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 .
Status of the Claims
Claims 2-4, 9, and 13 have been cancelled.
Claims 1, 5-8, 10-12, and 14-15 are pending and examined herein.
Priority
This application, filed 02/16/2022, is a 371 of PCT/US2020/039503, filed 06/25/2020, which claims benefit of 62/866,318, filed 06/25/2019, and 63/006,630, filed 04/07/2020. The benefit is acknowledged and the claims herein are treated as having an effective filing date of 06/25/2019.
Withdrawn Rejections/Objections
The rejection of claim 13 under 35 U.S.C. 112(b) is withdrawn in response to Applicant’s cancellation of claim 13.
The rejection of claims 4 and 9 under 35 U.S.C. 112(d) is withdrawn in response to Applicant’s cancellation of claims 4 and 9.
The rejection of claims 1, 2, 6, and 7 under 35 U.S.C. 102 is withdrawn in response to Applicant’s amendment.
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, 5-8, 10-12, and 14-15 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.
Claims 1 and 8 recite the limitation "wherein the biotin binding sites" in step “a)”. There is insufficient antecedent basis for this limitation in the claim. In this case, having biotin binding sites is not considered to be an inherent property of every streptavidin molecule.
Amended 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8, 10-11 and 14-15 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 5,863,740 A1 “INTERFERENCE ELIMINATING AGENT FOR APPLICATION IN IMMUNOASSAYS” (published 01/26/1999, IDS filed 05/06/2025, referred to herein as Engel).
Regarding claim 8, Engel teaches using biotin-saturated streptavidin (col. 3, lines 44-48) by combining the sample with the streptavidin to create a mixture (col. 5, lines 24-30) to mitigate interference (col. 4, lines 64-66) from anti-streptavidin antibodies (col. 5, lines 5-7). Engel teaches preparing the biotin-saturated streptavidin by removing excess free biotin (col. 4, lines 43-49), i.e. eliminating excess biotin before combining the biotin-saturated streptavidin with the sample.
Regarding claim 10, Engel teaches conjugating a non-biotin capture moiety to the streptavidin (col. 3, lines 27-31).
Regarding claim 11, Engel teaches that the streptavidin can be covalently bound by biotin (col. 3, lines 59-60) and/or the non-biotin capture moiety (col. 3, lines 33-36).
Regarding claim 14, Engel teaches that the biotinylation is mediated by non-covalently binding biotin to the streptavidin active sites, i.e. “simple saturation of the binding sites with biotin” (col. 3, lines 44-48).
Regarding claim 15, Engel teaches the use of monomeric streptavidin (Table 3, “SA”).
Amended 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.
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.
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 1 and 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Trambas et al., “Depletion of biotin using streptavidin-coated microparticles: a validated solution to the problem of biotin interference in streptavidin–biotin immunoassays” (published 06/29/2017, IDS filed 04/08/2023, referred to herein as Trambas) in view of US 5,863,740 A1 “INTERFERENCE ELIMINATING AGENT FOR APPLICATION IN IMMUNOASSAYS” (published 01/26/1999, IDS filed 05/06/2025, referred to herein as Engel).
Regarding claims 1, 6, and 7, Trambas teaches a method for mitigating interference in a liquid sample (abstract lines 5-6) comprising combining the sample with magnetic particles (p. 218, col. 1, para. 2, line 27) containing streptavidin (p. 217, col. 2, para. 5, lines 1-2, “streptavidin-coated magnetic microparticle”), mixing the mixture (p. 218, col. 1, para. 2, line 29), and separating the particle from the sample with a magnet (p. 218, col. 1, para. 2, lines 30-32) to collect the sample (p. 218, col. 1, para. 2, lines 39-41).
However, Trambas does not teach the use of streptavidin-coated particles saturated with a minimal excess of biotin (claim 1). Trambas does not teach the conjugation of a non-biotin capture moiety to the streptavidin (claim 5).
Regarding claim 1, Engel teaches using biotin-saturated streptavidin (col. 3, lines 44-48) by combining the sample with the streptavidin to create a mixture (col. 5, lines 24-30) to mitigate interference (col. 4, lines 64-66) from anti-streptavidin antibodies (col. 5, lines 5-7). Engel teaches preparing the biotin-saturated streptavidin by removing excess free biotin (col. 4, lines 43-49), i.e. eliminating excess biotin before combining the biotin-saturated streptavidin with the sample.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the streptavidin-coated particle, as taught by Trambas, with minimal biotin-saturation as taught by Engel. Doing so is considered using known methods for their intended purpose. In this case, Engel teaches using minimally biotin-saturated streptavidin for the removal of interference by anti-streptavidin. An artisan would have a reasonable expectation of success making this modification since modification of streptavidin with biotin is well-known in the art, as taught by Engel (col. 3, lines 61-61), and these molecules are known to capture interference molecules, such as anti-streptavidin antibodies (col. 5, lines 5-7), in immunoassays.
Regarding claim 5, Engel teaches coupling the streptavidin to other high molecular weight molecules “such as BSA or immunoglobulin which are often used to reduce interference in immunoassays” (col. 3. Lines 27-29).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the streptavidin-coated particle, as taught by Trambas, with conjugation of other molecules, as taught by Engel. Doing so would increase the variety of captured interference molecules of the streptavidin-coated particle taught by Trambas, thereby enabling an artisan to reduce interference by other molecules. An artisan would have a reasonable expectation of success making this modification since modification of streptavidin with biotin and other molecules is well-known in the art, as taught by Engel (col. 3, lines 61-61), and these molecules are known to capture interference molecules in immunoassays, as taught by Engel (col. 3, lines 27-30).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Engel in view of EZ-Link NHS-Biotin Reagents Handout by Thermo Scientific (published 2011, referred to herein as Thermo).
Regarding claims 12, Engel teaches the covalent binding of biotin to streptavidin (col. 3, lines 59-62). Engel teaches that the “methods for coupling biotin to the active centre of SA are known to a person skilled in the art” (col. 3, lines 61-62).
However, Engel does not specifically teach the use of any ester-derived biotin for the covalent attachment to streptavidin.
Thermo teaches “esters of biotin are the most popular type of biotinylation reagent” (p. 2, para. 2, line 1). Thermo teaches the use of ester-derived biotins such as NHS-biotin, NHS-LC-Biotin, and NHS-LC-LC-Biotin for the covalent attachment of biotin to proteins (p. 4, lines 1-15).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of covalent attachment of biotin as taught by Engel by using the modified biotin reagents taught by Thermo. Doing so would result in the same end result of covalently-attached biotin-saturated streptavidin molecules; hence, making this substitution would have been readily apparent and deemed to be a mere simple substitution of one known element for another to obtain predictable results (See MPEP 2141(III): Exemplary Rationales that supports a conclusion of obviousness). One skilled in the art would have a reasonable expectation of success because both Engel and Thermo disclose the covalent attachment of biotin to target proteins, i.e. streptavidin, using modified biotin reagents.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of copending Application No. 17/160196 in view of Engel.
Regarding claim 1 of the instant application, ‘196 discloses a method of reducing interference (claim 3, lines 10-11) by combining the sample with a particle comprising streptavidin (claim 3, lines 4-5), mixing the mixture to facilitate binding (claim 3, line 6), and removing the particle from the sample (claim 3, lines 8-9).
However, ‘196 does not disclose the use of streptavidin-coated particles saturated with a minimal excess of biotin.
Engel teaches using biotin-saturated streptavidin (col. 3, lines 44-48) by combining the sample with the streptavidin to create a mixture (col. 5, lines 24-30) to mitigate interference (col. 4, lines 64-66) from anti-streptavidin antibodies (col. 5, lines 5-7). Engel teaches preparing the biotin-saturated streptavidin by removing excess free biotin (col. 4, lines 43-49), i.e. eliminating excess biotin before combining the biotin-saturated streptavidin with the sample.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the streptavidin-coated particle, as disclosed by ‘196, with minimal biotin-saturation, as taught by Engel. An artisan would be motivated and have a reasonable expectation of success making this modification since modification of streptavidin with biotin and other molecules is well-known in the art, as taught by Engel (col. 3, lines 61-61), and these molecules are known to capture interference molecules, such as anti-streptavidin antibodies, in immunoassays, as taught by Engel (col. 3, lines 27-30).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 11/17/2025 have been fully considered but they are not persuasive for the following reasons:
Regarding the rejections of claims 4, 9, and 13 under 35 U.S.C. 112, the rejections have been withdrawn in response to Applicant’s amendment.
Regarding the remarks on the rejection of claims 1, 2, 6, and 7 under 35 U.S.C. 102 by Trambas, the rejection has been withdrawn in response to Applicant’s amendment.
Regarding the remarks on the rejection of claims 8-11 and 14-15 under 35 U.S.C. 102 by Engel, Applicant argues that Engel does not teach “wherein the biotin binding sites on the streptavidin are saturated with minimal excess biotin so that interference due to anti-streptavidin is removed or reduced”.
This argument is not persuasive. As described above under the amended rejection of claim 8 under 35 U.S.C. 102, Engel does teach preparing biotin-saturated streptavidin (col. 3, lines 44-48) by removing excess free biotin (col. 4, lines 43-49), resulting in minimal excess biotin, to remove anti-streptavidin interference (col. 5, lines 5-7).
Regarding the remarks on page 5 on the rejections of claims 3-5 and claims 12-13 under 35 U.S.C. 103, Applicant relies upon the claims as amended without presenting any further argument. As detailed above, claims 5 and 12-13 are rejected under 35 U.S.C. 103 based on the teaching of Engel of preparing biotin-saturated streptavidin (col. 3, lines 44-48) by removing excess free biotin (col. 4, lines 43-49), resulting in minimal excess biotin, to remove anti-streptavidin interference (col. 5, lines 5-7).
Regarding the remarks on the Double Patenting Rejection, the rejection is maintained as amended.
Conclusion
No claims are allowable.
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.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 February 12, 2026
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