Prosecution Insights
Last updated: April 18, 2026
Application No. 18/476,900

Protection of Next-Generation Probiotics during Processing

Non-Final OA §103§112
Filed
Sep 28, 2023
Examiner
DURYEE, ALEXANDER MARSH
Art Unit
1657
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Massachusetts Institute Of Technology
OA Round
3 (Non-Final)
31%
Grant Probability
At Risk
3-4
OA Rounds
2y 11m
To Grant
73%
With Interview

Examiner Intelligence

Grants only 31% of cases
31%
Career Allow Rate
26 granted / 84 resolved
-29.0% vs TC avg
Strong +42% interview lift
Without
With
+42.3%
Interview Lift
resolved cases with interview
Typical timeline
2y 11m
Avg Prosecution
35 currently pending
Career history
119
Total Applications
across all art units

Statute-Specific Performance

§101
10.2%
-29.8% vs TC avg
§103
34.1%
-5.9% vs TC avg
§102
10.3%
-29.7% vs TC avg
§112
31.8%
-8.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 84 resolved cases

Office Action

§103 §112
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 . 07/06/2025 Claim amendment is not in accordance with 37 CFR 1.121 (c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered). (1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of "canceled" or "not entered" may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment. (2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of "currently amended," and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of "currently amended," or "withdrawn" if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as "withdrawn— currently amended." (3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of "original," "withdrawn" or "previously presented" will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of "withdrawn" or "previously presented." Any claim added by amendment must be indicated with the status of "new" and presented in clean version, i.e., without any underlining. (4) When claim text shall not be presented; canceling a claim. (i) No claim text shall be presented for any claim in the claim listing with the status of "canceled" or "not entered." (ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as "canceled" will constitute an instruction to cancel the claim. DETAILED ACTION The previous rejections under 35 U.S.C. §112b, 102, and 103, are withdrawn in light of the claim amendment. Applicant’s amendments filed on 30 June 2025 and 06 July 2025 are entered. Claims 1, 8-9, 18-19, and 33 are amended, and claim 44 is new. Claims 1-3, 5, 8-9, 11-13, 15, 18-19, 26-27, 29-31, 33, 35, 38, and 44 are pending. Election/Restrictions New claim 44 is withdrawn from further consideration as being drawn to nonelected species, there being no allowable generic or linking claim. The election of species Pseudomonas chlororaphis was made without traverse in the reply filed on 22 November 2024. Claims 19, 35, 38 and 44 are withdrawn. Claims 1-3, 5, 8-9, 11-13, 15, 18, 26-27, 29-31, and 33 are under examination. Claim Objections Claims 18 and 33 are objected to because of the following informalities: Claim 18 recites a Markush group of prokaryotic cells which is convoluted because the conjunctions “and” and “or” are used throughout the Markush group. The extraneous and’s and or’s in the Markush group should be deleted, and only one conjunction “and” should be recited directly before the last listed alternative prokaryotic cell. Claim 33 recites the limitation “the composition comprises a formulation, the formulation comprising”. The extraneous “the formulation” should be deleted such that the limitation would read “…(a) the composition comprises a formulation comprising…”. 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 1-3, 5, 8-9, 11-13, 15, 18, 26-27, 29-31, and 33 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. (New rejection necessitated by amendment) Regarding claim 1, it is unclear if the one or more cryoprotectants are a component integrated within the coating comprising metal-phenolic networks (MPN)s, or if the cryoprotectants are a separate component from the cell having a coating comprising MPNs. Regarding claim 11, the parenthetical phrase “(including isoflavonoids and neoflavonoids)” renders the claim indefinite because it is unclear whether the contents of the parenthetical phrase are part of the claim limitation and intended to be limiting, or if the contents of the parenthetical phrases are merely suggestive. (New rejection necessitated by amendment) Regarding claim 18, it is unclear whether the contents of the parenthetical phrases “(i.e., Burkholderia cepacia)” and “(i.e. Brevundimonas vesicularis)” are part of the claim limitations and intended to be limiting, or if the contents of the parenthetical phrases are merely exemplary and thus not required. Claims 2-3, 5, 8-9, 11-13, 15, 18, 26-27, 29-31, and 33 are dependent on claim 1, so are indefinite for the same reasons. 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. (New rejection necessitated by amendment) Claim 31 is 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. Claim 31 recites that the composition comprising a plurality of the prokaryotic cells of claim 1 does not include a cryoprotectant. However, claim 1 recites that the prokaryotic cells comprise one or more cryoprotectants. Claim 31 does not include all the limitations of claim 1 upon which it depends, namely that the prokaryotic cells comprise a cryoprotectant. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements. 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. 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. (New rejection necessitated by amendment) Claims 1-2, 5, 8-9, 11-13, 15, 26, 29-31 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (CN108841756A, published November 20, 2018) in view of Reddy et al. (Role of Cryoprotectants on the Viability and Functional Properties of Probiotic Lactic Acid Bacteria during Freeze Drying, Food Biotechnology, 23:243–265, 2009). Regarding claims 1 and 15, Guo teaches a bacterial (prokaryotic) probiotic cell encapsulated by a polyphenol-metal ion complex, or metal-phenolic network (MPN) (Guo claim 1). Guo teaches the bacterial probiotic cells are Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus lactis, Streptococcus lactis, and Escherichia coli (Guo claim 6). However, Guo does not teach the prokaryotic cell having an MPN coating comprises one or more cryoprotectants. Reddy teaches prokaryotic bacterial cultures comprising one or more cryoprotects (Reddy Table 1 and Fig. 1). The survival and viability rates of the lyophilized prokaryotic bacterial cultures comprising cryoprotectants were significantly enhanced as compared to a control group without cryoprotectants (Reddy Fig. 1). It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to modify Guo’s prokaryotic probiotic cell encapsulated by a MPN to further comprise Reddy’s cryoprotectants. One of ordinary skill in the art would have been motivated to do so in order to enhance the survivability of Guo’s MPN encapsulated prokaryotic cells upon lyophilization. One of ordinary skill in the art would have had a reasonable expectation of success because Reddy teaches that survival and viability rates of lyophilized prokaryotic bacterial cultures comprising cryoprotectants are significantly enhanced as compared to a control. Regarding claim 2, Guo teaches MPN that encapsulates the probiotic bacteria (Guo Page 2 Last sentence), and one of ordinary skill in the art would understand that “encapsulation” means a complete coating over the entire cell surface since the general meaning of “encapsulates” is enclose. Regarding claim 5, Guo teaches a thickness of MPN in the range of 10 to 30nm (Guo claim 2), and that the coating comprises a single metal ion component and a single phenolic component (Guo claim 1 and Pg. 5 Example 1 para. 2). Regarding claims 8-9 and 11-13, Guo teaches the metal cation component of the complex, which can be Al, Fe (including Fe3+), Zn, Cu, Mn, Ni, Co, or V (Guo claim 3 and Pg. 5 Example 1 para. 2). Guo teaches the polyphenol component to be tannic acid, epicatechin, epigallocatechin gallate, catechin gallate, ellagic acid, waxberry tannin, black tree tannin, anthocyanin, or catechin (Guo claim 5). Guo teaches that each of these metal cations and polyphenol components are complexed together into a MPN (Guo claim 1 and Pg. 5 Example 1 para. 2). Regarding claim 26, Guo teaches lyophilization (or freeze-drying) of the MPN encapsulated bacterial probiotic cells (Guo claim 7). Regarding claims 29, Guo teaches the encapsulation of a plurality of bacterial (prokaryotic) probiotic cells with a polyphenol-metal ion complex, i.e. metal-phenolic network (MPN) (Guo claim 1). Regarding claims 30-31, Guo teaches that the MPN encapsulated bacterial probiotic cells are lyophilized (freeze-dried) (Guo claim 7). Guo is silent on the addition of cryoprotectants to the encapsulated bacterial probiotic cells prior to the lyophilization step, thus in one embodiment the lyophilized cells are taught to not include a cryoprotectant. Regarding claim 33, the encapsulated bacterial probiotic cells can be in powder form (Guo Page 3 Paragraph 5). (New rejection necessitated by amendment) Claims 3 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Guo in view of Reddy as applied to claims 1-2, 5, 8-9, 11-13, 15, 26, 29-31 and 33 above, and further in view of Li et al. (Mussel Byssus-Like Reversible Metal-Chelated Supramolecular Complex Used for Dynamic Cellular Surface Engineering and Imaging, Adv. Funct. Mater. 2015, 25, 3775–3784). Guo and Reddy do not teach the MPN coating to comprise 1-10 or more layers, nor the addition of one or more functional groups bound to the MPN encapsulation. Regarding claim 3, Li teaches a prokaryotic bacterial cell comprising a metal-phenolic network (MPN) that uniformly coats the outside surface of the cell (Li Page 3779 paragraph 2 sentences 1, 4, and 6), and that additional layers of the MPN coating on the prokaryotic cell may be added by repeating the encapsulation method multiple times to create layers of MPN (Li Page 3781 paragraph 2 sentence 7). Regarding claim 27, Li teaches the MPN of a cell is a convenient route for cell surface modification, including the addition of biomolecules to the MPN for improved biorecognition (Li Page 3777 Paragraph 3 sentences 4 and 8-9). It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to add multiple MPN layers to the prokaryotic probiotic cell of Guo in view of Reddy, and to bind functional biomolecules to those MPN encapsulated prokaryotic probiotic cells. One of ordinary skill in the art would have been motivated to do so to provide additional protection to the MPN coated cells because Li teaches that MPNs protect the encapsulated cells from unfriendly environments, including UV light irradiation and reactive oxygen damage (Li Abstract). One of skill in the art would have had a reasonable expectation of success in adding multiple MPN layers to the prokaryotic probiotic cell of Guo in view of Reddy because Li taught multicoating cells with MPNs by performing the MPN assembly step repeatedly. One of ordinary skill in the art would have been motivated to bind functional biomolecules to the MPN encapsulated prokaryotic probiotic cells of Guo in view of Reddy because Li teaches the addition of biomolecules to the MPN surface improves biorecognition capabilities, and thus impart bio-targeting capabilities to the encapsulated prokaryotic probiotic cells of Guo. One of skill in the art would have had a reasonable expectation of success in binding functional biomolecules to the MPN encapsulated prokaryotic probiotic cells because Li teaches the possibility of modifying MPN surfaces with functional groups such as biomolecules. (New rejection necessitated by amendment) Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Guo in view of Reddy as applied to claims 1-2, 5, 8-9, 11-13, 15, 26, 29-31 and 33 above, and further in view of Bertani et al. (Isolation and Characterization of Pseudomonas chlororaphis Strain ST9; Rhizomicrobiota and in Planta Studies, Plants 2021, 10, 1466, published 17 July 2021), Herrmann et al. (Challenges of formulation and quality of biofertilizers for successful inoculation, Appl Microbiol Biotechnol (2013) 97:8859–8873, published 15 September 2013), and Li et al. (Mussel Byssus-Like Reversible Metal-Chelated Supramolecular Complex Used for Dynamic Cellular Surface Engineering and Imaging, Adv. Funct. Mater. 2015, 25, 3775–3784). Guo and Reddy do not teach MPN encapsulation of Applicant’s elected prokaryotic bacterial species, Pseudomonas chlororaphis. Bertani teaches a plant-growth promoting rhizobacteria (PGPR) belonging to the Pseudomonas chlororaphis species, and further teaches that Pseudomonas chlororaphis acts as a plant probiotic due to its rhizosphere colonization abilities and plant associated beneficial phenotypes such as chemotaxis and motility, biofilm formation, phosphate solubilization, ACC deaminase, IAA production, and biocontrol (Bertani Pg. 2 first para.) Bertani teaches that Pseudomonas chlororaphis produces many antifungal compounds that inhibit the growth of various phytopathogens and protect plants such as maize and tomato (Bertani Pg. 2 first para.). However, Guo, Reddy, and Bertani do not teach a motivation as to why one skilled in the art would encapsulate the PGPR Pseudomonas chlororaphis in a protective matrix, such as an MPN. Herrmann teaches challenges associated with producing, distributing, and marketing bioinoculants (such as PGPR Pseudomonas chlororaphis), stating that there is a need to protect the cells during storage and transport because the bioinoculants are often stored in less than optimum conditions, such as high temperature and light exposure, and that those bioinoculants need to have an extended shelf life by being made to be robust or well protected to be able to survive in high numbers under harsh conditions (Herrmann Pg. 8860 paras. 2 and 6). Herrmann also teaches that the market potential for biofertilizer and bioinoculants is considerable in developed and developing countries (Herrmann Pg. 8860 para. 2). However, Guo, Reddy, Bertani, and Herrmann do not teach that MPNs offer any long-term protective effect to the encapsulated cells. Li teaches that MPNs can prolong cell viability over time and protect encapsulated cells from unfriendly environments, including UV light irradiation and reactive oxygen damage (Li Pg. 3777 para. 2 second column, Figs. 3b, 3c, and 7d, and Abstract). It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to encapsulate the elected prokaryotic bacterial species Pseudomonas chlororaphis taught by Bertani with an MPN. One of ordinary skill in the art would have been motivated to do so because P. chlororaphis was known in the art to be a beneficial plant probiotic PGPR bacteria capable of growth promoting and protecting plants, including commercially relevant plants such as maize and tomatoes. There is a known need in the art to protect PGPR cells such as P. chlororaphis during storage and transport due to harsh conditions, such as high light exposure, and those cells need to have an extended shelf life and survive in high numbers during transport and storage. It is also known that there is a considerable market potential for high-performing, quality bioinoculants such as those comprising P. chlororaphis. It is also known in the art that encapsulating bacteria (such as P. chlororaphis) in an MPN prolongs cell viability over time and protects the cells from harsh environments such as UV light irradiation and reactive oxygen species. One of skill in the art would have had a reasonable expectation of success because Guo and Li teach MPN encapsulation methods useful on prokaryotic bacterial cells such as P. chlororaphis, and Li teaches that MPN encapsulations would prolong cell viability over time and protect the cells from harsh environments such as UV light irradiation and reactive oxygen species. Response to Arguments Applicant’s arguments with respect to claims 1-3, 5, 8-9, 11-13, 15, 18, 26-27, 29-31, and 33 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Conclusion 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander M Duryee whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached on (571)-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657 /Alexander M Duryee/Examiner, Art Unit 1657
Read full office action

Prosecution Timeline

Sep 28, 2023
Application Filed
Dec 20, 2024
Non-Final Rejection — §103, §112
Jun 30, 2025
Response Filed
Jun 30, 2025
Response after Non-Final Action
Jul 06, 2025
Response Filed
Oct 22, 2025
Final Rejection — §103, §112
Feb 24, 2026
Request for Continued Examination
Mar 04, 2026
Response after Non-Final Action
Mar 20, 2026
Interview Requested
Apr 02, 2026
Non-Final Rejection — §103, §112 (current)

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Prosecution Projections

3-4
Expected OA Rounds
31%
Grant Probability
73%
With Interview (+42.3%)
2y 11m
Median Time to Grant
High
PTA Risk
Based on 84 resolved cases by this examiner. Grant probability derived from career allow rate.

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