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
Claims 1-2 and 5-10 are currently pending.
Election/Restriction
Applicant’s election without traverse of Group I (Claims 1-2 and 5-10, drawn to treatment of a liver disease) and the elected species indole-3-acetate (I3A) in the reply filed on 4/07/2026 is acknowledged.
Claims 3-4 and 11-20 are canceled. Pending Claims 1-2 and 5-10 are being examined on the merits herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in Paragraph 109 of the specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
Claim 2 is objected to because “the tryptophan metabolite contains” should instead read “the tryptophan metabolite is”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-2 and 5-10 are 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 regards as the invention.
Claims 1-2 recite “derivative” and “metabolite”. The specification does not offer a limiting definition of the terms. Some derivatives and metabolites are described in Paragraph 33 of the specification. It is unclear how derived or altered a tryptophan or I3A can be before would no longer be considered a derivative by one of ordinary skill in the art. Similarly, metabolism of tryptophan is complex, including many of the compounds recited in the specification. Tryptophan similarly is an amino acid used as in human metabolism to build more complex proteins and peptides. It is unclear what limitations “metabolite” confers or if any small molecule that is merely similar in any aspect or any protein or molecule containing tryptophan is to be included in the claim scope. For purposes of examination, indole is interpreted to be a derivative of indole-3-acetate which is a derivative/metabolite of tryptophan. Claims 5-10 are rejected by virtue of dependency.
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.
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.
Claims 1-2 and 5-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ma (Hepatology, Vol. 72, No. 4, 2020. 1191-1203).
Ma teaches “Indole Alleviates Diet-Induced Hepatic Steatosis and Inflammation” (Title). “indole is relevant to human NAFLD…indole mimetic and/or macrophage-specific PFKFB3 activation may be the viable preventive and/or therapeutic approaches for inflammation-associated diseases including NAFLD” (Abstract). Dosing in the model is oral in a liquid suspension (Page 1193; Figs. 2-3 and 6-7 Caption). Indole is interpreted to be a derivative of indole-3-acetate due to its structural similarity. Further, “supplementation of I3A decreased palmitate-induced lipogenic gene expression in AML12 hepatocytes and suppressed proinflammatory cytokine expression in RAW264.7 macrophages. However, it remains largely unknown whether and how indole exerts a protective role in NAFLD” (1193).
Claims 1-2 and 5-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ghahary (WO2014194407).
Ghahary teaches dosing xanthurenic acid (XA) to treat fibrosis (Abstract). Fibrotic conditions are taught to include specifically liver cirrhosis (Page 6, Lines 14-19). “xanthurenic acid [is] capable of stimulating MMPi and MMP3 expression, while inhibiting collagen and fibronectin expression” (Page 2, Lines 15-19). Delivery is oral in the form of a liquid solution or tablet (Page 17, Lines 10-34). Patients include human patients (Page 15, Lines 4-7 and Page 16, Lines 29-34). XA is a tryptophan metabolite (specification: Para 33) and therefore interpreted for examination to be a derivative of I3A, reading on Claims 2 and 6.
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.
Claims 1-2 and 5-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ma (Hepatology, Vol. 72, No. 4, 2020. 1191-1203) in view of Krishnan (Cell Reports 23, 1099–1111. April 24, 2018).
Ma teaches “Indole Alleviates Diet-Induced Hepatic Steatosis and Inflammation” (Title). “indole is relevant to human NAFLD…indole mimetic and/or macrophage-specific PFKFB3 activation may be the viable preventive and/or therapeutic approaches for inflammation-associated diseases including NAFLD” (Abstract). Dosing in the model is oral in a liquid suspension (Page 1193; Figs. 2-3 and 6-7 Caption). Indole is a derivative of indole-3-acetate. Further, “supplementation of I3A decreased palmitate-induced lipogenic gene expression in AML12 hepatocytes and suppressed proinflammatory cytokine expression in RAW264.7 macrophages. However, it remains largely unknown whether and how indole exerts a protective role in NAFLD” (1193).
Ma does not explicitly suggest orally dosing liquid suspensions of I3A to human patients.
Krishnann teaches “further studies are warranted in animal models and human subjects to determine whether I3A or other microbiota metabolites can effectively intervene in the pathogenesis of NAFLD” (1107).
Therefore, one of skill in the art seeking to treat the diseases described in Ma would find it obvious to use the dosing technique, taught in Ma with indole as applied to mice to be used in humans, wherein indole is instead replaced with I3A because Krishnan specifically encourages the use as claimed, rendering the method obvious to try. One of skill of the art would expect such a dosing regimen to be effective as claimed because both Ma and Krishnan teach anti-fibrotic and anti-inflammatory properties and potential of I3A before the effective filing date of the instant claims.
Conclusion
No claim is allowable.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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