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 .
Claim Status
The amended claim set filed on 30 July 2026 is acknowledged. Claims 1-8, 11-15, and 17-18 are currently pending. Of those, claims 2-6, 11, and 14 are amended. There are no new claims, and claims 15 and 17-18 are withdrawn. Claims 9-10, 16, and 19-20 are cancelled. Claims 1-8 and 11-14 will be examined on the merits herein.
Response to Amendment
Applicants’ arguments filed 30 July 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Non-Final Office Action mailed 30 April 2026 will be referred to as “NFOA”.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4 August 2026 was filed after the mailing date of the NFOA on 30 April 2026. The submission is in compliance with the provisions of 37 CFR 1.97 because of the payment of the appropriate fee. Accordingly, the information disclosure statement is being considered by the examiner.
Rejection(s) Withdrawn
The rejection of claims 5-6 and 11 under 35 U.S.C. 112(b) is withdrawn in view of the amendments to the claims.
Rejection(s) Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 103
Claims 1-8 and 11-14 remain rejected under 35 U.S.C. 103 as being unpatentable over Baram et al. (US 2019/0083550 A1; cited in IDS; herein “Baram”).
Regarding claims 1 and 7-8, Baram teaches a method for obtaining a composition comprising a co-culture of at least two distinct bacterial families having differing growth and/or proliferative conditions (para. 23) comprising dividing a plurality of bacterial genera (i.e., a complex community of microorganisms) into a plurality of bacterial solution subsets, i.e., at least two (para. 28), culturing each bacterial solution subset in a growth medium (i.e., in a bioreactor or device useful for cultivating microorganisms in which culture parameters can be controlled) and under proliferative conditions suitable for the proliferation of the individual subset (para. 29), and removing the growth medium (i.e., harvesting inocula) and recombining the individual subsets (i.e., mixing the harvested inocula) (para. 30). Baram teaches examples of culturing individual subsets in 8 different proliferative conditions (para. 127-136) and four different proliferative conditions (para. 142-143). Baram teaches that the proliferative condition for each subset may include a pH gradient based on the known pH of the sample’s origin tissue, and that the pH for the individual subsets may be between about 6.6 to about 7.5, about 5.6 to about 7.9, about 4.5 to about 8, about 4.0 to about 7.0, about 7.0 to about 7.5, or about 5.5 to about 7.5 (para. 93).
Regarding claims 2-6, Baram teaches that the incubation time of the proliferative conditions (i.e., a retention time greater than or equal to the incubation time) may be 1, 2, 3, 4, 5, 6, 10, 12, 15 hours, or any value therebetween, or at least 1, 2, 3, 4, 5, 6, 7, or 10 days (para. 92).
Regarding claim 11, Baram teaches that the plurality of bacterial genera comprising microbiota sample(s) is in the form of a suspension using saline solution (para. 24-25, 100, and 127).
Regarding claim 12, Baram teaches that the culturing of individual subsets may be repeated with changing the growth medium and proliferation conditions, e.g., pH (para. 102 and FIG. 1).
Regarding claim 13, Baram teaches that the composition comprising the recombined subsets is lyophilized (para. 103 and FIG. 1).
Regarding claim 14, Baram teaches that the plurality of bacterial genera (i.e., complex community of microorganisms) is derived from one or more samples from a fecal sample (para. 58).
However, Baram does not explicitly teach a first bioreactor with a pH between 4.5 and 5.8, a second bioreactor with a pH between 5.9 and 6.8, as in claim 1, bioreactors with different retention times of between 6 and 102 hours, as in claim 2, at least one bioreactor with a retention time of between 6 and 18 hours, as in claim 3, at least one bioreactor with a retention time of between 18 and 30 hours, as in claim 4, a first bioreactor with a retention time between 18 and 30 hours and a second bioreactor with a retention time of between 6 and 18 hours or between 42 and 54 hours, as in claim 5, a first bioreactor with a retention time of between 6 and 18 hours, a second bioreactor with a retention time between 18 and 30 hours, and a third bioreactor with a retention time of between 42 and 54 hours, as in claim 6, a first bioreactor with a pH between 5 and 5.6 and a second bioreactor with a pH between 6 and 6.6, as in claim 7, or a first bioreactor with a pH between 5.2 and 5.4, a second bioreactor with a pH between 6.2 and 6.4, and a third bioreactor with a pH between 7.2 and 7.4, as in claim 8.
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the method taught by Baram by optimizing the pH conditions of the cultures of the individual bacterial subsets and optimizing the retention time for each of the bacterial subsets, thereby arriving at the claimed invention. The person of ordinary skill in the art would have been motivated to make the modification because Baram teaches that the pH gradient for each subset is based on the pH of the sample’s origin tissue, so the pH conditions will vary based on the type of microbiota sample. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Baram teaches pH condition ranges and incubation time ranges broader than what is claimed, so one would predict that culturing microorganisms using the narrower claimed pH and time ranges would result in an expanded community of microorganisms at least as well as with the conditions taught by Baram. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Regarding the pH ranges of claims 1 and 7-8, Baram teaches proliferative conditions having a pH of 6.6-7.5, 5.6-7.9, 4.5-8, 7.0-7.5, and 5.5-7.5 (para. 93), all of which encompass or overlap with one or more of the claimed pH ranges. Regarding the time ranges of claims 2-6, Baram teaches incubation time of the proliferative conditions may be 1, 2, 3, 4, 5, 6, 10, 12, 15 hours, or any value therebetween, which includes times that fall within the ranges recited in claims 2-3 and 5-6, or at least 1, 2, 3, 4, 5, 6, 7, or 10 days, which includes times that fall within the ranges recited in claims 4-6. It is noted that 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.” 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.
Response to Arguments
Applicant argues (Remarks pg. 2-3) that Baram’s process is based on the deliberate separation of bacterial genera into individual subsets and the cultivation of each subset under different conditions, whereas the present invention follows a different technical approach and addresses a different technical objective, to expand a complex microbial community while preserving and/or optimizing its diversity and microbial profile and providing a homogenous and reproducible expanded product.
This argument has been fully considered but is not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., not separating bacterial into individual subsets for cultivation) are not recited in the rejected claim(s). As written, the claims do not require that the complex community of microorganisms comes from a particular source or have a certain composition prior to or during cultivation in the bioreactors. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues (Remarks, pg. 4-5) that Examples 1 and 2 of the instant specification show that the technical effect does not arise merely from culturing microorganisms at pH values selected within a known broad range, but from generating distinct and complementary complex inocula under different pH conditions and subsequently combining those inocula, which is not demonstrated by Baram.
This argument has been fully considered but is not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., generating distinct and complex inocula) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It is reiterated that the instant claim 1 does not require that the complex community of microorganisms being cultivated in the bioreactors be from a particular source or have a particular composition, and the claim does not require that the harvested inocula have any particular composition or characteristics (i.e., “distinct and complementary complex inocula”). However, Baram does, in fact, teach that the co-culture obtained comprises at least two “distinct” bacterial families (i.e., complex inocula) (para. 23).
Applicant argues (Remarks, pg. 5) that Baram’s subset-specific cultivation approach and the claimed multi-pH cultivation and mixing approach are not technically equivalent and that one of ordinary skill in the art would have had no reason to abandon Baram’s central teaching of separately optimizing the growth of predetermined bacterial subsets in favor of the claimed method.
Applicant also argues (Remarks, pg. 6) that Baram provides no teaching or suggestion directing the person of ordinary skill in the art toward the combination of: selecting pH from among the numerous parameters disclosed in Baram; depart form Baram’s subset-specific strategy; decide to cultivate a complex microbial community in at least three separate bioreactors; select three pH set points falling withing the three claimed non-overlapping pH ranges; and mix the resulting inocula with the expectation that their respective microbial profiles would complement one another. Thus, Applicant argues that the rejection relies on ex post facto reconstruction of the claimed method.
This argument has been fully considered but is not persuasive. Regarding the difference in approaches in Baram and the instant claims and the argument that one of ordinary skill in the art must “depart from Baram’s subset-specific cultivation strategy” in order to arrive at the claimed invention, because the instant claims do not require that the complex community of microorganisms being cultivated be from the same source or have a certain composition, there is no departure from the teachings of Baram necessary to arrive at the claimed method other than the optimization of pH set points and retention times as is described in para. 24-25 of the NFOA.
Regarding the other changes applicant argues would need to be made in order to arrive at the claimed invention, Baram teaches cultivation of a complex microbial community in four (i.e., at least three) different bioreactors in different proliferative conditions (see Baram, para. 142-143) and mixing the resulting inocula into a final co-culture (se Baram, para. 30).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the resulting inocula “complement one another”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The pH conditions taught by Baram encompass or overlap with the pH conditions set forth in the claims, and the modifications of choosing pH set points within the claimed ranges is well known within the art and can be performed by one of ordinary skill in the art with a reasonable expectation of successfully obtaining at least three bioreactors with pH set points withing the claimed ranges.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant argues (Remarks, pg. 6-7) that Baram does not identify the claimed three-pH cultivation method as a result-effective variable because Baram does not recognize the coordinated selection of several pH conditions, followed by mixing of the resulting complex inocula, as a variable affecting the result.
This argument has been fully considered but is not persuasive. MPEP 2144.05(III)(C) states: “Likewise, if the prior art does recognize that the variable affects the relevant property or result, then the variable is result-effective. Id. (‘A recognition in the prior art that a property is affected by the variable is sufficient to find the variable result-effective.’)” Baram teaches that the proliferative condition for each subset may include a pH gradient based on the known pH of the sample’s origin tissue (para. 93) and that the composition resulting from recombining the individual subsets comprises a co-culture of bacterial families having differing growth and/or proliferative conditions (para. 23 and 30). These teachings indicate that (a) Baram recognized that different bacteria proliferate at different pHs and thus cultivation at different pHs would change resulting harvested subset, and (b) that different combinations of bacterial families (i.e., the subsets or harvested inocula) cultivated under different proliferation conditions (e.g., pH) would affect the resulting composition made from recombining subsets. Thus, Baram does identify the selection of pH conditions and mixing of subsets as result-effective.
Applicant argues (Remarks, pg. 7-8) that Baram’s examples do not investigate pH as the distinguishing cultivation parameter and that Baram does not demonstrate that its process preserves the original quantitative microbial profile.
This argument has been fully considered but is not persuasive. Regarding the argument that Baram’s examples do not investigate pH as the distinguishing cultivation parameter, it is reiterated that the entirety of Baram is considered prior art under 35 U.S.C. 102(a)(1) and may be cited in support of an obviousness rejection. See MPEP 2123(II): “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971)” As set for the in the previous 103 rejection and in the response to the arguments above, Baram teaches a method comprising culturing each of a plurality of bacterial solution subsets in a growth medium (i.e., cultivating a complex community of microorganisms in at least two bioreactors) under proliferative conditions suitable for the proliferation of the individual subset, which may be a pH gradient (i.e., cultivating individual subsets in different bioreactors under different pH conditions) (par. 23, 28-29, and 93).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., preserving the original microbial profile) are not recited in the rejected claim(s). The claim requires “expanding a complex community of microorganisms”. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 7:30-3:30 ET.
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/BAILEY M MORGAN/
Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
