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
Currently, claims 1, 3, 5-7 are pending in the instant application. Claims 2, 4 have been canceled. This action is written in response to applicant’s correspondence submitted 12/18/2025. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is Final.
Withdrawn Rejections
The rejection of claim 5 under 35 USC 112(d) is withdrawn in view of the amendment to the claims.
Maintained Rejections
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.
Claim 6-7 is 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. This rejection was previously presented and has been rewritten to address the amendment to the claims.
Claim 6 and 7 recites a method for diagnosing asthma and asthma exacerbation (claim 7) however the method steps only include measuring expression of nectin-4 gene, comparing expression level of nectin-4 gene and determining the asthma. Claim 6 and claim 7 recite the same increase in expression of nectin-4 for diagnosing asthma or asthma exacerbation. Claim 7 requires comparing the subject to subjects with asthma. If nectin-4 in increased in asthma patients (as indicated in claim 6) it is unclear how claim 7 could identify exacerbation when an increase would indicate asthma. There is no indication that there is a higher increase in expression during exacerbation and it is unclear what level would be required to indicate asthma or exacerbation. Because it is unclear what is encompassed by the claims, the claims are indefinite. One of ordinary skill in the art would not be apprised of infringing on the claimed method because the metes and bounds of the claim are indefinite.
Response to Arguments
The response traverses the rejection on pages 1-2 of the remarks mailed 12/18/2025. The response asserts the claims have been amended to address the rejection. While the claims have removed the recitation of providing information for, the claims have not addressed the diagnosis of asthma or exacerbation as claim 7 recites diagnosing asthma or asthma exacerbation and it is unclear how one would distinguish either based on the recited active method step. For these reasons and reasons of record the rejection is maintained.
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 1, 3, 5-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a law of nature and an abstract idea. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, all of the claims are directed to a process.
Step 2A. Is the claim directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exception) and does the claim recite additional elements that integrate the judicial exception into a practical application?
Yes, claims 1-5 are drawn to a composition of matter, which is a law of nature. The claims are drawn to a composition of matter, which is a law of nature. Claims 2-3 recite an agent comprising a primer pair and a primer pair comprising SEQ ID NO 1 and SEQ ID NO 2. SEQ ID NO 1 and 2 encompass naturally occurring nucleic acids. There is no recitation within the claims that indicate that the nucleic acid claimed have any structural or functional characteristics that differ from the naturally occurring nucleic acids because the broadest reasonably interpretation of a detectably moiety includes additional nucleotide sequences.
Claims 6-7 are directed to law of nature/natural phenomenon. Claim 6-7 recites determining asthma of a subject based on the expression level of nectin-4. The recited relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of natural processes.
The claims also recite the judicial exception of an abstract idea and particularly mental processes. Claim 6-7 recites the abstract idea of a mental process. Claim 6-7 recites “a method for providing information” comprising the step of “comparing” the expression, “determining” the asthma. Neither the specification or the claims set forth limiting definition for determining or identifying and the claims do not set forth how determining, comprising, providing is accomplished. The broadest reasonable interpretation of the determining, comprising, providing step is a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information in a database or report regarding expression levels then draws a mental conclusion. Such “determining”. “comprising” and “providing” encompasses process that may be performed mentally and this is an abstract idea.
Having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
The claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions the claims recite measuring expression level of nectin-4 gene using a PCR kit. These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception.
The claimed nucleic acids do not display markedly different characteristic compared to the naturally occurring counterpart and there is no indication that mixing in a composition that the naturally occurring nucleic acid changes the structure, function or other properties of the nucleic acids. According the nucleic acids are a product of nature exception and the claim is directed to at least one exception. This judicial exception is not integrated into a practical application because the claims recite r primers that are naturally occurring and primers detect naturally occurring sequences. The recitation of agent or primer is nothing more than an attempt to generally link the product of nature to a technological environment and is a nominal extra solution component of the claim and does not structurally change the nucleic acid sequence. Many cited prior art references in this record demonstrate the primers are naturally occurring sequences.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? No.
Herein the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something “significantly more” so as to render the claims patent-eligible. The step of measuring expression level of nectin-4 gene merely instructs a scientist to use well established, routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. With regard to claims 1-5, besides the nucleic acids, the claims recite a kit in the preamble. At the time the invention was made, a kit or reaction mixture was well-established, routine and conventional. Additionally where a kit is recited at such a high level of generality it does not meaningfully limit the claim. Thus the claims as a whole does not amount to significantly more than each “product of nature” by itself and the claims do not qualify as eligible subject matter.
The step of measuring expression level in a sample isolated from a subject constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name particular biomarkers, nectin-4, whose level is to be determined however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such determining such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions. It is noted that the claimed primers were well known and routine in the art, as taught by DeRycke (Am J Clin Pathol, 2010, 134; 835-845) and Boylan (Oncotarget, 2017, vol 8, pp9717-9738)
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The prior art of DeRycke (Am J Clin Pathol, 2010, 134; 835-845) and Boylan (Oncotarget, 2017, vol 8, pp9717-9738) teaches RT-PCR detection of expression of nectin-4 gene using primers consisting of instant SEQ ID NO 1 and 2.
Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine expression of nectin-4 in biological samples including saliva samples. The claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
Response to Arguments
The response traverses the rejection on pages 2-5 of the remarks mailed 12/18/2025. The response asserts the claim is not directed to a composition of matter but drawn to measuring mRNA level by a specific agent such as a primer pair, probe, LNA or antisense nucleotide that specifically binds to nectin-4- gene and therefore patent eligible. This response has been reviewed but not found persuasive. The recitation of a probe or primer pair that specifically binds to nectin-4 gene is not significantly more than the recited law of nature. Specifically for claims 1, 3, 5 the claims are drawn to a product and the recitation of primer pair or probe that specifically binds nectin-4 gene is not markedly different than the naturally occurring sequence of nectin-4 gene. Additionally primer pair, probe, LNA and anti-sense does not add significantly more to the judicial exception for claims 6-7 as these were well known, routine, and conventional in the art.
The response asserts that the features of the application provide improvements to measure mRNA level of nectin-4 gene by using the agent artificially synthesized or engineered with specific chemical and structural features. The response asserts the LNA are not found in natural RNA, the claimed probe and antisense are synthetic labeled and engineered for target specific binding rather than naturally occurring molecules. The response asserts that these agents are crucial for generating a fluorescent signal to allow quantitative measurement of amplified DNA and therefore claim 1 is patent eligible. This response has been reviewed but not found persuasive. The claims do not recite a probe with a specific label and the primers, probe, and antisense are naturally occurring sequences that do not have a markedly different sequence than the naturally occurring sequence. With regard to the recited improvements, the specification nor the claims provide details of an unconventional solution and judicial exception cannot provide the improvement, the improvement can be provided by one or more additional elements (see MPEP 2106.05(a)). An example that the courts have indicated may not be sufficient to show an improvement to technology includes ii. Using well-known standard laboratory techniques to detect enzyme levels in a bodily sample such as blood or plasma, Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1355, 1362, 123 USPQ2d 1081, 1082-83, 1088 (Fed. Cir. 2017) (see MPEP 2106.05(a)). In the instant case the additional elements of the claim are well understood, routine, and conventional in the art and do not amount to an unconventional solution.
The response asserts the PCR kit can diagnose asthma or asthma exacerbation by measuring mRNA level of the nectin-4 gene. The response asserts because diagnosis is not only asthma but asthma exacerbation, it allows administration of an appropriate dose of a drug for asthma treatment. The response asserts that due to using an agent capable of measuring mRNA level of nectin-4 gene due to the structural features as described so that not only asthma but asthma exacerbation can be diagnosed so that appropriate dose of a drug can be administered. This response has been reviewed but not found persuasive. The claims do not recite or include administering appropriate dose of a drug. The claims recite only conventional, well-understood, and routine steps. Specifically, it was routine, well-understood and conventional to measure mRNA level of nectin-4 gene as taught by DeRycke. Because the additional elements recited within the claims are well known to detect mRNA level of nectin-4 gene using probe and primer pair, the additional elements do not result in an unconventional solution. For these reasons and reasons of record this rejection is maintained.
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, 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by DeRycke et al. (Am J Clin Pathol, 2010, 134 (5): 835-45).
DeRycke teaches RT-PCR. DeRycke teaches nectin-4 forward and reverse primer. The forward primer consists of SEQ ID NO 1 and the reverse primer consists of SEQ ID NO 2 (agent for measuring mRNA level of nectin04 gene) (primer pair, claim 2-3). DeRycke teaches a RT-PCR access kit (claim 4). The RT-PCR access kit comprises DNA polymerase, dNTPs and buffer (see RT-PCR). DeRycke teaches qRT-PCR and teaches a buffer, primer, and SYBRGreen supermix (see quantitative RT-PCR)(claim 5).
The recitation of “kit” in claims 1-5 is not defined in the specification and is given its broadest reasonable interpretation to include a plurality of items grouped together. Therefore DeRycke teaches a PCR kit and teaches a qRT-PCR kit that comprises dNTPs, DNA polymerase, and buffer.
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.
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.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Jang (J Allergy Clin Immunol, 2018, AB74, cited on IDS) in view of DeRycke et al. (Am J Clin Pathol, 2010, 134 (5): 835-45).
Jang teaches nectin-4 is increased in lung tissue of subjects with asthma. Jang teaches nectin-4 levels in plasma were decreased in non-treated asthmatic subjects compared to those of control subjects. Jang teaches nectin-4 expression by western blotting (see abstract). Jang does not teach measuring expression level of nectin-4 using a PCR kit.
However, DeRycke teaches using RT-PCR kit to detect expression levels of nectin-4. DeRycke teaches a PCR kit and teaches primers for detecting expression of nectin-4. DeRycke further teaches western blotting of Nectin-4 expression (see PCR, pg. 838). DeRycke teaches both mRNA and protein expression of Nectin-4 is overexpressed (see results, pg. 839).
Given the prior art teaches Nectin-4 expression can be detected by PCR or western blot, as taught by DeRycke, it would have been prima facie obvious to the ordinary artisan at the time the invention as made to substitute one known method, protein expression analysis as taught by Jang with PCR and mRNA expression as taught by DeRycke in order to achieve the predictable result of detecting mRNA expression of Nectin-4 in asthma patients. The ordinary artisan would have been motivated to substitute a known method, western blot expression analysis as taught by Jang with nectin 4 expression by PCR as taught by DeRycke because DeRycke teaches expression analysis of both western blot and PCR amplification and teaches both methods predictably measured nectin-4 overexpression, as such the ordinary artisan would have had an expectation of success.
Response to Arguments
The response traverses the rejections on pages 5-7 of the remarks mailed 12/18/2025. The response asserts that none of the cited references disclose an agent for measuring the mRNA levels of nectin-4 gene is at least one selected from the group consisting of a primer pair, probe, LNA and antisense nucleotide that specifically binds to the nectin-4 gene. The response asserts that DeRyckey teaches RT-PCR and nectin-4. The response provides a passage from DeRycke and asserts that DeRyckey fails to disclose a probe, LNA and antisense nucleotide that specifically binds to nectin-4 gene. The response further asserts that DeRycke using SYBR green assay to perform quantitative RT-PCR and is different from the claimed probe-based method. This response has been reviewed but not found persuasive. The claim recites selected from the group…primer pair, probe, LNA and antisense nucleotide. Additionally the claims are not limited to any probe-based method or require any specific probe method for measuring mRNA levels. The claims recite in the alternative agents for measuring mRNA expression which include, primer pair, probe, LNA or antisense nucleotides. The claims do not recite or require any probe detection method and the claims are not limited to LNA or antisense nucleotides for measuring mRNA. As such DeRycke teaches both a primer pair and probe that specifically binds to nectin-4 gene. The primers of DeRycke are both primer pairs and probes that specifically bind to nectin-4 gene.
The response asserts Jang does not cure deficiency of DeRycke as the cited references alone or in combination do not teach or suggest an agent for measuring the mRNA level of the nectin04 gene is at least one selected from the group consisting of a primer pair, probe, LNA, and antisense nucleotide that specifically binds to the nectin-4 gene. This response has been reviewed but not found persuasive. Jang was not cited to teach measuring mRNA level of nectin-4 gene. DeRycke teaches measuring mRNA level of nectin-4 gene by a probe and primer pair as such DeRycke teaches the claimed limitations. For these reasons and reasons of record this rejection is maintained.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699