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 .
Status of Claims
Claims 1-2, 5-8, 10-12, 14-15, and 17-31 are pending.
Priority
Claims 1-2, 5-8, 10-12, 14-15, and 17-31 are a 371 of PCT/AU 2022/051414 filed on November 25, 2022, which has priority to AUSTRALIA 2021903809 filed on November 25, 2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on May 24, 2024, was filed before the mailing of the First Office Action on July 11, 2026. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Specification
It is noted that the listing of references on page 43 in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, “the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because:
Figs 2A-C are not legible.
Fig. 9 is not legible.
Fig. 11 is not legible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). 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. The objection to the drawings will not be held in abeyance.
Additionally, the drawings are objected to because of the following informalities: There is description of color in the Specification of Figure 1, 3, 6, pg. 9 lines 16, 23, and 32, respectively, and Figure 13 on pg. 10 Line 20, and the various colors cannot be distinguished from each other since the figures are in black and white.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 27 is 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.
Claim 27 is rejected as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention. Claim 27 recites dependency to claim 26. However, in part (i) the claim limitation recites “any one of claims 1-30”. In addition, limitation (ii) recites “any one of claims 1-20”. The claim fails to define which limitations are incorporated from the referenced claims. Also, not all of claims 1-30 are pending.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 5-8, 10-12, 14-15, and 17-31 are rejected under 35 U.S.C. §103 as being unpatentable over Lazdins et al. [Potentiation of curing by a broad-host-range self-transmissible vector for displacing resistance plasmids to tackle AMR, PLoS One, 2020], in view of Humbert et al. [Entry exclusion of conjugative plasmids of the IncA, IncC, and related untyped incompatibility groups, J Bacteriol., 2019], in view of Oluwadare et al. [The role of the Salmonella spvB IncF plasmid and its resident entry exclusion gene traS on plasmid exclusion, Front. Microbiol., 2020], in view of Frose et al. [US 2019 348154 A1], in view of Expression Plasmids with Inducible Promoters (Hereinafter Expression Plasmids) [https://www.bio.davidson.edu/genomics/method/plasmid_inducible.html, 2002], in view of Doshi et al. [Multiple alternative promoters and alternative splicing enable universal transcription-based logic computation in mammalian cells, Cell Reports, 2020], in view of Tan [A modular polycistronic expression system for overexpressing protein complexes in E. coli, Protein Expression and Purification, 2001], in view of Gill et al. [Progress and prospects: the design and production of plasmid vectors, Gene Therapy, 2009], in view of Zuo et al. [Engineer probiotic bifidobacteria for food and biomedical applications – current status and future prospective, Biotechnology advances, 2020], in view of Perpetuo et al. [Engineering bacteria for bioremediation, Progress in Molecular and Environmental Bioengineering-from analysis and modeling to Technology Applications, 2010].
Regarding claim 1, Lazdins et al. teaches a recombinant plasmid where the plasmid variants comprise a gene conferring trait of interest [Abstract]. However, Lazdins et al. does not teach the use of entry exclusion systems (EES) from a plurality of plasmid variants.
For this limitation, Humbert et al. teaches that conjugative plasmids possess genetically encoded entry systems that function to impede DNA transfer into recipient cells already carrying a related plasmid [Abstract]. Furthermore, Humbert et al. discloses the eexC gene as mediating entry exclusion in IncC plasmids and demonstrates that this entry exclusion system is shared by both IncA and IncC incompatibility groups. Humbert et al. further teaches that entry exclusion is a conserved mechanism among conjugative plasmids that prevents redundant plasmid transfer. Based on this, it would have been prima facie obvious to a person of ordinary skill prior to the filing of the claimed invention to modify the systems and methods as taught by Lazdins et al. where a recombinant conjugative plasmid system could incorporate an entry exclusion system taught by Lazdins et al. given that Humbert et al. discloses that entry exclusion systems are conserved mechanisms that impede redundant plasmid transfer among conjugative plasmids. Given this, there is a reasonable expectation of success that a person of ordinary skill in the art would combine the teachings of both Lazdins et al. and Humbert et al. to develop a recombinant plasmid to include a known exclusion entry system that could include multiple incompatibility groups such as both IncA and IncA, as well as others, given that engineering recombinant plasmids incorporating known genetic elements and regulatory sequences are routine and well-established molecular biology techniques within the ordinary skill of the art.
For claim 2 where the trait of interest is an undesirable in a bacterial population, the trait of interest is antimicrobial resistance, or the recombinant plasmid comprises EES from at least three plasmid variants containing a gene conferring the trait of interest, Lazdins et al. teaches displacement that the recombinant conjugative plasmids is designed to displace plasmids encoding undesirable traits [Abstract] where an introduced resistance marker was able to cause displacement of target plasmids [Introduction ¶ 3].
For claim 5 where the EES are from different incompatibility groups, Humbert et al. teaches that entry exclusion systems are associated with different plasmid incompatability groups that include IncA and IncC plasmids, as well as identifying EES that function across both incompatability groups [Introduction ¶ 3]. Given that Humbert et al. teaches EES are conserved among plasmids of different incompatibility groups and perform the same known function, i.e. preventing redundant plasmid transfer, a person of ordinary skill in the art would have recognized EES from different incompatability groups as known alternative genetic components would have been suitable for incorporation into a recombinant plasmid of Lazdins et al., and therefore, would have achieved a predictable function for entry exclusion.
For claim 6 where the EES is from the same compatibility group, Humbert et al. teaches EES associated with specific plasmid incompatibility groups that include IncA and IncC [Abstract]. Additionally, Humbert et al. discloses that eexC entry exclusion gene is responsible for mediating entry exclusion in both IncA and IncC, and because EES were known to be associated with particular incompatibility groups [Introduction ¶ 3]. It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Lazdins et al. with the additional teachings of Humbert et al. where one or more entry exclusion systems of the same incompatability group could be chosen for incorporation into a recombinant plasmid. Given this, there would have been a reasonable expectation of success to combine the teachings of Lazdins et al. with Humbert et al. where a person of ordinary skill in the art would recognize to combine a known EES from the same incompatability group to incorporate into a recombinant plasmid.
For claim 7 where one or more EES is select from a Markush listing that includes IncA and IncC, Humbert et al. teaches the use of both IncA and IncC [Importance].
For claim 8 where the one or more EES are from plasmid variants of incompatability group F (IncF), Oluwadare et al. teaches that an IncF plasmid contains the resident entry exclusion gene traS, which functions in plasmid exclusion [Abstract, Introduction ¶ 3]. Based on this, Oluwadare et al. teaches an EES derived from a plasmid variant of incompatability group F. Therefore, there is a reasonable expectation of success that a person of ordinary skill in the art would incorporate the known IncF-derived exclusion entry system into the recombinant plasmid as taught by Lazdins et al. given that IncF EES was known to perform the predictable function of preventing plasmid transfer and represented a known genetic component suitable for insertion into a recombinant plasmid.
For claims 10 and 14, Frose et al. discloses nucleic acid sequences SEQ ID NOs 21353, 229897, 376067, 195506, 260273, 83598, and 286480 are between 88% and 100% identical to Applicant’s nucleic acid sequences SEQ ID NOs 1-3 and SEQ ID NOs 9-12. Here, Oluwadare et al. discloses the IncF plasmid exclusion gene traS which also functions as a IncF EES.
For claim 11 where the recombinant plasmid of claim 10 comprises the traS_F variant EES, the traS_R100 variant EES, and the traS-SLT variant EES, Frose et al. discloses nucleic acid sequences that include plasmid gene traS where the nucleic acid sequences are from 88% to 100% identical to Applicant’s claimed SEQ ID NOs 1-3 and 9-12 which include the variants of Applicant’s claim 11.
For claim 12 where the recombinant plasmid includes one or more EES from incompatability groups L, C, M, A, and any combination, please see the rational for claim 1 where IncA and IncC are discussed.
For claim 15 where the recombinant plasmid has an EES operably linked to a constitutive promoter or an inducible promoter, Expression Plasmids discloses the use of both constitutive promoters and inducible promoters along with their respective differences [Fig. 1, ¶ 2]. Expression Plasmids further explains that constitutive promoters are viral promoters and are always active versus inducible promoters which are not always active [¶ 2]. Given this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Lazdins et al. and Humbert et al. with the additional teachings of Expression plasmids given that the use of a of promoter, either constitutive or inducible, are well known design components in recombinant plasmid technology. Based on this, there is a reasonable expectation of success that a person would combine the teachings of Expression Plasmids with the teachings of both Lazdins et al. and Humbert et al. where a person of ordinary skill would have known to include a promoter, either inducible or constitutive, based on the particular need and that the use of promoters in recombinant plasmids is known component that allows the regulation and expression of the protein that was selected for expression.
For claim 17 where the recombinant plasmid EES are operably linked to separate promoters, Doshi et al. teaches the use of multiple promoters that are operably linked to individual transgenes in order to control expression of these transgenes independently [Figure 1 part A & B, Implementing OR Logic Using Alternative Promoter Architecture].
For claim 18 where the where one or more EES are operably linked to the same promoter, Tan teaches that a single promoter can be used to for polycistronic expression vectors where multiple proteins are co-expressed with a single promoter [Fig. 1 and Fig. 2].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of both Lazdins et al. and Humpert et al. with the additional teachings of either Doshi et al. or Tan where a person of ordinary skill would choose between a recombinant expression system that either uses multiple promoters that can be operably linked to each separate EES where the expression can be more precisely regulated or choose a single promoter system that is capable of coexpression of multiple EES at the same time. Therefore, there is a reasonable expectation of success that a person of ordinary skill in the art would be able to design a recombinant plasmid that contained multiple EES expression segments where these segments could be either be operably linked to their own promoter or where a single promoter was used and allowed coexpression of the EES segments.
For claims 19 and 20, Gill et al. discloses the use of a selectable marker, e.g. antibiotic resistance gene in Figure 1. There is a reasonable expectation of success that a person of ordinary skill in the art would include a selectable maker, e.g. an antibiotic resistance gene, given the use of such selectable markers are routine in the art and are used as a way of identifying and isolating cells that have successfully taken up the recombinant plasmid.
For claim 21 where a bacterial cell comprises a recombinant plasmid, Lazdins et al. discloses the engineered plasmids entering into gut bacteria [Figure 1 pCure probiotic].
For claim 22 where the bacteria are a probiotic bacterium, Zuo et al. discloses the use of probiotic bacteria such as Bifidobacteria which are found in the human gut [Abstract].
For claim 23 where the probiotic bacteria are selected from a Markush listing, Zuo et al. discloses that numerous studies have been carried out on E. coli, Lactococcus, Streptococcus, as well as, Lactobacillus [2.3 Genome engineering tools ¶ 3, 2.1 incorporation of foreign DNA].
For claim 24, Zuo et al. teaches that probiotic bacteria can be designed for both food and pharmaceutical applications [4. Rational design and engineer probiotic bifidobacteria for food and biomedical applications].
For claim 25 where the bacteria are lyophilized or formulated in food or beverage product, again, Zuo et al. discloses that probiotic bacteria can be included in food [Id.].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems of Lazdins et al. and Humbert et al. with the additional teachings of Zuo et al. where the probiotic bacteria containing the recombinant plasmids that express antimicrobial resistance further being placed in a food and/or beverage product for to be administered to a subject. Based on this, there would have a been a reasonable expectation of success that a person of ordinary skill would have combined the teachings of Zuo et al. with the with the teachings of both Lazdins et al. and Humbert et al. allowing probiotic bacteria containing an engineered plasmid that expresses multiple incompatability groups, e.g. IncA, IncC, and IncF, would be incorporated into a food and/or beverage product for consumption by a subject.
For claim 26, the same analysis for claims 1, 24, and 25 are applied here.
For claim 28 where the population of bacteria is a population of gut bacteria, and the method comprises administering the bacterial cells and/or composition to a subject in need. Zuo et al discloses the use of probiotic bacteria that are derived from the gut that have been engineered through the use of plasmids, which includes recombinant plasmids, can be used in pharmaceutical compositions, as well as food [4. Rational design and engineer probiotic bifidobacteria for food and biomedical applications]. There is a reasonable expectation of success that a person of ordinary skill in the art could have combined the recombinant plasmids of Lazdins et al. and Humbert et al. expression multiple variants of EES to be combined or introduced into gut bacteria that could then be utilized in a pharmaceutical composition and/or food/beverage for a subject in need to either consume or be administered.
For claim 29 where the subject is a human, Lazdins et al. discloses the administration of a probiotic treatment to a human [Figure 1].
For claim 30 where the bacteria containing recombinant plasmids is capable of colonizing plants, soil, or used in healthcare environments, water sources, etc., Although the reference does not disclose the use of bacteria, bioremediation has been used extensively in for degradation and/or removal of environmental pollutants as taught by Perpetuo et al. [Introduction]. Perpetuo et al. further discloses that biological agents, e.g. bacteria, phages, and engineered microbes, have been routinely used for removal of heavy metals in, i.e. soil environment [Id.].
For claim 31 where a food product or beverage comprises one or more bacterial cells that contain the recombinant plasmid with one or more EES, Zuo et al. discloses the use of probiotic bacteria included in both food and pharmaceutical applications [4. Rational design and engineer probiotic bifidobacteria for food and biomedical applications]. Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Lazdins et al. and Humbert et al. with the additional teachings of Zuo et al. to include bacteria, e.g. probiotic bacteria, that contain an engineered plasmid that contains one or more variants of EES that can be from either the same incompatability group or different incompatability groups that allows for a trait of interest to be exhibited, including antimicrobial resistance could be included in either a pharmaceutical composition of food product as taught by Zuo et al. Given this, there would have been a reasonable expectation of success that a person of ordinary skill would have recognized the teachings of Zuo et al. and would have combined with the teachings of both Lazdins et al. and Humbert et al. to develop a probiotic bacterium that contained an engineered plasmid that encoding entry exclusion systems from a variety of incompatability groups, e.g. IncA or IncC, that could then be administered either as a composition or in a food/beverage.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims allowed.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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