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 .
Response to Amendment/Disposition of Claims
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08 June 2026 has been entered.
Applicant’s Amendment filed on 08 June 2026 has been received and entered. Claims 1-3, 10-18, and 23-26 were pending, with Claims 1-3, 10-14, and 23-24 being withdrawn from further consideration as being drawn to nonelected inventions, there being no allowable generic or linking claims.
Of the claims currently under examination, Claims 15, 17, and 25 have been amended. No claims have been cancelled. No new claims have been added.
Accordingly, Claims 15-18 and 25-26 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0152318 A1, Published 18 May 2023. Applicant’s amended Specifications as presented on 11 December 2025 and 07 October 2022 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Response to Arguments
Applicant's arguments filed 08 June 2026 regarding the previous Office action dated 24 March 2026 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Specification
The use of the term LOCI, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Withdrawn Objections
(Objection Withdrawn) – The objection to Claims 17 and 25 for containing minor informalities is withdrawn in light of the amendments to the claims.
New Objections
(New Objection) – Claim 15 is objected to because of the following informalities: it is suggested that it say “(1) combining[[,]] in any order of addition:” instead of “(1) combining, in any order of addition:”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Withdrawn Rejections
(Rejection Withdrawn) – The rejection of Claims 15, and dependent claims 16-18 and 25-26 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
New Rejections
(New Rejection – necessitated by amendment) – Claims 15, and dependent claims 16-18 and 25-26 thereof, 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 15 recites the broad recitation “combining in any order”, and the claim also recites “wherein (a)-(c) are combined simultaneously, or wherein each of (a)-(c) are combined sequentially, or wherein two of (a)-(c) are combined sequentially”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Specifically, Applicant states that the components can be combined in any order and then proceeds to further limit how the components can be combined within the same claim. It is suggested that the claim be amended to recite these separate limitations as Markush groups wherein the recited limitations are claimed in the alternative, perhaps as a separate dependent claim, that the claim be amended to recite only one (1) of the possible limitations, or that these separate limitations are recited individually as their own dependent claims, but Applicant is free to amend the claim as they deem necessary.
Additionally, the limitation of “wherein two of (a)-(c) are combined sequentially” also renders the claim indefinite because it is unclear how the third member of (a)-(c) is combined with the other two. For instance, it could be combined simultaneously with one of the other two. It could also be combined sequentially after the other two are combined, which would fail to differentiate this option from the “wherein each of (a)-(c) are combined sequentially” option recited earlier in the claim. This lack of clarity renders the claim indefinite. It is suggested that the claim be amended to clarify the fate of the third member, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 15 is rejected on the grounds of being indefinite. Claims 16-18 and 25-26 are also rejected, since they depend upon Claim 15 but do not remedy the deficiencies of Claim 15.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
(New Rejection) – Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the detection of antibodies in whole blood or any portion thereof, saliva, tears, feces, urine, sputum, cerebrospinal fluid, skin, intestinal fluid, intraperitoneal fluid, cystic fluid, interstitial fluid, extracellular fluid, mucus, bladder wash, semen, pleural fluid, and nasopharyngeal fluid, does not reasonably provide enablement for the detection of antibodies in sweat. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a method for detecting the presence and/or concentration of antibodies against a microorganism in a human biological sample via a particle agglutination immunoassay, the method comprising the steps of: (1) combining in any order of addition: (a) the human biological sample suspected of containing antibodies against the microorganism; (b) a composition comprising a particle and at least one antigen of the microorganism directly or indirectly bound thereto; and (c) at least one anti-human immunoglobulin antibody; wherein (a)-(c) are combined simultaneously, or wherein each of (a)-(c) are combined sequentially, or wherein two of (a)-(c) are combined sequentially; (2) allowing the binding of (b) and (c) to antibodies against the microorganism present in (a), wherein the binding of (b) to at least one antibody against the microorganism present in (a) results in the formation of a complex, and wherein the binding of (c) to the antibodies against the microorganism present in (a) in two or more complexes results in the cross-linking and formation of aggregates of two or more particle-containing complexes that contain at least two of the antibodies against the microorganism present in (a); (3) detecting the aggregates to determine the presence and/or concentration of antibodies against the microorganism present in the sample, wherein the human biological sample is selected from the group consisting of whole blood or any portion thereof, urine, saliva, sputum, cerebrospinal fluid, skin, intestinal fluid, intraperitoneal fluid, cystic fluid, sweat, interstitial fluid, extracellular fluid, tears, mucus, bladder wash, semen, feces, pleural fluid, nasopharyngeal fluid, and combinations thereof.
State of the prior art/Predictability of the art. With regard to the art for detecting antibodies in bodily fluids, the art teaches that antibodies can be found in many bodily fluids, depending on the technique or techniques used. Singh et al. (Singh, P., Kumar, A., Karmakar, S., Lin, K.-C., Muthukumar, S., & Prasad, S. (2025). Monitoring TNF-⍺ monoclonal antibody via sweat cytokine profiling using the IBD AWARE®: A non-invasive approach to assess therapeutic response. Sensing and Bio-Sensing Research, 50, Article 100914.) used an antibody-based assay to detect antibody concentrations in the ng/mL range (see Table 1), while Katchman et al. (Katchman BA, Zhu M, Blain Christen J, Anderson KS. Eccrine Sweat as a Biofluid for Profiling Immune Biomarkers. Proteomics Clin Appl. 2018 Nov;12(6):e1800010.) was able to detect antibodies in sweat at the pg/mL range using LC-MS/MS (see Abstract in grey box). Coyle and Sibony (Coyle PK, Sibony PA. Viral antibodies in normal tears. Invest Ophthalmol Vis Sci. 1988 Oct;29(10):1552-8.) disclosed the use of an ELISA to detect anti-viral antibodies in tears and parotid saliva, in the µg/mL range, and serum, in the mg/dL range (see Figure 1). Watt et al. (Watt KA, Nussey DH, Maclellan R, Pilkington JG, McNeilly TN. Fecal antibody levels as a noninvasive method for measuring immunity to gastrointestinal nematodes in ecological studies. Ecol Evol. 2015 Dec 8;6(1):56-67.) also used an ELISA to detect fecal antibody levels (see Page 59, Left Column, Last Paragraph and Right Column, Paragraphs 1-2).
Mohandas et al. (Mohandas S, Balan S, Mourya DT. Urinary immunoglobulins in viral diagnosis: An overview. Indian J Med Res. 2022 Jan;155(1):11-21. doi: 10.4103/ijmr.IJMR_808_18. Erratum in: Indian J Med Res. 2022 Jan;156(1):169.) teach that anti-viral antibodies can be detected in urine using a variety of techniques, including commercial ELISA kits (see Tables 2 and 3). Von Hertzen et al. (von Hertzen L, Leinonen M, Surcel HM, Karjalainen J, Saikku P. Measurement of sputum antibodies in the diagnosis of acute and chronic respiratory infections associated with Chlamydia pneumoniae. Clin Diagn Lab Immunol. 1995 Jul;2(4):454-7.) disclose the detection of antibodies in sputum using an enzyme immunoassay and a micro-immunofluorescence assay (see Tables 1 and 2; Figure 1; Page 455, Left Column, Paragraph 2). Preßler et al. (Preßler H, Bünger I and Prüss H (2025) Novel cerebrospinal fluid anti-central nervous system IgG antibodies can identify immunotherapy-responsive neuropsychiatric disorders. Front. Immunol. 16:1612844.) teach the detection of autoantibodies in cerebrospinal fluid using ELISA and immunofluorescence (see Page 3, Left Column, Paragraphs 1-2; Figure 2). Deng and Li (Deng W, Li T. Skin as an autonomous immune organ: Antibody production and host protection. Acta Pharm Sin B. 2025 May;15(5):2795-2797. doi: 10.1016/j.apsb.2025.03.027. Epub 2025 Mar 13.) teach that the skin produces specific antibodies, such as IgG2b and IgG2c (see Figure 1).
Macpherson et al. (Macpherson A, Khoo UY, Forgacs I, Philpott-Howard J, Bjarnason I. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut. 1996 Mar;38(3):365-75.) teach the detection of antibodies in intestinal fluid or colonoscopic washings in the µg/mL range using sandwich ELISAs (see Figure 2). Confino et al. (Confino E, Harlow L, Gleicher N. Peritoneal fluid and serum autoantibody levels in patients with endometriosis. Fertil Steril. 1990 Feb;53(2):242-5.) disclose the detection of autoantibodies in peritoneal fluid and serum (see Figure 1). Witkin et al. (Witkin SS, Sarkar NH, Kinne DW, Breed CN, Good RA, Day NK. Antigens and antibodies cross-reactive to the murine mammary tumor virus in human breast cyst fluids. J Clin Invest. 1981 Jan;67(1):216-22.) teach detecting antibodies in the µg/mL range using ELISA (see Abstract). Janeway et al. (Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The distribution and functions of immunoglobulin isotypes.) disclose that antibodies can be detected in the blood, extracellular fluid, which includes interstitial fluid, and secretions such as the mucus epithelium of the intestinal and respiratory tracts (see Page 2, Paragraphs 1-2).
Andolz et al. (Andolz P, Bielsa MA, Martínez P, García-Framis V, Benet-Rubinat JM, Egozcue J. Detection of anti-sperm antibodies in serum, seminal plasma and cervical mucus by the immunobead test. Hum Reprod. 1990 Aug;5(6):685-9.) disclose the detection of anti-sperm antibodies in serum, seminal plasma, and cervical mucus (see Abstract; Table IV). Sarrigeorgiou et al. (Sarrigeorgiou I, Rouka E, Kotsiou OS, Perlepe G, Gerovasileiou ES, Gourgoulianis KI, Lymberi P, Zarogiannis SG. Natural antibodies targeting LPS in pleural effusions of various etiologies. Am J Physiol Lung Cell Mol Physiol. 2024 Jun 1;326(6):L727-L735.) teach the detection of antibodies in pleural fluid and serum using ELISA (see Abstract). Crescenzo-Chaigne et al. (Crescenzo-Chaigne B, Behillil S, Enouf V, Escriou N, Petres S, Ungeheuer MN, Ghosn J, Tubiana S, Bouadma L, van der Werf S, Demeret C; French COVID cohort study group. Nasopharyngeal and serological anti SARS-CoV-2 IgG/IgA responses in COVID-19 patients. J Clin Virol Plus. 2021 Dec;1(4):100041.) teach the detection of IgG and IgA in plasma and nasopharyngeal swab samples using ELISA (see Abstract). Lindan (Lindan, R. The significance of antibody coated bacteria in neuropathic bladder urines. Spinal Cord 19, 216–219 (1981).) teaches the detection of antibody-coated bacteria in urine specimens or bladder washes using fluorescein-tagged antihuman-globulin antibody (see Introduction).
Working examples. Only one working example is disclosed in the specification, wherein the assay is used to detect anti-SARS-CoV-2 antibodies in blood (see Example 1; Paragraphs 0085-0091).
Guidance in the specification. The specification provides guidance towards the detection of anti-SARS-CoV-2 antibodies in blood using amounts in the µg/mL range using the instantly claimed antibody-based assay (see Example 1; Table 1).
Amount of experimentation necessary. Additional research is required in order to determine how effective the instantly claimed method would be at detecting antibodies with concentrations below the µg/mL range or the ng/mL range, depending on the type of sample being analyzed.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed method.
Claim Rejections - 35 USC § 102
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.
(Rejection Maintained) – The rejection of Claims 15-18 and 25-26 under 35 U.S.C. 102(a)(2) as being anticipated by Lipkin et al. (US 2023/0184764 A1, earliest Priority Date 06 April 020) is maintained.
Response to Arguments
Applicant's arguments filed with respect to the rejection of Claims 15-18 and 25-26 under 35 U.S.C. 102(a)(2) have been fully considered but they are not persuasive.
In their Response, Applicant argues that “Lipkin fails to make an unambiguous disclosure of the specific mechanical and functional arrangement required by independent claim 15” and that “a PHOSITA” would not infer the method of claim 15 from Lipkin’s disclosure” (see Page 3 of Remarks, Last Paragraph). Applicant also argues that “Lipkin’s singular mentions of agglutination assay (See paragraphs [0036], [0084], and [0134] are done in passing, within a general laundry list of conventional assays or immunodetection techniques” and that there “are no technical details in Lipkin that would enable a PHOSITA to perform the agglutination assay of claim 15 without substantial and undue experimentation (see Page 4, First Paragraph). Additionally, Applicant argues that “Lipkin does not disclose the formation of aggregates of two or more particle-containing complexes as required by step (2) of amended claim 15, and Lipkin’s primary technical teachings are in fact incompatible with such aggregate formation” (see Page 4, Last Paragraph). Applicant then argues that the “mere presence of the word ‘bead’ in Lipkin’s paragraph [0023] does not transform Lipkin’s immobilization-focused teachings into a disclosure of the aggregate-forming method of amended claim 15”, “that simply identifying a bead as a solid support for peptide immobilization is categorically distinct from and unrelated to the formation of aggregates of two or more particle-containing complexes as required by step (2) of amended claim 15, and that Lipkin does not contain “any paragraph that discloses, describes, or even remotely suggests antigen-bearing particles and anti-human immunoglobulin antibodies operating together to enhance cross-linking and form the multi-particle aggregates required by step (2) of amended claim 15” (see Page 5, First Paragraph). Applicant further argues that the “immobilization-based methodology that pervades Lipkin’s technical disclosure is structurally and operationally incompatible with the formation of aggregates of two or more particle-containing complexes required by step (2) of amended claim 15” and that immobilization “by definition, prevents the physical coming-together of two more discrete particle-containing complexes that is the essential requirement of the aggregate-formation step of amended claim 15” (see Page 5, Last Paragraph). Furthermore, Applicant argues that “Lipkin does not disclose the requirement of amended claim 15 that the binding of element (c) to antibodies in two or more complexes enhances cross-linking, resulting in the formation of aggregates of two or more particle-containing complexes that contain at least two antibodies from (a)” and that this “limitation defines both the functional role of element (c) and the structural consequence of its binding with specificity and precision that finds no counterpart anywhere in Lipkin’s disclosure” (see Page 6, Paragraph 2). Applicant then argues that the relevant paragraphs of Lipkin “describe anti-human antibodies functioning exclusively as labeled detection reagents – passive reporters” and that this “is a fundamentally different functional role than that required by amended claim 15” because “in the claimed methods, element (c) is NOT a passive reporter – it is also an active structural participant whose engagement with target antibodies in multiple separate complexes physically links those complexes together” (see Page 6, Last Paragraph and Page 7, First Paragraph). Finally, Applicant argues that Lipkin “fails to disclose the bridging geometry required in claim 15” which “describes a specific molecular architecture in which element (c) simultaneously engages with target antibodies in two or more separate particle-antigen-antibody complexes, physically bridging them together” (see Page 7, Paragraph 2).
Examiner does not find these arguments persuasive. In response to Applicant’s arguments that the immobilized latex particles disclosed by Lipkin et al. is not compatible with “with the formation of aggregates of two or more particle-containing complexes required by step (2) of amended claim 15” and that immobilization “by definition, prevents the physical coming-together of two more discrete particle-containing complexes that is the essential requirement of the aggregate-formation step of amended claim 15”, Examiner rebuts this by stating that there is nothing in the instant claims which excludes the use of immobilized particles or elements of the assay. As such, the instant method reads on such assays using immobilization of any kind. If Applicant desires to exclude such assays, then the instant claims should be amended to explicitly exclude such assays. Applicant is reminded that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also > Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); < Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). MPEP 2123. Also, there is nothing to suggest that that the immobilized latex beads of Lipkin et al. cannot be connected to one another via formation of the antibody complexes, especially if the beads in question are in close enough proximity to each other. Examiner would also point to Applicant’s own Specification, specifically Paragraph 0095 of the PGPub of the instant application and Figure 4, which clearly show multiple latex particles brought together through the formation of multiple complexes. There is nothing in the instant claims or Lipkin et al. to suggest that the latex beads of the prior art cannot function in the same capacity as depicted in instant Figure 4. Additionally, in Paragraph 0045 of the PGPub of the instant Specification, it states that “the second composition can also assume the form of a particle, a bead, an immobilized or non-immobilized surface or substrate, and the like”. As such, Applicant’s argument against immobilized particles is rebutted by Applicant’s own Specification.
Applicant’s argument that Lipkin et al. merely recites an agglutination assay, fails to “provide reagent selection, assay configuration, operational parameters, or any mechanistic description of how an agglutination assay would be performed using Lipkin’s disclosed peptides” (see Page 4 of Remarks, First Paragraph), and that undue experimentation would be needed is rebutted by the fact that Lipkin et al. recites reagents needed to perform the disclosed assays, including peptides, labelling reagents, signal-generating reagents, and coating reagents, among others (see Paragraphs 0131-0138). It should be noted that instant Claim 15 does not list any reagents other than (a)-(c), which Likpin et al. also disclose. As such, Lipkin et al. recites all the structural parts required of the instant method. Specific assay conditions, such as concentrations, are all optimizable. They also aren’t recited in the instant claims. The assay configuration does not seem relevant as all of the reagents are ending up in the same place, such as a plate or cuvette, or whatever the device reading the reaction requires. With regard to the argument that Lipkin et al. is not enabled without substantial and undue experimentation due to the lack of technical details, if the prior art reference is not enabled, then Applicant is essentially admitting that instant Claim 15 is also not enabled because no specific reagent is recited. Conversely, if instant Claim 15 is enabled, then so is the prior art.
Applicant’s argument regarding cross-linking is unpersuasive because this is an inherent property of antibodies due to their characteristic Y-shape. There is no specific recitation of physical or chemical cross-linking aside from the antibody interactions themselves. “[M]ere recognition of those latent properties does not render the otherwise obvious [method] unobvious and thereby patentable.” In re Prindle, 297 F.2d 251, 254 (CCPA 1962). Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). MPEP 2112(II): No requirement that one of ordinary skill would have recognized the inherent property at the time of invention or before for art to be anticipatory. Even if Applicant had discovered the cross-linking property of antibodies, it still would not be inventive. It also does not overcome an anticipatory reference as the antibodies of the prior art would possess the same function.
In response to Applicant’s arguments regarding the anti-human antibodies of Lipkin et al. only serving as passive reporters and that they fail to form the is rebutted by the fact that the instant claims do not explicitly state how the detection is carried out and what is or what is not labelled in the instant method. Also, the way that the instant method is being claimed, no skilled artisan is going to envision that only one antibody is present. A PHOSITA would not be concerned that there would not be enough antibodies around to make the assay work.
Thus, for at least these reasons, the rejection of Claims 15-18 and 25-26 under 35 U.S.C. 102(a)(2) as being anticipated by Lipkin et al. is maintained.
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.
(New Rejection) – Claims 15-18 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Ziege et al. (U.S. patent No. 5,100,805, Issued 31 March 1992), in view of Muerhoff et al. (US 2023/0258638 A1, earliest Priority Date 13 April 2020) (cited in a previous Office Action).
Ziege et al. teach a system, method, and apparatus for an agglutination immunoassay for detecting biologically active substances, such as antibodies, in bodily fluids, such as blood, serum, urine, or plasma (see Abstract; Column 3, Lines 52-60; Column 7, Lines 12-19), wherein an antigen is attached to the surface of a carrier particle to detect the presence of a corresponding antibody in the sample being tested (see Column 2, Lines 6-8; Column 4, Lines 20-26). Ziege et al. also teach that the carrier particles agglutinate through the resulting antigen-antibody binding reaction, if the corresponding antibody is present in the sample being tested (see Column 2, Lines 1-5; Figure 2). Specifically, Ziege et al. teach that the sensitivity of the disclosed system is the result of the ability of the assay to quickly detect small changes in the mean particles size used in a given assay as a result of linking or agglutination of the particles in the presence of the specific agent which causes the particles to become linked or agglutinated, such as the antigen-coated particles becoming linked together by the antigen-antibody binding when the antibody is present in the sample (see Figure 2; Column 15, Lines 53-61). Additionally, Ziege et al. also teach an agglutination immunoassay wherein the signal generated and detected is proportional to the degree of agglutination in the fluid mixture (see Column 8, Lines 30-48; Figure 5). Specifically, Ziege et al. disclose that the reagent compositions permit the detection and measurement of extremely low concentrations of antibodies in a test sample in a simple and highly effective manner through the carrier particles and their coaction with light in the system which permit detection of an agglutination reaction at the earliest stages of said reaction (see Column 4, Lines 5-8 and Lines 26-30). The system of Ziege et al. also provides a means for illuminating such an agglutination reaction through a transparent container with high-intensity light and for detecting light scattered by the carrier particles during the agglutination reaction, wherein a detector detects light scattered by the mixture in a forward direction at an acute angle within a range from about 10° to about 20° relative to the path of the illuminating light and generates output signals proportional to the intensity of the detected scattered light and further includes a means to digitize the output signal of the detector; memory means for receiving and storing digital data representing the intensity of the detected scattered light at a specified time, or times, during a test, for storing standard curve data representing the concentration of a substance of interest as a function of detected light intensity at a specified time, or times, during a test (see Column Lines 40-56).
Ziege et al. does not teach a method for detecting the presence and/or concentration of antibodies against a microorganism wherein said microorganism is a virus, specifically SARS-CoV-2, a method comprising at least one anti-human immunoglobulin antibody, and a method wherein said particle coated with an antigen is a latex particle. These deficiencies are remedied by the use of Muerhoff et al.
Muerhoff et al. teach methods for detecting the presence of or determining an amount, quantity, concentration, and/or level of an antibody against at least one type of Betacoronavirus, such as SARS-CoV-2 (see Abstract), in one or more samples obtained from a subject, wherein said subject can be a human (see Paragraphs 0252, 0492), and wherein said one or more samples can be whole blood, serum, plasma, saliva, a nasal mucus specimen, a nasopharyngeal specimen (see Paragraph 0027), urine (see Paragraph 0205), sputum, cerebrospinal fluid (see Paragraph 0251), skin, sweat, mucus, semen, feces (see Paragraph 0492), and interstitial fluid (see Paragraph 0252).
Specifically, Muerhoff et al. teach methods comprising: a) contacting at least one biological sample from the subject, either simultaneously or sequentially, in any order, with at least one type of first specific binding partner comprising at least one Betacoronavirus isolated polypeptide or antigen, or a variant thereof, and at least one type of second specific binding partner comprising a detectable label, thereby producing one or more types of first complexes comprising the first specific binding partner-anti-Betacoronavirus antibody-second specific binding partner; and b) assessing a signal from the one or more types of first complexes, wherein the amount of detectable signal from the detectable label indicates the presence or amount of the anti-Betacoronavirus antibody in the sample (see Paragraphs 0014-0019).
Muerhoff et al. also teach methods wherein said first specific binding partner comprises at least one Betacoronavirus isolated polypeptide or antigen, or a variant thereof (see Paragraph 0016) and wherein said second specific binding partner is an anti-human IgG antibody or an anti-human IgM antibody (see Paragraph 0039).
Furthermore, Muerhoff et al. teach methods wherein the first specific binding partner may be immobilized onto a variety of supports, such as latex particles (see Paragraph 0475).
Additionally, the instant claims are silent as to whether or not the immunoglobulin antibody can also be labelled and whether or not any of the components are immobilized on a solid support.
A person having ordinary skill in the art would have been motivated to modify the teachings of Ziege et al. with those of Muerhoff et al. in order to develop an agglutination assay for detecting anti-SARS-CoV-2 antibodies in a biological sample. The agglutination assay of Ziege et al. would provide a simple, low-cost, reliable, accurate, and extremely sensitive immunoassay which requires no sample preparation and can be used in doctors’ offices, small labs, and other low-volume facilities but that is also readily adaptable to hospital and high-volume use. It would also provide a general format which can be modified depending on the specific disease and disease response being monitored and it would be obvious to modify the assay Ziege et al. in the context of an outbreak or pandemic, such as COVID-19, as taught by Muerhoff et al. The combination of these teachings renders the instant claims obvious as the end result of combination of the prior art references would be the agglutination assay of Ziege et al. adapted with the specific reagents of Muerhoff et al.. These specific reagents are a sample from a subject containing or suspected of containing an antibody against at least one type of Betacoronavirus, such as SARS-CoV-2, at least one type of first specific binding partner comprising at least one Betacoronavirus isolated polypeptide or antigen, or a variant thereof, and at least one type of second specific binding partner comprising a detectable label, wherein said first specific binding partner comprises at least one Betacoronavirus isolated polypeptide or antigen, or a variant thereof, wherein said second specific binding partner is an anti-human IgG antibody or an anti-human IgM antibody, and wherein the first specific binding partner, the Betacoronavirus isolated polypeptide or antigen, may be immobilized onto a variety of supports, such as latex particles. These specific reagents of Muerhoff et al. match reagents (a)-(c) of instant Claim 15 as those required to carry out an agglutination assay, such as the instantly claimed agglutination assay.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, Claims 15-18 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
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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(Rejection Maintained) – The provisional rejection of Claims 15-16 and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 60, 62-63, and 65 of copending Application No. 18/552,167 (reference application) is maintained.
(Rejection Maintained) – The provisional rejection of Claims 15-16 and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 37-44 of copending Application No. 18/691,351 (reference application) is maintained.
Response to Arguments
Applicant's arguments filed with respect to the provisional rejection of Claims 15-16 and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 60, 62-63, and 65 of copending Application No. 18/552,167 have been fully considered but they are not persuasive.
In their Response, Applicant argues that “all other rejections of the claims in the subject application have been overcome, and that the provision ODP rejections are the only remaining rejections in the subject application” and “should be withdrawn” (see Page 8 of Remarks, Paragraph 3). Examiner does not find these arguments persuasive as the provisional double patenting rejections are still not the only rejections remaining. As such, this rejection is maintained for reasons of record.
Applicant's arguments filed with respect to the provisional rejection of Claims 15-16 and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 37-44 of copending Application No. 18/691,351 have been fully considered but they are not persuasive.
Applicant presented the same arguments for both provisional double patenting rejections. Examiner rebuts these arguments as was done above. As such, this rejection is maintained for reasons of record.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Vold et al. (U.S. Patent No. 5,561,049, Issued 01 October 1996)
Vold et al. teach a method for detecting antibodies in a sample. This reference has not been utilized, as rejection would have been redundant to those set forth above.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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