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 .
This Office Action is in reply to Applicants’ correspondence of 03/25/2026.
Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Please Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
In the reply filed on 09/03/2025 Applicants elected, without traverse, the invention of Group I (methods of diagnosing using biomarkers), and the particular combination of biomarkers that is NEXMIF, RAB12, DPY19L2, RAB36, DSP, and POLB.
Claims 2, 6-7, 11-13, 17-18, 20, 30, 33, 42 and 45-47 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as set forth on page 2 of the Office Action of 11/26/2025.
Newly presented 49 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (specifically requiring non-elected biomarkers (claims 2 and 20), there being no allowable generic or linking claim.
Withdrawn Claim Objections
The objection to claim 1 is, as set forth on page 2 of the Office Action of 11/26/2025 is withdrawn in light of the amendments to the claims.
Withdrawn Claim Rejections - 35 USC § 112 - Indefiniteness
The rejections of claims under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth on pages 3-4 of the Office Action of 11/26/2025, are withdrawn in light of the amendments to the claims.
New Claim Rejections - 35 USC § 112 – Indefiniteness
Necessitated by Claim Amendments
Claims 1, 24, 48, 50-51 and 53 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.
Claims 1, 24, 48, 50 are unclear over the required steps of the claimed methods. The rejected claims are directed to methods of “diagnosing and treating sarcoidosis in a human subject”, as recited in the preamble of claim 1. The relevant steps of completing the methods are recited in claim 1 as:
diagnosing the human subject as having sarcoidosis based on an up- or down-regulation of the plurality of protein markers, as compared to the reference level for each protein marker, wherein the up regulation of DSP, RAB36, DPY19L2, and NEXMIF and the down regulation of RAB12 and POLB, is indicative of sarcoidosis;
treating the human subject diagnosed as having sarcoidosis, the treatment comprising administering an effective amount of one or more of corticosteroids, methotrexate, azathioprine, hydroxychloroquine, chloroquine, cyclophosphamide, pentoxifylline, thalidomide, infliximab, adalimumab, colchicine, or a nonsteroidal anti-inflammatory drug.
However, it is unclear if these recited steps are in fact a positive recitation of the detection of the diagnostically indicative compared protein amounts in the sample from the subject and a coordinate diagnosis of sarcoidosis in the subject. The lack of clarity arises when considering the recitation of the phrase “diagnosing … based on”, where it is unclear that the basis is required to be present and detected. In this regard consider the limitations of claim 51, which recites the same “diagnosing the human subject as having sarcoidosis” and “treating the human subject diagnosed as having sarcoidosis” steps, but also recites “and performing additional protein assays on the human subject with the granulomatosis disease who is not diagnosed as having sarcoidosis” indicating that the recitation of the compared gene expression associated with sarcoidosis is not a limitation that requires the presence of the compared levels.
Claims 51 and 53 are unclear over the recitation of the combination of the steps of the claims as “diagnosing the human subject as having sarcoidosis …; treating the human subject diagnosed as having sarcoidosis …; and performing additional protein assays on the human subject with the granulomatosis disease who is not diagnosed as having sarcoidosis”. The claims methods is performed as an analysis of a human subject (a single subject), so it is unclear how the method is intended to diagnosis sarcoidosis in combination with (i.e.: recitation of the conjunction “and”) performing additional analysis of the human subject who is not diagnosed as having sarcoidosis.
Withdrawn Claim Rejections – Improper Markush Group
The rejection of claims for containing an improper Markush grouping of alternatives, as set forth on pages 5-6 of the Office Action of 11/26/2025, are withdrawn in light of the amendments to the claims.
Maintained Claim Rejections - 35 USC § 101
Modified/Newly Applied – as Necessitated by Claim Amendments
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, 24, 48, 50, 51 and 53 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas (e.g.: mental processes, mathematical calculations) and a natural phenomenon without significantly more.
The claim(s) recite(s) methods of diagnosing, and include, for example “diagnosing the subject as healthy or having sarcoidosis based on the up- or down- regulation of the plurality of markers”, as recited in claim 1 (with a similar diagnostic step recited in claim 19). The claims are thus directed to the collection and comparing of information, which is and abstract idea that is a mental process (e.g.: MPEP 2106.04(a)(2)(III)(A)), the observation and evaluation of information to reach a judgment or conclusion. Where the evaluation of data to reach a conclusion is based in the asserted correlation between the presence of a biomarker and the presence of a pathological phenotype, such an association is accepted part of how a biological organism functions (i.e.: a gene expression:phenotype relationship), and as such this element of the claim is a natural phenomenon (e.g.: MPEP 2106.04(b)(I)). The claims additionally recite elements of values as a score, and a weighted score (claim 24) which fall under the mathematical calculation exception (see MPEP 2106.04(a)(2)(I)(C)).
The judicial exceptions of the claims are not integrated into a practical application because there are no clearly required practical steps related to the diagnosing of the subject. As noted earlier in this Office Action, while claims 1 recites steps as “diagnosing” and “treating”, the diagnosing is “based on” up- or down-regulation of protein biomarkers, but it is not clear that the required compared levels are in fact present and detected. This interpretation of the claims is supported by the recited limitations of claim 51, as noted earlier in this Office Action. In the case where there is no required positive diagnosis and associated treatment, there are no additional steps of the claims that are directed to applying or using the judicial exception(s) noted above (e.g.: MPEP 2106.04(d)(I)). The claims end with the diagnosing steps of the claims, which are themselves judicial exceptions as detailed above. Additionally, where the method of claim 51 may end with “performing additional protein assays”, such a step is recited at a high level of generality, with no particular additional method steps, and no particular outcome of any analysis, and as such is not an integration (e.g.: MPEP 2106.04(d)(2))
The claim(s) does/do not Include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims only broadly recite steps of assaying biomarker in a sample. However, such steps were well understood, routine and convention in the prior art (e.g.: MPEP 2106.05(d)). For example, where the claims may encompass the detection of mRNA transcripts as biomarkers, Talreja (2017) teaches whole transcriptome analysis of sarcoidosis-related samples using RNA-seq. And where the claims may encompass the detection of proteins as biomarkers, Guerrero et al (2020) teaches comprehensive proteomic analysis of sarcoidosis-related samples using mass spectrometry (MS)-based proteomics.
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 101 as being directed to a judicial exception to patentability without significantly more. Applicants’ arguments (p.10 of the Remarks of 03/25/2026) have been fully considered but are not persuasive to withdraw the rejection. Applicants have argued that the amended claims include “a particular treatment related to sarcoidosis and thus applies any exception in the claims by treating a human subject identified as having sarcoidosis with a sarcoidosis specific treatment.” This argument is not persuasive where, as set forth in the rejection and earlier in this Office Action, the claims do not clearly require the diagnosis of sarcoidosis and thus administration of a particular treatment. The argument is not persuasive when considering the breadth of claim 51 which includes a step of “performing additional protein assays”, which is not any specific treatment but only additional data gathering recited at a high level of generality.
Withdrawn Claim Rejections - 35 USC § 112 – Scope of Enablement
The rejection of claims under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as set forth on pages 8-12 of the Office Action of 11/26/2025, is withdrawn in light of the amendments to the claims.
New Claim Rejections - 35 USC § 112 – Written Description
Newly Presented as Necessitated by Claim Amendments
Claim 50 is 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.
Claim 50 is directed to the diagnosis of sarcoidosis (as recited in claim 1 form which claim 50 depends) bases of the compared expression levels of mimotopes (as recited in claim 50) of the particular proteins. A mimotope is a macromolecule, typically a peptide, that mimics the structure of an epitope (the specific part of an antigen recognized by an antibody). While they may not share the exact amino acid sequence of the original antigen, they bind to the same antibody. Thus the claims encompass any structures that may biding to the same antibody (any antibody) that is directed to the recited proteins; the claim thus encompasses a very broad genus of possible peptide sequence. The mimotopes have the functionality of being: (1) of similar 3D shape to any epitope of the recited proteins; and (2) having expression levels that are indicative of sarcoidosis. But the application as filed does not provide any guidance as to what peptides may be mimotopes of any protein epitopes, and which mimotopes are in fact associated with sarcoidosis. Consider the particular protein that is DSP (desmoplakin), which is asserted to have increased expression in sarcoidosis (as recited in the claims). The application as filed provide only a particular 20-mer peptide (SEQ ID NO: 5) that has some similarity to a specific portion of DSP (Table 7, specification page 63). But this particular teaching is not informative of any other different mimotopes of any other epitopes of DSP, where the DSP protein is over 2,800 amino acids in length (GenBank Locus EAW55215). Where the specification does not provide the skilled artisan with the ability to identify any mimotope of the recited proteins, or mimotopes that are indicative of sarcoidosis, the claim is properly rejected for having an inadequate written description in the application as originally filed.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
Prosecution Insights