DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
The amendment filed April 4, 2026, has been received and entered.
Claims 2, 3, 5-205, 207, and 210-217 are cancelled. Claims 218-226 are new.
Claims 1, 4, 206, 208, 209, and 218-226 are pending and examined on the merits.
Duplicate Claims Warning
Applicant is advised that should claim 222 be found allowable, claim 226 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Objections
Claims 220, 221, 224, and 225 are objected to because of the following informalities:
Claims 220 and 224 are objected to because the genus name (Methanobrevibacter as in paragraph [0018] of the specification) is omitted. Also, every recitation of a species should be italicized (e.g. Methanobrevibacter acididurans).
Likewise, claims 221 and 225 are objected to because every recitation of a species should be italicized. Additionally, claims 221 and 225 are objected to because the first letter of the recitation “Smithii” should not be capitalized. That is, the recitation “Methanobrevibacter smithii (M. Smithii)” should instead be set forth as “Methanobrevibacter smithii (M. smithii).”
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.
Claims 1, 4, 206, 208, 209, and 218-226 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.
The terms “low methanogen quantity” and “low quantity of methanogens” in claims 1, 4, and 206 are relative terms which render the claims indefinite. The terms “low methanogen quantity” and “low quantity of methanogens” are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what ranges of methanogen quantity are directed to a “low methanogen quantity” and a “low quantity of methanogens.” As such, claims 1, 4, 206, 208, 209, and 218-226 are rejected under 35 U.S.C. 112, second paragraph.
Claim 206 recites the limitation "the therapy" in the last line. There is insufficient antecedent basis for this limitation in the claim. There is no prior recitation of a “therapy.” It is unclear whether it refers to therapy for treating the disease or condition. Also, claim 206 is rendered indefinite by the recitation “the therapy is a methanogen” because it is unclear how it relates to the step of administering methanogens to the subject. It is unclear whether the methanogen of the therapy is distinct from the methanogens that are administered to the subject. It is unclear whether the methanogen (singular term) of the therapy is one, some, or all of the methanogens (plural term) that are administered to the subject having a methanogen quantity lower than the reference value. Since claim 206 is indefinite, then its dependent claims, claims 208, 209, and 223-225, are rendered indefinite. Therefore, claims 206, 208, 209, and 223-225 are rejected under 35 U.S.C. 112, second paragraph.
Claim 218 is indefinite because it is unclear how the reference value is 1,000 methanogens per ml of the biological sample since parent claim 1 requires that the reference value is 10,000 methanogens per ml of a biological sample.
Claims 220 and 221 are indefinite because it is unclear which of the methanogens of parent claim 1 is “the methanogen” of each of claims 220 and 221. It is unclear whether “the methanogen” of claims 220 and 221 is directed to the methanogens that are quantified and/or the methanogens that are the therapy of parent claim 1. Also, it is unclear whether the methanogen (singular term) of claims 220 and 221 is only one, some, or all of the methanogens (plural term) of parent claim 1.
Claim 223 is indefinite because it is unclear how the reference value is 1,000 methanogens per ml of the biological sample since parent claim 206 requires that the reference value is 10,000 methanogens per ml of a biological sample.
Claims 224 and 225 are indefinite because it is unclear which of the methanogens of parent claim 206 is “the methanogen” of each of claims 224 and 225. It is unclear whether “the methanogen” of claims 224 and 226 is directed to the methanogens that quantified, the methanogens that are administered to the subject having a methanogen quantity lower than the reference value, and/or the methanogen that is the therapy of parent claim 206. Also, it is unclear whether the methanogen (singular term) of claims 224 and 225 is only one, some, or all of the methanogens (plural term) of parent claim 206.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 218 and 223 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In particular, claims 218 and 223 fail to include all the limitations of parent claims 1 and 206, respectively, because the reference value is set forth in parent claims 1 and 206 as 10,000 methanogens per ml of a biological sample. The reference value of claims 218 and 223 is distinct from the reference value of parent claims 1 and 206, respectively.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
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 § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 4, 206, 208, 209, and 218-226 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Pimentel (US 2006/0246045. Listed on IDS filed 10/5/22) in view of Scanlan (BMC Microbiology. 2008. 8: 79. doi: 10.1186/1471-2180-8-79. 8 pages) and Armougom (US 2012/0252012).
Pimentel discloses treating disorders exhibiting diarrhea, including ulcerative colitis, by increasing the partial pressure of methane in the subject’s intestines by administering to the subject a methanogenic probiotic agent (paragraph [0015]). See also paragraph [0034] which defines the probiotic agent, which includes methanogenic bacterium such as Methanobrevibacter smithii. Pimentel also teaches increasing the partial pressure of methane in the intestines by administering a prebiotic agent that enhances the growth of methanogenic bacteria (paragraph [0035]). Ulcerative colitis is directed to the elected species for the disease or condition (instant claim 11).
Pimentel differs from instant independent claim 1 in that Pimentel does not expressly disclose that the therapy is administered to a subject who has or is determined to have a methanogen quantity that is lower than a reference value based on the recognition that the therapy is appropriate for subjects who have a methanogen quantity lower than the reference value, wherein the reference value is 10,000 methanogens per ml of a biological sample. Pimentel differs from instant independent claim 206 in that Pimentel does not expressly disclose subjecting a biological sample from a subject to analysis for methanogen quantity; and comparing the methanogen quantity to a reference value, wherein the reference value is 10,000 methanogens per ml of the biological sample, such that the methanogens are administered to the subject having a methanogen quantity lower than the reference value.
Scanlan discloses a study investigating and characterizing methanogen incidence and diversity in human fecal samples which employs a PCR and clone library methodology using one set of PCR primers specific to the α subunit of methyl-coenzyme M reductase (mcrA) (page 2, left column, last paragraph). The mcrA gene was chosen as a proxy for methanogen detection as this gene can be readily amplified from Mbb. smithii which is the dominant methanogen in the human gut (page 2, right column, first paragraph). Scanlan found that the percentage of individuals within the subjects having ulcerative colitis harbored methanogens at a low rate of 24% methanogen positive (mcrA gene) compared to the control group of 48% methanogen positive in healthy controls (page 2, right column, last paragraph; Table 1 on page 3).
Armougom discloses a method of detection and preferably of quantification of DNA extracted from a stool sample of an individual, especially for the molecular determination of the composition of the intestinal flora in the stool (paragraph [0001]). The method uses Methanobrevibacter smithii as an indicator of the quality of the extraction of the prokaryotic DNA from a stool sample (paragraph [0019]). The method of Armougom of extraction of DNA and real-time PCR quantification allowed their inventors to confirm that Methanobrevibacter smithii was present in 100% of individuals (paragraph [0025]). The quantitation of DNA extracted from a stool sample of an individual is characterized in that one controls on the quality of the extraction of the DNA by verifying whether a specific DNA of Methanobrevibacter smithii is detected, preferably quantified at a rate of at least 104 organisms of M. smithii per ml of said stool sample (paragraph [0028]). Armougom states that a quantification of 104 M. smithii organisms/ml of stool sample corresponds to the sensitivity threshold of detection below which one does not detect any DNA with the primers SEQ ID NO: 6 and 7 for the gene rpoB of M. smithii and the primers SEQ ID NO: 2 and 3 for the ribosomal RNA gene 16S of M. smithii (paragraph [0036]). Additionally, a study of 1500 stools coming from 1500 different individuals made it possible to determine a detection threshold of 104 M. smithii organisms per ml of stool sample, based on the combined detection of the rRNA 16S and rpoB genes, wherein the detection threshold of 104 organisms per ml of stool sample was not reached for 3% of the individuals (paragraph [0196]).
Before the effective filing date of the claimed invention, given that there is a tie between methanogenic bacteria in the intestines and the partial pressure of methane (given that methanogenic bacteria addresses the need for increase of methane partial pressure and based on paragraph [0035] of Pimentel for enhancing methanogen growth), it would have been obvious to the person of ordinary skill in the art to measure the methanogen bacteria quantity of a sample from the subject (obvious to use a stool sample since the methanogenic bacteria are in the intestines based on paragraph [0035] of Pimentel) to determine if the quantity is low (i.e. lower than any particular level, directed to a reference level) when performing the method of Pimentel in treating ulcerative colitis. In particular, it would have been obvious to the skilled artisan that the subject having ulcerative colitis is in need of the methanogenic bacteria agent (Methanobrevibacter smithii) administration as taught by Pimentel when the stool sample from the subject tests as negative for methanogens (in particular, M. smithii) given that Scanlan found only 24% of subjects having ulcerative colitis being positive for methanogens based on detecting the mcrA gene.
Further still, before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to use the method for the determination and quantification of M. smithii of Armougom when practicing the method of Pimentel in order to measure the methanogen bacteria quantity of a stool sample to determine if the subject having ulcerative colitis is negative for M. smithii (thus in need of M. smithii administration). One of ordinary skill in the art would have been motivated to do this because the method of Armougom successfully detected and quantified M. smithii is stool samples and because the method of Armougom is disclosed as an advantageous alternative to known methods, including the method of Scanlan, which Armougom disclosed as being disadvantageous by asserting that those known methods are not reliable in terms of extraction and quantification of the prokaryotic DNA of the stool, and are not practically adapted to a use in routine analysis (paragraphs [0011] and [0012] of Armougom, in which paragraph [0012] cites Scanlan). Since the sensitivity threshold of the method of Armougom is 104 organisms of M. smithii per ml of stool sample, then the skilled artisan would have recognized that the stool sample is negative for M. smithii if it is not detected by the method of Armougom, which is directed to being lower than a reference value which is 104 organisms of M. smithii (i.e., 10,000 methanogens) per ml of the stool sample. Based on the stool sample being negative, i.e., less than 104 organisms of M. smithii per ml of the stool sample, then it would have been obvious that the methanogenic bacteria agent (M. smithii) should be administered to the subject having ulcerative colitis according to the method of Pimentel.
Therefore, Pimentel in view of Scanlan and Armougom renders obvious instant claims 1, 4, 206, 208 (stool), 209 (the method of Armougom uses quantitative polymerase chain reaction (qPCR) based on at least paragraphs [0019], [0025], [0036]), 219 (stool), 220 (M. smithii), 221, 222 (elected species ulcerative colitis), 224 (M. smithii), 225, and 226 (elected species ulcerative colitis).
Regarding instant claims 218 and 223, it would have been obvious to the person of ordinary skill in the art that a stool sample is negative for M. smithii by the method of Armougom if it is not detected by the method of Armougom, which is any quantity of M. smithii lower than 104 organisms of M. smithii per mL of a stool sample from the subject having ulcerative colitis, including lower than 1,000 organisms of M. smithii (i.e. 1,000 methanogens) per mL of the stool sample, when performing the method rendered obvious by Pimentel in view of Scanlan and Armougom. Therefore, instant claims 218 and 223 are rendered obvious.
Response to Arguments
Applicant’s arguments, filed April 6, 2026, with respect to the objection of claim 214, the rejections under 35 U.S.C. 112(b) of claims 207, 210, 211, and 214, the rejection under 35 U.S.C. 101 of claims 206-211 and 214, and the rejection under 35 U.S.C. 103 of claims 1, 4, 11, 206-208, 210, 211, and 214 as being unpatentable over Pimentel, have been fully considered and are persuasive. In particular, the claim objection has been overcome by the amendment to claim 214. The rejections under 35 U.S.C. 112(b) have been rendered moot by the canceling of claims 207, 210, 211, and 214. The rejection under 35 U.S.C. 101 has been overcome by the amendment to claim 206. The rejection under 35 U.S.C. 103 has been overcome by the amendments to claims 1 and 206, since Pimentel does not disclose a reference value of 10,000 methanogens per ml of a biological sample. Therefore, the objection and these rejections have been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of the newly cited references Scanlan and Armougom, as necessitated by the amendments. Also, the amendments necessitated new claim objections and new grounds of rejection under 35 U.S.C. 112(b) and 112(d). Furthermore, the amendments to the claims do not address the rejection under 35 U.S.C. 112(b) due to the recitations of “low methanogen quantity” and “low quantity of methanogens” on page 3 of the last Office Action. Applicant asserts that claim 1 and its dependent claims refer to a low methanogen quantity relative to a reference value. However, claim 1 does not recite that a low methanogen quantity is a methanogen quantity lower than the reference value. Instead, claim 1 recites that the therapy is administered to the subject who has or is determined to have “a methanogen quantity lower than a reference value…”
Conclusion
No claims are allowed.
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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Sef
/SUSAN E. FERNANDEZ/Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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