DETAILED ACTION
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 with traverse of claims 1-13 and 15 in the reply filed on 6/08/2026 is acknowledged. The traversal is on the ground(s) that the methods of claims 14 and 16 require the composition of claim 1. This is not found persuasive because none of Applicant’s arguments touch on the specific reasoning that the three groups of inventions are independent and/or distinct from each other; namely, the elected composition of Invention I can be used in materially different processes of Inventions I and III and that method Inventions II and III have a materially different design from each other.
The requirement is still deemed proper and is therefore made FINAL.
Claims 14 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/08/2026.
Claims 1-13 and 15 are under consideration on the merits.
Claim Objections
Claim 1 objected to because of the following informalities: “proteinthat” is likely a typo for “protein that”. Appropriate correction is 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, 3, 8, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hutchings et al. (WO 2011/135370; provided in the IDS dated 4/10/2024).
Hutchings teaches a recombinant Staphylococcus sp. bacterium heterologously expressing the tatABC genes (claims 1 and 6) and expressing an additional heterologous protein (claim 9), which is capable of secreting the heterologous protein (claims 10 and 16), anticipating claims 1, 3, 8, and 9.
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, 3, 5-9, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Hutchings et al. (WO 2011/135370; provided in the IDS dated 4/10/2024) in view of Date et al. (US 8,597,907; Reference A).
The teachings of Hutchings are relied upon as set forth above in rejecting claims 1, 3, 8, and 9 as anticipating under 35 U.S.C. § 102. Claim 10 of Hutchings as cited above reads in-part on claim 5. Hutchings further teaches fusing Tat signal peptides to the 5’ end of the protein coding sequence (the 1st paragraph on page 22), reading in-part on claims 5 and 6. Hutchings further teaches a nucleic acid encoding for Streptomyces coelicolor tatA, tatB, and tatC (Figure 3 and page 7, the paragraph starting “FIGURE 3….”), reading on claim 6. Hutchings teaches a vector comprising tatABC and said vector introduced into a host bacterium (claim 15), reading on claim 13.
Regarding claim 5, Hutchings does not teach a heterologous protein in a 5’ to 3’ direction. Regarding claim 7, Hutchings does not teach the heterologous Tat protein is derived from Corynebacterium sp. Regarding claim 15, Hutchings does not teach water as a species of pharmaceutical acceptable carrier of diluent.
Date teaches methods of producing secreted heterologous proteins in coryneform bacteria, the coryneform bacteria comprising a nucleic acid sequence encoding a Tat system-dependent signal peptide region and a nucleic acid sequence encoding a heterologous protein in the direction from 5′-end to 3′-end (Abstract), reading on claim 5. Date teaches Tat protein derived from Corynebacterium glutamicum (Example 6), reading on claim 7. Date teaches culturing the gene-introduced transformant bacteria in a nitrogen source comprising nitrogen water to produce secreted heterologous protein (Column 11, lines 29-48), reading on claim 15.
Regarding claim 5, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further modify the bacterium of Hutchings to express the heterologous protein in the 5’ to 3’ direction according to Date. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Hutchings and Date are directed towards recombinant bacterium expressing heterologous proteins (of interest) and Tat. The skilled artisan would have been motivated to do so because modification would predictably yield a recombinant bacterium recombinantly expressing a secreted heterologous protein of interest; see M.P.E.P. § 2143(I)(A).
Regarding claim 7, a person of ordinary skill in the art would have had a reasonable expectation of success in substituting the Tat protein derived from Corynebacterium glutamicum for the Tat protein derived from Streptomyces coelicolor because the Tat proteins derived from Corynebacterium glutamicum and Streptomyces coelicolor are both explicitly taught as being useful for THE SAME PURPOSE as heterologously expressed in bacterium to drive secretion and production of recombinant heterologous protein(s) of interest. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “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.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Regarding claim 15, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the ammonia water of Date to the heterologous protein production methods of Hutchings. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Hutchings and Date are directed towards recombinant bacterium expressing heterologous proteins (of interest) and Tat. The skilled artisan would have been motivated to do so because Date teaches that ammonia water is a predictably advantageous source of nitrogen in the heterologous protein production methods of Hutchings.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 2, 4, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Hutchings and Date as applied to claims 1 and 5 above, and further in view of Hyde et al. (US 2011/0184387; Reference B).
The teachings of Hutchings and Date are relied upon as set forth above. Date further teaches Corynebacterium glutamicum deficient in TatC (Example 4), reading in-part on claim 2.
Regarding claim 2, Date does not necessarily provide a motivation to modify Hutchings with a bacterium lacking an endogenous Tat secretion system apparatus. Regarding claim 4, Hutchings and Date do not teach Lactococcus lactis, Bifidobacterium longum, or Lactobacillus reuteri. Regarding claim 11, Hutchings and Date do not teach any promoter derived/obtained from Lactococcus sp. or Lactobacillus sp.
Hyde teaches auxotrophic microorganisms comprising a pH inducible promoter coupled to at least one heterologous generic element encoding for at least on therapeutic agent ([0007]) and for administration to subjects (Example 1). Hyde teaches Lactococcus lactis, Bifidobacterium longum, and Lactobacillus reuteri as suitable species of microorganisms ([0112]), reading on claim 4. Hyde teaches that the microorganism is inducible to produce the at least one agent by at least one twin-arginine translocation system (i.e. Tat; [0153]), reading on claims 2, 4, and 11. Hyde teaches acid-inducible promoters obtained from Lactococcus sp. and Lactobacillus sp. (i.e. P3, F1F0-ATPase promoter, gadC, gadD, or glutamate decarboxylase promoter; [0102]-[0103]), reading on claims 2 and 11.
Regarding claim 2 and 11, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further delete endogenous TatC and add a pH inducible promoter to the recombinant microorganisms of Hutchings in view of Date and Hyde. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Hutchings and Date are directed towards recombinant bacterium expressing heterologous proteins (of interest) and Tat, and because Hutchings and Hyde teaches producing an agent/protein of interest through Tat. The skilled artisan would have been motivated to do so because the combination deleting endogenous TatC and a pH inducible promoter coupled the recombinant Tat of Hutchings would predicably improve Hutchings recombinant microorganisms by allowing a person of ordinary skill in the art to more precisely control when the recombinant Tat system of Hutchings is “on” such as to produce a secreted and heterologous protein of interest.
Regarding claim 4, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the Staphylococcus sp. of Hutchings with the Lactococcus lactis, Bifidobacterium longum, or Lactobacillus reuteri of Hyde. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Hutchings and Hyde teaches producing an agent/protein of interest through Tat. The skilled artisan would have been motivated to do so because Hyde teaches Lactococcus lactis, Bifidobacterium longum, and Lactobacillus reuteri as exemplary species of and predictably advantageous auxotrophic microorganisms recombinantly expressing therapeutic agents for downstream treatment of subjects, and so the substitution would predictably improve upon Hutchings.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Hutchings and Date as applied to claims 1 and 5 above, and further in view of Van Dijl et al. (EP 0444759; Reference N).
The teachings of Hutchings and Date are relied upon as set forth above. Hutchings further teaches recombinant gram-positive bacterium expressing heterologous tatABC (claim 4), reading in-part on claim 12.
Regarding claim 12, Hutchings and Date do not teach a nucleic acid encoding for a signal peptidase.
Van Dijl teaches overexpression of the signal peptidase in a suitable host species, which leads to an enhanced rate of protein processing. (Abstract), reading on claim 12. Van Dijl teaches that there is a need in this art to improve secretion of heterologous protein secretion by gram positive microorganisms to eliminate the need for elaborate purification methods for the (intracellular) heterologous protein (page 2, lines 11-23), reading on claim 12. Van Dijl teaches that overexpression of the E. coli lep gene (i.e. signal peptidase I or SPase I) in a suitable plasmid in E. coli improves the production rate of chimeric β-lactamases (Example VII), reading on claim 12.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to ad the nucleic acid encoding for E. coli lep gene (i.e. signal peptidase I or SPase I) of Van Dijl to the recombinant microorganism of Hutchings. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Hutchings and Van Dijl are directed towards recombinant gram-positive bacterium which heterologously express and secrete a protein of interest. The skilled artisan would have been motivated to do so because Van Dijl teaches that there is a need in this art to improve secretion of heterologous protein secretion by gram positive microorganisms to eliminate the need for elaborate purification methods and that the addition of a nucleic acid encoding for the E. coli Iep gene would solve this problem by improving the production rate of heterologous protein(s) of interest and would thus improve Hutchings gram-positive bacterium.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 1, 3, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hutchings et al. (WO 2011/135370; provided in the IDS dated 4/10/2024) in view of Matsuda et al. (US 10,387,798; Reference C).
The teachings of Hutchings are relied upon as set forth above in rejecting claims 1, 3, 8, and 9 as anticipating under 35 U.S.C. § 102.
Regarding claim 10, Hutchings does not teach a heterologous protein comprising FGF1 and/or FGF2.
Matsuda teaches a coryneform bacterium is described that has been
modified to have a specific mutation so as to harbor a phoS gene, and when cultured, is able to produce a heterologous protein by secretory production (Abstract). Matsuda teaches the bacterium recombinant genes encoding for tatA, tatB, tatC, or tatE as part of the Tat secretory system (Column 2, line 58 through Column 3, line 7 and Column 4, lines 5-9), reading on claim 10. Matsuda teaches heterologous protein(s) comprising growth factors of interest such as acidic fibroblast growth factor (aFGF or FGF1) or basic fibroblast growth factor (bFGF or FGF2) (Column 36, lines 32-45), reading on claim 10
It would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the generic heterologous protein of Hutchings with FGF1 and/or FGF2 of Matsuda in Hutchings recombinant microorganism. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Hutchings and Matsuda are directed towards recombinant bacterium expressing heterologous proteins (of interest) and Tat. The skilled artisan would have been motivated to do so because Matsuda teaches FGF1 and/or FGF2 as exemplary species of proteins and growth factors of interest, and so the substitution would predictably improve up Hutchings bacterium to then produce FGF1 and/or FGF2; see M.P.E.P. § 2143(I)(B).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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