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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/22/2025 has been entered.
Status of the Application
Claims 1-10 and 12-23 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 09/22/2025 are acknowledged. Claims 7-10, 12-19, and 21-23 remain withdrawn, as being drawn to an unelected invention or specie. Claims under consideration in the instant office action are claims 1-6 and 20.
Applicants' arguments, filed 09/22/2025, have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-6 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Laine (WO 2015/067857, as disclosed in IDS) in view of Colombo et la. (Congenital myopathies, Neurology, 2015, 84(1), pp. 28-35) and Goldman et al. (Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention, Epilepsia, 2016, 57(1), pp. 17-25).
Laine teaches “methods for determining whether an individual carries at least one genetic risk factor predisposing to or causing fetal or infant death.” (see abstract). Laine teaches “As used herein, the term "sudden and unexpected death of infancy" (SUDI) refers to any death in the first year of life which is sudden, unexpected, and initially unexplained. The deaths that remain unexplained even after a thorough case investigation including performance of a complete autopsy, examination of the death scene and the review of clinical history are defined as "sudden infant death syndrome" (SIDS).” (pg. 6, lines 8-13). Laine teaches “The present diagnostic method may comprise determining the presence or absence of any known disease-associated mutation in a gene set forth above, or it may comprise sequencing the gene panel thus enabling not only determining the presence or absence of said disease-associated mutations but also identification of previously unknown mutations in a gene in question. Microarray-based technologies are non-limiting examples of methods suitable for determining the presence or absence of genetic markers such as mutations. Briefly, these techniques comprise hybridizing of an amplified DNA sample with an array of specific DNA probes spotted on a solid surface. Thus, multiple mutations associated with multiple genes and multiple diseases can be assayed in a single run. Means and methods suitable for this purpose are readily available in the art.” (pg. 30, first and second paragraphs). Laine teaches ACADM as a gene associated with such disorders (see claim 6). Laine teaches that “Applying TruSeq® technology requires that, for each gene to be sequenced, two oligonucleotide probes, which hybridize upstream and downstream of the region of interest, are designed and synthetized. Each probe contains a unique, target specific sequence and a universal adapter sequence. An extension- ligation reaction is used to unite the two probes and create a library of new template molecules with common ends. Adapter-ligated DNA is then subjected to PCR amplification, which adds indexes and sequencing primers to both ends.” (pg. 30, lines 21-31). Laine teaches that “International patent publication WO 2006/019984 discloses a method and kit for testing a human individual for one gene predisposing to sudden infant death syndrome (SIDS), namely SCN5A.” (pg. 2, lines 7-9).
Laine does not teach preparing a panel wherein one or more polynucleotides encoding a gene is ACTA1 or a polynucleotide encoding SCN1A.
Colombo et al. is drawn towards “the natural history of congenital myopathies (CMs) due to different genotypes.” (see abstract). Colombo et al. teaches “ACTA1 and NEB were the genes most frequently implicated in NM. All ACTA1 mutations were de novo dominant with the exception of patient 14 with a homozygous recessive mutation inherited from asymptomatic parents, and patient 13 who carried the same dominant mutation as her mildly affected mother. Neonatal onset was the main presentation in both subgroups, but ACTA1 patients had a higher rate of neonatal complications compared with NEB. All NEB cases acquired independent ambulation, while motor abilities of patients with the ACTA1 mutation were more variable, with 10 of 15 (66.74%) achieving independent ambulation.” (pg. 32, left column, first paragraph).
Goldman et al. is drawn towards “the role of genetic factors in sudden unexpected death in epilepsy (SUDEP). In this, we draw on research in sudden cardiac death (SCD) and sudden infant death syndrome (SIDS).” (pg. 17, left column, first paragraph). Goldman et al. teaches “The Scn1a deficient models mirror the complex human phenotype, exhibiting spontaneous seizures, autonomic instability, and seizure-driven vagal activation preceding sudden death. Administration of parasympatholytics reduced the incidence of ictal bradycardia and SUDEP in the model. A knock-in mouse model carrying the human mutation SCN1A-R1407X displayed a 21% premature death rate, spontaneous seizures, and a prolonged QT interval due to the increased sodium channel–dependent cardiac current in cardiomyocytes. Cardiac arrhythmias in this model often preceded apparent convulsive seizures, thus indicating that some SCN1A variants might predispose to sudden death through neurocardiac or sole cardiac mechanisms. There is also experimental evidence that mortality risk in DS is influenced by the affected neuronal cell type and regionally specific differences in Scn1a brain expression; selective Nav1.1 deficiency in inhibitory c-aminobutyric acid (GABA)ergic neurons led to a more severe epileptic phenotype and early and frequent sudden death as compared to mice with constitutive Scn1a deficiency.” (pg. 19, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to prepare a panel wherein one or more polynucleotides encoding a gene is ACTA1 or a polynucleotide encoding SCN1A, as suggested by Colombo et al. and Goldman et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Colombo et al. teaches ACTA1 as a prevalent gene mutation of congenital myopathies, and Goldman et al. teaches that some SCN1A variants might predispose to sudden death through neurocardiac or sole cardiac mechanisms, with a reasonable expectation of success absent evidence of criticality of the particular product.
Response to Arguments
Applicant argues that “the vast majority of SUDP cases are not linked to SCD, and the vast majority of SCD cases are not linked to SUDP. In point of fact, the prior art is devoid of any teachings drawing such a connection. Instead, as explained in the present application, "The etiologic model for SUDP is the Triple-Risk Model of SIDS, which maintains that sudden death occurs due to a combination of latent biological vulnerabilities (e.g., genetic factors) and external factors (e.g., sleep environment) during key developmental stages of enhanced susceptibility." See Application, paragraph [0128]. It is therefore well known in the art that SUDP is not easily distilled down to single causes ( e.g., cardiac disease). Given these distinctions, there is no basis for the person of ordinary skill to conclude that an SCD marker would also be an SUDP marker… Goldman fails to establish a reasonable expectation of success for the person of ordinary skill in using an SUDEP marker, such as SCNlA, as an SCD marker. This is because Goldman fails to draw a link between the two conditions, at best, Goldman speculates that the "potential overlap [between genetic risk in SCD and] genetic risk in SUDEP remains to be explored." See Goldman, page 18, right column, last paragraph (emphasis added). The mere invitation to explore an area of research does not provide a person of ordinary skill with a reasonable expectation of success in employing a SUDEP marker, such as , such as SCNlA, as a marker of SCD.” The Examiner respectfully disagrees since Goldman et al. states that “Evidence suggests likely genomic complexity and a degree of overlap among sudden cardiac death, sudden infant death syndrome, and SUDEP” (see Key Points, pg. 18). Goldman et al. also teaches that “Structural cardiac disease accounts for approximately 60% of sudden death in that occurs in the young before 35 years of age. In the presence of familial disease, candidate gene testing will identify mutations in ~60% hypertrophic, 25% dilated, and 40% arrhythmogenic right ventricular cardiomyopathies. Diagnostic yield in patients with SADS rests in the profiling of genes responsible for LQTS, BrS, and catecholaminergic polymorphic ventricular tachycardia (CPVT): cardiac potassium channel alpha and beta subunits KCNQ1, KCNH2, KCNE1, and KCNE2; the cardiac sodium channel alpha subunit SCN5A; and the sarcoplasmic reticulum calcium release channel, the Ryanodine receptor (RyR2), respectively. The mutation prevalence in these genes is estimated at around 15–20%. Careful cardiologic evaluation of the family can increase the detection rate from 22% to 53%. It is now known that those at greatest risk may carry multiple genetic variants. Multiple mutation carriers represent approximately 7% of LQTS probands, and they present with more severe disease.” (pg. 18, left column, first paragraph). Given that Laine teaches analyzing genes “associated with arrhythmogenic diseases, at least one gene associated with, cardiomyopathies,” (pg. 2, lines 20-30), one of ordinary skill in the art would have been motivated to prepare a panel comprising a polynucleotide encoding SCN1A.
Conclusion
Claims 1-6 and 20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691