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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/17/2026 has been entered.
Claim Status
Currently, claims 1, 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 06/17/2026 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 Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims.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 Non-Final.
Withdrawn Rejections
The rejection of claim 6-7 under 35 USC 112(b) is withdrawn in view of the amendment to the claims.
The rejection of claim 1 and 5 under 35 USC 101 is withdrawn in view of the amendment to the claims.
The rejection of claims 1 and 5 under 35 USC 102 as being anticipated by DeRycke et al. (Am J Clin Pathol, 2010, 134 (5): 835-45) is withdrawn in view of the amendment to the claims.
The rejection of claims 6-7 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 (Am J Clin Pathol, 2010, 134 (5): 835-45) is withdrawn in view of the amendment to the claims.
New Grounds of Rejection
Claim Rejections - 35 USC § 112(a) – New Matter
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.
Claim 6-7 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. This is a new matter rejection.
The amendment to claim 6 to recite a “first therapeutic dose” is not supported by the disclosure and raises the issue of new matter. The amendment to claim 7 to recite “a second therapeutic dose of the asthma treatment drug” and “the second therapeutic dose being higher than the first therapeutic dose of the first subject” is not supported by the disclosure and raises the issue of new matter. The specification teaches by using the PCR kit comprising the primer pair consisting of SEQ ID NO 1 and 2, asthma exacerbation and asthma can be diagnosed, thereby administering an appropriate dose of a drug for asthma treatment (see para 97). While the disclosure provides support for administering an appropriate dose of a drug for asthma treatment, the disclosure does not provide support for a first therapeutic dose of an asthma treatment drug and second therapeutic dose of an asthma treatment drug. The specification does not provide support for administering a second therapeutic dose higher than the first therapeutic dose. The specification provides no support for a first and second therapeutic dose.
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 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Birch (J Virology, 2013, vol 87, pp 4756-4761)
Birch teaches RT-PCR of Nectin-4 expression. Birch teaches a Nectin-4 probe that comprises FAM at the 5’ end of the probe and TAMAR at the 3’ (fluorescent label at 5’ end and quencher at 3’ end) (see pg., 4758, 1st column). Birch teaches PCR comprises a DNA polymerase, dNTPs and buffer, thus teaching a RT-PCR kit (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 is rejected under 35 U.S.C. 103 as being unpatentable over Jang (KR101997142B1, cited on IDS, translation provided, pp 1-9, published 3/15/2019) in view of Birch (J Virology, 2013, vol 87, pp 4756-4761).
Jang teaches measuring expression of nectin-4 in subjects with asthma. Jang teaches mRNA level is determined by expression of mRNA in a biological sample to diagnose asthma and includes RT-PCR (see page 3). Jang teaches measuring expression levels of subject before and after asthma treatment, teaches expression level decreases after treatment (see pg. 4), thus teaching administering asthma treatment to a first patient that has an increased expression of nectin-4. Jang teaches nectin-4 levels in plasma were increased in asthmatic subjects compared to those of control subjects (See fig 3). Jang teaches nectin-4 expression by using a PCR kit but does not teach a probe with a fluorescent label at the 5’ end or quencher at the 3’ end.
However, Birch teaches RT-PCR of Nectin-4 expression. Birch teaches a Nectin-4 probe that comprises FAM at the 5’ end of the probe and TAMAR at the 3’ (fluorescent label at 5’ end and quencher at 3’ end) (see pg., 4758, 1st column). Birch teaches PCR comprises a DNA polymerase, dNTPs and buffer, thus teaching a RT-PCR kit (claim 5).
Given the prior art teaches Nectin-4 expression can be detected by RT-PCR and includes a probe with a fluorescent label at the 5’ end and a quencher at the 3’ as taught by Birch, it would have been prima facie obvious to the ordinary artisan at the time the invention as made to substitute one known component, the probe taught by Jang with the probe taught by Birch 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 component of the RT-PCR taught by Jang with a known probe that includes fluorescent labels as taught by Birch to allow for high specificity and accuracy in measuring nectin-4 overexpression.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Jang (KR101997142B1, cited on IDS, translation provided, pp 1-9) in view of Birch (J Virology, 2013, vol 87, pp 4756-4761) as applied to claim 6 above, and further in view of Aoki (Clin. Experimental Allergy, 39, 213-221).
The method of Jang in view of Birch is set forth above. Jang in view of Birch does not teach a second sample and determining exacerbated asthma.
Aoki teaches gene expression analysis of asthma exacerbation and stable condition. Aoki teaches asthma stable group and asthma exacerbation group. Aoki teaches treating subjects with bronchodilator and methylprednisolone (see pg. 214, 2nd column). Aoki teaches that patients with stable and exacerbated asthma have higher levels of gene expression during asthma exacerbation (see pg. 214, 1st column).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include analysis of asthma exacerbated subjects as taught by Aoki in the method of Jang to allow for additional subjects to be diagnosed. The ordinary artisan would have been motivated with a reasonable expectation of success to include subjects with exacerbated asthmas as taught by Aoki in the method of Jan in view of Birch because Jang in view of Birch teaches gene expression analysis of asthma patients and Aoki teaches analysis of both standard and exacerbated asthma patients. The ordinary artisan would have had an expectation of success that expression levels of nectin 4 would increase in exacerbated asthmatic patients as taught by Aoki to allow for diagnosis and treatment of exacerbated asthmatic patients using the method of Jang in view of Birch.
Claims 6 is rejected under 35 U.S.C. 103 as being unpatentable over Bunyavanich (CA3017582A1) in view of Birch (J Virology, 2013, vol 87, pp 4756-4761).
Bunyavanich teaches measuring expression of nasal samples in subjects with asthma and non-asthmatic controls and identifying subject with asthma (see pg. 5). Bunyavanich teaches after identifying subjects with asthma utilizing appropriate therapeutic compositions of the subject with asthma (see pg. 6). Bunyavanich teaches a kit that comprises oligonucleotides directed toward one or more genes in the asthma gene panel, DNA polymerase, buffer and dNTPs (see pg. 20, lines 29-31 cont’d to pg. 21). Bunyavanich teaches the kit includes reagents that comprise nucleotide analogs and labeling moiety (see pg. 21, lines 3-6). Bunyavanich teaches expression level can be determined by TaqMan RT-PCR (see pg. 16). Bunyavanich teaches nectin-4 (PVRL4) expression is increased in asthma patients (See table 2). Bunyavanich teaches nectin-4 expression by using a PCR kit but does not teach a probe with a fluorescent label at the 5’ end or quencher at the 3’ end.
However, Birch teaches RT-PCR of Nectin-4 expression. Birch teaches a Nectin-4 probe that comprises FAM at the 5’ end of the probe and TAMAR at the 3’ (fluorescent label at 5’ end and quencher at 3’ end) (see pg., 4758, 1st column). Birch teaches PCR comprises a DNA polymerase, dNTPs and buffer, thus teaching a RT-PCR kit (claim 5).
Given the prior art teaches Nectin-4 expression can be detected by RT-PCR and includes a probe with a fluorescent label at the 5’ end and a quencher at the 3’ as taught by Birch, it would have been prima facie obvious to the ordinary artisan at the time the invention as made to substitute one known component, the probe taught by Bunyavanich with the probe taught by Birch 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 component of the RT-PCR taught by Bunyavanich with a known probe that includes fluorescent labels as taught by Birch to allow for high specificity and accuracy in measuring nectin-4 overexpression.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Bunyavanich (CA3017582A1) in view of Birch (J Virology, 2013, vol 87, pp 4756-4761) as applied to claim 6 above, and further in view of Aoki (Clin. Experimental Allergy, 39, 213-221).
The method of Bunyavanich in view of Birch is set forth above. Bunyavanich in view of Birch does not teach a second sample and determining exacerbated asthma.
Aoki teaches gene expression analysis of asthma exacerbation and stable condition. Aoki teaches asthma stable group and asthma exacerbation group. Aoki teaches treating subjects with bronchodilator and methylprednisolone (see pg. 214, 2nd column). Aoki teaches that patients with stable and exacerbated asthma have higher levels of gene expression during asthma exacerbation (see pg. 214, 1st column).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include analysis of asthma exacerbated subjects as taught by Aoki in the method of Bunyavanich to allow for additional subjects to be diagnosed. The ordinary artisan would have been motivated with a reasonable expectation of success to include subjects with exacerbated asthmas as taught by Aoki in the method of Bunyavanich in view of Birch because Bunyavanich in view of Birch teaches gene expression analysis of asthma patients and Aoki teaches analysis of both standard and exacerbated asthma patients. The ordinary artisan would have had an expectation of success that expression levels of nectin 4 would increase in exacerbated asthmatic patients as taught by Aoki to allow for diagnosis and treatment of exacerbated asthmatic patients using the method of Bunyavanich in view of Birch.
Maintained Rejections
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 6-7 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. This rejection was previously presented and is rewritten to address the amendment to the claims.
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?
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 comprises the step of “comparing” the expression and “determining” asthma. Neither the specification nor 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 and comprising 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” and “comparing” 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.
Additionally, the claims recite administering a therapeutic dose of an asthma treatment drug to the first subject determined to have asthma (claim 6) and a second therapeutic dose of an asthma treatment drug to the second subject. The administering step occurs when the first or second subject is determined to have asthma. The claim does not require that the subject has asthma and the determining asthma occurs “based on a determination that the expression level…is higher than the expression level of the nectin-4 gene of the normal control group”. There is no active process step of detecting a higher expression level nor does the claim require a detection of a higher expression as the determining step only makes the comparison if the expression is higher or not. Therefore, the administering step is not integrated to the judicial exception
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.
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 page 2 of the remarks mailed 06/17/2026. The response asserts that citing of DeRycke and Boylan is not evidence of widely prevalent and common use. This response has been reviewed but not found persuasive. It was known in the art and widely prevalent in the art to detect nectin-4 expression by PCR, as taught by DeRycky, Boylan, Jang (2018), Jang (KR1020190027399) and Birch (2013). Additionally, the amendment to the claims to include administering therapy is not significantly more than the recited judicial exceptions because this step does not integrate the judicial exception. For these reasons and reasons of record this rejection is maintained.
Conclusion
No claims are allowable.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699
Prosecution Insights