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 .
Response to Amendment
Applicant’s amendment filed 06/09/2026 is acknowledged. Claim 12 is amended, claims 19-29 are newly canceled and claims 30 and 31 are new. Claims 12-16, 30 and 31 are under examination.
Rejections Withdrawn
Any previous rejections over claims 19-29 are hereby withdrawn in response to Applicant’s cancelation of those claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 103
The following rejections under 35 U.S.C. 103 are withdrawn in response to Applicant’s amendment of claim 12 limiting the method to diagnosing, monitoring and treating inflammatory bowel disease or ulcerative colitis, which the applied prior art does not teach.
Claims 12-16 as being unpatentable over Weissleder et al. (WO 2012/129325—of record) in view of Nath (Trends in Molecular Medicine, 2014, 20: 332-342) and Rajan et al. (HUMAN VACCINES & IMMUNOTHERAPEUTICS, 2016, VOL. 12, NO. 9, 2219-2231).
Claims 12, 14-16 and 19 as being unpatentable over d’Alessandro et al. (J Med Virol. 2020; 92: 2216-2220; Epub Jun 9—of record) in view of Nath (Trends in Molecular Medicine, 2014, 20: 332-342) and the letter by Wang et al. (Cell Research (2020) 30:269–271).
Double Patenting
The provisional rejection of claims 12, 13, 16, 19 and 25-27 on the ground of nonstatutory double patenting as being unpatentable over claims 26-45 of copending Application No. 18/009,204 (reference application) in view of Nath (Trends in Molecular Medicine, 2014, 20: 332-342) is withdrawn in response to Applicant’s amendment of claim 12 limiting the method to diagnosing, monitoring and treating inflammatory bowel disease or ulcerative colitis, which the claims of the reference application do not recite.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 12-16 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subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is maintained for the following reason is withdrawn in response to Applicant’s amendment to recite proper Markush language as set forth at MPEP 2117.
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
The rejection of claims 12-16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement is maintained for reasons of record and the following. In addition, new claims 30 and 31 are hereby included in this rejection. Applicant’s amendment has addressed the issue with regard to diagnosing and monitoring colitis or inflammatory bowel disease reciting the specific MUC1 and MUC13 mRNA isoforms. Nevertheless, the claims remain broad with respect to the encompassed treatments: monoclonal antibodies, small molecules and antisense therapy. No antibodies or small molecules that target the mucin isoforms are disclosed in the instant specification. The post-filing date art of Breugelmans et al. (Cells 2023, 12, 1224—of record) suggests that JAK inhibitors might be useful small molecules for treating IBD, but also underscores the complexity regarding treatment:
[O]pposing effects on disease activity during acute and chronic DSS-induced colitis were noticed: the presence of MUC13 was protective during the acute phase whereas it was harmful during chronic DSS administration. IL-22-induced JAK/STAT signaling was clearly implicated in the regulation of MUC1 and MUC13 expression, further suggesting a potential use of JAK inhibitors to interfere with aberrant mucin expression and subsequent barrier function in the inflamed mucosa of IBD patients, as has also been highlighted in other diseases including cancer and COVID-19. Of note, as the pathophysiology of IBD involves mutual interactions of numerous inflammatory pathways that can affect mucin expression and function, future studies are encouraged to further investigate these pathways in relation to the cumulative effects of transmembrane mucin signaling on intestinal barrier function in IBD. (Citations omitted by examiner).
In addition, the specification discloses at paragraph [0098]: “the exact mechanisms by which these mucins affect barrier integrity and to prove their functional role in barrier integrity in IBD require further investigation”. Indeed, the specification concludes that the invention provides a starting point for investigating mucin isoform expression in disease (see paragraph [0115]):
In conclusion, mucin isoform expression is altered upon inflammation in IBD patients, highlighting its potential for disease surveillance or treatment. Moreover, these novel insights could be extrapolated to other inflammatory diseases and cancer that involve a dysfunctional mucosal epithelial barrier. The unexplored world of mucin isoforms provides thus a unique opportunity to understand their biological significance, utility as biomarker and pathology-specific targeting.
Thus, the evidence of record suggests that multiple pathways may be affected and further studies are needed.
Regarding antisense therapy, relevant literature indicates that treatment with antisense, siRNA and shRNA is complex. For instance, the review by Hu et al. (Signal Transduction and Targeted Therapy (2020) 5:101) provides background on the state of the art of siRNA therapy. Hu et al. outline the challenges to siRNA therapy (p. 2, left column, 2nd paragraph):
Although siRNA holds promising prospects in drug development, several intracellular and extracellular barriers limit its extensive clinical application. Naked and unmodified siRNA possesses some disadvantages, such as (1) unsatisfactory stability and poor pharmacokinetic behavior and (2) the possible induction of off-target effects. The phosphodiester bond of siRNA is vulnerable to RNases and phosphatases. Once it is systematically administered into circulation, endonucleases or exonucleases throughout the body will quickly degrade siRNA into fragments, thus preventing the accumulation of intact therapeutic siRNA in the intended tissue. In theory, siRNA only functions when its antisense strand is completely base-paired to the target mRNA. However, a few mismatches are tolerated by the RNA-induced silencing complex (RISC), which may lead to undesired silencing of those genes with a few nucleotide mismatches.
Hu et al. review the techniques undertaken to deal with the challenges of siRNA therapy, which serve to underscore the complexity of the field. For instance, base modification is a promising technique, but one that is “basically at the stage of research and development” (see discussion under “Base modification in the paragraphs bridging the left and right columns of p. 6). Regarding siRNA delivery, Hu et al. teach:
Only 1–2% of internalized LNP [lipid nanoparticle]-loaded siRNAs were released into the cytoplasm, and this only occurred within a limited time frame after internalization. Hence, further understanding the escape mechanism and how to enhance the escape efficiency is of great importance for siRNA drug development (p. 11, left column, 1st paragraph). Citations omitted by examiner.
In spite of progress made in the field of siRNA drug development and delivery, Hu et al. underscore the complexity of a field that is still in its developmental stage. Coupled with the breadth of the possible targets in treating barrier dysfunction diseases, the complexity of antisense treatment underscores the high level of experimentation the skilled artisan would have to take to practice the claimed treatment methods. However, patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be patentable. Tossing out the mere germ of an idea does not constitute an enabling disclosure. Reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. See Genentech v. Novo Nordick A/S (CAFC) 42 USPQ2d 1001 (1997).
Due to the large quantity of experimentation necessary to identify monoclonal antibodies, small molecules and antisense therapies for treating ulcerative colitis and IBD, the lack of direction/guidance presented in the specification regarding to the same, the complexity of the invention, and the breadth of the claims which fail to recite limitations on the identity of antibodies, small molecules and antisense molecules capable of targeting the mucin isoforms having increased expression and treating the encompassed diseases, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Response to Arguments
Applicant argues at p. 10 that paragraphs [0013] and [0099]-[0100] address therapeutic targets.
This argument has been fully considered, but is not found persuasive. This argument does not address the issues raised in the Office action mailed 03/10/2026 at pages 14-16 regarding the breadth of antibody and small molecule therapies or the complexity regarding antisense therapies. Paragraph [0013] merely states: “the present invention provides a mucin isoform as defined herein, for use as a new therapeutic target…said mucin isoform may be specifically targeted by monoclonal antibodies, small molecules or antisense technology.” Paragraphs [0099]-[0100] emphasize the potential of MUC1 and MUC13 as targets for future therapies yet to be developed:
Targeting the barrier, and particularly MUC1 and MUC13, could also have therapeutic potential. These transmembrane mucins have already shown their potential in antibody-based therapy in different cancer types, including colon cancer, making them valuable therapeutic targets in medicine…Inhibiting inflammation-induced MUC1 and MUC13 isoforms to restore intestinal barrier integrity may thus achieve greater efficacy with fewer side effects…Overall, it is highlighted here that aberrantly expressed Muc1 and Muc13 might be involved in intestinal mucosal barrier dysfunction upon inflammation by affecting tight junction and cell polarity proteins and that they can act as possible targets for novel therapeutic interventions.(Emphasis added by examiner).
The examiner does not take issue with MUC1 and MUC13 as possible targets for novel future therapeutic interventions, however, patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be patentable. Tossing out the mere germ of an idea does not constitute an enabling disclosure. Reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. See Genentech v. Novo Nordick A/S (CAFC) 42 USPQ2d 1001 (1997). The particular small molecules and antibodies used to treat these diseases should be recited in the claims. The evidence in the specification is not commensurate with the scope of the claimed invention.
Written Description
The rejection of claims 12-16 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 is maintained for reasons of record and the following. In addition, new claims 30 and 31 are hereby included in this rejection.
Response to Arguments
Applicant argues at p. 10 that paragraphs [0013] and [0099]-[0100] address therapeutic targets.
This argument has been fully considered, but is not found persuasive. This argument does not address the issues raised in the Office action mailed 03/10/2026 at pages 18-21 regarding the description of the encompassed treatments. The claims require treatment of treating a disease characterized by barrier dysfunction comprising administering monoclonal antibodies, small molecules and antisense therapy. Diseases characterized by barrier dysfunction are defined in the instant specification as “partial or complete disruption of the natural function of an internal barrier…[including] brain barriers, the gastrointestinal mucosal barrier, the respiratory mucosal barrier, the reproductive mucosal barrier and the urinary mucosal barrier (see paragraph [0047]). Claim 12 encompasses treatment capable of targeting the mucin isoforms having increased expression. The instant specification defines treatment of barrier dysfunction diseases with an antibody or small molecule that specifically target the mucin isoforms (pages 4-6), however, the encompassed monoclonal antibodies or small molecules are not disclosed in the application as originally filed.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The specification discloses that the different mucin isoforms may be specifically targeted by monoclonal antibodies and small molecules (see paragraphs [0013]; [0063]; [0100]), but does not disclose any particular structure for said therapies.
Regarding antibodies, the state of the art teaches antibody variable regions are composed of a heavy and light chain, each involved in providing for binding specificity. Townsend et al. (Frontiers in Immunology, 7, 388 2016) teach “[v]ariability in the antigen binding site is achieved by V(D)J recombination via heavy and light chain pairing”, with the “most diverse” regions being the 6 CDR regions in the heavy and light chain. While the heavy chain is the most diverse, light chains are also important for antibody-binding specificity, swapping light chains can “change the antigen specificity of the antibody” (see paragraph bridging pages 1-2). Furthermore, the light chain repertoire is extremely diverse being encoded by kappa and lambda gene segments, each with different V and J genes (see Townsend, p. 2, left column, 1st two paragraphs; p. 4, right column, 1st paragraph). See also Janeway et al. (Chapter 4-The generation of diversity in immunoglobulins in Immunobiology: The Immune system in health and disease, 5th edition, New York, Garland Science, 2001), which teaches that the “antibody repertoire in humans is at least 1011”, with a large degree of diversity in both heavy and light chains (see 1st paragraph). Furthermore, the diversity of the immunoglobulin repertoire is mediated in part by different combinations of heavy and light chain V regions that pair to form a unique antibody binding site. See, for example, Rabia et al. (Biochem. Engin. J. 137, 365-374, 2018), which teaches that “the maximal chemical diversity of antibody CDRs is unimaginably large…[and] it is extremely challenging to define the sequence determinant of antibody specificity” (see p. 368 left column, 4th paragraph). The prior art teaches that small changes in the amino acid structure of the CDRs can have large effects on activity. For instance, Piche-Nicholas et al. (MAbs. 2018; 10: 81-94. doi: 10.1080/19420862.2017.1389355—of record) teaches that the “binding affinity of IgG
Molecules…to FcRn that differed by only a few amino acid residues in CDRs revealed
that small changes in CDRs, as minute as one amino acid residue change, could alter
affinity to FcRn up to 79-fold.” See p. 89, right column, last paragraph of Piche-Nicholas
et al. In the instant case, there is not even the identification of any CDRs. Thus, the claims encompass a genus of treatments, but without providing adequate description of a number of species that are representative of this genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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