2DETAILED 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 .
Status of Claims
Acknowledgement is made of Applicants amendments filed 08-18-2025. The claims 8-9 and 23-24 recite the status as “previously presented” instead of “withdrawn.” Applicants must correct the status of the withdrawn claims, 8-9 and 23-24 in the next communication. Claims 1, 3-4, 10-19 and 25-28 read on the elected species and are currentlyunder examination.
Priority
The present application claims benefit of provisional application no. 63/281,640 effectively filed on November 11, 2021.
Status of Claims
Claims 1, 3-4, 10-19 and 25-28 are pending for examination.
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, 3-4, 10-19, and 25-28 are remain 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.
Applicant’s response filed 08/18/2025 was incomplete. Specifically, Applicant did not address the merits of this rejection.
The term “at risk” in claims is a relative term which renders the claim indefinite. The term “at risk” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. -.
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 ch 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, and 14 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 claims contain 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.
Applicant's arguments filed 08-18-2025 have been fully considered but they are not persuasive.
Applicants traverse the instant rejection of the grounds that: “Without agreeing to the Office's position and solely to advance prosecution, claims 1 and 14 have been amended by incorporating the features of claims 3, 8, and 9 in
the alternative and claims 18, 23, and 14 in the alternative, respectively. Thus, Applicant's specification contains sufficient written description conveying Applicant's possession of the now claimed subject matter. Accordingly, Applicant respectfully requests that the rejection under 35 U.S.C. §112(a) be withdrawn.”
Contrary to Applicant’s assertions, claims 1 and 14 have been amended to recite “wherein the SCN11A inhibitor comprises an inhibitory nucleic acid molecule that hybridizes to an SCN11A nucleic acid molecule, a small molecule, or an antibody.” However, the structure of the “SCN11A inhibitory nucleic acid molecule” remains structurally undefined. Additionally, the claims do not provide the nucleotide sequence of the SCN11A target sequence, such that a person of skill in the art would be able to predict the structure of the inhibitory nucleic acid. Additionally, the claim requires that the nucleic acid inhibitor function to “hybridizes to an SCN11A nucleic acid molecule, a small molecule, or an antibody. Applicants have not demonstrated possession of an inhibitory nucleic acid that hybridizes to a small molecule or antibody, wherein the inhibitor is capable of treating a headache or a migraine or at risk of developing a headache or a migraine.
Moreover, Applicant has not specifically set for the target for the elected inhibitory type of SCN11A inhibitor wherein the SCN11A inhibitor comprises an inhibitory nucleic acid molecule that hybridizes to an SCN11A nucleic acid molecule, a small molecule, or an antibody. The scope of the nucleic acid inhibitor may target DNA encoding SCN11A, mRNA encoding SCN11A, or naturally occurring antisense RNA targeting SCN11A mRNA. The ambiguity associated with the nucleic acid inhibitor target also increases the complexity of the inhibitor. Without the knowledge of the structure of the SCN11A target, the person of skill in the art would not be able to predict the Applicant was in possession of the full scope of the claimed invention,
As previously stated:
The claimed invention is drawn to a method treating a subject by administering any inhibitor of SCNA11 inhibitor that must function to inhibit the Voltage-Gated Channel Alpha Subunit11 (SCN11A). The specification defines an inhibitor as comprising RNA, DNA, or both, inhibitory nucleic acids, antisense nucleic acid molecules, small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs), nuclease agents, small molecules, non-selective sodium blocker and antibodies.
When claims 1, and 14 are analyzed in light of the specification, the claims encompass any inhibitor of SCNA11 including RNA, DNA, or both, inhibitory nucleic acids, antisense nucleic acid molecules, small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs), nuclease agents, small molecules, non-selective sodium blocker and antibodies. Thus, the claims encompass a genus of inhibitor defined solely by function where the inhibitor must be capable of functioning to decrease expression of SCN11A.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant application the specification discloses that the SCN11A inhibitor can comprise an inhibitory RNA, DNA, or both RNA and DNA nucleic acid molecule that can target any region of an SCN11A nucleic acid molecule (page 35). Page 36 of the specification discloses that the nucleic acid molecule can be linked to a heterologous nucleic acid sequence, such as a vector or as an exogenous donor sequence or a label. The specification also discloses that the nucleic acid molecule can comprise, nucleotides or non-natural or modified nucleotides (page 36). The specification defines a nucleotide non-natural or modified nucleotides as encompassing dideoxynucleotides, biotinylated, aminated, deaminated, alkylated, benzylated, fluorophor-labeled nucleotides, and nucleotides which contain a modification to either the base, sugar, or phosphate moieties (page 37). While the specification generally describes properties of nucleic acid inhibitors, it does not describe the complete structure including the sequence of any nucleic acid inhibitor.
The specification also discloses that the inhibitor may comprise nuclease agent that induces one or more nicks or double-strand breaks at a recognition sequence(s) or a DNA- binding protein that binds to a recognition sequence within an SCN11A genomic nucleic acid molecule located within a coding region of the SCN11A gene, or within regulatory regions that influence the expression of the gene. (page 40). The specification further discloses that the recognition sequence can be located within a broad range of about 10, to about 1,000 nucleotides from the start codon (page 41). It is disclosed that suitable nuclease agents and DNA-binding proteins may encompass zinc finger protein or zinc finger nuclease (ZFN) pair, Transcription Activator- Like Effector (TALE) protein or Transcription Activator-Like Effector Nuclease (TALEN), or Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) systems (page 40-42).
The specification discloses that the SCN11A inhibitor encompasses a non-selective sodium blocker such as lignocaine, mexiletine, carbamazepine, menthol, mibefradil, or an inorganic l(Ca) blocker (page 48).
The specification does not teach the complete structure of any antibody or small molecule SCN11A inhibitor.
Claims 1 and 14 encompass any of the above recited inhibitors which comprise many possible combinations of sequences, arrangements of nucleotides or non-natural or modified nucleotides, and nucleases.
While the genus encompasses a large number of variants and molecules that have the same activity, inhibition of SCNA11 in kind and the genus encompasses a large number of variants and molecules that have a different structure, the instant invention encompasses many possible combinations of sequences, and molecules of the inhibitor of claims 1, and 14. The specification does not describe the complete structure of a representative number of any species of the large genus of any inhibitors.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only claimed identifying characteristic is inhibition of SCN11A. Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of the SNC11A inhibitor all members of the claimed genus will have that characteristic.
Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AlA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
In conclusion, Applicant’s disclosure of an in SCN11A inhibitor of the claimed broad genus is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Response to Arguments
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 (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 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.
Claims 1, 3, and 4 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Collard et. al. (US2013/0096183A1 Pub. Date: Apr. 18,2013; Effective filing date: Jun. 23, 2011).
Applicant's arguments filed 08-18-2025 have been fully considered but they are not persuasive. Applicants argued the following: “[A]pplicant respectfully notes that the Office mischaracterizes Collard and that Collard discloses exactly the opposite, i.e., a method of augmenting the function of and/or expression of a Sodium Voltage-Gated channel alpha subunit (SCNA) such as SCN11A. Collard discloses the existence of a natural antisense transcript that "naturally" down-regulates the mRNA (i.e., sense transcript) encoding the sodium channel, voltage-gated, alpha subunit (SCNA) in vivo. Collard teaches and is entirely directed to the targeting of this natural antisense transcript, as opposed to the SCNA sense transcript itself. This targeting results in the down-regulation of the natural antisense transcript, which in turn causes the upregulation (i.e., augmentation) of the function of and/or expression of the SCNA transcript and protein for purpose of treating diseases caused by the down-regulation of SCNA protein.”
Contrary to Applicant’s assertions it is clear that a naturally occurring antisense RNA transcript targeting SCNA mRNA, would naturally reduce the level of SCN11A in the cell. The naturally occurring antisense transcript binds SCNA mRNA and reduces the overall amount of SCN11A in the cell. Thus, it would be expected that blocking SCN11A antisense would result in an increase in SCN11A mRNA, and SCN11A protein. However, if the SCN11A nucleic acid inhibitor targets SCN11A mRNA, that would result in the inhibition of SCN11A of the protein and the mRNA. Moreover, instant claims, 1, and 3-4, do not recite the type of target that the inhibitor hybridizes to, antisense or sense RNA, a person of skill in the art would not be able to definitively say that the cited references teach away from the claims. Applicant cannot say there is teaching away, because the claims do not recite the particular inhibitor used to target SCN11A, is the inhibitor designed to target SCN11A, mRNA, DNA, antisense or sense RNA. The target of the inhibitor, would predict the overall function of the inhibitor.
Applicant’s arguments are not persuasive.
The claims remain rejected for the reasons of record, see below:
Regarding claim 1: Collard discloses a method of inhibiting the function of and/or expression of a Sodium Voltage-Gated channel alpha subunit (SCNA) such as SCN11A by means of an antisense oligonucleotide such as an siRNA to treat a diseases or disorder associated with the expression of SCNAs, such as neurological diseases or disorders including but not limited to headaches and migraines (see abstract, [0005], [0075], [0084], [0205]).
Regarding claim 3: Collard discloses an inhibitory nucleic acid molecule that hybridizes to at least a portion of the target nucleic acid such as SCN11A (see, [0084], [0098].
Regarding claim 4: Collard discloses an inhibitory siRNA nucleic acid molecule which hybridizes to at least a portion of the target nucleic acid and modulates its function (see [0005], [0046], [0054]).
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.
Claims 10-19, and 25-28 remain rejected under 35 U.S.C. 103 as being unpatentable over Collard et. al. (US2013/0096183A1 Pub. Date: Apr. 18,2013; Effective filing date: Jun. 23, 2011), Clube et. al. (US9139648 B1; Date Published: Sep. 22, 2015; Effectively Filed Date: Mar. 23, 2015), Liang et. al. (Molecular Pain, 9:31, 2013), and Zhang et. al. (American Journal of Human Genetics 93(5), 957–966. 2013).
Applicant's arguments filed 08-18-2025 have been fully considered but they are not persuasive.
Applicant traverses the rejection and respectfully requests reconsideration thereof. According to Applicants “Collard not only does not teach or suggest the claimed subject matter (neither itself nor in combination with Cube, Liang and/or Zhang) but teaches away from it, as explained in section II above. This is a classical example of "teaching away," when persons in the field of the invention "would be led in a direction divergent from the path that was taken by the applicant."
As set forth above, since the structure of the inhibitor and the target of the inhibitor is not clearly defined in the claims, applicants cannot definitively say that the reference teaches away. Applicant’s arguments are not persuasive, the claims remain rejected for the reasons of record.
Regarding claim 10-13: Collard discloses the combinations of antisense compounds and other non-antisense therapeutic drugs including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, to treat SCN11A associated diseases or disorders [0237].
Collard does not disclose detecting the presence or absence of an SCN11A predicted loss-of-function variant (such as a stop-gain or heterozygous variant) nucleic acid molecule in a biological sample from the subject.
However, Clube teaches a method comprising determining the presence or absence of a nucleotide sequence that encodes for a Nav1.9 (SCN11A) protein or variant thereof from a biological sample and determining whether the subject is heterozygous or homozygous for Nav1.9 (SCN11A) nucleotide sequence mutations such as the stop-gain loss-of-function mutation (rsID78812471) disclosed in the instant application (see column 543, lines 44-54; column 544, lines 4-7; and table 26).
Additionally, Liang teaches that inhibitory mutations in the SCN11A gene are associated with a reduction of pain in response to inflammatory mediators such as those that mediate migraines and headaches (see pg. 7, col. 1, par. 3-4). Furthermore, Zhang teaches that gain-of-function mutations in SCN11A can be causative of pain disorders and that this channel plays an important role in the generation of pain hypersensitivity in both subacute and chronic inflammatory models (see abstract; and pg. 965, column 1, paragraph 1).
It would have been obvious to one skilled in the art to modify Collard’s method of treating an SCN11A associated disease or disorder by adding a step of determining the presence or absence of a nucleotide sequence that encodes for a Nav1.9 (SCN11A) protein or variant thereof from a biological sample as taught by Clube and determining whether the subject is heterozygous or homozygous for Nav1.9 nucleotide sequence mutations such as a loss-of-function mutation. The artisan would have been motivated to modify Collard’s method of treatment with Clube’s method of detecting SCN11A mutations because Liang teaches that inhibitory mutations reduce headache and migraine associated pain, and Zhang teaches that gain-of-function mutations can be causative of inflammatory pain disorders. Patients with loss-of-function mutations would be at a reduced risk of developing headaches or migraines. Conversely, patients with gain-of-function mutations would be at an increased risk of developing an inflammatory pain disorder (such as headaches or migraines). Detection of either type of mutation in a patient would then inform the ideal candidate to be treated with the claimed invention in the instant application.
Regarding claim 14-17: Collard discloses a method of inhibiting the function of and/or expression of a Sodium Voltage-Gated channel alpha subunit (SCNA) such as SCN11A by means of antisense oligonucleotides such as an siRNA that hybridize to at least a portion of the target nucleic acid to treat a diseases or disorder associated with the expression of SCNAs, such as neurological diseases or disorders including but not limited to headaches and migraines in a subject (see abstract, [0005], [0046], [0075], [0084], [0205]). Collard also discloses the combinations of antisense compounds and other therapeutic non-antisense drugs including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, to treat SCN11A associated diseases or disorders [0237].
Collard does not disclose detecting the presence or absence of an SCN11A predicted loss-of-function variant (such as a stop-gain variant) nucleic acid molecule in a biological sample from the subject wherein the subject is reference (loss-of-function mutation absent), heterozygous, or homozygous for the loss-of-function variant.
However, Clube teaches a method comprising determining the presence or absence of a nucleotide sequence that encodes for a Nav1.9 (SCN11A) protein or variant thereof from a biological sample and determining whether the subject is heterozygous or homozygous for Nav1.9 nucleotide sequence mutations such as the stop-gain loss-of-function mutation (rsID78812471) disclosed in the instant application (see column 543, lines 44-54; column 544, lines 4-7; and table 26).
Additionally, Liang teaches that inhibitory mutations in the SCN11A gene are associated with a reduction of pain in response to inflammatory mediators such as those that mediate migraines and headaches (see pg. 7, col. 1, par. 3-4). Furthermore, Zhang teaches that gain-of-function mutations in SCN11A can be causative of pain disorders and that this channel plays an important role in the generation of pain hypersensitivity in both subacute and chronic inflammatory models (see abstract; and pg. 965, column 1, paragraph 1).
It would have been obvious to one skilled in the art to modify Collard’s method of treating an SCN11A associated disease or disorder by adding a step of determining the presence or absence of a nucleotide sequence that encodes for a Nav1.9 (SCN11A) protein or variant thereof from a biological sample as taught by Clube and determining whether the subject is heterozygous or homozygous for Nav1.9 nucleotide sequence mutations such as a loss-of-function mutation. The artisan would have been motivated to modify Collard’s method of treatment with Clube’s method of detecting SCN11A mutations because Liang teaches that inhibitory mutations reduce headache and migraine associated pain, and Zhang teaches that gain-of-function mutations can be causative of inflammatory pain disorders. Patients with loss-of-function mutations would be at a reduced risk of developing headaches or migraines. Conversely, patients with gain-of-function mutations would be at an increased risk of developing an inflammatory pain disorder (such as headaches or migraines). Detection of either type of mutation in a patient would then inform the ideal candidate to be treated with the claimed invention in the instant application.
Regarding claim 18-19: Collard discloses a method of inhibiting the function of and/or expression of a Sodium Voltage-Gated channel alpha subunit (SCNA) such as SCN11A by means of antisense oligonucleotides such as an siRNA that hybridize to at least a portion of the target nucleic acid to treat a diseases or disorder associated with the expression of SCNAs, such as neurological diseases or disorders including but not limited to headaches and migraines in a subject (see abstract, [0005], [0046], [0075], [0084], [0205]). Collard also discloses the combinations of antisense compounds and other therapeutic non-antisense drugs including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, to treat SCN11A associated diseases or disorders [0237].
Regarding claim 25-28: Collard discloses a method of treating a headache or migraine in a subject (see abstract, [0005], [0046], [0075], [0084], [0205]). The specification in the instant application defines a subject at risk of developing a headache or migraine as any subject (page 5). Collard’s method of treatment can thus be determined to encompass the subjects as described in the instant application. Collard also discloses the use of nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, to treat SCN11A associated diseases or disorders [0237].
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L EPPS-SMITH whose telephone number is (571)272-0757. The examiner can normally be reached M-F, 10:00 AM-6:30 PM.
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/JANET L EPPS -SMITH/Supervisory Patent Examiner, Art Unit 1646