DETAILED ACTION
Applicant’s response filed 9/26/2025 has been fully considered. The following rejections and/or objections are either reiterated or newly applied.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Claims 31-51 are pending and under consideration in this action. Claim 30 was canceled in the amendment filed 9/26/2025, and claims 1-29 were previously canceled.
Priority
This application is a CON of U.S. 16/836,245, filed 03/31/2020, now abandoned, which is a CON of U.S. 16/054,332, filed 08/03/2018, now abandoned, which is a CON of U.S. 14/169,289, filed 01/31/2014, now abandoned. U.S. 14/169,289 claims domestic benefit to U.S. Provisional Application No. 61/759,432, filed 02/01/2013, as reflected in the filing receipt mailed 12/06/2021. The claim for domestic benefit is acknowledged. As such, the effective filing date of claims 31-51 is 02/01/2013.
Specification
The objection to the abstract of the disclosure is withdrawn in view of Applicant’s amendment to the abstract filed 9/26/2025.
Claim Objections
Withdrawn Objections
The objections to claims 31 and 32 is withdrawn in view of Applicant’s amendments to the claims filed 9/26/2025.
Newly Recited Objections
Claims 41 and 43 are objected to because of the following informalities:
Claims 41 and 43 recite the phrase “at least one of major vault protein (MV)” in lines 12 and 8 of the claims, respectively, which should be corrected to “at least one of major vault protein (MVP)”, for clarity and consistency.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
Withdrawn Rejections
The rejection of claims 30-38 under 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn because Applicant has canceled claim 30.
Newly Recited Rejections
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 31-44 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 claim(s) contains 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly recited and necessitated by claim amendment.
Regarding claim 39, the original disclosure lacks support for “conducting, by at least one processing unit, a measurement of a level of a plurality of biomarkers from a sample from a subject undergoing said treatment regimen for SLE using a multiplexed assay format”. The instant specification (Pg. 9) discloses:
“The specific methods/algorithms for using biomarker levels to make these determinations, as described herein, may optionally be implemented by software running on a computer that accepts the biomarker levels as input and returns a report with the determinations to the user. This software may run on a standalone computer or it may be integrated into the software/computing system of the analytical device used to measure the biomarker levels.”
The software running on a computer as described is only programmed to "accept the biomarker levels as input and return a report with the determinations to the user". As this is the only reference to a computer in the specification, the specification is lacking support for a processing unit that conducts a measurement of a level biomarkers from a sample. Accordingly, these limitations introduce new matter. Claims 31-38 and 40 are also rejected due to their dependency from claim 39.
Regarding claim 41, the original disclosure lacks support for “at least one memory unit”, “at least one processing unit programmed according to software instructions on said at least one memory unit”, “at least one assay system component configured to be controlled by said at least one processing unit”, and “wherein said at least one processing unit is configured to: control said at least one assay system component to conduct a measurement of a level of a plurality of biomarkers in a sample…”. Similar to the explanations provided above for claim 39, the specification is lacking support for an assay system with memory, a processor, an assay system component configured to be controlled by the processor, and wherein the processor is configured to control the assay system component. Accordingly, these limitations introduce new matter. Claim 42 is also rejected due to its dependency from claim 41.
Regarding claim 43, the original disclosure lacks support for a “non-transitory computer readable medium comprising software instructions stored thereon that, when executed by at least one processing unit, cause the at least one processing unit to: conduct, via control of an assay system, a measurement of a level of a plurality of biomarkers in a test sample”. Similar to the explanation provided above for claims 39 and 41, the specification lacks support for a processing unit and software instructions that cause the processing unit to conduct a measurement of a level of biomarkers. Accordingly, these limitations introduce new matter. Claim 44 is also rejected due to its dependency from claim 43.
Claim Rejections - 35 USC § 112(b)
Withdrawn Rejections
The rejection of claims 30-38 under 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn because Applicant has canceled claim 30.
The rejection of claim 31 under 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for lacking antecedent basis for the limitation “said test sample” is withdrawn in view of Applicant’s amendments to the claims filed 9/26/2025.
Newly Recited Rejections
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 31-40 and 45-51 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.
This rejection is newly recited and necessitated by claim amendment.
Claim 39 recites the limitation “a multiplexed measuring method for evaluating the efficacy of a treatment regimen” in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim, since there is no prior mention of this phrase earlier in the claim. This rejection can be overcome by amendment of claim 39 to recite “a multiplexed measuring method for evaluating an efficacy of a treatment regimen”. Claims 31-38 and 40 are also rejected due to their dependency from claim 39.
Claim 45 recites the limitation “configured to measure the level of a plurality of biomarkers” in lines 1-2 of the claim. There is insufficient antecedent basis for this limitation in the claim, since there is no prior mention of this phrase earlier in the claim. This rejection can be overcome by amendment of claim 45 to recite “configured to measure a level of a plurality of biomarkers”. Claims 46-51 are also rejected due to their dependency from claim 45.
Claim Rejections - 35 USC § 101
Withdrawn Rejections
The rejection of claims 30-38 under 35 U.S.C. 101 because the claimed invention is allegedly directed to an abstract idea without significantly more is withdrawn because Applicant has canceled claim 30.
Newly Recited Rejections
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 31-51 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
This rejection is newly recited and necessitated by claim amendment.
Step 1:
In the instant application, claims 31-40 are directed towards a method, claims 41-42 are directed towards a system, claims 43-44 are directed towards a manufacture, and claims 45-51 are directed towards an apparatus, which falls into one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claim 31 recites a mental process (i.e., an observation of how the measurement was performed) in “where said conducting of a measurement comprises using one reaction volume comprising said sample”.
Claim 32 recites a mental process (i.e., an evaluation of two levels) in “comparing said level of said plurality of biomarkers and said baseline level”.
Claims 33 and 47 recite a mental process (i.e., an observation of the contents of the format) in “wherein said multiplexed assay format further comprises one or more diluents”.
Claims 34 and 51 recite a mental process (i.e., an observation of the label of an antibody) in “wherein said detection antibodies are labeled with an electrochemiluminescent (ECL) label”.
Claims 35 and 48 recite a mental process (i.e., an observation of the contents of the assay format) in "wherein said multiplexed assay format further comprises an ECL read buffer".
Claim 36 recites a mental process (i.e., an observation of the contents of the vials) in "wherein said multiplexed assay format comprises one or more vials, containers, or compartments further comprising a set of calibrator proteins".
Claim 37 recites a mental process (i.e., an observation of the state of the calibrator proteins) in "wherein said set of calibrator proteins comprise a lyophilized blend of proteins".
Claim 38 recites a mental process (i.e., an observation of the state of the calibrator proteins) in "wherein said set of calibrator proteins comprise a liquid formulation of calibrator proteins".
Claims 39, 41, and 43 recite a mental process (i.e., an evaluation of the treatment regimen) in “evaluate/evaluating whether the subject is responsive to said treatment regimen”.
Claims 40, 42, and 44 recite a mental process (i.e., an evaluation of two levels) in “wherein said evaluating in (b) comprises comparing said level to a normal control level of said biomarkers”.
Claim 46 recites a mental process (i.e., an observation of the contents of the format) in “further comprises one or more assay reagents used in said assay, said one or more assay reagents provided in one or more vials, containers, or compartments of said format”.
Claim 49 recites a mental process (i.e., an observation of the contents of the protein array) in “wherein said protein array comprises at least three of major vault protein (MVP), ribosomal protein S 13, Sjogren syndrome type B antigen (SSB), and tripartite motif-containing 21 protein (TRIM21).”
Claim 50 recites a mental process (i.e., an observation of the contents of the protein array) in “wherein said protein array comprises each of major vault protein (MVP), ribosomal protein S13, Sjogren syndrome type B antigen (SSB), and tripartite motif-containing 21 protein (TRIM21)”.
These recitations are similar to the concepts of collecting information, and displaying certain results of the collection and analysis is Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). The following claims recite limitations that equate to additional elements:
Claims 31-32, and 39-44 recite “at least one processing unit”.
Claim 32 recites “measuring a baseline level of said plurality of biomarkers”.
Claim 39 recites “conducting a measurement of a level of a plurality of biomarkers from a sample from a subject undergoing said treatment regimen for SLE using a multiplexed assay format, said format comprising: (i) a protein array for detecting autoreactive antibodies against autoantigens, wherein said autoantigens comprise at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif containing 21 protein (TRIM21); and (ii) a set of labeled detection antibodies in one or more vials, containers, or compartments”.
Claim 41 recites “at least one memory unit”, “at least one processing unit programmed according to software instructions on said at least one memory unit”, “at least one assay system component configured to be controlled by said at least one processing unit”, and “wherein said at least one processing unit is configured to: control said at least one assay system component to conduct a measurement of a level of a plurality of biomarkers in a sample from a subject undergoing a treatment regimen for SLE using a multiplexed assay format, said format comprising: (i) a protein array for detecting autoreactive antibody levels against autoantigens, wherein said autoantigens comprise at least one of major vault protein (MV) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif containing 21 protein (TRIM21); and (ii) a set of labeled detection antibodies in one or more vials, containers, or compartments”.
Claim 43 recites “a non-transitory computer readable medium comprising software instructions stored thereon that, when executed by at least one processing unit, cause the at least one processing unit to…”, and “conduct, via control of an assay system, a measurement of a level of a plurality of biomarkers in a test sample from a subject undergoing a treatment regimen for SLE using a multiplexed assay format, said format comprising: (i) a protein array for detecting autoreactive antibody levels against autoantigens, wherein said autoantigens comprise at least one of major vault protein (MV) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif containing 21 protein (TRIM21); and (ii) a set of labeled detection antibodies in one or more vials, containers, or compartments”.
Claim 45 recites “a multiplexed assay format configured to measure the level of a plurality of biomarkers, the format comprising: a protein array for detecting autoreactive antibody levels against autoantigens, the autoantigens comprising at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21); wherein the format comprises a set of labeled detection antibodies in one or more vials, containers, or compartments”.
Regarding the above cited limitations in claims 31-32, 39-44 of (i) at least one processing unit (claims 31-32, 39-40, 42, and 44); (ii) at least one memory unit (claim 41); (iii) at least one processing unit programmed according to software instructions on said at least one memory unit (claim 41); (iv) at least one assay system component configured to be controlled by said at least one processing unit (claim 41); and (v) a non-transitory computer readable medium comprising software instructions stored thereon that, when executed by at least one processing unit, cause the at least one processing unit to… (claim 43). These limitations require only a generic computer component, which does not improve computer technology. Therefore, these limitations equate to mere instructions to implement an abstract idea on a generic computer, which the courts have established does not render an abstract idea eligible in Alice Corp. 573 U.S. at 223, 110 USPQ2d at 1983.
Regarding the above cited limitations in claims 32, 39, 41, 43, and 45 of (vi) measuring a baseline level of said plurality of biomarkers (claim 32); (vii) conducting a measurement of a level of a plurality of biomarkers from a sample from a subject undergoing said treatment regimen for SLE using a multiplexed assay format, said format comprising: (i) a protein array for detecting autoreactive antibodies against autoantigens, wherein said autoantigens comprise at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif containing 21 protein (TRIM21); and (ii) a set of labeled detection antibodies in one or more vials, containers, or compartments (claims 39, 41, and 43); and (viii) a multiplexed assay format configured to measure the level of a plurality of biomarkers, the format comprising: a protein array for detecting autoreactive antibody levels against autoantigens, the autoantigens comprising at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21); wherein the format comprises a set of labeled detection antibodies in one or more vials, containers, or compartments (claim 45). These limitations equate to insignificant, extra-solution activity of mere data gathering because these limitations gather data before or after the recited judicial exceptions of evaluating whether a subject is responsive to the treatment regimen (see MPEP § 2106.04(d)). As such, claims 31-51 are directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to well-understood, routine and conventional (WURC) limitations (MPEP § 2106.05(d)). The instant claims recite same additional elements described in Step 2A, Prong Two above.
Regarding the above cited limitations in claims 31-32, 39-44 of (i) at least one processing unit; (ii) at least one memory unit; (iii) at least one processing unit programmed according to software instructions on said at least one memory unit; (iv) at least one assay system component configured to be controlled by said at least one processing unit; and (v) a non-transitory computer readable medium comprising software instructions stored thereon that, when executed by at least one processing unit, cause the at least one processing unit to. These limitations equate to instructions to implement an abstract idea on a generic computing environment, which the courts have established does not provide an inventive concept (see MPEP § 2106.05(d) and MPEP § 2106.05(f)).
Regarding the above cited limitations in claims 32, 39, 41, 43, and 45 of (vi) measuring a baseline level of said plurality of biomarkers; (vii) conducting a measurement of a level of a plurality of biomarkers from a sample from a subject undergoing said treatment regimen for SLE using a multiplexed assay format, said format comprising: (i) a protein array for detecting autoreactive antibodies against autoantigens, wherein said autoantigens comprise at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif containing 21 protein (TRIM21); and (ii) a set of labeled detection antibodies in one or more vials, containers, or compartments; and (viii) a multiplexed assay format configured to measure the level of a plurality of biomarkers, the format comprising: a protein array for detecting autoreactive antibody levels against autoantigens, the autoantigens comprising at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21); wherein the format comprises a set of labeled detection antibodies in one or more vials, containers, or compartments. These limitations equate to laboratory techniques that are WURC limitations in the life science arts (see MPEP § 2106.05(d)). Determining the level of a biomarker in blood by any means is a WURC limitation in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017).
These additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 31-51 are not patent eligible.
Response to arguments under 35 U.S.C. 101
Applicant’s arguments filed 9/26/2025 have been fully considered but they are not persuasive.
Applicant argues that claims 31-38 have been amended to no longer recite alleged mental processes (Applicant’s Remarks, Pg. 9, Para. 3). Applicant’s arguments are not persuasive for the following reasons.
MPEP 2106.04(a)(2)(III) recites:
The courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’" (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same). Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions.
As described in Step 2A, Prong One above, claims 31-38 all recite limitations that have been identified as mental processes. For example, claim 32 recites the limitation “comparing said level of said plurality of biomarkers and said baseline level”. The broadest reasonable interpretation (BRI) of this limitation is an evaluation or comparison of two biomarker levels, which has been identified as a mental process that can reasonably be performed in the human mind. The limitations described in claims 31 and 33-38 have also been identified as mental processes, as they are all observations of the assay format. For example, claim 35 recites the limitation “wherein said multiplexed assay format further comprises an ECL read buffer”. This limitation has been identified as a mental process, as it is merely an observation of the assay format, which can reasonably be performed in the human mind. This argument is thus not persuasive.
Claim Rejections - 35 USC § 103
Withdrawn Rejections
The rejection of claims 30-31 and 33-35 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Glezer et al. in view of Kemp et al. and Hanly et al. is withdrawn because Applicant has canceled claim 30.
The rejection of claim 32 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Glezer et al. in view of Kemp et al., Hanly et al., and Furie et al. is withdrawn because Applicant has canceled claim 30.
The rejection of claims 36-38 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Glezer et al. in view of Kemp et al., Hanly et al., and Nechansky et al. is withdrawn because Applicant has canceled claim 30.
Newly Recited Rejections
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 31-33 and 39-47 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hanly et al. (Comparison between multiplex assays for autoantibody detection in systemic lupus erythematosus. J lmmunol Methods. 358(1-2): 75-80 (2010); published 5/1/2010; previously cited) in view of Kemp et al. (lmmunoscreening of phage-displayed cDNA-encoded polypeptides identifies B cell targets in autoimmune disease. Biochem Biophys Res Commun. 298(1): 169-177 (2002); published 10/4/2002; previously cited).
This rejection is newly recited and necessitated by claim amendment.
Regarding claims 39, 41, and 43, Hanly et al. teaches a method to evaluate multiplex assays for autoantibody detection in patients with systemic lupus erythematosus (SLE), where the patients enrolled in the study are taking a variety of medications (i.e., a multiplexed measuring method for evaluating the efficacy of a treatment regimen in a patient diagnosed with systemic lupus erythematosus (SLE)) (Title; Pg. 77, Table 2; and Pg. 77, Col. 1, Para. 1). Hanly et al. further teaches that serum samples were retrieved from the lupus clinic serum bank and examined for a panel of autoantibodies using the BioPlex 2200 ANA screen (Pg. 76, Col. 2, Para. 1). The serum is from patients with SLE, where the patients enrolled in the study are taking a variety of medications (i.e., a plurality of biomarkers from a sample from a subject undergoing said treatment regimen for SLE) (Pg. 77, Table 2, and Pg. 77, Col. 1, Para. 1). The BioPlex 2200 system was used to measure a panel of autoantibodies as per the manufacturer's directions (i.e., conducting a measurement of a plurality of biomarkers using a multiplexed assay format and a protein array for detecting autoreactive antibodies against autoantigens) (Pg. 76, Col. 2, Para. 2). Hanly et al. further teaches that analysis was performed using the software R (i.e., on a computer which contains at least one processing unit) (Pg. 76, Col., 2, Para. 5). Hanly et al. further teaches that the BioPlex 220 system was used to measure a panel of autoantibodies. The panel includes autoantibodies to SS-B/La (i.e., wherein said autoantigens comprise at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21)) (Pg. 76, Col. 2, Para. 2). Hanly et al. further teaches that in the QuantaPlex ENA8 assay kit, which also includes the SS-B/La autoantibody, reactivity was assayed in a laser bead assay on a Luminex 100 flow fluorimeter (i.e., a set of labeled detection antibodies in one or more vials, containers, or compartments) (Pg. 76, Col. 2, Para. 3). Hanly et al. further teaches that patients were evaluated upon enrollment into the registry and every 12 months thereafter. Laboratory data and serum samples from the enrollment visit as well as 2nd or 3rd clinic visits were analyzed (i.e., evaluating whether the subject is responsive to said treatment regimen) (Pg. 76, Col. 1, Para. 4).
Regarding claim 31, Hanly et al. teaches that the new immunoassays described herein have the ability to detect multiple analytes concurrently in a single biological sample (i.e., wherein said conducting of a measurement comprises using one reaction volume comprising said sample) (Pg. 76, Col. 1, Para. 1).\
Regarding claim 32, Hanly et al. teaches that patients were evaluated upon enrollment into the registry and every 12 months thereafter. Laboratory data and serum samples from the enrollment visit as well as 2nd or 3rd clinic visits were analyzed (i.e., measuring a baseline level of said plurality of biomarkers (e.g., at enrollment) and comparing said level of said plurality of biomarkers and said baseline level (e.g., at 2nd or 3rd visits 12 or 24 months later)) (Pg. 76, Col. 1, Para. 4).
Regarding claims 33 and 47, Hanly et al. teaches that antibodies were quantified using serial dilutions of test samples if required (i.e., wherein said multiplexed assay format further comprises one or more diluents) (Pg. 76, Col. 2, Para. 2).
Regarding claims 40, 42, and 44, Hanly et al. teaches that autoantibody specificities were reported as positive or negative using a cutoff level of antibody that corresponded to the 99th percentile of values obtained from normal controls provided by the manufacturers (i.e., wherein said evaluating in (b) comprises comparing said level to a normal control level of said biomarkers) (Pg. 76, Col. 2, Para. 2).
Regarding claim 41, Hanly et al. further teaches that analysis was performed using the software R (i.e., on a computer linked to the assay system, which contains at least one memory unit, at least one processing unit programmed according to the software instructions on said at least one memory unit, and at least one assay system component configured to be controlled by said at least one processing unit) (Pg. 76, Col., 2, Para. 5).
Regarding claim 43, Hanly et al. further teaches that analysis was performed using the software R (i.e., on a computer, a non-transitory computer readable medium comprising software instructions stored thereon that, when executed by at least one processing unit, cause the at least one processing unit to…) (Pg. 76, Col. 2, Para. 2).
Regarding claim 45, Hanly et al. teaches the limitations of a protein array for detecting autoreactive antibody levels against autoantigens, the autoantigens comprising at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21) and wherein the format comprises a set of labeled detection antibodies in one or more vials, containers, or compartments as described for claim 39 above.
Regarding claim 46, Hanly et al. teaches that serum samples were retrieved from the lupus clinic serum bank and examined for a panel of autoantibodies using the BioPlex 2200 ANA screen (Pg. 76, Col. 2, Para. 1). The BioPlex 2200 system includes autoantibodies to dsDNA, chromatin, ribosomal P, SS-A/Ro, SS-B/La, Sm, Sm/RNP, U1-RNP, topoisomerase 1, Jo-1 and centromere B (CENP-B) (i.e., which further comprises one or more assay reagents used in said assay, said one or more assay reagents provided in one or more vials, containers, or compartments of said format) (Pg. 76, Col. 2, Para. 2).
Hanly et al. does not teach wherein said autoantigens comprise at least one of major vault protein (MVP) and ribosomal protein S13.
Regarding claims 39, 41, 43, and 45, Kemp et al. teaches that the characterization of self-antigens can contribute an understanding of the etiology of autoimmune disorders as well as to the development of new therapies. Using systemic lupus erythematosus as a model system, novel autoantibody targets including ribosomal protein S20, ribosomal protein S13, ubiquitin-like protein PIC1 (PIC1), and transcription factor-like protein MRG15 were discovered (i.e., wherein said plurality of biomarkers comprises antibodies against at least one of the major vault protein (MVP) and the ribosomal protein S13) (Abstract).
Therefore, regarding claims 31-33 and 39-47, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multiplex assay method for autoantibody detection of Hanly et al. with the teachings of Kemp et al. because characterization of self-antigens is essential for understanding the immunopathological mechanisms in autoimmunity, which may in turn lead to the development of effective therapies and novel diagnostic assays for autoimmune disease (Kemp et al., Pg. 170, Col. 1, Para. 2). One of ordinary skill in the art would be able to combine the teachings of Hanly et al. with Kemp et al. with reasonable expectation of success due to the same nature of the problem to be solved, since both are drawn towards an assay for detection of autoantibodies in systemic lupus erythematosus. Therefore, regarding claims 31-33 and 39-47, the instant invention is prima facie obvious (MPEP § 2142).
Claims 34-35, 48, and 51 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hanly et al. in view of Kemp et al. as applied to claims 31-33 and 39-47 above, and further in view of Glezer et al. (U.S. Patent No. 8,012,745 82; published 09/06/2011; previously cited).
This rejection is newly recited and necessitated by claim amendment.
Hanly et al. in view of Kemp et al., as applied to claims 31-33 and 39-47 above, does not teach wherein said detection antibodies are labeled with an electrochemiluminescent (ECL) label and wherein said multiplexed assay format further comprises an ECL read buffer.
Regarding claims 34 and 51, Glezer et al. teaches that the labels are preferably electrochemiluminescent labels (i.e., wherein said detection antibodies are labeled with an electrochemiluminescent (ECL) label) (Col. 76, Lines 47-48).
Regarding claims 35 and 48, Glezer et al. teaches that the liquid reagents may include a wash buffer, an extraction buffer, an assay diluent, and/or an ECL read buffer (i.e., wherein said multiplexed assay format further comprises an ECL read buffer) (Col. 6, Lines 61-67).
Therefore, regarding claims 34-35, 48, and 51, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multiplex assay method for autoantibody detection of Hanly et al. in view of Kemp et al. with the teachings of Glezer et al. because the development of assay kits for point of care measurements allows care providers or patients to quickly make decisions based on diagnostic information, instead of waiting days to receive laboratory results (Glezer et al., Col., 1, Lines 31-38). One of ordinary skill in the art would be able to combine the teachings of Hanly et al. in view of Kemp et al. with Glezer et al. with reasonable expectation of success due to the same nature of the problem to be solved, since both are drawn towards an assay for detection of autoantibodies in disease. Therefore, regarding claims 34-35, 48, and 51, the instant invention is prima facie obvious (MPEP § 2142).
Claims 36-38 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hanly et al. in view of Kemp et al. as applied to claims 31-33 and 39-47 above, and further in view of Nechansky et al. (Comparison of the Calibration Standards of Three Commercially Available Multiplex Kits for Human Cytokine Measurement to WHO Standards Reveals Striking Differences. Biomarker Insights. 3:227-235 (2008); published 4/18/2008; previously cited).
This rejection is newly recited and necessitated by claim amendment.
Hanly et al. in view of Kemp et al., as applied to claims 31-33 and 39-47 above, does not teach wherein one or more vials, containers, or compartments further comprise a set of calibrator proteins; wherein said set of calibrator proteins comprise a lyophilized blend of proteins; and wherein said set of calibrator proteins comprise a liquid formulation of calibrator proteins.
Regarding claim 36, Nechansky et al. teaches a comparison of calibration standards in commercially available multiplex kits (Title). Nechansky et al. further teaches that freeze dried recombinant human interferon gamma (IFNγ), freeze dried human natural tumor necrosis alpha (TNFα), freeze dried human recombinant interleukin-4 (IL4), and freeze dried human recombinant interleukin-2 (IL2) were used as calibration standards (Pg. 228, Col. 2, Para. 2). Nechansky et al. further teaches that for IFNγ, the WHO calibrator performed better than all other standards when measured with the Biosource and the Linco kit (i.e., wherein one or more vials, containers, or compartments further comprise a set of calibrator proteins) (Pg. 230, Col. 2, Para. 2)
Regarding claim 37, Nechansky et al. teaches that the four WHO reference standards (IFNγ, TNFα, IL4, and IL2) were freeze dried (i.e., wherein said set of calibrator proteins comprise a lyophilized blend of proteins) (Pg. 228, Col. 2, Para. 2).
Regarding claim 38, Nechansky et al. teaches that each standard was reconstituted according to the accompanying dataset, aliquoted, and stored at -80°C (i.e., wherein said set of calibrator proteins comprise a liquid formulation of calibrator proteins) (Pg. 228, Col. 2, Para. 2).
Therefore, regarding claims 36-38, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multiplex assay method for autoantibody detection of Hanly et al. in view of Kemp et al. with the teachings of Nechansky et al. because multiplex assay kits are convenient, and allow for a multi-parameter analysis within a short time period using only minute amounts of precious serum samples (Nechansky et al., Pg. 227, Introduction, Para. 1). One of ordinary skill in the art would be able to combine the teachings of Hanly et al. in view of Kemp et al. with Nechansky et al. with reasonable expectation of success due to the same nature of the problem to be solved, since both are drawn towards an assay for detection of antibodies in disease. Therefore, regarding claims 36-38, the instant invention is prima facie obvious (MPEP § 2142).
Claim 49 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hanly et al. in view of Kemp et al. as applied to claims 31-33 and 39-47 above, and further in view of Rhodes et al. (TRIM21 is a trimeric protein that binds IgG Fc via the B30.2 domain. Molecular Immunology. 44(9): 2406-14 (2007); published 11/21/2006).
This rejection is newly recited and necessitated by claim amendment.
Regarding claim 49, Hanly et al. teaches the limitation of wherein said protein array comprises Sjogren syndrome type B antigen (SSB) as described for claim 39 above. Hanly et al. further teaches the incorporation of the Ro52 autoantibody in recomLine ANA/ENA immunoassay (Pg. 76, Col. 2, Para. 4).
Regarding claim 49, Kemp et al. teaches the limitation of wherein said protein array comprises ribosomal protein S13 as described for claim 39 above
Hanly et al. in view of Kemp et al., as applied to claims 31-33 and 39-47 above, does not teach wherein the protein array comprises major vault protein (MVP) or tripartite motif-containing 21 protein (TRIM21).
Regarding claim 49, Rhodes et al. teaches that autoantibodies to TRIM21 (Ro52) are a common serological feature of patients with Sjogren’s syndrome and systemic lupus erythematosus (SLE) (i.e., wherein the protein array comprises tripartite motif-containing 21 protein (TRIM21)) (Abstract).
Therefore, regarding claim 49, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multiplex assay method for autoantibody detection of Hanly et al. in view of Kemp et al. with the teachings of Rhodes et al. because patients with SLE have a multitude of circulating autoantibodies which are proven biomarkers for the diagnosis and pathogenesis of the disease. These may appear sequentially and antedate the full clinical expression of disease and then persist or disappear over time. Thus, the measurement of a panel of autoantibodies has become an important part of the overall assessment of SLE patients in clinical practice (Hanly et al., Pg. 78, Col. 2, Para. 3 – Pg. 79, Col. 1, Para. 1). One of ordinary skill in the art would be able to combine the teachings of Hanly et al. in view of Kemp et al. with Rhodes et al. with reasonable expectation of success due to the same nature of the problem to be solved, since both are drawn towards the detection of autoantibodies for systemic lupus erythematosus. Therefore, regarding claim 49, the instant invention is prima facie obvious (MPEP § 2142).
Response to arguments under 35 U.S.C. 103
Applicant’s arguments filed 9/26/2025 have been fully considered but they are not persuasive.
Applicant argues that Kemp and Hanly fail to correct Glezer’s deficiencies. Glezer in combination with Kemp and Hanly is wholly silent to the detection of autoantibodies against MVP and TRIM21 in evaluating a patient with SLE. Thus, the combination of Glezer, Kemp and Hanly fail to suggest all the elements in a claim (Applicant’s Remarks, Pg. 9, Para. 6 – Pg. 10, Para. 2). Applicant’s arguments are not persuasive for the following reasons:
Newly recited independent claim 39 (as well as claims 41, 43, and 45) recite: “a protein array for detecting autoreactive antibodies against autoantigens, wherein said autoantigens comprise at least one of major vault protein (MVP) and ribosomal protein S13, and at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21)” (emphasis added). As described above, Hanly et al. teaches that the panel of autoantibodies includes SSB/La (i.e., at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21)), while Kemp et al. teaches that the autoantigen ribosomal protein S13 (i.e., at least one of major vault protein (MVP) and ribosomal protein S13). Since the claims do not require all four autoantibodies, Hanly et al. in view of Kemp et al. teaches all the elements in the claim. This argument is thus not persuasive.
Applicant argues that even if Glezer, Kemp, and Hanly did suggest each element of the claimed invention, a person having ordinary skill in the art would not have been motivated to combine the disclosures to arrive at the claimed invention. Nothing in the teachings of Glezer or Kemp would suggest that a person of skill in the art would reasonably expect consistency or reliability in measuring anti-RPS13 autoantibodies in assays when evaluating a patient with SLE. One would not assume the need for detection of the highly validated anti-SSB autoantibody in combination with anti-RPS13 or anti-MVP autoantibodies (Applicant’s Remarks, Pg. 10, Para. 3). Applicant’s arguments are not persuasive for the following reasons:
Hanly et al. discloses the evaluation of three multiplexed assays for measurement of multiple autoantibodies and their association with global disease activity in systemic lupus erythematosus (Abstract). Hanly et al. also discloses that there many factors, conceptual and practical, that underlie the need to develop new assays for the measurement of autoantibodies (Pg. 78, Col. 2, Para. 3). As indicated by Applicant, Hanly et al. does not explicitly disclose the incorporation of anti-RPS13 autoantibodies in the evaluated assays. However, Hanly et al discloses that patients with SLE have a multitude of circulating autoantibodies which are proven biomarkers for the diagnosis and pathogenesis of the disease. These may appear sequentially and antedate the full clinical expression of disease and then persist or disappear over time. Thus, the measurement of a panel of autoantibodies has become an important part of the overall assessment of SLE patients in clinical practice (Pg. 78, Col. 2, Para. 3 – Pg. 79, Col. 1, Para. 1). Because the circulating autoantibodies change over time, evaluating new panels of autoantibodies, such as the inclusion of alternative autoantibodies (e.g., anti-RPS13, anti-MVP, or anti-TRIM21) in the panel, would be vital in the assessment and treatment of SLE patients in the clinic. Therefore, Hanly et al. provides the motivation to test and validate new panels of antibodies. This argument is thus not persuasive.
Applicant argues that the teachings of Furie and Nechansky do not overcome the aforementioned deficiencies of the combination of Glezer, Kemp, and Hanly because they also do not teach the detecting of the unique combination of autoantibodies against at least one of MVP and RPS13, and at least one of SSB and TRIM21. Thus, the previously presented arguments also apply to dependent claims 32 and 36-38 (Applicant’s Remarks, Pg. 11, Para. 2). Applicant’s arguments are not persuasive for the following reasons:
Applicant’s amendments to the claims have rendered the use of Furie et al. moot, while Nechansky et al. is still relied upon for the rejection of claims 36-38 as detailed above. As described in the arguments directly above, Hanly et al. in view of Kemp et al. teaches all the limitations in independent claim 39 (as well as independent claims 41, 43, and 45). Hanly et al. teaches that the panel of autoantibodies includes SSB/La (i.e., at least one of Sjogren syndrome type B antigen (SSB) and tripartite motif-containing 21 protein (TRIM21)), while Kemp et al. teaches that the autoantigen ribosomal protein S13 (i.e., at least one of major vault protein (MVP) and ribosomal protein S13) (emphasis added). Therefore, Nechansky et al. is not relied upon to teach a protein array for detecting a unique combination of autoantibodies agai