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 .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
Applicants’ amendment of the claims filed 12 September 2025 has been entered. Applicants’ remarks filed 12 September 2025 are acknowledged.
Claims 2-6, 8-9, 13-14, 20-31 and 35 are cancelled. Claim 36 is added. Claims 1, 7, 10-12, 15-19, 32-34 and 36 are pending. Claims 1, 7, 10-12 and 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 18-19, 32-34 and 36 are under examination to the extent they read on the elected species: A-a) wherein the agent that activates AhR is an AhR agonist.
Claim Objections/Rejections Withdrawn
It is noted that claim 19, which was inadvertently deleted from the listing of claims filed 11 February 2025, has been added back.
The objections to claims 18 and 35 for typographical errors and informalities are withdrawn in response to Applicants’ amendment of the claim 18 and cancellation of claim 35.
The rejection of claim 35 under 35 U.S.C. 102(a)(1), as being anticipated by Sokol et al. (WO 2017/032739 A1, Int’l. Pub. Date: 2 March 2017), is withdrawn in view that claim 35 has been cancelled.
The rejection of claims 18, 31-32 and 34-35 under 35 U.S.C. 102(a)(1), as being anticipated by Cervantes-Barragan et al. (Science, 2017, Vol. 357(6353):806-810), is withdrawn in response Applicants’ amendment of independent claim 18 to recite a composition “for oral administration”.
The rejection of claim 33 under 35 U.S.C. 103, as being unpatentable over Cervantes-Barragan et al., in view of Sokol et al. (WO 2017/032739 A1), is withdrawn in response Applicants’ amendment of the claims as above.
Claim Rejections Maintained
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.
Amended and newly added claims 18-19, 32-34 and 36 remain rejected under 35 U.S.C. 101, because the claimed invention is not directed to patent eligible subject matter.
Applicants argue that the claimed AhR agonist and bacterial probiotic are integrated into an oral composition that further comprises one or more adjuvants acceptable for oral ingestion. Applicants argue that the oral composition provides an inventive concept over prior art. Applicants further argue that the claimed invention is comparable to claim 4 of Example 44 (Denveric Acid) of Appendix 1 (October 2019 Update) of the Subject Matter Eligibility Guidelines.
Applicants’ arguments have been fully considered but have not been found to be persuasive.
The claimed oral composition does not provide an inventive concept over prior art in view of Sokol (see the 103 section). The additional element of “one or more adjuvants acceptable for oral ingestion” reads on water. Further, the instant case is not comparable to claim 4 in Example 44 (Denveric Acid) of the Subject Matter Eligibility Guidelines (October 2019 Update). In claim 4 of Example 44, denveric acid is short-acting and protamine does not have glycemic control characteristics, however, a mixture of the two naturally occurring compounds has the characteristics of long-acting and capable of glycemic control, which is marked different. In the instant case, the claimed AhR agonist exhibits the activity of stimulating AhR, and the Lactobacillus probiotic exhibits AhR-activating property. A mixture of the AhR agonist and the AhR-activating Lactobacillus probiotic would exhibit the property of increasing the AhR activity, which is not marked different from the natural occurring compounds by themselves. Thus, the claims are directed to a product of nature without significantly more,
Accordingly, the instant claims are not patent-eligible.
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 of this title, 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.
Amended and newly added claims 18-19, 32-34 and 36 remain rejected under 35 U.S.C. 103, as being unpatentable over Sokol et al. (WO 2017/032739 A1, Int’l. Pub. Date: 2 March 2017).
Ground of Rejection
Sokol teaches a pharmaceutical composition for preventing or treating inflammatory bowel diseases comprising at least one agent selected from the group consisting of AhR agonists, bacterial probiotics with AhR agonist activity, and IL-22 agonist, wherein the AhR agonist is selected from a group including, e.g., indole derivatives, tryptophan catabolites, indole-3-aldehyde (IAld), and tryptamine, and wherein the bacterial probiotic is selected from, e.g., Lactobacillus reuteri, CNCM 1-5022 (SB6WTF6, Lactobacillus reuteri), and CNCM 1-5023 (SB6WTG6, Lactobacillus reuteri) (see claims; p. 2, lines 12-15; and p. 11, line 19). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a pharmaceutical composition comprising an AhR agonist (e.g., an indole derivative, a tryptophan catabolite, indole-3-aldehyde (IAld), or tryptamine) and a bacterial probiotic (e.g., Lactobacillus reuteri). One of ordinary skill in the art would have been motivated to do so, because Sokol teaches a pharmaceutical composition for preventing or treating inflammatory bowel diseases comprising at least one agent selected from the group consisting of AhR agonists, bacterial probiotics with AhR agonist activity, and IL-22 agonist, wherein the AhR agonist is, e.g., an indole derivative, a tryptophan catabolite, indole-3-aldehyde (IAld), or tryptamine, and the bacterial probiotic is, e.g., Lactobacillus reuteri. A skilled artisan would have a reasonable expectation of success in preventing or treating inflammatory bowel diseases with the pharmaceutical composition.
Response to Applicants’ Argument
Applicants argue that the claimed combination exhibits unexpected synergistic effect between the particularly claimed AhR agonists and an AhR-activating Lactobacillus probiotic to yield AhR activity that is useful to treat gluten-induced disease. Applicants argue that FIG. 19B shows that a composition comprising the claimed agonists (high trp diet) combined with a Lactobacillus probiotic significantly increased AhR activity in a mouse model for gluten-induced disease, as compared to the low trp diet control. Applicants argue that Sokol generally teaches AhR agonists, but fails to specifically teach combining the particularly claimed AhR agonists with an AhR-activating Lactobacillus probiotic; and Sokol simply provides a broad starting point for one of skill in the art to pick and choose from and amounts to undue experimentation. Applicants further argue that while Sokol indicates that kynurenine may be a useful AhR agonist, the present application, however, teaches away from using kynurenine, because the catabolism of Trp by IDO (to produce kynurenine) leads to chronic inflammation and is not desirable. Applicants argue that the unexpected properties cannot be ignored because it is relevant to the claimed composition.
Applicants’ arguments have been fully considered but have not been found to be persuasive.
Sokol teaches a pharmaceutical composition for preventing or treating inflammatory bowel diseases comprising at least one agent selected from the group consisting of AhR agonists, bacterial probiotics with AhR agonist activity, and IL-22 agonist. Sokol teaches that the bacterial probiotic with AhR agonist activity is selected from CNCM I-5019, CNCM I-5020, CNCM I-5021, CNCM I-5022, and CNCM I-5023 (see claim 1) (all of the listed probiotics are Lactobacillus). Sokol teaches that the AhR agonist is selected from, e.g., indole derivatives, tryptophan catabolites, indole-3-aldehyde (IAld), and tryptamine. Sokol specifically names the AhR agonists as presently claimed. One of ordinary skill in the art would have been motivated to combine the AhR agonist as taught by Sokol (e.g., indole derivatives, tryptophan catabolites, indole-3-aldehyde (IAld), and tryptamine) with the Lactobacillus probiotic with a reasonable expectation of success, because Sokol teaches a pharmaceutical composition useful for preventing or treating inflammatory bowel diseases comprising at least one agent selected from the group consisting of an AhR agonist (e.g., an indole derivative, a tryptophan catabolite, indole-3-aldehyde (IAld), and tryptamine), a bacterial probiotic with AhR agonist activity (i.e., a Lactobacillus probiotic), and IL-22 agonist. A person skilled in the art would recognize that Sokol provides sufficient teaching, suggestion, and motivation to arrive at a composition as presently claimed without undue experimentation.
With respect to Applicants’ argument that the present application teaches away from using kynurenine as the AhR agonist, however, claim 18 encompasses kynurenine as the AhR agonist. The specification of the present application describes that “Examples of agonist of AhR include, … tryptophan catabolites such as tryptophan catabolites of the microbiota, e.g. kynurenine, …” (paragraph [0040]). Further, Sokol teaches other AhR agonists as presently claimed, e.g., indole-3-aldehyde (IAld) and tryptamine, that can be used in the pharmaceutical composition.
With respect to Applicants’ argument that the specification demonstrates the unexpected synergistic effect between the particularly claimed AhR agonists and an AhR-activating Lactobacillus probiotic to yield AhR activity that is useful to treat gluten-induced disease, however, the claims of the present application are drawn to a composition, not a method of treatment for a gluten-induced disease. Sokol teaches and suggests pharmaceutical compositions comprising the same agents that can be used in a method for preventing or treating an inflammatory bowel disease. MPEP 2144 states that: the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). Further, a person skilled in the art would expect that combining an AhR agonist with a bacterial probiotic with AhR agonist activity would significantly increase AhR activity because both agents exhibit the property of stimulating AhR activity. Furthermore, while the specification shows that combining Trp with a Lactobacillus probiotic significantly increased AhR activity, there is no evidence that any of the claimed AhR agonists would have such effects. Therefore, the disclosure does not demonstrate unexpected results of the claimed invention.
For the foregoing reasons, the rejection is maintained.
Double Patenting
Amended and newly added claims 18-19, 32-34 and 36 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,736,927.
Applicants argue that the ‘927 patent is based on the U.S. national entry of Sokol et al. (WO 2017/032739), and the arguments set out above are applicable with respect to this rejection of the claims.
Applicants’ arguments with regard to Sokol (WO 2017/032739) have been addressed above. The claims of the ‘927 patent render obvious of a pharmaceutical composition comprising an AhR agonist and a bacterial probiotic with AhR agonist activity as recited in the instant claims.
Therefore, the nonstatutory double patenting rejection is maintained.
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 Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/XIAOZHEN XIE/Primary Examiner, Art Unit 1674 October 10, 2025
Prosecution Insights