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
1. Applicant’s preliminary amendment filed on July 15, 2025 is acknowledged. Claims 1-18 and 20 have been canceled. Claims 19, 21, 23-26, 31, and 33-34 have been amended. Claims 19 and 21-34 are currently pending and under examination.
Information Disclosure Statement
2. The information disclosure statement (IDS) submitted on July 15, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. An initialed copy is attached hereto.
Specification
3. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, see for example page 34. 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.
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.
4. Claims 19 and 21-34 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
The instant claims are drawn to a method of treating a disease or disorder in a subject, the method comprising determining if the subject has a gain-of-function mutation or a loss-of-function mutation in an ion channel or receptor and if the mutation is a gain-of-function mutation or a loss-of-function mutation, administering to the subject a therapy suitable for the gain-of-function mutation or the loss-of-function mutation in an amount and for a duration sufficient to treat the disease or disorder.
The claims are broad in that the method is to treat any disease or disorder in a subject by administering any therapy suitable for gain-of-function mutation or the loss-of-function mutation. However, the specification focuses on describing dynamic action potential clamp predicting functional separation in mild familial and 5 severe de novo forms of SCN2A Epilepsy. The disclosure discusses mutations in SCN2A, encoding the voltage-gated sodium channel type Hoc subunit (Nav1.2) cause familial and sporadic brain disorders. Familial mutations were first identified in self-limited, pharmacoresponsive epilepsy typically arising from gain-of-function mutations, whereas de novo mutations were only more recently discovered and have been recognized as the most frequent cause of neurodevelopmental disorder. The phenotypic spectrum of SCN2A mutations is broad, ranging from age-limited, pharmacoresponsive epilepsy with normal development, to severe conditions with refractory epilepsy and severe developmental impairment (DEE). The specification goes on to teach that within the DEEs, distinct phenotypes are emerging among individuals with SCN2A variation. Particularly, there is a group of patients with seizure onset in the early infantile period (‘early-onset’) in whom sodium channel blockers such as phenytoin and carbamazepine may improve seizures, and a group with seizure onset later in infancy (‘later-onset’ group, >3 months) in whom sodium channel blockers are rarely effective. It has been postulated that the difference in clinical features and treatment response are due to differential effects of the SCN2A mutations on Nav1.2 channel function. De novo SCN2A variants exhibiting Nav1.2 channel gain-of-function are typically associated with epilepsy, whereas it has been proposed that partial or complete Nav1.2 channel loss-of-function would invariably lead to autism spectrum disorder. However, more recently, loss-of-function has been also associated with ‘later-onset’ epilepsy, suggesting the genotype-phenotype correlation may be more complex.
The specification describes a detailed functional analysis of two of the most recurrent SCN2A variants, R1882Q and R853Q. A comprehensive clinical evaluation for all R1882Q and R853Q cases where records or literature data was available. In addition, they implemented dynamic action potential clamp analysis to the study of SCN2A variants in epilepsy and showed how this approach has the potential to provide a rapid and definitive prediction of neuron scale phenotypic consequences. They deployed the dynamic action potential clamp approach to analyze the impacts of the R853Q and R1882Q DEE variants as well as the L1563V variant previously associated with inherited benign familial neonatal infantile seizures (BFNIS). R853Q and R1882Q are the most frequently identified SCN2A variants and are associated with specific phenotypes. They go on to state that we not only showed how successfully dynamic action potential clamp analysis could recapitulate and surpass voltage clamp findings but also demonstrated how it could be superior to intuitive interpretation when faced with biophysical changes that have opposing effects on excitability. Our dynamic action potential clamp data directly demonstrated that the early onset R1 882Q DEE variant resulted in increased neuronal excitability and that the late-onset R853Q DEE variant results in decreased neuronal excitability.
The specification appears to closely follow patients with SCN2A mutations noting that sodium channel blockers were mainly beneficial in the R1882Q group. Further, individuals with R1882Q mutations had early-onset developmental and epileptic encephalopathies (DEE) with focal seizures beginning on the first day of life; some showed marked improvement with phenytoin, and some had benefit with other sodium channel blockers. However, despite improved seizure control with phenytoin, there was no difference in developmental impairment in responders compared with non-responders, suggesting that seizure control is not sufficient to reverse the developmental impairment associated with the SCN2A mutation.
Individuals with the R853Q mutation had later-onset DEE, with median onset of seizures at the age of 8 months, usually preceded by some degree of developmental delay. The seizure type at onset was epileptic spasms in most. In these individuals, the response to sodium channel blockers was mixed. Seizures did not improve with phenytoin; indeed, worsening was reported in one. Improved seizure control was, however, reported with other sodium channel blockers in three patients (lamotrigine, carbamazepine, both rendering a patient seizure-free; and oxcarbazepine). Movement disorders, such as dystonia, were seen in both groups; however, severe choreoathetosis only occurred with the R853Q mutation. In two of these patients, the choreoathetosis preceded seizure onset. In both groups, most patients had other types of seizures arising over time, refractory seizures and significant developmental delay.
On the contrary, the specification does not provide adequate support for the claims as drafted. How does this method treat any and all diseases and disorders? How is the gain of function/loss of function determined? How is a “suitable” therapy determined? Will one form of suitable therapy work to treat all of the diseases and disorders encompassed by the claim? Applicant should consider claiming the invention in a way that correlates the therapy (by structure) to the function because the specification provides no guidance regarding which therapies are capable of breadth of the required function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications under the 35 USC §112 paragraph 1, “Revision 1” of Written Description Requirement (66 FR 1099-1111, March 25, 2008) state, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention (ld. At 1104). Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 102
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.
5. Claim(s) 19 and 21 -34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Petrou et al., US 2011/0294155 A1; Published: 12/1/11.
Independent claim 19 is drawn to a method of treating a disease or disorder in a subject, the method comprising determining if the subject has a gain-of-function mutation or a loss-of-function mutation in an ion channel or receptor and if the mutation is a gain-of-function mutation or a loss-of-function mutation, administering to the subject a therapy suitable for the gain-of-function mutation or the loss-of-function mutation in an amount and for a duration sufficient to treat the disease or disorder.
Petrou discloses an invention based on the surprising finding that a dynamic clamp can be used to determine the activity of compounds at one or more ion channel or receptor types that are involved in providing a waveform in a biological cell. Accordingly, in one aspect the present invention provides a method of assaying a compound for its ability to modulate an ion channel or receptor type, the method comprising: a) providing a dynamic clamp in electrical contact with a biological cell (or part thereof) in which one or more ion channel or receptor types for providing a waveform are functional and in which one or more ion channel or receptor types for providing a waveform are either not present or not functional; b) causing the dynamic clamp to apply a signal simulating the function of at least one of the one or more ion channel or receptor types that are either not present or not functional in the biological cell (or part thereof) based on modulation of the ion channel or receptor types that are functional in the biological cell (or part thereof) to thereby provide the waveform at the biological cell (or part thereof); c) exposing at least one of the one or more functional ion channel or receptor types to a compound; and d) detecting modulation of the waveform at the biological cell (or part thereof), wherein modulation of the waveform is indicative of a compound that modulates the at least one functional ion channel or receptor types (see paragraphs 0011-16; meets claim 21-22).
Moreover, a waveform at a biological cell (or part thereof) is generally produced by virtue of a functional inter-relationship between a number of different types of ion channels or receptors. Modulation of one, or a group of ion channels or receptors results in electrophysiological changes at the membrane of the cell, causing further ion channels to be modulated, resulting in a waveform. Ion channels including, for example, sodium channels, potassium channels, calcium channels, chloride channels and hyperpolarization-activated cation channels may involved (see paragraph 0049; meets claims 26-27).
In one embodiment, the dynamic clamp applies a voltage signal to the biological cell (or part thereof), and modulation of the waveform at the biological cell (or part thereof) is detected measuring a current signal at the biological cell (or part thereof). In this embodiment the voltage is clamped (see paragraph 0053; meets claim 24). In another embodiment, the dynamic clamp applies a current signal to the biological cell (or part thereof), and modulation of the waveform at the biological cell (or part thereof) is detected by measuring a voltage signal at the biological cell (or part thereof). In this embodiment the current is clamped (see paragraph 0055; meets claim 25).The dynamic clamp in electrical contact with a cell expressing sodium channels may be used to assist in producing and monitoring consecutive waveforms (action potentials) at that cell. Furthermore, it is illustrated that by modifying this system by modulating these sodium channels with a compound, the resultant waveform generated is affected (see paragraph 0168; meets claim 23).
Further, in one embodiment, the ion channel or receptor type to be modulated is an N-type calcium channel or an L-type calcium channel. The N-type calcium channel may be an alpha(2)delta calcium channel subunit. In another embodiment, the L-type calcium channel may be Cav0.2. Compounds that modulate N-type calcium channels may be useful in the treatment or amelioration of pain indications. On the other hand, compounds that modulate L-type calcium channels may be useful in the treatment or amelioration of a variety of cardiac diseases (see paragraph 0135; meets claim 19).
Petrou discloses that sodium channels are integral membrane proteins, and in cells such as neurons, sodium channels play a key role in the production of action potentials. Consequently, compounds affecting sodium channel function will generally have a more direct and significantly greater impact on the action potential of the biological cell than those compounds affecting calcium and chloride channel function. In one embodiment, the sodium channel is a Nav1.1 channel (voltage gated sodium channel, type I, alpha subunit; gene: SCN1A), a Nav1.2 channel (voltage gated sodium channel, type II, alpha subunit; gene: SCN2A), a Nav1.3 channel (voltage gated sodium channel, type III, alpha subunit; gene: SCN3A), a Nav1.4 channel (voltage gated sodium channel, type IV, alpha subunit; gene: SCN4A), a Nav1.5 channel (voltage gated sodium channel, type V, alpha subunit; gene: SCN5A), a Nav1.6 channel (voltage gated sodium channel, type VIII, alpha subunit; gene: SCN8A), a Nav1.7 channel (voltage gated sodium channel, type IX, alpha subunit; gene: SCN9A); a Nav1.8 channel (voltage gated sodium channel, type X, alpha subunit; gene: SCN10A); or a Nav1.9 channel (voltage gated sodium channel, type XI, alpha subunit; gene: SCN11A). In another embodiment, the sodium channel is a Nav1.5 channel. In a further embodiment, the sodium channel is a Nav1.4 channel (see paragraph 0137; meets claims 28-30).
Further, Petrou discloses new pharmaceuticals for a wide variety of diseases or conditions may be identified. For example, such diseases or conditions may include, but are not limited to, arrhythmia, short QT syndrome, long QT syndrome, pain, neuropathic pain, fibromyalgia, epilepsy, cognition and memory disorders, movement disorders, affective disorders, mood disorders, skeletal muscle diseases, smooth muscle diseases, blood pressure and tremors (see paragraph 0153). The Office takes the position that the cognition disorder as recited encompasses encephalopathy, thereby meeting claim 31).
As it pertains to claims 32-34, Petrou discloses that the method according to the present invention is applicable for a wide variety of diseases or conditions, for example, such diseases or conditions may include, but are not limited to, epilepsy, cognition and memory disorders, movement disorders, and mood disorders (see paragraph 0153). That said, the office takes the position that the method as claimed is the same as what is taught in the art, said encephalopathy and epilepsy necessarily encompasses those recited in claims 32-34, absent evidence to the contrary.
Conclusion
6. No claim is allowed.
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 August 21, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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