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 .
Election/Restrictions
Applicant’s amendment submitted 1/2/2026 is acknowledged.
Amended claims 1-6, 9-14, and 27-28 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 1/2/2026 is in compliance with 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
Response to Arguments
Applicant's arguments filed 1/2/2026 have been fully considered but they are not fully persuasive. Applicant’s amendment to the claims overcame the previous rejection of claim 28 under 35 U.S.C. §112(b), which is hereby withdrawn. However, the previous rejections under 35 U.S.C. §103 and for Nonstatutory Double Patenting are also maintained. Additionally, a new rejection under 35 U.S.C. §112(b) is made. See rejections below.
Removed Rejections
The previous rejection of claim 28 under 35 U.S.C. §112(b) is withdrawn due to amendment.
Maintained Rejections
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous Rejection Maintained) Claims 1-6, 9-14, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Fujimoto, et al. (PGPub US 20090280507 A1, published 11/12/2009; hereinafter referred to as “Fujimoto”) in view of Le Bert, et al. (Nature. 2020 Aug;584(7821):457-462. doi: 10.1038/s41586-020-2550-z. Epub 2020 Jul 15. PMID: 32668444; hereinafter referred to as “Le Bert”) and Crouch, et al. (J Clin Microbiol. 1984 Mar;19(3):388-93. doi: 10.1128/jcm.19.3.388-393.1984. PMID: 6325490; hereinafter referred to as “Crouch”) as evidenced by Poly-L-lysine hydrobromide P1274 (Sigma-Aldrich. 9-page printout. Retrieved on 1/16/2025. Website: ttps://www.sigmaaldrich.com/US/en/product/sigma/p1274; hereinafter referred to as “Sigma-Aldrich P1274”).
Applicant’s arguments have been fully considered but are not persuasive:
Applicant presents the following arguments:
The Examiner has failed to demonstrate prima facie obviousness under 35 U.S.C. §103 because the cited references, alone or in combination, fail to provide a motivation to combine the references with a reasonable expectation of success and even if combined, fail to teach or suggest all of the elements of the presently claimed invention.
As acknowledged by the Examiner (Office Action, pg. 7), the combination of Fujimoto and Le Bert fails to teach or suggest the use of a polycation in antibody binding assays. The Examiner cites Crouch (as evidenced by Sigma-Aldrich) as allegedly teaching the use of poly-L-lysine with a molecular weight above 500 Daltons in ELISA assays. However, the only mention of poly-L-lysine (or any polycation) in Crouch is on page 389, column 1, under the subject heading of: Methods for binding monoclonal antibodies to microtiter plates.
Not only does Crouch as evidenced by Sigma-Aldrich not teach or suggest the claim element of allowing a complex of a first specific binding partner, the sample SARS-CoV-2 nucleocapsid protein, and a second specific binding partner to form in the presence of a diluent solution comprising at least 1 ng/ml of at least one polycation having a molecular weight of about 500 Daltons or greater prior to assessing the signal from the complex, Crouch as evidenced by Sigma-Aldrich explicitly teaches away from this claim element by teaching the removal of the poly-L-lysine before binding the antibody to the microtiter plate. The removal of any poly-L-lysine from the plate is in direct contrast to the methods of the presently claimed invention, which utilize a solution (diluent) comprising the polycation during the formation of a complex of a first specific binding partner, the sample SARS-CoV-2 nucleocapsid protein, and a second specific binding partner.
There is no teaching or suggestion in Crouch as evidenced by Sigma-Aldrich of forming a complex between a first specific binding partner, the sample SARS-CoV-2 nucleocapsid protein, and a second specific binding partner in the presence of poly-L-lysine (or any polycation). In contrast, the present specification (See e.g., Tables A and B) demonstrates that the addition of a diluent solution comprising poly-L-lysine or additional cations with molecular weights over 500 Daltons (See e.g., paragraph [0294]) to the formation of a complex of first specific binding partner, the sample SARS-CoV-2 nucleocapsid protein, and a second specific binding partner unexpectedly increased the sensitivity of the detection of the target.
Accordingly, Applicant submits that the combination of references cited by the Examiner fails to teach or suggest all of the elements of the presently claimed invention. In addition, one of ordinary skill in the art, reading Fujimoto, Le Bert, and Crouch as evidenced by Sigma-Aldrich would not have been led to combine the references with a reasonable expectation of success to arrive at the presently claimed invention because Crouch as evidenced by Sigma-Aldrich teaches away from using a diluent solution comprising polycation in the formation of a complex between a first specific binding partner, the sample SARS-CoV-2 nucleocapsid protein, and a second specific binding partner.
Consequently, Applicant submits that the Examiner has failed to demonstrate prima facie obviousness under 35 U.S.C. §103. Thus, the rejection should be withdrawn.
Applicant’s arguments are not persuasive:
Every element of the claimed invention is disclosed by the cited art. The claims require detecting at least one complex comprising a first specific binding partner, a SARS-CoV-2 nucleocapsid protein, and a second specific binding partner comprising at least one detectable label, wherein the complex is allowed to form in the presence of a diluent solution comprising at least 1 ng/ml of at least one polycation having a molecular weight of about 500 daltons or greater prior to assessing the signal of the complex, wherein the contacting is performed in the diluent solution (claim 1), and independent claim 9 further elaborates that the contacting of a biological sample may be performed either simultaneously or sequentially in any order. The cited references disclose an indirect ELISA where poly-L-lysine hydrobromide, a polycation, is bound to ELISA plates (Crouch), and first and second antibodies both binding specifically to SARS-CoV-1 nucleocapsid, the secondary antibody also being labeled, are used in ELISAs to detect SARS-CoV-1 nucleocapsid (Fujimoto), and that SARS-CoV-1 and SARS-CoV-2 nucleocapsid proteins exhibit high sequence conservation in many regions (Le Bert). In the ELISAs described by Crouch, poly-L-lysine hydrobromide is present in the wells, and indeed in close proximity to the primary antibody-nucleocapsid-secondary antibody complex, because the primary antibody is bound to the plate by poly-L-lysine hydrobromide. The primary antibody-nucleocapsid-secondary antibody complex is formed within the diluent solution of the ELISA plate. It would have been obvious to use poly-L-lysine hydrobromide because antibodies would have adhered to it, and the method’s function is to detect the antibodies.
Motivation is not the only rationale for combining elements taught by the prior art. See MPEP §2143. In the instant rejection, the rationale was that use of poly-L-lysine will adsorb the antibodies to the ELISA plate. The examiner provided a known prior art element useful for the reasons of record in the obvious method, which is that poly-L-lysine adsorbs antibodies to the plate. Motivation is not required for a rejection under 35 U.S.C. §103, it is merely one of multiple possible rationales.
Crouch discloses immunoassays for detecting bovine enteric coronavirus. Applicant is attacking Crouch individually because it did not provide SARS-CoV-2 teachings, however that is not persuasive, as Crouch is used in an obviousness rejection, and so it is not required to supply every element of the claims.
Regarding Applicant’s alleged unexpected result, wherein the addition of a diluent solution comprising poly-L-lysine or additional cations with molecular weights over 500 Daltons (See e.g., paragraph [0294]) to the formation of a complex of first specific binding partner, the sample SARS-CoV-2 nucleocapsid protein, and a second specific binding partner unexpectedly increased the sensitivity of the detection of the target, inclusion of poly-L-lysine for binding antibodies to an ELISA plate would cause the antibody to adsorb to the plate, and would consequently increase sensitivity of the assay. Further, Applicant’s alleged unexpected result is not commensurate in scope with the claimed invention, as Tables A and B are specific to Poly-L-Lysine being the polycation, whereas the claims are drawn to a generic polycation. Additionally, Applicant has provided no statistics to demonstrate that the increased sensitivity is statistically significant.
The claimed invention is rendered obvious by the cited references, as described above. Crouch does not teach away from the claimed invention. The mere fact that excess Poly-L-lysine is removed from the plates prior to the antibody binding to the microtiter plates in Crouch does not teach away from the claimed invention. Indeed, as restated by Applicant, Crouch (page 389, column 1) teaches that poly-L-lysine was allowed to absorb to the plate for 30 minutes. Accordingly, the polycation poly-L-lysine bound to the plate remained present in the microtiter plates for subsequent binding assays.
Double Patenting
(Previous Rejection Maintained) Claims 1-6, 9-14, and 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 13-15, & 23-24 of copending Application No. 18/045,845 in view of Fujimoto and Crouch as evidenced by Sigma-Aldrich P1274 (supra). This is a provisional nonstatutory double patenting rejection.
Applicant’s arguments have been fully considered but are not persuasive:
Applicant presents the following arguments:
Crouch fails to teach or suggest the claim element of forming a complex between a specific binding partner, the sample SARS-CoV-2 nucleocapsid, and a second specific binding partner in a diluent comprising at least 1 ng/ml of a polycation with a molecular weight greater than 500 Daltons, wherein the contacting is performed in the diluent solution. Accordingly, as described above, the claims are not obvious in the ‘845 application in combination with Fujimoto and Crouch as evidenced by Sigma-Aldrich.
Applicant’s arguments are not persuasive:
Contrary to Applicant’s assertion, the Examiner has determined that the combination of references render obvious the claim element of forming a complex between a specific binding partner, the sample SARS-CoV-2 nucleocapsid, and a second specific binding partner in a diluent comprising at least 1 ng/ml of a polycation with a molecular weight greater than 500 Daltons, wherein the contacting is performed in the diluent solution. Accordingly, the NSDP rejection is proper.
New 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.
Claims 1-6 are 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.
Claim 1 recites the limitation "the contacting" in lines 13-14. There is insufficient antecedent basis for this limitation in the claim. It is not clear whether the “the contacting” refers to the binding of a first specific binding partner with the sample SARS-CoV-2 nucleocapsid, the SARS-CoV-2 nucleocapsid protein binding to a second specific binding partner, the polycation binding to one or more of the components, or all of the above. Accordingly, the metes and bounds of the claims are unclear, and the claims are indefinite. Claims 2-6 depend from claim 1 but fail to resolve the lack of clarity, and so are also rejected.
Conclusion
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.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is 571-272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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, Michael Allen can be reached at (571)270-3497. 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.
/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
Prosecution Insights