Detailed Action
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 .
No Information Disclosure Statement has been filed.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0004] states “indoxylsulphate”, there should be a space and conformity with the rest of the specification for “sulfate” instead of “sulphate”.
Paragraph [0045] states “indoxy lsulfate”, should state “indoxyl sulfate”.
Paragraph [0045] states “Result show”, should be “Result shows” or “Results show”
Appropriate correction is required.
Drawings
The drawings are objected to because Figures 3A and 3B have the x-axis labeled as “Contration of IS” instead of “Concentration of IS”. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
CLAIM STATUS
Claims examined: 1-14
Claims rejected: 1-14
Claims objected to: 11
Claim Objections
Claim 11 is objected to because of the following informalities: Lines 1 and 2, “in any one or more pharmaceutical preparation, a nutritional preparation, or a food preparation”. Should read “in any one or more pharmaceutical preparations, a nutritional preparation, or a food preparation”.
Appropriate correction is required.
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.
Claim 14 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 14: A method of using Indoxyl Sulfate as an anticancer agent for treatment of colorectal cancer in a subject.
Claim 14 is a method claim that does not have definite steps. The broadest reasonable interpretation of the claim is indefinite and it does not allow someone of ordinary skilled in the art to know how to use Indoxyl Sulfate as an anticancer agent.
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 1-5 rejected under 35 U.S.C. 101 because the claims are directed to a natural phenomenon/product of nature (Indoxyl Sulfate). Specification paragraphs [0003-0006] describe Indoxyl Sulfate as an Indole derivative produced by gut microbiota and liver cytochrome oxidases. Based on the information the applicant discloses, there is no indication that Indoxyl Sulfate as an anticancer agent has any characteristics (structural, functional, or otherwise) that are different than naturally occurring Indoxyl Sulfate. Because there is no difference between the claimed and naturally occurring agent, the claimed agent does not have markedly different characteristics from what occurs in nature, and thus is a “product of nature” exception.
Claims 2-4 recite additional elements of claim 1 that include a concentration range and specific concentrations that Indoxyl Sulfate will be present at. Varying the amounts of Indoxyl Sulfate used does not create markedly different properties for the compound.
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.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 2, and 5 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tanaka (Tohru Tanaka, Motowo Nakajima, Kiwamu Takahashi, and Taaki Abe, “Erythropoietin production-promoting agent”, US Patent Application No. US 2014/0288172 A1, Pub. Date 9/25/2014).
Tanaka teaches a pharmaceutical composition comprising 1 mM Indoxyl sulfate, 0.3 µM 5-aminolevulinic acid hydrochloride, and 0.15 µM sodium ferrous citrate as an erythropoietin production-promoting agent used therapeutically to treat renal anemia (Specification, page 5, Table 1 and paragraph [0087-0088]). Tanaka also teaches a pharmaceutically acceptable excipient for use with the therapeutic agent (Specification, page 4, [0073]).
Because Tanaka teaches a pharmaceutically acceptable composition comprising Indoxyl Sulfate and an excipient to treat renal anemia, it would be capable of carrying out the intended use of treating colorectal cancer therapeutically.
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.
Claim(s) 6-11, 13-14 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).
Amigorena teaches in Claim 1, an AHR agonist used in combination with at least one immune checkpoint modulator to treat cancer. Claim 2 teaches “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”.
Amigorena also teaches an “immune checkpoint modulator”, defined as cancer immunotherapy in the specification (Pg 19, line 31-32).
Amigorena teaches 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).
The specification teaches colon and rectum cancer as solid forms of cancer that the therapeutic could treat (Pg. 25, lines 29-30).
The specification teaches, 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).
The specification teaches that the term “patient” is defined as a human, and other mammalian subjects (Pg. 3, lines 28-30).
It would have been obvious for one of ordinary skill in the art before the effective filing date to teach all the limitations of claims 6-11, 13-14, because Amigorena teaches Indoxyl Sulfate was disclosed as an AHR agonist used therapeutically to treat cancer in a subject in the claims, and the specification lists embodiments that cover the remaining limitations, like treating colon and rectum cancer and metastatic cancer. Anyone in the arts could easily combine the teachings in the claims and specification and develop a method, as disclosed in the claimed application.
Claim(s) 3 and 4 is/are rejected under 35 U.S.C. 103 as being obvious over Tanaka (Tohru Tanaka, Motowo Nakajima, Kiwamu Takahashi, and Taaki Abe, “Erythropoietin production-promoting agent”, US Patent Application No. US 2014/0288172 A1, Pub. Date 9/25/2014) in view of Doyle (Glynda Rees Doyle, Jodie Anita McCutcheon, “Clinical Procedures for Safer Patient Care”, Publication Date: November 23, 2015, Chapter 7, 7.5 Intravenous Medications by Direct IV Route).
Tanaka teaches a pharmaceutical composition comprising 1 mM Indoxyl sulfate, 0.3 µM 5-aminolevulinic acid hydrochloride, and 0.15 µM sodium ferrous citrate as an erythropoietin production-promoting agent used therapeutically to treat renal anemia (Specification, page 5, Table 1 and paragraph [0087-0088]).
Tanaka discloses preferred dosage administration that includes 1 mg to 3000 mg a day of the erythropoietin production promoting agent and dose optimization [0074]. Administration routes can include intravenous injections according to the specification [0070 and 0072].
Tanaka does not teach Indoxyl Sulfate present at a concentration of 5 mM or 10 mM in a pharmaceutical agent.
Doyle teaches administration of medications intravenously at a maximum volume of 20 mL(Pg. 483).
Below are the calculations for the concentration of Indoxyl Sulfate in a 20 mL IV injection, based on the dosage mass provided by Tanaka for Indoxyl Sulfate, and the IV injection volume provided by Doyle.
𝑹𝒆𝒄𝒐𝒎𝒎𝒆𝒏𝒅𝒆𝒅 𝒅𝒐𝒔𝒂𝒈𝒆 𝒎𝒂𝒔𝒔 𝒐𝒇 𝒆𝒓𝒚𝒕𝒉𝒓𝒐𝒑𝒐𝒊𝒆𝒕𝒊𝒏 p𝒓𝒐𝒅𝒖𝒄𝒕𝒊𝒐𝒏− 𝒑𝒓𝒐𝒎𝒐𝒕𝒊𝒏𝒈 𝒂𝒈𝒆𝒏𝒕 (𝒎𝒈) 𝒙 𝒄𝒐𝒏𝒗𝒆𝒓𝒔𝒐𝒏 𝒇𝒂𝒄𝒕𝒐𝒓 𝒇𝒐𝒓 𝒎𝒈 𝒕𝒐 𝒈 𝒙
𝒎𝒐𝒍𝒆𝒄𝒖𝒍𝒂𝒓 𝒘𝒆𝒊𝒈𝒉𝒕 𝒐𝒇 𝑰𝒏𝒅𝒐𝒙𝒚𝒍 𝑺𝒖𝒍𝒇𝒂𝒕𝒆 𝒙
𝒄𝒐𝒏𝒗𝒆𝒓𝒔𝒐𝒏 𝒇𝒂𝒄𝒕𝒐𝒓 𝒇𝒐𝒓 𝒎𝒐𝒍 𝒕𝒐 𝒎𝒎𝒐𝒍 𝒙 𝒗𝒐𝒍𝒖𝒎𝒆 𝒐𝒇 𝒊𝒏𝒕𝒓𝒂𝒗𝒆𝒏𝒐𝒖𝒔 𝒊𝒏𝒋𝒆𝒄𝒕𝒊𝒐𝒏 (𝑳) = 𝒄𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏 𝒐𝒇 𝑰𝒏𝒅𝒐𝒙𝒚𝒍 𝑺𝒖𝒍𝒇𝒂𝒕𝒆 𝒊𝒏 𝒂 𝟎. 𝟎𝟐 𝑳 𝑰𝑽 𝒊𝒏𝒋𝒆𝒄𝒕𝒊𝒐𝒏
By this conversion, 1 mg indoxyl sulfate results in a 0.235 mM solution for a 0.02 L IV injection. 300 mg results in a 703.5 mM solution for a 0.02 L IV injection. Based on the calculated IV dosage concentration of Indoxyl Sulfate, as disclosed by Tanaka and in view of Doyle, claims 3 and 4 in the present application fall within the provided dosage range.
The courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See 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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that 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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim(s) 12 is/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”, Application No. US2020031876, Published 11/19/2020).
Amigorena teaches a method for treating and preventing colorectal cancer with an AHR agonist used in combination with at least one immune checkpoint modulator (Claim 1, Pg. 25, lines 29-30, Specification, pg. 3 line 36-37 and pg. 4 lines 1-2). Claim 2 discloses an “AhR agonist for use according to claim 1, wherein the AhR agonist is a tryptophan metabolite, Indoxyl sulfate.
Amigorena does not teach a specific dosage range for a 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]).
It would have been obvious for one of ordinary skill in the art before the effective filing date to teach all the limitations of Claim 12 because Amigorena teaches Indoxyl Sulfate as an AHR agonist, and Dneprovskaia teaches a dosage range of “0.25 mg/kg to about 120 mg/kg or more”, that AHR agonists are therapeutically administered to humans. The broadest reasonable interpretation of “0.25 mg/kg to about 120 mg/kg or more”, encompasses the range “100 mg/kg body weight to 125 mg/kg body weight” disclosed in Claim 12.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIERRA M ROCHELLE whose telephone number is (571)272-9962. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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/C.M.R./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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