Detailed action
Response to Amendments
The amendment filed 07/08/2026 has been entered. Newly amended Claims 1, 6, 11, and 14 are pending in the application. Applicant’s amendments to the specification, and drawings have overcome objections previously set forth in the Non-Final Office action mailed 04/09/2026.
Applicant’s amendments to Claims 11 and 14 have overcome objections for minor informalities, and 35 U.S.C. § 112(b), rejections previously set forth in the Office Action mailed 04/09/2026. Applicants’ amendment to Claim 1 overcomes the 35 U.S.C. § 102(a)(1) rejection for as being anticipated by Tanaka, for claims 1, and 3-5 previously set forth in the Office Action mailed 04/09/2026. Applicants’ amendment to Claim 1, overcomes the 35 U.S.C. § 103 rejection for as being obvious in view of Tanaka, and in further view of Doyle for claims 3 and 4 previously set forth in the Office Action mailed 04/09/2026. Claims 2 and 12 are cancelled, and Claims 1, 3-11, and 13-14 are examined on the merits herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
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, and 3-5 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 was amended to “An anticancer agent comprising consisting of a therapeutically effective amount of Indoxyl Sulfate for treatment of colorectal cancer, wherein the Indoxyl Sulfate is present at a concentration range of 0.038mM to 10mM.” The use of “consisting of” is closed claim language, suggesting there is only Indoxyl sulfate in the anticancer agent, but the Indoxyl Sulfate is present at a specific concentration range. A concentration requires the presence of at least one other ingredient, like a solvent. It is unclear if the claim can have a solvent, or if it is limited to only include Indoxyl Sulfate.
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, and 3-5 rejected under 35 U.S.C. 101 because the claims are directed to a composition of matter, containing a natural phenomenon/product of nature (Indoxyl Sulfate), and an unidentified diluent. This rejection is maintained but has been modified to address the claim amendments.
Claim 1 recites “An anticancer agent comprising consisting of a therapeutically effective amount of Indoxyl Sulfate for treatment of colorectal cancer, wherein the Indoxyl Sulfate is present at a concentration range of 0.038mM to 10mM.” The claim lists Indoxyl Sulfate at a specified concentration range in an anticancer agent, suggesting a diluent is in solution with Indoxyl Sulfate. In this case, the Broadest reasonable interpretation (BRI) of the claim, does not cover the naturally occurring agent Indoxyl Sulfate, but the composition of matter of Indoxyl Sulfate and an unidentified diluent. Specification paragraphs [0003-0006] describe Indoxyl Sulfate as an Indole derivative produced by gut microbiota and liver cytochrome oxidases.
The BRI of the diluent of claim 1, is water, and water is a naturally occurring product of nature. The components of Indoxyl Sulfate and water are separately natural products, and together in solution, they do not display markedly changed by their combination into a mixture. The mixture of Indoxyl Sulfate and water does not change the characteristics of either component, because each component continues to have the same properties in the mixture, as it had alone.
Also, prior to applicants’ invention, it was well-understood, routine, and conventional in the field, to mix Indoxyl Sulfate with a diluent like water. Thus, the mixing of water and Indoxyl Sulfate, when recited at this high level of generality, does not meaningful limit the claim, and the claim as a whole does not amount to significantly more than each product of nature by itself, and does not qualify as eligible subject matter.
Claims 3 and 4 recite specific concentrations that Indoxyl Sulfate will be present at, instead of the concentration range provided in Claim 1. Varying the amounts of Indoxyl Sulfate used does not create markedly different properties for the anticancer agent.
Claim 5, recites an additional element of a pharmaceutically acceptable excipient, but an excipient is routine in pharmacology, and the addition of an excipient with Indoxyl Sulfate does not produce a materially different product, or change any characteristics (structural, functional, or otherwise) about Indoxyl Sulfate.
Because the claims do not include any additional features that could add significantly more to the exception, the claims do not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
Response to Applicant’s Arguments
Applicant's arguments filed 07/08/2026 have been fully considered but they are not persuasive.
Applicant argues that Claim 1, as amended, discloses a therapeutically effective amount of Indoxyl Sulfate ranging from 0.038mM to 10mM to specifically treat colorectal cancer, and the additional of these limitations, adds significantly more than the exception directed to the naturally occurring agent, Indoxyl Sulfate.
The applicant has not established that mixing Indoxyl Sulfate with an undisclosed diluent, changes the structure, function, or other characteristics of the separate components.
The specification states “Gut microbiota produces indole compounds by degrading aromatic amino acid i.e. tryptophan which further get transformed into Indoxyl Sulfate (IS) with the help of liver cytochrome oxidases” (Pg. 1, [0003]). Applicant has not established that Indoxyl Sulfate produced by gut microbiota and liver cytochrome oxidases, a naturally occurring product of nature, mixed with a diluent, reasonably assumed as water, amounts to significantly more than the products of nature. Mixtures of Indoxyl Sulfate and diluents such as water, are well-understood, routine, and conventional in the field.
The courts found, “See, e.g., Funk Bros., 333 U.S. at 130, 76 USPQ at 281 (comparing claimed mixture of bacterial species to each species as it occurs in nature); Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 (although claimed as a pair, individual primer molecules were compared to corresponding segments of naturally occurring gene sequence); In re Bhagat, 726 Fed. Appx. 772, 778-79 (Fed. Cir. 2018) (non-precedential) (comparing claimed mixture of lipids with particular lipid profile to “naturally occurring lipid profiles of walnut oil and olive oil”).
Claims 3 and 4 recite specific concentrations that Indoxyl Sulfate will be present at, instead of the concentration range provided in Claim 1. Varying the amounts of Indoxyl Sulfate used does not create markedly different properties for the anticancer agent.
Claim 5, recites an additional element of a pharmaceutically acceptable excipient, but an excipient is routine in pharmacology, and the addition of an excipient with Indoxyl Sulfate does not produce a materially different product, or change any characteristics (structural, functional, or otherwise) about Indoxyl Sulfate.
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.
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.
Claims 6-11, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Amigorena (Sebastian Amigorena, Elodie Segura, “Agonist of Aryl Hydrocarbon receptor for use in cancer combination therapy”, US Patent Application No. WO 2019057744 A1, Pub. Date 3/28/2019) in view of Dneprovskaia (Elena V. Dneprovskaia, Michael S. Holzwarth, “Compounds and Methods of Treating Cancer”, WO 2020231739 A2, Pub. Date: 11/19/2020).
Regarding Claim 6 and 10, Amigorena discloses an AHR agonist used in combination with at least one immune checkpoint modulator to treat cancer (Claim 1). Amigorena discloses “AhR agonist for use according to claim 1, wherein the AhR agonist is a tryptophan metabolite, preferably the tryptophan metabolite is selected from the group comprising Kynurenic acid, Kynurenine, 6-formylindolo[3,2b] carbazole (FICZ) and Indoxyl sulfate” (Claim 2). The specification teaches colon and rectum cancer as solid forms of cancer that the therapeutic could treat (Pg. 25, lines 29-30).
Regarding Claims 7 and 8, Amigorena discloses an “immune checkpoint modulator”, defined as cancer immunotherapy in the specification (Pg 19, line 31-32).
Regarding Claim 9, Amigorena discloses, a specific embodiment that achieves “eradication, removal, or control of primary, regional, and/or metastatic cancer” (Specification, pg. 3 line 36-37 and pg. 4 lines 1-2).
Regarding Claim 11, Amigorena discloses an embodiment of the invention that includes “the pharmaceutical composition comprising the AHR agonist and/or the immune checkpoint modulator further comprises a pharmaceutically acceptable carrier and/or vehicle”, and defines a pharmaceutically acceptable carrier as an excipient (Specification, pg. 26 lines 14-24).
Regarding Claim 13, Amigorena discloses that the term “patient” is defined as a human, and other mammalian subjects (Pg. 3, lines 28-30).
Amigorena does not disclose “wherein the Indoxyl Sulfate is administered in a dosage amount ranging from 100 mg/kg body weight to 125 mg/kg body weight of the subject under treatment”.
Dneprovskaia teaches AhR agonists administered therapeutically to human/mammals to treat cancer in the dosage range of “0.25 mg/kg to about 120 mg/kg or more of body weight” (Specification, paragraph [0142 and 0166]).
The dosage amount of Indoxyl Sulfate disclosed in instant Claim 6, “100 mg/kg body weight to 125 mg/kg body weight”, overlaps with the dosage range of AhR agonists disclosed in Dneprovskaia, 0.25 mg/kg to about 120 mg/kg or more of body weight. The courts found that, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) The prior art taught carbon monoxide concentrations of “about 1-5%” while the claim was limited to “more than 5%.” The court held that “about 1-5%” allowed for concentrations slightly above 5% thus the ranges overlapped.
Regarding Claims 6-11, and 13, it would have been prima facie obvious for one of ordinary skill in the arts before the effective filing date to combine the method of using Indoxyl Sulfate as an AhR agonist to treat colon and rectum cancer in mammals disclosed in Amigorena, with the method disclosed in Dneprovskaia for administering AhR agonists to mammals to treat cancer, because both methods treat cancer with AhR agonists.
Regarding Claim 14, Amigorena teaches “Typically the AHR agonist and the immune checkpoint modulator are in separate compositions” (Dosage, Pg. 26).
Instant Claim 14 states, “A method of using Indoxyl Sulfate as an anticancer agent for treatment of colorectal cancer in a subject comprising: administering the anticancer agent consisting of a therapeutically effective amount of the Indoxyl Sulfate”.
Amigorena teaches a method of administering Indoxyl Sulfate as an anticancer agent to treat colorectal cancer, and teaches Indoxyl Sulfate administered as a separate composition than the immune checkpoint modulator. Instant Claim 14, as stated above, uses “comprising” as open-ended claim language for the method of using Indoxyl Sulfate as an anticancer agent. Comprising being open ended, means that the method could include using Indoxyl Sulfate as an anticancer agent, with an immune checkpoint modulator, as disclosed in Amigorena, but the active step of administering the anticancer agent, only includes Indoxyl Sulfate. This limitation is met with the “separate compositions” disclosed in Amigorena.
Regarding Claim 14, it would have been prima facie obvious for one of ordinary skill in the arts before the effective filing date to use the method disclosed in Amigorena to meet the limitations of instant Claim 14, because Amigorena teaches Indoxyl Sulfate used as an anticancer agent, and administered at a therapeutically effective amount.
Response to Applicant’s Arguments
Applicant argues that Claim 6, as amended to recite the features of cancelled claim 12, is no longer disclosed in the prior art (Amigorena) because it fails to disclose the new limitations.
Amigorena teaches all of the limitations of Claim 6, except “wherein the Indoxyl Sulfate is administered in a dosage amount ranging from 100mg/Kg body weight to 125mg/Kg body weight of the subject under treatment”. However, the dosage limitations were part of previous claim 12 which was properly rejected under 35 U.S.C § 103 as being obvious in view of Amigorena and in further view of Dneprovskaia. The examiner notes that the proper 10-digit document number for Dneprovskaia was provided in the non-final rejection but was mistakenly listed as a US document (rather than a WO document) on the 892.
The applicant has not established a compelling argument regarding why two methods of treating the same disease, cancer, using the same mechanism of action, AHR agonists, would not yield predictable results, therefore the rejection is maintained for Claims 6-11, and 13-14. Further, applicant has not provided evidence that the claimed dosage range provides unexpected results compared to the closest prior art.
Conclusion
No claim is allowable.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action.
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.
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/C.M.R./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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