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
The amendment filed January 22nd, 2026 is acknowledged. Regarding the Office Action mailed July 22nd, 2025:
The objections to the specification are withdrawn in view of the amendments.
The objections to the claims are withdrawn in view of the amendments.
Maintained or modified rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1, 3, 26, and 37 have been amended. Claims 6, 8-11, 13-18, 20-25, 28-34, 38-80, 82-85, 87-91, and 94-98 have been canceled. Claims 1-5, 7, 12, 19, 26-27, 35-37, 81, 86, 92-93, and 99-101 are pending. Claims 2, 5, 7, 12, 19, 81, 86, 92-93, and 99-101 are withdrawn from consideration as being drawn to non-elected species. Claims 1, 3-4, 26-27, and 35-37 are under examination and discussed in this Office action.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 includes an unnecessary “and” before “(d) implementing SLE clinical management”. Appropriate correction is required.
Claim Rejections - 35 USC § 101 – Modified – Necessitated by Amendment
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 1, 3-4, 26-27, and 35-37 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon and abstract ideas without significantly more. While the claims are directed to a process, and therefore meet step 1 of the subject matter eligibility test (see MPEP 2106.03), the claims recite the natural correlation between expression levels of particular biomarkers and the likelihood of a future systemic lupus erythematosus (SLE) disease event in an SLE subject, and abstract ideas like generating and determining, as well as mathematical concepts like applying a predictive model. The correlation is a natural phenomenon because it describes a consequence of natural processes in the human body (e.g. expression levels of biomarkers as they relate to SLE). The abstract ideas can be considered mental processes, in the case of generating and determining, and mathematical concepts in the case of the predictive model.
While the Applicant has amended the claims to recite “implementing SLE clinical management comprising one or both of monitoring of the SLE subject having classified SLE, and administering a treatment to the SLE subject having classified SLE who has a likelihood of future SLE disease activity”, this recitation amounts to either no treatment at all, or a treatment disclosed with such generality as to not be “particular” (see MPEP 2106.04(d)(2)(a)). Thus, the claimed clinical management cannot serve as a practical application and still constitutes an issue under 35 U.S.C. 101. The rejection is as follows:
Step 2A of the subject matter eligibility test requires a two-pronged analysis. Prong One asks: does the claim recite an abstract idea, law of nature or natural phenomenon? As discussed in MPEP 2106.04(II)(A)(1), the meaning of “recites” is “set forth” or “describes”. That is, a claim recites a judicial exception when the judicial exception is “set forth” or “described” in the claim. In the instant case, the claims describe a natural phenomenon and abstract ideas: the natural correlation between expression levels of particular biomarkers and the likelihood of a future systemic lupus erythematosus (SLE) disease event in an SLE subject, and abstract ideas like generating and determining, as well as mathematical concepts like applying a predictive model.
Prong Two of the analysis under step 2A asks: does the claim recite additional elements that integrate the judicial exception into a practical application of the judicial exception? As discussed in MPEP 2106.04(II)(A)(2), “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B.” The considerations to be used are set forth at MPEP 2106.05(a) through (c) and (e) through (h). Turning to those sections of the MPEP:
MPEP 2106.05(a) has to do with improvements to the functioning of a computer or to any other technology or technical field. The claims at issue do not improve the functioning of a computer or other technology. While the instant claims recite steps of obtaining a dataset of expression levels of biomarkers from a test sample from an SLE subject, where the sample is blood, serum, or plasma; generating a Lupus Flare Predictive Index (LFPI); determining the likelihood of a disease activity event based on the LFPI; the specific calculation requirements for determining the LFPI; implementing clinical management comprising one or both of monitoring and administering an unspecified treatment; obtaining the dataset via assessing expression levels of biomarkers from the test sample; and the future disease activity event being a future flare, increased disease activity not rising to the level of a flare event, stable disease activity, or decreased disease activity, the claims do not improve upon techniques for determining expression level, collection of samples, or mathematical calculations. The claims merely use existing methods for these steps. Note that MPEP 2106.05(a) indicates that “[u]sing well-known standard laboratory techniques to detect enzyme levels in a bodily sample” is an example that the courts have indicated may not be sufficient to show an improvement to technology. That the above steps were known in the prior art will be shown below.
MPEP 2106.05(b) has to do with whether the claims involve the use of a particular machine. In this case, the claims do not involve the use of a particular machine. While the instant claims recite steps of obtaining a dataset of expression levels of biomarkers from a test sample from an SLE subject, where the sample is blood, serum, or plasma; generating a Lupus Flare Predictive Index (LFPI); determining the likelihood of a disease activity event based on the LFPI; the specific calculation requirements for determining the LFPI; implementing clinical management comprising one or both of monitoring and administering an unspecified treatment; obtaining the dataset via assessing expression levels of biomarkers from the test sample; and the future disease activity event being a future flare, increased disease activity not rising to the level of a flare event, stable disease activity, or decreased disease activity, no machines are required by the claim, and certainly no particular machines. Even if some conventional machine were recited in the claims, like an ELISA reader to evaluate expression levels, further considerations such as the particularity or generality of the recited machine must be taken into account, as well as whether the involvement of the machine is merely extra-solution activity. MPEP 2106.05(g) describes “extra-solution activity”, noting that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra-solution activity.
MPEP 2106.05(c) has to do with whether the claims involve a particular transformation. Here, none of the limitations of the claims involve a particular transformation. For example, obtaining a sample for testing does not transform that sample into something else. Similarly, measuring expression of a biomarker does not transform that biomarker into something else.
MPEP 2106.05(e) has to do with “other meaningful limitations”. The additional limitations imposed upon the natural correlation between expression levels of particular biomarkers and the likelihood of a future systemic lupus erythematosus (SLE) disease event in an SLE subject, and abstract ideas like generating and determining, as well as mathematical concepts like applying a predictive model in the instant case have to do with obtaining a dataset of expression levels of biomarkers from a test sample from an SLE subject, where the sample is blood, serum, or plasma; generating a Lupus Flare Predictive Index (LFPI); determining the likelihood of a disease activity event based on the LFPI; the specific calculation requirements for determining the LFPI; implementing clinical management comprising one or both of monitoring and administering an unspecified treatment; obtaining the dataset via assessing expression levels of biomarkers from the test sample; and the future disease activity event being a future flare, increased disease activity not rising to the level of a flare event, stable disease activity, or decreased disease activity. These limitations are not considered “meaningful limitations”. MPEP 2106.05(e) states: “The phrase "meaningful limitations" has been used by the courts even before Alice and Mayo in various contexts to describe additional elements that provide an inventive concept to the claim as a whole.” However, as will be discussed below, these limitations do not arrive at an inventive concept. In addition, as has been discussed, they represent insignificant extra-solution activity, i.e. “data gathering”.
MPEP 2106.05(f) raises the question as to whether the additional elements recited in the claim represent “mere instructions to apply an exception”. Here, the judicial exception is the natural correlation between expression levels of particular biomarkers and the likelihood of a future systemic lupus erythematosus (SLE) disease event in an SLE subject, and abstract ideas like generating and determining, as well as mathematical concepts like applying a predictive model. The additional elements recited in the claims (i.e. obtaining a dataset of expression levels of biomarkers from a test sample from an SLE subject, where the sample is blood, serum, or plasma; generating a Lupus Flare Predictive Index (LFPI); determining the likelihood of a disease activity event based on the LFPI; the specific calculation requirements for determining the LFPI; implementing clinical management comprising one or both of monitoring and administering an unspecified treatment; obtaining the dataset via assessing expression levels of biomarkers from the test sample; and the future disease activity event being a future flare, increased disease activity not rising to the level of a flare event, stable disease activity, or decreased disease activity) do amount to mere instructions to apply the correlation, since the collection of particular biological samples, obtaining expression levels of biomarkers, and calculating a predictive model serve as mere conventional steps taken for the purpose of gathering data about the likelihood of a future SLE disease activity event, which any practical use of the natural correlation and abstract ideas would require.
MPEP 2106.05(g) has to do with whether the additional elements of the claim amount to insignificant extra-solution activity. MPEP 2106.05(g) notes that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra - solution activity. Likewise, MPEP 2106.05(g) notes that “[p]erforming clinical tests on individuals to obtain input for an equation” also represents insignificant extra-solution activity. This aligns closely with the instant claims, where the additional elements of the claims amount to obtaining a dataset of expression levels of biomarkers from a test sample from an SLE subject, where the sample is blood, serum, or plasma; generating a Lupus Flare Predictive Index (LFPI); determining the likelihood of a disease activity event based on the LFPI; the specific calculation requirements for determining the LFPI; implementing clinical management comprising one or both of monitoring and administering an unspecified treatment; obtaining the dataset via assessing expression levels of biomarkers from the test sample; and the future disease activity event being a future flare, increased disease activity not rising to the level of a flare event, stable disease activity, or decreased disease activity.
MPEP 2106.05(h) has to do with whether the additional elements amount to more than generally linking the use of a judicial exception to a particular technological environment or field of use. Here, the recitation of the method being used to determine the likelihood of a future SLE disease activity event in a SLE subject is considered a “field of use”. However, as MPEP 2106.05(h) indications, such limiting to a particular “field of use” does not confer patentability on otherwise ineligible subject matter.
Having considered the factors discussed in MPEP 2106.05 (a)-(c) and (e)-(h), it is clear that the additional elements recited in the claims, whether considered individually or as a combination, do not integrate the judicial exceptions into a practical application of those exceptions in such a way as to provide meaningful limits on the use of the judicial exceptions. The judicial exceptions are the natural correlation between expression levels of particular biomarkers and the likelihood of a future systemic lupus erythematosus (SLE) disease event in an SLE subject, and abstract ideas like generating and determining, as well as mathematical concepts like applying a predictive model, and the claims amount to using known steps to observe these judicial exceptions.
In addition, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (as set forth in step 2B of the subject matter eligibility test; see MPEP 2106-III) because it was known in the prior art to determine the likelihood of a future SLE disease activity event in an SLE subject using biomarkers and a predictive model.
James (WO2018140606A1; cited in the IDS filed March 30th, 2023) teaches a method of determining the likelihood of a future systemic lupus erythematosus SLE disease activity event in a SLE subject comprising obtaining a dataset comprising expression levels of biomarkers from a test sample from the SLE subject (Pages 5-6, paragraph [0015]), generating a predictive model based on the expression levels in the obtained dataset (Pages 5-6, paragraph [0015]), and (c) determining likelihood of a future SLE disease activity event in the SLE subject based on the predictive model (Pages 5-6, paragraph [0015]); and (d) implementing SLE clinical management comprising administering a treatment to the SLE subject having classified SLE who has a likelihood of future SLE disease activity (Page 6, paragraph [0016]). James teaches on the math behind generating the predictive model based on the expression levels of the biomarkers (Pages 71-72, paragraph [0248]). James teaches administering a treatment to the SLE subject (Page 6, paragraph [0016]). James teaches obtaining a blood, serum or plasma sample from the SLE subject; and assessing expression levels of biomarkers from the test sample from the SLE subject (Pages 5-6, paragraph [0015]). James teaches wherein the future SLE disease activity event is a future flare event (Pages 5-6, paragraph [0015]).
Therefore, the additional elements beyond the judicial exceptions do not represent an inventive concept, because it was known in the prior art to determine the likelihood of a future SLE disease activity event in an SLE subject using biomarkers and a predictive model.
Response to Arguments
Applicant's arguments filed January 22nd, 2026 have been fully considered but they are not persuasive.
The Applicant first summarizes the amendment to claim 1 introducing monitoring and/or administering a treatment to an SLE patient (Page 16 of the Remarks filed January 22nd, 2026). The Applicant then provides context for treatment from the instant specification, further stating that Step 2A, Prong 2 of the subject matter eligibility analysis asks whether a judicial exception has been integrated into a practical application (Page 16 of the Remarks filed January 22nd, 2026). The Applicant argues that the practical application is implementing clinical management involving monitoring or treatment (Page 16 of the Remarks filed January 22nd, 2026).
In response to these arguments, the Examiner would like to note that, as has been stated in the above rejection, the recitation of “implementing SLE clinical management comprising one or both of monitoring of the SLE subject having classified SLE, and administering a treatment to the SLE subject having classified SLE who has a likelihood of future SLE disease activity” amounts to either no treatment at all, or a treatment disclosed with such generality as to not be “particular” (see MPEP 2106.04(d)(2)(a)). Thus, the claimed clinical management cannot serve as a practical application and still constitutes an issue under 35 U.S.C. 101. Therefore, the arguments are not persuasive.
Claim Rejections - 35 USC § 102/103 – Modified – Necessitated by Amendment
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, 26-27, and 35-37 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over James (WO2018140606A1; cited in the IDS filed March 30th, 2023).
Regarding instant claim 1, James teaches a method of determining the likelihood of a future systemic lupus erythematosus SLE disease activity event in a SLE subject (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]), comprising: (a) obtaining a dataset comprising expression levels of biomarkers from a test sample from the SLE subject (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]), wherein the biomarkers comprise: at least the four chemokine(s) or adhesion molecules C-C motif chemokine ligand 2 (CCL1)/monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1 alpha (MIP-1α), C-X-C motif chemokine ligand 10 (CXCL 10)/IFN-gamma-inducible protein 10 (IP-10), and C-C motif chemokine ligand (CCL7)/monocyte chemotactic protein-3 (MCP-3) (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]); at least the two tumor necrosis factor receptor (TNFR) superfamily member molecules tumor necrosis factor receptor I (TNFRI) and tumor necrosis factor receptor II (TNFRII) (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]); at least the two regulatory mediator molecules a total transforming growth factor beta (total TGF-β) and interleukin-10 (IL-10) (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]); and at least the one SLE mediator molecule a stem cell factor (SCF) (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]); (b) generating a Lupus Flare Predictive Index (LFPI) based on the expression levels in the obtained dataset (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]; Pages 71-72, paragraph [0248]); and (c) determining likelihood of a future SLE disease activity event in the SLE subject based on the LFPI (Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]); and (d) implementing SLE clinical management comprising administering a treatment to the SLE subject having classified SLE who has a likelihood of future SLE disease activity (Page 6, paragraph [0016]). Alternatively, James teaches the method of claim 1 as cited above, wherein the generation of a Lupus Flare Predictive Index (LFPI) based on the expression levels in the obtained dataset and determining a likelihood of a future SLE disease activity event in the SLE subject based on the LFPI are obviated by James teaching the same method of mathematically computing the LFPI while instead calling it a soluble mediator score, and using that score to determine the likelihood that an SLE patient will have a flare event (Pages 5-6, paragraph [0015]; Page 7, paragraph [0024]; Pages 71-72, paragraph [0248]; see the rejection of claim 26), which the instant disclosure states is an option for a future SLE disease activity event (instant specification, paragraph [0006]). It would be obvious to one of ordinary skill in the art that equivalent analysis methods would lead to the determining the same number, whether it is called an LFPI or a soluble mediator score. Therefore, James anticipates the method of claim 1 or obviates the method of claim 1.
Regarding instant claim 3, James teaches the method of claim 1, wherein the biomarkers further comprise the one T-helper type-1 (Th1) cytokines interferon-gamma (IFN-γ) (Pages 5-6, paragraph [0015]).
Regarding instant claim 4, James teaches the method of claim 3, wherein the at least one Th1 cytokine comprises interferon-gamma (IFN-γ) (Pages 5-6, paragraph [0015]).
Regarding instant claim 26, James teaches the method of claim 1, wherein generating the LFPI based on the expression levels comprises applying a predictive model, the predictive model comprising, for the expression level of each biomarker: log-transforming the expression level (Pages 71-72, paragraph [0248]); standardizing the expression level (Pages 71-72, paragraph [0248]); obtaining a corresponding coefficient for the biomarker (Pages 71-72, paragraph [0248]); the corresponding coefficient representing an association between expression levels of the biomarker with pre-flare risk and a measurement of future SLE clinical disease activity (Pages 71-72, paragraph [0248]); and weighting the standardized expression level with the corresponding coefficient to obtain a LFPI subscore for the biomarker (Pages 71-72, paragraph [0248]); and summing the LFPI subscores to obtain the LFPI (Pages 71-72, paragraph [0248]). Alternatively, James teaches the method of claim 26 as cited above, wherein the claimed steps for generating an LFPI are obviated by James teaching the same method of mathematically computing the LFPI while instead calling it a soluble mediator score, and using that score to determine the likelihood of a flare event (Pages 5-6, paragraph [0015]; Page 7, paragraph [0024]; Pages 71-72, paragraph [0248]), which the instant disclosure states is an option for a future SLE disease activity event (instant specification, paragraph [0006]). It would be obvious to one of ordinary skill in the art that equivalent analysis methods would lead to the determining the same number, whether it is called an LFPI or a soluble mediator score. Therefore, James anticipates the method of claim 26 or obviates the method of claim 26.
Regarding instant claim 27, James teaches the method of claim 26, wherein for each expression level, the corresponding coefficient is obtained from a linear regression model testing associations between the measurement of SLE clinical disease activity and the pre-flare expression levels of the biomarker (Pages 71-72, paragraph [0248]). See claim 26 for the analysis of the same math obviating determining the same number, regardless of what that number is called.
Regarding instant claim 35, James teaches the method of claim 1, wherein the implementing clinical management comprises the administering a treatment to the SLE subject having classified SLE (Page 6, paragraph [0016]).
Regarding instant claim 36, James teaches the method of claim 1, wherein obtaining the dataset comprising expression levels of biomarkers comprises: obtaining a blood, serum or plasma sample from the SLE subject; and assessing expression levels of biomarkers from the test sample from the SLE subject (Pages 5-6, paragraph [0015]).
Regarding instant claim 37, James teaches the method claim 1, wherein the future SLE disease activity event is a future flare event (Pages 5-6, paragraph [0015]).
Response to Arguments
Applicant's arguments filed January 22nd, 2026 have been fully considered but they are not persuasive.
The Applicant first cites case law related to anticipation and how it is considered (Page 16 of the Remarks filed January 22nd, 2026). The Applicant then states that the cited art fails to disclose:
selecting at least four chemokine(s) selected from their claimed list, as well as not disclosing further optional selections (Page 17 of the Remarks filed January 22nd, 2026);
discriminating between native and total TGF-β, which are argued to have distinctly different configurations with structural differences, and further disclosing optional regulatory mediator molecules that would result in different algorithmic outcomes (Page 17 of the Remarks filed January 22nd, 2026);
selecting at least one SLE mediator from SCF and Resistin, as well as not disclosing Resistin and further including options not claimed (Page 17 of the Remarks filed January 22nd, 2026);
determining the likelihood of future SLE disease activity based on the L-FPI (Page 17 of the Remarks filed January 22nd, 2026);
administering clinical management of monitoring, treatment, or both (Page 18 of the Remarks filed January 22nd, 2026).
In response to these arguments, the Examiner would first like to note that claimed options for each type of biomarker that at least need to be included have adequately been taught by James (see above rejection of claim 1). The arguments directed towards biomarkers that James additionally teaches are not persuasive given that the claim language of claim 1 is non-limiting. While the Applicant has provided options for each type of biomarker that at least need to be included, the “comprising” language at “wherein the biomarkers comprise” indicates that any other biomarkers may also be included when generating the LFPI. With regards to James not teaching optional biomarker selections that are claimed, it is noted that the Applicant’s response to species election (see Remarks filed June 30th, 2025) that was maintained limited the options required to be taught to those elected, which are adequately taught by James (see above rejection of claim 1). Furthermore, it is irrelevant if James does or does not disclose particular biomarkers beyond those elected because their very optionality means that they are not required by the claim. Therefore, given the current claim language, this argument is not persuasive.
With regard to discriminating between native and total TGF-β, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., discriminating between native and total TGF-β) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, James teaches on assessing expression of TGF-β in general (see James Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]), which reasonably encompasses total TGF-β given that any form of TGF-β will still be representative of TGF-β expression in general. Therefore, this argument is not persuasive.
The Applicant then argues that the mediator combinations as disclosed in claim 1 are different than those disclosed by James, which does not portend same or similar results or algorithm, and it would therefore be inappropriate to conflate the mediator buckets of James with the buckets of the present application (Page 18 of the Remarks filed January 22nd, 2026). The Applicant further argues that each unique combination results in a unique permutation, which affects the LFPI score, its ability to discern future disease, and clinical management (Page 18 of the Remarks filed January 22nd, 2026). The Applicant argues that the selection of mediators as claimed yields a different LFPI score, different impact on the LFPI, and its ability to discern future disease activity (Page 18 of the Remarks filed January 22nd, 2026).
In response to these arguments, it appears that the Applicant is arguing James does not teach likelihood of future SLE disease activity and administering clinical management because James teaches on different combinations of biomarkers than what is instantly claimed. These differences then cause differences in calculating LFPI, which results in differences in determining disease activity and treatment. However, as has been noted above, the “comprising” language at “wherein the biomarkers comprise” in claim 1 indicates that, while it is further defined that there needs to be at least a certain number of each category of biomarkers defined by the claim, any other biomarkers beyond those claimed may also be included when generating the LFPI. James sufficiently teaches all biomarker options required by the claims (see James Pages 5-6, paragraph [0015]; Page 7, paragraph [0022]), and also that all biomarker options can be assessed to determine an LFPI, and further used to determine disease activity and treatment. Therefore, given the current claim language, this argument is not persuasive.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-4, 26-27, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 19034795 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are directed towards determining the likelihood of a future SLE disease activity event in an SLE subject, where the future event is a flare event; selections of the same biomarkers for determining the likelihood of the event; applying a predictive model to generate a score which determines the likelihood of the event; obtaining expression levels from blood, plasma, or serum; and clinical management of treating the SLE subject. Any additional limitations of the claims of copending Application No. 19034795 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-4, 26-27, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of copending Application No. 19049240 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are directed towards determining SLE disease activity in an SLE subject; selections of the same biomarkers for determining the likelihood of the event; applying a predictive model to generate a score which determines the likelihood of the event; obtaining expression levels from blood, plasma, or serum; and clinical management of treating the SLE subject. While the instant claims are specifically directed towards determining the likelihood of future SLE disease activity, this would necessarily detect disease activity as in the ‘724 application when using the biomarkers claimed in both sets of claims, obviating this variation. Any additional limitations of the claims of copending Application No. 19049240 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-4, 26-27, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18016384 in view of James (WO2018140606A1; cited in the IDS filed March 30th, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other.
Both sets of claims are directed towards determining SLE disease activity in an SLE subject; selections of similar biomarkers for determining the likelihood of the event; applying a predictive model to generate a score which determines the likelihood of the event; and obtaining expression levels from blood, plasma, or serum. While the instant claims are specifically directed towards determining the likelihood of future SLE disease activity, this would reasonably detect a pre-flare event as in the ‘384 application when using the biomarkers claimed in both sets of claims, obviating this variation.
The ’384 claims do not require the biomarkers CCL3/MIP-1α, CXCL10/IP-10, TGF-β, IL-10, and SCF; or clinical management of monitoring or administering treatment. However, James teaches the biomarkers of the instant case, as well as treating the SLE subject, in the above 103 rejection (see rejection for claims 1, 3-4, 26-27, and 35-37), obviating these variations.
Any additional limitations of the claims of copending Application No. 18016384 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-4, 26-27, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-17, and 19-20 of copending Application No. 17411724 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are directed towards determining SLE disease activity in an SLE subject; selections of the same biomarkers for determining the likelihood of the event; applying a predictive model to generate a score which determines the likelihood of the event; obtaining expression levels from blood, plasma, or serum; and clinical management of treating the SLE subject. While the instant claims are specifically directed towards determining the likelihood of future SLE disease activity, this would necessarily detect disease activity as in the ‘724 application when using the biomarkers claimed in both sets of claims, obviating this variation. Any additional limitations of the claims of copending Application No. 17411724 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-4, 26-27, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10393739B2, in view of James (WO2018140606A1; cited in the IDS filed March 30th, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are directed towards determining SLE disease activity in an SLE subject; selections of the same biomarkers for determining the activity; and obtaining expression levels from blood, plasma, or serum. While the instant claims are specifically directed towards determining the likelihood of future SLE disease activity, this would necessarily detect disease activity as in the ‘739 patent when using the biomarkers claimed in both sets of claims, obviating this variation.
The ’739 claims do not require applying a predictive model to generate a score which determines disease activity and clinical management of monitoring or administering treatment. However, James teaches a predictive model to generate a score which determines disease activity and treating the SLE subject and treating the SLE subject in the above 103 rejection (see rejection for claims 1, 3-4, 26-27, and 35-37), obviating these variations.
Any additional limitations of the claims of U.S. Patent No. 10393739B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1, 3-4, 26-27, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11585810B2, in view of James (WO2018140606A1; cited in the IDS filed March 30th, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are directed towards determining SLE disease activity in an SLE subject; selections of the same biomarkers for determining the activity; applying a predictive model to generate a score which determines disease activity; and obtaining expression levels from blood, plasma, or serum. While the instant claims are specifically directed towards determining the likelihood of future SLE disease activity, this would necessarily detect disease activity as in the ‘810 patent when using the biomarkers claimed in both sets of claims, obviating this variation.
The ’810 claims do not require clinical management of monitoring or administering treatment. However, James teaches treating the SLE subject in the above 103 rejection (see rejection for claims 1, 3-4, 26-27, and 35-37), obviating this variation.
Any additional limitations of the claims of U.S. Patent No. 11585810B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1, 3-4, 26-27, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12140592B2, in view of James (WO2018140606A1; cited in the IDS filed March 30th, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are directed towards determining the likelihood of future SLE disease activity in an SLE subject, where the future event is a flare event; selections of the same biomarkers for determining the likelihood of the event; applying a predictive model to generate a score which determines the likelihood of the event; obtaining expression levels from blood, plasma, or serum; and clinical management of treating the SLE subject.
The ’592 claims do not require the biomarkers CCL2/MCP-1 or IL-10. However, James teaches the biomarkers of the instant case in the above 103 rejection (See rejection for claims 1, 3-4, 26-27, and 35-37), obviating the addition of these biomarkers for detecting SLE disease activity.
Any additional limitations of the claims of U.S. Patent No. 12140592B2 are encompassed by the open claim language “comprising” found in the instant claims.
Response to Arguments
Applicant's arguments filed January 22nd, 2026 have been fully considered but they are not persuasive.
The Applicant first summarizes the rejections from the previous Office Action (Pages 18-19 of the Remarks filed January 22nd, 2026). The Applicant then summarizes the amendment to claim 1, asserting that these amendments are unique from those disclosed by the cited references (Page 19 of the Remarks field January 22nd, 2026).
In response to this argument, it is noted that these amendments are either accounted for in the reference applications and patents, or obvious over the reference of James, as has been analyzed above. Therefore, this argument is not persuasive.
The Applicant argues that it is known to one skilled in the art that concurrent disease activity and future SLE disease activity are not equivalent or related stages of disease and therefore do not inform each other (Page 19 of the Remarks filed January 22nd, 2026). The Applicant argues that the combination, weighting, and contextual measurement of mediators of disease distinguish subdivisions of disease activity (Page 20 of the Remarks filed January 22nd, 2026). The Applicant argues that different combinations of meditators result in unique LFRI scores and different outcomes (Page 20 of the Remarks filed January 22nd, 2026). The Applicant argues that the specific groupings of mediators are different from those in the cited references and any resultant clinical management could never be reproduced by the groupings of the references (Page 20 of the Remarks filed January 22nd, 2026).
In response these arguments, as noted above, any argument directed towards the combination of biomarkers is not persuasive given that the claim language of instant claim 1 is non-limiting. While the Applicant has provided options for each type of biomarker that at least need to be included, the “comprising” language at “wherein the biomarkers comprise” indicates that any other biomarkers may also be included, reasonably encompassing any biomarkers claimed in the reference patents and applications. Any other variations are obvious given James. Furthermore, while the Applicant may argue that there are different combinations, weighting, and contextual measurement of mediators, there are no distinct differences that are not also readily encompassed by the “comprising” claim language of the instant case. Therefore, given the current claim language, these arguments are not persuasive.
The Applicant argues that the subset of subjects for whom the method is utilized is highly relevant to the objectives and operation of the methods (Page 20 of the Remarks filed January 22nd, 2026). The Applicant provides an example for U.S. Patent No. 12140592, stating that it is directed towards a subject who has not reached clinical disease classification, while the instant case is for determining a likelihood of future SLE activity in a subject having classified SLE (Page 20 of the Remarks filed January 22nd, 2026). The Applicant argues that this then represents distinctly different methods, directed to different patient populations, for different purposes (Page 20 of the Remarks filed January 22nd, 2026).
In response to these arguments, it is noted that there is no distinct difference in subjects between the instant case and the reference patents and applications. In this argument, the Applicant has specifically called out U.S. Patent No. 12140592. Turning to the specification of U.S. Patent No. 12140592, it appears that “a subject who has not reached clinical disease classification of SLE” is “a systemic lupus erythematosus (SLE) patient prior to reaching clinical disease classification” (U.S. Patent No. 12140592, column 1, lines 64-67), which can reasonably be interpreted as a subject with classified SLE that is at risk for a future SLE disease activity as recited in the instant case. Ultimately, every application and patent referenced is directed towards looking for disease activity in an SLE patient with biomarkers that are encompassed by the non-limiting claim language of the instant application. There is no clear distinction between the reference applications and patents and the instant case as currently claimed. Therefore, given the current claim language, these arguments are not persuasive.
Conclusion
All claims stand rejected.
THIS ACTION IS MADE FINAL. 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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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683