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 .
Claim Status
Claims 1-19 and 21-22 are pending following the Reply filed 12/10/2025. Claims 9-19 and 21-22 are withdrawn. Claims 1-8 are presently considered.
Election/Restrictions
Applicant’s election of Group I (claims 1-8) in the reply filed on 12/10/2025 is acknowledged. Applicant did not expressly state in the reply whether the election was with or without traverse. Because applicant did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 9-19 and 21-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/10/2025.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The present application claims status as a 371 (National Stage) of PCT/EP2022/052877 filed on 02/07/2022. Applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) of application EP21305165.9 filed on 02/08/2021 is acknowledged. The present application and all claims are being examined with the earliest effective filing date of 02/08/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed 08/01/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: the phrase, “having at 90% of identity” in line 2 appears to contain a typographical error and is understood to mean “having at least 90% of identity” (see, e.g., specification at pg. 2, lines 29-31). Please amend the claim accordingly. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: the claim contains the first recitation of the term “E. coli” in its abbreviated form, while the full, unabbreviated form is introduced later in the claims (see claim 4). Because this is the first recitation of the term, it should be presented in its unabbreviated form, i.e., “Escherichia coli (E. coli)”. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: in light of the correction to claim 2 (discussed above), “Escherichia coli (E. coli)” in line 2 can be amended to recite “E. coli”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: for clarity, please amend the phrase, “consisting of p14, p10, or p9 promoter” in line 2 to recite “consisting of a p14, p10, or p9 promoter”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: it is understood from the recitation of “respectively” that each SEQ ID NO corresponds to a single selected promoter (“p14, p10, or p9”). For clarity, please amend the phrase, “SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8” in line 3 to recite “SEQ ID NO:6, SEQ ID NO:7 or SEQ ID NO:8”. Appropriate correction is required.
Claim Interpretation
Applicant is advised that the recitation of “comprising a nucleic acid sequence set forth in SEQ ID NO: X” is normally interpreted as comprising a sequence of two or more nucleotides contained within the recited SEQ ID NO, whereas the recitation of “comprising the nucleic acid sequence set forth in SEQ ID NO: X” is normally interpreted as comprising the full-length of the recited SEQ ID NO.
In the instant case, claim 8 recites a p14, p10, or p9 promoter “having respectively a nucleic acid sequence as set forth in SEQ ID NO: 6, SEQ ID NO: 7, [or] SEQ ID NO: 8”. It is interpreted that the transitional phrase, “having”, is intended to carry the same meaning as “comprising” in light of the instant specification (see pg. 83, para. [0221]).
Hence, the phrase, “having respectively a nucleic acid sequence as set forth in” recited in claim 8 is given its broadest reasonable interpretation of comprising any sequence of two or more nucleotides contained within the respective SEQ ID NO.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1, 3 and 6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Based upon an analysis with respect to the claims as a whole, these claims do not recite something significantly different than the judicial exception. The rationale for this determination is explained below and is in keeping with the latest guidance regarding analysis of judicially excepted subject matter:
Step 1: It must first be determined if the claims are directed to a statutory category and, if so, proceed to step 2A, Prong One. The claims are directed to a fusion protein and fall within the statutory category of a composition of matter.
Step 2A, Prong One: Prong One requires the Examiner to evaluate whether the claims recite a judicial exception and, if so, proceed to Prong Two.
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
The Markedly Different Characteristics Analysis
The first step in the analysis is to select the appropriate counterpart to the nature-based product. When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart. See MPEP § 2106.04(c)(II)(A).
The second step in the analysis is to identify appropriate characteristics to compare. Appropriate characteristics must be possessed by the claimed product, because it is the claim that must define the invention to be patented. Cf. Roslin, 750 F.3d at 1338, 110 USPQ2d at 1673. See MPEP § 2106.04(c)(II)(B).
The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. See MPEP § 2106.04(c)(II)(C).
Analysis:
Independent claim 1 recites a fusion protein wherein a VtrA polypeptide having an amino acid sequence having at least 90% of identity with the amino acid sequence that ranges from the amino acid residue at position 134 to the amino acid residue at position 253 in SEQ ID NO: 1 is fused to a DNA binding domain. Here, the scope of the claim includes VtrA polypeptides comprising the full length of SEQ ID NO: 1.
Rivera-Cancel, et al. (cited in the IDS filed 08/01/2023) teach that VtrA derived from Vibrio parahaemolyticus contains an N-terminal DNA-binding domain of the OmpR family that is attached to the inner membrane by a single transmembrane helix, and a C-terminal periplasmic domain (see pg. 367, col. 1, para. 2). Rivera-Cancel, et al. teach that V. parahaemolyticus was demonstrated to sense bile salts via the C-terminal periplasmic domain of VtrA (see pg. 370, col. 2, para. 2). In view of the instant specification, the fusion protein of the claimed invention is disclosed as having the same bile acid sensing characteristics and associated structures as the VtrA taught by Rivera-Cancel, et al. (see instant specification at pg. 4, lines 11-27). In view of UniProt Q87GI4_VIBPA (cited on Form 892), the “OmpR” type domain (DNA-binding domain) in VtrA ranges from amino acid residues 3 to 103, and the helical transmembrane domain ranges from residues 134 to 253 (see pg. 2, lines 6-14). The full-length UniProt sequence is also identical to SEQ ID NO: 1.
Thus, in view of the prior art, a “fusion protein” comprising the full-length of the UniProt sequence would inherently comprise a DNA-binding domain and a region comprising amino acid residues 134 to 253 of SEQ ID NO: 1, which is taught in the prior art to have the same bile acid binding characteristics required by the invention. Moreover, a naturally-occurring VtrA polypeptide derived from Vibrio parahaemolyticus (as shown in the UniProt sequence discussed above) meets all of the limitations of the claim 1. Hence, the naturally occurring counterpart is itself included within the scope of the claim, has the same structure set forth in the limitations of the claim, and would be expected to have the same inherent characteristics as the claimed product.
Claim 3 recites the fusion protein of claim 1 wherein the VtrA polypeptide is fused either directly or via a linker to the DNA binding domain. Here, the naturally-occurring VtrA polypeptide comprising residues 134 to 253 of SEQ ID NO: 1 is already fused to a DNA binding domain (residues 3 to 103) via a linking sequence. Hence, the natural counterpart is still within the scope of the claim, has the same structure set forth in the limitations of the claim, and does not have any markedly different characteristics compared to the claimed product.
Claim 6 recites a polynucleotide that encodes for the fusion protein of claim 1. As the prior art teaches VtrA is naturally expressed in a cellular organism, the organism necessarily possesses a polynucleotide that encodes the protein. Hence, the DNA sequence encoding VtrA in Vibrio parahaemolyticus is the closest naturally occurring counterpart, while the claim encompasses any polynucleotide that encodes VtrA, which includes the natural counterpart itself. Hence, the claimed product includes polynucleotides with the same structure and characteristics as the polynucleotide found in nature, which would not be expected to have any markedly different characteristics from the nature-based product.
Thus, the claims recite the judicial exception of a VtrA polypeptide comprising a DNA binding domain and a polynucleotide encoding said polypeptide, which occur in nature and have the same inherent characteristics as their natural counterparts. Hence, the recited judicial exceptions are directed to natural products without any markedly different characteristics compared to their counterparts in nature.
Step 2A, Prong Two:
Step 2A, prong 2 requires the Examiner to evaluate whether the claim recites
additional elements that integrate the exception into a practical application of that exception and, if not, proceed to step 2B. In order to integrate the recited judicial exception into a practical application, the claim will apply, rely on, or use the judicial exception that imposes a meaningful limit such that the claim is more than a drafting effort to monopolize the judicial exception.
Examiners evaluate integration by identifying additional elements in the claim beyond the judicial exception and evaluating those elements individually and in combination to determine
whether they integrate the exception in to a practical application. Examples that have been found
by the Courts in which the exception was not integrated into a practical application include:
- Mere instructions to implement an abstract idea on a computer
- Adding generic instructions that the judicial exception should be used ("apply it")
-Adding insignificant extrasolution activity to the exception ("mere data gathering")
- Generally linking the use of the exception to a particular technological environment or
field of use
Analysis:
In the instant case, the claims do not recite any additional elements, beyond the judicial exceptions themselves, to integrate the judicial exception into a practical application.
See MPEP 2106.04(II)(A)(2) which states, “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application”.
Hence, the claims are still directed to the judicial exception under Step 2A, Prong Two.
Step 2B:
Step 2B requires the Examiner to first identify whether there are any additional elements (features/limitations/steps) recited in the claim beyond the judicial exception(s), and then evaluate those additional elements individually and in combination to determine whether they contribute to an inventive concept (i.e., amount to significantly more than the judicial exception(s)).
Analysis:
In the instant case, the claims do not recite any additional elements, beyond the judicial exceptions themselves, and therefore cannot amount to significantly more than the judicial exception(s).
In conclusion, claims 1, 3 and 6 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
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.
(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.
Claim(s) 1 and 3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by UniProt Q87GI4_VIBPA (cited on Form 892).
Regarding claim 1, UniProt entry Q87GI4_VIBPA is identified as a putative transcriptional regulator ToxR (see pg. 1, line 6, “DE”) derived from Vibrio parahaemolyticus strain RIMD 2210633 (see pg. 1, line 8, “OS”). As shown in the following alignment, Q87GI4_VIBPA (bottom) comprises an amino acid sequence that is identical to instant SEQ ID NO: 1 (top):
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The UniProt sequence comprises a “DNA-binding” domain from amino acid residues 3 to 103 (see pg. 2, lines 1 and 6-14). Hence, this prior art sequence comprises an amino acid sequence which is identical to amino acid residues 134 to 253 of instant SEQ ID NO: 1, which is fused to a region identified as a DNA binding domain, meeting all of the structural limitations set forth in the claim.
Regarding claim 3, the UniProt sequence comprises a DNA-binding domain from amino acid residues 3 to 103, and a VtrA polypeptide region comprising residues 134 to 253. Hence, the UniProt sequence comprises a linking sequence between the DNA binding domain and the “VtrA polypeptide” from amino acids 104 to 133, which meets the limitation of being “fused… via a linker”.
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.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voigt et al. (US 20180073031 A1; cited on Form 892), hereafter, “Voigt”, and further in view of Bonnet et al. (WO 2018224611 A1; cited in the IDS filed 08/01/2023), hereafter, “Bonnet”, and further in view of Rivera-Cancel et al. (cited in the IDS filed 08/01/2023), hereafter, “Rivera”, as further evidenced by UniProt Q87GI4_VIBPA (cited on Form 892).
Regarding claim 1, Voigt teaches that a portion of bile acids synthesized in the liver enter the colon to be modified by the resident gut microbiota, resulting in secondary bile acids, which are implicated to be causative agents for colon and liver cancer, as well as being biomarkers for inflammatory bowel disease (see pg. 1, para. [0004]). Voigt also suggests that determining the presence of bile acid in a biological sample from a patient may be indicative of liver disease or liver dysfunction and be useful when treating such conditions (see pg. 2, paras. [0024], [0026]).
Voigt discloses engineered nucleic acid molecules that act as sensors for bile acids, wherein the nucleotide sequence encodes a bile acid sensor protein that binds to a bile acid (see pg. 1, para. [0009]). Voigt teaches the bile acid sensor comprises a protein from a species of Vibrio, wherein the binding to bile acids leads to a conformational change, leading to the release of DNA and allowing for transcription of the gene by RNA polymerase to take place (see pg. 3, para. [0042]). Voigt discloses exemplary bile acid sensor polypeptides that are derived from Vibrio cholera and Vibrio fischeri (see pg. 3, para. [0042]).
Voigt does not explicitly teach a fusion protein comprising the bile acid sensor protein and a DNA binding domain.
Bonnet teaches that in vitro diagnostic tests (IVDs) are growing in importance in the global health arena because of their noninvasive nature and resulting ease of use and scale; however, conventional detection methods for IVDs are often expensive and complex, and thus difficult to implement in resource-limited settings (see pg. 1, lines 9-12). Bonnet teaches that whole-cell biosensors based on bacteria have proven to be applicable for the detection and quantification of a wide range of analytes, but are limited by slow response times and the inability to engineer ligand-tailored sensors (see pg. 1, lines 16-17 and 27-33).
As a solution to these challenges, Bonnet discloses chimeric receptors that can be used in whole-cell sensors for detecting analytes of interest (see Abstract), wherein the chimeric receptor polypeptide (i.e., fusion protein) comprises: i) a first DNA binding domain, ii) at least one binding domain having specificity for an analyte, and iii) a linker between the DNA binding domain and the analyte-specific binding domain (see pg. 2, lines 14-16). Bonnet teaches the DNA binding domain is a “CadC transcriptional activator” which is a membrane-integrated transcriptional regulator of Escherichia coli, representative of ToxR-like proteins that combine sensory, signal transduction, and DNA-binding activities within a single polypeptide (see pg. 2, line 30 to pg. 3, line 1). Here, the “bile acid sensor protein that binds to a bile acid” taught by Voigt reads on Bonnet’s teaching of a “binding domain having specificity for an analyte”.
Voigt and Bonnet do not teach the analyte-specific binding domain (bile acid sensor) comprising a VtrA polypeptide.
Rivera teaches that some intestinal bacteria are able to use bile salts as a cue for intestinal location to regulate virulence factors, but the mechanisms used for bile acid sensing have been poorly characterized (see pg. 366, col.1, para. 1 to col. 2, para. 2). In Rivera’s study, Vibrio parahaemolyticus was demonstrated to sense bile salts via a heterodimeric receptor formed by the periplasmic domains of inner-membrane proteins VtrA and VtrC, and Rivera discloses that proteins with the same domain arrangement are widespread in Vibrio and related bacteria (see Abstract). Rivera teaches that ToxR and ToxS in V. cholerae adopt the same domain topology as VtrA and VtrC in V. parahaemolyticus, and ToxR has also been reported to respond to the presence of bile (see pg. 369, col. 1, para. 3 to col. 2, para. 1). Rivera also teaches that evidence suggests that ToxR plays a secondary role by enhancing VtrA’s transcription factor activity (see pg. 369, col. 2, para. 2). Rivera discloses that the V. parahaemolyticus strain used in the study was “RIMD2210633” (see pg. 368, col. 1, para. 1).
UniProt entry Q87GI4_VIBPA is identified as a putative transcriptional regulator ToxR (see pg. 1, line 6, “DE”) derived from Vibrio parahaemolyticus strain RIMD 2210633 (see pg. 1, line 8, “OS”). As shown in the following alignment, Q87GI4_VIBPA (bottom) comprises an amino acid sequence that is identical to instant SEQ ID NO: 1 (top):
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It would have been obvious at the time of filing for a person of ordinary skill in the art to have combined the teachings of Voigt, Bonnet and Rivera to have arrived at the claimed invention for at least the following reasons: (1) Voigt and Bonnet both teach compositions and methods for the detection of analytes using bacterial polypeptides; (2) Voigt and Rivera teach bacterial polypeptides which sense bile acids, which Voigt teaches can be used to detect bile acids; (3) Bonnet and Rivera teach ToxR-like proteins, such as VtrA, which bacteria use to sense the presence of bile acids; (4) Rivera demonstrates that VtrA is used by Vibrio parahaemolyticus to sense bile salts and suggests elements derived from ToxR-like proteins (such as the DNA binding domain taught by Bonnet) may enhance VtrA transcription factor activity; and (5) Bonnet teaches fusion proteins comprising a DNA binding domain connected to an analyte-specific binding domain for improved in vitro testing. Hence, one would have been motivated to combine these teachings in order to provide an improved chimeric polypeptide capable of more effectively responding to the presence of bile acids in a sample to determine or monitor a liver or bowel disease. As Rivera teaches VtrA to be used by Vibrio to sense bile salts, one would have immediately envisaged substituting the bile acid sensor polypeptide taught by Voigt with the VtrA polypeptide as the analyte-specific binding domain of the fusion protein taught by Bonnet. Further, the sequence for this polypeptide was readily available in public databases at the time of filing and could have been easily identified based on Rivera’s disclosure. Because these polypeptides are taught by the prior art to inherently possess the required mechanisms for sensing such molecules in bacteria, one would have recognized there to be a reasonable expectation for success when combining these teachings. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 2, Bonnet teaches the DNA binding domain is a “CadC transcriptional activator” derived from Escherichia coli, as discussed above. Bonnet teaches the CadC transcriptional activator DNA binding domain comprises an amino acid sequence according to SEQ ID NO: 2 (see pg. 3, lines 11-13). A shown in the following alignment, Bonnet’s SEQ ID NO: 2 (bottom) comprises an amino acid sequence that is identical to instant SEQ ID NO: 3 (top):
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Regarding claim 3, Bonnet teaches the chimeric receptor polypeptide comprises a linker between the DNA binding domain and the analyte-specific binding domain, as discussed above. Hence, it would have been obvious to have the VtrA polypeptide fused via a linker to the DNA binding domain.
Regarding claim 4, as shown in the following alignment, Bonnet’s SEQ ID NO: 2 (bottom) further comprises an amino acid sequence that is identical to instant SEQ ID NO: 4 (top):
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Note that Bonnet’s SEQ ID NO: 2 comprises both a DNA binding domain identical to instant SEQ ID NO: 3 from residues 1 to 107 and a linker sequence identical to instant SEQ ID NO: 4 from residues 108 to 155, as shown above. Hence, Bonnet’s DNA binding sequence already comprises the claimed linker represented by instant SEQ ID NO: 4.
Regarding claim 5, note that instant SEQ ID NO: 5 comprises, in sequence from N-terminus to C-terminus, instant SEQ ID NO: 3 (CadC transcriptional activator DNA binding domain), instant SEQ ID NO: 4 (linker), and residues 134 to 253 of SEQ ID NO: 1 (VtrA).
Rivera teaches that VtrA contains an N-terminal DNA-binding domain of the OmpR family that is attached to the inner membrane by a single transmembrane helix, and a C-terminal periplasmic domain (see pg. 367, col. 1, para. 2). Rivera teaches that V. parahaemolyticus was demonstrated to sense bile salts via the C-terminal periplasmic domain of VtrA (see pg. 370, col. 2, para. 2). Hence, a person of skill would have recognized that the transmembrane domain should be included in the fusion protein for anchoring the fusion protein to the cell membrane, and the C-terminal periplasmic domain should be included in the fusion protein for sensing bile acids.
In view of Q87GI4_VIBPA, the “OmpR” type domain (DNA-binding domain) in VtrA ranges from amino acid residue 3 to residue 103, and the helical transmembrane domain ranges from residues 134 to 153 (see pg. 2, lines 6-14). Hence, a person of skill would have recognized that the minimal structure required for VtrA to be functional in the fusion protein would be an amino acid sequence comprising the C-terminus of VtrA beginning at amino acid residue 134, because this region would be expected to contain the required transmembrane and periplasmic domains. This results in the following truncated VtrA sequence:
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Fusing the CadC transcriptional activator taught by Bonnet (SEQ ID NO: 2) with the truncated VtrA sequence above, results in the following fusion protein sequence:
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As shown in the following alignment, instant SEQ ID NO: 5 (top) is identical to the fusion protein sequence above (bottom):
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Thus, it would have been obvious for the fusion protein to have comprised an amino acid sequence with at least 90% identity with instant SEQ ID NO: 5, because this sequence is one that a person of ordinary skill would have necessarily arrived at when constructing a fusion protein to detect bile acids in view of the prior art combination.
Regarding claim 6, Bonnet teaches a further aspect of the invention relates to a nucleic acid encoding for a chimeric receptor of the invention (see pg. 7, lines 7-8; claim 9). Hence, it would have been obvious to have provided a polynucleotide that encodes the fusion protein.
Regarding claim 7, Bonnet teaches an expression cassette comprising the nucleic acid molecule operably linked to control sequences allowing expression in a prokaryotic cell (see pg. 7, lines 1-3).
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voigt, Bonnet, Rivera and UniProt Q87GI4_VIBPA as applied to claims 1-7 above, and further in view of Crafton et al. (US 20030017533 A1; cited on Form 892), hereafter, “Crafton”.
Regarding claim 8, Bonnet teaches that “[s]uitable expression control sequences include
promoters that are applicable in the target host organism. Such promoters are well known to the
person skilled in the art for diverse hosts from prokaryotic organisms and are described in the
literature” (see pg. 7, lines 25-29).
Bonnet does not explicitly teach the expression cassette comprising a p14, p10, or p9 promoter.
Crafton teaches isolated polynucleotides comprising C. glutamicum promoters which may be used to regulate, i.e., either increase or decrease gene expression (see Abstract). Crafton teaches that one way to improve the productivity of a microbial strain is to increase the expression of genes that control the production of a metabolite (see pg. 1, para. [0007]). Crafton teaches promoters useful for regulating and enhancing the production of a variety of products in host cells (see pg. 2, para. [0019]) which include the trc promoter represented by SEQ ID NO: 26 (see pg. 21, para. [0153]). As shown in the following alignment, Crafton’s SEQ ID NO: 26 (top) comprises a nucleic acid sequence that is identical to instant SEQ ID NO: 6 (bottom):
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Hence, while Crafton does not refer to this promoter as a “p14” promoter, it comprises the same structure and is therefore equivalent to the promoter of the claim.
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Crafton with that of the aforementioned references, because all references used in the rejection relate to the expression of genes in bacteria. One would recognized from Bonnet that suitable expression control sequences include promoters that are well known in the art, including the promoters taught by Crafton. One would have also recognized that is well within the ordinary skill in the art to select and use such promoters, which Crafton teaches are useful for regulating the expression level of a given gene, such as in the case of the expression cassettes taught by Bonnet. One would have recognized that each of the claimed elements (i.e., promoter, DNA binding domain, etc.) could be combined by known methods and, as each element merely performs the same function as it does separately, the results of the combination would have been predictable with a reasonable expectation of success. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Conclusion
No claims are allowed.
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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651