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
This Non-Final Office Action is responsive to the communication received 8/10/2026.
Election/Restrictions
Applicant’s election without traverse in the Reply filed on 8/10/2026 of Group I, Claim(s) 1-19 and 22-24 is acknowledged.
Applicant has elected in the Reply filed on 8/10/2026 the following species:
A. the transcription activator domain is a synthetic tetramer of VP16 (Herpes simplex virus protein 16) named VP64 (claim 6)
Because applicant did not distinctly and specifically point out the supposed errors in the species election requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The Restriction/Election Requirements are thus deemed proper and are made FINAL.
Claims 1-24 are pending.
Claims 20-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 8/10/2026.
Claims 1-19 and 22-24 are under examination in this Office Action.
Claim Rejections - 35 USC § 112 - 2nd paragraph
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 6 and 8 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 6 and 8 are vague and indefinite as to whether the claim is meant as worded to limit the secondary structure to "(which may comprise repetitions of “IIXXII (SEQ ID NO:6),” like those present in NTF-1)" or not. The above phrase renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. If there are situations where the above phrase is required, it is now clear what situations would trigger the requirement to include the above phrase.
Claim Rejections - 35 USC § 112-1st paragraph (Written Description)
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ):
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 1-19 and 22-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention. Claims 2-19 and 22-24 depend directly or indirectly from claim 1.
The specification discloses engineered genetic circuits, such as SEQ ID NO 1, SEQ ID NO 3 and those in Table 1 and Figures 28 to 35 which meet the written description and enablement provisions of 35 USC 112, first paragraph. However, claim(s) 1-19 and 22-24 is(are) directed to encompass derivatives and analogs, which only correspond in some undefined way to specifically instantly disclosed chemicals. None of these derivatives and analogs, meet the written description provision of 35 USC § 112, first paragraph, due to lacking chemical structural information for what they are and chemical structures are highly variant and encompass a myriad of possibilities. The specification provides insufficient written description to support the genus encompassed by the claim.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of the above specifically disclosed chemical structures, the skilled artisan cannot envision the detailed chemical structure of the encompassed derivatives, analogs, etc., regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The chemical structure itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmacentical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood , 107 F.3d at 1572, 41 USPQ2d at 1966.
Therefore, only the above chemically structurally defined chemicals, but not the full breadth of the claim(s) meet the written description provision of 35 USC § 112, first paragraph. A search of the prior art fails to identify any examples of engineered genetic circuits. The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.)
Claim Rejections - 35 USC § 103(a)
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103(a) 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.
5. Secondary considerations (objective evidence of nonobviousness): a) commercial success; b) long felt need; c) evidence of unexpected results; d) skepticism of experts; and e) copying.
Common Ownership of Claimed Invention Presumed
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the Examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the Examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-19 and 22-24 are rejected under 35 U.S.C. 103(a) as being unpatentable over Leonard et al. (09/27/2018) PCT International Patent Application Publication WO 2018/175856 A1 cited in the 3/16/2023 IDS corresponding to US Patent Application Publication 2020/0024608 A1 (hereinafter referred to as "Leonard") in view of Slomovic et al. Nature Methods volume 12 pages 1085 to 1090 and supplemental materials cited in the 3/16/2023 IDS (hereinafter known as "Slomovic").
With regards to claims 1-10, 17-19 and 22-24, Leonard teaches:
a) as in claims 1-10, 17-19 and 22-24, an engineered genetic circuit comprising: (a) one or more engineered proteins selected from the group consisting of: an engineered protein that activates gene expression, wherein the engineered protein comprises a DNA binding domain, a transcription activator domain, and at least one split transcription factor on the C-terminus or N-terminus of the DNA binding domain and/or the transcription activator domain; (ii) an engineered protein that inhibits gene expression, the engineered protein comprising a DNA binding domain, a transcription inhibitor domain, and at least one split transcription factor on the C-terminus or N-terminus of the DNA binding domain and/or the transcription inhibitor domain; and (iii) a combination of two engineered proteins comprising a first engineered protein comprising a DNA binding domain fused to a dimerization domain, and a second engineered protein comprising a transcription regulator domain fused to a dimerization domain, wherein the dimerization domains of the two engineered proteins dimerize in the presence of a stimulus to which the dimerization domains of the two engineered proteins bind, and wherein and the first engineered protein and the second engineered protein each comprise at least one split transcription factor; and (b) one or more engineered expression vectors comprising a minimal promoter and one or more DNA binding sites for the DNA binding domains of the engineered proteins of (a); comprising the engineered protein of (i) and the engineered protein of (ii); wherein the DNA binding domain of the one or more engineered proteins of (i), (ii), and (iii) comprises one or more zinc fingers; wherein the DNA binding domain of the one or more engineered proteins of (i), (ii), and (iii) comprises 2, 3, or more zinc fingers; wherein the engineered proteins are fusion proteins comprising heterologous domains; wherein the transcription activator domain of the engineered protein of (i), (ii), and/or (iii) comprises a domain from a transcription activator that is a synthetic tetramer of VP16 (VP64); wherein the engineered protein of (ii) inhibits activation of transcription by the engineered protein of (i); wherein the transcription regulator domain of the second engineered protein of the combination of engineered proteins of (iii) is a transcription activator domain that is a synthetic tetramer of VP16 (VP64); wherein the engineered proteins of (i) or (ii) are present in an exogenous extracellular sensor; wherein the extracellular sensor comprises: (a) a ligand binding domain, (b) a transmembrane domain, (c) a protease cleavage site, and (d) the engineered protein of (i) or (ii); wherein the circuit components are eukaryotic; wherein the circuit components are mammalian; wherein the stimulus is a ligand; a host cell comprising the engineered genetic circuit; wherein the cell is eukaryotic; wherein the cell is mammalian (see [0005] to [0010] and [0058] to [00117]).
Leonard does not explicitly teach:
a) as in claims 1 and 11-16, genetic circuits comprising a split intein; wherein the split intein is a wild-type split intein; wherein the at least one split intein is a mutated split intein; wherein the at least one split intein is appended to the N-terminus of the engineered protein; wherein the split intein comprises 1 or an amino acid sequence that possesses at least about 99% identity thereto; wherein the at least one split intein is appended to the C-terminus of the engineered protein; wherein the split intein comprises 3 or an amino acid sequence that possesses at least about 99% identity thereto.
With regards to claims 1 and 11-16, Slomovic teaches:
a) as in claims 1 and 11-16, genetic circuits comprising a split intein; wherein the split intein is a wild-type split intein; wherein the at least one split intein is a mutated split intein; wherein the at least one split intein is appended to the N-terminus of the engineered protein; wherein the split intein comprises 1 or an amino acid sequence that possesses at least about 99% identity thereto; wherein the at least one split intein is appended to the C-terminus of the engineered protein; wherein the split intein comprises 3 or an amino acid sequence that possesses at least about 99% identity thereto (see entire document especially Figure 1, Online Methods, and pages 1085 to 1087).
One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have had a reasonable expectation of success in arriving at the Applicant's invention as claimed with the above cited references before them. Slomovic teaches the advantages of split inteins in genetic circuits allow for highly tunable and layered gene networks (see page 1089). One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have recognized the advantages of substituting Slomovic's genetic circuits comprising split inteins for Leonard's genetic circuits comprising TF1 and TF2 to enable for highly tunable and layered gene networks. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the time of the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Christian Boesen whose telephone number is 571-270-1321. The Examiner can normally be reached on Monday-Friday 9:00 AM to 5:00 PM.
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/CHRISTIAN C BOESEN/Primary Examiner, Art Unit 1684
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