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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/22/25 has been entered.
Response to Amendment
This action is written in response to applicant’s arguments received on 3/19/25.
The rejection of claims 1-14 under 35 USC 103 are overcome by amendment.
Amended claims 1-14 are under examination herein.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS filed on 12/23/25 has been fully considered except where references have been lined through.
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.
Regarding claim 1, the claim requires “wherein the freeze-dried biomass has a stability in terms of cell membrane integrity”. This limitation would be inherently met by measuring the CFU of the biomass as the biomass needs intact cell membranes to grow as colonies or could also be met by the AFU measurement. Therefore, it is unclear how the limitation relates to the AFU, the CFU, or both. Further, it is unclear if this phrase requires a certain level of stability of the cell membrane or cell membrane integrity.
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.
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.
Claims 1-4 and 6-13 are rejected under 35 U.S.C. 103 as being unpatentable over DePablo (US20040043374A1, of record) and Martin ("A way to follow the viability of encapsulated Bifidobacterium bifidum subjected to a freeze-drying process in order to target the colon: Interest of flow cytometry." European Journal of Pharmaceutical Sciences 49.2 (2013): 166-174, of record). Claim 1 is further evidenced by MRS 1 and 2(retrieved from https://d163axztg8am2h.cloudfront.net/static/doc/2e/c7/3ee1c2346f6a5ca08af55031bda7.pdf on 6/10/25 and https://www.weberscientific.com/mrs-agar-isolation-and-cultivation-of-lactobacilli?srsltid=AfmBOooJnJ75hwOByA_AQiPTGTK24g3lrPoGdaMcu8C05fIEJl7Mu3KN). Claim 4 is further evidenced by Potassium Pyrophosphate (of record). Claim 11 is further evidenced by Thermo (retrieved from https://www.thermofisher.com/order/catalog/product/C195 on 9/18/24).
Regarding claim 1 and 6, DePablo teaches preservation methods and compositions for biological materials (title). DePablo teaches that the method can be used in freeze drying (claim 15). DePablo teaches bacteria can be preserved in the method (example 1). DePablo teaches that sucrose is preferred in the invention (polyhydroxy) ([0039]). DePablo teaches potassium diphosphate can be used in the invention (potassium pyrophosphate) ([0092]). DePablo teaches the bacteria can be mixed with the protective solution and freeze dried (obtaining a cryoprotected biomass and forming a freeze-dried biomass) ([0062-0063]). DePablo teaches the pH of the media should be maintained at an optimal value for the biologicals and the pH of the solution should be in in the range of 5-10 (adjusting pH value of the biomass) ([0054]). Therefore it would be obvious to one of ordinary skill in the arts to adjust the pH.
DePablo does not explicitly teaching fermenting a previously prepared biomass or concentrating the biomass.
Martin teaches the application of flow cytometry to freeze dried bacteria (abstract). Martin teaches the bacteria were incubated overnight (fermenting a previously prepared biomass), and incubated in MRS media (adjusting the pH of the fermented biomass) and the cells were concentrated to 3.108 CFU/mL (p167 section 2.1). The wash step (comprising pelleting and then diluting the bacteria) makes it obvious to carry out a concentration step where necessary to reach the desired final concentration. As evidenced by MRS 1, MRS media is buffered (principals) and MRS 2 shows the media is at a pH of 6.5 (user quality control), and it would have thus been obvious to adjust the pH to the buffered value. This value falls within the claimed range and therefore the range is prima facia obvious. AFUs would inherently be greater than CFUs and the cell membrane integrity limitation is also inherent in cells having a measurable CFU.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the bacterial cell preparation of Martin in the method of DePablo. One of ordinary skill in the art would be motivated to do so because this method of bacterial cell preparation has been successfully used to culture bacteria before freeze drying and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as both DePablo and Martin are in the same field of endeavor of freeze-drying bacteria.
Regarding claim 2, Martin teaches the bacteria is washed and resuspended (reconcentrated) (p167 section 2.1).
Regarding claim 3, Martin teaches the bacteria is washed and resuspended (reconcentrated) (p167 section 2.1). DePablo teaches the pH should be maintained at an optimal value for the biologicals and the pH of the solution should be in in the range of 5-10 (adjusting pH value of the biomass) ([0054]). This range fully encompasses the claimed pH range and therefore the claimed pH range is prima facia obvious. Further, as DePablo teaches that the pH needs to be maintained at an optimal value to support the biologicals one of ordinary skill in the arts would be motivated to experiment with the pH to arrive at the claimed range.
Regarding claim 4, as evidenced by Potassium Pyrophosphate the potassium pyrophosphate of DePablo is also known as pyrophosphoric acid (p7 depositor supplied synonyms).
Regarding claim 7, DePablo teaches that citric acid can be included ([0055]).
Regarding claim 8, Martin teaches the concentration of cells after freeze-drying can be from just under 1x106 cells/gram to over 1x107 cells/gram (fig 2). This overlaps with the claimed range and therefore the claimed range is prima facia obvious.
Regarding claims 9 and 10, DePablo teaches that one or more techniques including freezing, freeze-drying, vacuum-drying, ambient, air-drying, and/or spray-drying can be used ([0061]). DePablo teaches the freeze-dried samples can be dried at 50 oC (primary drying followed by secondary drying, subliming the ice as evidenced by claim 10) (example 3).
Regarding claim 11, Martin teaches the freeze-dried bacteria can be contacted with propidium iodide (fluorescent dye as evidenced by instant specification [0146]) and Carboxyfluorescein diacetate (cFDA) (p168 section 2.7). As evidenced by Thermo, cFDA is fluorescent (p2 product overview). Martin teaches flow cytometry can then be used to assess cell viability measured by the intact cell membrane (p168 section 2.7).
Regarding claim 12, Martin teaches that the flow cytometry can demonstrate total cells (whole plot), damaged cells, live cells, and dead cells (p171 section 3.3, fig 3 and table 2). Therefore, one of ordinary skill in the arts understands that the claimed correlation applies as the total amount of cells show in fig 3 consists of both the active/live cells and the damaged/dead cells.
Regarding claim 13, Martin teaches the flow cytometry can be used to monitor the freeze-drying step (p173 conclusion).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over DePablo (US20040043374A1, of record) and Martin ("A way to follow the viability of encapsulated Bifidobacterium bifidum subjected to a freeze-drying process in order to target the colon: Interest of flow cytometry." European Journal of Pharmaceutical Sciences 49.2 (2013): 166-174, of record), as applied to claims 1-4 and 6-13 above, and further in view of Binhua (GB2338244A).
Regarding claim 5, DePablo and Martin do not teach the use of L-cysteine in the protective media.
Binhua teaches protective materials for microbes (title). Binhua teaches that L-cystine improves the viability of lyophilized (freeze-dried) bacteria (p8 last partial paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include L-cystine in the protective media of DePablo and Martin discussed above. One of ordinary skill in the art would be motivated to do so because Binhua teaches that increases the viability of the freeze-dried bacteria. There would be a reasonable expectation of success as DePablo, Martin, and Binhua are in the same field of endeavor of protecting dried bacteria.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over DePablo (US20040043374A1, of record) and Martin ("A way to follow the viability of encapsulated Bifidobacterium bifidum subjected to a freeze-drying process in order to target the colon: Interest of flow cytometry." European Journal of Pharmaceutical Sciences 49.2 (2013): 166-174, of record) as applied to claims 1-4 and 6-13 above, and further in view of Bergenholtz (A case study on stress preconditioning of a Lactobacillus strain prior to freeze-drying." Cryobiology 64.3 (2012): 152-159).
Regarding claim 14, DePablo and Martin do not explicitly teach crushing the freeze-dried biomass.
Bergenholtz studies stress on bacteria during freeze-drying (title). Bergenholtz teaches the freeze-dried bacteria can be crushed for SEM analysis (p154 Scanning electron microscopy section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to crush the freeze-dried bacteria of DePablo and Martin above, as taught by Bergenholtz. One of ordinary skill in the art would be motivated to do so because crushing freeze-dried bacteria have been successfully used on freeze-dried bacteria, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as DePablo, Martin, and Bergenholtz are in the same field of endeavor of freeze-dried bacteria.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-6, 8, 11, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2-5, 8, and 14-15 of co-pending Application No. 17/604,369 in view of DePablo (citation above).
Claim 1, 4-6, 8, 11, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2-5, 8, and 14-15 of U.S. Patent No. US12509713B2. Although the claims at issue are not identical, they are not patentably distinct from each other because
Regarding claims 1, 4-8, and 11-13, Co-pending claims 1, 4 and 8 of ‘713 teaches a method for preparing a biomass of freeze-dried bacterial cells, comprising the steps of: fermenting, concentrating, mixing with a cryoprotectant solution comprising a phosphate ion and a polyhydroxy substance, and freeze- drying the cryoprotected biomass. ‘713 teaches concentrating the bacterial cells to a range of 1x10° cells/g to 1x10" cells/g. ‘369 further teaches contacting the fermented biomass with fluorescent dyes and detecting by flow cytofluorometry. 713 teaches the correlation of AFU and CFUs (specification p13-14, fig 3) 713 teaches the cell membrane integrity can be assessed (specification p13-14, fig 3).
While ‘713 does not explicitly teach the adjustment of pH, as discussed above, DePablo teaches the pH of the media should be maintained at an optimal value for the biologicals and the pH of the solution should be in in the range of 5-10 (adjusting pH value of the biomass) ([0054]).
Regarding claim 13, claims 2-3 of ‘713 teaches monitoring the process parameters that govern the fermenting step, concentrating step, and the mixing step.
Regarding claim 12, claim 5 of ‘713 teaches a correlation of TFU = AFU +nAFU.
Regarding claims 6-7, claims 14-15 of 713 teaches cryoprotectant solution comprising a phosphate ion and a polyhydroxy substance, and optionally L-cysteine (see claims 6-7 of ‘345).
Response to Arguments
Applicant's arguments filed 12/22/25 have been fully considered but they are not persuasive. Applicant argues that the cited references do not teach adjusting the pH (p7). DePablo teaches the pH of the media should be maintained at an optimal value for the biologicals and the pH of the solution should be in in the range of 5-10 (adjusting pH value of the biomass) ([0054]). Therefore, one of ordinary skill in the arts would be motivated to monitor and adjust the pH to ensure cell viability. See above for details. Additionally, DePablo teaches that the protectant solution pH should be adjusted and then added to the cells (effectively adjusting the pH of the cellular composition) before a concentration step is performed (example 1). As Depablo teaches that the protectant pH should be adjusted and also that the pH needs to be maintained in specific ranges, it is obvious to one of ordinary skill to ensure the pH is adjusted correctly. One of ordinary skill in the arts understands that adding a buffer at a specified pH would allow for the cell biomass pH to be adjusted to the pH of the buffer. Further, Martin teaches that a previously fermented cell biomass is added to a buffered media which would result in the cell biomass pH being adjusted.
Applicant argues that the combination of Martin and DePablo would change the principal of operation. As discussed above, the presence of a wash step makes it obvious to carry out a concentration step to obtain the final concentration taught by Martin.
Applicant argues the specific steps order is not met (p9). MPEP 2144.04 states that “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results”
Applicant argues numerous parts of the specification that are not reflected in the claim set and therefore are not persuasive (p10-13).
Applicant argues that the unexpected results per the declaration are persuasive (p14-16). The declaration table present on p4 shows results in terms of CFU>AFU rather than the claim amendments of AFU>CFU and therefore the declaration argues that the unexpected results are the ability to maintain a vitality index close to ore exceeding 100% in terms of CFU>AFU. This does not match the claim amendments presenting the AFU>CFU and therefore the declaration cannot be considered commensurate in scope with the claim amendments.
The declaration references figs 1-4 and there could be a level of AFU/CFU ratio that could constitute unexpected results if applicant can explain why the levels presented in figs 1-4 are unexpected and the claims are amended accordingly.
Additionally, the declaration table found on page 5 could support a finding of unexpected results if the claims are amended accordingly.
Applicant argues that the claim amendments overcome the double patenting rejection. This is not persuasive, see the rejection above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TREVOR L KANE whose telephone number is (571)272-0265. The examiner can normally be reached M-F 7:00 am-4:00pm.
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/TREVOR KANE/Examiner, Art Unit 1657
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657