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
This application claims benefit of provisional application 63/495426, filed April 11, 2023. Claims 1-20 are pending in this application and examined on the merits herein.
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 1-14 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Proviso (ii) at the end of step (a) ends with the phrase “or and”. It is unclear from the construction of this limitation whether it is intended to require both of steps (a) and (b) or only one of steps (a) or (b), given that both “or” and “and” appear in the claim.
Claim 1 refers to the biomarkers identified in Fig. 8K, 9H, and 14. Claims 8 and 15 refer to the compounds listed in table 1A, 1B, 2, or 3. According to MPEP 2173.05(s), “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." In the present case, the scope of the claims could be practically defined simply by reciting each of the intended compounds individually in the claim. Therefore these claims are indefinite.
Claim 11 is directed to the method of claim 8. However, the claim adds the additional limitation, “further comprising at least one additional therapeutic agent.” A method comprises various process steps but does not specifically comprise a chemical substance such as a therapeutic agent. Therefore the statement of the claim in this manner creates doubt as to what the actual statutory category of the claimed invention is, rendering the claim indefinite.
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 5-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang et al. (Reference included with PTO-892)
Independent claim 1 is directed to a method of diagnosing leaky gut in a subject comprising measuring the expression level of a polynucleotide or peptide which is one of the biomarkers identified in figure 8K, 9H, or 14. Looking to figure 8K, the biomarkers are L-argininosuccinate, 3-hydroxybutyric acid, and Ribose phosphate. Looking to figure 9H, the markers are serum argininosuccinate or taurine. Looking to figure 14, the biomarkers are Argininosuccinate synthase, (Ass1) Argininosuccinate lyase, (Asl) and inducible nitric oxide synthase. (Nos2)
Tang et al. discloses a study of intestinal metabolism of patients having osteoarthritis. (p. 3 left column second paragraph) Blood from experimental animals suffering from OA was tested for various inflammatory markers including iNOS, which is the same as Nos2. (p. 3 right column second paragraph) Furthermore the animals suffering from OA were found to have increased expression of iNOS, and increased intestinal permeability, both of which were reduced upon treatment of the OA. (p. 6 left column last paragraph) Therefore measuring iNOS in these animals is seen to be a diagnostic method according to claims 1 and 2, as well as claim 5 because the marker was upregulated.
Regarding claims 6 and 7, the treatment as described in p. 3 right column first paragraph of Tang includes administration of probiotic bacteria which are considered to be a nutraceutical according to these claims.
Claims 1-3 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shah et al. (Reference included with PTO-892)
Independent claim 1 is directed to a method of diagnosing leaky gut in a subject comprising measuring the expression level of a polynucleotide or peptide which is one of the biomarkers identified in figure 8K, 9H, or 14. Looking to figure 8K, the biomarkers are L-argininosuccinate, 3-hydroxybutyric acid, and Ribose phosphate. Looking to figure 9H, the markers are serum argininosuccinate or taurine. Looking to figure 14, the biomarkers are Argininosuccinate synthase, (Ass1) Argininosuccinate lyase, (Asl) and inducible nitric oxide synthase. (Nos2)
Shah et al. discloses a study aimed at identifying markers of increased intestinal permeability. (p. 2 last paragraph) The ratio of argininosuccinic acid to trans-aconitic acid was seen to be one such marker. (p. 8 figure 5, p. 7 second paragraph) Therefore Shah et al. anticipates methods of diagnosing leaky gut according to claims 1-3 and 5.
Claims 15, 16, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (Reference included with PTO-892)
Independent claim 15 is directed to a method of treating a leaky gut syndrome comprising administering to a subject in need thereof one or more of the nutraceutical compounds listed in tables 1A, 1B, 2, and 3. Dependent claim 16 further narrows the compounds to indole acetamide, methylnicotinamide, carnosine, and indolepropionic acid.
Chen et al. discloses a study of the effect of indolepropionic acid (IPA) on obesity. (p. 5986 right column second paragraph) This compound was seen to be deficient in the serum of obese patients. (p. 5986 right column last paragraph) Obese mice fed a diet containing orally administered IPA exhibited reduced body weight and other symptoms associated with obesity such as glucose tolerance. (p. 5987 right column) In particular, obesity was accompanied by impaired gut barrier function, which was reversed by administration of IPA. (p. 5989 right column) Administering this compound to obese experimental animals having impaired gut barrier function therefore anticipates claims 15, 16, 19, and 20.
Claims 15, 16, 18, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Davison et al. (Reference included with PTO-892)
Independent claim 15 is directed to a method of treating a leaky gut syndrome comprising administering to a subject in need thereof one or more of the nutraceutical compounds listed in tables 1A, 1B, 2, and 3. Dependent claim 16 further narrows the compounds to indole acetamide, methylnicotinamide, carnosine, and indolepropionic acid.
Davison et al. discloses that exercise stress can lead to exertional heat stroke, of which altered gut permeability is one symptom. (p. 526 right column first paragraph) Davison et al. further discloses treatment with the combination therapy zinc carnosine, having the therapeutic agents zinc and carnosine in a 1:1 ratio. (p. 526 right column last paragraph) Subjects undergoing strenuous exercise were orally administered zinc carnosine and colostrum. (p. 528 left column last paragraph – p. 529 left column second paragraph) The combination of these therapeutic agents was seen to reduce the increase in gut permeability caused by intense exercise, thereby anticipating the present claims. (p. 531 left column last paragraph – right column first paragraph)
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 15, 16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Reference included with PTO-892)
Independent claim 15 is directed to a method of treating a leaky gut syndrome comprising administering to a subject in need thereof one or more of the nutraceutical compounds listed in tables 1A, 1B, 2, and 3. Dependent claim 16 further narrows the compounds to indole acetamide, methylnicotinamide, carnosine, and indolepropionic acid.
Li et al. discloses a study of the effect of indolepropionic acid (IPA) in intestinal barrier homeostasis. (p. 1487 right column second paragraph) Colonic cells in culture were exposed to IPA, and the intestinal barrier integrity was assessed. (p. 1468 left column second and third paragraphs, right column first paragraph) While Li et al. does not specifically disclose administering IPA to a living subject, it would have been obvious to one of ordinary skill in the art at the time of the invention to use this compound in a living subject. In particular, Li et al. suggests (1487 left column first paragraph, p. 1493 left column second paragraph, p. 1493 right column second and third paragraphs) that impairment of the intestinal barrier is a factor in various diseases including intestinal inflammatory disease.
Therefore the invention taken as a whole is prima facie obvious.
Claims 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. as applied to claims 15, 16, and 19 above, and further in view of Rawls et al. (PCT international publication WO2021/216841, Reference included with PTO-892)
The disclosure of Li et al. is discussed above. While Li et al. suggests treating intestinal inflammatory conditions, the reference does not specifically suggest treating inflammatory bowel disease, ulcerative colitis, or Crohn’s disease. Rawls et al. discloses a method of treating or preventing a gastrointestinal disorder in a subject, comprising providing to the subject a tryptophan catabolite including indolepropionic acid. (p. 2 lines 25-31) In a particular embodiment the gastrointestinal disorder is colitis or Crohn’s disease. (p. 3 lines 11-12)
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the IAP composition described by Li et al. to a subject suffering from Crohn’s disease, for example. One of ordinary skill in the art would have found this to be obvious as Li et al. discloses treating intestinal inflammatory diseases in general and Rawls et al. discloses treating this particular intestinal inflammatory disease.
Therefore the invention taken a s a whole is prima facie obvious.
Claims 6-9, and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Shah et al. as applied to claims 1-3 and 5 above, and further in view of Li et al. (Reference included with PTO-892)
The disclosure of Tang et al. is discussed above. While Tang et al. does not specifically disclose a method further comprising administering a compound to treat leaky gut, as discussed above, Li et al. discloses a study of the effect of indolepropionic acid (IPA) in intestinal barrier homeostasis. (p. 1487 right column second paragraph) Colonic cells in culture were exposed to IPA, and the intestinal barrier integrity was assessed. (p. 1468 left column second and third paragraphs, right column first paragraph)
Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to administer the treatment described by Li et al. to a subject diagnosed with leaky gut as described by Shah et al. One of ordinary skill in the art would have seen the disclosure in the art of both a method of diagnosing a condition and a method of treating the same condition as suggesting using the therapeutic method to treat a patient identified by the diagnostic method. Furthermore with respect to present claim 14, it would additionally have been obvious to one of ordinary skill in the art to perform the diagnostic method of Shah an additional time after treatment with IPA in order to monitor the effectiveness of the treatment.
Therefore the invention taken a s a whole is prima facie obvious.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 8/4/2026
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