CTFR 17/595,015 CTFR 99821 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 The amendment filed 16 April 2026 and the supplemental amendment filed 20 May 2026 are acknowledged. Claims 1, 4, 6-9, 11-13, 24, and 35 have been amended. Withdrawal of Objections The objection to claims 4-14, 17, 21-22, 24, and 35-36 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiply dependent claim is withdrawn in view of the amendment to the claims. The objection to claim 1 for informalities is withdrawn in view of the amendment to the claims. Election/Restrictions Applicant's election with traverse of Group I, claims 1-24 and 35-36 drawn to products, namely compositions and kits used to detect allograft rejection in the reply filed on 27 October 2025 is previously acknowledged. The traversal is on the ground(s) that the Applicants "dispute the assertion in the Office Action that the five claim groups lack a common inventive concept" (Remarks 10/27/2025 p. 2). This is not found persuasive because the Office Action did not assert that the five claim groups lack a common inventive concept. A. The requirement is still deemed proper and is therefore made FINAL. Applicant further elects the species: A. CSF2 B. ENO1 C. Non-porous D. Non-porous E. Beads; and F. Fluorescently labeled. 08-05 AIA Claim s 25- are previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention , there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 27 October 2025 . 08-05 AIA Claim s 15, 16, 18, 19, 20, 23 are previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species , there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 27 October 2025 . 08-05 AIA Claim s 6, 8, 14, 17, which were previously not examined due to multiple dependency, are newly withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species , there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 27 October 2025 . Claim Status Claims 1-36 are pending. Claims 6, 8, 14-20, 23 and 25-34 are withdrawn from consideration as described in the Restriction/election section above. Claims 1-5, 7, 9-13, 17, 21-22, 24, and 35-36 are under consideration in the instant office action. Withdrawal of Rejections The rejection of claims 1-3 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 is withdrawn in view of the amendment to the claims. The rejection of claims 1-3 under 35 U.S.C. 102(a)(1) as being anticipated by McCutcheon, Krista, Edward O'Hara, and David Fei. "Multiplexed serum measurement of IgG, IgA, IgM, and IgE antibody responses to therapeutic biologicals." Immunological investigations 34.2 (2005): 199-213 published 2005 as evidenced by Meager, et al. "Spontaneously occurring neutralizing antibodies against granulocyte–macrophage colony ‐ stimulating factor in patients with autoimmune disease." Immunology 97.3 (1999): 526-532 published July 1999; Ye, Yao, et al. "Anti α-enolase antibody is a novel autoimmune biomarker for unexplained recurrent miscarriages." EBioMedicine 41 (2019): 610-622 published 1 March 2019; and Chou J, Wong J, Christodoulides N, Floriano PN, Sanchez X, McDevitt J. Porous bead-based diagnostic platforms: bridging the gaps in healthcare. Sensors (Basel). 2012 Nov 9;12(11):15467-99. doi: 10.3390/s121115467. PMID: 23202219; PMCID: PMC3522972 published 9 November 2012 is withdrawn in view of the amendment to the claims . Claim Objections 07-29-01 AIA Claim 35 is objected to because of the following informalities: Claim 35 recites a kit comprising "reagents for detecting the binding of the one or more homogenous populations of binding agents to the antibodies". However, claims 1 and 22 from which claim 35 depends, include embodiments with a single binding agent that "recognizes and specifically binds an antigen-binding site of an antibody" (claim 1). The plural "antibodies" in claim 35 is therefore unclear. The Examiner suggests amending the claim to recite "reagents for detecting the bind . Appropriate correction is required. Claim Rejections - 35 USC § 102- New, necessitated by amendment 07-15 AIA Claim s 1, 3-5, 7, 9-12, 22, 24 and 35-36 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Leclerc, Claude, et al. "Immobilized cytokines as biomaterials for manufacturing immune cell based vaccines." Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials 86.4 (2008): 1033-1040 as evidenced by ThermoFisher Scientific “Dynabeads™ M-450 Epoxy – FAQs” captured 28 May 2026, Web and ThermoFisher Scientific “Dynabeads™ M-450 Epoxy” captured 21 September 2019, Web . Regarding claims 1, 3, 4, 7, 9-10, 12, and 22 Leclerc et. al. discloses recombinant human GM-CSF (p. 1034 “Reagents” section; reads on CSF2 claim 22, reads on polypeptide claim 12) that was covalently immobilized on Dynabeads M-450 Epoxy (p. 1034 “Cytokine immobilization on Beads” section; reads on a solid-phase substrate, wherein the solid-phase substrates are beads). Leclerc et. al. teaches that the GM-CSF coupled to beads was detected using a GM-CSF specific antibody (p. 1034 “Cytokine immobilization on Beads” section; reads on recognizing and specifically binding to an antigen-binding site of an antibody that is directed against and specific to GM-CSF). Regarding claim 3, as evidenced by ThermoFisher Scientific “Dynabeads™ M-450 Epoxy – FAQs” captured 28 May 2016, Web, Dynabeads are non-porous (See “What are Dynabeads magnetic beads?” section). Regarding claims 5 and 7, as evidenced by ThermoFisher Scientific “Dynabeads™ M-450 Epoxy” captured 21 September 2019, Web, the beads are polystyrene and magnetic. Regarding claim 11, Leclerc et. al. discloses GM-CSF adsorbed on AS or conventional glass slides reads on solid phase substrate wherein the binding agent is attached to the surface of the solid-phase substrates by affinity. Regarding claim 35, Leclerc teaches that the GM-CSF coupled to beads was detected using a GM-CSF specific antibody “revealed by an FITC labeled anti-rat IgG antibody MP1-22E9 or IgG2a control isotype (clone R35-95) and analyzed by flow cytometry” (p. 1034 “Cytokine immobilization on Beads” section; reads on a kit comprising the composition of claims 1 or 22, and reagents for detecting the binding of one or more homogenous populations of binding agents to the antibodies). Regarding claims 36, the claims are directed at the kit of claim 35 further comprising a reference sample. Regarding “reference sample”, the instant specification describes a “reference sample is used to correlate and compare the results obtained from a test sample” [0060]. The specification goes on to provide non-limiting definitions of reference samples including “Reference samples can be any biological sample as used herein”. Thus, the broadest reasonable interpretation of “reference sample” is any sample, including non-biological samples, used as a reference or control as compared to a test sample. Leclerc et. al. discloses uncoated beads (p. 1035 right column ¶1, Fig. 1 b-c), and compares the uncoated beads to the GM-CSF beads (Fig. 1 b-c); the uncoated beads therefore read on the kit further comprising a reference sample. Regarding claim 24, the claim is directed at the composition of claim 1 wherein “at least one solid-phase substrate is detectably distinguishable from at least one other solid-phase substrate”. The examiner notes that neither of the solid-phase substrates of the claim that meet the functional limitation of being detectably distinguishable are required to be the solid-phase substrate of claim 1; further claim 1 does not require at least one other solid-phase substrate. Therefore, the broadest reasonable interpretation is that the additional solid-phase substrate may be any solid phase substrate; and that the claim reads on claim 1 wherein the composition of claim 1 has the property of being distinguishable from any other solid phase substrate, or composition of claim 1 further comprising any two other solid phase substrates that have the property of being distinguishable from each other. Leclerc et. al. discloses uncoated beads (p. 1035 right column ¶1, Fig. 1 b-c) and that GM-CSF can be detected on conjugated beads (Fig. 1a); therefore, the GM-CSF beads of Leclerc are inherently distinguishable from the uncoated beads of the additional solid-phase substrate . 07-15 AIA Claim s 1-3, 7, 12-13, and 22 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by U.S. 20030003516 A1 to Robinson et. al. published 2 January 2003 (Of record, IDS dated 2/8/2022) . Claim interpretation: Instant claim 2 is directed towards “The composition of claim 1, wherein the collection of solid-phase substrates further comprises one or more additional homogenous populations of binding agents, wherein each additional homogenous population of binding agents specifically binds to an antibody that is directed against a single antigen selected from the group consisting of: […]”. Regarding “binding agent” the instant specification states “The term “binding agent” refers to a molecule that specifically recognizes and binds to a target molecule of interest” [0049]. The instant specification does not define the term “specifically binds”; as defined in the art, specific binding means the selective interaction of an agent with a particular target above other targets (e.g. McBride JM, Eckmann JP, Tlusty T. General Theory of Specific Binding: Insights from a Genetic-Mechano-Chemical Protein Model. Mol Biol Evol. 2022 Nov 3;39(11):msac217. doi: 10.1093/molbev/msac217. PMID: 36208205; PMCID: PMC9641994; PTO-892 2/23/2026; Abstract). Thus, the broadest reasonable interpretation of the claim is that the claim requires a composition comprising a collection of solid-phase substrates coated with one or more homogenous binding agents capable of selective interaction with an antibody, wherein the antibody is directed against a single antigen selected from the group consisting of the list of target antigens recited. In particular, the Examiner notes that nothing in the claims requires the binding agent specifically binds to a particular epitope of an antibody directed against a single target antigen (e.g. the antigen binding domain) or that that binding agent must interact selectively with certain single antigen-directed antibodies above others. This claim interpretation was also discussed with Applicant as applied to claims 1 and 2 in the interview conducted 5 May 2026; however, only claim 1 was amended in the supplemental amendment. Regarding claims 1, 2, 12, 13, and 22, Robinson et. al. teaches an array, defined as a collection of addressable elements and that they can be based on beads, wherein the addressable elements are antigens or epitopes [0036]; antigens or epitopes read on binding agents that recognize and specifically bind an antigen-binding site of an antibody that is directed against and specific to a single antigen. Robinson et. al. teaches arrays may be a broad based antigenic panel or array for multiple diseases [0056]. Robinson et. al. teaches that antigen panels or arrays for autoimmune diseases include Tg for Grave’s disease [0063] and SS-B for systemic lupus erythematosus [0061] (reads on polypeptide, claim 12). Regarding claim 3, all beads are either non-porous or porous. Regarding claim 7, the labeling of the array included fluorochromes (reads on fluorescent label; [0072]). Regarding claim 13, Robison et. al. discloses the composition wherein the solid-phase substrates are coated with more than three different homogenous populations of binding agents that bind to at least three different antigens; Robinson discloses 15 different antigens on the antigen panel array for SLE alone and many more for the other autoimmune diseases, and therefore a broad antigenic array or an array for multiple disease would include at least 3 antigens [0057-0063] . Claim Rejections - 35 USC § 103 07-22-aia AIA Claim s 2, 11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20030003516 A1 to Robinson et. al. published 2 January 2003 (Of record, IDS dated 2/8/2022) as applied to claim 1 above, and further in view of Meager, et al. "Spontaneously occurring neutralizing antibodies against granulocyte–macrophage colony ‐ stimulating factor in patients with autoimmune disease." Immunology 97.3 (1999): 526-532 (PTO-892 2/23/2026) and as evidenced by Ye, Yao, et al. "Anti α-enolase antibody is a novel autoimmune biomarker for unexplained recurrent miscarriages." EBioMedicine 41 (2019): 610-622 published 1 March 2019 (PTO-892 2/23/2026) . Claim interpretation: Instant claim 2 is directed towards “The composition of claim 1, wherein the collection of solid-phase substrates further comprises one or more additional homogenous populations of binding agents, wherein each additional homogenous population of binding agents specifically binds to an antibody that is directed against a single antigen selected from the group consisting of: […]”. Regarding “binding agent” the instant specification states “The term “binding agent” refers to a molecule that specifically recognizes and binds to a target molecule of interest” [0049]. The instant specification does not define the term “specifically binds”; as defined in the art, specific binding means the selective interaction of an agent with a particular target above other targets (e.g. McBride JM, Eckmann JP, Tlusty T. General Theory of Specific Binding: Insights from a Genetic-Mechano-Chemical Protein Model. Mol Biol Evol. 2022 Nov 3;39(11):msac217. doi: 10.1093/molbev/msac217. PMID: 36208205; PMCID: PMC9641994; PTO-892 2/23/2026, Abstract). Thus, the broadest reasonable interpretation of the claim is that the claim requires a composition comprising a collection of solid-phase substrates coated with one or more homogenous binding agents capable of selective interaction with an antibody, wherein the antibody is directed against a single antigen selected from the group consisting of the list of target antigens recited. In particular, the Examiner notes that nothing in the claims requires the binding agent specifically binds to a particular epitope of an antibody directed against a single target antigen (e.g. the antigen binding domain) or that that binding agent must interact selectively with certain single antigen-directed antibodies above others. This claim interpretation was also discussed with Applicant as applied to claims 1 and 2 in the interview conducted 5 May 2026. The teachings of Robinson et. al. in regards to claim 1 are in the 102 rejection above. Robinson et. al. further teaches a particular embodiment of an autoantigen microarray comprising 192 distinct putative autoantigens related to rheumatic diseases in quadruplicate including La (synonym for SS-B). Regarding claim 11, Robinson et. al. teaches the autoantigens were spotted ([0136], reads on conjugated by affinity). Robinson et. al. teaches “In addition, we spotted antibodies specific for human IgG and IgM (.alpha.-IgG and .alpha.-IgM)” [0136]. As evidenced by Ye et. al., at least one anti-ENO1 antibody is IgG (Fig. 1, Abstract, p. 617 left column section 3.4); therefore, the microarray of Robinson et. al. includes comprises an additional homogenous binding agent wherein the binding agent specifically binds an antibody that is directed against ENO1. Robinson et. al. does not teach explicitly the composition comprising the collection of solid-phase substrates coated with one or more homogenous populations of binding agents, wherein each homogenous population of binding agents recognizes and specifically binds an antigen-binding site of an antibody that is directed against and specific to CSF2 (elected species), wherein the collection of solid-phase substrates further comprises one or more additional homogenous populations of binding agents, wherein each additional homogenous population of binding agents specifically binds to an antibody that is directed against a single additional antigen selected from the group consisting of ENO1 (elected species). This deficiency is resolved by Meager et. al. Meager et. al. teaches that autoimmune disease had sporadic occurrence of low to moderate levels of autoantibodies to GM-CSF in 41 of 425 patients (Abstract, Table 1). Meager et. al. teaches that GM-CSF autoantibodies were most common in myasthenia gravis (MG) patients (Abstract). Meager et. al. teaches that one of the MG patients was negative for antiacetylcholine receptor autoantibodies (Abstract, “Patient B” section). It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to modify the autoantigen microarray panel to test for autoantibodies found in a variety of autoimmune diseases as taught by Robinson et. al. to include an antigen panel or array for the rheumatic disease myasthenia gravis as taught by Robinson et. al., wherein the antigen panel for myasthenia gravis includes GM-CSF (reads on elected species CSF2), in order to benefit from testing for GM-CSF autoantibodies found in myasthenia gravis patients, including MG patients without AChR antibodies as taught by Meager et. al. This would have a reasonable expectation of success because Robinson et. al. teaches that a variety of antigens associated with autoantibodies in a variety of diseases can be used in the array. The inclusion of CSF2 would result in a microarray comprising all elected species (binding to anti-CSF2 and the IgG anti-ENO1 antibody of Ye et. al.), because as described in the claim interpretation section above, claim 2 does not require the further binding agent to bind to the antigen-binding portion of the antibody . Allowable Subject Matter Claim interpretation: Claim 21 is directed towards a composition comprising a collection of solid-phase substrates coated with one or more homogenous populations of binding agents, wherein each population of homogenous binding agents recognizes and specifically binds an antigen-binding site of an antigen directed against and specific to a single antigen selected from the group of claim 1; wherein the solid-phase substrates are coated with at least three different homogenous populations of binding agents that bind to at least three different antigens; and wherein the substrates are coated with multiple different homogenous populations of binding agents that bind to the antibodies consisting of antibodies to tubulin, LPHN1, SNRPN, KRT18, KRT8, LGALS3, SNRPB2, DEXI, Collagen II, GAPDH, ENO1, AGRN, EMCN, SSB, PLA2R1, GSTT1, VCL, CSF2, LGALS8, STAT6, IL-6, and SHC3. The broadest reasonable interpretation of the claim is therefore that the collection of solid-phase substrates is a closed population coated with only and exactly binding agents to tubulin, LPHN1, SNRPN, KRT18, KRT8, LGALS3, SNRPB2, DEXI, Collagen II, GAPDH, ENO1, AGRN, EMCN, SSB, PLA2R1, GSTT1, VCL, CSF2, LGALS8, STAT6, IL-6, and SHC3. 12-151-08 AIA 07-43 12-51-08 Claim 21 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion Claims 1-5, 7, 9-13, 22, 24, and 35-36 are rejected. Claim 21 is objected to as dependent on a rejected claim. Although additional species were found in the course of examination, the species were not rejoined because the claims are also rejected over the elected species. 07-40 AIA Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL . See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /KATHLEEN CUNNINGCHEN/Examiner, Art Unit 1646 /GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678 Application/Control Number: 17/595,015 Page 2 Art Unit: 1646 Application/Control Number: 17/595,015 Page 3 Art Unit: 1646 Application/Control Number: 17/595,015 Page 4 Art Unit: 1646 Application/Control Number: 17/595,015 Page 5 Art Unit: 1646 Application/Control Number: 17/595,015 Page 6 Art Unit: 1646 Application/Control Number: 17/595,015 Page 7 Art Unit: 1646 Application/Control Number: 17/595,015 Page 8 Art Unit: 1646 Application/Control Number: 17/595,015 Page 9 Art Unit: 1646 Application/Control Number: 17/595,015 Page 10 Art Unit: 1646 Application/Control Number: 17/595,015 Page 11 Art Unit: 1646
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