DETAILED ACTION
Notice of 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 without traverse of Group I, claim 1 in the reply filed on 13 February 2026 is acknowledged. The requirement is deemed proper and therefore made Final.
Status of Application
Claims 1-7 are pending; Claims 2-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claim 1 is subject to examination on the merits.
Priority
The instant application is a CON of US 16764799 (now US Patent 12139730) which is a 371 of PCT/JP2018/042915 filed 21 November 2018 which claims benefit of foreign priority document JP 2017-225221 filed 22 November 2017 is acknowledged. Said document has been received in the parent application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/05/2026; 02/14/2025; 05/30/2024 (x2) and 04/12/2024 (x2) have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Claim Rejections - 35 USC § 112(a)
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.
Written Description:
Claim 1 is rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
The claim is drawn to a complex comprising a nucleic acid sequence-recognizing module and a proteolysis tag, wherein the module is linked to the proteolysis tag, the module specifically binds to a target nucleotide sequence in a double stranded DNA, wherein the complex is further bound with a nucleic acid altering enzyme that converts one or more nucleotides in the target nucleotide sequence to a different nucleotide, deletes one or more nucleotides in the target nucleotide sequence, or inserts one or more nucleotides in the target nucleotide sequence, wherein the nucleic acid altering enzyme is a deaminase or a DNA glycosylase, and wherein the nucleic acid sequence-recognizing module is selected from the group consisting of CRISPR-mutant Cas, zinc finger motif, TAL effector and PPR motif.
Thus, the claim is drawn to a large and variable genus of “proteolysis tags”, and wherein said complex can be covalently or non-covalently linked and when covalently linked (e.g. fusion protein), it can be in any order. However, the specification is very limited to its examples, which are not deemed representative of the entire diverse and variable genus of complexes comprising a huge variety of proteolysis tags, further having any order. Namely, the specification is limited to fusion proteins having one of four proteolysis tags -LVA/LAA/AAV/ASV- at the Cterm. The specification loosely defines a proteolysis tag as such (See paragraph [0063], PG-Pub):
In the present invention, the “proteolysis tag” mainly consists of a peptide containing not less than 3 hydrophobic amino acid residues, wherein the peptide shows a shortened half-life of protein when added to a complex for genome editing as compared to that without addition to the complex. As such amino acid, glycine, alanine, valine, leucine, isoleucine, methionine, proline, phenylalanine, and tryptophan can be mentioned. The proteolysis tag of the present invention only needs to contain any three of these amino acid residues at the C-terminal, and other constitution is not particularly limited. It may be a peptide consisting of the three amino acid residues. A peptide in which a part or all of the aforementioned hydrophobic amino acid residues is/are substituted by serine or threonine is also encompassed in the proteolysis tag of the present invention. While preferable aforementioned three amino acid residues are not particularly limited, leucine-valine-alanine (LVA), leucine-alanine-alanine (LAA), alanine-alanine-valine (AAV) and the like, whose high effects were acknowledged in Escherichia coli and Pseudomonas putida (Andersen J. B. et al., Apll. Environ. Microbiol., 64: 2240-2246 (1998)), can be mentioned and, as one containing serine, alanine-serine-valine (ASV) and the like can be mentioned. In addition, the data base of tm RNA tag peptide (e.g., tmRDB, ag.auburn.edu/mirror/tmRDB/peptide/peptidephylolist.html) and the like can be referred to for the proteolysis tag containing these three amino acid residues. Specifically, YAASV (SEQ ID NO: 324), YALAA (SEQ ID NO: 325), ANDENYALAA (SEQ ID NO: 181) and AANDENYALAA (SEQ ID NO: 182) known as tmRNA tag peptides of Escherichia coli, GKQNNLSLAA (SEQ ID NO: 183), GKSNNNFALAA (SEQ ID NO: 184), GKENNNFALAA (SEQ ID NO: 185), GKTNSFNONVALAA (SEQ ID NO: 186), GKSNONLALAA (SEQ ID NO: 187) and GKONYALAA (SEQ ID NO: 188) known as tmRNA tag peptides of genus Bacillus, ANDDNYALAA (SEQ ID NO: 189), ANDDQYGAALAA (SEQ ID NO: 190), ANDENYGQEFALAA (SEQ ID NO: 191), ANDETYGDYALAA (SEQ ID NO: 192), ANDETYGEYALAA (SEQ ID NO: 193), ANDETYGEETYALAA (SEQ ID NO: 194), ANDENYGAEYKLAA (SEQ ID NO: 195) and ANDENYGAQLAA (SEQ ID NO: 196) known as tmRNA tag peptides of genus Pseudomonas, AKNTNSYALAA (SEQ ID NO: 197), AKNTNSYAVAA (SEQ ID NO: 198), AKNNTTYALAA (SEQ ID NO: 199), AKNTNTYALAA (SEQ ID NO: 200) and AKNNTSYALAA (SEQ ID NO: 201) known as tmRNA tag peptides of genus Streptococcus and the like can be unlimitatively mentioned. The proteolysis tag typically consists of 3-15 amino acid residues, but is not limited to this range. In one embodiment, proteolysis tag consists of 3-5 amino acid residues. Those of ordinary skill in the art can appropriately select the proteolysis tag according to the kind of host bacterium and the like. In the present specification, unless otherwise specified, the capital letter of the alphabet indicates a one-letter code for the amino acid, and the amino acid sequence is indicated from left to right, from N-terminal to C-terminal.
However, as can be interpreted from this definition, the “proteolysis tag” of the claims comprises an enormous genus of peptide tags, always at the C-terminus of the fusion protein (not in a complex), and which can be any combination of at least 3 hydrophobic amino acids, or those which have any or all of the hydrophobic amino acids are exchanged for serine or threonine. However, it is not clear which combinations, other than LVA/LAA/AAV/ASV truly have the functional requirement of promoting degradation of the fusion proteins. For example, SSA or SSS or PFM all meet the definition of a proteolysis tag as defined by the specification, but it is unclear if these, or any of the other thousands of combinations are able to act as proteolysis tags because even for a “simple” minimum three amino acid tag the unpredictability is significant as to whether or not the structure meets the functional requirement. As such, these four representative species of LVA/LAA/AAV/ASV are not representative of the genus of proteolysis tags as claimed in the complex in terms of structure and function.
The MPEP in section 2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed. The courts have stated:
"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 (Fed. Cir. 1997); In re Gostelli, 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 shows possession of the claimed invention by "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." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
US20170073670
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12139730. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘730 necessarily anticipate the instant claim.
The instant claim is drawn to: A complex comprising a nucleic acid sequence-recognizing module and a proteolysis tag, wherein the module is linked to the proteolysis tag, the module specifically binds to a target nucleotide sequence in a double stranded DNA, wherein the complex is further bound with a nucleic acid altering enzyme that converts one or more nucleotides in the target nucleotide sequence to a different nucleotide, deletes one or more nucleotides in the target nucleotide sequence, or inserts one or more nucleotides in the target nucleotide sequence, wherein the nucleic acid altering enzyme is a deaminase or a DNA glycosylase, and wherein the nucleic acid sequence-recognizing module is selected from the group consisting of CRISPR-mutant Cas, zinc finger motif, TAL effector and PPR motif.
The claims to the ‘730 patent in their broadest are drawn to: A complex comprising a nucleic acid sequence-recognizing module and a proteolysis tag,
wherein the module is linked to the proteolysis tag, the module specifically binds to a target nucleotide sequence in a double stranded DNA, and the tag consists of a peptide at the C-terminal of the module containing 3 hydrophobic amino acid residues, wherein the 3 hydrophobic amino acid residues are leucine-valine-alanine, leucine-alanine-alanine, alanine-alanine-valine, or alanine-serine-valine, wherein the complex is further bound with a nucleic acid altering enzyme that converts one or more nucleotides in the target nucleotide sequence to a different nucleotide, deletes one or more nucleotides in the target nucleotide sequence, or inserts one or more nucleotides in the target nucleotide sequence, wherein the nucleic acid altering enzyme is a deaminase or a DNA glycosylase, and wherein the nucleic acid sequence-recognizing module is selected from the group consisting of CRISPR-mutant Cas, zinc finger motif, TAL effector and PPR motif. Claims 6-15 are drawn to methods of using the same complex for altering a target site of dsDNA.
Thus, the difference between the two sets of claims is the instant claim comprises any kind of proteolysis tag (e.g. drawn to a genus of proteolysis tags), whereas the claims to the ‘730 patent are drawn to four specific proteolysis tags (LVA, LAA, AAV or ASV). However, the species always anticipate the genus and as such, the claims to the ‘730 patent anticipate the instant claim.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 26 February 2026