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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/22/2026 has been entered.
Claims 10, 16, 17, 21, 23, 24, 28, 29, 31, 33, 34 and 39-42 are pending in this application, Claims 23, 24, 28, 29, 31, 33 and 34 are acknowledged as withdrawn, Claims 10, 16, 17, 21 and 39-42 were examined on their merits.
The Examiner notes that the rejection of Claims 40 and 41 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), first paragraph, as failing to comply with the written description requirement, should have been indicated as withdrawn in the Final Action mailed 10/29/2025.
The rejection of Claims 10, 16, 17, 21, 39, 40, 41, 42 and 43 under 35 U.S.C.
§ 103 as being unpatentable over Jacobs et al. (US 2014/0273275 A1), as evidenced
by Emili et al. (US 2005/0048564 A1), both of record, and further in view of Stone et al.
(2014), Zinellu et al. (2016), Baraldo et al. (2015), Lockett et al. (2013), Kats-Ugurlu et
al. (2011), and Dilberti et al. (1984), has been withdrawn due to the Applicant’s amendments to the claims filed 04/10/2026.
Claim Rejections - 35 USC § 112
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 10, 16, 17, 21 and 39-42 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. Claim 10 recites, “measuring in the digested sample a representation of one or more protein biomarkers by correlating the mass spectrometry data to the one or more peptides”. It is unclear what is meant by a “a representation” of one or more protein biomarkers, can a single protein provide a “a representation”? Does the limitation refer to an unspecified quality of, or state of the proteins?
Claim 40 states, “wherein the representation of one or more protein biomarkers is indicated in a 72 plex including protein biomarkers having SEQ ID NOs 1-72”. It is unclear what is meant by “the representation” of one or more protein biomarkers and further how they are “indicated” in a 72plex. Does this mean that all of the one or more protein biomarkers are also present in the complete listing of all 72 protein biomarkers? Claim 41 recites, “generating a heat map of the protein biomarkers in the 72plex”. It is unclear if the heat map is generated using data obtained in Claim 10 and if so, would this require analysis of all 72 of the claimed protein biomarkers? Claims 16, 17, 21, 39 and 42 are rejected as being dependent upon rejected Claim 10 and for failing to resolve the indefiniteness thereof.
Regarding claim 39, the phrase "including" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For purposes of examination, the Examiner has construed any treatment or therapy for the disease as meeting the limitation.
Claim Rejections - 35 USC § 101
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 10, 16, 17, 21 and 39-42 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to a Law of Nature/Natural Phenomenon without significantly more. The claim(s) recite(s) obtaining a biological sample from a human subject, wherein the subject has or is at risk of having a disease, wherein the disease is renal failure, obtaining a digested sample by contacting the biological with one or more proteases, wherein the digested sample comprises one or more peptides, assaying the digested sample by mass spectrometry so as to obtain mass spectrometry data of the biological sample, measuring in the digested sample a representation of one or more protein biomarkers by correlating the mass spectrometry data to the one or more peptides, detecting 7 or more protein biomarkers in the biological sample and obtaining a biomarker signature for the human subject by correlating the one or more peptides to the 7 or more protein biomarkers. The Judicial Exceptions are the natural correlation between the presence or risk of renal failure in a human subject and protein biomarkers found in a biological sample from said subject, see the MPEP at 2106.04(b), I. The claim also recites a Mental Step/Abstract Idea of “correlating” one or more peptides to the 7 or more protein biomarkers, see the MPEP at 2106.04(a)(2), III. These judicial exception are not integrated into a practical application because they amount no more than a general linkage of the use of the Judicial Exception(s) to particular field of use, detecting protein biomarkers characteristic of renal failure or the risk thereof in human subjects. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because of the following analysis:
Step 1) Is the claim to a process, machine, manufacture or composition of matter?
Yes, the claims are to a process.
Step 2A, P1) Does the claim recite an Abstract Idea, Law of Nature or Natural Phenomenon?
Yes, as discussed above the claims recite a Law of Nature or Natural Phenomenon and an Abstract Idea.
Step 2A, P2) Does the claim recite additional elements that integrate the Judicial Exceptions into a practical application?
No, because the limitations do not result in any improvement to the technology or technical field, apply or use the JEs to effect a particular treatment of prophylaxis for a disease or medical condition, implement or use the JEs with a particular integral machine or manufacture, effect a transformation or reduction of a particular article to a different state or thing or apply or use the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Step 2B) Does the claim recite additional elements that amount to significantly more than the JE?
No, the use of mass spectrometry to assay, detect and measure protease digested biological samples for many of the claimed protein biomarkers is well known, routine and conventional activity. See for example, Jacobs et al. (US 2014/0273275 A1), cited in the prior action and Cantley et al. (2016), cited below.
Claims 16, 17 and 21 merely further define the type of mass spectrometry and its function, as well as reciting the further Abstract Ideas/Mental Steps of “are correlated”. Claim 39 recites administration of general (thus non-particular) treatments and/or therapies to the human subject, see the MPEP at 2106.04(d)(2). Claims 39 and 40 are drawn to the organization and presentation of the collected data and are insignificant extra-solution activity of data gathering and output, see the MPEP at 2106.05(g). Claim 42 recites another Abstract Idea/Mental Steps of “comparing” the obtained data to reference data from healthy subjects to “diagnose” the disease or risk of developing the disease.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 10, 16, 17, 21, 39 and 42 are rejected under 35 U.S.C. § 103 as being unpatentable over Cantley et al. (2016), as evidenced by Emili et al. (US 2005/0048564 A1), of record, in view of Anderberg et al. (US 2015/0241419 A1), Anderberg et al. (US 2011/0195429 A1), Anderberg et al. (US 2016/0003850 A1), Arthur et al. (US 2014/0038203 A1), Anderberg et al. (US 2011/0229915 A1), Anderberg et al. (US 2012/0231472 A1) and Anderberg et al. (US 2013/0203074 A1).
Cantley et al. teaches a method comprising: obtaining trypsin digested urine samples comprising one or more peptides from human kidney transplant subjects used as a model for kidney injury/repair/disease (Pg. 8, Discussion, 2nd paragraph) and control subjects;
assaying the digested samples with tandem MS/MS and Triple-TOF hybrid triple quadrupole (q1/q2/q3) TOF mass spectrometry to obtain mass spectrometry data from the samples;
measuring in the digested samples a representation of the one or more protein biomarkers by correlating the MS data to the one or more peptides and obtaining/detecting a biomarker signature by correlating the one or more peptides to the one or more protein biomarkers (Pgs. 3-4, “Extended Multiple Reaction Monitoring [xMRM]” and Pg. 15, Fig. 1 and Pgs. 19-24, Table 1)
and wherein the detected biomarker signature is compared to a reference biomarker signature to identify biomarkers correlated with kidney injury (Pg. 9, Lines 21-31), and reading on Claims 10, 16, 17 and 42.
With regard to Claim 21, Emili et al. evidences that Mass Spectrometry (MS) is
currently the technology of choice for identifying proteins present in biological mixtures
and tandem mass spectrometry (MS/MS) provides a means for fragmenting mass-
selected precursor peptide ions and measuring the mass-to-charge ratio (m/z) of any
product daughter ions produced.
Thus, the protease digested proteins of Cantley et al, including protein biomarkers, would produce peptides correlated with those biomarkers and the tandem mass spectrometry (MS/MS) method of Cantley et al. when performed on those protease digested proteins, including protein biomarkers, would inherently produce precursor and product peptides correlated with those peptides.
The teachings of Cantley et al. were discussed above.
Cantley et al. did not teach a method wherein sample is obtained from a human subject having or at risk of having renal failure, and the biomarkers are:
ceruloplasmin, haptoglobin, coagulation factor x, angiotensinogen, complement C3, complement C5 and apolipoprotein E, as required by Claim 10;
or further comprising administering a treatment or therapy to the subject for the renal failure, as required by Claim 39.
Anderberg et al. (‘419) teaches measurement of ceruloplasmin as a biomarker for the diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury) (Pg. 3, Paragraph [0013]),
wherein mass spectrometry may be used to determine the presence or amount of analytes (Pg. 10, Paragraph [0068]);
and wherein once a diagnosis is obtained, the clinician can readily select a treatment regimen that is compatible with the diagnosis, such as initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, kidney transplantation, delaying or avoiding procedures that are known to be damaging to the kidney, modifying diuretic administration, initiating goal directed therapy, etc. The skilled artisan is aware of appropriate treatments for numerous diseases discussed in relation to the methods of diagnosis described herein (Pg. 15, Paragraph [0103]).
Anderberg et al. (‘429) teaches measurement of haptoglobin as a biomarker for the diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury) (Pg. 3, Paragraph [0013]),
and wherein mass spectrometry may be used to determine the presence or amount of analytes (Pg. 18, Paragraph [0090]).
Anderberg et al. (‘850) teaches measurement of coagulation factor x as a biomarker for the diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury) (Pg. 3, Paragraph [0013]),
and wherein mass spectrometry may be used to determine the presence or amount of analytes (Pg. 17, Paragraph [0084]).
Arthur et al. teaches methods for predicting the onset, progression, or severity of kidney disease such as acute kidney injury (AKI). In some aspects, one or more proteins from a biological sample such as a urine sample may be used to predict the onset, progression, or severity of AKI (aka acute renal failure), in a subject, comprising measuring at least one biomarker protein in a urine sample from said subject, wherein said biomarker protein is selected from the group consisting of: angiotensinogen, alpha-1 antitrypsin and antithrombin III (Pg. 1, Paragraphs [0009]-[0010]),
wherein he measuring may comprise mass spectrometry, LC-MS/MS, selective reaction monitoring (SRM), or multiple reaction monitoring (MRM), MALDI-MS/MS, MALDI-MS, surface enhanced laser desorption/ionization (SELDI), or capillary electrophoresis mass spectrometry (CE-MS) (Pgs. 2-3, Paragraph [0013]).
Anderberg et al. (‘915) teaches measurement of one or more markers selected from the group consisting of Epidermal growth factor, Complement C3, Interleukin-4, Interleukin-1 alpha, Tubulointerstitial nephritis antigen, Transforming growth factor beta-1, Bone morphogenetic protein 7, Osteopontin, Netrin-1, and Growth-regulated alpha protein (collectively referred to herein as "kidney injury markers, and individually as a "kidney injury marker") can be used for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function,
reduced renal function, and/or acute renal failure (also called acute kidney injury) (Pg. 3, Paragraph [0021]),
and wherein mass spectrometry may be used to determine the presence or amount of analytes (Pg. 16, Paragraph [0106]).
Anderberg et al. (‘472) teaches measurement of one or more biomarkers selected from the group consisting of C--C motif chemokine 23, Transmembrane glycoprotein NMB, Brain-derived neurotrophic factor, Cathepsin S, Transforming growth factor beta-2 (and in certain embodiments its pro-form), Urokinase-type plasminogen activator, Angiopoietin-2, Matrilysin, Carcinoembryonic antigen-related cell adhesion molecule 1, Creatine kinase MB, Insulin, Immunoglobulin M, Immunoglobulin E, Macrophage migration inhibitory factor, Galectin-3, Transforming growth factor beta-3 (and in certain embodiments its pro-form), Heparan sulfate, Cadherin-3, Complement C5 (and in certain embodiments, its C5a form), Platelet factor 4, Platelet basic protein, and Stromelysin-2 (each referred to herein as a "kidney injury marker") can be used for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury) (Pg. 3, Paragraph [0017]),
and wherein mass spectrometry may be used to determine the presence or amount of analytes (Pg. 21, Paragraph [0112]).
Anderberg et al. (‘074) teaches measurement of one or more biomarkers selected from the group consisting of Tumor necrosis factor receptor superfamily member 8, Alpha-Fetoprotein, Thyroxine-binding globulin, Prostate-specific antigen (free form), Apolipoprotein A, Apolipoprotein E, Thyrotropin subunit beta, Platelet-derived growth factor B/B dimer, C-C motif chemokine 7, C-C motif chemokine 26, Complement C4-B, Corticotropin, Interferon alpha-2, Interleukin-4 receptor alpha chain, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Interleukin 21, Interleukin 23 alpha subunit, Interleukin-28A, Interleukin-33, Lutropin subunit beta, Matrix Metalloproteinase-1, Neural cell adhesion molecule 1, Pigment epithelium-derived factor, Vascular endothelial growth factor receptor 2,
Vascular endothelial growth factor receptor 3, and IgG4 (each referred to herein as a "kidney injury marker") can be used for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury),
and wherein mass spectrometry may be used to determine the presence or amount of analytes (Pg. 29, Paragraph [0122]).
It would have been obvious to those of ordinary skill in the art to modify the method of detecting by mass spectrometry protein biomarkers for kidney injury/repair/disease in human subject samples of Cantley et al. with the use of the protein biomarkers and disease treatment taught by the Anderberg et al. references and Arthur et al. because this would provide additional biomarkers for the assessment of a particular kidney disease and treatment thereof in a human subject. Those of ordinary skill in the art would have been motivated to make this modification in order to apply the general detection of kidney injury/repair/disease based on biomarker measurements with the detection of specific biomarkers correlated with a specific kidney condition and then treating the condition. There would have been a reasonable expectation of success in making this modification because all the references are generally drawn to the same field of endeavor, that is the mass spectrometric detection of protein biomarkers for determining kidney injury/disease.
Response to Arguments
Applicant’s arguments with respect to claim(s) 10, 16, 17, 21 and 39-43 have been considered but are moot because the new grounds of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 05/14/2026
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