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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/11/2026 has been entered.
Status of the Claims
Claims 38-41 have been added. Claims 1-2, 4-11, 13, 16-17, 25, and 28-41 are pending and examined herein.
Priority
This application, filed 07/15/2022, is a 371 of PCT/US2021/013734, filed 01/15/2021, which claims benefit of 62/961, 392, filed 01/15/2020. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 01/15/2020.
Withdrawn Objections/Rejections
The rejection of claims 1-2, 4-11, 13, 16-17, 25, and 28-37 under 35 U.S.C. 102 has been withdrawn in response to Applicant’s amendments.
The rejection of claim 2 under 35 U.S.C. 112(b) and (d) has been withdrawn in response to Applicant’s amendment.
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, 4-11, 13, and 16-41 are rejected under 35 U.S.C. 103 as being unpatentable over US 10,093,920 B2, “PROTEIN DISPLAY” (patent dated 10/09/2018, referred to herein as Beasley) in view of US 2018/0282405 A1, “CYTOPLASMIC EXPRESSION SYSTEM” (published 10/04/2018, referred to herein as McClain).
Regarding claims 1, 4, and 5, Beasley teaches a method of selecting host cells (col. 2, lines 1-13) having genetic diversity comprising a plurality of genetic variants (col. 17, lines 46-48) wherein host cells comprise a polynucleotide sequence encoding a gene product of interest (col. 2, lines 1-6). Beasley teaches culturing the host cells (col. 2, lines 1-6), then labelling the cells with a detectable moiety, “SNAP ligand” (col. 31, lines 43-45) based on expression level (col. 31, lines 45-48) or a predetermined activity of the gene product of interest (col. 17, lines 32-35). Beasley teaches that the labeling and detection of the label occurs in the cytoplasm (col. 18, lines 33-37). Beasley teaches that the host cells are E. coli (col. 5, lines 48-49).
Regarding claim 2, Beasley teaches that the genetic diversity is polynucleotide sequence variation of one or more expression constructs (col. 17, lines 46-56).
Regarding claim 6, Beasley teaches that the predetermined property of the expressing host cells comprises proper folding of the gene product of interest (col. 18, lines 35-37).
Regarding claim 7, Beasley teaches measuring relative expression level of the gene product of interest (col. 31, lines 45-48).
Regarding claim 8, Beasley teaches selecting with FACS (col. 19, lines 50-56).
Regarding claims 9 and 10, Beasley teaches selecting clones with a desired activity (para. 17, lines 16-20). However, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to perform routine optimization of the size of the selected population in the claimed invention to make and use the claimed invention. As noted in In re Aller, 105 USPQ 233 at 235, more particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that arriving at the claimed percentage isolated was anything other than routine, that the properties of the percentage isolated from the optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Optimization of parameters is a routine practice that would be obvious for the artisan to employ. See MPEP § 2144.05. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of Yim et al., “Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS)” (IDS dated 03/20/2023, previously referred to in the office action dated 07/01/2025), which teaches isolation of populations of 0.28%, 1.87%, and 5.53% (Table 1, 15* round) in order to capture a sufficient number of cells in the subpopulation for further analysis during a bacterial library screening and selection assay.
Regarding claim 11, Beasley teaches that the gene product of interest is an antibody, which is a polypeptide lacking a signal peptide (col. 4, lines 40-43).
Regarding claim 13, Beasley teaches that the detectable moiety is a fluorescent polypeptide, i.e. the SNAP ligand (col. 31, lines 41-45).
Regarding claim 16, Beasley teaches that the polynucleotide sequence encoding the gene product of interest is an expression vector (col. 11, lines 65-67).
Regarding claim 17, Beasley teaches that the expression vector is an extrachromosomal expression vector (col. 12, lines 2-3).
Regarding claim 25, Beasley teaches that the host cells are prokaryotic cells (col. 12, lines 55-62).
Regarding claims 28-31, Beasley teaches recovering polynucleotides from the subset of labeled cells, sequencing the polynucleotides, then constructing a library based on the DNA sequence information (col. 20, lines 16-24).
Regarding claim 32-37, Beasley teaches transforming parental host cells with the library of selected expression vectors from recovered polynucleotides (col. 32, lines 6-10), culturing the cells and expressing the gene product of interest (col. 32, lines 11-13), then determining the level of expression of the gene product of interest with gel electrophoresis (col. 32, lines 13-18).
Regarding claims 38-41, Beasley teaches that an artisan will be able to readily determine bacterial strains suitable for expressing polypeptides (col. 12, lines 55-57).
However, Beasley does not teach a strain genetically modified to have an oxidizing cytoplasm and grow at high cell density in fermentation culture (claims 1, 4, and 5). Beasley does not teach host cells with altered gene function to affect the redox environment of the cytoplasm (claim 38) by altering a gene listed in claim 39. Beasley does not teach host cells with a reduced level of gene function of a protein that metabolizes an inducible promoter (claim 40) by altering a gene listed in claim 41.
McClain teaches a method of using host cells capable of growth at high cell density in fermentation and have oxidizing cell cytoplasm (para. 0068, lines 1-7). McClain teaches that the host cells are used for producing antibodies and antibody fragments (para. 0107, lines 6-7), including single-chain antibodies (para. 0125, lines 10-11). McClain teaches that a strain with these characteristics, EB0001, has a mutation in trxB and araBAD (para. 0141, lines 1-4 and para. 0143, lines 1-5). McClain teaches that using these strains enables efficient production of soluble and active proteins, which are properly folded, including having correctly formed disulfide bonds, in a manner that is capable of scaling up to commercial production levels (para. 0008, lines 18-23).
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 method taught by Beasley by using the host cells taught by McClain. An artisan would have been motivated to use this strain because, as taught by McClain, it enables efficient production of soluble and active proteins, including antibodies and antibody fragments. An artisan would have a reasonable expectation of success in making this change because the strain taught by McClain is taught to be used for antibody production, as in the method taught by Beasley.
Response to Arguments
Applicant’s arguments with respect to claims 1-2, 4-11, 13, 16-17, 25, and 28-37 under 35 U.S.C. 102 have been considered but are moot because the rejection under 35 U.S.C. 102 has been withdrawn in response to Applicant’s amendment.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 May 4, 2026
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