DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
2. The information disclosure statement (IDS) submitted on 08/06/24 was filed and entered. The submission is in compliance with the provisions of 37 CFR 1.97 and has been considered by the Examiner.
Election/Restrictions
3. Applicant’s election of Group III, in the reply filed on 01/08/26, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
4. With regards to Applicant’s assertion that newly added claims 21-25 could be grouped with the elected Group III (see Remarks, page 7), the Office disagrees and notes that, as these claims are drawn to methods, they would have not have been grouped with the product claims of Group III.
Claim Status
5. The amendment, filed 01/08/26, has been entered. Claims 1-5 and 11-25 are pending. Claims 6-10 are cancelled. Claims 11-25 are newly added. Claims 1-5 are amended. Claims 1-4, 11-13, and 21-25 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/08/26. Claims 5 and 14-20 are under examination.
Objection to Drawings
6. The drawings are not of sufficient quality to permit examination. Specifically, information in Figures 1, 3 and 6 are not discernable. Accordingly, replacement drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to this Office action. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Applicant is given a shortened statutory period of TWO (2) MONTHS to submit new drawings in compliance with 37 CFR 1.81. Extensions of time may be obtained under the provisions of 37 CFR 1.136(a) but in no case can any extension carry the date for reply to this letter beyond the maximum period of SIX MONTHS set by statute (35 U.S.C. 133). Failure to timely submit replacement drawing sheets will result in ABANDONMENT of the application.
Objection to Specification
7. The abstract of the disclosure is objected to because: insufficient length and information and contains legal phraseology (e.g. “said”). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). Applicant is reminded of the proper content of an abstract of the disclosure:
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use. Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Nucleotide and/or Amino Acid Sequence Disclosures Objection
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
8. Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
See sequences in Tables 1 and 2, pages 9-11, without corresponding SEQ ID NOs.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Claim Rejections - 35 USC § 101
9. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
10. Claims 5 and 14-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e. law of nature; nature-based products; naturally occurring bacteria) without significantly more.
The claims recite an obligate anaerobic bacterium, wherein said obligate anaerobic bacterium comprises a circuit of strictly anaerobically-induced expression of an essential gene consisting of (a) strictly anaerobically-activated promoter; and (b) an essential gene under the regulation of the promoter in (a); wherein the promoter in (a) has a binding site to an anaerobically activated transcription factor, and wherein said essential gene is dapE or dapA (see claim 5); which reads on naturally occurring facultative anaerobic bacteria under anaerobic conditions and/or naturally occurring obligate anaerobic bacteria, both of which are naturally capable of diaminopimelate (DAP) biosynthesis, as evidenced by, for example, Fuchs et al. 2000 (Characterization of a Bordetella pertussis Diaminopimelate (DAP) Biosynthesis Locus Identifies dapC, a novel gene coding for an N-Succinyl-L,L-DAP aminotransferase; Journal of Bacteriology 182(13): 3626-36310 which teaches E. coli and Bordetella naturally contain dapE and dapD genes under the control of promoters; and Lombardo et al.1997 (Regulation of Salmonella typhimurium pepT gene by cyclic AMP receptor protein (CRP and FNR acting at a hybrid CRP-FNR site; Journal of Bacteriology 179(6): 1909-1917) which teaches E. coli and Salmonella naturally contain pepT promoters. Therefore, the product claims are directed to a statutory category and thus Step 1 of the Subject Matter Eligibility analysis is yes.
However, this judicial exception is not integrated into a practical application because the naturally occurring bacteria capable of the naturally occurring biosynthetic pathway does not appear to be markedly different from its naturally occurring counterpart, in its natural state, because it is not required to be modified in any way (i.e. see independent claim 5). Therefore, although the product claims are directed to a statutory category, they are also directed to a judicial exception (i.e. nature-based products; naturally occurring bacteria having naturally occurring biosynthetic pathways; Step 2A prong 1 is yes) that is not integrated into a practical application (i.e. Step 2A, prong 2 is no).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements in claims 5, 17, 18, 19 or 20 (i.e. for claims 18 and 20, the limitations are interpreted as intended use, see the verbs “…is cultured” and “…requires”). For claim 14, Fuchs teaches there are analogous DAP biosynthetic pathways in Corynebacterium, Bacillus, E. coli, Mycobacterium, Salmonella and Helicobacter (i.e. are also judicial exceptions). For claims 15 and 16, Lombardo teaches the pepT promoter naturally occurs in E. coli and Salmonella (e.g. see page 1909, introduction; are also judicial exceptions). Thus, there are insufficient addition elements to amount to significantly more than the judicial exception because there is no indication that any additional element changes any structural or functional features of the judicial exception; thus all components function as they would individually and naturally. Further, a mere mixture or aggregation of products, natural or not, does not structurally and/or functionally change the nature-based product from what exists in the environment and that in order to be eligible, every embodiment within the broadest reasonable interpretation of the claim must be eligible. Thus, taken alone, the additional element(s) do/does not amount to significantly more than the above identified judicial exceptions (i.e. naturally occurring facultative bacteria under anaerobic conditions and/or naturally occurring obligate anaerobic bacterial species). Looking at the limitations as an ordered combination adds nothing that is not already present when looking at the elements taken individually because the additional element(s) are recited at a high level of generality and are well-understood, routine, conventional activities already engaged in by the scientific community; see Huang (US 2013/0295054). Consequently, the additional element(s) are not sufficient to make the judicial exception eligible for patent protection (i.e. Step 2B is no).
Therefore, based upon consideration of all of the relevant factors with respect to the claim as a whole, the claims are held to claim a law of nature and natural products, and are consequently rejected as ineligible subject matter under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
9. 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.
10. Claims 14, 16 and 18-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 14 is indefinite because of the use of parentheses. Although parenthesis may be appropriate when defining an abbreviation or acronym, the inclusion of parentheses for phrases (e.g. see lines 2-3), raises uncertainty as to whether the feature in the parentheses is optional or always present. Thus, clarification is required to ascertain the metes and bounds of these claims. The Office suggests the use of commas or semicolons or appropriate language for a list of alternatives.
Also regarding claim 14, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention; See MPEP § 2173.05(d). The term introduces ambiguity of scope because it is unclear if the claim was intended to be limited to the specific “preferred” embodiment, or if the claim encompasses the broader grouping identified. A broad limitation together with a narrow limitation that falls within the broad limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired and raises a question or doubt as to whether the feature introduced by the narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims; See MPEP § 2173.05(c). Thus, clarification is required.
Other dependent claims do not clarify the issues identified above; thus, clarification is required to remove scope ambiguity.
Claim Rejections - 35 USC § 102
11. 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.
12. 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
13. Claims 5 and 14-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huang et al. 2013 (US 2013/0295054) as evidenced by Fuchs et al. 2000 (Journal of Bacteriology 182(13): 3626-3631).
Huang teaches modified obligate anaerobe bacterial cells, including Escherichia coli, comprising strictly hypoxia regulated essential gene expressing cassettes, comprising hypoxia-conditioned promoters having an inducer binding sites and wherein the essential gene is dapA and the promotor is pepT having an FNR binding site (i.e. transcription factor; e.g. see [0007-9, 0013, 0015-16] and Huang claims 30-36 and 42; meeting limitations found in instant claims 5, 14, 15, and 16).
With regards to the limitations “…wherein said obligate anaerobic bacterium is cultured in vitro under aerobic conditions, and requires addition of 2,6-diaminoheptanedioic acid into the culture medium” found in dependent claims 18 and 20, it is noted that these limitations do not appear to add a structural element to the product claims and thus have been interpreted as the intended use of claimed product; see MPEP 2144.07.
With regards to the presence of additional essential genes, including dapD and dapF, found in dependent claims 17 and 19; Huang is silent.
Nevertheless, Fuchs teaches E. coli naturally contains all three of dapD, dapE, and dapF genes (see introduction, right column) and therefore it is the Office’s position that the modified E. coli taught by Huang necessarily also contains these genes because there are no positively recited steps to remove them (i.e. these genes are recognized as essential for bacterial cell wall synthesis); however, since the Office does not have the facilities for examining and comparing Applicant’s modified obligate anaerobic bacteria with the modified obligate anaerobic bacteria of the prior art reference, the burden is now upon the Applicant to show a novel and an unobvious distinction between the material structural and functional characteristics of the claimed modified obligate anaerobic bacteria with that of the prior art; See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. Further, MPEP 2112.01 states that “When the PTO shows a sound basis for believing that the inventions of the Applicant and the prior art are the same, the Applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Accordingly, Huang (as evidenced by Fuchs) anticipates the invention as claimed.
Provisional Double Patenting
14. 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.
15. Claims 5 and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-7, 12-14, 17-19, 21, 23-25, and 27-31 of co-pending Application No. 18/727638 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to substantially the same bacteria having the same structural requirements for essential genes, promoters, and species. For example:
Instant claims are drawn to an obligate anaerobic bacterium, wherein said obligate anaerobic bacterium comprises a circuit of strictly anaerobically-induced expression of an essential gene consisting of (a) strictly anaerobically-activated promoter; and (b) an essential gene under the regulation of the promoter in (a); wherein the promoter in (a) has a binding site to an anaerobically activated transcription factor, and wherein said essential gene is dapE or dapA (see claim 5); wherein the bacteria is a bacterium of the family Enterobacteriaceae, Staphylococcus, Streptococcus, Pneumococcus, Bacillus anthracis, Corynebacterium diphtheriae, or Salmonella (see claim 14); wherein said anaerobically activated promoter is selected from the group consisting of Pept, Fnr-SP, Hip1, I141018, Ptet- arcA, Ptet-Fnr, R1074, Ssbp1 and YsgAP (see claims 15 and 16); and wherein the bacteria further comprises a circuit of strictly anaerobically-induced expression of an essential gene, and wherein said essential gene is selected from the group consisting of dapB, dapD, argD, dapF, murE, murF and lysA (see claims 17 and 19).
Similarly, co-pending claims are drawn to modified bacteria, wherein the bacterium comprise a hypoxia regulated essential gene expression cassette comprising an essential gene of the bacterium under the control of a strictly hypoxia inducible promoter, and the bacterium is deficient in at least one gene involved in or regulating the endogenous anti-oxidative stress response pathway or a functional expression product thereof, as compared to an unmodified starting strain (see claim 1); and further wherein the strictly hypoxia inducible promoter is selected from the group consisting of pepTp, fnrSp, ysgAp, ssbp1, Hip1, BBa I14018, BBa R1074, Ptet-arcA, and Ptet-Fnr; and preferably wherein the essential gene is selected from dapA, dapB, dapD, dapE, argD, dapF, and any combination thereof; and wherein the essential gene is selected from dapA and dapE; wherein the starting strain is Salmonella typhimurium SL7207; and further comprises a pH regulated expression cassette, wherein the pH regulated expression cassette comprises a gene encoding a bacteria-derived hemolysin protein under the control of a promoter that is active under acid pH condition.
Therefore the co-pending claims, have more specific requirements (e.g. and the bacterium is deficient in at least one gene involved in or regulating the endogenous anti-oxidative stress response pathway or a functional expression product thereof), are a species of the instant claims’ broader genus and thereby anticipate the instant claims; see MPEP 2131.02.
Conclusion
16. No claims are allowed.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. 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, Dan Kolker can be reached on (571)-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
18. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARY MAILLE LYONS/Examiner, Art Unit 1645
February 9, 2026