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 .
Election/Restrictions
Applicant's reply to the Restriction Requirement, dated February 5, 2026, has been received. By way of this submission, Applicant has amended the specification and claims 1, 4-5, and 44, and introduced new claim 45. Applicant has elected, without traverse, Group I: claims 1-5 and 44-45, and the species of a constitutive promoter.
Claims 1-5, 19-27, 29-32, 34, and 44-45 are pending. Claims 19-27, 29-32, and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 February 5, 2026.
Claims 1-5 and 44-45 are therefore under examination before the Office.
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 1-5 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.
"[T]he purpose of the written description requirement is to 'ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.'" Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), "[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
"[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A "representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) ("The '128 and '485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus."). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number" of species.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 ("The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.")
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is "had possession of the claimed subject matter as of the filing date. Demonstrating possession "requires a precise definition" of the invention. To provide this precise definition" for a claim to a genus, a patentee must disclose "a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus" (see Amgen at page 1358).
Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – "a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials", which may be present in "functional terminology when the art has established a correlation between structure and function" (Amgen page 1361).
In the instant case, the claims are drawn to a heme-responsive promoter sequence comprising a nucleic acid sequence at least 70% homologous to SEQ ID NO: 104. As SEQ ID NO: 104 comprises 190 base pairs, the claim allows up to 57 possible base pair alterations, without restriction or limitation to their location. This results in a vast genus of possible sequences, not all of which would possess the claimed function. The claims broadly encompass any sequence with the claimed property of being response to heme, however, Applicant's specification only describes three such sequences within this genus. The specification fails to disclose a representative number of species falling with the scope of the genus or structure common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus of the claimed heme-responsive promoter sequence.
A "representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The "structural features common to the members of the genus" needed for one of skill in the art to 'visualize or recognize' the members of the genus takes into account the state of the art at the time of the invention.
Mutations in promoter sequences can have significant impact on sequence functionality. For example, de Vooght (Clin Chem. 2009 Apr;55(4):698-708) teaches that mutations in the promoter region of a gene may disrupt the normal processes of gene activation by disturbing the ordered recruitment of transcription factors at the promoter, vastly altering gene expression, and such mutations in a promoter may cause small quantitative defects, which may be hard to detect. Even if the promoter of an autosomal gene is completely downregulated as result of mutation, half of the normal amount of protein is present, which is often enough to prevent severe disease. This demonstrates a lack of a structure/function correlation between sequence and functionality of a promoter.
For this reason, the skilled artisan would not have been in possession of the vast repertoire of sequences encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of heme-responsive promoter sequence broadly encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
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.
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.
Claims 1-4 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Debnath (WO2018183685A1).
Debnath teaches a sequence SEQ ID NO: 24, which comprises a sequence that is greater than 70% similar to Applicant's SEQ ID NO: 104, as evidenced by the alignment below:
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Debnath further teaches that a promoter may be operably linked to a slpA sequence (page 10, lines 22-24), which is pertinent to claims 2 and 3).
Debnath further teaches a sequence SEQ ID NO: 11, which comprises a sequence that is greater than 70% similar to Applicant's SEQ ID NO: 104, as evidence by the alignment below:
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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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Lu (US20170058282A1, cited in IDS) in view of Debnath (WO2018183685A1).
Lu teaches a heme-responsive transcription factor and a genetic circuit responsive to the heme-responsive transcription factor, and the heme-responsive transcription factor is from Lactococcus lactis (para. 0009). Lu further teaches that this genetic circuit comprises a promoter that is responsive to the heme-responsive transcription factor, and the promoter may be operably linked to one or more hrtO operator sites (para. 0012 and 0058).
Lu also teaches an hrtO nucleic acid sequence of ATGACACAGTGTCAT (SEQ ID NO: 15 in Lu) (para. 0083).
However, Lu does not teach a slpA promoter sequence.
Debnath teaches a lactic acid bacterial cell, comprising a constitutive promoter sequence that has been altered to include one or more transcription repressor protein binding sites (page 3, lines 12-13).
Debnath further teaches that the promoter sequence may be the slpA promoter sequence from L. acidophilus, or the clpC promoter L. fermentum BR11 (page 27, line 10). Debnath also teaches a slpA promoter sequence of SEQ ID NO: 2 (page 10, line 22 through page 11, line 2) with homology to Applicant's SEQ ID NO: 104 as follows:
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It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Lu and Debnath to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Lu and Debnath are concerned with linking operator sequences to promoter sequences. Starting from the system of Lu, which comprises one or more hrtO operator sites linked to a promoter, one of ordinary skill could apply the slpA promoter of Debnath by simple substitution to arrive at the claimed invention. Each component would perform its normal, usual function and affect a predictable result.
While Lu and Debnath do not explicitly teach the sequences of Applicant's SEQ ID NOs: 104, 102, and 105, Lu and Debnath teach the sequences of the hrtO operator, the slpA promoter, and the clpC promoter (SEQ ID NO: 7 of Debnath). Applicant's specification at page 3 defines SEQ ID NO: 104 as the 5′ UTR of the slpA promoter from Lactobacillus acidophilus NCFM modified with two hrtO repressor binding sites from Lactobacillus lactis, SEQ ID NO: 105 as the nucleic acid sequence of the heme-responsive promoter clpC from Lactobacillus fermentum BR11, modified with the 5′ UTR of the slpA promoter from Lactobacillus acidophilus NCFM, and SEQ ID NO: 102 as the nucleic acid sequence of the heme-responsive version of the slpA promoter from Lactobacillus acidophilus NCFM modified with two hrtO repressor binding sites. As Lu and Debnath teach these sequences and their combinations, a person of ordinary skill, upon combining the above features into the claimed invention, would naturally also make a DNA sequence comprising Applicant's SEQ ID NOs: 102, 104 or 105.
Allowable Subject Matter
Claims 44 and 45 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644