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 .
Election/Restrictions
Applicant’s election without traverse of claims 117-123 (Group II) in the reply filed on 07/06/2026 is acknowledged.
Claims 104-116 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/06/2026.
Accordingly, claims 117-123 are pending and under consideration.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest effective filing date to which the instant application is entitled is 02/10/2021.
Information Disclosure Statement
Receipt of information disclosure statements on 06/16/2026 and 06/26/2025 is acknowledged. The signed and initialed PTO-1449‘s have been mailed with this action.
Drawings
The drawings filed 12/07/2023 are accepted.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at least at paragraphs [0006] and [0110]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the instant disclosure includes sequences, which are not appropriately identified in a sequence listing.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See Tables 1 and 2.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claim 118 is objected to because of the following informalities:
Claim 118 recites in part “wherein the cell is a located in a brain of an individual” (bolded emphasis added), which improperly includes an intervening “a.” This is presumed to be a simple typographical error. It would be remedial to amend the instant claim to remove the intervening “a.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) – Written Description
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 117-123 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.
Claims 117-122 and 123 are drawn to a set of antisense oligonucleotides that hybridize to a target nucleic acid sequence of a long non-coding RNA (lncRNA), wherein the lncRNA regulates expression of FOXG1. The rejected claims thus comprise a set of lncRNAs that encompass both upregulating and downregulating FOXG1 expression, wherein targeting said lncRNAs results in downregulating or upregulating FOXG1 expression, respectively. The instant claim language thus also encompasses any lncRNA that indirectly modulates FOXG1 expression, for example by acting on an interacting partner of FOXG1 (such interacting partners are reviewed in Hettige and Ernst, 2019).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes upregulation of FOXG1 expression in vitro by targeting lncRNAs that downregulate FOXG1 expression directly (see Examples 1 and 2), thereby upregulating FOXG1 expression. No description is provided of downregulation of FOXG1 expression in vitro by targeting lncRNAs that upregulate FOXG1 expression, thereby downregulating FOXG1 expression. Neither is any description provided of a lncRNA that indirectly modulates FOXG1 expression, for example by acting on an interacting partner of FOXG1. Such lncRNAs are within the scope of the instant claim language but lack support from the instant specification.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of upregulation of FOXG1 expression by targeting lncRNAs that downregulate FOXG1 expression. The results are not necessarily predictive of downregulation of FOXG1 expression by targeting lncRNAs that upregulate FOXG1 expression. Thus, it is impossible for one to extrapolate from the few examples described herein those lncRNAs and antisense oligonculeotides targeting the same that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe modulation of FOXG1 expression by targeting lncRNAs that upregulate FOXG1 expression, thereby downregulating FOXG1 expression.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 117-123.
Claim Rejections - 35 USC § 112(a) - Enablement
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 117-122 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 in vitro upregulation of FOXG1 in a cell by targeting a lncRNA downregulating FOXG1 with an antisense oligonucleotide, does not reasonably provide enablement for in vivo modulation of FOXG1 expression by targeting a lncRNA regulating FOXG1 with an antisense oligonucleotide in the brain of a human 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/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claims 117-122 are broadly drawn to a method of modulating FOXG1 expression in a cell by targeting a lncRNA regulating FOXG1 with an antisense oligonucleotide. The phrase “in a cell” encompasses both in vitro and in vivo applications, as said cell may be a cell in a subject such as a human subject. The nature of the invention is complex in that per the instant claim language, one of ordinary skill in the art must be able to design antisense oligonucleotides targeting unspecified lncRNAs that regulate FOXG1 expression that are capable of both increasing and decreasing (i.e. modulating) FOXG1 expression. Dependent claims 120 and 122 explicitly recite that the instantly claimed method is applicable to correcting reduced FOXG1 expression or a deficiency thereof despite independent claim 117 encompassing both upregulation and downregulation of FOXG1.
Breadth of the claims: The claims broadly encompass administration of an antisense oligonucleotide targeting a lncRNA regulating the expression of FOXG1, thereby modulating expression of FOXG1. The instant claim language encompasses both increasing and decreasing expression of FOXG1, which must be applicable to individuals with reduced FOXG1 expression or a FOXG1 deficiency (i.e. FOXG1 syndrome). The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples: The specification describes design and administration that increase FOXG1 expression by targeting lncRNAs FOXG1-AS1, LINC01551, and LINC02282 in vitro (Examples 1 and 2). These examples are aligned with the principles disclosed at paragraph [0003] of the instant specification, which teaches that the instant invention is drawn to antisense oligonucleotides that increase the amount of functional FOXG1 protein in a cell, thereby restoring or increasing FOXG1 function. No description is provided of decreasing FOXG1 expression by targeting lncRNAs that regulate FOXG1 expression. Furthermore, no description is provided of any in vitro or in vivo disease modeling of a how a FOXG1 disease or disorder such as FOXG1 syndrome responds to increased FOXG1 expression achieved via the methods taught therein.
Predictability and state of the art: Hettige and Ernst, 2019 (hereinafter Hettige) discloses that FOXG1 dosage is linked to a number of neurodevelopmental disorders (Figure 1). For example, excess FOXG1 is linked to intellectual disability and epilepsy, while deficient FOXG1 (i.e. FOXG1 syndrome as recited at claim 122) is linked to severe intellectual disability, epilepsy, microcephaly, and delayed motor development (also reviewed in Akol et al., 2022, which is post-filing art applied for evidentiary purposes only). Hettige further discloses that FOXG1 dosage states cannot be modeled linearly or simplistically, as FOXG1 interacts with different players and may be governed by substrate affinity or phosphorylation states, meaning FOXG1 exerts its effects by both how and when it is expressed, how FOXG1 is stabilized or degraded, and is also influenced by background genetics (see section “CONCLUSION”). Therefore, any interventions targeting FOXG1 in an in vivo cell, particularly in the brain of a treated individual, must take these considerations into account to avoid eliciting any undesirable phenotypic effects, meaning a simple increase (or decrease) of FOXG1 expression would not reasonably be predicted to fully correct the symptoms of improper FOXG1 expression. When considering a cell in vivo (particularly in the brain of a treated individual), all of these teachings must be taken into account. Furthermore, the art is silent as to targeting lncRNAs that upregulate FOXG1 expression, thereby downregulating FOXG1 expression.
Therefore, the state of the art establishes that one of ordinary skill in the art would reasonably predict that increasing expression of FOXG1 would have utility in correcting FOXG1 syndrome, although such interventions do not currently exist at the clinical level (reviewed in Akol et al., 2022).
Amount of experimentation necessary: The quantity of experimentation needed to carry out the full scope of the claimed method is large. One could not rely upon guidance provided in the instant disclosure of prior art, as neither the instant disclosure nor the prior art discloses antisense oligonucleotides that are capable of modulating FOXG1 expression in vivo by targeting lncRNAs regulating FOXG1 expression, thereby correcting FOXG1 deficiency, as in FOXG1 syndrome. Therefore, one of ordinary skill in the art would be required to identify lncRNAs that regulate FOXG1 expression (both directly and indirectly) and to design and validate novel antisense oligonucleotides, all of which must be applicable to in vivo administration to a human brain and subsequent modulation of FOXG1 expression. The art is silent as to such methods, and the instant specification does not supply any working examples that support in vivo administration and therapeutic outcomes.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 117-122 are not considered to be fully enabled by the instant disclosure.
Claim 123 is 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 in vitro upregulation of FOXG1 in a cell by targeting a lncRNA downregulating FOXG1 with an antisense oligonucleotide, thereby restoring expression of FOXG1, does not reasonably provide enablement for treating or ameliorating any FOXG1 disease or disorder in an individual by targeting a lncRNA regulating FOXG1 with an antisense oligonucleotide, nor does it reasonably provide enablement for treating or ameliorating a FOXG1 disease or disorder in an individual at risk of having the FOXG1 disease or disorder. 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.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claim 123 is drawn to a method of treating or ameliorating a FOXG1 disease or disorder in an individual that has or is at risk of having the FOXG1 disease or disorder, said method comprising administering an antisense oligonucleotide that targets a lncRNA regulating the expression of FOXG1, thereby modulating FOXG1 expression to treat or ameliorate a FOXG1 disease in the individual. The nature of the invention is complex in that per the instant claim language, one of ordinary skill in the art must be able to design antisense oligonucleotides targeting unspecified lncRNAs that regulate FOXG1 expression that are capable of both increasing and decreasing (i.e. modulating) FOXG1 expression, thereby treating or ameliorating any FOXG1 disease or disorder.
Breadth of the claims: The claims broadly encompass the administration of an antisense oligonucleotide targeting a lncRNA regulating the expression of FOXG1 for purposes of treating or ameliorating a FOXG1 disease or disorder, wherein said targeting must modulate FOXG1 expression such that both increasing and decreasing FOXG1 expression must treat or ameliorate a FOXG1 disease or disorder. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples: The specification describes design and administration that increase FOXG1 expression by targeting lncRNAs FOXG1-AS1, LINC01551, and LINC02282 in vitro (Examples 1 and 2). These examples are aligned with the principles disclosed at paragraph [0003] of the instant specification, which teaches that the instant invention is drawn to antisense oligonucleotides that increase the amount of functional FOXG1 protein in a cell, thereby restoring or increasing FOXG1 function. No description is provided of decreasing FOXG1 expression by targeting lncRNAs that regulate FOXG1 expression. Furthermore, no description is provided of any in vitro or in vivo disease modeling of a how a FOXG1 disease or disorder such as FOXG1 syndrome responds to increased FOXG1 expression achieved via the methods taught therein.
Predictability and state of the art: As set forth above, Hettige and Ernst, 2019 (hereinafter Hettige) discloses that FOXG1 dosage is linked to a number of neurodevelopmental disorders (Figure 1). For example, excess FOXG1 is linked to intellectual disability and epilepsy, while deficient FOXG1 (i.e. FOXG1 syndrome) is linked to severe intellectual disability, epilepsy, microcephaly, and delayed motor development (also reviewed in Akol et al., 2022). Hettige further discloses that FOXG1 dosage states cannot be modeled linearly or simplistically, as FOXG1 interacts with different players and may be governed by substrate affinity or phosphorylation states, meaning FOXG1 exerts its effects by how and when it is expressed, how FOXG1 is stabilized or degraded, and also is influenced by background genetics (see section "CONCLUSION"). Therefore, any therapeutic interventions targeting FOXG1 must take these considerations into account to avoid eliciting any undesirable phenotypic effects, meaning a simple increase (or decrease) of FOXG1 expression would not be reasonably predicted to fully treat the symptoms of improper FOXG1 expression. While Akol et al., 2022 (hereinafter AkoI) post-dates the earliest effective filing date of the instant application, it is hereby applied for evidentiary purposes to establish the state of the art regarding treating of FOXG1 diseases or disorders such as FOXG1 syndrome. Akol discloses that although recent scientific advancements have opened promising and important new avenues in FOXG1 research, clinical interventions to treat FOXG1 diseases or disorders by targeting FOXG1 have not yet been realized (abstract). While Akol discloses that RNA therapies and antisense oligonucleotide therapies have been investigated, these investigations have resulted in only a few publications and no clinical treatments (page 5, paragraph 3). Notably, the disclosure of Akol is drawn to antisense oligonucleotides that target FOXG1 directly, not antisense oligonucleotides that target lncRNAs that regulate FOXG1 expression.
However, targeting of lncRNAs for treatment of neurological disorders is known in the art (reviewed in Qureshi and Mehler, 2013). Per Qureshi and Mehler, 2013, targeting lncRNAs rather than genes directly offers mechanistic and also potentially effective approaches for distinguishing and mitigating disease pathology that are complementary to, and likely more precise than such methods (page 639, column 1, paragraph 4). However, the art is silent as to in vivo therapeutic strategies for FOXG1 diseases or disorders wherein antisense oligonucleotides targeting lncRNAs regulating FOXG1 expression are administered to subjects in need thereof.
Furthermore, as is known to those of ordinary skill in the art, lncRNAs are capable of both activating and repressing target gene expression, meaning each lncRNA either activates or represses the expression of a specific target gene (reviewed in Gil and Ulitsky, 2019). Therefore, one of ordinary skill in the art would reasonably predict that targeting a lncRNA regulating FOXG1 would result in only increased or decreased expression of FOXG1 such that diseases or disorders amenable to treatment with such antisense oligonucleotides targeting a lncRNA must be drawn to only decreased or increased expression of FOXG1, respectively, in order to be effectively treated by the instantly claimed methods. As set forth above, FOXG1 dosage states cannot be modeled linearly or simplistically, as FOXG1 interacts with different players and may be governed by substrate affinity or phosphorylation states, meaning FOXG1 exerts its effects by how and when it is expressed, how FOXG1 is stabilized or degraded, and also is influenced by background genetics (see section "CONCLUSION" of Hettige). One of ordinary skill in the art would therefore not reasonably predict that an antisense oligonucleotide targeting a lncRNA regulating FOXG1 expression would be capable of treating any disease or disorder of FOXG1, which encompasses diseases or disorders involving both increased and decreased expression of FOXG1 (reviewed in Hettige and Ernst, 2019), as the instant claim language is not limited to diseases or disorders associated with decreased expression of FOXG1, nor does it address the complicated dynamics of FOXG1 expression and regulation.
To date, most therapies of FOXG1 syndrome have aimed at treating symptoms, including seizures, with interventions such as hormonal therapy and anti-epileptic drugs (reviewed in Seltzer et al., 2014). At the time of filing, no therapeutic intervention targeting FOXG1 via an antisense oligonucleotide targeting a lncRNA regulating expression thereof was known in the art, and the instant specification is silent as to the role of modulating (i.e. increasing) FOXG1 expression in treating FOXG1 disease or disorders, including both FOXG1 syndrome and FOG1 overexpression.
Amount of experimentation necessary: The quantity of experimentation needed to carry out the full scope of the claimed method is large. One could not rely upon guidance provided in the instant disclosure of prior art, as neither the instant disclosure nor the prior art discloses antisense oligonucleotides that are capable of modulating FOXG1 expression in vivo by targeting lncRNAs regulating FOXG1 expression, thereby correcting FOXG1 deficiency, as in FOXG1 syndrome. Therefore, one of ordinary skill in the art would be required to identify lncRNAs that regulate FOXG1 expression (both directly and indirectly) and to design and validate novel antisense oligonucleotides, all of which must be applicable to in vivo administration to a human brain and subsequent modulation of FOXG1 expression. The art is silent as to such methods, and the instant specification does not supply any working examples that support in vivo administration and therapeutic outcomes.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claim 123 is not considered to be fully enabled by the instant disclosure.
Regarding the limitations drawn to the treatment or amelioration of a FOXG1 disease or disorder in an individual at risk of having the FOXG1 disease or disorder, the Examiner notes that under broadest reasonable interpretation, the instant claim language reads on a method of prevention.
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.
In this case, the claims are considered to encompass preventing a FOXG1 disease or disorder in a subject at risk of having the FOXG1 disease or disorder. Looking to the prior art for guidance, a search of the prior art did not identify any methods which utilize antisense oligonucleotides targeting lncRNAs regulating FOXG1 expression which could effectively prevent any FOXG1 disease or disorder in a subject. In fact, no prior art was identified which taught effective prevention of any FOXG1 disease or disorder using any agent similar to the agents utilized in the instant claims. The specification also does not provide any working example demonstrating prevention of any FOXG1 disease or disorder in a subject. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the specification with respect to preventing a FOXG1 disease or 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 prevention of any FOXG1 disease or disorder in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
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 involved, 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.
Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled to their full scope. It is noted that amending the claims to, for example, a method of treating FOXG1 syndrome in a subject in need thereof (as set forth above), would obviate this rejection.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim 117 is rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0305689 A1 (hereinafter Sætrom) in view of Velmeshev et al., 2013 (hereinafter Velmeshev; as cited in Applicant IDS), as evidenced by Arthanari et al., 2014 (hereinafter Arthanari) and GeneCards Entry FOXG1-AS1 (hereinafter GeneCards).
With regard to claim 117, which recites “a method of modulating expression of FOXG1 in a cell, comprising contacting the cell with a composition comprising an antisense oligonucleotide that hybridizes to a target nucleic acid sequence of a long non-coding RNA (lncRNA), wherein the lncRNA regulates expression of FOXG1,” Sætrom discloses small activating RNAs (saRNAs) that have a high degree of complementarity to a region with a target antisense RNA transcript, thereby up-regulating expression of a target gene by targeting said saRNA to a naturally-occurring antisense transcript of a sense strand of the targeted gene in a target cell (paragraphs [0006] and [0050]). The natural antisense transcript may be a non-coding RNA transcript lacking any extensive open reading frame, including FOXG1-AS1 (paragraphs [0006] and [0101]). Sætrom explicitly discloses targeting non-coding FOXG1-AS1 for purposes of modulating expression thereof (paragraph [0101]). Velmeshev teaches that FOXG1-AS is the antisense transcript of FOXG1, and further that FOXG1-AS is a naturally-occurring antisense transcript of FOXG1 that has a regulatory effect on FOXG1 (page 4, column 2, paragraph 2; page 5, column 2, paragraph 2). Per Arthanari, naturally-occurring antisense transcripts represent a subset of long non-coding RNAs that contain transcripts with sequence complementarity to other RNAs (page 1, column 2, paragraph 1). Accordingly, it is considered that Velmeshev teaches that FOXG1-AS is a long non-coding RNA produced from FOXG1 and is associated with regulation of expression of the same, thereby motivating modulation of FOXG1 by targeting FOXG1-AS, as in Sætrom. The Examiner notes that FOXG1-AS and FOXG1-AS1 are aliases for each other and refer to the same naturally-occurring antisense transcript (GeneCards). Thus, the art teaches targeting a lncRNA (i.e. FOXG1-AS) that regulates expression of FOXG1 for purposes of modulating expression of FOXG1.
Given that Sætrom discloses upregulation of target genes by targeting non-coding transcripts such as long non-coding RNAs, including FOXG1-AS1, and that Velmeshev discloses that FOXG1-AS is a long non-coding RNA (as per Arthanari) associated with regulation of FOXG1 expression, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to target FOXG1-AS1 with an antisense oligonucleotide as in Sætrom to predictably modulate expression of FOXG1 (per the teachings of Velmeshev). One would have been motivated to make such a modification in order to receive the expected benefit of modulating expression of FOXG1.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
While Applicant’s claims are drawn to modulation of FOXG1 expression by targeting lncRNAs that regulate FOXG1 expression, Applicant’s disclosure only addresses FOXG1-AS1, LINC01551, and LINC02282 lncRNAs. These are not the only lncRNAs that have been linked to FOXG1 expression. Zhang et al., 2019 (hereinafter Zhang) discloses that lncRNA MSTRG.95128 has a cis-target of FOXG1 (abstract). However, Zhang does not disclose how MSTRG.95128 regulates FOXG1 (i.e. whether it upregulates or downregulates FOXG1). The prior art is silent as to MSTRG.95128 and its role in regulating FOXG1. As noted above, the instant claim set is broadly drawn to any lncRNA that regulates FOXG1 expression, although the instant disclosure is drawn to increasing FOXG1 expression by targeting lncRNAs that downregulate FOXG1 expression. Given that lncRNAs are known to both upregulate and downregulate target gene expression (reviewed in Gil and Ulitsky, 2019, as set forth above), for purposes of clarity, the instant claim set would benefit from including language that establishes both the targeted lncRNAs and their functional effects, as those of ordinary skill in the art would therefore be reasonably apprised of the metes and bounds of protection sought, as well as the therapeutic implications of the technology claimed therein.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-F 8-5.
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/SARAH E ALLEN/ Examiner, Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637
