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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/06/2026 has been entered.
Claims 12, 28 and 29 are amended. Claims 12-16 and 19-29 are under examination.
Effective Filing Date
As noted at p. 2 of the Office action mailed 11/12/2025, the effective filing date of the instant application is 06/30/2020. Specifically, the foreign priority document does not provide support in the manner of 112(a) for antisense or small molecule therapy. In addition, the foreign priority document is silent with respect to the number of exons in the MUC1 and MUC13 mRNA isoforms. Applicant is invited to indicate where specifically in the foreign priority document provides inherent or implicit support for the amendment to claim 12.
Rejections Withdrawn
Claim Rejections - 35 USC § 101
The rejection of claims 12-16 and 19-29 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter is withdrawn in response to Applicant’s amendment filed 02/06/2026. Applicant’s amendment affirmatively requires treatment.
New Objection/New Rejections
Claim Objections
Claim 21 is objected to because of the following informalities. The claim recites “pancreas cancer” but “pancreatic cancer” is more common. Appropriate correction is required.
Notice for all US Patent Applications filed on or after March 16, 2013: In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 12-16 and 19-21 are rejected under 35 U.S.C. 103 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). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Weissleder et al. teach a method in which increased levels of MUC1, including 21 of its isoforms, can be used to detect epithelial cancers, including “pancreatic, lung, breast, prostate, renal, ovarian or colon cancer” (see p. 11, Table A; p. 14, last paragraph; claim 1). Weissleder et al. teach that mRNA or proteins can be measured via PCR or immunohistochemistry, respectively (see p. 7, 1st paragraph; p. 17, 2nd paragraph). Weissleder et al. contemplate that their methods can improve monitoring and diagnosis of disease in order to improve treatment and contemplate such treatment including immunotherapy (see p. 7, 1st paragraph; p. 10, 3rd paragraph; p. 18, 1st full paragraph).
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Weissleder et al. do not teach how many exons are contained within the MUC1 isoforms, nor do they explicitly teach that the contemplated immunotherapy involves administration of monoclonal antibodies. Regarding the isoforms, Weissleder et al. report NM_002456.5, NM_001018016.2, also known as the isoforms MUC1/X and MUC1/ZD. Nath teaches that MUC1/X and MUC1/ZD contain six exons, including the transmembrane domain (see Figure 2(c)). Regarding immunotherapy, Rajan et al. teach that the monoclonal antibody PD-1, plays an important role in cancer treatment (see abstract; p. 2219, left column, 1st paragraph; p. 2225, sentence bridging left and right columns; p. 2227, right column, 2nd paragraph).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that some of the isoforms listed in Table A (p. 11) of Weissleder and colleagues contain 6 or 7 exons because the structures of MUC1 isoforms were known in the art (see Nath). Further, it would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that immunotherapy encompasses monoclonal antibody therapy because Rajan et al. define it as such (see cited portions above). The person of ordinary skill in the art would have been motivated to administer a monoclonal antibody such as an anti-PD-1 because Rajan et al. disclose that monoclonal antibody immunotherapy enhances traditional cancer treatments such as chemotherapy and radiation. Further, radiation therapy “increases the availability of tumor antigens for presentation to immune cells”, thus making monoclonal antibody immunotherapy even more effective (see p. 2227, right column, 2nd paragraph). Furthermore, the person of ordinary skill in the art could have reasonably expected success because anti-PD-1 monoclonal antibodies are effective “against a wide spectrum of solid tumors and hematological malignancies” (see p. 2228, left column, last paragraph).
Thus, the claims do not contribute anything non-obvious over the prior art.
Claims 12, 14-16, 19 and 25-27 are rejected under 35 U.S.C. 103 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). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. The reference by d’Alessandro et al. teaches that KL-6 (a synonym for MUC1) serum levels were significantly higher in patients with severe COVID-19 than either those with mild cases or healthy controls as measured by an antibody-based KL-6 assay (see abstract; p. 2217 under paragraph 2.2; p. 2219, Figure 1). Based upon the definition set forth in the instant specification, the phrase “mucin isoform” is interpreted as a member of the set of similar mRNA molecules/encoded proteins originating from a single mucin gene, thus the broadest reasonable interpretation is that this “set” includes MUC1 (i.e., KL-6).
The second factor to consider is to ascertain the differences between the prior art and the instant claims. The reference by d’Alessandro et al. does not teach how many exons are contained within KL6 (MUC1), nor does it explicitly teach therapy involving small molecules. Regarding the isoforms, Nath teaches that MUC1 contains seven exons, including the transmembrane domain (see Figure 2(A)-(B)). Regarding treatment, Wang et al. teach that remdesivir and chloroquine were both identified early in the pandemic as being effective in treating SARS-CoV2 (see p. 269, right column, 2nd and 3rd paragraphs). Chloroquine is known as a small molecule drug.
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that MUC1 contains 7 exons because the structure of MUC1 and its isoforms were known in the art (see Nath). Further, it would have been obvious to the person of ordinary skill in the art at the time of the filing to treat SARS-CoV2 with remdesivir or chloroquine because it was a novel illness and these drugs were identified early as having anti-coronaviral activity (see p. 270, Figure 1). The person of ordinary skill in the art would have been motivated to administer remdesivir or chloroquine because in addition to being shown to have anti-coronaviral activity in vitro, both drugs have a long track record of use in vivo (see p. 729, last paragraph). Furthermore, there were few options for SARS-CoV2 treatment at the time of filing, thus, the person of ordinary skill would be motivated to try all available options. Finally, the person having ordinary skill in the art could have reasonably expected success because of the promising in vitro results reported by Wang and colleagues.
Thus, the claims do not contribute anything non-obvious over the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 12, 13, 16, 19 and 25-27 are provisionally rejected 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). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application teach methods for diagnosing and treating a subject with a coronaviral infection (e.g., a SARS-CoV-2 infection), comprising: providing a biological sample from the subject; determining the presence of mucins in the biological sample, the mucins encompassing MUC13, MUC1; MUC13 mRNA isoforms and MUC 1 mRNA isoforms, among others; diagnosing the subject with a coronaviral infection based upon a higher level of the mucin(s) (e.g., MUC13, MUC13, MUC1 isoforms or MUC13 mRNA isoforms) in the biological sample; and administering a treatment to the subject wherein the treatment reduces production of the mucin; wherein determining the presence of the mucin in the biological sample comprises quantifying an mRNA expression level of said mucins and wherein the biological sample is a mucous sample or a blood sample.
The differences between the instant claims and those of the reference application are as follows. The claims of the reference application do not teach how many exons contained within the MUC1 isoforms. Nath teaches a number of MUC1 isoforms that contain six or seven exons, including the transmembrane domain (see Figure 2(A)-(C)). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that some of the isoforms encompassed by the claims of the reference application contain 6 or 7 exons because the structures of MUC1 isoforms were known in the art (see Nath). Further, the reference application provides a more detailed list of mucins that are indicative of coronaviral infection, contemplated therapies (small molecules and monoclonal antibodies) as well as the identity of the samples. Nevertheless, the more detailed and specific recitation (species) in the claims of the reference application anticipates the more general recitation (genus) in the instant claims.
This is a provisional nonstatutory double patenting rejection.
Rejections Maintained
Claim Rejections - 35 USC § 112(b)
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.
The rejection of claims 12-16 and 19-29 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. First, Applicant’s amendment to recite “and treating” is acknowledged. This amendment addresses the issue raised by the examiner concerning ambiguity about whether treatment was required. However, the amendment does not address the issue raised with regard to claim 12, which still recites “wherein treatment is selected from the group consisting of: monoclonal antibodies, small molecules or antisense therapy”. Proper Markush language would be “monoclonal antibodies, small molecules and antisense therapy” when using “consisting of”. See MPEP 2117 for how to set forth alternatives, namely, “a material selected from the group consisting of A, B, and C” or “wherein the material is A, B, or C”.
Claims 13-16 and 19-29 are also rejected for depending upon indefinite claims.
Response to Arguments
Applicant’s argument at pages 11-12 does not address this issue.
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 12-29 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. Applicant’s arguments regarding the inflamed and non-inflamed conditions at pages 9-10 of the Remarks filed 02/06/2026 are persuasive, and the statement of enablement is updated in order to reflect that.
The specification is enabling for diagnosing, monitoring and treating:
(1) cancer using the methods taught in the prior art of Weissleder et al. and Rajan et al.;
(2) SARS-CoV2 using the methods taught in the prior art of d’Alessandro et al. and Wang et al. and
(3) colitis or inflammatory bowel disease (IBD) comprising determining increased expression of MUC1 mRNA isoforms selected from the group consisting of: PB 136.9,136.22, PB.136.2, PB.136.4, PB.136.18, PB.136.15, PB.136.14, PB.136.19, PB.136.21, PB.136.29, PB.136.37, PB.136.38, PB.136.6 and PB.136.24, or determining increased expression of MUC13 mRNA isoforms selected from the group consisting of: PB.1087.18, PB.1087.50, PB.1087.61, PB.1087.64, PB.1087.6, PB.1087.63, PB.1087.21, PB.1087.20, PB.1087.25, PB.1087.68, PB.1087.32, PB.1087.27, PB.1087.31, PB.1087.52, PB.1087.53, PB.1087.58 and PB.1087.56.
The specification does not reasonably provide enablement for the claims as broadly recited. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claims remain broad with respect to the diseases characterized by barrier dysfunction. Further, insomuch as the claims encompass treatment with an antibody or small molecule that specifically targets the mucin isoforms (pages 4-6), the recited monoclonal antibodies or small molecules are not disclosed in the application as originally filed. The specification teaches that MUC1 and MUC13 isoform expression levels were increased in the two mouse models of colitis (see paragraph [0095]). The specification discloses (paragraph [0098]):
Taken together, the results from our study clearly show the association of aberrant Muc1 and Muc13 expression with intestinal mucosal barrier dysfunction during the course of colitis. A model-specific response was observed, indicating a complex transcriptional regulation of mucin expression that results from the combined effects of the host inflammatory response, the microbiome and the type and course of disease. Nevertheless, the exact mechanisms by which these mucins affect barrier integrity and to prove their functional role in barrier integrity in IBD require further investigation.
Regarding the large genus of conditions encompassed by “disease[s] characterized by barrier dysfunction”, the prior art teaches that some MUC1 isoforms are increased in certain conditions and cancers. For instance, Weissleder et al. (WO 2012/129325—of record) teach a method in which increased levels of MUC1, including 21 of its isoforms, can be used to detect epithelial cancers, including “pancreatic, lung, breast, prostate, renal, ovarian or colon cancer” (see p. 11, Table A; p. 14, last paragraph; claim 1). In addition, Ohshimo et al. (WO2010071228—of record) teach that “[s]erum KL-6 [another term for “MUC1”] levels in CF patients were significantly increased compared to healthy control subjects” (see paragraph [0044]). However, neither the instant specification or the art suggests that the claimed methods could be used to diagnose or monitor neurodegenerative disorders, respiratory infections or any gastrointestinal disorders other than colitis and IBD.
The claims are broad with respect to the encompassed treatments: monoclonal antibodies, small molecules or 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 which MUC1 and MUC13 isoforms are increased in which of the large genus of encompassed diseases (other than colitis and IBD), targets for treatment of the encompassed diseases and monoclonal antibodies, small molecules and antisense therapies therefor, the lack of direction/guidance presented in the specification regarding to the same, the absence of working examples other than the reporting of MUC1 and MUC13 isoforms being increased in IBD and colitis, the complex nature of the invention, and the breadth of the claims which fail to recite limitations on the conditions being diagnosed, monitored and treated, the treatments themselves, 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
At pages 9-10, Applicant argues that Tables 5, 6 and S2 enable the skilled artisan to know which MUC1/MUC13 isoforms are associated with both non-inflamed and inflamed IBD: “[k]nowing the different isoforms that are associated with ‘inflamed’ and ‘non-inflamed’ conditions enables practitioners and those of skill in the art to make informed decisions regarding individualized treatment, including altering and/or adapting treatments to specific patients”.
This argument has been fully considered and it is found persuasive that certain MUC1/MUC13 isoforms are expressed in inflamed and other are expressed in non-inflamed IBD. Nevertheless, the claims are still broad with respect to the conditions treated as well as the treatments administered, and Applicant’s arguments and amendments do not address these issues.
Written Description
The rejection of claims 12-16 and 19-29 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. Applicant’s arguments regarding the inflamed and non-inflamed conditions at pages 9-10 of the Remarks filed 02/06/2026 are persuasive, and the rejection is updated herein in order to reflect that. The claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
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).
Response to Arguments
At pages 9-10, Applicant argues that Tables 5, 6 and S2 enable the skilled artisan to know which MUC1/MUC13 isoforms are associated with both non-inflamed and inflamed IBD: “[k]nowing the different isoforms that are associated with ‘inflamed’ and ‘non-inflamed’ conditions enables practitioners and those of skill in the art to make informed decisions regarding individualized treatment, including altering and/or adapting treatments to specific patients”.
This argument has been fully considered and it is found persuasive that certain MUC1/MUC13 isoforms are expressed in inflamed and other are expressed in non-inflamed IBD. Nevertheless, the application as originally filed does not disclose a representative number of species of monoclonal antibodies or small molecules encompassed by the treatment step, and Applicant’s arguments and amendments do not address these issues.
Conclusion
No claim is allowed.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675