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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/23/2026 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or
under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of
PCT/US2021/026927 filed 04/12/2021 which claims benefit of Application No. 63/008,472 filed
04/10/2020. Based on the filing receipt, the effective filing date of this application is April 10,
2020 which is the filing date of Application No. 63/008,472 from which the benefit of priority is
claimed.
Status of Claims
Claims 2-5, 8-9, 11, and 13 are cancelled.
Claims 1, 6-7, 10, 12, 14-23 are pending and examined herein.
Withdrawn Rejections
The rejection of claim 10 on the grounds of 35 U.S.C. 112(b) has been withdrawn, necessitated by amendments filed 04/23/2026 which amended claim 10 to depend on independent claim 1.
The rejection of claims 1, 6-7, 10, 12, 14-23 on the grounds of 35 U.S.C. 103 has been withdrawn, necessitated by amendments filed 04/23/2026 which amended claim 1 to include biotin depletion by 90%. New rejections are discussed below.
The rejection of claims 11 and 13 on the grounds of 35 U.S.C. 103 has been withdrawn, necessitated by amendments filed 04/23/2026 which cancelled claims 11 and 13.
The rejection of claims 1, 6, 10-11, and 13-23 on the grounds of nonstatutory double patenting as being unpatentable over copending Application No. 17/160,196 has been withdrawn, due to the abandonment of the copending application.
New Rejections/Objections
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites, “combining a biological sample with a second particle comprising a streptavidin capture moiety for a biotin interference”. The claim should recite, “combining a biological sample with a second particle comprising a streptavidin capture moiety for .
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1, 6-7, 10, 12, 14-23 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
Independent claim 1 is directed to a method comprising “a capture moiety”. The application’s specification discloses, “As referred to herein, "capture moiety" is selected from the group consisting of an antibody, a binding fragment of an antibody, a IgG, a IgM, a IgA, IgE, IgD a receptor, a ligand of a receptor, a hormone, a receptor of a hormone, an enzyme, a substrate of an enzyme, a single stranded oligonucleotide, a single stranded polynucleotide, a double stranded oligonucleotide, a double stranded polynucleotide, an antigen, a peptide, a polymer, an aptamer, and a protein” (see para. [00144]). The claims impose no restriction on the size of the capture moiety.
The scope of the claims therefore covers methods comprising a large genus of capture moieties characterized by substantial variability.
Regarding the predictability or unpredictability in the art, the capture moieties as claimed include antibodies. Antibodies can often be functionally promiscuous or multi-specific which can lead to antibodies binding to more than one antigen, as evidenced by Jain (“Antibody specificity and promiscuity”, published 2019-02-05). In addition, the capture antibodies as claimed include aptamers. Liu (“The specificity and selectivity of aptamer depends on the binding epitope: insights from aptamer Hislxl-2a”, published 2026-06-22) discloses, “due to their structural diversity and the still-limited understanding of their recognition mechanisms, they continue to face challenges related to specificity and selectivity in practical applications” (see, p. 1, under “ABSTRACT”). Due to multi-specificity and challenges related to specificity, antibodies and aptamers are capture moieties with a level of unpredictability that requires the applicant to provide evidence that they have considered a sufficient number of capture moieties.
The specification does not disclose the reduction to practice of a sufficient number of specific capture moieties having the necessary functional characteristics. The specification suggests art-recognized methods of using capture moieties and provides prophetic examples. See “Example 4” of the applicant’s specification. Examples 1-3 and 5-6 of the applicant’s specification reduced to practice the following capture moieties: streptavidin, TSH, PTH, SARS-CoV-2 S1-RBD and S1-NTD, rabbit IgG, human IgA, human IgG, and human IgM. However, considering the vast genus of capture moieties claimed by the invention, including aptamers which are not reduced to practice, there is insufficient disclosure of capture moieties falling within the claimed genus.
The disclosure of general methods that use capture moieties is insufficient to describe the claimed broad genus of capture moieties. The Federal Circuit addressed an analogous situation in University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004), finding that disclosure of “assays for screening compounds, including peptides, polynucleotides, and small organic molecules to identify those that inhibit the expression or activity of the PGHS-2 gene product,” did not satisfy the written description requirement for claims requiring administration of a “compound that selectively inhibits PGHS-2.” Rochester, 119 F.3d at 918, 927; see also Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company, 598 F.3d 1336, 1344 (Fed. Cir. 2010) (recognizing distinction between requirements for written description and enablement).
Furthermore, there is also no disclosure of any partial structure common to the members of the genus of capture moieties that would correlate with function (in this case, the claimed function of selectively binding to the “antigen-specific antibody”).
The importance of structure/function correlations was recently highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centocor Biologics, App. No. 2013-1338, -1346 (Fed. Cir., July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).
There is no partial structure or other identifying characteristics disclosed, common to the members of the genus of capture moieties having sufficiently high binding affinity, that would allow one skilled in the art to envision that Appellant has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus.
For all of these reasons, the specification does not demonstrate possession of the entire genus of capture moieties having the claimed functional characteristics of specifically binding to an antigen-specific antibody.
Claims 6-7, 10, 12, 14-23 depend on independent claim 1 and are, therefore, rejected under 35 U.S.C. 112(a) as well.
Claim Rejections - 35 USC § 103
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.
Claims 1, 6-7, 12, 14-16, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Stayton (US 20110003392 A1, published 2011-01-06, cited in IDS filed 04/07/2023) in view of Soldo (US 20180292394 A1, published 2018-10-11, cited in PTO-892 dated 08/27/2025), Koenig (US 20170096479 A1, published 2017-04-06, cited in IDS filed 04/07/2023), Rowe (“Detection of Antibody to Avian Influenza A (H5N1) Virus in Human Serum by Using a Combination of Serologic Assays”, published 1999-04-01, cited in PTO-892 dated 08/27/2025), and Favresse (“Neutralization of biotin interference: preliminary evaluation of the VeraTest Biotin™, VeraPrep Biotin™ and BioT-Filter®”, published 2020-02-24). The following 103 rejections have been modified, necessitated by amendments filed 04/23/2026.
Stayton teaches a method for isolating an antigen-specific antibody from a biological sample, the method comprising: a) combining the sample with a first particle comprising a capture moiety for the antigen-specific antibody to provide a mixture; b) mixing the mixture to provide particle complexes to the antibody; and c) separating the particle from the biological sample; thereby isolating the antibody from the biological sample, as in claim 1 (see, e.g., method for isolating proteins from a biological sample – para. [0168]: “The method of the invention achieves homogeneous capture, labeling, purification, enrichment, and high-sensitivity detection of protein biomarkers from plasma in a non-instrumented and readily multiplexed format”; the protein is an antibody – para. [0101]: “In one embodiment, the diagnostic target is an antibody and the capture moiety is an antigen”; combining the sample with a first particle comprising a capture moiety for the antigen-specific antibody to provide a mixture – para. [0013]: “contacting a liquid medium to be tested for the presence of a diagnostic target with a plurality of stimuli-responsive particles”; mixing the mixture to provide particle complexes to the antibody – para. [0013]: “wherein the plurality of stimuli-responsive particles is contacted with the liquid medium for a pre-determined period of time sufficient to effect binding of the diagnostic target”; separating the particle from the biological sample; thereby isolating the antibody from the biological sample – para. [0066]). It is understood that plasma is equivalent to a biological sample.
Stayton teaches the method further comprises comparison of a signal associated with the target with a standard curve for the target, as in claim 7 (see, e.g., para. [0214]: “The integrated green channel pixel intensity at the anti-PfHRP2 test line of the lateral flow membranes was measured as a function of recombinant biomarker concentration to generate the standard curve”).
Stayton teaches wherein the capture moiety comprises human and/or non-human animal immunoglobulin, as in claim 12 (see, e.g., para. [0102]: “A capture molecule (e.g., capture moiety) and a target molecule (e.g., diagnostic target) form a binding pair […] The exemplary proteins include antibodies (monoclonal, polyclonal, chimeric, single-chain or other recombinant forms)”).
Stayton teaches an enriched antibody made by the method of claim 1, as in claim 15 (see, e.g., para. [0100]). In paragraph [00102] on page 21, the applicant’s specification defines enrichment “as the complete or partial particle capture and binding of target analyte(s) or biomarker to the particles from a biological sample”. The complete or partial particle capture and binding of target analyte(s) to the particles from a biological sample is recited by Stayton above.
Stayton teaches the antigen-specific antibody is a pathogen-specific antibody, as in claim 16 (see, e.g., para. [0100]).
Stayton teaches the antigen-specific antibody is against a foreign protein, as in claim 22 (see, e.g., para. [0100]). It is understood that viral proteins are foreign proteins.
Stayton teaches the antigen-specific antibody is a human antibody, as in claim 23 (see, e.g., para. [0100]). It is understood that the antibodies against hepatitis B virus, hepatitis C virus, and the AIDS virus are human antibodies.
Stayton fails to teach the method further comprises dissociating the antigen-specific antibody from the particle by cleavage or elution of the antibody from the particle, as in claim 1. Stayton fails to teach the method further comprises subjecting the released antibody to characterization, as in claim 1. Stayton fails to teach the method wherein the first and/or second particle is provided as a lyophilized product, as in claim 14.
However, Soldo teaches dissociating the antigen-specific antibody from the particle by elution and characterizing the released antibody, as in claim 1 (see, e.g., para. [0116]: “A method of measuring the amount, mass, molarity, concentration, or yield of targeted biomarker captured and enriched by the microparticulate binding surface whereby the biomarker is eluted”).
Stayton and Soldo are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the elution technique of Soldo in the assay of Stayton. An artisan would be motivated to do so because the sample enrichment of Soldo can be used to support the LC-MS/MS Diagnostics market when the elution of the target is paired with LC-MS/MS analysis (see, e.g., Soldo, para. [0053]; and para. [0059]). LC-MS/MS is incompatible with the particles of the Stayton assay unless the targets are eluted from the particles before LC-MS/MS analysis. The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 14, Soldo teaches the method wherein the first and/or second particle is provided as a lyophilized product (see, e.g., para. [0062]: “the microparticles can be lyophilized”).
Stayton and Soldo are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the lyophilization technique of Soldo in the assay of Stayton. An artisan would be motivated to do so because lyophilization is a well-known technique in the art to preserve biological reagents. An artisan would expect the reagents of Stayton to be compatible with lyophilization because of the reagents’ similarity to the reagents of Soldo. The artisan would have a reasonable expectation of success based on the disclosures given.
Stayton and Soldo teach as set forth above. They also teach depleted samples can be subsequently analyzed with immunoassays (see, e.g., Soldo, para. [0060]). But, Stayton and Soldo fail to teach the method wherein the characterization comprises forming a complex with an anti-immunoglobulin conjugated to a detectable label, as in claim 1. Stayton and Soldo fail to teach the detectable label is a fluorescent label, as in claim 6. However, in a patent application on methods of identifying antibody variants with improved properties, Koenig rectifies these deficiencies.
Koenig teaches the method wherein the characterization comprises forming a complex with an anti-immunoglobulin conjugated to a detectable label, specifically a fluorescent label, as in claims 1 and 6 (see, e.g., forming a complex with an anti-immunoglobulin conjugated to a detectable label - para. [0380]: “The second antibody may itself be labeled with a detectable moiety (direct sandwich assays) or may be measured using an anti-immunoglobulin antibody that is labeled with a detectable moiety (indirect sandwich assay)”; fluorescent label – para. [0376]: “ Labels include, but are not limited to, labels or moieties that are detected directly (such as fluorescent, chromophoric, electron-dense, chemiluminescent, and radioactive labels)”).
Stayton, Soldo, and Koenig are analogous to the field of the claimed invention because they are all in the field of immunoassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the characterization of Koenig in the assay of Stayton as modified by Soldo. An artisan would be motivated to do so because Koenig discloses that the antibody “may be measured using an anti-immunoglobulin antibody that is labeled” and “detected directly” (see para. [0380] and para. [0376]). Koenig also discloses that the technique is a “known assay method” (see para. [0378]). An artisan would recognize that the known measurement technique of Koenig would be useful for measuring the antibodies bound by the assay of Stayton as modified by Soldo. The artisan would have a reasonable expectation of success based on the disclosures given.
Stayton, Soldo, and Koenig teach as set forth above, but fail to teach the anti-immunoglobulin antibody is not isotype specific, as in claim 1. However, in a journal article on detection of antibody to avian influenza virus in human serum, Rowe rectifies this deficiency.
Rowe teaches western blotting for detection of antibodies from a biological sample with anti-immunoglobulin antibodies that are not isotype specific, as in claim 1 (see, e.g., p. 938, col 2, under “H5N1 Western blotting.”: “Horseradish peroxidase-conjugated goat anti-human IgG, IgM, or IgG-IgA-IgM (Kirkegaard & Perry Laboratories, Inc.) was added to each well”). It is understood that the Horseradish peroxidase-conjugated goat anti-human IgG-IgA-IgM is not isotype specific because it detects three different isotypes.
Stayton, Soldo, Koenig, and Rowe are analogous to the field of the claimed invention because they are all in the field of immunoassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the anti-immunoglobulin antibody of Rowe into the assay of Stayton as modified by Soldo and Koenig. The artisan would be motivated to use the anti-human immunoglobulin antibody of Rowe because of the ability to combine the measurement of three different types of immunoglobulins, i.e. IgG, IgA, and IgM in a sample (see, e.g., p. 940, col. 2, under “TABLE 3”). The artisan would have a reasonable expectation of success based on the disclosures given.
Stayton, Soldo, Koenig, and Rowe teach as set forth above. They also teach pre-treating samples with particles to deplete interference (see, e.g., Soldo, para. [0059]). However, they fail to teach the method further comprises a pretreatment with a) combining a biological sample with a second particle comprising a streptavidin capture moiety for biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted comprising a biotin amount reduced by 90% , as in claim 1.
However, Favresse teaches a) combining a biological sample with a second particle comprising a streptavidin capture moiety for biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted comprising a biotin amount reduced by 90% , as in claim 1 (see, e.g., p. e132, under “Table 1:”, under “Streptavidin beads, ng/mL mean elimination rate, %”, row “Mean”: “99.95”, and p. e130, col. 2, para. 3: “We used the streptavidin beads treatment adapted from the procedure described by Piketty et al. [6]. Briefly, five volumes of streptavidin reagent (0.72 mg/mL in HEPES-bovine serum albumin buffer, pH 7.4; Roche Diagnostics) were spun for 10 min at 3500 rpm and the supernatant was carefully discarded. One volume of serum (1 mL) was then added on the streptavidin particles pellet, incubated and shaken for 1 h at RT at 36 rpm (rotamix, CAT, Ingenieurbüro, GmbH). Beads were then removed by centrifugation for 10 min at 3500 rpm”).
Stayton, Soldo, Koenig, Rowe, and Favresse are analogous to the field of the claimed invention because they are all in the field of immunoassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the biotin interference removal of Favresse into the assay of Stayton as modified by Soldo, Koenig, and Rowe. An artisan would have been motivated to do so because Favresse discloses, “Interferences of biotin with immunoassays is a real safety concern, as the consequences potentially impact medical decision and patient care. Convenient techniques exist to detect and overcome the biotin interference and could be available in almost all clinical laboratories [13]. Our study shows that the streptavidin beads treatment and the VeraPrep Biotin™ appeared to be the best solution to efficiently deplete patients’ samples from biotin” (see, p. e133, col. 1, para. 4). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Stayton (cited above), Soldo (cited above), Koenig (cited above), Rowe (cited above), and Favresse (cited above), as applied to claims 1, 6-7, 12, 14-16, and 22-23 above, and further in view of Durbin, et al. (“Development of a Multiplex Glycan Microarray Assay and Comparative Analysis of Human Serum Anti-Glycan IgA, IgG, and IgM Repertoires”, published 2018-12-07, cited in PTO-892 dated 08/27/2025). The following 103 rejections have been modified, necessitated by amendments filed 04/23/2026.
Stayton, Soldo, Koenig, Rowe, and Favresse teach as set forth above, but they fail to teach the anti-immunoglobulin antibody comprises at least two of anti-IgA, anti-IgG, and anti-IgM, each conjugated to a distinct label, as in claim 10. However, in a journal article on a multiplex assay for analysis of human serum anti-glycan antibodies, Durbin rectifies these deficiencies.
Durbin teaches multiple isotype-specific anti-immunoglobulin antibodies used to measure IgA, IgG, and IgM in a multiplex assay with a distinct label conjugated to each anti-immunoglobulin, as in claim 10 (see p. 16882, under “ABSTRACT”).
Stayton, Soldo, Koenig, Rowe, Favresse, and Durbin are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the isotype-specific anti-immunoglobulin antibodies with distinct labels of Durbin into the assay of Stayton as modified by Soldo, Koenig, Rowe, and Favresse. The artisan would have been motivated to do so because Durbin discloses that the isotype-specific anti-immunoglobulin antibodies with distinct labels allows for a “multiplex assay to simultaneously detect IgA, IgG, and IgM” (see p. 16882, under “ABSTRACT”). The artisan would have a reasonable expectation of success based on the disclosures given.
Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Stayton (cited above), Soldo (cited above), Koenig (cited above), Rowe (cited above), and Favresse (cited above), as applied to claims 1, 6-7, 12, 14-16, and 22-23 above, in view of Okba (“SARS-CoV-2 specific antibody responses in COVID-19 patients”, published on medRxiv 2020-03-20, cited in PTO-892 dated 08/27/2025). The following 103 rejections have been modified, necessitated by amendments filed 04/23/2026.
Stayton, Soldo, Koenig, Rowe, and Favresse teaches as set forth above, but fail to teach the antigen-specific antibody is specific to the pathogen SARS-CoV-2, as in claim 17. Stayton, Soldo, Koenig, Rowe, and Favresse also fail to teach the capture moiety is a spike protein, specifically the S1 subunit domain, as in claims 18 and 19. However, in a medRxiv journal article on serological tests for COVID-19 patients, Okba rectifies these deficiencies.
Okba teaches measuring pathogen-specific antibodies for SARS-CoV-2 using the S1 domain of the SARS-CoV-2 spike protein as the capture moiety, as in claims 17-19 (see, e.g., p. 5, under “ELISA”, para. 1).
Stayton, Soldo, Koenig, Rowe, Favresse, and Okba are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of Stayton as modified by Soldo, Koenig, Rowe, and Favresse to detect antibodies to SARS-CoV-2 using the S1 domain of the SARS-CoV-2 spike protein as the capture moiety such as taught by Okba. An artisan would be motivated to detect antibodies to SARS-CoV-2 because Okba discloses, “Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies” (see p. 1, under “Abstract”). A skilled artisan would have been motivated to use the S1 domain of the SARS-CoV-2 spike protein as the capture moiety as taught by Okba because Okba discloses, “S1 is a [sic] more specific than S as an antigen for SARS-CoV-2 serological diagnosis” (see p. 6, para. 4). Okba further discloses, “the specificity of S1 as an antigen for SARS-CoV-2 serology was further supported by the fact that 87-100 % of the cohort A-C sera included in this study were seropositive for the endemic HCoVs as determined by the S1 protein microarray” (see p. 7, para. 1). The artisan would have a reasonable expectation of success based on the disclosures given.
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Stayton (cited above), Soldo (cited above), Koenig (cited above), Rowe (cited above), and Favresse (cited above), as applied to claims 1, 6-7, 12, 14-16, and 22-23 above, in view of Lu, et al. (“Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer”, published 2008-02-27, cited in PTO-892 dated 08/27/2025). The following 103 rejections have been modified, necessitated by amendments filed 04/23/2026.
Stayton, Soldo, Koenig, Rowe, and Favresse teach as set forth above, but fail to teach the antigen-specific antibody is an autoantibody, specifically a tumor-specific autoantibody, as in claims 20 and 21. However, in a review of immunity directed against tumor-associated antigens as biomarkers for early diagnosis of cancer, Lu rectifies these deficiencies.
With respect to claims 20 and 21, Lu teaches detecting autoantibodies in human serum, wherein the autoantibodies are tumor-specific autoantibodies (see, e.g., p. 1388, under abstract; p. 1391, under “Figure 1.”; and p. 1991, under “Detecting Serum Antibody Response to a Panel of TAAs”, para. 1).
Stayton, Soldo, Koenig, Rowe, Favresse, and Lu are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of Stayton as modified by Soldo, Koenig, Rowe, and Favresse to detect autoantibodies in human serum, wherein the autoantibodies are tumor-specific autoantibodies as taught by Lu. An artisan would be motivated to do so because Lu discloses, “It is now possible to potentially harness the immune response elicited by cancer growth as a potential diagnostic tool. Humoral immunity, or the development of autoantibodies against tumor-associated proteins, may be used as a marker for cancer exposure. Unlike circulating proteins that are shed by bulky tumors, serum autoantibodies are detectable even when antigen expression is minimal” (see p. 1388, under abstract). The artisan would have a reasonable expectation of success based on the disclosures given.
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.
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Claims 1, 6, and 10, 12, 14-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18, 40, and 43 of U.S. Patent No. 10,948,484 (referred to as ‘484 henceforth) in view of Okba, Soldo, Koenig, Durbin, Rowe, and Favresse (all cited above). The following double patenting rejections have been modified, necessitated by amendments filed 04/23/2026.
With respect to claims 1, 15-19, 22, and 23, ‘484 teaches a method for isolating a biomarker from a biological sample, the method comprising: a) combining the sample with a first particle comprising a capture moiety for the biomarker to provide a mixture; b) mixing the mixture to provide particle complexes to the biomarker; and c) separating the particle from the biological sample; thereby isolating the biomarker from the biological sample (see, e.g., claim 17 of ‘484). In paragraph [00102] on page 21, the applicant’s specification defines enrichment “as the complete or partial particle capture and binding of target analyte(s) or biomarker to the particles from a biological sample”. The complete or partial particle capture and binding of target analyte(s) to the particles from a biological sample is recited by ‘484 above.
With respect to claim 1, ‘484 teaches the method further comprises a pretreatment with a) combining a biological sample with a second particle comprising a capture moiety for an interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the interference; c) removing or eliminating the second particle complexes to provide a depleted solution (see, e.g., claim 1 of ‘484).
With respect to claim 12, ‘484 teaches wherein the capture moiety comprises human and/or non-human animal immunoglobulin (see, e.g., claim 20 of ‘484).
With respect to claim 1, ‘484 fails to teach the method further comprises dissociating the antigen-specific antibody from the particle, as in claim 1. ‘484 fails to teach the dissociating comprises cleavage or elution of the antibody from the particle, as in claim 1. ‘484 fails to teach the method further comprises subjecting the released antibody to characterization, as in claim 1.
However, in a US patent application on sample depletion and enrichment, Soldo rectifies these deficiencies. Soldo teaches a method of measuring the amount, mass, molarity, concentration or yield of targeted biomarker captured and enriched by the microparticulate binding surface.
With respect to claim 1, Soldo teaches dissociating the antigen-specific antibody from the particle by elution and characterizing the released antibody (see, e.g., para. [0116]: “A method of measuring the amount, mass, molarity, concentration, or yield of targeted biomarker captured and enriched by the microparticulate binding surface whereby the biomarker is eluted”).
‘484 and Soldo are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the elution technique of Soldo in the assay of ‘484. An artisan would be motivated to do so because the sample enrichment of Soldo can be used to support the LC-MS/MS Diagnostics market when the elution of the target is paired with LC-MS/MS analysis (see, e.g., Soldo, para. [0053]; and para. [0059]). LC-MS/MS is incompatible with the particles of the ‘484 assay unless the targets are eluted from the particles before LC-MS/MS analysis. The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 14, ‘484 teaches as set forth above, but fails to teach the method wherein the first and/or second particle is provided as a lyophilized product. However, in a US patent application on sample depletion and enrichment, Soldo rectifies these deficiencies. Soldo teaches a method of measuring the amount, mass, molarity, concentration or yield of targeted biomarker captured and enriched by the microparticulate binding surface.
With respect to claim 14, Soldo teaches the method wherein the first and/or second particle is provided as a lyophilized product (see, e.g., para. [0062]: “the microparticles can be lyophilized”).
‘484 and Soldo are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the lyophilization technique of Soldo in the assay of ‘484. An artisan would be motivated to do so because lyophilization is a well-known technique in the art to preserve biological reagents. An artisan would expect the reagents of ‘484 to be compatible with lyophilization because of the reagents’ similarity to the reagents of Soldo. The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claims 1 and 6, ‘484 and Soldo teach as set forth above. They also teach depleted samples can be subsequently analyzed with immunoassays (see, e.g., Soldo, para. [0060]). But, ‘484 and Soldo fail to teach the method wherein the characterization comprises forming a complex with an anti-immunoglobulin conjugated to a detectable label, as in claim 1. ‘484 and Soldo fail to teach the detectable label is a fluorescent label, as in claim 6. However, in a patent application on methods of identifying antibody variants with improved properties, Koenig rectifies these deficiencies.
With respect to claims 5 and 6, Koenig teaches the method wherein the characterization comprises forming a complex with an anti-immunoglobulin conjugated to a detectable label, specifically a fluorescent label (see, e.g., forming a complex with an anti-immunoglobulin conjugated to a detectable label - para. [0380]: “The second antibody may itself be labeled with a detectable moiety (direct sandwich assays) or may be measured using an anti-immunoglobulin antibody that is labeled with a detectable moiety (indirect sandwich assay)”; fluorescent label – para. [0376]: “ Labels include, but are not limited to, labels or moieties that are detected directly (such as fluorescent, chromophoric, electron-dense, chemiluminescent, and radioactive labels)”).
‘484, Soldo, and Koenig are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the characterization of Koenig in the assay of ‘484 as modified by Soldo. An artisan would be motivated to do so because Koenig discloses that the antibody “may be measured using an anti-immunoglobulin antibody that is labeled” and “detected directly” (see para. [0380] and para. [0376]). Koenig also discloses that the technique is a “known assay method” (see para. [0378]). An artisan would recognize that the known measurement technique of Koenig would be useful for measuring the antibodies bound by the assay of ‘484 as modified by Soldo. The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claims 1 and 15, ‘484, Soldo, and Koenig fail to teach the biomarker is an antigen-specific antibody. ‘484 fails to teach the antigen-specific antibody is specific to the pathogen SARS-CoV-2, as in claims 16 and 17. ‘484 also fails to teach the capture moiety is a spike protein, specifically the S1 subunit domain, as in claims 18 and 19. ‘484 fails to teach the antigen-specific antibody is against a foreign protein, as in claim 22. ‘484 fails to teach the antigen-specific antibody is a human antibody, as in claim 23. However, in a medRxiv journal article on serological tests for COVID-19 patients, Okba rectifies these deficiencies.
Okba teaches measuring antigen-specific antibodies, specifically pathogen-specific antibodies for SARS-CoV-2 using the S1 domain of the SARS-CoV-2 spike protein as the capture moiety, as in claims 1, 15-19, and 22 (see, e.g., p. 5, under “ELISA”, para. 1). It is understood that viral proteins are foreign proteins. Okba teaches the antigen-specific antibodies are human antibodies, as in claim 23 (see, e.g., p. 3, under “Materials and methods”, under “Serum Samples”, under “EMC samples”).
‘484, Soldo, Koenig, and Okba are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of ‘484 modified by Soldo and Koenig to detect antibodies to SARS-CoV-2 using the S1 domain of the SARS-CoV-2 spike protein as the capture moiety such as taught by Okba. An artisan would be motivated to detect antibodies to SARS-CoV-2 because Okba discloses, “Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies” (see p. 1, under “Abstract”). An artisan would have been motivated to use the S1 domain of the SARS-CoV-2 spike protein as the capture moiety as taught by Okba because Okba discloses, “S1 is a [sic] more specific than S as an antigen for SARS-CoV-2 serological diagnosis” (see p. 6, para. 4). Okba further discloses, “the specificity of S1 as an antigen for SARS-CoV-2 serology was further supported by the fact that 87-100 % of the cohort A-C sera included in this study were seropositive for the endemic HCoVs as determined by the S1 protein microarray” (see p. 7, para. 1). The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 1, ‘484, Soldo, Koenig, and Okba teach as set forth above, but fail to teach the anti-immunoglobulin antibody is not isotype specific. However, in a journal article on detection of antibody to avian influenza virus in human serum, Rowe rectifies this deficiency.
Rowe teaches western blotting for detection of antibodies from a biological sample with anti-immunoglobulin antibodies that are not isotype specific, as in claim 1 (see, e.g., p. 938, col 2, under “H5N1 Western blotting.”: “Horseradish peroxidase-conjugated goat anti-human IgG, IgM, or IgG-IgA-IgM (Kirkegaard & Perry Laboratories, Inc.) was added to each well”). It is understood that the Horseradish peroxidase-conjugated goat anti-human IgG-IgA-IgM is not isotype specific because it detects three different isotypes.
‘484, Soldo, Koenig, Okba, and Rowe are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the anti-immunoglobulin antibody of Rowe into the assay of ‘484 as modified by Soldo, Koenig, and Okba. The artisan would be motivated to use the anti-human immunoglobulin antibody of Rowe because of the ability to combine the measurement of three different types of immunoglobulins, i.e. IgG, IgA, and IgM in a sample (see, e.g., p. 940, col. 2, under “TABLE 3”). The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 10, ‘484, Soldo, Koenig, Okba, and Rowe teach as set forth above, but fail to teach the anti-immunoglobulin antibody comprises at least two of anti-IgA, anti-IgG, and anti-IgM, each conjugated to a distinct label, as in claim 10. However, in a journal article on a multiplex assay for analysis of human serum anti-glycan antibodies, Durbin rectifies these deficiencies.
Durbin teaches multiple isotype-specific anti-immunoglobulin antibodies used to measure IgA, IgG, and IgM in a multiplex assay with a distinct label conjugated to each anti-immunoglobulin, as in claim 10 (see p. 16882, under “ABSTRACT”).
‘484, Soldo, Koenig, Okba, Rowe, and Durbin are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the isotype-specific anti-immunoglobulin antibodies with distinct labels of Durbin into the assay of ‘484 as modified by Soldo, Koenig, Okba, and Rowe. The artisan would have been motivated to do so because Durbin discloses that the isotype-specific anti-immunoglobulin antibodies with distinct labels allows for a “multiplex assay to simultaneously detect IgA, IgG, and IgM” (see p. 16882, under “ABSTRACT”). The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claims 20 and 21, ‘484, Soldo, Koenig, Okba, and Rowe teach as set forth above, but fails to teach the antigen-specific antibody is an autoantibody, specifically a tumor-specific autoantibody, as in claims 20 and 21. However, in a review of immunity directed against tumor-associated antigens as biomarkers for early diagnosis of cancer, Lu rectifies these deficiencies.
With respect to claims 20 and 21, Lu teaches detecting autoantibodies in human serum, wherein the autoantibodies are tumor-specific autoantibodies (see, e.g., p. 1388, under abstract; p. 1391, under “Figure 1.”; and p. 1991, under “Detecting Serum Antibody Response to a Panel of TAAs”, para. 1).
‘484, Soldo, Koenig, Okba, Rowe, and Lu are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of ‘484 as modified by Soldo, Koenig, Okba, and Rowe to detect autoantibodies in human serum, wherein the autoantibodies are tumor-specific autoantibodies as taught by Lu. An artisan would be motivated to do so because Lu discloses, “It is now possible to potentially harness the immune response elicited by cancer growth as a potential diagnostic tool. Humoral immunity, or the development of autoantibodies against tumor-associated proteins, may be used as a marker for cancer exposure. Unlike circulating proteins that are shed by bulky tumors, serum autoantibodies are detectable even when antigen expression is minimal” (see p. 1388, under abstract). The artisan would have a reasonable expectation of success based on the disclosures given.
‘484, Soldo, Koenig, Okba, Rowe, and Lu teach as set forth above. However, they fail to teach the method further comprises a pretreatment with a) combining a biological sample with a second particle comprising a streptavidin capture moiety for biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted comprising a biotin amount reduced by 90% , as in claim 1.
However, Favresse teaches a) combining a biological sample with a second particle comprising a streptavidin capture moiety for biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted comprising a biotin amount reduced by 90% , as in claim 1 (see, e.g., p. e132, under “Table 1:”, under “Streptavidin beads, ng/mL mean elimination rate, %”, row “Mean”: “99.95”, and p. e130, col. 2, para. 3: “We used the streptavidin beads treatment adapted from the procedure described by Piketty et al. [6]. Briefly, five volumes of streptavidin reagent (0.72 mg/mL in HEPES-bovine serum albumin buffer, pH 7.4; Roche Diagnostics) were spun for 10 min at 3500 rpm and the supernatant was carefully discarded. One volume of serum (1 mL) was then added on the streptavidin particles pellet, incubated and shaken for 1 h at RT at 36 rpm (rotamix, CAT, Ingenieurbüro, GmbH). Beads were then removed by centrifugation for 10 min at 3500 rpm”).
‘484, Soldo, Koenig, Okba, Rowe, Lu, and Favresse are analogous to the field of the claimed invention because they are all in the field of immunoassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the biotin interference removal of Favresse into the assay of ‘484 as modified by Soldo, Koenig, Okba, Rowe, and Lu An artisan would have been motivated to do so because Favresse discloses, “Interferences of biotin with immunoassays is a real safety concern, as the consequences potentially impact medical decision and patient care. Convenient techniques exist to detect and overcome the biotin interference and could be available in almost all clinical laboratories [13]. Our study shows that the streptavidin beads treatment and the VeraPrep Biotin™ appeared to be the best solution to efficiently deplete patients’ samples from biotin” (see, p. e133, col. 1, para. 4). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claims 1, 6, 10, and 15-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, 19, and 49 of copending Application No. 17/263,809 (referred to as ‘809 henceforth) in view of Koenig, Durbin, Soldo, Okba, Rowe, and Favresse (all cited above). The following double patenting rejections have been modified, necessitated by amendments filed 04/23/2026.
With respect to claim 1, ‘809 teaches a method for isolating an antigen-specific antibody from a biological sample, the method comprising: a) combining the sample with a first particle comprising a capture moiety for the antigen-specific antibody to provide a mixture; b) mixing the mixture to provide particle complexes to the antibody; and c) separating the particle from the biological sample; thereby isolating the antibody from the biological sample (see, e.g., method for isolating proteins from a biological sample - claim 1 of ‘809; the protein is an antibody - claim 49 of ‘809; combining the sample with a first particle comprising a capture moiety for the antigen-specific antibody to provide a mixture - claim 1 of ‘809; mixing the mixture to provide particle complexes to the antibody - claim 1 of ‘809; separating the particle from the biological sample; thereby isolating the antibody from the biological sample – claim 1 of ‘809). ‘809 teaches dissociating the antigen-specific antibody from the particle by elution and characterizing the released antibody (see, dissociation by cleavage – claim 18 of ‘809; further characterization – claim 19 of ‘809).
With respect to claim 1, ‘809 teaches the method further comprises a pretreatment with a) combining a biological sample with a second particle comprising a capture moiety for an interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the interference; c) removing or eliminating the second particle complexes to provide a depleted solution (see, e.g., claim 1 of ‘809).
With respect to claim 15, ‘809 teaches an enriched antibody made by the method of claim 1 (see claim 1 of ‘809). In paragraph [00102] on page 21, the applicant’s specification defines enrichment “as the complete or partial particle capture and binding of target analyte(s) or biomarker to the particles from a biological sample”. The complete or partial particle capture and binding of target analyte(s) to the particles from a biological sample is recited by ‘809 above.
With respect to claim 22, ‘809 teaches the antigen-specific antibody is against a foreign protein (see claim 49 of ‘809). It is understood that mouse proteins are foreign proteins.
With respect to claim 23, ‘809 teaches the antigen-specific antibody is a human antibody (see claim 49 of ‘809).
With respect to claims 1 and 6, ‘809 teaches depleted samples can be subsequently analyzed with a diagnostic test (see, e.g., claim 5 of ‘809). But, ‘809 fails to teach the method wherein the characterization comprises forming a complex with an anti-immunoglobulin conjugated to a detectable label, as in claim 1. ‘809 fails to teach the detectable label is a fluorescent label, as in claim 6. However, in a patent application on methods of identifying antibody variants with improved properties, Koenig rectifies these deficiencies.
Koenig teaches the method wherein the characterization comprises forming a complex with an anti-immunoglobulin conjugated to a detectable label, specifically a fluorescent label, as in claims 1 and 6 (see, e.g., forming a complex with an anti-immunoglobulin conjugated to a detectable label - para. [0380]: “The second antibody may itself be labeled with a detectable moiety (direct sandwich assays) or may be measured using an anti-immunoglobulin antibody that is labeled with a detectable moiety (indirect sandwich assay)”; fluorescent label – para. [0376]: “ Labels include, but are not limited to, labels or moieties that are detected directly (such as fluorescent, chromophoric, electron-dense, chemiluminescent, and radioactive labels)”).
‘809 and Koenig are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the characterization of Koenig in the assay of ‘809. An artisan would be motivated to do so because Koenig discloses that the antibody “may be measured using an anti-immunoglobulin antibody that is labeled” and “detected directly” (see para. [0380] and para. [0376]). Koenig also discloses that the technique is a “known assay method” (see para. [0378]). An artisan would recognize that the known measurement technique of Koenig would be useful for measuring the antibodies bound by the assay of ‘809. The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 1, ‘809 and Koenig teach as set forth above, but fail to teach the anti-immunoglobulin antibody is not isotype specific. However, in a journal article on detection of antibody to avian influenza virus in human serum, Rowe rectifies this deficiency.
Rowe teaches western blotting for detection of antibodies from a biological sample with anti-immunoglobulin antibodies that are not isotype specific, as in claim 8 (see, e.g., p. 938, col 2, under “H5N1 Western blotting.”: “Horseradish peroxidase-conjugated goat anti-human IgG, IgM, or IgG-IgA-IgM (Kirkegaard & Perry Laboratories, Inc.) was added to each well”). It is understood that the Horseradish peroxidase-conjugated goat anti-human IgG-IgA-IgM is not isotype specific because it detects three different isotypes.
‘809, Koenig, and Rowe are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the anti-immunoglobulin antibody of Rowe into the assay of ‘809 as modified by Koenig. The artisan would be motivated to use the anti-human immunoglobulin antibody of Rowe because of the ability to combine the measurement of three different types of immunoglobulins, i.e. IgG, IgA, and IgM in a sample (see, e.g., p. 940, col. 2, under “TABLE 3”). The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 10, ‘809, Koenig, and Rowe teach as set forth above, but fail to teach the anti-immunoglobulin antibody comprises at least two of anti-IgA, anti-IgG, and anti-IgM, each conjugated to a distinct label, as in claim 10. However, in a journal article on a multiplex assay for analysis of human serum anti-glycan antibodies, Durbin rectifies these deficiencies.
Durbin teaches multiple isotype-specific anti-immunoglobulin antibodies used to measure IgA, IgG, and IgM in a multiplex assay with a distinct label conjugated to each anti-immunoglobulin, as in claim 10 (see p. 16882, under “ABSTRACT”).
‘809, Koenig, Rowe, and Durbin are analogous to the field of the claimed invention because they are all in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the isotype-specific anti-immunoglobulin antibodies with distinct labels of Durbin into the assay of ‘809 as modified by Koenig and Rowe. The artisan would have been motivated to do so because Durbin discloses that the isotype-specific anti-immunoglobulin antibodies with distinct labels allows for a “multiplex assay to simultaneously detect IgA, IgG, and IgM” (see p. 16882, under “ABSTRACT”). The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claim 14, ‘809, Koenig, and Rowe teach as set forth above, but fails to teach the method wherein the first and/or second particle is provided as a lyophilized product. However, in a US patent application on sample depletion and enrichment, Soldo rectifies these deficiencies. Soldo teaches a method of measuring the amount, mass, molarity, concentration or yield of targeted biomarker captured and enriched by the microparticulate binding surface.
Soldo teaches the method wherein the first and/or second particle is provided as a lyophilized product, as in claim 14 (see, e.g., para. [0062]: “the microparticles can be lyophilized”).
‘809, Koenig, Rowe, and Soldo are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the lyophilization technique of Soldo in the assay of ‘809 as modified by Koenig and Rowe. An artisan would be motivated to do so because lyophilization is a well-known technique in the art to preserve biological reagents. An artisan would expect the reagents of ‘809 to be compatible with lyophilization because of the reagents’ similarity to the reagents of Soldo. The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claims 16-19, ‘809, Koenig, and Rowe fail to teach the antigen-specific antibody is specific to the pathogen SARS-CoV-2, as in claims 16 and 17. ‘809, Koenig, and Rowe also fail to teach the capture moiety is a spike protein, specifically the S1 subunit domain, as in claims 18 and 19. However, in a medRxiv journal article on serological tests for COVID-19 patients, Okba rectifies these deficiencies.
Okba teaches measuring antigen-specific antibodies, specifically pathogen-specific antibodies for SARS-CoV-2 using the S1 domain of the SARS-CoV-2 spike protein as the capture moiety, as in claims 16-19 and 22 (see, e.g., p. 5, under “ELISA”, para. 1). It is understood that viral proteins are foreign proteins. Okba teaches the antigen-specific antibodies are human antibodies, as in claim 23 (see, e.g., p. 3, under “Materials and methods”, under “Serum Samples”, under “EMC samples”).
‘809, Koenig, Rowe, and Okba are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of ‘809 as modified by Koenig and Rowe to detect antibodies to SARS-CoV-2 using the S1 domain of the SARS-CoV-2 spike protein as the capture moiety such as taught by Okba. An artisan would be motivated to detect antibodies to SARS-CoV-2 because Okba discloses, “Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies” (see p. 1, under “Abstract”). An artisan would have been motivated to use the S1 domain of the SARS-CoV-2 spike protein as the capture moiety as taught by Okba because Okba discloses, “S1 is a [sic] more specific than S as an antigen for SARS-CoV-2 serological diagnosis” (see p. 6, para. 4). Okba further discloses, “the specificity of S1 as an antigen for SARS-CoV-2 serology was further supported by the fact that 87-100 % of the cohort A-C sera included in this study were seropositive for the endemic HCoVs as determined by the S1 protein microarray” (see p. 7, para. 1). The artisan would have a reasonable expectation of success based on the disclosures given.
With respect to claims 20 and 21, ‘809, Koenig, and Rowe teach as set forth above, but fail to teach the antigen-specific antibody is an autoantibody, specifically a tumor-specific autoantibody, as in claims 20 and 21. However, in a review of immunity directed against tumor-associated antigens as biomarkers for early diagnosis of cancer, Lu rectifies these deficiencies.
With respect to claims 20 and 21, Lu teaches detecting autoantibodies in human serum, wherein the autoantibodies are tumor-specific autoantibodies (see, e.g., p. 1388, under abstract; p. 1391, under “Figure 1.”; and p. 1991, under “Detecting Serum Antibody Response to a Panel of TAAs”, para. 1).
‘809, Koenig, Rowe, and Lu are analogous to the field of the claimed invention because they are both in the field of bioassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of ‘809 as modified by Koenig and Rowe to detect autoantibodies in human serum, wherein the autoantibodies are tumor-specific autoantibodies as taught by Lu. An artisan would be motivated to do so because Lu discloses, “It is now possible to potentially harness the immune response elicited by cancer growth as a potential diagnostic tool. Humoral immunity, or the development of autoantibodies against tumor-associated proteins, may be used as a marker for cancer exposure. Unlike circulating proteins that are shed by bulky tumors, serum autoantibodies are detectable even when antigen expression is minimal” (see p. 1388, under abstract). The artisan would have a reasonable expectation of success based on the disclosures given.
‘809, Koenig, Rowe, and Lu teach as set forth above. However, they fail to teach the method further comprises a pretreatment with a) combining a biological sample with a second particle comprising a streptavidin capture moiety for biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted comprising a biotin amount reduced by 90% , as in claim 1.
However, Favresse teaches a) combining a biological sample with a second particle comprising a streptavidin capture moiety for biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted comprising a biotin amount reduced by 90% , as in claim 1 (see, e.g., p. e132, under “Table 1:”, under “Streptavidin beads, ng/mL mean elimination rate, %”, row “Mean”: “99.95”, and p. e130, col. 2, para. 3: “We used the streptavidin beads treatment adapted from the procedure described by Piketty et al. [6]. Briefly, five volumes of streptavidin reagent (0.72 mg/mL in HEPES-bovine serum albumin buffer, pH 7.4; Roche Diagnostics) were spun for 10 min at 3500 rpm and the supernatant was carefully discarded. One volume of serum (1 mL) was then added on the streptavidin particles pellet, incubated and shaken for 1 h at RT at 36 rpm (rotamix, CAT, Ingenieurbüro, GmbH). Beads were then removed by centrifugation for 10 min at 3500 rpm”).
‘809, Koenig, Rowe, Lu, and Favresse are analogous to the field of the claimed invention because they are all in the field of immunoassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the biotin interference removal of Favresse into the assay of ‘809 as modified by Koenig, Rowe, and Lu An artisan would have been motivated to do so because Favresse discloses, “Interferences of biotin with immunoassays is a real safety concern, as the consequences potentially impact medical decision and patient care. Convenient techniques exist to detect and overcome the biotin interference and could be available in almost all clinical laboratories [13]. Our study shows that the streptavidin beads treatment and the VeraPrep Biotin™ appeared to be the best solution to efficiently deplete patients’ samples from biotin” (see, p. e133, col. 1, para. 4). An artisan would have had a reasonable expectation of success based on the given disclosures.
These are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 04/23/2026 have been fully considered but they are not persuasive.
Rejections under 35 U.S.C. 103
The applicant begins arguments by stating that the newly amened claim 1, which adds “and wherein the method further comprises a pretreatment, the pretreatment comprising a) combining a biological sample with a second particle comprising a streptavidin capture moiety for a biotin interference to provide a mixture; b) mixing the mixture to provide second particle complexes to the biotin interference; c) removing or eliminating the second particle complexes to provide a depleted solution, said depleted solution comprising a biotin amount reduced by 90% as compared to the original biological sample”, is not taught or suggested by the prior art and provides improved analysis methods. However, the amendment necessitated new grounds of rejection, which included the prior art reference, Favresse (cited above). Favresse teaches the amended limitation and discloses the improvement to analysis methods (see rejection above).
The applicant then points to the amendment to claim 1 to request withdrawal of the all 103 rejections. However, as stated above, the Favresse teaches the limitation of amended claim 1.
Double Patenting Rejections
The applicant requests that the double patenting rejections are held in abeyance until claims are allowable in the present application. However, until the double patenting rejections are no longer applicable, they will be maintained.
Conclusion
No claims are allowed.
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/MICHAEL CAMERON SVEIVEN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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