The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment filed on 11-20-2023 is acknowledged. Claims 1, 22, 58-59, 62, 65, 68, 79 and 83 have been amended. Claims 5, 42, 44 and 54 have been canceled. Claims 1, 10, 13, 18-19, 22, 58-60, 62, 65, 68-69 and 79-83 are pending. Claims 18-19, 60 and 69 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 10, 13, 22, 58-59, 62, 65, 68 and 79-83 are currently under examination. It should be noted that claims 18-19, 60 and 69 have improper claim status identifiers (claims are either “withdrawn” or “previously presented”). Said identifiers must be corrected in order for any response to this action to be considered fully responsive.
Information Disclosure Statement
The Information Disclosure Statement filed on 7-25-2025 has been considered. An initialed copy is attached hereto.
It should be noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Declaration
The declaration of Dr. Amanda Prince under 37 C.F.R. 1.132 filed on 7-25-2025 has been fully considered.
Claim Rejections Withdrawn
The rejection of claims 1, 10, 13, 22, 58-59, 62, 65, 68 and 79-83 under 35 U.S.C. 103 as being unpatentable over Prieux-Klotz et al. (Targeted Oncology Vol. 12, pages 301-308) and Honda et al. (WO 2013/080561 – of record) as evidenced by Lopetuso et al. (Gut Pathogens Vol 5 No. 23, pages 1-8 – IDS filed on 2-28-2023) is withdrawn in light of the amendment thereto.
New Grounds of Rejection
35 USC § 103
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 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.
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.
Claims 1, 10, 13, 22, 58-59, 62, 65, 68 and 79-83 are rejected under 35 U.S.C. 103 as being unpatentable over Prieux-Klotz et al. (Targeted Oncology Vol. 12, pages 301-308), Honda et al. (WO 2013/080561 – of record), and Chaput et al. (Annals of Oncology Vol. 28, Issue 6, pages 1368-1379 – IDS 2-28-2023).
Prieux-Klotz et al. disclose the use of checkpoint inhibitors for the treatment of malignant disease such as advanced malignant melanoma, lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, gastric cancer, colorectal cancer, ovarian cancer, Merkel cell carcinoma and Hodgkin lymphoma (see page 302) and that said treatments have gastrointestinal side-effects such as diarrhea and colitis (see abstract) and that checkpoint inhibitor-induced colitis is similar to IBD (see page 304).. Prieux-Klotz et al. further disclose that immune checkpoint inhibitor therapies include the use of Ipilimumab, pembrolizumab, nivolumab or atezolizumab (see Table 1 on page 302).
Prieux-Klotz et al. differs from the rejected claims in that they don’t explicitly disclose the use of bacteria from Clostridium clusters IV and XIVa in immune checkpoint inhibitor therapies or the specific treatment regimens set forth in claim
Chaput et al. disclose that the use of checkpoint inhibitors (ipilimumab) alters the gut microbiota (including Clostridium species) in patients with checkpoint inhibitor colitis (see Table 1 and page 1377).
Honda et al. disclose that the addition of bacteria from Clostridium clusters IV and XIVa treat IBD, colitis and diarrhea (see paragraph [0055], Table 2 and paragraph [0068]); that said compositions can comprise combinations of Clostridium saccharogumia, Flavonifractor plautii, Clostridium hathewayi, Blautia coccoides, Clostridium bolteae, Clostridium indolis, Anaerotruncus colihominis, Clostridium lavalense, Clostridium symbiosum, Clostridium ramosum, Eubacterium contortum and Clostridium scindens (see paragraph [0058] and [0101]; that said bacterial compositions can be administered orally (see paragraph [0071]); that said bacterial compositions can be used in conjunction with therapeutic compositions (see paragraph [0030] [0078]); that said bacterial compositions induce the expansion of regulatory T cells (see abstract); that the induction of regulatory T cells can be measured utilizing standard hallmarks of regulatory T cells (see paragraph [0098] for example).
Given the nexus between the gut microbiome and checkpoint inhibitor-induced colitis and the similarity between checkpoint inhibitor-induced colitis and IBD, it would have been obvious for the skilled artisan to utilize the methods of the bacteria of Honda et al. to alleviate the side effects of immune checkpoint inhibitor therapies outlined in Prieux-Klotz et al. in order to increase the efficacy of the treatment and the general well-being of the patient. Given that Prieux-Klotz et al. disclose that immune checkpoint inhibitors can cause colitis and that Honda et al. disclose that bacteria from Clostridium clusters IV and XIVa are effective in treating colitis, it would have been equally obvious for the skilled artisan to utilize bacteria from Clostridium clusters IV and XIVa in the methods of Prieux-Klotz et al. to mitigate colitis associated with of immune checkpoint inhibitor therapies.
One would have had a reasonable expectation of success since Honda et al. disclose the effective use of Clostridium clusters IV and XIVa bacteria to treat colitis and its effects (i.e. adverse conditions associated with immune checkpoint inhibitor therapies).
With regard to the treatment regimens set forth in claims 58, 62, 65, 66 and 80-82, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235(CCPA 1955).
With regard to claim 59, the KSR decision sets forth “if a technique has been used to improve one device, and a person of skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill”. Given that demonstrates that the induction of regulatory T cells can be measured utilizing common indexes (hallmarks) and the use of IL17 as a measurement of regulatory T cells is well established in the art, the use of IL17 levels as a measurement of regulatory T cells is well within the capabilities of one of ordinary skill in the art. Hence, the requirements of obviousness under the KSR decision are met.
With regard to claim 83, given eosinophilia is the means by which diagnosticians differentiate between ulcerative colitis and eosinophilic colitis, it would have been obvious for the skilled artisan to measure eosinophil levels to determine whether the colitis was due to the checkpoint inhibitor treatment or eosinophilia.
Conclusion
No claim is allowed.
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.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 October 31, 2025