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 .
Priority
This application claims benefit of priority to Provisional Applications 63/256,690 filed 10/18/2021 and 63/304,195 filed 01/28/2022. This application is also a 371 of PCT/US2022/078214 filed 10/17/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Support for the instant invention can be found in Provisional Application 63/256,690 filed 10/18/2021, thus, the effective filing date of the claimed invention for the purposes of applying prior is 10/18/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 07/17/2024 and 08/06/2026 have been acknowledged and considered.
Drawings
The Drawings filed 04/17/2024 are accepted by the Examiner.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1, 8, 12-22, 29 and 51, in the reply filed on 08/06/2026 is acknowledged. The traversal is on the grounds that the cited prior art, Campbell et al., does not anticipate the amended instant claims because Campbell et al. does not disclose the specific combination of an ompT gene deletion, a lon gene deletion and lack of a nucleotide sequence encoding ManA. This is not found persuasive because the technical feature is not a special technical feature as it does not make a contribution over the prior in view of Campbell et al. as explained in the Restriction Requirement mailed 05/06/2026. Additionally, claim 1 is not limited to the specific combination of an ompT gene deletion, a lon gene deletion and a manA deletion. While claim 1 requires an ompT gene deletion, a lon gene deletion and a manA deletion, the claim recites “comprising,” which is open language. Meaning, every gene listed in Table 1 of Campbell et al. could be deleted from the genome of the E. coli cell and it would still read on instant claim 1 as the only requirements of instant claim 1 are a modified E. coli strain with an ompT gene deletion, a lon gene deletion and a manA deletion. It remains the Examiner’s position that the technical feature is not a special technical feature as it does not make a contribution over the prior in view of Campbell et al. who disclose a reduced genome strain of E. coli MG1655 wherein the reduced genome can lack one or more genes set forth in Table 1, which includes ompT, lon and manA. Therefore, it would have been obvious to one of ordinary skill in the art to delete any number of genes listed in Table 1 of Campbell et al., including the three claimed.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s elections of species without traverse of Escherichia coli as the specific microorganism (1), ManA as the gene product not encoded by the microorganism’s genome (2), a plasmid as the location of the recombinant protein (3) and SEQ ID NO: 34 as the specific RNA polymerase (4) in the reply filed on 08/06/2026 is acknowledged.
Amendments/Claim Status
In the reply filed 08/06/2026, Applicant amended claims 1, 14 and 17-18 and canceled claims 8, 12-13 and 16. Claims 35-36 and 52-54 are withdrawn by the Examiner as they are not encompassed by the elected group. Claim 19 is withdrawn by the Examiner as it is not encompassed by the election of species (3) electing a plasmid.
Claims 1, 14-15, 17-22, 29, 35-36 and 51-54 are pending.
Claims 19, 35-36 and 52-54 are withdrawn for not being encompassed by the elected group/species.
Claims 1, 14-15, 17-18, 20-22, 29 and 51 are under examination.
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.
Claim 29 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 29 recites “the T7 RNA polymerase comprises: (a) an E350W substitution; and/or (b) a D351V substitution, relative to a wild-type T7 RNA polymerase comprising the amino acid sequence of SEQ ID NO: 34” in lines 2-6. It is unclear how ‘relative to a wild-type T7 RNA polymerase’ is intended to limit the T7 RNA polymerase. For example, it is unclear if the claim is intended to encompass any T7 RNA polymerase that specifically has an E350W and/or D351V substitution, if the T7 RNA polymerase is any T7 RNA polymerase that has a Glutamic Acid (E) to Tryptophan (W) and/or Aspartic Acid (D) to Valine (V) substitution at positions corresponding to positions 350 or 351 when in pairwise alignment with instant SEQ ID NO: 34 or if the T7 RNA polymerase is instant SEQ ID NO: 34 with E350W and/or D351V substitutions. Thus, it is unclear exactly how ‘relative to a wild-type T7 RNA polymerase’ is intended to limit the T7 RNA polymerase, rendering claim 29 indefinite.
Claim Rejections - 35 USC § 103
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.
Claims 1, 14, 17-18, 20-22 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Szpirer et al. (US 20170211118 A1, 07/27/2017) in view of Veeravalli et al. (TW 202031899 A, 09/01/2020).
Regarding claim 1, Szpirer et al. disclose a host cell for producing peptides, polypeptides and proteins of interest (See entire document, Abstract). The host cell is Escherichia coli (E. coli) and the host cell comprises inactivation of at least one of the genes tonA, galK, araB, araA, lon, ompT, rcsA, hsdR, mrr, endA and recA (Paragraph [0019]). Preferably, the genes tonA, galK, araB, araA, lon, ompT, rcsA, hsdR, mrr, endA and recA are deleted (Paragraph [0054]).
Szpirer et al. do not disclose the host cell genome does not comprise a nucleotide sequence encoding ManA.
However, Veeravalli et al. disclose host cells for producing polypeptides or proteins (See entire document, Abstract). Veeravalli et al. further disclose a specific E. coli strain lacking endogenous protease activity with a ΔmanA ΔompT genotype for producing proteins (Page 5, Paragraph 1).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have removed the manA gene in the genetically modified host cell of Szpirer et al. because this was a known and effective genotype used in E. coli for producing proteins as taught by Veeravalli et al. Thus, it would be obvious to make a genetically modified E. coli cell that does not comprise a nucleotide sequence encoding manA for producing proteins as this was a known gene deletion in E. coli for producing proteins as it amounts to combining prior art elements according to known methods to yield predictable results. See MPEP 2143(I)(A).
Regarding claim 14, as stated above regarding claim 1, Szpirer et al. disclose the genes hsdR, endA and recA are deleted (Paragraph [0054]). The hsdR gene being deleted reads on the genome’s EcoKI restriction system being inactivated.
Regarding claim 17, it is noted ‘derived from E. coli MG1655’ is interpreted to mean the parent strain is MG1655. Szpirer et al. disclose strains derived from E. coli that can be used in the invention include strains from E. coli K-12, E. coli B or E. coli W, such as MG1655 (Paragraph [0043]).
Regarding claims 18, 20-22 and 51, Szpirer et al. disclose a plasmid comprising an expression system wherein a nucleic acid sequence encoding a recombinant protein wherein the expression system comprises a T7 RNA polymerase gene (Paragraph [0015]).
Claims 1, 14-15 17-18, 20-22 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Szpirer et al. (US 20170211118 A1, 07/27/2017) in view of Veeravalli et al. (TW 202031899 A, 09/01/2020) and Campbell et al. (US 20130011874 A1, 01/10/2013) (Of Record) as evidenced by Anton et al. (PLOS One, 05/26/2015).
Regarding claim 15, as stated above regarding claim 1, Szpirer et al. disclose the genes tonA, galK, araB, araA, lon, ompT, rcsA, hsdR, mrr, endA and recA are deleted (Paragraph [0054]).
Szpirer et al. do not disclose the genotype has a Δ(hsdMS-symeE-mcrBC) ΔmanA.
However, Campbell et al. disclose reduced genome strains of E. coli MG1655 that have improved growth rate, protein expression, DNA production, DNA yield and DNA quality (See entire document, Abstract). Restriction modification system genes and other endogenous nucleases whose products may destroy foreign DNA are a type of nucleic acid sequence that can be deleted (Paragraph [0052]). Campbell et al. further disclose a specific strain with specific genes deleted, including genes b2945, b2699 and b4345-b4358 (Claim 19 of Campbell et al.). Gene b2945 is an endA gene, b2699 is a recA and genes b4345-b4358 includes genes mcrC (b4345), mcrB (b4346), yjiW (b4347), hsdS (b4348), hsdM (b4349), hsdR (b4350), mrr (b4351) (Table 1 of Campbell et al.). Thus, as the entire block of genes including mrr-hsdRMS-mcrBC) was deleted, it appears, absent evidence to the contrary, that the symE gene would also be deleted as the symE gene is part of that gene block as evidenced by Anton et al. (Table 3 of Anton et al.). Anton et al. disclose the deletion of the (mcr-hsd-mrr) block results in the deletion of mcrCB, symER, hsdSMR and mrr) (Table 3 of Anton et al.).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have deleted the entire gene block of (mrr-hsdMS-symeE-mcrBC), all being restriction modification system genes, in the genetically modified microorganism of Szpirer et al. because Campbell et al. disclose the deletion of said block for creating a genetically modified E. coli MG1655 strain with improved protein expression and Szpirer et al. is directed to a genetically modified E. coli MG1655 strain with specific gene mutations for producing protein as it amounts to combining prior art elements according to known methods to yield predictable results. See MPEP 2143(I)(A).
Claims 1, 14, 17-18, 20-22, 29 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Szpirer et al. (US 20170211118 A1, 07/27/2017) in view of Veeravalli et al. (TW 202031899 A, 09/01/2020) and Elich et al. (WO 2020185811 A1, 09/17/2020).
Regarding claim 29, see 112b above. Szpirer et al. do not disclose their T7 RNA polymerase has an E350W or D351V substitution relative to the amino acid sequence of SEQ ID NO: 34.
However, Elich et al. disclose T7 RNA polymerase to synthesize mRNA transcripts (See entire document, Abstract). Elich et al. further disclose SEQ ID NO: 14, a T7 RNA polymerase with an E350W and a D351V substitution (Page 27). SEQ ID NO: 14 (Db) of Elich et al. shares 99.6% sequence identity to instant SEQ ID NO: 34 (Qy) with the only difference being an E350W and a D351V substitution. A sequence alignment is provided below.
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856
662
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286
652
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Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the T7 RNA polymerase (SEQ ID NO: 14) of Elich et al. as the T7 RNA polymerase in the genetically modified microorganism of Szpirer et al. because Szpirer et al. do not require a specific T7 RNA polymerase and the T7 RNA polymerase disclosed by Elich et al. was a known and effective T7 RNA polymerase in the prior art as it amounts to simple substitution of one known element for another to obtain predictable results. Examples of rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B).
Conclusion
Claims 1, 14-15, 17-18, 20-22, 29 and 51 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY T WHITE whose telephone number is (571)272-0683. The examiner can normally be reached Monday - Friday 8:30 - 5:00 EST.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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