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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/07/2026 has been entered.
Status of the Claims
Claims 2-4, 9, and 13 have been cancelled.
Claims 1, 5-8, and 14 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Withdrawn Rejections/Objections
The rejection of claims 1, 5-8, 10-12, and 14-15 under 35 U.S.C. 112(b) is withdrawn in response to Applicant’s amendment.
The rejection of claim 1 under Double Patenting has been withdrawn in response to the abandonment of application 17/160,196.
The rejection of claims 8, 10-11, and 14-15 has been withdrawn in response to Applicant’s amendment.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 and 5-7 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.
The term “minimal excess” in claim 1 is a relative term which renders the claim indefinite. The term “minimal excess” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what amount of excess biotin would be considered embodied by the claim or how to determine the threshold wherein a method would be determined to include too much biotin.
The term “predominately monomeric” in claim 1 is a relative term which renders the claim indefinite. The term “predominately monomeric streptavidin” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how much monomeric streptavidin is required to be present in order to be considered predominant. Further, it is unclear whether the monomeric streptavidin is required to be considered predominant in comparison to other forms of streptavidin, the number of other components in or on the particle, or some other measure.
Claims 5-7 are rejected for being dependent upon rejected claim 1.
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. Engel teaches the use of monomeric streptavidin (Table 3, “SA”).
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).
Claims 8 and 14 are 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 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. 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). Engel teaches conjugating the QSAv with an additional non-biotin capture moiety (col. 3, lines 27-31).
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).
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.
Response to Arguments
Applicant's arguments filed 04/07/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on the rejection of claims 8, 10-11, and 14-15 under 35 U.S.C. 102, the rejection has been withdrawn in response to Applicant’s amendment.
Regarding the remarks on the rejection of claims 1 and 5-7 under 35 U.S.C. 103, Applicant argues that the rejection should be withdrawn in response to Applicant’s inclusion of the limitation of claim 15 into claim 1.
This argument is not persuasive. Claim 15 was not an allowable claim and the inclusion of the limitation of claim 15 into claim 1 does not render it allowable. See the rejection of claim 1, above, under 35 U.S.C. 103.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 24, 2026
