DETAILED ACTION
Claim Rejections - 35 USC § 102/103
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Bashor (US 20200199568).
With respect to claim 1, Bashor discloses a method for adaptive evolution of living cells in which cells are cultured in a plurality of culture vessels (Figure 1:“Culture Array”). At least one liquid culture medium and living cells (Figure 1:“Culture/Wetware”) are introduced into each of the culture vessels. The cells are then cultured in suspension according to a given selection regime using predefined parameters until a determined growth stage is reached. For example, paragraphs [0007]-[0021] state that cultures are exposed to a stress ramp function based on an increasing or decreasing level of antibiotic, antiseptic, temperature, nutrient, pH, etc. in order to produce a population of enhanced fitness. Paragraphs [0005] and [0006] teach that suspensions of living cells are combined from at least two culture vessels to obtain a mixed suspension. Paragraph [0210] provides one example in which the mixed suspension is homogenized through constant stirring (“the automated vial-to-vial transfer device was used to transfer 2 mL from each haploid culture into the same vial. This co-culture was grown at 30° C. with constant stirring, but no dilutions, until reaching a density of OD 0.8”). See also paragraph [0035]. Cells are then recovered, resuspended and distributed into at least two culture vessels. These steps are repeated as many times as necessary to acquire a phenotype of interest in the culture vessels.
In the event that Bashor does not expressly teach the specific order of introducing, combining, homogenizing, distributing and repeating steps set forth in the claimed sequence, it is further noted that Bashor teaches in paragraphs [0031], [0035], [0076], [0077] and [0086] that automated vessel-to-vessel transfers are effectuated according to programmed guidance and data obtained by sensors. Bashor encourages those of ordinary skill to combine, mix, homogenize and distribute cell cultures in the array of vessels in a variety of ways to test and volve stable multi-species communities (“a multi-objective, DIY platform that gives users complete freedom to define the parameters of automated culture growth experiments”). Accordingly, it would have been obvious to create cell co-cultures by combining evolved cells from different vessels into a single vessel for further conditioning and testing, distributing the homogenized suspension back into at least two culture vessels, and repeating the process to acquire a phenotype of interest.
With respect to claim 2, Bashor discloses the method as described above. Bashor further teaches in paragraph [0011] that the living cells may be eukaryotic cells or prokaryotic cells.
With respect to claim 3, Bashor discloses the method as described above. Bashor describes throughout the reference various continuous culture regimes characterized by chemostat and turbidostat conditions.
With respect to claim 4, Bashor discloses the method as described above. As previously discussed, Bashor states that predefined culture parameters may include temperature and pH.
With respect to claims 5 and 6, Bashor discloses the method as described above. Bashor indicates that mixing occurs in at least one culture vessel used as a mixing vessel.
With respect to claim 7, Bashor discloses the method as described above. Bashor states that homogenization occurs through agitation of the mixed suspension. See, for example, paragraphs [0039] and [0278].
With respect to claims 8, 9 and 11-13, Bashor discloses the method as described above. As discussed above, it would have been obvious to ensure that the Bashor array of culture vessels includes a dedicated starting culture vessel and a mixing/destination vessel. It would have been obvious to ensure that a portion of the homogenized suspension is either returned to the starting culture vessel and/or at least two culture vessels. Bashor states that all of the culture vessels are fluidically connected and that fluid flow between them is automated using pumps and valves. See paragraphs [0044]-[0046], [0061] and [0062]. All of the hardware necessary for routing culture fluid through any order of vessels is provided.
With respect to claims 10 and 17, Bashor discloses the method as described above. Bashor further states that the selective regime and/or the predefined culture parameters used during a culture cycle may be the same as those used during the preceding culture cycle in order to reinforce the applied stress ramp function and culture fitness function. Alternatively, the applied stress may be increased to further differentiate a phenotype of interest.
With respect to claim 14, Bashor discloses the method as described above. Bashor further teaches in paragraph [0011] that the living cells may be human cells, animal cells or plant cells.
With respect to claim 15, Bashor discloses the method as described above. Any one of the culture vessels within the culture vessel array of Bashor may be designated as an independent mixing vessel.
With respect to claim 16, Bashor discloses the method as described above. Bashor teaches in at least paragraph [0032] that agitation is performed mechanically using a stir bar.
With respect to claims 18-20, Bashor discloses the method as described above. As previously discussed, Bashor states that predefined culture parameters may include temperature and pH. Furthermore, Bashor describes throughout the reference various continuous culture regimes characterized by chemostat and turbidostat conditions.
Response to Arguments
Applicant's arguments filed 22 December 2025 have been fully considered but they are not persuasive.
Applicant primarily argues that Bashor does not teach transferring or redistributing the contents of one vessel into two or more different vessels (i.e., step (e) of claim 1). However, Bashor teaches in at least paragraph [0214] an embodiment in which aliquots from a homogenized suspension of mixed living cells are distributed into at least two different culture vessels for purposes of cell selection (“30 µL aliquots were diluted into 3 mL of liquid selection media (SD-Ura for MATα, SD-Leu for MATα, or SD-Ura-Leu for diploids) and grown for 16 h, then mixed with glycerol and frozen as before. Cells were additionally streaked onto solid selection agar (SD-Ura for MATα, SD-Leu for MATα, or SD-Ura-Leu for diploids) in order to isolate single colonies for sequencing”). In this example, cells are distributed into three different culture vessels containing different selection media. Furthermore, those of ordinary skill would have found it obvious to distribute cells into a plurality of different culture vessels for a variety of different reasons other than selective growth. Parallel processing and testing in different culture vessels under the same or different conditions allows for an efficient multiplexed evaluation of the original cell suspension.
Conclusion
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.
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/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799