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
In the reply on 25 August 2026 Applicant has amended claims 90, 97, 104; cancelled claims 2-86 and added new claims 106-107.
Therefore, claims 1 and 87-107 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 87-101, and 103-105 drawn to a transmissible element for transmission to a recipient bacterium in the reply filed on 25 August 2026 is acknowledged. The new claims 106-107 are within the scope of the elected invention.
Claims 102 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 87-101, and 103-107 are under current examination.
Priority
This application was filed 07/03/2024, which claims benefit to the foreign application GB2310227.0 filed on 07/04/2023. MPEP 2304.01(c) states: Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action, 37 CFR 41.154(b) and 41.202(e).
Thus, the earliest possible priority for the instant application is 07/03/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/25/2026, and 12/03/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, and the signed and initialed PTO Forms 1449 are mailed with this action.
Claim Rejections - 35 USC § 112 (a)
(Written description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 87-101, and 103-107 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor, at the time the application was filed, had possession of the claimed invention.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
REQUIREMENTS TO ESTABLISH ACTUAL REDUCTION TO PRACTICE
"In an interference proceeding, a party seeking to establish an actual reduction to practice must satisfy a two-prong test: (1) the party constructed an embodiment or performed a process that met every element of the interference count, and (2) the embodiment or process operated for its intended purpose." Eaton v. Evans, 204 F.3d 1094, 1097, 53 USPQ2d 1696, 1698 (Fed. Cir. 2000).
The same evidence sufficient for a constructive reduction to practice may be insufficient to establish an actual reduction to practice, which requires a showing of the invention in a physical or tangible form that shows every element of the count. Wetmore v. Quick, 536 F.2d 937, 942, 190 USPQ 223, 227 (CCPA 1976). For an actual reduction to practice, the invention must have been sufficiently tested to demonstrate that it will work for its intended purpose, but it need not be in a commercially satisfactory stage of development. See, e.g., Scott v. Finney, 34 F.3d 1058, 1062, 32 USPQ2d 1115, 1118-19 (Fed. Cir. 1994) (citing numerous cases wherein the character of the testing necessary to support an actual reduction to practice varied with the complexity of the invention and the problem it solved). If a device is so simple, and its purpose and efficacy so obvious, construction alone is sufficient to demonstrate workability. King Instrument Corp. v. Otari Corp., 767 F.2d 853, 860, 226 USPQ 402, 407 (Fed. Cir. 1985).
For additional cases pertaining to the requirements necessary to establish actual reduction to practice see DSL Dynamic Sciences, Ltd. v. Union Switch & Signal, Inc., 928 F.2d 1122, 1126, 18 USPQ2d 1152, 1155 (Fed. Cir. 1991) ("events occurring after an alleged actual reduction to practice can call into question whether reduction to practice has in fact occurred"); Fitzgerald v. Arbib, 268 F.2d 763, 765-66, 122 USPQ 530, 531-32 (CCPA 1959) ("the reduction to practice of a three-dimensional design invention requires the production of an article embodying that design" in "other than a mere drawing"); Birmingham v. Randall, 171 F.2d 957, 80 USPQ 371, 372 (CCPA 1948) (To establish an actual reduction to practice of an invention directed to a method of making a product, it is not enough to show that the method was performed. "[S]uch an invention is not reduced to practice until it is established that the product made by the process is satisfactory, and this may require successful testing of the product."). See MPEP 2138.05.
Claim 1 encompasses a transmissible element for transmission to a genus of recipient bacterium and a genus of nucleic acid for the production of a genus of first molecule of interest (MOI). However, the specification doesn't have adequate support in the disclosure for any recipient bacterium, and any nucleic acid for the production of any MOI.
Teaching And Working Examples of the Specification:
The specification discloses that the conjugative plasmid isolated from E. coli., wherein the conjugative plasmid is a β10 conjugative plasmid from E. coli (e.g. as shown in Example 3 herein). The donor (host) cell comprising a conjugative plasmid as described herein is an E.coli (such as a symbioflor E coli, e.g. G6/7) (Example 3) (p. 17 1st ¶). Specification also discloses Conjugative plasmid p3024 is made by amplifying the casS base-editor system and a kanR cassette using primers oli9580 x oli9579 from p2970 and recombineering it into p2806 in b230. This creates strain b8286 containing p3024, which comprises both the MOI production pathway (including an exporter of the first MOI as G4), ancl the CasS-base editor. The strain is full genome sequenced to verify correct modifications (see FIG. 12) (p. 114 lns 1-5). High levels of MOI are produced by those receiving a conjugative plasmid carrying the MOI production pathway (p2806 and p3024), yet the introduction of a premature stop codon by p3024 leads to a significant increase in the detected levels of MOI, and no MOI is being produced when the pathway is not present in the conjugative plasmid (p2464 and p2986), see FIG. 14 (p. 115 lns 21-24). Therefore, specification only has support for E coli as a recipient bacterium, and very specific strain b8286 containing p3024 plasmid for higher levels of MOI are produced. Accordingly, the specification fails to identify the transmissible element for transmission to any recipient bacterium, and any nucleic acid for the production of any MOI. However, specification didn’t establish actual reduction to practice for any specific MOI. Therefore, an actual reduction to practice of an invention directed to the transmissible element for transmission to any recipient bacterium, and any nucleic acid for the production of any MOI of instant product is not established at the time of filling and POSITA cannot predictably any recipient bacterium of instant product that exercise the instant invention of any nucleic acid for the production of any MOI. Accordingly, the successful testing of the product of the current invention is not shows reduced to practice, therefore, it is not established that the product is satisfactory.
MPEP § 2163, besides an actual reduction to practice, Applicant may prove possession of the claimed invention by a showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention. Further, as per MPEP § 2163, “[f]or some arts, there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement.”
State of the Art at the Time of Filing:
The teaching of Arroyo-Olarte et al. (Microorganisms 2021, 9, 844; cited in PTO892; hereinafter “Arroyo-Olarte”) teaches that CRISPR is not predictable or universally functional for every bacterium, because only about half of all bacterial species naturally have CRISPR-Cas systems and editing success depends heavily on the specific host (abstract). Arroyo-Olarte further discloses that the genome editing (e.g., CRISPR-Cas-mediated genome editing) in bacteria encompasses a wide array of laborious and multi-step methods such as suicide plasmids. In another art, Peters et al. (Current Opinion in Microbiology 2015, 27:121–126; cited in PTO892; hereinafter “Peters”) disclose a replicative plasmids containing a complete CRISPRi system (i.e., dcas9 and sgRNA), a plasmid origin of replication (oriR), and an origin of transfer (oriT) can be mated from specific E. coli stain into other bacteria (fig. 2d of Peters). Therefore, it is obvious that the nucleic acid modifier (e.g., CRISPR) is not able to function in any recipient bacterium, and the prior arts do not support a generic recipient bacterium to optimize the production, consumption, or degradation of the first MOI in the recipient bacterium.
Separately, Neil et al. (Mol Syst Biol. 2021 Oct 19;17(10):e10335; cited in PTO892; hereinafter “Neil”) discloses the development of a genetically engineered conjugative probiotic (COP) strain that leverages TP114 for the mobilization of CRISPR-cas9 (Fig 1A) and demonstrate the feasibility of this approach by eliminating antibiotic-resistant E. coli in the gastro-intestinal (GI) tract and by treating a Citrobacter rodentium (CR) infection in a mouse model (p. 2 left hand side 1st ¶). Therefore, it is obvious that Neil predictably use conjugative probiotic (COP) strain that leverages TP114 for specific recipient E. coli. Accordingly, it is obvious that prior art does not establish at the time of filling and POSITA cannot predictably any recipient bacterium of instant product that exercise the instant invention of any nucleic acid for the production of any MOI.
Conclusion:
With these evidence, the transmissible element for transmission to any recipient bacterium, and any nucleic acid for the production of any MOI of instant product is not well established at the time of filling and the ordinary artisan cannot predictably identify any recipient bacterium in a subject. Therefore, one of the skills in the art would neither expect nor predict any recipient bacterium, and any nucleic acid for the production of any MOI.
Therefore, it concludes that the claimed genus of any recipient bacterium, and any nucleic acid for the production of any MOI doesn't have an adequate written description. It concludes that a skilled artisan would find the specification inadequately described. Accordingly, the Applicant did not sufficiently possess the broader invention as claimed in claim 1 and dependent claims 87-101, and 103-107.
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 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 applicant regards as the invention.
Claim 1 has recited “at least one nucleic acid” for production MOI and further recited “a Pathway Modulation System (PMS) encodes a CRISPRi system”. However, it is not unclear from the claim language whether the nucleic acid encoding the MOI and nucleic acid component encoding the CRISPRi system of the PMS are contained in the same vector or in separate vectors. Accordingly, the relationship between the recited nucleic acid for producing MOI and the PMS encoded CRISPRi system in unclear, such that the metes and bounds of claim 1 cannot be determined with reasonable certainty. Therefore, clarification of the relationship between these recited components are required.
Claim Rejections - 35 USC § 102
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.
Claims 1, 87-88, 91, 97, 99, and 103-107 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Neil et al., (Molecular systems biology, 17(10), p.MSB202110335; cited in PTO892; hereinafter “Neil”).
With respect to claims 1, 87-88, 91, 97, 99, 103, Neil discloses conjugative plasmid TP114 (e.g., transmissible element) to deliver CRISPR-cas systems programmed to precisely eliminate antibiotic-resistant bacteria represents a promising approach but requires high in situ DNA transfer rates. Neil further discloses conjugative delivery vehicle for CRISPR-cas9 that can eliminate > 99.9% (e.g., degradation) of targeted antibiotic-resistant Escherichia coli in the mouse gut microbiota using a single dose (Figure 2; abstract), therefore, Conjugative transfer in the mouse gut microbiota was next assessed by administering the recipient EcN KN02 strain by gavage. Therefore, Neil teaches the donor bacterium comprising the transmissible element (see p. 4 “Highly efficient DNA delivery by eB-TP114” ¶).
With respect to claims 104-107, Neil discloses the method comprising administering to the subject Eliminating antibiotic-resistant E. coli in the gastro-intestinal (GI) tract and by treating a Citrobacter rodentium (CR) infection in a mouse model, therefore, Neil teaches the treatment of a condition (e.g., antibiotic-resistant Escherichia coli) in a subject in need thereof (p. 2 left hand side 1st ¶). Neil further teaches a pharmaceutical composition comprising a) the donor bacterium and b) a pharmaceutically acceptable excipient or carrier (PBS) (see p. 2 “The COP system as a microbiome editing tool” ¶).
Accordingly, Neil anticipates the instant claims 1, 87-88, 91, 97, 99, and 103-107.
Subject Matter Free of Art
Neil discloses conjugative plasmid TP114 (e.g., transmissible element) to deliver CRISPR-cas systems programmed to precisely eliminate antibiotic-resistant bacteria represents a promising approach but requires high in situ DNA transfer rates. However, claims 89-90, 92-96, 98, 100 are objected, because Neil does not teach or reasonably suggest the MOI is a metabolite selected from the group consisting of L-DOPA, indole-3-acetic acid, and butyrate. Further, Neil does not teach or reasonably suggest the nucleic acid in 5' to 3' direction, a promoter, a sequence encoding a signal peptide, and at least one nucleic acid for the expression of the first MOI. Since claims 89-90, 92-96, 98, 100 depend on rejected base independent claim 1. Claims 89-90, 92-96, 98, 100 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 101 is objected because art does not teach or reasonably suggest the SEQ ID NO: 1-5 (see ABSS report filed 09/08/2026). Since claim 101 depends on rejected base independent claim 1. Claim 101 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic, can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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