DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received August 18, 2025 are acknowledged.
Claims 3, 4, 6, 9-12, 17, 19-21, 23-27, and 33-39 have been canceled.
Claims 1, 13-15, 18, 22, 28, 30, and 31 have been amended.
Claim 40 has been added.
Claims 1, 2, 5, 7, 8, 13-16, 18, 22, 28, 30-32, and 40 are pending in the instant application.
Claims 13, 28, and 30-32 stand withdrawn from consideration as being drawn to a nonelected invention. See 37 CFR 1.142(b) and MPEP § 821.03, for reasons of record set forth in the restriction requirement mailed August 16, 2024.
Claims 1, 2, 5, 7, 8, 14-16, 18, 22, and 40 are under examination in this office action.
Information Disclosure Statement
The IDS form received 9/9/2025 is acknowledged and the references cited therein have been considered.
Claim Rejections - 35 USC § 112
Claims 1, 2, 5, 7, 8, 14-16, 18, 22, and 40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant has broadly claimed methods of preventing and treating food allergy by administering either indole-3-carboxaldehyde (CA) or indoxyl 3 sulfate (I3S) which are recited as having the functional property of inducing regulatory T cells which express RORgt. To support such broad claims the specification discloses that administration of indol-3-aldehyde to mice expanded the number of such regulatory T cells and was protective in a mouse model system of food allergy (see Figures 5 and 6 in particular).
The instant claims recite that the administration methods treat or prevent food allergy, and paragraph [00171] of the instant specification indicates that prevention encompasses 100% efficacy as compared to normal controls (i.e. total prevention in all individuals all the time at any dose and any administration interval with any “agent”). The causes of food allergies are myriad and not completely understood but have environmental as well as genetic components (see for example Yu et al. as well as Islam et al, both of record). In view of such complexity of an incompletely understood and varied phenomenon, it seems unreasonable that the instant claimed methods are capable of “prevention” commensurate in scope with the total, 100% efficacy as set forth in the instant specification, especially as treated mice still experienced symptoms subsequent to allergen challenge even if such responses were attenuated to a statistically significant degree as compared to controls (see for example Figure 6A). Further, claims such as claim 7 which depends directly from independent claim 1 recites that the subject has been diagnosed with at least one food allergy, and logically it is impossible to prevent the onset of a food allergy if the patient has already been diagnosed with a food allergy Thus, while administration may attenuate severity of preexisting food allergies and inhibit the development of food allergies in individuals presently asymptomatic but at risk, it does not appear reasonable that the instant claimed methods are capable of “prevention” as presently recited.
Applicant's arguments filed August 18, 2025 have been fully considered but they are not persuasive. Applicant argues that the “agent” of the independent claims has been amended to be either indole-3-carboxaldehyde (CA) or indoxyl 3 sulfate (I3S) and thus the rejection should be withdrawn.
This arguments has been considered and is not fully persuasive as the prior rejection raised issues regarding “agent” which have been overcome via amendment as well as the expected level of efficacy as encompassed by “prevention” for which no argument appears to have been set forth. As was discussed in the rejection, “prevention” encompasses complete efficacy, and it should be noted that in applicant’s model system while symptoms of allergy were strongly attenuated they could still be observed (again see Figure 6A for example). Thus while the data indicate that artisans very reasonably could prophylactically administer CA to a patient at risk for developing an allergic reaction for the purpose of inhibiting the development of said allergic reaction, it does not appear reasonable to “prevent” such a reaction in all individuals all of the time, especially in people who are already symptomatic. The rejection is maintained.
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 claim 17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been rendered moot by its cancelation as part of the response received August 18, 2025.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claims 1, 2, 5, 7-9, and 15-18 under 35 U.S.C. 102(a)(1) as being anticipated by Hammerschmidt-Kamper et al. has been withdrawn in view of applicant’s claim amendments received August 18, 2025 which add additional limitations not disclosed in the cited art.
The rejection of claims 1, 2, 5, 7, 8, and 15-18 under 35 U.S.C. 102(a)(1) as being anticipated by Chatila et al. (WO 2017/079450, of record) has been withdrawn in view of applicant’s claim amendments received August 18, 2025 which add additional limitations not disclosed in the cited art.
Claim Rejections - 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 (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.
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.
Claims 1, 2, 5, 7, 8, 14-16, 18 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Alaniz et al. (WO 2017/161268, of record) in view of Rivas et al. (of record as citation 47 on the 7/22/2022 IDS).
Alaniz et al. teach methods of eliciting regulatory T cells expressing FoxP3 from naïve T cells (i.e. induced T regulatory cells or ITreg) in vivo by administration of the tryptophan derived microbiota metabolite indole-3 aldehyde for the treatment of inflammatory conditions including allergies, colitis, inflammatory bowel disease, and enteropathy (see entire document, particularly the title, abstract, claims, and pages 3 and 4). It should be noted that as evidenced by paragraph [0099] of the instant application indol-3-aldehyde and indole-3-carboxaldehyde are different names for the exact same small molecule. Such methods are disclosed as treating, preventing, ameliorating and reducing conditions involving excessive inflammation which include allergies, and as such the administrations occur prior as well as subsequent to the emergence of clinical signs and symptoms of allergy (see for example claims 21-23). It is further disclosed that the phenotype of induced regulatory T cells can change due to the extracellular cytokine environment, and that such changes can be reduced (discussed by Alaniz et al. as “increasing the stability”) by exposure to tryptophan metabolites including indol-3-aldehyde (see for example lines 16-24 of page 4 as well as pages 12-15). Notably, they disclose that their induced Tregs do not revert to an inflammatory phenotype even when in present in a pro-inflammatory environment such as one including IL-4 (see particularly the paragraph spanning pages 16 and 17). Such teachings differ from the instant claimed invention in that while the methods of Alaniz et al. treat allergies, the species of food allergies is not explicitly disclosed.
Rivas et al. disclose that food allergies are a major human health problem and that regulatory T cells expressing FoxP3 are less abundant and more prone to apoptosis in a mouse model of food allergies as compare to wild type controls (see entire document, particularly the abstract, introduction, and page 519). They disclose that IL-4 reprograming of regulatory T cells leads to allergenic sensitization (see for example page 516 and Figure 4) and a decrease in the number of allergen specific (see discussion section in particular). They further disclose that augmenting the numbers of induced allergen specific FoxP3 expressing regulatory T cells in the absence of IL-4 signaling is expected to be beneficial in achieving oral tolerance to food allergens (see for example the last sentence of the discussion section).
Therefore, it would have been obvious to practice the methods disclosed by Alaniz et al. on subjects suffering from food allergy. This is because Alaniz et al. teach their methods are suitable for inflammatory conditions including allergy generically as well as for treating inflammation in gastrointestinal disorders including colitis, IBD, and enteropathy while Rivas et al. disclose that food allergies are a major human health problem. Further, the induced Treg of Alaniz et al. are disclosed as being resistant to becoming pro-inflammatory in response to IL-4, and thus the iTreg of Alaniz et al. would maintain their ability to reduce inflammation and treat allergy even in situations wherein high concentrations of extracellular IL-4 are expected such as occur in food allergy as taught by Rivas et al.
Applicant's arguments filed August 18, 2025 have been fully considered but they are not persuasive. Applicant argues on many grounds. Applicant begins by arguing that indole-3-carboxaldehyde is taught in a laundry list of reagents by Alaniz et al. and therefore there is no direction to that particular reagent. Applicant also argues that the regulatory T cells taught by Alaniz et al. are negative for RORgt which is different from what is recited in the instant claims. Thus, applicant asserts the rejection should be withdrawn.
Applicant’s arguments have been considered but are not persuasive. As set forth in the rejection of record, the difference between the methods of Alaniz et al. and that which is presently claimed is that the methods of Alaniz et al. are taught for treating allergies generically while the instant claims specifically require the subgenus of food allergies. Thus there is no question of unpredictability as Alaniz et al. teach that all of their reagents work to treat allergy, of which food allergy is a subgenus, and the rejection of record discloses why artisans would be motivated to pursue this particular subgenus within the larger genera of “allergies”. With regard to cell types, applicant is reminded that the claimed methods are for administration of a particular drug to a particular patient population, for which the claims further recite the intended results of such an administration. These “intended results” in no way alter a) that which is administered or b) the patient upon whom the administration is practiced. As set forth in the rejection of record, artisans would have been motivated to practice the methods of treating allergy as taught by Alaniz et al. on the subgenus of food allergy patients. That applicant has discovered a more complete scientific explanation for why indole-3-carboxaldehyde treats allergies due to the elicitation of particular cell types upon administration does alter the claim to be more than administering a particular drug to a particular patient. Indeed, a product and it functional properties are inseparable such that if the same product is administered to the same patient any and all outcomes must occur even if not disclosed or observed in the art. Thus preforming the administration methods of Alaniz et al. on allergy patients will elicit the cell types recited in the instant claims even if not disclosed by Alaniz et al. as food allergy is a species within the larger genus of all allergies, and as discussed in the rejection of record food allergies are a very obvious population within the genus of all allergies, and artisans enjoy more than a reasonable expectation of success as Alaniz et al. teach their methods work on all allergies, and again, food allergy is a species within that larger genus. In view of all of the above applicant’s arguments are not persuasive.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Alaniz et al. (WO 2017/161268, of record) in view of Rivas et al. (of record as citation 47 on the 7/22/2022 IDS) as applied to claims 1, 2, 5, 7, 8, 14-16, 18 and 40 above, and further in view of Rachid et al. (of record as citation 44 on the 7/22/22 IDS) and in view of Yang et al. (of record).
The inventions rendered obvious by the combined teachings of Alaniz et al. and Rivas et al. have been discussed above and differ from the instant claimed invention in that they do not disclose measuring the titer of RORgt expressing regulatory T cells prior to administering tryptophan metabolites including indole-3-aldehyde to treat food allergy.
Rachid et al. disclose that individuals having low intestinal microorganism biodiversity are at increased risk to develop food allergies (see entire document, particularly the abstract).
Yang et al. disclose that regulatory T cells expressing both Foxp3 and RORgt suppress intestinal inflammation, with such cells being phenotypically closer to regulatory T cels than Th17 inflammatory T cells, with Treg cells expressing both Foxp3 and RORgt being the most suppressive with regard to gut specific responses (see entire document, particularly the abstract as well as the section spanning pages 449-450 as well as Figure 7). Such cells are stable and do not convert to Th17 cells even under proinflammatory conditions in vivo (see particularly the paragraph spanning pages 453 and 454 as well as Figures 5 and 6) and therefore are highly specialized to regulate immune responses at intestinal sites (see particularly the last sentence of the paragraph spanning the left and right columns of page 445). It is also disclosed that such cells are significantly more prevalent in individuals have complex intestinal microbiota as compared to those lacking microbial diversity (see particularly Figure 1).
Therefore, it would have been obvious to a person of ordinary skill in the art to measure the amount of intestinal regulatory T cells expressing both Foxp3 and RORgt prior to administration of microbial tryptophan metabolites such as indol-3-aldehyde to treat food allergy. This is because regulatory T cells expressing both Foxp3 and RORgt are largely missing in individuals who have low intestinal microbial diversity as taught by Yang et al. and individuals with low microbial diversity are at increased risks of having food allergies as taught by Rachid et al. Thus such individuals would likely see the most benefit from being administered compounds such as indole-3-aldehyde which induce regulatory T cells which express Foxp3 and do not become pro-inflammatory even in environments characterized by high levels of Il-4 such as is seen in food allergies. Note that such an administration is reasonably expected to increase the numbers of such cells which will suppress intestinal inflammation thereby ameliorating signs and symptoms of food allergy.
Applicant's arguments filed August 18, 2025 have been fully considered but they are not persuasive. Applicant argues that the base obviousness rejection is not tenable, that the additional cited teachings do not rectify its deficiencies, and therefore the rejection should be withdrawn.
These arguments have been considered and are not persuasive as applicant’s arguments concerning the base obviousness rejection are not persuasive as discussed above.
No claims are allowable.
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 Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641