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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-10, 13-14, 18-21, 23, and 26-27 and the species of a first genus being gram negative and a second genus being gram positive, SEQ ID NOs: 157, 143, 384, 544, and E33K in the reply filed on 29 August 2025 is acknowledged. For the purposes of examination, the species of a first genus being gram positive and a second genus being gram negative (see Claim 2), the species of a first genus being gram positive and the second genus being gram positive (see Claim 3), SEQ ID NOs: 5, 366, 381, 395, 143, 262, 325, 366, and 381 (see Claim 10), SEQ ID NO: 235 (see Claim 18), and SEQ ID NO: 516 (see Claim 20) have been rejoined.
Claims 30-31, 33, and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 29 August 2025.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claim Rejections - 35 USC § 112
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 1-9, 13, 18-21, 23, and 26-27 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(s) contains subject matter which 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claims 1, 13, 19, the claims broadly claim a genus of any SSAP from any bacteriophage that can infect a bacterial cell of a second genus or is from a prophage in the genome of a second genus. Accordingly, the claims are interpreted as claiming a very large genus of SSAPs from bacteriophages that can infect, or prophages that are integrated into the genome of, a second genus of bacterial cells that is different from the first genus.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would leave one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP 2163. A claimed genus may be satisfied through sufficient descriptions of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with known or disclosed correlation between function and structure. MPEP 2163(3)a(II). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
As the claims currently recite, as described above, the claim is directed towards a genus of SSAPs from bacteriophages that can infect, or prophages that are integrated into the genome of, a second genus of bacterial cells that is different from the first genus. While claiming a genus of structures is not prohibited, there must be a sufficient number of species disclosure in the specification such that the claimed genus was represented by a representative number of species or the teachings of the specification.
In the instant case, the instant specification does not provide a representative number of species of any [emphasis added] SSAP from bacteriophages that can infect, or prophages that are integrated into the genome of, a second genus of bacterial cells that is different from the first genus.
Prior Art
Regarding the state of the prior art, Lin (Research in microbiology 161.4 (2010): 308-314) is drawn towards a study concerned with the isolation and characterization of a novel bacteriophage, ϕAB2, that is able to infect A. baumannii cells (Abstract). Lin teaches that ϕAB2’s ability to infect other host cells selected from A. calcoaceticus, E. coli, K. pneumoniae, and P. aeruginosa was tested and screened for in order to determine if the bacteriophage had host specificity or if the bacteriophage was able to infect a wide range of host cells (pg. 310). Lin teaches that the bacteriophage was only able to infect the A. baumannii cells and was unable to infect the other bacterial host cells (pg. 310).
Thus, the prior art shows that prior to the effective filing date of the claimed invention it was not predictable that any SSAP derived from any bacteriophage was able to infect a bacterial cell of a different cell from a second genus. Rather, the prior art shows that a bacteriophage’s ability to infect different genera of bacterial cells needed to be tested in order to determine if the bacteriophage had host specificity or if it was able to infect a broad range of hosts.
Working Examples
With regard to working examples, the specification provides little evidence on the possession of a sufficient number of species which are encompassed by the claimed genus. MPEP 2163 teaches that “for 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. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed [emphasis added].”
In the instant case, the specification does not describe nor contain any discussion relating to any bacteriophages, or SSAPs derived from bacteriophages, that are capable infecting different genera of bacteria. Further, the instant specification only teaches the use of three SSAPs from Lactobacillus prophages (pg. 5-72; see Table 1). Three species of SSAPs from prophages alongside no discussion of bacteriophages that are capable infecting different genera of bacteria does not provide a sufficient number of species for the claimed genus of SSAPs.
Thus, the instant specification does not provide written description for the entirety of the claimed genus of “SSAP[s] from a bacteriophage that can infect, or a prophage that are integrated into the genome of, a second genus of bacterial cells that is different from the first genus” (see Claims 1, 13, and 19).
Conclusion
The specification does not identify a representative number of species of the claimed genus of any SSAP from any bacteriophage that can infect a bacterial cell of a second genus or is from a prophage in the genome of a second genus. Further, the prior art shows that prior to the effective filing date of the claimed invention that the ability for a bacteriophage to infect different genera of cells was unpredictable and required experimentation in order to determine. Therefore, a person of ordinary skill in the art would not have concluded that Applicant was in possession of the invention as claimed. Thus, claims 1, 13, and 19 is rejected under 35 U.S.C. 112(a).
Regarding claims 2-9, 18, 20-21, 23, 26, and 17, as the claims are ultimately dependent on claims 1, 13, or 19 and do not rectify the 35 USC 112(a) rejection above, the claims are also rejected under 35 USC 112(a).
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 4, 6, and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 4, the claim further limits the gram-negative bacterial cell. However, the claim lacks clear antecedent basis because there are two recitations of a “bacterial cell” that is “gram negative” in claim 2, one that is of a first genus and one that is of a second genus. It is not clear which of these two bacterial cells that are gram negative is being referred to by “the gram negative bacterial cell” in claim 4.
Regarding claim 6, the claim further limits the gram-positive bacterial cell. However, the claim lacks clear antecedent basis because there are two recitations of a “bacterial cell” that is “gram positive” in claim 2, one that is of a first genus and one that is of a second genus. It is not clear which of these two bacterial cells that are gram negative is being referred to by “the gram positive bacterial cell” in claim 6.
Regarding claim 18, MPEP 2173.05(s) states "Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim". In the current case, it would be practical to define the claimed SSB without reference to a table by amending the claim to recite the SSB SEQ ID NOs in the claimed Table 1.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-5, 8, 21, 23, and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Church (PG Pub No. WO 2017/184227 A2). The rejection of claims 2 and 4-5 are further evidenced by Mu (Mu (Frontiers in microbiology 9 (2018): 757) and Sondi (Journal of colloid and interface science 275.1 (2004): 177-182). The rejection of claim 3 is further evidenced by Mu (Mu (Frontiers in microbiology 9 (2018): 757) and Samul (Acta Biochimica Polonica 60.4 (2013).
Regarding claim 1, Church is drawn to an invention concerned with altering a target nucleic acid sequence within a cell (Abstract). Church teaches the use of an E. coli cell (i.e., a recombinant bacterial cell of a first genus) that comprised an SSAP from L. reuteri (i.e., a bacterial cell of a second genus different from the first genus) (pg. 35-36; see Example V).
Regarding claims 2 and 4-5, Mu is drawn towards a review study concerned with the role of L. reuteri in human health and disease (Abstract). Mu teaches that L. reuteri is a gram positive bacterium (pg. 2). Sondi is drawn towards a study concerned with a case study on E. coli as a model for gram negative bacteria (Abstract). Sondi teaches that E. coli is a gram negative bacterium (pg. 179).
Therefore, as evidenced by Mu and Sondi, the E. coli cell of Church is inherently a gram-negative bacterium and the L. reuteri of Church is inherently a gram positive bacterium.
Regarding claim 3, Church further teaches that host cells may be from members of the genera Clostridium (pg. 13-14). Mu is drawn towards a review study concerned with the role of L. reuteri in human health and disease (Abstract). Mu teaches that L. reuteri is a gram positive bacterium (pg. 2). Samul is drawn towards a study concerned with the roles of bacteria from the Clostridium genus (Abstract). Samul teaches that bacteria of the Clostridium genus are gram-positive bacteria (pg. 515).
Therefore, as evidenced by Mu and Sondi, the Clostridium host cell of Church is inherently a gram positive bacterium and the L. reuteri of Church is inherently a gram positive bacterium.
Regarding claim 8, Church teaches that a cognate L. reuteri single-stranded binding protein was introduced alongside its SSAP in order to enable recombination in E. coli (pg. 36).
Regarding claims 21 and 23, Church teaches that the disclosure provides a method of genome editing by including one or more or both of a recombinase and a corresponding single-stranded DNA- binding protein into a cell where one or more or both of a recombinase and a corresponding single- stranded DNA binding protein is foreign to the cell and where a donor nucleic acid sequence is introduced into the genome of the cell (pg. 3). Church teaches that the donor nucleic acid may be foreign or exogenous nucleic acids that are not part of a cell’s natural nucleic acid composition (i.e., the exogenous nucleic acid comprises a nucleotide modification relative to a target locus) (pg. 9-10).
Regarding claim 27, Church teaches that the vector comprised an RBS-containing motif downstream of the SSAP stop codon (pg. 35).
Claim(s) 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yin (Iscience 14 (April 26 2019): 1-14).
Regarding claim 13, Yin is drawn towards a study concerned with single-stranded DNA binding proteins in P. aeruginosa (Abstract). Yin teaches the use of a P. aeruginosa SSAP, termed BAS, that was able to be integrated into a recombinant P. fluorescens, syringae, and putida cells (i.e., recombinant bacterial cells) and induce recombination (pg. 2-3; see Figure 3). Yin teaches that the SSAP was placed under the expression of an inducible promoter (i.e., a non-native promoter) (pg. 3, 5).
Claim(s) 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Handa (Journal of Biological Chemistry 276.20 (2001): 16992-16997).
Regarding claim 19, Handa is drawn towards a study concerned with chimeras between single-stranded binding proteins (i.e., SSBs) from E. coli and M. tuberculosis (Abstract). Handa teaches the use of a chimeric SSB, termed MtuEcoSSB, which contains the N-terminal portion from an M. tuberculosis SSB (i.e., a first SSB) and the C-terminal domain (comprised of 48 amino acids) from an E. coli SSB (i.e., a C-terminus of a second SSB comprising at least 7 amino acids) that was able to be expressed within a yeast host strain (i.e., a recombinant bacterial cell) (pg. 16993-16994; see FIG. 2).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 6-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Church (PG Pub No. WO 2017/184227 A2) as evidenced by Mu (Frontiers in microbiology 9 (2018): 757) and Sondi (Journal of colloid and interface science 275.1 (2004): 177-182) as applied to claims 1-5, 8, 21, 23, and 27 above, and further in view of Church (WO 2017/184227 A2).
Regarding claims 6-7, Church as evidenced by Mu and Sondi anticipate claims 2 and 4 as described above. Church further teaches that S. aureus cells (i.e., S. aureus host cells) may be utilized for in the methods of recombination described in the disclosure (pg. 15).
Church as evidenced by Mu and Sondi does not teach that the gram-positive bacterial cell is a gram positive S. aureus cell (Claims 6-7).
However, one of ordinary skill in the art would have further considered the teachings of Church as both references are common fields of endeavor pertaining to the use of gram positive SSAPs in gram negative cells.
Church further teaches that single stranded annealing proteins (i.e., SSAPs) may be referred to as recombinases (pg. 2). Church teaches that exemplary recombinases for use in recombineering methods described in the disclosure are listed in Tables 1-6 (pg. 17). Church teaches that, in Table 4, recombinases from S. aureus may be utilized by the invention (pg. 42, 44, 49, 51; see Table 4).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the L. reuteri SSAP of Church as evidenced by Mu and Sondi for an S. aureus recombinase (i.e., an S. aureus SSAP). A person of ordinary skill in the art would have recognized that the two proteins have a common function as evidenced by their names and the teachings of Church stating that the SSAPs may be interchangeably utilized. Therefore, a person of ordinary skill in the art would have had a reasonable expectation of success because Church teaches that an SSAP from L. reuteri was able to be successfully expressed in E. coli bacterial cells in order to induce recombination and further teaches that S. aureus recombinases (i.e., S. aureus SSAPs) could be utilized by the invention.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Church (PG Pub No. WO 2017/184227 A2) as applied to claims 1-5, 8, 21, 23, and 27 above, and further in view of Smith (PloS one 2.12 (2007): e1271).
Regarding claim 3, Church anticipates claims 1-5, 8, 21, 23, and 27 as described above. Further, Church teaches that a recombinase (i.e., an SSAP) from C. botulinum may be utilized (pg. 40; see Table 4). Church teaches that the method of recombineering requires, as a minimally functional set, an SSAP paired with its phylogenetically-matched SSB homolog in a foreign host cell (pg. 37).
Church does not teach or suggest that the SSB is from C. botulinum (Claim 9).
However, one of ordinary skill in the art would have considered the teachings of Smith as both references are common fields of endeavor pertaining to the study of C. botulinum.
Smith is drawn towards a study concerned with analysis of neurotoxin complex genes in C. botulinum plasmids (Abstract). Smith teaches that a C. botulinum single-stranded binding protein (i.e., an SSB), K03111, was identified and present on a plasmid within C. botulinum (pg. 6-7).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the SSB anticipated by Church for an SSB from C. botulinum, as described by Smith. A person of ordinary skill in the art would have been motivated to do so in order to utilize a minimally functional set of phylogenetically-matched SSAP and SSB in order to enable recombination. A person of ordinary skill in the art would have had a reasonable expectation of success because Church teaches the use of a C. botulinum SSAP and further teaches that utilizing SSAPs and SSBs from phylogenetically-matched organisms results in recombination in a foreign host cell, while Smith teaches the identification of a C. botulinum SSB.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Church (PG Pub No. WO 2017/184227 A2) as applied to claims 1-5, 8, 21, 23, and 27 above, and further in view of O’Donnell (PG Pub No. WO 01/09164 A2).
Regarding claim 18, Church anticipates claims 1-5, 8, 21, 23, and 27 as described above. Further, Church teaches that a recombinase (i.e., an SSAP) from S. pyogenes may be utilized (pg. 40; see Table 4). Church teaches that the method of recombineering requires, as a minimally functional set, an SSAP paired with its phylogenetically-matched SSB homolog in a foreign host cell (pg. 37).
Church does not teach or suggest that the SSB comprises the claimed SEQ ID NO: 235 (Claim 18).
However, one of ordinary skill in the art would have considered the teachings of O’Donnell as both references are common fields of endeavor pertaining to the use of S. pyogenes SSBs.
O’Donnell is drawn towards a study concerned with O’Donnell teaches the use of an SSB from S. pyogenes that comprises 100% sequence identity to the claimed SEQ ID NO: 235 (pg. 51-52, pg. 137; see Claim 83 and SEQ ID NO: 30 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Church such that the SSAP and SSB were both from S. pyogenes, wherein the SSB comprised an amino acid sequence having 100% identity to the claimed SEQ ID NO: 235, as described by O’Donnell. A person of ordinary skill in the art would have been motivated to do so in order to utilize a cognate SSB alongside the S. pyogenes SSAP described in Church. A person of ordinary skill in the art would have had a reasonable expectation of success because Church teaches that heterologous cognate SSAPs and SSBs were able to induce recombination in E. coli cells while O’Donnell teaches that the claimed SEQ ID NO: 235 was a known S. pyogenes SSB.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Handa (Journal of Biological Chemistry 276.20 (2001): 16992-16997) as applied to claim 19 above, and further in view of Church (PG Pub No. WO 2017/184227 A2).
Regarding claim 20, Handa anticipates claim 19 as described above.
Handa does not teach or suggest that the C-terminus of the chimeric SSB comprises a sequence selected from SEQ ID NO: 516 (Claim 20).
However, one of ordinary skill in the art would have considered the teachings of Church as both references are common fields of endeavor pertaining to the use of E. coli SSBs.
Church is drawn to an invention concerned with altering a target nucleic acid sequence within a cell (Abstract). Church teaches the use of E. coli SSAPs and SSBs that can be utilized to enable recombination in target cells (pg. 2-3). Church teaches the use of an E. coli SSB that comprises a C-terminus that has 100% sequence identity to the claimed SEQW ID NO: 516 (pg. 78; see SEQ ID NO: 11).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the 48 amino acids of a C-terminal domain from an E. coli SSB, as described by Handa, for the C-terminal domain of an E. coli SSB, as described by Church. A person of ordinary skill in the art would have had a reasonable expectation of success because Handa teaches that a chimeric SSB may be created via the use of the CV-terminus of an E. Coli SSB and Church teaches that the claimed SEQ ID NO: 516 was known to be present within the C-terminus of an E. coli SSB.
Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Church (PG Pub No. WO 2017/184227 A2) as applied to claims 1-5, 8, 21, 23, and 27 above, and further in view of Nyerges (Proceedings of the National Academy of Sciences 113.9 (2016): 2502-2507).
Regarding claim 26, Church anticipates claims 1-5, 8, 21, 23, and 27 as described above.
Church does not teach or suggest that the recombinant bacterial cell comprises a dominant negative MutL protein (Claim 26).
However, one of ordinary skill in the art would have considered the teachings of Nyerges as both references are common fields of endeavor pertaining to methods of recombination within E. coli cells.
Nyerges is drawn towards a study concerned with the suppression of a gene within a methyl-directed mismatch repair (i.e., MMR) system in E. coli in order to achieve a transient suppression of DNA repair in E. coli, which is necessary for efficient oligonucleotide integration within the cell (Abstract). Nyerges teaches the use of a set of plasmids, termed “pORTMAGE”, that expressed λ Red recombinase enzymes, as well as a dominant-negative mutator allele of MutL, under the control of the cI857 temperature-sensitive repressor (pg. 2503). Nyerges teaches that utilizing pORTMAGE allowed for efficient modification of multiple target loci in E. coli, without any observable off-target mutagenesis and prior modification of the host genome (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the E. coli cell anticipated by Church such that it comprised a dominant negative MutL protein, as described by Nyerges. A person of ordinary skill in the art would have been motivated to do so in order to promote efficient modification of target loci in E. coli without off-target mutagenesis. A person of ordinary skill in the art would have had a reasonable expectation of success because both Church and Nyerges teach the use of recombinase systems that can edit loci in E. coli cells while Nyerges further teaches that utilizing a dominant negative MutL protein in E. coli promotes modification of loci in the E. coli by the recombinase systems.
Closest Prior Art
Regarding claim 10, the closest prior art is Doucette-Stamm (PG Pub No. US 2007/0021600 A1). Doucette-Stamm is drawn towards a study concerned with isolated polypeptide and nucleic acid sequences derived from Enterococcus faecalis that are useful in diagnosis and therapy of pathological conditions (Abstract). Doucette-Stamm teaches the use of an amino acid sequence comprising 100% identity to the claimed SEQ ID NO: 5 (see Claim 1 and SEQ ID NO: 6101 in attached sequence alignment). Doucette-Stamm teaches that the SEQ ID NO: 6101 is an isolated polypeptide from Enterococcus faecalis ([0044]).
However, Doucette-Stamm nor the prior art teaches or suggest that the claimed SEQ ID NO: 5 is an SSAP (see Claim 10). Further, Doucette-Stamm nor the prior art teaches or suggests the use of a recombinant gram-negative E. coli cell comprising an SSAP comprising the claimed SEQ ID NO: 157, wherein the SSB comprises the claimed SEQ ID NOs: 300, 382, 384, or 389 (see Claim 10). Doucette-Stamm nor the prior art teaches or suggests the use of a recombinant gram-positive L. lactis cell comprising an SSAP comprising the claimed SEQ ID NO: 5, wherein the SSB comprises the claimed SEQ ID NOs: 366, 381, or 395 (see Claim 10). Doucette-Stamm nor the prior art teaches or suggests the use of a recombinant gram-positive L. lactis cell comprising an SSAP comprising the claimed 143, wherein the SSB comprises the claimed SEQ ID NOs: 262, 325, 366, or 381 (see Claim 10).
Therefore, Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 14, the closest prior art is Stewart (PG Pub No. US 2003/0036198 A1). Stewart is drawn towards an invention concerned with a method for cloning DNA molecules using a homologous recombination mechanism (Abstract). Stewart teaches the use of an E. coli Redβ protein (i.e., a single-stranded annealing protein) having 48.9% sequence identity with the claimed SEQ ID NO: 24 ([0014]-[0016], [0092]; see SEQ ID NO: 13 in attached sequence alignment).
However, Stewart nor the prior art teaches or suggests the use of a single-stranded annealing protein that comprises the amino acid sequence of the claimed SEQ ID NO: 24 (see Claim 14).
Therefore, Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636