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 .
DETAILED ACTION
Applicant’s amendments filed on September 29, 2021 and remarks filed on March 12, 2025 are acknowledged. Claims 3-11 were amended. Claims 1-11 are pending and are examined on the merits herein.
This action is NON-FINAL due to new grounds of rejection not necessitated by amendment.
Information Disclosure Statement
The listing of references 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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (Biotechnology and Bioprocess Engineering 2014).
Regarding claims 1, 3, and 11, Zhang et al. teaches that to set up an efficient and cost-effective whole-cell bioconversion process for D-HPG production, a recombinant E. coli strain was constructed by co-expressing D-hydantoinase and N-carbamoylase from Agrobacterium sp (sections 2.2 and 2.3). Then a cheap medium formulation, which uses glycerol and corn steep liquor (CSL) as carbon and nitrogen sources and without addition of any foreign inducer, was developed for high level of enzyme expression (section 2.3). Zhang et al. also teaches that galactose, melibiose, and raffinose in CSL (section 3.1) were found to be capable of inducing T7 promoter [abstract].
Claims 1, 2, 4, and 10 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Rahman et al. (US 2005/0186661), as evidenced by Zhang et al. (Biotechnology and Bioprocess Engineering 2014).
Regarding claims 1, 2, 4, and 10, Rahman et al. teaches production of protease from Bacillus stearothermophilus F1 from the culture medium for optimum production [0001]. Rahman et al. teaches that the concentration of isopropyl-1-thio-D-galactopyranoside (IPTG) for induction of the bacteriocin-release-protein (BRP) system is about 40 µM [0020]. Further, the bacteriocin-release-protein (BRP) system is used to extracellularly express the recombinant F1 protease in E. coli [0091]. Rahman et al. teaches that 1 ml seed culture of B. stearothermophilus F1 in tripticase soy broth (TSB) was inoculated into 50 ml of culture medium (BSM) and incubated at 60ºC with shaking at 100 rpm for 24 hours [0044]. Further, corn steep liquor was added to BSM [0045] and enzyme production was detected with corn steep liquor [0050].
Zhang et al. is cited only to s how that corn steep liquor contains galactose, melibiose and raffinose (paragraph bridging pages 78-79).
Claims 1, 2, 5, 6, and 11 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Hardy et al. (WO 87/00863).
Regarding claims 1, 5, 6, and 11, Hardy et al. teaches a culture of strain ER 1037 was grown for 18h in L-broth and 90 ml of this culture was inoculated into 500 ml of a medium comprising corn steep liquor, 10g and D-mannitol, 20g [page 24, last paragraph bridging to page 25]. Hardy et al. also teaches that several mutants were obtained that could not use any of 2,5-DKG, 2-KDG or 2-KLG as sole carbon sources. One such mutant was transformed with plasmid pCBR13 to form strain ER1037, which was then tested for its ability to convert glucose to 2-KLG [page 24, first paragraph]. Figure 5(b) shows pcBR13 with a Lac promoter.
Regarding claim 2, Hardy et al. teaches that extracts of E.coli treated with the lac inducer isopropyl β-D-thiogalactopyranoside (IPTG) contained about five times more enzyme than extracts from uninduced cells [page 17, last paragraph]. Therefore, the lac promoter is inducible by IPTG.
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 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Hardy et al. (WO 87/00863) as applied to claims 1, 2, 5, 6, and 11 above, and further in view of Nakase (US 9,926,348).
Regarding claims 7-9, the teachings of Hardy et al. are discussed above.
However, Hardy et al. does not teach wherein the recombinant protein is a structural protein or spider silk fibroin.
Nakase teaches a method for producing a fibroin-like protein by culturing Escherichia coli having a gene encoding the fibroin-like protein in a medium, inducing expression of the gene encoding the fibroin-like protein, and collecting the fibroin-like protein, wherein the accumulation of an organic acid at the time of inducing the expression is reduced [abstract]. Further, the expression of a fibroin-like protein can be induced by adding, to the medium, for example, isopropyl-β-D-thiogalactopyranoside (IPTG) [column 18, third full paragraph]. Nakase also teaches that the term “fibroin-like protein” refers to fibroin and a fibrous protein having a structure similar to that of fibroin [column 4, last paragraph]. In addition, the term “fibroin” refers to a fibrous protein that is a component of spider's thread or silkworm's thread [column 5, first paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the production method of Hardy et al. wherein the recombinant protein is a structural protein or spider silk fibroin because Hardy et al. taught a culture of strain ER 1037 was grown for 18h in L-broth and 90 ml of this culture was inoculated into 500 ml of a medium comprising corn steep liquor, 10g and D-mannitol, 20g [page 24, last paragraph bridging to page 25]. Hardy et al. also taught that several mutants were obtained that could not use any of 2,5-DKG, 2-KDG or 2-KLG as sole carbon sources. One such mutant was transformed with plasmid pCBR13 to form strain ER1037, which was then tested for its ability to convert glucose to 2-KLG [page 24, first paragraph]. Figure 5(b) shows pcBR13 with a Lac promoter and Hardy et al. taught that the lac promoter is inducible by IPTG. Nakase taught a method for producing a fibroin-like protein by culturing Escherichia coli having a gene encoding the fibroin-like protein in a medium, inducing expression of the gene encoding the fibroin-like protein, and collecting the fibroin-like protein, wherein the accumulation of an organic acid at the time of inducing the expression is reduced. Nakase also taught that the term “fibroin-like protein” refers to fibroin and a fibrous protein having a structure similar to that of fibroin and the term “fibroin” refers to a fibrous protein that is a component of spider's thread or silkworm's thread. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements according to known methods to yield predictable results.
Response to Arguments
Applicant's arguments filed March 12, 2025 have been fully considered but they are not persuasive.
Applicant asserts the following:
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Applicant points to Tables 4, 5, and 8 of the instant specification indicating that the combination of galactose and at least two of mannitol, raffinose, and melibiose provides for a significant increase in protein production. Applicant asserts that Maria merely describes a large number of various carbon sources that could be used. Applicant further asserts that Maria does not identify any of galactose, raffinose, mannitol, and melibiose, or a combination of at least three of the sugars, as particularly advantageous and instead identifies glycerol as a preferred carbon source.
These arguments are not found persuasive. Zhang et al. taught that to set up an efficient and cost-effective whole-cell bioconversion process for D-HPG production, a recombinant E. coli strain was constructed by co-expressing D-hydantoinase and N-carbamoylase from Agrobacterium sp. Then a cheap medium formulation, which uses glycerol and corn steep liquor (CSL) as carbon and nitrogen sources and without addition of any foreign inducer, was developed for high level of enzyme expression. Zhang et al. also taught that galactose, melibiose, and raffinose in CSL were found to be capable of inducing T7 promoter. Therefore, based on the teachings of the prior art, it is not surprising or unexpected that Applicant observed an increase in protein production when using a medium containing galactose and at least two selected from the group consisting of mannitol, raffinose, and melibiose. In addition, in an assertion of unexpected results, one must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). See MPEP 716.02(e). With respect to Applicant’s
arguments in reference to the Maria reference, Maria teaches that advantageous carbon sources include galactose, raffinose, and mannitol. Although Maria does list various other carbon sources and teaches that glycerol is preferred, Maria does not teach away nor disparage the use of galactose, raffinose, and mannitol.
Conclusion
No claims are allowed.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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