Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION Status of the Application Claims 1-10 are pending and are currently under examination. Information Disclosure Statement The information disclosure statements filed on 10/17/2023 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because of the following reasons: Some of the F oreign patent documents are not in English and only the Abstract that is in English will be considered. The remining documents have been considered. Claim Objections Claim 7 is objected to because of the following informalities: The claim recites “A kit for assisting to diagnose tuberous sclerosis complex…” and would be clearer i f rephrased as “A kit for diagnosing a Tuberous s clerosis complex…” Appropriate correction is required . Claim Rejections - 35 USC § 102 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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention. Claim(s) 1 and 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brisac et al . ( "IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-κB pathway." Journal of hepatology 65.5 (2016): 972-979. ). Claim interpretation: Claim 1 is drawn to a biomarker for Tuberous sclerosis complex wherein the biomarker is the IQGAP2 gene and is therefore interpreted as just a IQGAP2 gene and any prior art describing the gene will meet the limitations of the claim 1 . Claim 2 is drawn to a IQGAP2 gene that is mutated, silenced or down-regulated and is therefore interpreted as just a IQGAP2 gene that is mutated, silenced or down-regulated and any prior art describing the gene will meet the limitations of the claim 2 . Brisac et al. teach an IQGAP2 gene that has been silenced using a siRNA (see results page 973). Thus Brisac et al. anticipates claims 1 and 2. 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 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 set forth in Graham v. John Deere Co. , 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claim 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. ( Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Volume 1822, Issue 6 , June 2012, Pages 875-884 ). Xie et al. teach primers for detecting IQGAP2 in cells (see page 877 2.10). Thus the primers would be considered a reagent for detecting IQGAP2 given the broadest reasonable interpretation of a reagent, which is not defined in the specification. With regards to the claimed directed to kits, a kit is considered obvious in view of a teaching of the compound because a kit merely contains the compound and instructions for use. It is noted that claims directed to a kit are considered obvious over the composition. USPTO personal need not give patentable weight to printed matter absent a new and unobvious functional relationship between the printed matter and the composition (see MPEP 2106.01). It is considered obvious to formulate the product into a kit with instructions for use. Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed. Claim Rejections - 35 USC § 112 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 appl icant regards as his invention. Claims 3 -10 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 pre-AIA the applicant regards as the invention. Claim 3 recites a method of diagnosing and/or treating Tuberous sclerosis complex comprising applying the biomarker of claim 1. It is unclear what the context of “applying the biomarker of claim 1” encompasses. For methods of diagnosing, is the biomarker applied to a cell or tissue and what is being detected such that it would give results for diagnosing Tuberous sclerosis complex ? Further how is it applied such as , is the biomarker contacted with a cell or tissue and what is being measured. For methods of treatment, it is unclear how the biomarker is being applied to a cell or subject that results in some form of treatment in the cell or a subject. Thus the claim is indefinite and will not be further examined on the merits because it cannot be determined, without assumption, what further steps are included in the method of diagnosing or treating to be above to accruable search the invention. Claim 4 recites a method of preparing a reagent for diagnosing Tuberous sclerosis complex or a medicament for treating Tuberous sclerosis complex comprising applying the biomarker of claim 1 as a target. It is unclear how applying a biomarker of claim 1 as a target would b e in the steps of preparing a reagent for diagnosing Tuberous sclerosis complex or preparing a medicament for treating Tuberous sclerosis complex. How is the biomarker of claim 1 as a target also a reagent or a medicament. The recitation of “a target” , given the broadest reasonable interpretation, would indicate something in the method would target the biomarker, however the is no claim limitation that explains what the target does or what targets the gene . Thus the claim is indefinite and will not be further examined on the merits because it cannot be determined, without assumption, what further steps are included in the method of preparing a reagent or medicament. Clam s 5 -7 depends from claim 4 and is indefinite for depending on claim 4 and will not be further examined on the merits because it cannot be determined, without assumption, what further steps are included in the method of preparing a reagent or medicament of claim 4. Claim 9 is indefinite because it recites “determining a risk of Tuberous sclerosis complex…based on the detection results”. This limitation is indefinite because it is unclear what type of measurement of detection results will allow for determining the level of risk. The claim does not recite whether a certain level of the gene mutation or expression level will indicate the subjects risk compared to a control sample. Claim 10 is indefinite because it is unclear what a “gene module” or an “analysis module” encompasses. The word module is not defined in the specification and the broadest reasonable interpretation of the word module would indicate the gene module and the analysis module are a type of machine or program used to analyze data. It is unclear how the modules are configured to detect a gene mutation or expression level or configured to obtain a detection result. Further the claims recites “a detrimental mutation” and is unclear because the metes and bounds of what is considered a detrimental mutation is not defined in the claims or in the specification. If Applicant presents a claim interpretation that is different than posited by the Examiner, that will not prevent the next Office Action from going Final if new claim rejections are necessary due to the new claim interpretation. Claim Rejections - 35 USC § 112 T he following is a quotation 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 35 U.S.C. 112 (pre-AIA), first paragraph: 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 s 3 , 9 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a method of silencing IQGAP2 expression in cells and methods of enhancing activity of mTOR1 after silencing IQGAP2, does not reasonably provide enablement for methods of treating Tuberous sclerosis complex and does not provide enablement for a system using a detection module or analysis module or a method of claim 9 to indicate the risk level of Tuberous sclerosis complex without mutations in a subject . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. The breadth of the claims and nature of the invention: Claim 3 is drawn to treating Tuberous sclerosis complex with no mutation in the TSC1 or TSC2 gene by applying a biomarker IQGAP2. Claims 9 and 10 are drawn to detecting the risk level of Tuberous sclerosis complex by measuring a gene mutation. The nature of the invention relies upon applying the IQGAP2 to a subject, by any method and encompassing any procedure to apply the biomarker to a subject and detecting any IQGAP2 mutation and determining the risk level of Tuberous sclerosis complex with no mutation in the TSC1 or TSC2 gene . Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the a pplication was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. The state of the prior art: The prior art describes Tuberous sclerosis complex is an autosomal dominant disorder characterized by skin manifestations and formation of multiple tumors in different organs, mainly in the central nervous system. Tuberous sclerosis is caused by the mutation of one of two tumor suppressor genes, TSC1 or TSC2 ( see Rosset, Clévia, Cristina Brinckmann Oliveira Netto, and Patricia Ashton-Prolla. "TSC1 and TSC2 gene mutations and their implications for treatment in Tuberous Sclerosis Complex: a review." Genetics and molecular biology 40.1 (2017): 69-79 abstract ). Rosset et al, do not teach Tuberous sclerosis complex does not have mutations TSC1 or TSC2 and does not teach treatment with IQGAP2 gene. The level of one of ordinary skill: While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention. Because the state of the prior art does not provide evidence of the degree of predictability that methods for treating Tuberous sclerosis complex without mutations TSC1 or TSC2 with IQGAP2 gene or methods of determining the risk of Tuberous sclerosis complex , one of ordinary skill in the art would look for guidance or direction in the instant specification. The level of predictability in the art: “ The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability. ” (MPEP 2164.03 ). The amount of direction provided by the inventor: The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004). The existence of working examples: The working embodiment in the instant application describes a method of silencing IQGAP2 expression in cells and methods of enhancing activity of mTOR1 after silencing IQGAP2. The working embodiments do not describe the claimed methods of treatment or methods of determining the risk level by detecting any mutation in the IQGAP2 gene . 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). While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art. The quantity of experimentation needed to make or use the invention based on the content of the disclosure : The prior art is undeveloped for the role IQGAP2 plays in treatment of Tuberous sclerosis complex without mutations TSC1 or TSC2 and w ithout further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Kimberly Chong at FILLIN "Phone number" \* MERGEFORMAT (571)272-3111 . The examiner can normally be reached Monday thru Friday between FILLIN "Work schedule?" \* MERGEFORMAT M-F 8:00am-4:30pm . If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. 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The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. For more information about the PAIR system, see http://pair-direct.uspto.gov. For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199. /KIMBERLY CHONG/ Primary Examiner Art Unit 1636