Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
This Office Action is a response to Applicant’s Amendment to the claims and Election filed February 23, 2026.
Claims 3 and 5 have been amended. New claim 17 is acknowledged.
Claims 1-5, 9-12 and 15-17 are pending in the instant application.
Election/Restrictions
Applicant’s election (without traverse) of Group I (claims 1-5 and 17) in the reply filed on February 23, 2026 is acknowledged.
Accordingly, claims 9-12, 15 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-5 and 17 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant's information disclosure statement (IDS) filed March 28, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant's IDS filed July 5, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Priority
Acknowledgment is made of Applicant's claim for foreign priority based on KR 10-2021-0000957 filed 01/05/2021. The certified copy has been placed in the file.
Drawings
The Drawings filed on July 5, 2023 are acknowledged and have been accepted by the Examiner.
Nucleotide Sequence Disclosures
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. §1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §1.821-1.825 for the reason(s) set forth below or on the attached Notice To Comply with Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures. The disclosure contains sequences which fall under the purview of 37 CFR 1.821 through 1.825 as requiring SEQ ID NOs., but which are not so identified. For example, see page 21, Example 4. This is an example and does not indicate that the Examiner has made an exhaustive review of the application. Applicant must fully comply with the sequence rules for any response to this action to be considered fully responsive.
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 applicant regards as his invention.
Claims 1-5 and 17 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.
The claims are rejected under 35 U.S.C. 112, second paragraph, as being incomplete for omitting essential steps, such omission not including how to inhibit dormancy of quiescent neural stem cells (qNSCs). See MPEP § 2172.01.
The present Specification at Example 4 and Kim et al. (Molecular Psychiatry (2022) 27:2751-2765) teach neural stem cells (NSCs) reside in stem cell niches in the subventricular zone (SVZ) and the hippocampus subgranular zone (SGZ). Both disclose inhibiting dormancy of qNSCs is accomplished by injection of histone methyltransferase inhibitors into the SVZ and/or hippocampus SGZ/dentate gyrus (DG) of 8-week-old Shank3-deficient mice.
Neither the present Specification nor Kim et al. provide an example of inhibition of dormancy of qNSCs without this specific mode of administration/delivery.
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 1-5 and 17 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 treating autism spectrum disorder, the method comprising inhibiting dormancy of quiescent neural stem cells (qNSCs), does not reasonably provide enablement for a method of preventing autism spectrum disorder, the method comprising inhibiting dormancy of qNSCs. 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/or use the invention commensurate in scope with these claims. This is a scope enablement rejection.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988).
Wands states on page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The claims are drawn to a method of preventing or treating autism spectrum disorder, the method comprising inhibiting dormancy of quiescent neural stem cells (qNSCs). The inventions are in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
It should be made clear that, the enabling specification must teach those skilled in the art to make and use the full scope of the claimed invention without undue experimentation. “Although not explicitly stated in section 112, to be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without "undue experimentation." Vaeck, 947 F.2d at 495, 20 USPQ2d at 1444; Wands, 858 F.2d at 736-37, 8 USPQ2d at 1404; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (the first paragraph of section 112 requires that the scope of protection sought in a claim bear a reasonable correlation to the scope of enablement provided by the specification).” In re Wright (CAFC) 27 USPQ2d 1510 at 1513. Although a working example is not required to enable an invention, the skilled artisan must be able to practice the claimed invention without undue experimentation. See also, MPEP §2164.02, which states in part: 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). Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The prior art does not teach a method of preventing autism spectrum disorder, the method comprising inhibiting dormancy of qNSCs.
The present description provides an example a novel strategy to control qNSCs activity as a potential therapeutic target for the treatment of autism in a Shank3 deficiency autism mouse model. See Examples. The data presented in the Specification does not rise to the level of prevention. Regarding “preventing” disorder/disease, it is noted that “preventing” encompasses complete (i.e., 100%) and permanent prevention. One of skill in the art would recognize that the complete prevention of any disease, including autism spectrum disorder would be very difficult and there would be a low level of expectation of success (i.e., highly unpredictable). In fact, The Mayo Clinic downloaded from Autism spectrum disorder - Symptoms and causes - Mayo Clinic on March 11, 2026 discloses that there's no known way to prevent autism spectrum disorder.
The specification does not provide any working example demonstrating a method of preventing autism spectrum disorder, the method comprising inhibiting dormancy of qNSCs. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the Specification with respect to preventing autism spectrum disorder, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful disease prevention in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
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).
Furthermore, in In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case here where there is a relatively incomplete understanding in the biotechnological field involving preventing autism spectrum disorder, as described above, and the lack of a reasonable correlation between the narrow disclosure in the Specification and the broad scope of protection sought in the claims.
Without 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. Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled over the scope claimed.
Thus, in view of the breadth of the claims, the lack of guidance, and the lack of working examples, the instant specification is not found to be enabling for preventing autism spectrum disorder comprising inhibiting dormancy of qNSCs. It would require undue experimentation and making a substantial inventive contribution for the skilled artisan to discover how to make and/or use the claimed invention in its full scope.
******
Claims 1-5 and 17 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.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
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.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the Specification the scope of what is being claimed and that applicant was in possession of the claimed genus.
The claims are drawn to a method of preventing or treating autism spectrum disorder, the method comprising inhibiting dormancy of quiescent neural stem cells (qNSCs), comprising administering an activity inhibitor of histone lysine methyltransferase.
The present Specification discloses:
“The lysine methyltransferase may be selected from Kmt2a, Kmt2b, Kmt2c, Kmt2f, Kmt2g, ASH, and Sc/Sp, specifically, one or more proteins selected from Kmt2a and Kmt2c”; and
Kmt2a or Kmt2c inhibitor may be, but is not limited to, an interfering RNA, a ribozyme, a DNAzyme, a PNA (peptide nucleic acids), an antisense oligonucleotide, a peptide, an antibody, or an aptamer which is specific to the gene encoding the protein
The claims are rejected because there is insufficient description of the genus of histone lysine methyltransferase inhibitors that are encompassed by the claims.
As indicated above, to provide adequate description and evidence of possession of a claimed genus, the Specification must provide sufficient distinguishing identifying characteristics of the genus. In this case, the broad and particularly nonlimited claims encompass an activity inhibitor of histone lysine methyltransferase. However, the Specification only provides working examples wherein Kmt2a and Kmt2c specific shRNA or the Kmt2a inhibitor, OICR-9429 carries out the functionality of treating autism spectrum disorder, comprising inhibiting dormancy of qNSCs. See Examples.
The present invention demonstrates that only Kmt2a and Kmt2c specific shRNA or OICR-9429 functions as claimed. Therefore, only Kmt2a and Kmt2c interfering RNA and OICR-9429 have been reduced to practice. Given only three species of a broad genus of activity inhibitor of histone lysine methyltransferase, one of skill in the art would not recognize Applicant as having possession of the genus of inhibitors encompassed by the claims.
The art of Kim et al. (Molecular Psychiatry (2022) 27:2751-2765) demonstrate that autism phenotypes associated with Shank3 deficiency can be effectively rescued by inhibiting H3K4me3 activity in the qNSCs with Kmt2a and Kmt2c shRNA or OICR-9429 pharmacological inhibition.
The Examiner would like to again direct Applicant to the section 2163 of the MPEP which states:
An applicant may show that an invention is complete by disclosure of (for some biomolecules), examples of identifying characteristics include a sequence, structure, binding affinity, binding specificity, molecular weight, and length
Furthermore, MPEP 2163 discloses:
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the Specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar (19 USPQ2d 1111, CAFC 1991), it was concluded that:
"...applicant must also convey, with reasonable clarity to those skilled in art, that
Applicant, as of filing date sought, was in possession of invention, with invention
being, for purposes of "written description" inquiry, whatever is presently claimed."
The present invention fails to provide sufficient “blaze marks” to direct a person of ordinary skill in the art to the activity inhibitor of histone lysine methyltransferase used in the method as claimed. The instant Specification does not contain markers or a roadmap to the claimed invention and therefore lacks written description.
Applicant is reminded that sufficient blaze marks within the Specification allow a genus to be "sufficiently disclosed by 'either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can visualize or recognize the members of the genus.'" (citing Ariad, 598 F.3d at 1350). Accordingly, blaze marks have been described within the Specification as descriptions that "single out particular trees in a forest, rather than simply 'pointing to trees.'" (quoting Fujikawa, 93 F.3d at 1570).
There is no record or description which would demonstrate conception of those activity inhibitors of histone lysine methyltransferase which treat autism spectrum disorder, comprising inhibiting dormancy of qNSCs, other than Kmt2a and Kmt2c shRNA and OICR-9429. Therefore, the claims fail to meet the written description requirement by encompassing structures or sequences which are not described in the Specification.
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification and the art as filed does not provide sufficient descriptive support for the myriad of activity inhibitors of histone lysine methyltransferase that function as claimed. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
Prior Art not relied upon
The following is art pertinent to Applicant’s disclosure but not relied upon:
Wang et al. (Molecular Psychiatry (2020) 25:2517-2533). Wang et al. teach amelioration of autism-like social deficits by targeting histone methyltransferases EHMT1/2 in Shank3-deficient mice. However, Wang et al. do not teach a method of treating autism spectrum disorder, the method comprising inhibiting dormancy of quiescent neural stem cells (qNSCs).
WO 2018119065 A1 teach histone deacetylase inhibitors for therapy of autism spectrum disorder. However, WO 2018119065 does not teach a method of treating autism spectrum disorder, the method comprising inhibiting dormancy of quiescent neural stem cells (qNSCs).
NOTE: The present Specification discloses inhibiting dormancy of qNSCs is accomplished by injection of a histone methyltransferase inhibitor into the subventricular zone (SVZ) and/or hippocampus subgranular zone (SGZ)/dentate gyrus (DG) of 8-week-old Shank3-deficient mice. See Example 4. Also, see Kim et al. (Molecular Psychiatry (2022) 27:2751-2765).
Claims Free of the Prior Art
Claims drawn to a method of treating autism spectrum disorder, the method comprising inhibiting dormancy of quiescent neural stem cells (qNSCs) by administering an activity inhibitor of histone lysine methyltransferase, wherein the activity inhibitor of histone lysine methyltransferase is OICR-9429, Kmt2a interfering RNA, or Kmt2c interfering RNA, and wherein the activity inhibitor of histone lysine methyltransferase is administered to the subventricular zone (SVZ) or hippocampus subgranular zone (SGZ) of the brain are free of the art.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635