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 .
The amendment filed 17 August 2026 has been received, entered and considered. The following information has been made of record in the instant amendment:
1. No Claims have been canceled.
2. New Claims 12-13 have been added.
3. Claims 1-2 and 6 have been amended.
4. Remarks drawn to rejections under 35 USC 112 and 103.
The following objection(s)/rejection(s) has/have been overcome:
The rejection of Claims 2 and 6 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph has been overcome by amendment.
Claims 1-13 are pending in the case. Claims 7-11 have been withdrawn from consideration as being drawn to non-elected invention. Claims 1-6 and 12-13 are under prosecution.
The following rejections are necessitated by Applicant's amendment filed 17 August 2026 wherein the limitations in pending claims 1-2 and 6 have been amended.
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.
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.
Claim(s) 1-6 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al (Environmental Pollution, 2020, 265, 1-11; of record) in view of Wei et al (BMC Microbiology, 2016, 16:255, 1-9; of record) and further in view of Lee et al (Int. J. Mol. Sci, 2021, 22, 3566, 1-26; of record) and Geros et al (Immunology, 2020, 161, 186-199; of record).
Lin et al teaches that the usage of antibiotics in treating pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. Inulin restored the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively (Abstract; page 2, part 2.2; page 7, part 3.4; page 9, parts 4.3, 4.4; page 10-Conclusions; part of the limitation of claim 1 regarding patient population, and plant fiber; limitation of claim 2-inulin). Lin does not teach the use of mitochondrial complex 1 inhibitor as in claim 1, the other plant derived fibers as in claim 2, and the limitations of claims 3-6.
Wei teaches that pectin may help maintain the balance of gut microbiota (page 1, right col., lines 1-4; pectin as in claim 2).
Lee et al teaches that metformin recovered dysbiosis in HFD-rats and without metformin, the composition of intestinal microbiota is affected by several factors including other medication (page 7, last para; page 9, second full para; page 17, part 5; metformin as in claim 3). Since Lee teaches that gut dysbiosis can take place due to other medication, one of ordinary skill in the art will have a reasonable expectation of success that administration of metformin to a subject would alleviate antibiotic-induced gut dysbiosis as in claim 1. In view of the teaching of Lee one of ordinary skill in the art would have a reasonable expectation of success that phenformin, mito-metformin and other metformin analogs would also alleviate antibiotic-induced gut dysbiosis (as in claim 3.
Lin, Wei and Lee do not teach administering mitochondrial complex 1 inhibitor as in claims 1 and 4-6.
Geros et al teaches that failure to sequester iron locally resulted in dysbiosis and persistent gut inflammation (page 191, left col., last two lines through right col., line 2). Siderophores are small molecules produced by bacteria with high affinity for Fe3+. Siderophores include carboxylates, catecholates, hydroxamates and phenolates. In addition to supplying iron for growth, the siderophore enterobactin has been proposed to inhibit iron-dependent host defense proteins such as myeloperoxidase. Lipocalin 2 restricts the growth of bacteria that rely solely on enterobactin in a number of in vivo and invitro models. Microbial composition of the gut microbiota undergoes temporal and spatial variations as a result of antibiotic exposure. Siderophore based therapies extend to probiotic bacteria that can more effectively compete with Salmonella for iron (page 193, left col., first para below sub-heading through right col., line 2; page 194, left col., lines 1-7 in para below sub-heading; page 195, right col., first para; limitation of claim 4-iron chelator; limitation of claims 5-6-siderophores, lipocalin and 2,5-dihydroxybenzoic acid which is a carboxylate). From this teaching of Geros one of ordinary skill in the art will recognize that an iron chelator like enterobactin and lipocalin can be used in combination with plant derived fibers like inulin and pectin for alleviating gut dysbiosis. In view of this teaching and that of Lin, Wei and Lee, one of ordinary skill in the art will also use the other plant derive fibers recited in claim 2, and all the other mitochondrial complex 1 inhibitors as in claims 3-6. Administration of a plurality of plant derived fibers as in claims 12-13 is also rendered obvious since inulin and pectin are taught in the art to restore gut microbiota.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to arrive at the claimed method of alleviating antibiotic induced gut dysbiosis.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, plant-derived fibers are known in the art to alleviate antibiotic-induced gut dysbiosis. Mitochondrial complex 1 inhibitors are also known to have a role in dysbiosis. Thus, it is obvious to arrive at the claimed method of dietary fiber supplementation to alleviate antibiotic-induced gut dysbiosis in a patient via administration of plant-derived fibers and mitochondrial complex 1 inhibitors.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. Method improvement is the motivation. In addition, Lin et al teaches that inulin sowed the best alleviation on amoxicillin induced antibiotic resistant genes (ARG) blooming (page 8, left col., last para, lines 17-19). Siderophores like lipocalin also have a role in dysbiosis (Geros). Therefore, it is obvious to combine the two components and administer the combination in the claimed method.
It has been held that it is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for the same purpose in order to form a third composition that is to be used for the very same purpose. The idea of combining them flows logically from their having been taught individually in the prior art. See In re Kerkhoven, 205 USPQ 1069, CCPA 1980.
Response to Applicants’ Remarks
Applicant has traversed the rejection of claims under 35 USC 103 arguing that claim 1 has been amended to recite only supplementation before and during antibiotic therapy. Lin and Wei only describe treatment after fecal transplantation and/or antibiotic administration. This kind of preventive treatment is not described by Lee or Geros. Because these recited elements are absent form the combined references, applicants respectfully request that the rejection of claim 1 be withdrawn.
Lee describes administering metformin to subjects having type II diabetes to evaluate its effect on gut dysbiosis resulting from diabetes, for the purpose of developing a better understanding of the mechanism of metformin as an antidiabetic medication. One skilled in the art would have no reason to believe that the effects seen in this study would also be present in non-diabetic patients, such as those receiving antibiotic therapy. Geros teaches that siderophores can be produced by pathogenic bacteria to circumvent iron withholding. Since pathogenic bacteria increase their ability to thrive by releasing siderophores, this would aggravate rather than decrease the dysbiosis by increasing the number of pathogenic bacteria. For these reasons withdrawal of the rejection is requested. (Remarks-pages 4-5).
Applicants’ arguments have been considered but are not found to be persuasive. From the teachings of Lin and Wei it is obvious that administration of inulin and pectin to a patient undergoing antibiotic treatment will alleviate gut dysbiosis. Lin and Wei may describe treatment after fecal transplantation and/or antibiotic administration. However, this is not a teaching or suggestion that it cannot be given before or during antibiotic treatment. Since antibiotic treatment is known in the art to cause gut dysbiosis one of ordinary skill in the art will administer inulin and pectin to a patient before or during antibiotic treatment to alleviate gut dysbiosis. This need not be expressly taught in the prior art. It is well within the skill level of the artisan to recognize this from the teachings of Lin.
Lee may describe administering metformin to subjects having type II diabetes to evaluate its effect on gut dysbiosis resulting from diabetes, for the purpose of developing a better understanding of the mechanism of metformin as an antidiabetic medication. Since Lee teaches that gut dysbiosis can take place due to other medication, one of ordinary skill in the art will have a reasonable expectation of success that administration of metformin to a subject would alleviate antibiotic-induced gut dysbiosis. Moreover, the recitation of a patient in claim 1 is broad and includes both diabetic and non-diabetic patients. Irrespective of whether the patient is diabetic or not the artisan would still have a reasonable expectation that metformin will alleviate gut dysbiosis in non-diabetic patients too.
Applicant argues that Geros teaches siderophores can be produced by pathogenic bacteria to circumvent iron withholding. Since pathogenic bacteria increase their ability to thrive by releasing siderophores, this would aggravate rather than decrease the dysbiosis by increasing the number of pathogenic bacteria. If this is the case, then applicant has not explained why they are using siderphores as a mitochondrial complex 1 inhibitor as in claim 6. No examples are disclosed in the specification using siderophores which show that they do help in alleviating gut dysbiosis as claimed and what is different or unexpected in using siderophores in the claimed method. Moreover, the administration of pectin and inulin as taught in the prior art should offset any aggravation that may be seen.
The combined teachings of the prior art render the instant claims obvious. The rejection is maintained.
Conclusion
1. Elected claims 1-6 (Group I) and 12-13 are rejected.
2. Group II Claims 7-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
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.
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/GANAPATHY KRISHNAN/ Primary Examiner, Art Unit 1693
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