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 .
Status of Claims
Claims 1 and 3-16 are currently pending and under examination on the merits in the instant application.
Information Disclosure Statement
The listing of references in the specification, see page 36, 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.
The information disclosure statement (IDS) submitted on May 14, 2024 has been considered by the examiner. Note that foreign document citation number 1 is not considered because the information provided in the IDS is incorrect and furthermore, the legible copy corresponding to the WO document number is completely irrelevant to the field of the invention. Furthermore, the WO document’s disclosure is in non-English language.
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 and 3-16 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.
Claims 1 and 3-16 as broadly written read on any B. licheniformis cell transformed with a cassette comprising the upstream prsA promoter comprising from at least 50% to at least 85% identity to SEQ ID NO:29 operably linked to the prsA gene comprising from at least 50% to at least 80% identity to SEQ ID NO:30 and as evidenced by the definition of the prsA gene and the prsA promoter as disclosed in paragraphs 0141-0142 and as claimed in claims 3-4, 8-9, and 14-15.
The instant specification at best describes a recombinant B. licheniformis strain, “ZM1319”, comprising deletions of serA1, lysA, rghR2, and dltA transformed with a construct comprising the upstream homology arm for the amyL locus sequence (SEQ ID NO:23) operably linked to SEQ ID NO:29 operably linked to SEQ ID NO:30 operably linked to the terminator sequence of SEQ ID NO:31 operably linked to the downstream homology arm for the amyL locus sequence of SEQ ID NO:32. See paragraphs 0194-0198. This specific single bacteria species comprising specific genomic deletions is not a representative number of species within the genus of genomically different “recombinant Bacillus licheniformis cell”, and similarly, the single specific construct comprising SEQ ID NOs:23 and 29-32 from the 5’ end to the 3’ end orientation is not a representative number of species of the claimed “cassette” as interpreted above.
Now, it is noted that claims 6-7 and 12-13 require that the recombinant cell should produce an increased amount of the POI relative to a control Bacillus cell. It is noted that the instant specification at best describes two specific strains, ZM1351 and WAAA197, which appear to have two cassettes of amylase 1 or 2 (SEQ ID NO:36 or SEQ ID NO:42) are integrated into the serA and lysA loci into the “ZM1319” transformed with the construct comprising SEQ ID NOs:23 and 29-32, wherein the two strains produce amylase 1 or 2. The two specific B. licheniformis strains further modified to express SEQ ID NO:36 or SEQ ID NO:42 in the serA and lysA loci, thereby producing amylase 1 or amylase 2, respectively, are not a representative number of recombinant cell species within the claimed genus, nor are the two specific enzymes, amylase 1 and amylase 2, representative of the entire genus of “protein of interest (POI)” or the subgenus of “enzyme” as broadly claimed in the instant case.
Most importantly, the two recombinant cell strains, ZM1351 and WAAA197, which are not whatsoever representative of the entire genus of the instantly claimed B. licheniformis cell, do not show the required “increased amount of the POI” compared to the control as required by the claims as evidenced by the data provided in Tables 6 and 7 reproduced below.
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282
824
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274
820
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As clearly shown above, the two bacteria cell strains overexpressing prsA at the amyL locus provided a meager fraction (0.04 and 0.07) higher than the claimed control cell. There is no disclosure as to how many replicate experiments are performed, nor is there any disclosure that the 1.04 or 1.07 value compared to 1.00 is an art-accepted statistically significant or scientifically meaningful “increase” when there is no disclosure of margin of error in measurements.
Furthermore, even if the numerical values in Tables 6-7 should be deemed a scientifically acceptable “increase” compared to the control, the “ZM1351” strain compared to “LDN665” and “WAAA197” strain compared to “WAAA57” are not representative of the entire genus of claims 6-7 and 12-13.
In view of the foregoing, it is concluded that the instant specification fails to adequately describe the claimed subject matter/genus in the manner to reasonably convey that the instant co-inventors had possession of the claimed subject matter/genus as of the filing date sought in the instant case.
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.
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, 4-8, 10-14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. (US 2020/0318086 A1) in view of Ganuza et al. (US 2022/0112478 A1) and Helianti et al. (HAYATI Journal of Biosciences, 2016, 23:125-131).
Andersen discloses a genetically modified B. licheniformis cell having “amyL gene integrated at the amyL, xyl and gnt loci and one additional prsA gene inserted at the mprL locus”, wherein the “additional prsA gene” is found to “lead to over-expression of the PrsA chaperone from B. licheniformis”, wherein “Over-expression of the PrsA chaperone is described in literature to further increase alpha-amylase productivity.” See paragraphs 0281 and 0305.
Andersen teaches that the host cells are cultivated by fermentation. See paragraph 0244.
Andersen does not teach the prsA gene integrated at the amyL locus via a construct comprising a prsA promoter operably linked to the prsA gene.
Ganuza discloses the “DNA sequence of B. licheniformis PrsA” identified as SEQ ID NO:7, which is 100% identical to SEQ ID NO:30 claimed in the instant case. See paragraph 0051.
Ganuza teaches that B. subtilis, which is modified to co-express B. licheniformis PrsA from the pel locus and B. licheniformis amyL inserted into the amyE locus, results in an increased level of (about 1.40) alpha-amylase secretion compared to control, wherein “there is a continuous need for improving production yield and thereby process profitability in the production of enzymes” by a host cell using “fermentation”. See paragraphs 0003, 0157, 0162-0163, and 0208-0209; Table 2.
Helianti teaches that a recombinant Bacillus cell comprising a construct comprising “the endoxylanase gene and its promoter” produces endoxylanase with “higher endoxylanse activity” compared to a non-recombinant cell. See pages 128-129.
It would have been obvious to one of ordinary skill in the art before the effective filing date to try integrating the prsA gene at the amyL locus in place of the mprL locus of Andersen’s genetically modified B. licheniformis cell with a reasonable expectation of success because the amyL locus was one of art-recognized B. licheniformis loci into which a gene can be integrated, and because Andersen’s genetically modified B. licheniformis cell already comprises two other additional loci (xyl and gnt loci) that are integrated with the amyL gene, which would be expected to produce alpha-amylase at a higher level when the prsA gene is over-expressed in the cell in view of the teachings of Andersen and Ganuza, wherein genetically modifying a Bacillus host cell for the purpose of improving enzyme production yield was an art-recognized need and goal as evidenced by Andersen and Ganuza. It would also have been obvious to one of ordinary skill in the art to utilize a construct comprising a prsA gene promoter operably linked to the art-recognized prsA gene sequence such as Ganuza’s SEQ ID NO:7 when integrating the prsA gene at the amyL locus because use of an endogenous gene promoter operably linked to the gene of interest for expressing the gene of interest at a higher level in a recombinant Bacillus cell was an art-recognized technology/methodology available and known in the relevant art as evidenced by Helianti.
It is noted that the “wherein” clause limitation relating to “the control cell” recited claims 6-7 and 12-13 does not structurally alter the instantly claimed modified cell thus the aforemenitoned limitation recited in the instant claims would inherently provide an increased level of production of an enzyme compared to the control cell, absent objective evidence to the contrary.
In view of the foregoing, claims 1, 4-8, 10-14, and 16 taken as a whole would have been prima facie obvious before the effective filing date.
Claims 1 and 3-16 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. (US 2020/0318086 A1) in view of Doig et al. (WO 2021/146411 A1, applicant’s citation).
Andersen discloses a genetically modified B. licheniformis cell having “amyL gene integrated at the amyL, xyl and gnt loci and one additional prsA gene inserted at the mprL locus”, wherein the “additional prsA gene” is found to “lead to over-expression of the PrsA chaperone from B. licheniformis”, wherein “Over-expression of the PrsA chaperone is described in literature to further increase alpha-amylase productivity.” See paragraphs 0281 and 0305.
Andersen teaches that the host cells are cultivated by fermentation. See paragraph 0244.
Andersen does not teach the prsA gene integrated at the amyL locus via a construct comprising a prsA promoter operably linked to the prsA gene.
Doig teaches making a genetically modified B. licheniformis cell comprising overexpressing PrsA by integrating a construct comprising a PrsA promoter comprising SEQ ID NO:100 operably linked to a PrsA ORF comprising SEQ ID NO:101 into the genome of the cell, wherein the modified cell produces an increased amount of amylase. See paragraph 0006.
It is noted that SEQ ID NO:100 and SEQ ID NO:101 of Doig are 100% identical to SEQ ID NO:29 and SEQ ID NO:30 claimed in the instant case, respectively.
It would have been obvious to one of ordinary skill in the art before the effective filing date to try integrating the prsA gene at the amyL locus in place of the mprL locus of Andersen’s genetically modified B. licheniformis cell with a reasonable expectation of success because the amyL locus was one of art-recognized B. licheniformis loci into which a gene can be integrated, and because Andersen’s genetically modified B. licheniformis cell already comprises two other additional loci (xyl and gnt loci) that are integrated with the amyL gene, which would be expected to produce alpha-amylase at a higher level when the prsA gene is over-expressed in the cell in view of the teachings of Andersen and Doig. It would also have been obvious to one of ordinary skill in the art to utilize Doig’s construct comprising SEQ ID NO:100 operably linked to SEQ ID NO:101 when integrating the prsA gene at the amyL locus because Doig’s construct was known to be useful in overexpressing the prsA gene in B. licheniformis with a resultant effect of an increased production level of amylase.
It is noted that the “wherein” clause limitation relating to “the control cell” recited claims 6-7 and 12-13 does not structurally alter the instantly claimed modified cell thus the aforemenitoned limitation recited in the instant claims would inherently provide an increased level of production of an enzyme compared to the control cell, absent objective evidence to the contrary.
Accordingly, claims 1 and 3-16 taken as a whole would have been prima facie obvious before the effective filing date.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 3-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,534,716 B2 in view of Anderson et al. (US 2020/0318086 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘716 patent claims drawn to a modified B. licheniformis cell comprising the B. licheniformis prsA promoter comprising SEQ ID NO:100 operably linked to the B. licheniformis prsA ORF comprising SEQ ID NO:101, wherein the modified cell produces an increased amount of a secreted enzyme and a method for producing the modified cell, wherein SEQ ID NO:100 and SEQ ID NO:101 of the ‘716 patent claims are 100% identical to SEQ ID NO:29 and SEQ ID NO:30 claimed in the instant case, respectively. It is noted that the scope of “POI” that “is a secreted protein”, which is a “secreted enzyme” as claimed in the ‘716 patent claims is defined to read on “amylase” as evidenced by the ‘716 patent specification. See column 9, lines 24-26.
Regarding the “amyL locus” of a B. licheniformis cell into which the prsA gene cassette integrated as claimed in the instant claims, it would have been obvious to choose the amyL locus as the locus of the B. licheniformis cell of the ‘716 claims to integrate the nucleic acid comprising SEQ ID NO:100 operably linked to SEQ ID NO:101 of the ‘716 patent claims because the amyL locus was one of art-recognized B. licheniformis loci into which a gene can be integrated as evidenced by Andersen.
It is noted that the “wherein” clause relating to “the control cell” recited in the instant claims does not structurally alter the already patented modified cell and furthermore, such limitation recited in the instant claims would be inherent in the modified cell that is rendered obvious in the instant rejection, absent objective evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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