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 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. 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 46-69 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 46-69 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 between a plurality of skin disease states, wherein the gene expression data comprises a plurality of gene sets e ach comprising a plurality of genes. The step is drawn to an analysis that can be performed by the human mind and is therefore an abstract idea. Claims 48, 49, 50, 57, 59, 63 describe the type of skin disease and therefore are also abstract ideas. Claims 49, 51, 52, 54, 55, 64, 65, and 67-68 recite the molecular endotype and therefore are also abstract ideas. Claims 61-62 are drawn to gene expression data sets and there abstract ideas. Step 2A Prong Two : Consideration of Practical Application Claims 53, 56, 58, 60, 64, 66 , 67 and 69 are drawn to administering “the drug , ” and “administering guselkumab, Risankizumab, Ustekinumab, or any combination thereof to the subject.” These limitations do not integrate the abstract idea into a practical application because “the drug” is not a particular treatment. The limitations where a specific drug is recited (i.e. claims 58, 60, 64, and 67) 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 administration of the correct drug, i.e. guselkumab, Risankizumab, Ustekinumab, or any combination thereof to the subject.” Instead, t hese claims are drawn to a tangential step equivalent to instructions to “apply it,” as described in MPEP 2106.05(f). 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 “the drug” and “administering guselkumab, Risankizumab, Ustekinumab, or any combination thereof to the subject,” and specific drugs as claims 51, 53, 54, 56, 58, 60, 66 , 67 and 69. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because administering a drug and administering e.g. guselkumab, Risankizumab, or Ustekinumab for a skin disease is routine, conventional and well understood. Administering the drugs recited in claims 51, 53, 54, 56, 58, 60, 66, 67 and 69 is routine, conventional and well understood. 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. Claim Rejections - 35 USC § 112-1 st paragraph The following is a quotation of the first paragraph of 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claim s 51-53, 54-56, 64-68 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention. This is a New Matter rejection. Claim 51 is drawn to a first molecular endotype of SSc indicating a propensity to respond to nintedanib or pirfenidone . The specification (page 11-2, par. 18) supports administering a treatment to a patient when classified as l upus, PSO, AD, and/or SSc disease state . The specification states that a pharmaceutical agent can be used to target and/or inhibit VEGFR (e.g., nintedanib, pirfenidone) , TGFB fibroblasts (e.g., nintedanib, pirfenidone) . The specification does not disclose that either nintedanib or pirfenidone can be used specifically for systemic sclerosis. Claim 51 is therefore deemed to be new matter. Claims 52-53 depend therefrom. Claim 54 is drawn to a molecular endotype of systemic sclerosis (SSc) indicates propensity of a subject to respond to BIIB059 or daxdilimab. The specification (page 11-2, par. 18) supports administering a treatment to a patient when classified as l upus, PSO, AD, and/or SSc disease state . The specification states that a pharmaceutical agent can be used to target and/or inhibit ILT7 (e.g., Daxdilmab) or dendritic cells (e.g., BIIB 059, Daxdilmab) . The specification does not disclose that either Daxdilimab or BIIB059 can be used specifically for systemic sclerosis. Claim 54 is therefore deemed to be new matter. Claims 55-56 depend therefrom. Claim 64 is drawn to a molecular endotype of DLE indicates a propensity to respond to a drug selected from botezomib, carfilzomib, ixazomib, daratumumab, isatuximab, elotuzumab, mycophenolate, or mofetil. The specification (page 11-2, par. 18) supports administering a treatment to a patient when classified as l upus, PSO, AD, and/or SSc disease state . The specification states that a pharmaceutical agent can be used to target and/or inhibit proteasome (e.g., bortezomib, carfilzomib, ixazomib); CD38 (e.g., daratumumab, isatuximab); SLAMF7 (e.g., elotuzumab); IMPDH (mycophenylate mofetil) . The specification does not teach botezomib, carfilzomib, ixazomib, daratumumab, isatuximab, elotuzumab, mycophenolate, or mofetil specifically for administration for DLE. Claim 64 is therefore new matter. Claim 65-68 depend therefrom. Claim 6 7 is drawn to a molecular endotype of DLE indicates a propensity to respond to a drug selected from belimumab, inebilizumab, rituximab, glofitamab, or obinutuzumab. The specification (page 11-2, par. 18) supports administering a treatment to a patient when classified as l upus, PSO, AD, and/or SSc disease state . The specification states that a pharmaceutical agent can be used to target and/or inhibit BlyS (e.g., belimumab); CD19 (e.g., inebilizumab); CD20 (e.g., rituximab, obinutuzumab); CD20/CD3 (e.g., glofitamab) . However, the specification does not disclose that from belimumab, inebilizumab, rituximab, glofitamab, or Obinutuzumab are specifically administered to treat DLE. Claim 67 is therefore new matter. Claim 68 depends therefrom. Claim Rejections - 35 USC § 112-2 nd paragraph 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 appl icant regards as his invention. Claim s 54-56 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. Claim 54 recites “a second molecular endotype” which renders the claim unclear because the claims from which claim 54 depends does not recite a first or any other endotype. Claims 55-56 depend from claim 54 and are therefore also unclear. Claim 69 recites administering “the drug to the subject,” that has “the second molecular endotype.” There is insufficient antecedent basis for these limitations because the claims from which claim 69 depends do not recite a drug or a first endotype. It is therefore unclear which drug is to be administered and what the second endotype is second to. Claim Rejections - 35 USC § 103 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). Clai m 46-50 are rejected under 35 U.S.C. 103(a) as being unpatentable over Milano et al. (PLoS vol. 3 (2008) pgs. 1-19). 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 46, step (a) . Milano et al. teach determining distinct gene expression profiles for dSSc and l SSc (page 3-5, section “Overview of the gene expression profiles ” )(i.e. classify between a plurality of skin disease states), as in claim 46, step (a). Milano et al. teach analyzing gene expression for dSSC and ISSc (Abstract)(i.e. disease states comprise systemic sclerosis (SSc) or any combination thereof), as in claim 48 and 49 . Milano et al. teach that SSc is associated with inflammatory response (page 5, col. 2, par. 3), as in 47, 48 and 50 . 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 46, step (c). 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. It would be obvious to one of ordinary skill to combine the SSc disease classification as taught by Milano et al. with software for electronically outputting results of skin disease state classification, as also taught by Milano et al. Combining the elements taught in Milano et al. for classification and electronic output is merely a combination of known elements that would yield a predictable result, as set forth in KSR. Claim 51 is rejected under 35 U.S.C. 103(a) as being unpatentable over as applied to claim s 46-50 above, and further in view of Ju et al (US 2022/0064604). Milano et al. teach claims 46-50 as set forth above. Milano et al. do not teach a molecular endotype of SSc indicates that a subject will respond to nintedanib or pirfenidone, as in claim 51. Ju et al. teach treating systemic sclerosis with pirfenidone and nintedanib (par. 00217-00218) and that gene expression of ACTA2 and COLIA1 were significantly reduced in the group treated with pirfenidone and nintedanib (par. 0218), as in claim 51. 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. Claim 54 is rejected under 35 U.S.C. 103(a) as being unpatentable over Milano et al. as applied to claim s 46-50 above, and further in view of Chaichian et al. (J. Clinical Invest. Vol. 129 (2019) pgs. 958-961) Milano et al. teach claims 46-50 as set forth above. Milano et al. do not teach a molecular endotype of SSc 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 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 Chaichian et al. for 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 Milano et al. with Chaichian et al. because both teach determining skin related diseases. Claim s 57, 59, 61, 63-64 and 69 are rejected under 35 U.S.C. 103(a) as being unpatentable over Milano et al. as applied to claim s 46-50 above, and further in view of Berekmeri et al. (Non-invasive Diagnosic vol. 10 (2019) pgs 1-12) in view of Sjowall et al. (Lupus vol. 26 (2017) pgs. 1333-1338) . Milano et al. teach claims 46-50 as set forth above. Milano et al. do not teach profiling psoriasis, as in claim 57. Milano et al. do not teach atopic dermatitis and one gene as in claims 59 and 61. Milano et al. do not teach a molecular endotype of DLE indicates the propensity of the subject to respond to bo r tezomib, as in claim 63-64 and 69 . Berekmeri et al. teach gene expression profile for psoriasis (page 4, col. 2, par. 2), as in claim 57. Berekmeri et al. teach elevated CCL17 as associated with atopic inflammation (i.e. atopic dermatitis)(page 5, col. 2. Par. 2)(i.e. at least one gene from Table 4B23), as in claims 59 and 61. Berekmeri et al. teach gene expression of discoid Lupus erythema tosus (page 6, col. 2, par. 3), as in claims 63, 64 and 69. Sjowall et al. teach administering bortezomib to treat systemic lupus erythematosus which is synonymous with DLE, as in claims 63-64 and 69. 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 Berekmeri et al. for genes related to psoriasis, atopic dermatitis, and DLE, and further with the teachings of Sjowall et al. for administering bortezomib to treat systemic lupus erythematosus. The teachings of Milano et al., Berekmeri et al. and Sjowall et al. amount to a combination of known elements that, when combined would yield a predictable result of using gene profiling to determine skin disease and determined treat DLE with bor tezomib. Claim s 59 and 60 a r e rejected under 35 U.S.C. 103(a) as being unpatentable over Milano et al. as applied to claims 46-50 above, and further in view of Berekmeri et al. (Non-invasive Diagnosic vol. 10 (2019) pgs 1-12) in view of Steinhoff et al. (Skin Health and Disease vol. 2 ( March, 2022) pgs . 1-4) . Milano et al. teach claims 46-50 as set forth above. Milano et al. do not teach administering Guselkumab, as in claim 60. Berekmeri et al. teach elevated CCL17 as associated with atopic inflammation (i.e. atopic dermatitis)(page 5, col. 2. Par. 2), as in claim 59. Steinhoff et al. teach Guselkumab to treat atopic dermatitis (Title and abstract), as in claim 60. 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 Berekmeri et al. for genes related to atopic dermatitis, and further with the teachings of Steinhoff et al. for Guselkumab to treat atopic dermatitis. Steinhoff et al. provide motivation by teaching that adding Guselkumab to treatment reduced inflammation and recurrent infections (Abstract). One of ordinary skill would have expectation of success at combining Milano et al., Berekmeri et al. and Steinhoff et al. because both Berekmeri et al. and Steinhoff et al. teach atopic dermatitis. Claims 58 is rejected under 35 U.S.C. 103(a) as being unpatentable over Milano et al. in view of Berekmeri et al. as applied to claims 46-50 and 57 above, and further in view of Hu et al. (Nature Immunology, vol. 21 (2020) pgs. 736-745). Milano et al. teach claims 46-50 as set forth above. Berekmeri et al. teach gene expression profile for psoriasis (page 4, col. 2, par. 2), as in claim 57. Milano et al. in view of Berekmeri et al. do not teach administering disulfiram or alvelestat, as in claim 58. Hu et al. teach disulfiram blocks pyroptosis (Abstract) wherein it is known by those of ordinary skill in the art that pyroptosis is a form of inflammatory cell death that drives inflammation in conditions like psoriasis. 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 Berekmeri et al. for genes related to atopic dermatitis, and further with the teachings of Hu et al. for administering disulfiram. Hu et al. provide motivation by teaching that disulfiram blocks pyroptosis which is known to drive psoriasis. One of ordinary skill would have expectation of success at combining Milano et al., Berekmeri et al. and Hu et al. because all teach skin diseases. 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 EF S 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 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. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Anna Skibinsky/ Primary Examiner, AU 1635