The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 35-43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and/or natural phenomenon without significantly more. The claim(s) recites method of diagnosing lupus nephritis in a subject, the method comprising the steps of: (a) obtaining a biological sample from a subject; (b) detecting a presence of at least one biomarker in the sample, wherein at least one of the biomarkers is IL-16, Galectin-1, CD163, CD206, FOLR2, proteinase 3 (PRTN3), or a combination thereof; and (c) diagnosing the subject as having lupus nephritis if at least one of IL-16, Galectin-1, CD163, CD 206, FOLR2, or PRTN3 is detected in the sample. This judicial exception is not integrated into a practical application because the claim is based on a naturally occurring correlation between the diagnosed condition and the biomarker and the data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because obtaining a sample and detecting the presence of at least one biomarker are simple data gathering steps that do not add a meaningful limitation to the method.
Claim 53 is 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. The claim language requires "a set of reagents to measure the levels of protein biomarkers in a biological sample, wherein the protein biomarkers comprise CD163, IL-16, GAL1, PRTN3, CD206, FOLR2, or a combination of two or more thereof thereof". A “set of reagents” would appear to require a plurality of reagents, however, the “CD163, IL-16, GAL1, PRTN3, CD206, FOLR2, or a combination of two or more thereof” language appears to include a reagent for a single protein biomarker as well as reagents for a plurality of the protein biomarkers. Thus it is not clear if the scope of the claim includes a single reagent or if the set is required to include a plurality of reagents. Furthermore, if the set of reagent is required to have a plurality of reagents with only one of them being for one of the protein biomarkers, then it is not clear what if any limitation is placed on the other reagents in the set. For examination purposes, examiner will treat claim 53 as covering a single reagent for a single protein biomarker.
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.
Claims 35, 38-41, 43-44, 47-50 and 53 are rejected under 35 U.S.C. 102(a0(1) as being anticipated by Mejia-Vilet (Journal of the American Society of Nephrology 2020. With respect to claim 35, Mejia-Vilet teaches a method of diagnosing lupus nephritis in a subject, the method comprising the steps of: (a) obtaining a biological sample from a subject (see the final paragraph on page 1336); (b) detecting a presence of at least one biomarker in the sample, wherein at least one of the biomarkers is IL-16, Galectin-1, CD163, CD206, FOLR2, proteinase 3 (PRTN3), or a combination thereof (see the first paragraph in the right column on page 1337); and (c) diagnosing the subject as having lupus nephritis if at least one of IL-16, Galectin-1, CD163, CD 206, FOLR2, or PRTN3 is detected in the sample (see at least figures 1-2 and the paragraph bridging the columns of page 1339). Thus claim 35 is anticipated. With respect to claims 38-39, the first paragraph in the right column on page 1337 teaches that plasma and urine were measured and the paragraph bridging the columns of page 1339 teaches that urinary CD163 differentiates active from inactive LN. With respect to claims 40-41 there is not differentiation between types of lupus nephritis so that both types would be expected to be detected (see for example figure 2 and its associated discussion). With respect to claims 43-44, the first paragraph in the left column on page 1337 teaches that concurrent corticosteroid treatment was determined for all patients with lupus. The patients were classified as receiving no corticosteroids, low-dose corticosteroids (prednisone equivalent of #7.5 mg/d), or moderate/high-dose corticosteroids (prednisone equivalent .7.5 mg/d). In both cohorts, patients with lupus were followed monthly during the first 6 months of treatment and then at least quarterly for the first year. As a result claims 43-44 are anticipated. With respect to claims 47-50, see the relative explanation for claims 38-41 above. With respect to claim 53, the first paragraph in the right column on page 1337 teaches that a commercial ELISA kit was used following manufacturer’s instructions (DuoSet DY1607; R&D systems, Minneapolis, MN).
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 35, 38-41, 43-44, 47-50 and 52-53 are rejected under 35 U.S.C. 103 as being unpatentable over Mejia-Vilet as applied to claims 35, 38-41, 43-44, 47-50 and 53 above, and further in view of Wong (Clinical Investigations 2015). Mejia-Vilet does not teach other biomarkers that can be used for a similar diagnosis.
In the paper Wong studied development of acute kidney injury in patients with sepsis and found that it is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. They derived and tested a multi-biomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock. In the study, candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects. The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91–0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72–0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. Thus they derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation. The first full paragraph on page 1648 teaches that the previous transcriptomic studies used a messenger RNA expression signature and found 21 genes with predictive capacity for septic AKI (SAKI). In the current study, they were only able to identify suitable immunoassay reagents to measure the protein products of five of the previously identified genes in serum samples. The resulting five candidate serum protein biomarkers were elastase 2 (ELA2), fibroblast growth factor 13 (FGF13), matrix metalloproteinase 8 (MMP8, at least one of those claimed in claim 52), olfactomedin 4 (OLFM4), and proteinase 3 (PRTN3). The serum concentrations of the candidate biomarkers were measured using a multiplex magnetic bead platform (MILLIPLEX MAP) designed for this project by the EMD Millipore. Biomarker concentrations were measured in a Luminex 100/200 System according the manufacturers’ specifications. The paragraph bridging the columns of page 1649 teaches that further accuracy for estimating the risk of day 3 SAKI was achieved with three of the five candidate biomarkers (ELA2, MMP8, and PRTN3). FGF13, OLFM4, age, and gender did not improve predictive accuracy. The last full paragraph on page 1651 teaches that the three biomarkers in the model are proteases, primarily derived from neutrophils. These general characteristics are consistent with the concept that inflammatory mechanisms play an important role in the development of SAKI. MMP8 was previously reported as a candidate biomarker for detecting renal allograft rejection. Genetic ablation or pharmacologic inhibition of MMP8 delays renal recovery in mice subjected to renal ischemia, which is consistent with the MMP8-based decision node in the model. PRTN3 serves as the autoantigen for Wegener’s granulomatosis, an autoimmune systemic vasculitide that commonly leads to kidney injury, and this is also consistent with the two PRTN3-based decision nodes in the model. Neutrophil extracellular traps containing PRTN3 and ELA2 are detectable in kidney biopsies from patients with autoimmune glomerulonephritis. Incorporation of MMP8 and ELA2 with clinical data used to calculate a “renal angina index” has been shown to predict AKI in critically ill children. they noted that an ELA2-based decision node in the model may allow for distinguishing subjects who initially present with SAKI, but are more or less likely to have improved kidney function by day 3 of septic shock. Collectively, these data support mechanistic links between the candidate biomarkers and the pathophysiology of SAKI, which warrant further exploration.
With respect to the above claims, it would have been obvious to one of ordinary skill in the art at the time the application was filed to perform experiments such as taught by Wong to determine a panel of biomarkers and include at least PRTN3 and MMP8 into that panel because they are recognized proteins related to kidney health or have been found in biopsies of autoimmune glomerulonephritis (lupus nephritis) related to inflammation so that they would have been expected to be related to one or more properties associated with lupus nephritis.
Claims 45-46 and 54 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the combination of protein biomarkers is not taught or fairly suggested by the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The additionally cited art is related to biomarkers for lupus nephritis. It is noted that the above applied reference is exemplary of the art and that at least some of the cited references could have also been used to reject the above claims for different protein biomarkers (see for example the Aendekerk abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Arlen Soderquist whose telephone number is (571)272-1265. The examiner can normally be reached 1st week Monday-Thursday, 2nd week Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571)272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARLEN SODERQUIST/Primary Examiner, Art Unit 1797
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