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 .
Information Disclosure Statement
The IDS filed 12/16/2024 and 7/22/2026 have been considered by the Examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application 63/21699 filed 6/30/2021 is acknowledged.
Status of Claims
Claims 70-78 are new
Claims 1-45, 47, 48, 50, 53, 56-60, 63-69 are cancelled.
Claims 46, 49, 51, 52, 54, 55, 61, 62, and 70-78 are under examination.
Claim Rejections - 35 USC § 101
Claims 47, 48, 50, 53, 56-60, 63-69 are cancelled.
The instant rejection is maintained and modified in view of Amendments filed 7/22/2026.
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 46, 49, 51, 52, 54, 55, 61, 62, and 70-78 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 46, 49, 51, 52, 54, 55, 61, 62, and 70-78 are drawn to a method, so a process.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s)
1. analyzing gene expression data set to classify the skin disease state of the subject, wherein the gene expression data comprises a plurality of gene sets each comprising a plurality of genes, as in claims 46, 70, 73 and 76.
The step is drawn to an analysis that can be performed by the human mind and is therefore an abstract idea.
Claims 49, 51, 52, 54, 55, 72, 75 and 78 recite the molecular endotype and therefore are also abstract ideas.
Claims 61-62, 71, 74 and 77 are drawn to gene expression data sets and therefore are the data used in the abstract idea which renders the claim part of the abstract idea.
Step 2A Prong Two: Consideration of Practical Application
Claims 46, 70, 73 and 76 recite administering “a drug,” capable of treating one of the respective diseases wherein the drug is dupilumab capable of treating atopic dermatitis, disulfiram or alvelestat for psoriasis; anifrolumab, belimumab, inebilizumab, rituximab, glofitamab, or obinutuzumab for DLE; and nintedanib or pirfenidone for SSc.
The administration step in claims 46, 70, 73 and 76 do not integrate the abstract idea into a practical application because the recited abstract idea is generic and does not require any analysis related to a specific disease requiring the subsequent administration of the drug. Instead, these claims are drawn to a tangential step equivalent to instructions to “apply it,” as described in MPEP 2106.05(f). The abstract idea does not actually recite analyzing information for any specific disease and determining any specific disease (i.e. atopic dermatitis, psoriasis, DLE and SSc). The abstract idea is therefore not integrated into the practical application of administering the specific treatment.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses 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: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. Administering dupilumab capable of treating atopic dermatitis, disulfiram or alvelestat for psoriasis; anifrolumab, belimumab, inebilizumab, rituximab, glofitamab, or obinutuzumab for DLE; and nintedanib or pirfenidone for SSc.
2 outputting a report indicative of a classification of the skin disease state of the subject, wherein the skin disease state is atopic dermatitis (claim 46), psoriasis (claim 70), discord lupus (DLE)(claim 73), systemic sclerosis (SSc)(claim 76).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the administered drugs are well known, routine and conventional. Outputting information related to a skin disorder is also well known activity and an extra solution activity as described in MPEP 2106.05(g).
Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 7/22/206 have been fully considered but they are not persuasive.
Applicants argue (Remarks, page 8) that the claims are patent eligible under Step 2A, Prong Two because amended claim 46 integrates the judicial exception into a practical application of treating the subject with a particular drug for atopic dermatitis.
In response, it is acknowledged that a particular treatment is recited as an additional element. However, the abstract idea is not integrated into the additional element because claim 46 is drawn to a generic analysis of genes for a generically recited skin disease state of the subject. The claim does not recite any determination of a particular disease based on the analysis such that the analysis could be integrated into the particular treatment for the disease. Instead, with respect to the particular treatment, these claims are drawn to a tangential step equivalent to instructions to “apply it,” as described in MPEP 2106.05(f). The abstract idea does not actually recite analyzing information for any specific disease and determining any specific disease (i.e. atopic dermatitis, or psoriasis, DLE and SSc for new claims 70-78). The abstract idea is therefore not integrated into the practical application of administering the specific treatment.
Claim Rejections - 35 USC § 112-1st paragraph
The rejection of claims 51-53, 54-56, 64-68 under 35 U.S.C. 112, first paragraph are withdrawn in view of Applicant’s amendments filed 7/22/2026.
Claim Rejections - 35 USC § 112-2nd paragraph
The rejection of claims 54-56 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of Applicant’s amendments filed 7/22/2026.
The following rejection is necessitated by Applicants amendments filed 7/22/2026.
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 46, 49, 51, 52, 54, 55, 61, 62, and 70-78 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 pre-AIA the applicant regards as the invention.
Claims 46, 70, 73, and 76 recite analyzing gene expression data to classify “the skin disease state of the subject.” There is lack of antecedent basis for this limitation in the claim. The claim does not recite any subject with or having been determined to have a skin disease. Therefore it is unclear what “the skin disease state of the subject” is referring to. It is suggested that the claim be amended to recite “a skin disease state of the subject” or recite the specific skin disease that is intended by “the skin disease.”
Claim 51 recites “the first molecular endotype of the plurality of molecular endotypes.” There is lack of antecedent basis for this limitation. Claim 51 depends from claim 46. Perhaps claim 51 is intended to depend from claim 49 which does recite “a first molecular endotype.” Correction is required.
Claim 52 recites “the gene set of” Tables 4B -28, -10, -25, -8, -22, -16, -14, -13, -23, -7, -15, -3 or combination thereof. There is lack of antecedent basis for “the gene set.” It is unclear which genes “the gene set” is referring to. The claim does not set forth the metes and bounds of which genes would be considered to be “the gene set” of the listed tables and which genes would be considered as part of “the gene set.”
Claim 55 also recites “the gene set” of Table 4A -12, -16 or both. There is lack of antecedent basis for “the gene set.” As for claim 52, it is not clear which genes are included in “the gene set” of claim 55.
Claims 52, 55, 61, 62, 71, 74 and 77 reference tables by reciting table numbers, the contents of which are disclosed in the specification. USPTO Guidance requires adherence with MPEP 2173.05(s) which states that:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Therefore, Applicants are required to incorporate the intended subject matter from the Tables directly into the claims.
Claim Rejections - 35 USC § 103
The rejection of claims 46-50 under 35 U.S.C. 103(a) as being unpatentable over Milano et al. (PLoS vol. 3 (2008) pgs. 1-19) is withdrawn in view of Applicant’s amendments filed 7/22/2026.
The rejection of claim 51 under 35 U.S.C. 103(a) as being unpatentable over Milano in view of Ju et al (US 2022/0064604) is withdrawn in view of Applicant’s amendments filed 7/22/2026.
The rejection of claims 59 and 60 under 35 U.S.C. 103(a) as being unpatentable over Milano et al. in view of Berekmeri et al. in view of Steinhoff et al. is withdrawn in view of Applicant’s amendments filed 7/22/2026.
The rejection of claims 58 under 35 U.S.C. 103(a) as being unpatentable over Milano et al. in view of Berekmeri et al. in view of Hu et al. is withdrawn in view of Applicant’s amendments filed 7/22/2026.
The following rejections are necessitated by Applicant’s amendments filed 7/22/2026.
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 46, 49, 51, 52, 54, 55 and 61 are rejected under 35 U.S.C. 103(a) as being unpatentable over Mobus et al. (Journal of Allergy and Clinical Immunology vol 147 (2021) pgs. 213-223).
Mobus et al. teach gene signatures associated with atopic dermatitis (Abstract and pg. 215, col. 2, par. 2-3) including CCL17 and CCL22 (i.e. Table 4B-23)(i.e. analyzing gene expression dataset to classify disease state wherein gene expression data comprises a plurality of gene sets comprising a plurality of genes), as in claim 46, step (a).
Mobus et al. classify atopic dermatitis as related to progressive upregulation of signature genes; Mobus et al. does not specifically teach outputting a report however it is well known to one of ordinary skill in the art to output results of a determination of a disease (i.e. outputting a report indicative of a classification of the skin disease which is atopic dermatitis), as in claim 46, step (b).
Mobus et al. teach administering Dupilumab to patients with atopic dermatitis (Abstract); Dupilumab led to a stronger increase in level of epidermal differentiation markers than cyclosporine (Abstract)(i.e. administering to the subject a dupilumab), as in claim 46, step (c).
Mobus et al. teach nonlesional (AN) and lesional skin (AL)(page 214, col. 1, par. 1) with different transcriptome expression (page 215, col. 2, par. 2-3)(i.e. molecular endotype the skin disease); and that the AN and AL respond differently to treatment (page 221, col. 1, lines 6-7 from bottom)(i.e. the first molecular endotype indicates a propensity to respond to the drug), as in claims 49 and 51.
Mobus et al. teach CCL17 associating with AL and AN (page 215, col. 2, par. 3)(i.e. Table 4B-23), as in claim 52.
Mobus et al. teach S100A8 and S100A9 (i.e. Table 4A-12)(Figure 5, right column) as a gene associated with dupilumab high responders, as in claim 55.
Mobus et al. teach teach IL12B and IL23A (i.e. Table 4B-14)(page 221, col. 1, par. 1, 3rd line from end), as in claim 61.
Claim 54 is rejected under 35 U.S.C. 103(a) as being unpatentable over Mobus et al. as applied to claims 46, 49, 51, 52, 54, 55 and 61 above, and further in view of Chaichian et al. (J. Clinical Invest. Vol. 129 (2019) pgs. 958-961).
Mobus et al. teach claims 46, 49 and 51 as set forth above.
Milano et al. do not teach a second molecular endotype that indicates the propensity of the subject to respond to BIIB059, as in claim 54.
Chaichian et al. teach systemic lupus erythematosus (SLE) pathogenesis and inhibiting pathways in skin with BIIB059, where BIIB059 improved cutaneous lupus disease activity (Abstract).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the method of Mobus et al. for gene expression profiling to determine a classification of skin disease states, with the teaching of Chaichian et al. for determining systemic lupus erythematosus and treating with BIIB059. Chaichian et al. provide motivation by teaching that BIIB059 inhibited pathways in skin and is hoped to provide answers in immunopathogenesis (page 960, col. 2, par. 3). One of skill in the art would have had a reasonable expectation of success at combining Mobus et al. with Chaichian et al. because both teach determining skin related diseases.
Claims 70-72 are rejected under 35 U.S.C. 103(a) as being unpatentable over Guttman-Yassky et al. (herein G-Y et al.)(Journal of Allergy and Clinical Immunology vol. 124 (2009) pgs. 1235-1244) in view of Marikovsky et al. (US 6,288,110).
G-Y et al. teach upregulated and down regulated gene signatures for psoriasis as a way to distinguish psoriasis from atopic dermatitis (Abstract and Figure 1); G-Y et al. teach classifying disease related alterations that are unique to each disease and also shared by both diseases (page 1236, col. 2, par. 1)(i.e. analyzing gene expression data to classify disease state of a subject), as in claim 70, step (a).
G-Y et al. teach a report indicative of a classification of psoriasis (Figure 1), as in claim 70, step (b).
G-Y et al. teach (Figure 1) CXCL1 (i.e. Table 4B-25), as in claim 71.
G-Y et al. do not teach administering disulfiram or alvelestat to a subject, as in claim 70, step (c).
G-Y et al. do not teach that the endotype indicates a propensity of the subject to respond to the drug, as in claim 72.
Marikovsky et al. teach (col. 2, lines 32-38) that disulfiram inhibits release of interleukin-1 (which is well known in the art to be associated with psoriasis) and specifically teaches the proposal of disulfiram for the treatment of IL-1 mediated inflammations such as psoriasis, as in claim 70, step (c).
Marikovsky et al. teach that a subject with psoriasis releases IL-1 (i.e. molecular endotyping the skin disease) and could be treated with disulfiram; (i.e. a molecular endotyping the skin disease wherein the molecular endotype of a plurality of endotypes indicates a propensity of the subject to respond to the drug), as in claim 72.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the method of Guttman-Yassky et al. for gene expression signatures for classifying psoriasis with the teaching of Marikovsky et al. for treating psoriasis with disulfiram. Guttman-Yassky et al. provide motivation by teaching that administration of disulfiram inhibits IL-1 which is associated with inflammation in psoriasis. One of skill in the art would have had a reasonable expectation of success at combining Guttman-Yassky et al. with Markiovsky et al. because both teach psoriasis as a disease requiring treatment.
Claims 73-75 are rejected under 35 U.S.C. 103(a) as being unpatentable over Jabbari et al. (Journal of Investigative Dermatology vol. 134 (2014) pgs. 87-95.) in view of Mumford et al. (Mumford "Refractory discoid lupus erythematosus responds to rituximab." Australasian Journal of Dermatology vol. 62 (2020) e341)
Jabbari et al. teach comparison of the discoid lupus erythematosus (DLE) transcriptome to that of psoriasis (Abstract); Jabbari et al. teach gene signatures that are uniquely up- and down- regulated compared to normal and psoriasis skin (page 88, col. 2, par. 3 and page 91, Figure 3c)(i.e. analyzing gene expression data set to classify skin disease state of a subject wherein gene expression data comprises a plurality of gene sets with a plurality of genes), as in claim 73, step (a).
Jabbari et al. teach a report indicative of a classification of DLE (Figure 3), as in claim 73, step (b).
Jabbari et al. teach that DLE is associated with increased cellular signature of B cells (page 88, col. 1, par. 1)(i.e. molecular endotyping) which makes the gene signatures for B cells in Table 4A-1 inherent, as in claim 74 and claim 75.
Jabbari et al. do not teach administering anifrolumab, belimumab, inebilizumab, rituximab, glofitamab or Obinutuzumab to a subject, as in claim 73, step (c).
Jabbari et al. do not teach that the molecular endotype indicates a propensity of the subject to respond to the drug, as in claim 75.
Mumford et al. teach administering rituximab to a subject with DLE who showed significant response to B-cell depletion therapy with rituximab wherein the patient had a positive response to rituximab (pages e343-e343), as in claim 73, step (c).
Mumford et al. suggest that DLE is associated with B-cell expression (i.e. molecular endotype) and that rituximab depleted B-cells. The combination of teachings make obvious a molecular endotype that would respond to rituximab, as in claim 75.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the method of Jabbari et al. for gene expression signatures for classifying DLE with the teaching of Mumford et al. for administering rituximab to a subject with DLE . Mumford et al. provide motivation by teaching that administration of rituximab had a positive effect in reducing DLE in a subject. One of skill in the art would have had a reasonable expectation of success at combining Jabbari et al. with Mumford et al. because both teach DLE as skin disorder associated with B cell expression.
Claims 76-78 are rejected under 35 U.S.C. 103(a) as being unpatentable over Milano et al. (PLoS vol. 3 (2008) pgs. 1-19) in view of Ju et al (US 2022/0064604).
Milano et al. teach (page 2, col. 2, par. 2) studies have demonstrated that the skin of patients with dSSc can be easily distinguished from normal controls at the level of gene expression (i.e. analyzing a gene expression data set to classify the skin disease state, wherein the gene expression data comprises a plurality of sets comprising a plurality of genes), as in claim 76, step (a).
Milano et al. teach determining distinct gene expression profiles for dSSc and lSSc (page 3-5, section “Overview of the gene expression profiles”)(i.e. classify between a plurality of skin disease states), as in claim 76, step (a).
Milano et al. teach analyzing gene expression for dSSC and ISSc (Abstract)(i.e. classification of the skin disease state is systemic sclerosis (SSc)), as in claim 76, step (b).
Milano et al. do not specifically teach electronically outputting a report indicative of a classification of skin disease state for a patient, as in claim 76, step (b). Milano et al. however teach (page 2, col. 2, par. 2) prognosis of SSc in patients which suggests that a classification is output. Milano et al. also teach a PCA software viewer (page 7, col. 2, par. 1) which suggests that results of a classification can be output electronically.
Milano et al. do not specifically teach administering nintedanib or pirfenidone, as in claim 76, step (c).
Milano et al. do not teach a molecular endotype of SSc indicates that a subject will respond to nintedanib or pirfenidone, as in claim 78.
Ju et al. teach treating systemic sclerosis with pirfenidone and nintedanib (par. 00217-00218) and that gene expression of ACTA2 (i.e. claim 77, Table 4B-27) and COL1A1 were significantly reduced in the group treated with pirfenidone and nintedanib (par. 0218), as in claims 76, step (c) and claims 77 and 78.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the method of Milano et al. for gene expression profiling to determine a classification of skin disease states, one of being systemic sclerosis (SSc) with the teaching of Ju et al. for treating systemic sclerosis with pirfenidone and nintedanib. Ju et al. provide motivation by teaching that fibrosis factors are reduced after treatment pirfenidone and nintedanib (par. 0281). One of skill in the art would have had a reasonable expectation of success at combining Milano et al. with Ju et al. because both teach determining patients with SSc.
Response to Arguments
Applicant's arguments filed 7/22/2026 have been fully considered but they are not persuasive.
Applicant’s arguments are directed to rejections that are withdrawn herein, in view of Applicant’s substantial amendments. Applicant’s arguments are moot in view of the newly applied above rejections which are necessitated by amendments filed 7/22/2026.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-7035. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Anna Skibinsky/
Primary Examiner, AU 1635
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