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
Claims 1-17 and 19-38 are pending. Claims 18 and 39-63 are cancelled.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See line 30 on page 42.
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1 and 9 are objected to because of the following informalities: “coding for a secretion enhancing protein” is redundant because the claim also recites “secretion enhancing protein gene.” Appropriate correction is required.
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.
Claims 1-17 and 19-38 are 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 1 recites an engineered Trichoderma filamentous fungus host cell comprising an endogenous secretion enhancing protein gene under the control of a native promoter coding for a secretion enhancing protein, and an exogenously introduced secretion enhancing protein gene expressing said secretion enhancing protein under the control of said native promoter. Claim 1 is indefinite because there are at least two different reasonable interpretations for “a native promoter.” In biotechnology, native promoters are usually naturally occurring DNA sequences from a specific gene that control its expression. However, here, it is unclear whether the promoter is limited to the native promoter for the gene encoding the secretion enhancing protein. In one interpretation, the native promoter corresponds to the promoter for the endogenous secretion enhancing protein gene. In a second interpretation, the native promoter is any promoter from a native gene of the Trichoderma filamentous fungus host cell. Claim 1 is further indefinite because there are multiple reasonable interpretations for “an exogenously introduced secretion enhancing protein gene expressing said secretion enhancing protein under the control of said native promoter.” In one interpretation, the exogenously introduced secretion enhancing protein is under the control of the same native promoter as the endogenous secretion enhancing protein. In a second interpretation, the exogenously introduced secretion enhancing protein is the same protein as the endogenous secretion enhancing protein gene under the control of a native promoter, but the exogenously introduced secretion enhancing protein is not required to be under the control of the same native promoter. Finally, the placement of “coding for a secretion enhancing protein” directly after “a native promoter” also leads to multiple reasonable interpretations of this limitation. In one interpretation, the promoter codes for the secretion enhancing protein. In a second interpretation, the limitation “coding for a secretion enhancing protein” refers back to the gene.
Claims 2-17 are rejected for depending from a rejected base claim and not rectifying the source of indefiniteness discussed above.
Claim 19 also recites “an endogenous secretion enhancing protein gene under the control of a native promoter coding for a secretion enhancing protein, , and an exogenously introduced secretion enhancing protein gene expressing said secretion enhancing protein under the control of said native promoter” and is thus indefinite for the same reasons discussed above with respect to claim 1.
Claim 38 recites “a supernatant obtained using the method of claim 35, wherein the supernatant contains a substantial amount of chymosin, but not a substantial amount of the filamentous fungus. Claim 38 ultimately depends from claim 19, which is drawn to a method with a single active method step: expressing a heterologous gene in said host cell to provide said secretable polypeptide. Claim 38 is indefinite because the method of claim 35, which depends from claim 19, does not include any step directly resulting in a supernatant. Claim 35 does not recite, for example, a step of centrifugation.
Claims 20-38 are rejected for depending from a rejected base claim and not rectifying the source of indefiniteness discussed above.
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 1-17 and 19-38 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Goedegebuur et al. (US 2014/0087443 A1) as evidenced by addGene (2019 website).
“Native promoter” in claims 1 and 19 is interpreted as any promoter from a native gene of the Trichoderma filamentous fungus host cell. The exogenously introduced secretion enhancing protein is interpreted as the same protein as the endogenous secretion enhancing protein gene under the control of a native promoter, but the exogenously introduced secretion enhancing protein is not required to be under the control of the same native promoter. The limitation “coding for the secretion enhancing protein” is interpreted as referring to the gene.
Regarding claim 1, Goedegebuur teaches an engineered chymosin-producing strain of T. reesei comprising a bip1 expression vector ([0060] and [0074]). Bip1 is a secretion enhancing protein (Goedegebuur claim 1). Bip1 is also endogenous protein of T. reesei ([0068]). The bip1 expression vector is exogenously introduced ([0068]). Endogenous bip1 is necessarily under the control of a native promoter because every gene must have a promoter in order for the initiation of transcription to occur by the binding of RNA polymerase to DNA as evidenced by AddGene (paragraphs 1-2 on page 1). Thus, Goedegebuur teaches an engineered T. reesei comprising both an endogenous bip1 secretion enhancing protein under the control its own native promoter and exogenously introduced bip1 expression vector. The level of bip1 in the engineered T. reesei is enhanced relative to T. reesei without the expression vector due to the presence of additional copies of the gene in the cell for translation to bip1.
Regarding claims 1 and 19, Goedegebuur teaches a method for production of a secretable polypeptide in a filamentous fungal host comprising expressing a secretion enhancing protein in a filamentous host containing a secretable polypeptide, wherein the secretion enhancing protein is bip1 and the secretable polypeptide is a chymosin (Goedegebuur claim 1). The filamentous fungal host is T. reesei (Goedegebuur claim 4). The chymosin is bovine chymosin (Goedegebuur claim 6), so the T. reesei host cell comprises a heterologous (not native) gene. The chymosin is expressed through a promoter of the filamentous fungal host (Goedegebuur claim 7). In some embodiments, the chymosin is expressed under a cbhl promoter in T. reesei (Goedegebuur claim 8).
Regarding claims 2-4 and 20-23, Goedegebuur teaches that the sequence of bip1 is SEQ ID NO: 16 (Table 1 on page 3), which is 100% identical to the instant SEQ ID NO: 16 (OA Appendix A).
Regarding claims 5-6 and 24-25, Goedegebuur teaches that the host cell is T. reesei ([0060] and [0074]).
Regarding claims 7-9, 11, 26-27, and 29 Goedegebuur’s engineered T. reesei comprises the coding sequence for bovine chymosin (heterologous gene) and chymosin is secreted into the media ([0060], [0076]-[0077]).
Regarding claims 13-16, 27, and 31-34, Goedegebuur teaches that the chymosin is produced as a fusion protein under the control of the cbh1 promoter: the open reading frame comprising the T. reesei CBHI secretion signal sequence, the T. reesei CBHI catalytic core and linker region, and the bovine prochymosin B protein are flanked by the promoter and terminator sequence of the T. reesei cbh1 gene ([0060]).
Regarding claims 17 and 35, Goedegebuur teaches secreting chymosin as a CBHI-prochymosin fusion protein ([0080]). Goedegebuur teaches that in some embodiments the desired polypeptide may be fused to a CBHI polypeptide, or portion thereof, that is altered to minimize or eliminate catalytic activity ([0046]).
Regarding claim 36, Goedegebuur teaches the secretion level of bovine chymosin in T. reesei can be at least 50 mg/liter when the host cells grow in a fermenter
environment ([0048]).
Regarding claims 37-38, Goedegebuur teaches collecting supernatants by centrifugation of the fermentation broth and then measuring chymosin activity ([0076]). The supernatants are from the host cell cultures producing the fusion protein of chymosin and CBHI ([“CHY1-2” [0060]). Goedegebuur also teaches the supernatant does not contain a substantial amount of the expression host ([0051]).
Regarding claims 10, 12, 28, and 30, the amino acid translation of Goedegebuur’s bovine prochymosin nucleic acid SEQ ID NO: 42 ([0013]) is 100% identical to the instant SEQ ID NO: 48 (OA Appendix D).
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 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.
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Goedegebuur et al. (US 2014/0087443 A1) as evidenced by UniProt A0A2H2ZY35_TRIPA (2018 website), UniProt A0A024S895_HYPJR (2014 website), and addGene (2019 website).
This rejection applies to the embodiment in which the secretion enhancing protein is ppi1 or sil1.
Goedegebuur teaches an engineered chymosin-producing strain of T. reesei comprising a bip1 expression vector ([0060] and [0074]). Bip1 is a secretion enhancing protein (Goedegebuur claim 1). Bip1 is also endogenous protein of T. reesei ([0068]).
Additionally, Goedegebuur teaches the secretion enhancing proteins ppi1 and sil1 (Table 1 on page 3). Both ppi1 (peptidyl prolyl isomerase) and sil1 are endogenous proteins of T. reesei as evidenced by UniProt A0A2H2ZY35_TRIPA (see protein and organism names) and UniProt A0A024S895_HYPJR (see protein and organism names), See OA Appendix E and F for the alignment of the instant SEQ ID NO: 25 (ppi1) and 30 (sil1) to the UnitProt sequences. Both ppi1 and sil1 are necessarily under the control of a native promoter because each gene must have a promoter for RNA polymerase to bind to the DNA and initiate transcription as evidenced by addGene (paragraphs 1-2 on page 1).
Goedegebuur teaches SEQ ID NO: 25, which is ppi1 (Table 1 on page 3), which is identical to the instant SEQ ID NO: 25 (OA Appendix B).
Goedegebuur teaches SEQ ID NO: 30, which is sil1 (Table 1 on page 3), which is identical to the instant SEQ ID NO: 30 (OA Appendix C).
Goedegebuur teaches that the secretion enhancing protein can be used to increase the secretion of any suitable polypeptide in a host ([0040]).
However, Goedegebuur does not exemplify an engineered Trichoderma filamentous fungus host cell comprising either ppi1 or sil1 or a method for production of a secretable polypeptide in the engineered Trichoderma filamentous fungus host cell comprising either ppi1 or sil1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace bip1 in the engineered T. reesei host cell of Goedegebuur with either ppi1 or sil1 and to express the secretion enhancing proteins under the control of the promoter cbh1, which is native to T. reesei. The person of ordinary skill in the art would have been motivated to try any of the finite list of secretion enhancing proteins taught by Goedegebuur in Table 1. The person of ordinary skill in the art would have had a reasonable expectation of success in introducing genes encoding the secretion enhancing proteins ppi1 or sil1 under the control of the cbh1 promoter. The introduction of exogenous copies of ppi1 or sil1 would have increased the secretion level of the ppi1 or sil1, respectively, in the host cell.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657