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 CCL20, blood sample and antibiotic treatment in the reply filed on 3/16/2026 is acknowledged.
Claims 8, 15, 16, 17, 18-24 all recite non-elected targets, samples, and/or treatments and are WITHDRAWN from prosecution in view of elected CCL20.
Upon a finding of allowable subject matter species which share a special technical feature with the elected species will be considered for rejoinder.
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.
Claims 1, 2, 7, 9-12 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite because the (d) determining step is unclear. It is unclear what it means that a subject has “proinflammatory mucosal dysbiosis.” The specification does not define this term, and it is not an established term of art. The term appears as a parenthetical following the phrase “disease-relevant colonization of the gut mucosal surface” (see Abstract) but this phrase is vague as well because it there is no clear definition of what makes colonization of the gut mucosal surface “disease- relevant” or even what disease is being referenced. Furthermore, it is unclear how “proinflammatory” mucosal dysbiosis is different from “dysbiosis.” There is no clear understood meaning of “proinflammatory mucosal dysbiosis” either given in the specification or the prior art and as a consequence, the metes and bounds of this step are unclear.
Additionally, the phrase “with loss of homeostasis” is unclear because it is not clear what this means or implies for the patient. Homeostasis is generally understood to be the self-regulating process by which living organisms maintain a stable internal environment. It is not clear what is meant here when the claim recites “loss of homeostasis” because it is not clear what aspect of homeostasis is being determined to be lost. Is the “determining” assessing that all self-regulation has failed?
The specification does not define these two terms nor the combined condition of “proinflammatory mucosal dysbiosis with loss of homeostasis” beyond stating, for example in paragraph 52 that this condition is present when IL17C is elevated and one or more of IL17A, CXCL9, CCL11, CXCL11, FGF23, and IL6 are elevated. Therefore, the metes and bounds of the claim are unclear.
Claim 1 is also indefinite when it refers to a level “elevated relative to a respective established range” because “elevated” is a relative word there is no clear definition in the claims or specification what is required for the level to be considered “elevated.”
Claim 1 is indefinite in part (e) when it refers to “the subject determined to have proinflammatory mucosal dysbiosis” because the claim does not previously require making this determination. The “determining” in part (d) is conditional, only occurring “when” certain criteria are met, and so if the individual tested does not meet these criteria, the determining is not required, and thus, there is not proper antecedent basis for “the subject” referred to in part (e) of the claim. Due to the “when” in part (d), and due to the fact that there is no claim limitation requiring that the level of one or more of IL17A, IL6, CXCL9,CCL11, or FGF23 is elevated, the administering step of (e) is also conditional.
Any claim not enumerated in the rejection is indefinite because it depends from claim 1 and incorporates all of the issues enumerated for claim 1.
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 1, 2, 7, 9, 11 and 12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a law of nature without significantly more.
The claim(s) recite(s) “characterizing the measured…determining the measured level is elevated” which is a mental process judicial exception (see claim 1, step (b)). The claims further recite “determining that the subject has proinflammatory mucosal dysbiosis with loss of homeostasis” which is a mental process judicial exception. This step also requires a mental process judicial exception of comparing the level of one or more markers to a respective established range to determine when it is elevated. Claim 1 describes that there is a relationship between marker levels and “proinflammatory mucosal dysbiosis with loss of homeostasis” which is a naturally occurring correlation is a law of nature judicial exception. This is an additional statement of a natural correlation/law of nature judicial exception.
This judicial exception is not integrated into a practical application because the measuring steps recited in the claims are data gathering steps necessary to practice the judicial exceptions; they do not apply or use the judicial exceptions in any way. Claim 1 recites “administering to the subject determined to have proinflammatory mucosal dysbiosis with loss of homeostasis” a therapeutically effective amount of an antibiotic agent but this does not integrate the judicial exception because (1) it is not required in all embodiments of the claim due to the conditional nature of determining step (d) and (2 it is not a specific treatment. There is no evidence of record that any antibiotic would treat “have proinflammatory mucosal dysbiosis with loss of homeostasis.” The specification has shown that IL17C in serum is elevated and associated with all major genra of the Enterobacteriaceae family (p. 23, lines 5-6), and there is no evidence of record that treating with any antibiotic would be a specific treatment for remedying this cause of “dysbiosis.”
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to the judicial exception are data gathering steps that are recited at an extremely high level of generality such that they encompass employing any well-established routine method for gathering the requisite data. Such methods were known, see Friedrich et al. cited herein as well as IDS references Yamaguchi and Song, all of which demonstrate detecting IL17C and other marker levels in samples. Claim 1 recites “treating the characterized intestinal inflammation status” and this does not amount to significantly more than the judicial exception because it is not a specific treatment, it is so general that it is a mere statement of “apply it.” Furthermore, it is a contingent limitation, and not required in all embodiments of the claim, only “when” certain criteria are met.
Response to Remarks
The response asserts that the claim requires administration of “particular” treatment, however, as noted in the rejection, (1) the administering step is contingent because step (d) is contingent and (2) “antibiotic agent” is not particular to dysbiosis that is indicated by increased IL17-C and increased one or more of the additional markers, consistent with the teachings in the spec which teach that increased IL17-C in serum is elevated and associated with all major genra of the Enterobacteriaceae family.
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.
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.
Claim(s) 1, 2, 7, and 9-12, is/are rejected under 35 U.S.C. 103 as being unpatentable over Friedrich et al. 2015, cited above in view of Andersson et al. (PLoS ONE 2017; 12(10): e0186142.; 16 pages plus additional supplementary Table 3).
Friedrich teaches a method comprising measuring an IL17C level in a biological sample obtained from a subject and characterizing the measured IL17C level within an established range.
Namely, the reference teaches obtaining human colonic tissue and human blood and serum from patients and controls (p. 955, 2nd column). The reference teaches detecting IL17C protein and mRNA in samples.
The reference teaches that IL-17C mRNA and serum levels are elevated in patients with IBD. The reference teaches a range (i.e. an established range) of IL-17C expression in serum of healthy controls that is 15.4-26.5 pg/ml and a range for patients having ulcerative colitis (UC) as being 28.1-59.6 pg/ml (p. 944, 1st col). The reference teaches detecting the level in the patient with the highest value of 29.6, which is in the top 10%, top 5% and top 2% of the range taught for all tested subjects- namely 15.4-59.6. Thus, the reference teaches determining, in a blood sample, an elevated IL17C level from a patient that has UC.
With regard to claim 2, the reference teaches patients with ulcerative colitis. This is an inflammatory bowel disease.
With regard to claim 7, the biological sample was a serum sample.
With regard to claim 9, the established range of IL17C values includes both patients having UC and controls, that is subjects not suffering from intestinal inflammation.
While the reference teaches testing additional markers, the reference does not teach determining the serum concentration of CCL20 or any one of the markers recited in claim 1(d).
Andersson teaches measuring the concentration of a variety of markers in patients having Ulcerative Colitis and Crohn’s Disease, including CCL20, IL17A, IL-6, CXCL9 , CCL11, CXCL11, and FGF-23. The reference teaches that each of these is dysregulated in the serum of either UC patients of CD patients. See Figure 1. For example, the reference teaches that CXCL9 is increased 1.25 fold in UC patients relative to healthy controls. See Table 2. Further, the reference provided supplemental data that give the range of values detected for all subjects.
It would have been obvious to have modified the method taught by Fredrich et al. and to have assayed additional markers of UC and/or CD in the IBD patients and controls. One would have been motivated to do so to provide a more complete set of information regarding known markers for disease.
With regard to steps (d) and (e) these steps are contingent. The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. See MPEP 2111.04.
Claim(s) 1, 2, 7, and 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fredrick and Andersson as applied to claims 1, 2, 7, and 9-12 above, and further in view of Ledder (Transl Pediatr 2019;8(1):42-55).
This rejection is written to address the embodiments of the claims wherein steps (d) and (e) are practiced.
The teachings of Fredrick and Andersson are given previously and are fully incorporated here.
These teach that patients with IBD, and specifically patients with UC have increased plasma levels of IL17C compared to a reference range and increased CXCL9. They do not teach treating a patient having these increases with an antibiotic.
Ledder teaches evidence of antibiotics for the treatment of ulcerative colitis. The reference discusses many different modes of treating UC patients with antibiotics. For example, the reference teaches that UC patients who received antibiotics as an adjunct to IV steroids were less likely to receive hospital rescue therapy. See page 47. The reference teaches that the signal from available studies suggests that antibiotics may have a complementary role in IBD management (p. 48). The reference states “it already seems that manipulation of gut flora with antibiotics have a complimentary and potentially symbiotic role with current treatments which target mucosal immunity. Each medication class has a potential role and the delicate symphony of IBD management requires judicious utilization of various treatment options which needs to be conducted with a blend of experience, evidence, and at times a little flare.” See p. 49.
It would have been obvious to have modified the methods taught by Fredrick and Andersson to have treated CD patients with antibiotics in order to give patients the benefit of the complementary role of antibiotics in IBD management.
Fredrick, Andersson and Ledder do not teach state “determining that a subject as proinflammatory mucosal dysbiosis with loss of homeostasis.” The “determining” does not result in any manipulative difference between prior art method and the claimed method, it merely directs how one thinks about the outcome of the method. Here, step (d) “determining” limitation is a non-functional descriptive step. The limitation adds no novelty to the method, which is otherwise obvious in view of the prior art, because there is no novel and unobvious functional relationship between the descriptive language and the manipulative steps of the claim. The determining does not have any further function, it does not transform the process of detecting a polymorphism. Irrespective of what one mentally determines, the actual manipulative method, detecting markers and treating the patients, is the same and the selecting adds no additional outcome for any individual patient. MPEP 2111.05.
In general, however, it is noted that having IBD, particularly UC, is a condition that includes evident loss of homeostasis with regard to gut health. Furthermore, as taught by Ledder, the microbiome may directly contribute to IBD development (p. 42). Ledder further teaches that it has long been recognized that inflamed mucosa has a reduced diversity of mucosa-associated bacteria, and a relative increase in Enterobacteriaceae and Fusobacterium. This change has been termed “dysbiosis.” Therefore, by diagnosing patients as having IBD and US, as in the Fredrick paper, it is inherent to the diagnosis that the patients have loss of homeostasis (they are ill) and the have gut dysbiosis.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Song teaches that microbiota drove IL-17C production in intestinal epithelial cells. The reference teaches that antibiotic treatment blocked induction of IL-17C, which suggests that the microbiome is critical for IL-17C induction. The reference suggests that dysregulated Enterobacteriaceae, such as E. coli induce IL-17C expression in epithelial cells. See p. 147-148. Song et al. Immunity 40, 140–152, January 16, 2014.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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 Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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