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 .
Claim Status and formal matters
This action is in response to papers filed 8/14/2025.
Claims 11, 15, 19, 23, 29,32, 35-36, 401, 43, 66, 74-79, 87-89 are pending.
Claim 23 has been amended.
Applicant’s election of group I, in vitro, determining/genotyping, position 99,219 SEQ ID NO 3 in the reply filed on 3/27/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 11, 15, , 19, 32, 36, 40, 66, 73-79, 87-89 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/ invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/27/2025.
Claims 23, 29, 35, 43 are being examined.
The sequence compliance issue has been withdrawn in view of the amendment to the specification.
Priority
The instant application was filed 11/12/2021 is a Continuation of 16881167 , filed 05/22/2020, and claims priority from provisional application 62851296 , filed 05/22/2019.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims23, 29, 35, 43 objected to because of the following informalities:
Claim 23 has been amended to recite, “SYNJ2 variant rs2256014.” The response asserts this is defined on page 30 lines 4-6. While the cited section provides guidance of what is encompassed by a SYNJ2 variant rs2256014, it does not explicitly define it. Claims are clearer and more concise when the requirements of the claims are explicit. Thus the claim should be amended to identify which allele is the variant allele.
Claim 29 is objected to as requires, “wherein the genotyping assay comprises sequencing at least a portion of the nucleotide sequence of the SYNJ2 genomic nucleic acid molecule in the biological sample, wherein the sequenced portion comprises a position corresponding to position 99,219 according to SEQ ID NO:3, or the complement thereof; wherein when the sequenced portion of the SYNJ2 genomic nucleic acid molecule in the biological sample comprises a thymine at a position corresponding to position 99,219 according to SEQ ID NO:3; then the SYNJ2 genomic nucleic acid molecule in the biological sample is a SYNJ2 predicted loss-of-function variant genomic nucleic acid molecule.” The independent claim is limited to SYNJ2 variant rs2256014. Thus it is unclear why the claim is reciting, “SYNJ2 predicted loss-of-function variant genomic nucleic acid molecule.” It is unclear if this is an attempt to broaden the scope of the claim. Further it is unclear why a dependent claim requires sequencing of a portion, while the independent claim require detection of a single allele.
Claim 35 depends from 29 and requires, “wherein the detecting step comprises sequencing the entire SYNJ2 genomic nucleic acid molecule.” This appears to be referencing the determining step of claim 23, as there is no detecting step. Further it is unclear why the whole gene would be sequenced if the independent claim requires a single nucleotide.
Claim 35 is not concise as it recites, “wherein the nucleic acid molecule is present within a cell obtained from the human subject.” However, the independent claim does not recite “human subject.” This objection can easily be overcome by placing an indefinite article prior to human subject.
Response to Arguments
These is a new ground of objection.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 23, 29, 35, 43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and an abstract idea without significantly more.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II. (This is directed to step 1 of the 2019 Patent Subject Matter Eligibility Guidelines, referred to herein as “2019 PEG”).
Claims Analysis:
The claims have been analyzed to determine whether they recite a judicial exception (JE) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014), PerkinElmer, Inc. v. Intema Ltd., 496F. App 'x 65 (Fed. Cir. 2012)]. (This is directed to step 2A, prong 1 of the 2019 PEG). The claims were then analyzed to determine whether they recite an element or step that integrates the JE into a practical application [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)] (this is directed to step 2A, prong 2 of the 2019 PEG). In the absence of a step(s) or element(s) that integrate the JE into a practical application, the additional elements/steps have been considered to determine whether they add significantly more to the JE [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014), PerkinElmer, Inc. v. Intema Ltd., 496F. App 'x 65 (Fed. Cir. 2012)] (this is directed to step 2B of the 2019 PEG and step 2 of the Mayo/Alice test). It was found that the present claims fail to meet the elements required for patent eligibility.
The instant claims 223, 29, 35, 43 are directed to methods of treating and therefore are directed to one of the four statutory categories of invention.
The claimed invention of claims 23, 29, 35, 43 have been amended to recite, “ A method of treating a patient with a therapeutic agent that treats or inhibits hearing loss, wherein the patient is suffering from hearing loss, the method comprising the steps of: determining whether the patient carries a nucleic acid molecule with the Synaptojanin-2 (SYNJ2) variant rs2256014 by: obtaining or having obtained a biological sample from the patient; and performing or having performed a genotyping assay on the biological sample to determine if the patient has a genotype comprising the SYNJ2 variant rs2256014; and when the patient has a genotype not comprising the SYNJ2 variant rs2256014, then administering to the patient the therapeutic agent that treats or inhibits hearing loss in a standard dosage amount; and when the patient is heterozygous or homozygous for the SYNJ2 variant rs2256014, then administering the SYNJ2 variant rs2256014 indicates the patient has an increased risk of developing hearing loss; and wherein the therapeutic agent is D-methionine, a combination of ebselen and allopurinol, or resveratrol. However, the relationship between the predicted SYNJ2 variant rs2256014 and hearing loss is an abstract idea, as indicated in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012) (MPEP 2106.04(b)). Likewise, “determining whether the patient has a “SYNJ2 predicted-loss-of function rs2256014 variant is an abstract idea because a determination can occur entirely within the mind. The steps of “having obtained a biological sample” and “having performed a genotyping assay to determine if the patient has a genotype” are an abstract idea. It is noted that a mental process that a physician should follow when testing a patient is an abstract idea because it is an example of managing personal behavior (2106.04(a)(2)). Here, the steps of “having obtained” and “having performed” may just be merely mental processes, as they are not being actively recited. Additionally, “determining whether” an extension product comprises a particular nucleotide is an abstract idea because it can occur entirely within the mind (claim 23). Further it is noted that in the presence or absence of the SYNJ2 variant rs2256014 allele the claims encompass treating the subject with the standard dosage amount of the therapeutic. Thus the claims encompass the same treatment for all subjects regardless of genotype.
The next step involves determining if there are any steps or elements that integrate the JE’s into a practical application.
T the step of “performing or having performed a genotyping assay on the biological sample to determine if the patient has a genotype comprising the SYNJ2 variant rs2256014” (claim 23) is a mere data gathering step. Additionally, analyzing DNA to provide sequence information or detect allelic variants is well-understood, routine, and conventional (MPEP 2106.05(d)(II)). Likewise, sequencing at least a portion of the nucleotide sequence of the SYNJ2 genomic nucleic acid molecule is a mere data gathering step (claim 29). Additionally, the step of sequencing nucleic acid sequences is well-understood, routine, and conventional (MPEP 2106.05(d)(II)). Likewise, contacting the sample with a primer, extending the primer, and determining the presence of a nucleotide are mere data gathering steps. Additionally, the step of PCR is well-understood, routine, and conventional (MPEP 2106.05(d)(II)). Amplifying, labeling, and contacting and detecting are mere data gathering steps. Additionally, the step of performing PCR, hybridizing a probe, and amplifying and sequencing are all well-understood, routine, and conventional activities (MPEP 2106.05(d)(II)). As particular reagents are not recited, the claims are also well-understood, routine, and conventional, as the step of determining the level of a biomarker in blood by any means is well-understood, routine, and conventional (MPEP 2106.05(d)(II)).
In instant claims 23, 29, 35 and 43, the step of determining if the patient has a SYNJ2 variant by obtaining or having obtained a sample and performing or having performed a genotyping assay is a mere data gathering step. The steps of analyzing DNA to provide sequence information or detect allelic variants, and determining the level of a biomarker are all well-understood, routine, and conventional activities (MPEP 2106.05(d)(II)).
As currently recited, “administering or continuing to administer to the patient the therapeutic agent” is not a “particular treatment” because no specific treatments are recited. Additionally, the recitation of “administering or continuing to administer” the therapeutic agent is an abstract idea because it is merely the management of human behavior. Other similar processes to this personal behavior include a process that a physician follows when testing a patient or considering historical information when inputting data (MPEP 2106.04(a)(2)). The “continuing to administer” does not require the changing of behavior regardless of the SYNJ2 outcome, and therefore, the “continuing to administer” is similar to merely monitoring a patient (an abstract idea). Likewise, the “standard dosage amount” for both the presence (“the same as or greater than a standard dosage amount”) and absence of SYNJ2 variant does not integrate the administration into a practical application. Regarding claim 29, sequencing at least a portion of the nucleotide sequence of the SYNJ2 genomic nucleic acid molecule is a mere data gathering step. Additionally, the step of sequencing nucleic acid sequences is well-understood, routine, and conventional (MPEP 2106.05(d)(II)). Regarding claim 32, contacting the sample with a primer, extending the primer, and determining the extension product is mere data gathering. The use of PCR to amplify and detect DNA, hybridizing a gene probe, and analyzing DNA to detect allelic variants are all well-understood, routine, and conventional activities (MPEP 2106.05(d)(II)).
In the presence or absence of the SYNJ2 variant rs2256014 allele the claims encompass treating the subject with the standard dosage amount of the therapeutic. Thus the claims encompass the same treatment for all subjects regardless of genotype. Thus the claim is merely generically treating the subject and thus has a different fact pattern than Vanda.
Therefore, the judicial exceptions of the claims 23, 29, 35, 43 are not integrated into a practical application.
Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” No novel technique or inventive concept is added by these claims. Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
It is additionally noted that steps such as “diagnosing”, “predicting”, or “determining” merely recite the natural correlation. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294.
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena and abstract ideas exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Further Dahl (WO2009094713) and Submitted SNP(ss) Details: ss104378217(https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ss.cgi?subsnp_id=ss104378217, 9/10/2008) and Campbell (Hearing Research 226 (2007) 92–103).demonstrates all the steps are routine and conventional.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 23, 29, 35 and 43is/are rejected under 35 U.S.C. 103 as being unpatentable over Dahl (WO2009094713) and Submitted SNP(ss) Details: ss104378217(https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ss.cgi?subsnp_id=ss104378217, 9/10/2008) and Campbell (Hearing Research 226 (2007) 92–103).
With regards to claim 23, Dahl teaches, “0023] Accordingly, the present invention provides a method for identifying a sensory neuropathy in an individual, said method comprising screening for a mutation in a gene or gene expression product associated with the Synaptojanin-2 (Synj2) pathway, which mutation is indicative of a sensory neuropathy or risk of developing same, wherein the presence of the mutation provides an indication of the sensory neuropathy.” (0158). Dahl teaches, “[0103] The present invention further contemplates a method of treating an individual with a sensory neuropathy such as a hearing condition.” Dahl teaches, “0027] The present invention is directed to any mutation in Synj2 (or its gene product) associated with deafness or other sensory including peripheral neuropathy. The present invention is also directed to any mutation in Synj2 [heterozygous or homozygous] (or its gene product) associated with deafness, alone or in combination with any mutation(s) in gene(s) associated with deafness such as connexin26, cdh23, pendrin, myosin7a, usherin or TMCl (or their gene products) or a site of interaction between Synj2 and one or more of connexin (including other connexin genes such as connexin26), cdh23, pendrin, usherin, and/or TMCl or genes associated with deafness or other sensory neuropathy. The present invention also encompasses any mutation in any gene in the phosphoinositide signaling pathway (Synj2 pathway) associated or linked with a sensory including peripheral neuropathy. Examples of genes in addition to those listed above include FIG4, MTMR2, SBF2, FGD4, SPASTI, ZIN and Synjl.” Dahl teaches, “0002] The present invention relates generally to the detection and treatment of a sensory defect including peripheral neuropathy in a mammal, including a human. More particularly, the present invention provides diagnostic assays and therapeutic targets for hearing impairment and other sensory defects including peripheral neuropathies. “
Dahl does not specifically teach rs2256014 or treating with the recited treatments.
However, ss104378217 teaches rs2256014.
Campbell teaches, “Thus far in animal studies, as reviewed in this paper, D-met has shown efficacy in protecting against cisplatin-induced, carboplatin-induced, aminoglycoside induced ototoxicity and permanent noise-induced hearing loss. The additional experiments presented in this paper provide further support for future clinical trials.” (page 100, 1st column, bottom)
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to examine any known mutation in SYNJ2 including the T allele of rs2256014 in subjects with hearing loss and treat the subject with a standard dose of D-methionine. The artisan would be motivated to examine all mutations in SYNJ2 as Dahl claims A method for identifying a sensory neuropathy in an individual, said method comprising screening for a mutation in a gene or gene expression product associated with the Synaptojanin-2 (Synj2) pathway, which mutation is indicative of a sensory neuropathy or risk of developing same, wherein the presence of the mutation provides an indication of the sensory neuropathy. The artisan would be motivated to treat with D- methionine as Campbell teaches it treats numerous types of hearing loss. Thea artisan would have a reasonable expectation of success as the artisan is merely suing known methods to detect known sequences in known genes associated with hearing loss in subjects with hearing loss and treating with known treatments for hearing loss.
With regards to claim 29, ss104378217 teaches rs2256014
With regards to claim 35, Dahl teaches, “According, the genes of the present invention are intended to include coding sequences, intervening sequences and regulatory elements controlling transcription and/or translation. A genetic locus is intended to include all allelic variations of the DNA sequence on either or both chromosomes.(0047).
With regards to claim 43, Dahl teaches, “0060] Accordingly, another aspect of the present invention provides a diagnostic assay for a genetic profile predetermined to be associated with a hearing impairment or other sensory neuropathy, the method comprising obtaining or extracting a DNA sample from cells or a proteomic sample from a subject and screening for or otherwise detecting the presence of a mutation in a gene or a gene product selected from:.”
Response to Arguments
This is a new ground of rejection necessitated by amendment to clarify the mutation and limit the claim to specific treatments.
Summary
No claims are allowed.
Conclusion
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 STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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