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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to a method of producing a synthetic nucleic acid comprising sequence similarity or complementarity to SEQ ID NOs:28 or 29, in the reply filed on 08/26/2025 is acknowledged. The traversal is on the ground(s) that the two groups are “inexorably linked” (page 7) because SEQ ID NOs:28-29 are the starting regulatory nucleic acids of the method of claim 1, a method which produces synthetic regulatory nucleic acids, and SEQ ID NOs:25-43 and 45-47 are synthetic regulatory nucleic acids. This is found persuasive. The restriction requirement has been withdrawn.
Applicant's election with traverse of starting regulatory nucleic acid molecules of SEQ ID NO:28 and synthetic regulatory nucleic acid molecules of SEQ ID NO:37 in the reply filed on 08/26/2025 is acknowledged. The traversal is on the ground(s) that the species of Group A (SEQ ID NO:28-29) and of Group B (SEQ ID NOs:33-43, 45-47) are alternatives, and are not identical. This is not found persuasive because an election of species is made between distinct species (i.e., not identical) and because are not obvious variants of each other (while they are used as alternatives, the species of each group are not variants of one another). As the species are distinct, election is proper.
The requirement is still deemed proper and is therefore made FINAL.
Claims Status
Claims 3-7 is/are cancelled. Claims 1-2, 8-22 is/are currently pending. Claims 1-2, 8-22 is/are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. A hyperlink were found on page 40 line 18. Applicant is advised to review the specification in order to ensure that all hyperlinks are identified and appropriately removed.
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.
Claim 1-2, 8-22 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.
To satisfy the written description requirement, a patent 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. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire 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. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claim 1 recites a method of producing one or more synthetic regulatory nucleic acid molecule “in a bacterial cell” (lines 1-4). However, the disclosure has only described a method of producing one or more synthetic regulatory nucleic acid molecules in a Bacillus or Escherichia cell (pages 9-10; pages 47-51). Furthermore, the disclosure only describes the necessary structures and compositions for the claimed method for use in Bacillus or Escherichia cells. As such, an artisan would not be able to determine that the applicants were in possession of a method of producing one or more synthetic regulatory nucleic acid molecules in a bacterial cell that is not a Bacillus or Escherichia cell. Claims 2, 9-14, 16, and 20-22 read on the breadth of bacterial cells of claim 1, and so lack sufficient written description.
Claim 1 recites a step of “identifying at least one starting regulatory nucleic acid molecule”; however, neither the claims nor the specification describe what action a step of “identifying” entails. An artisan would not be able to determine whether a step of “identifying” entails an action of selecting, recognizing, screening, or a different action, and thus would be unable to determine the scope of step (a) of claim 1. As claims 2, 8-14, 16, and 20-22 depend on claim 1 but do not further describe a step of “identifying” a nucleic acid, claims 2, 8-14, 16, and 20-22 are also rejected for failing to fulfill the written description requirement.
Claim 1 recites “a coding region encoding a protein” wherein “high expression of said coding region in a bacterial cell burdens said bacterial cell leading to reduced or abolished growth” (lines 6-7, 11-12), and “a gene” operably linked to the same synthetic regulatory nucleic acid as the “coding region” (lines 18-20). This creates an enormous genus of “coding regions” and “genes” that is not sufficiently defined in the disclosure. On page 7 of the specification, examples of a “coding region burdening a bacterium expressing said coding region under control of a strong constitutive promoter” are provided, but a definition is not provided. The disclosure teaches that the protein encoded by the coding region could be over 150kDa, could be a nuclease, deaminase, glycosylase, “enzyme interfering with the bacterial metabolism”, or “transporter or transmembrane proteins interfering with substrate uptake or detoxification of the bacterial cell”. These are presented as potential embodiments and not definitions or limitations of the genus. On page 9, lines 10-14, the “functional expression of a coding region means that the expression of such coding region is at least detectable for example by RNA detection methods”; based on this definition, the “gene” of claim 1 can be any gene. However An artisan would not be able to conclude based on these embodiments what the bounds of the recited genus are (e.g., whether the classes of proteins described are representative of the full scope of the genus of coding regions which, when highly expressed, burden a bacterial cell), nor whether the applicants were in possession of the full scope of the recited genus. Dependent claims 2, 8-14, 16, 20-22 do not further describe or limit this genus of coding regions, and as such, claims 1-2, 8-14, 16, 20-22 are considered to lack sufficient written description of the recited coding regions.
Claim 1 recites “at least one starting regulatory nucleic acid molecule conferring constitutive expression in a bacterial cell” (lines 1-2). This creates an enormous genus of regulatory nucleic acid molecules. However, the only species of this genus which are described are promoters of SEQ ID NOs:28 and 29 (see claim 14; page 45 lines 17-18). Promoters of SEQ ID NOs:28-29 are not representative of the entire genus of regulatory nucleic acids, which is not limited to promoter sequences, nor are they representative of promoter sequences, generally. Furthermore, regarding claims 16 and 20-22, the only “synthetic regulatory nucleic acid molecules” produced by the method of claim 1 which are described are the nucleic acid molecules of SEQ ID NOs:34-47 (see Table 1 and page 46 lines 3-8). SEQ ID NOs:34-47 are only species of variant promoters produced by the method of claim 1 using a starting promoter of SEQ ID NO:28 (for SEQ ID NOs:34-40) and SEQ ID NO:29 (for SEQ ID NOs:41-47). These sequences are not representative of the entire genus of synthetic regulatory nucleic acid molecules produced by the method of claim 1 using any starting regulatory nucleic acid molecule, not limited to promoters of SEQ ID NOs:28-29. An artisan would only be able to determine that the applicants were in possession of a method using a starting regulatory nucleic acid of SEQ ID NOs:28-29 and synthetic regulatory nucleic acid molecules produced by this method, of SEQ ID NOs:34-40. As such, claims 1-2, 8-22 lack sufficient written description.
Claims 14-15 recite sequences at least 90% identical to SEQ ID NOs:28-29, 35-43, and 45-47, comprising at least 20 consecutive base pairs identical to 20 consecutive base pairs of SEQ ID NOs:28-29, 35-43, and 45-47, or capable of hybridizing at least 20 consecutive base pairs of a sequence in SEQ ID NOs:28-29, 35-43, and 45-47. Only sequences 100% identical to SEQ ID NOs:28-29, 35-43, and 45-47 are disclosed; moreover, sequences of as few as 20 consecutive nucleotides from SEQ ID NOs:28-29, 35-43, and 45-47 are not disclosed. Furthermore, a representative number of species have not been sufficiently described by other relevant identifying characteristics (i.e., other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic is that these sequences function as “regulatory” nucleic acid molecules (see claim 14 lines 1-2 and claim 15 line 1). Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of the genus, all members of the claimed genus will that characteristic. Further, no identifying characteristics of the modified sequences are disclosed. As such, claims 14 and 15, and claims 17-19 dependent on claim 15 which do not further describe or limit the genus of modified sequences, lack sufficient written description.
Furthermore, claims 14 and 15 recite sequences which “under high stringent conditions” hybridize. The only reference to “high stringent conditions” in the specification describes a “high stringent wash” (page 22 lines 26-30). Here, the specification describes a “high stringent wash” as having conditions “comparable” to a wash as described as “Wash condition 4”, “Wash condition 5”, “Wash condition 6”, “Wash condition 7”, or “Wash condition 8” (page 22 lines 17-22). While the wash conditions of Wash conditions 4-8 are clearly described, it is not clear what would constitute a wash with conditions “comparable” to these—i.e., it is not clear what unspecified combinations of reagents, solvents, temperatures, or other parameters would be considered “high” or “low” stringency. Furthermore, only “high stringent wash” conditions are described; a “wash” is not the only condition under which two nucleic acid sequences could hybridize. The disclosure does not describe any other type of condition (i.e., not a wash condition) under which the nucleic acid sequences may hybridize. Claims 17-19 depend on claim 15 but do not further describe or limit the recited term “high stringent conditions”. As such, claims 14-15 and 17-19 lack sufficient written description of “high stringent conditions”.
Based on the above, claims 1-2 and 8-22 lack sufficient written description and are rejected under 35 USC 112(a).
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.
Claim(s) 15, 17-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (US9771607B2, published 09/26/2017).
Regarding claim 15, Chen teaches a synthetic regulatory nucleic acid molecule comprising at least 20 consecutive base pairs identical to 20 consecutive base pairs of SEQ ID NO:37 (see alignment below between SEQ ID NO:11 of Chen and instant SEQ ID NO:37) (col. 3 lines 31-48; col. 5 lines 42-43, SEQ ID NO:11 is labeled “Pveg”).
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163
662
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SEQ ID NO:11 of Chen is distinct from instant SEQ ID NOs:28-29 (see alignments below).
SEQ ID NO:28:
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158
663
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SEQ ID NO:29:
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152
657
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Regarding claims 17-18, Chen teaches a vector comprising an expression vector comprising the regulatory nucleic acid molecule (col. 3 lines 31-48; col. 5 lines 42-43, SEQ ID NO:11 is labeled “Pveg”).
Regarding claim 19, Chen teaches a microorganism (a bacterium B. subtilis) comprising the regulatory nucleic acid molecule (col. 3 lines 31-48).
Claim(s) 15, 17-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu (CN107699533A, published 02/16/2018, provided with IDS filed 09/01/2022).
Regarding claim 15, Liu teaches a synthetic regulatory nucleic acid molecule comprising at least 20 consecutive base pairs identical to 20 consecutive base pairs of SEQ ID NO:37 (see alignment below between SEQ ID NO:2 of Liu and instant SEQ ID NO:37) (page 15 of provided copy, “Example 2”).
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158
661
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SEQ ID NO:2 of Liu is distinct from instant SEQ ID NOs:28-29, see alignments below.
SEQ ID NO:28:
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157
665
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SEQ ID NO:29:
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154
661
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Regarding claims 17-19, Liu teaches a microorganism B. subtilis comprising a vector (plasmid) comprising an expression vector comprising the synthetic regulatory nucleic acid molecule (page 15 of provided copy, “Example 2”).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/RAM R SHUKLA/ Supervisory Patent Examiner, Art Unit 1635