introduction” section).
Most teaches the search for biomarkers in the synapses and more specifically RNA signatures in the brain using microarray hybridization (see page 539, right column). Most teaches the use of total homogenates (TH) from amygdala and synaptoneurosomes (SN) to analyze mRNAs signature (transcriptome) of addiction model animals compared to control animals (see Table 1).
Most teaches differences between control and addiction model mice using brain samples. Among the genes’ expression changes observed, Most teaches miR-137 and SYNCRIP’s expression changing (see Table 5).
Therefore, Most teaches the analysis of the expression of miR-137 and SYNCRIP in brain tissue, and identifies SYNCRIP and miR-137 ‘s expressions as relevant in a drug addiction model.
Therefore, it would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have used the sequence taught by NCBI-NM_019666 in the gene therapy taught by Mikoshiba. One with ordinary skills in the art, motivated in administering a mouse sequence to mouse addiction model as taught by Most, for treatment of addiction-mediated neurodegeneration as taught by Mikoshiba and Deng, could have used the NCBI-NM_019666’ s sequence for SYNCRIP gene therapy with a reasonable expectation of success and arrived at the claimed invention.
Regarding miR-137 levels, Cheng confirms miR-137 as an important gene for psychiatric risk (see title). Cheng also teaches that in mice, miR-137’s conditional loss of function causes repetitive behavior and impairs sociability, and dysregulation of synaptic plasticity (see title, abstract and page 1693, left column).
Smith teaches that microRNAs regulate synaptic plasticity underlying drug addiction (see title). Smith teaches that drug such as cocaine, exerts its effects primarily through blockade of the dopamine transporter, thus increasing synaptic dopamine transmission. Subsequent increases in dopamine receptor stimulation occur in the ventral striatum to mediate the acute rewarding effects of the drug (see age 4, right column, “Cocaine” section, first paragraph.
Among the microRNAs discussed, Smith teaches that circulating microRNAs can be biomarkers for addiction (see page 6, right column, “Circulating miRNA as biomarkers for addiction” section). Among microRNAs, Smith teaches that miR-137 is a biomarker of interest, that is found with increased levels specifically in the dorsolateral striatum after extinction training and reinstatement in addiction-prone rats (see page 5, left column, second paragraph).
Therefore, it would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have combined the teachings of Mikoshiba/Deng, NCBI-NM_019666 and Most, with the teachings of Cheng and Smith, using a gene therapy method to treat methamphetamine addiction using SYNCRIP gene in a vector as taught by Mikoshiba, and added a step of measuring levels of SYNCRIP in brain striatum to check for effective expression at the target site. One of ordinary skills in the art, motivated in monitoring the gene therapy could have introduced this step of measuring SYNCRIP expression level in the brain and circulating miR-137 levels. One with ordinary skills in the art motivated in establishing a treatment method could have treated the animal model and monitor its efficiency using miR-137 as biomarker. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Response to Arguments
Applicant’s arguments with respect to claim 1 have been considered but are moot because the new ground of rejection does not rely on same combinations of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
However, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Mikoshiba teaches gene therapy for neurological disorder, and especially neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease, using SYNCRIP gene. Deng teaches that methamphetamine chronic exposure leads to neuronal cell death, therefore neurodegeneration. Thus, Mikoshiba’s method of treatment of neurological disorders encompasses its use in methamphetamine addiction. The combination of references Mikoshiba, Deng, NCBI-NM_019666 renders the gene therapy using SYNCRIP gene for methamphetamine addiction obvious; the combinations further comprising Most, Cheng and Smith renders monitoring treatment using striatum level of SYNCRIP and serum level of miR-137 obvious.
Therefore, the combination of Mikoshiba, Deng, NCBI-NM_019666 , Most, Cheng and Smith renders claim 1 obvious. The claim stands rejected.
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.
The following rejection is modified from previous Office Action dated 10/23/2025 as necessitated by Applicant’s amendments filed 01/12/2026:
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-6 of U.S. Patent No. 11,920,195 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1, claim 5 of USPAT’195 recites “ A method for diagnosing or treating drug addiction comprising a) measuring the synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) gene or its expression level in a biological sample separated from a subject, b) diagnosis the subject as having drug addiction if the measured expression level of the SYNCRIP gene is higher than that in a normal control group, and c) administering an agent expressing SYNCRIP or promoting the activity of SYNCRIP to the subject diagnosed as having drug addiction”.
claim 6 of USPAT’195 recites “The method according to claim 5, wherein the SYNCRIP gene has the sequence set forth in SEQ ID NO: 1”.
Response to Arguments
Applicant’s arguments with respect to the NSDP rejection have been fully considered and are not persuasive.
Applicant argues on pages 18-20 of Remarks that:
“Amended claim 1 does not include any diagnostic step required in claim 5 of the ‘195 Patent”.
In response, Patent’195 claim encompasses a method of diagnosing and a
method of treating. Claim 5 (c ) of PAT’195 states “administering an agent expressing SYNCRIP or promoting the activity of SYNCRIP to the subject diagnosed as having a drug addiction”. A nucleic acid encoding SYNCRIP is encompassed in “An agent expressing SYNCRIP” limitation; Methamphetamine addiction is encompassed in “drug addiction” limitation. Therefore Patent’195 teaches the claim 1’s limitations.
“The pathological Model in the ‘195 Patent differs fundamentally from that of amended claim 1”.
In response, Patent’195 ‘s claim 5 (c ) does not claim any pathological model in
particular. The claim is broadly drawn to a subject having a drug addiction. Similarly, claim 1 of instant application does not present any pathological model, and is drawn to treating methamphetamine addiction in any subject.
“The therapeutic mechanism in amended claim 1 differs from that in the ‘195 Patent.”
In response, Claim 5 (c ) does not specify the structure of the agent, which can
be any agent capable of “expressing SYNCRIP”, which can be any nucleic acid encoding for SYNCRIP, and any vector comprising said nucleic acid.
“Amended claim 1 includes a limitation absent from all claims of the ‘195 Patent: Restoration of serum microRNA-137 levels”.
In response, this particular limitation in claim 1 is subjected to rejections under 35 U.S.C. § 112(a) and §112(b) and is not considered in this NSDP.
Also, this limitation drawn to an end-result, does not add patentable weight to the claim. Anyone applying the method step of increasing the expression of SYNCRIP would be expected to obtain the same result, i.e., “restoring serum microRNA-137 levels”, as it is an inherent feature/result of increasing the expression of SYNCRIP gene, SYNCRIP/hnRNP-Q2 being a regulator of global translation and miRNA-mediated repression of specific mRNAs as taught by Svitkin (Svitkin, Y.V. et al. “Control of translation and miRNA-dependent repression by a novel Poly(A) binding protein, hnRNP-Q”. PLOS Biology, Vol.11, No. 5 (2013), p: e1001564), or as it is a simple natural phenomenon occurring during methamphetamine abstinence as described by Kim (Kim, B. et al. “SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence”. Acta Pharmaceutica Sinica B, Vol. 12, No. 8 (2022), pp: 3281-3297).
Therefore, the rejection is maintained. Claim 1 stands rejected.
Conclusion
No claim is allowed.
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.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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