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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-8 and 10-19, and the species of SEQ ID NO: 3 in the reply filed on 04 December 2025 is acknowledged. Claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The search and examination has been extended to SEQ ID NO: 1 and claim 9.
Claims 1-8 and 10-19 are pending and being examined on the merits.
Priority
The application claims priority to application 63/363,817 filed 04/29/2022.
Information Disclosure Statement
The information disclosure statement filed 06/15/2023 has been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 33 and 35. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term ThermoFisher, Kaluza Software, Dionex, Merck, Agilent Technologies, Sigma, Carl Zeiss, Biosearch Technologies, Cell signaling, Santa-Cruz, Roche, Abcam, Applied Biosystems, GIBCO, STEM CELL, Corning, to name a few, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. A cursory review of the specification has revealed these trademarks or names. It would be remedial to check the specification for additional trademarks or names and amend all upon amendment.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities: Thermofisher is spelled incorrectly on page 33, line 16.
Appropriate correction is required.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Misnumbered claims 15 (non-withdrawned)-16 been renumbered to 17-18.
Claims 1-4, 6, 9-10, 12-14, 16, and 19 are objected to because of the following
informalities: GATA6-ASJ is spelled incorrectly based on the specification spelling of GATA6-AS1.
Appropriate correction is required.
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.
Claim 19 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.
Claim 19 recites, a kit comprising “means for determining the level of GATA6-ASJ lncRNA in an individual”. The BRI given to the word kit is a product comprising a collection of materials. It is unclear what material is encompassed by the definition of ‘means for determining the level of GATA6-ASJ lncRNA in an individual’.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 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 19 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 19 recites “A kit comprising (i) means for determining the level of GATA6-ASJ lncRNA in an individual”. The specification does not provide a definition or explanation how a skilled artisan is to ascertain “means for determining the level of GATA6-ASJ lncRNA”. The is no disclosure of any particular structure, material, or acts to determining the level of GATA6-ASJ lncRNA in an individual. The specification does not demonstrate that applicant has made an invention that achieves the claimed function because the invention is not described with sufficient detail that one of ordinary skill in the art can reasonably conclude that the inventor had possession of the claimed invention.
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 10-13 and 16-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nature-based product without significantly more. Claim 10 recites a pharmaceutical composition comprising GATA6-ASJ lncRNA, or an expression vector encoding GATA6-ASJ lncRNA. Based on the limited background information, there is no indication that the claimed GATA6-ASJ lncRNA, including those defined by the SEQ ID NOs of claim 13, has any characteristics (structural, functional, or otherwise) that are different from the naturally occurring GATA6-ASJ lncRNA. Because there is no difference between the claimed and naturally occurring GATA6-ASJ lncRNA, the claimed GATA6-ASJ lncRNA does not have markedly different characteristics, and thus is a “product of nature” exception. Accordingly, the claim is directed to an exception. This judicial exception is not integrated into a practical application because while the claim additionally include a pharmaceutically acceptable carrier, this additional elements does not amount to significantly more because the specification teaches that this carrier could be water which is also a product of nature.
Subject Matter Eligibility Test for Products and Processes
Step 1 – Is the Claim to a Process, Machine, Manufacture, or Composition of Matter? YES
Claims 10 is directed to a pharmaceutical composition comprising GATA6-ASJ lncRNA, or an expression vector encoding GATA6-ASJ lncRNA, and a pharmaceutically acceptable carrier The claim is a product, which is a statutory category.
Step 2A, Prong One – Does the Claim Recite a judicial exception? YES
The claims recite ‘a pharmaceutical composition comprising GATA6-ASJ lncRNA, or an
expression vector encoding GATA6-ASJ lncRNA, and a pharmaceutically acceptable carrier’. Yang (Yang et al. Stem Cell Reports. Vol. 15. 694–705. September 8, 2020) teaches that GATA6-AS1, an lncRNA divergently transcribed from the GATA6 locus, is highly expressed during endoderm differentiation [abstract]. Therefore, the claims recite the judicial exception of a product of nature.
Step 2A, Prong Two – Does the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
In the instant case, the claims recites “and a pharmaceutically acceptable carrier”. The specification teaches that carrier could be water which is also a product of nature. This additional limitations do not integrate the judicial exception into a practical application. Additionally, claims 11-12 and 16-18 fail to recite any additional elements that would integrate the judicial exception into a practical application.
Step 2B – Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claim as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05
In the instant case, the claims does not recite any additional elements that amount to significantly more or markedly different than the judicial exception. Additionally, Claims 11-12 and 16-18 are intended use claims for the pharmaceutical composition comprising GATA6-ASJ lncRNA and also does not include any additional elements that amounts to significantly more to integrate the judicial exception into practical application.
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.
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 1, 4-8, 10-11, and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao (Xiao et al. Gastroenterology 2018;154:599–611) in view of Laudisi (Laudisi et al. Journal of Crohn's and Colitis, 2022, 301–311) and Yang (Yang et al. Stem Cell Reports. Vol. 15. 694–705. September 8, 2020).
Regarding claims 1 and 7, Xiao teaches long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions, but little is known about their role in maintaining the integrity of the intestinal epithelium [abstract]. Xiao teaches that uc.173 was differentially expressed between intestinal mucosa of fasted vs non-fasted mice [abstract; pg. 601, col. 2, para 5-6; Fig. 1]. Xiao teaches that increasing the levels of uc.173 by transfection of a plasmid vector expressing uc.173 in Caco-2 cells and in cultured organoids isolated from the small intestine in mice promotes growth of the intestinal epithelium [pg. 602, col. 2, para 2 – pg. 603, col. 2, para 1; Fig. 2, Supp Fig. 2]. Xiao teaches that the intestinal mucosal tissues obtained from patients with Crohn’s disease, i.e., an inflammatory bowel disease, exhibited a significant decrease in the levels of uc.173 when compared with those observed in controls (without mucosal injury or inflammation) [pg. 605, col. 1, para 1]. Xiao teaches that inhibition of intestinal mucosal growth occurs commonly in various pathologies and disrupts the epithelium integrity, leading to bacterial translocation and predisposing the mucosa to destructive inflammation, thereby directly correlating the inhibition of intestinal mucosal growth to intestinal inflammation [pg. 600, col. 1, para 1]. Xiao teaches that the findings strongly support the notion that uc.173 is a critical regulator of the gut epithelium homeostasis and its induction enhances growth of the small intestinal mucosa, i.e., prevents intestinal inflammation. [pg. 605, col. 1, para 1].
Xiao do not teach administering GATA6-AS1 lncRNA or an expression vector encoding GATA6-AS1 lncRNA in an individual for preventing chronic intestinal inflammation.
Laudisi teaches that intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs), such as ulcerative colitis [UC] and Crohn’s disease [CD], and that transcriptome analysis performed on colon samples taken from healthy controls (CTRs) and IBD patients revealed that GATA6 was significantly decreased in the IBD epithelium compared with CTR [pg. 302. col. 1, para 2; section 3.1; Fig. 1; abstract]. Laudisi teach that reduced expression of GATA6 promotes intestinal barrier dysfunction, thus amplifying intestinal inflammatory pathology [section 3.2-3.5; Fig. 2-5; abstract].
Yang teaches that GATA6-AS1 interacts with SMAD2/3 and activates the transcription of GATA6 [abstract].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention that administration of a GATA6-AS1 lncRNA or an expression vector encoding GATA6-AS1 lncRNA to an individual could increase GATA6 and be used as a method of treating and preventing IBDs such as UC or CD. One of ordinary skill would be motivated to use GATA6-AS1 lncRNA as a treatment given Laudisi’s teaching that a decrease in GATA6 promotes intestinal dysfunction, Yang’s teaching that GATA6-AS1 activates the transcription of GATA6, and Xiao’s teaching that the administration of a long noncoding RNAs, which is normally expressed at reduced levels in intestinal mucosal tissues obtained from patients with IBDs, enhances growth of the small intestinal mucosa, thereby preventing intestinal inflammation.
Regarding claims 4-5, Xiao teaches that the transfections of vectors were performed using Lipofectamine, i.e., a lipid-based delivery system.
Regarding claims 6 and 10, while Xiao does not teach injection of the lncRNA, Xiao teaches delivering locked nucleic acid (LNA)-modified anti-uc.173 oligonucleotides into a subject via intraperitoneal injections (i.e., comprising a carrier). It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the method as taught and suggested by Xiao and Laudisi where the GATA6-ASJ lncRNA is administered by intraperitoneal injection which is known in the art to comprise a carrier. One of ordinary skill would be motivated to make the modification since Xiao teaches the ability to deliver oligonucleotides by injection.
Regarding claim 11, the teachings of Xiao and Laudisi are discussed above as applied to claims 1 and 10.
Regarding claims 14-15, the teachings of Xiao and Laudisi are discussed above as applied to claims 1, 4-5, and 10.
Regarding claim 16, the teachings of Xiao and Laudisi are discussed above as applied to claims 1, 6, and 10.
Regarding claim 17, the teachings of Xiao and Laudisi are discussed above as applied to claims 1, 7, and 10-11.
Claims 2 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao (Xiao et al. Gastroenterology 2018;154:599–611) in view of Laudisi (Laudisi et al. Journal of Crohn's and Colitis, 2022, 301–311) and Yang, as applied to claims 1 and 10-11 and further in view of Spurlock (US 20190106732A1).
The teachings of Xiao, Yang and Laudisi are discussed above as applied to claims 1 and 10-11 and similarly apply to claims 2 and 12.
Xiao, Yang and Laudisi do not teach where the individual has been diagnosed by a method that comprises measuring GATA6-ASJ lncRNA in the gastrointestinal tract of said individual, detecting a reduced level of GATA6-ASJ lncRNA as compared with a reference level, and thereby providing a positive diagnosis for chronic intestinal inflammation and/or IBD in the individual.
Spurlock teach that differential expression (i.e., increased or decreased expression) of long non-coding RNAs (lncRNAs) are used to diagnose inflammatory diseases such as IBD [abstract; 0006, 0035]. Spurlock teaches a method of identifying presence or absence of a disease, the method comprising: conducting an assay on RNA obtained from a patient sample to measure an expression level of a long noncoding RNA (lncRNA) in said sample; and identifying a positive screen as a level of lncRNA that differs by a statistically-significant amount from a reference expression level of said lncRNA [claim 1].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the method as taught and suggested by Xiao, Yang and Laudisi where the individual receiving the GATA6-ASJ lncRNA could have also be diagnosed by a method that comprises measuring GATA6-ASJ lncRNA in the gastrointestinal tract of said individual, detecting a reduced level of GATA6-ASJ lncRNA as compared with a reference level, and thereby providing a positive diagnosis for chronic intestinal inflammation and/or IBD in the individual. One of ordinary skill would have been motivated to use the GATA6-ASJ lncRNA levels as a means for diagnosis given Laudisi teaching that GATA6 was significantly decreased in the IBD epithelium and Spurlock teaching that differential expression of long non-coding RNAs (lncRNAs) are used to diagnose inflammatory diseases such as IBD.
Claims 3 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao (Xiao et al. Gastroenterology 2018;154:599–611) in view of Laudisi (Laudisi et al. Journal of Crohn's and Colitis, 2022, 301–311) Yang (Yang et al. Stem Cell Reports. Vol. 15. 694–705. September 8, 2020), as applied to claims 1 and 10 and further in view of NG_032677.2 (NG_032677.2, Homo sapiens GATA binding protein 6 (GATA6), RefSeqGene on chromosome 18, 1/25/2021).
The teachings of Xiao, Yang and Laudisi are discussed above as applied to claims 1 and 10 and similarly apply to claims 3 and 13.
Xiao, Yang and Laudisi do not teach wherein said GATA6-ASJ lncRNA comprises or consists of a sequence that is about 90-100% identical to any one of SEQ ID No. 1 or 3.
NG_032677.2 teach the sequence of Homo sapiens GATA binding protein 6 (GATA6). NG_032677.2 teach a sequence from nucleotides 2453-5458 which is 100% identical to SEQ ID NO: 1. NG_032677.2 teaches three sequences: 2458-2872, 3168-3726, and 3875-4117, who together encompass a sequence that is 100% identical to SEQ ID NO: 3.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the method as taught and suggested by Xiao, Yang and Laudisi where the GATA6-ASJ lncRNA comprises or consists of either nucleotides 2453-5458 or a combination of nucleotides 2458-2872, 3168-3726, and 3875-4117 of NG_032677.2. This modification would amount to a simple substitution of one GATA binding protein 6 sequence for another known GATA binding protein 6 sequence.
Claims 8 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao (Xiao et al. Gastroenterology 2018;154:599–611) in view of Laudisi (Laudisi et al. Journal of Crohn's and Colitis, 2022, 301–311) and Yang (Yang et al. Stem Cell Reports. Vol. 15. 694–705. September 8, 2020), as applied to claims 1 and 10-11 and further in view of Sohn (Sohn et al. J. Clin. Invest. 111:121–128 (2003). doi:10.1172/JCI200315937).
The teachings of Xiao, Yang and Laudisi are discussed above as applied to claims 1 and 10-11 and similarly apply to claims 8 and 18.
Xiao, Yang and Laudisi do not teach where the treatment is administered in combination with a TGM2 antagonist.
Sohn teaches that transglutaminase 2 (TGase2, i.e., TGM2) is a calcium-dependent enzyme that catalyzes the covalent cross-linking of the γ-carboxamide groups of a peptide bound glutamine residue with the ε-amino group of a peptide-bound lysine residue, and has increased expression in many inflammatory diseases, such as celiac disease and Crohn disease [pg. 121, col. 2, para 2]. Sohn teaches that an increase of TGase activity in diseases associated with inflammation [pg. 126, col. 2, para 2]. Sohn teaches that a TGase 2 inhibitor might have anti-inflammatory properties [pg. 126, col. 2, para 2]. Sohn teach recombinant peptides (ex. R2) that exhibit inhibitory effect on TGase 2 activity and provide the best protection against inflammation [Fig. 1B; Fig. 3A].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the method as taught and suggested by Xiao, Yang and Laudisi by additionally administering a TGM2 antagonist, such as R2 as taught by Sohn, in combination with the GATA6-ASJ lncRNA. One of ordinary skill would be motivated for the advantage of decreasing TGM2 activity and providing additional protection against mucosal inflammation.
Allowable Subject Matter
Claim 9 is allowed. The prior art does not teach or reasonably suggest a motivation to use a GATA6-ASJ lncRNA to increase mitochondrial membrane potential and/or mitochondrial respiration
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
Prosecution Insights