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 .
Claims 1-5, 7, 8, 10-12, 15-22, 29, and 34 are pending and examined on merits.
Claim Objections
Claim 12 is objected to because of the following informalities: GFP, EPEA, and UBC6e are abbreviations that need to be spelled out at their first occurrence. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 contains the trademark/trade name “nanobody”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a single domain antibody or VHH and, accordingly, the identification/description is indefinite.
Claim 1 recites “more than one piece” but it is not clear what the metes and bounds are for the limitation. “The specification discloses a catalytic domain (first “piece”) and a stalk domain (a second “piece”). There is no other “piece” disclosed in the specification except those claimed in claim 1.
Claims 1 and 2, 16 are confusing as to the meets and bounds of “a split” glycosyl hydrolase” but it is not clear the scope of the term. The specification discloses a split 0-GlcNAcase but does not disclose any other a split glycosyl hydrolase.
Claims 1, 2, 4, 5 and 16 are confusing. It is not clear what is the metes and bounds are for the term “split”. The specification at Fig 1B copied below shows a clear distinction between a “split” form and a “truncated” form. However, claims define a truncated form is included in a split.
The specification discloses:
FIG. 1B shows a schematic of the engineered OGA to achieve protein selectivity. OGA was engineered into a split and truncated form with limited inherent substrate activity.
As described in Fig. 1B, a split and a truncated form of OGA are different but claims 4 and 5 indicate that a truncated forms is also a split.
Claim 7 is confusing because claim 7 defines “the catalytic domain comprises amino acid residues 1-400 of SEQ ID NO: 1”.
The specification discloses:
[0116] The long splice variant of human OGA is a 103-kDa hydrolase containing a catalytic domain, a stalk domain, and a pseudo-histone acetyltransferase (HAT) domain interspersed by several disordered regions (Gao, Y., Wells, L., Comer, F. I., Parker, G. J. & Hart, G. W. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J. Biol. Chem. 2001, 276, 9838-45). Three groups recently reported the crystal structure of OGA by testing several truncated constructs and screening for domain boundaries in vitro (Li, B., Li, H., Lu, L. & Jiang, J. Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. Nat. Struct. Mol. Biol. 2017, 24, 362-369; Roth, C. et al. Structural and functional insight into human O-GlcNAcase. Nat. Chem. Biol. 2017, 13, 610-612; Elsen, N. L. et al. Insights into activity and inhibition from the crystal structure of human O-GlcNAcase. Nat. Chem. Biol. 2017, 13, 613-615). A nominally functional OGA variant was identified taking into account its structure that targeted a substrate of interest in living cells using three constructs with or without the nanobody: (1) the catalytic domain alone [OGA(cat)], (2) a construct lacking the C-terminal HAT domain [OGA(AHAT)], and (3) a construct with a glycine-serine linker replacing a disordered region in OGA(AHAT) [OGA(GS-AHAT)] (FIGS. 6A and 6B) (Li, B., Li, H., Lu, L. & Jiang, J. Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. Nat. Struct. Mol. Biol. 2017, 24, 362-369). To evaluate the enzymatic activities of these constructs in living cells, Nup62 tagged with GFP and a Flag-tag at the N terminus for detection, and an EPEA-tag at the C terminus for enrichment (GFP-Nup62, FIG. 6C) were used as a target protein due to the elevated levels of O-GlcNAc across multiple glycosites (Rexach, J. E. et al. Quantification of O-glycosylation stoichiometry and dynamics using resolvable mass tags. Nat. Chem. Biol. 2010, 6, 645-51). After co-expression of GFP-Nup62 with one of the three OGA constructs in HEK 293T cells, GFP-Nup62 was immunoprecipitated and O-GlcNAcylation levels were probed with the RL2 antibody against O-GlcNAc. OGA(AHAT) and OGA(GS-AHAT), reduced O-GlcNAc on GFP-Nup62 comparable to full-length human OGA (fl-OGA), but OGA(cat) was inactive, suggesting that the catalytic domain and the stalk domain, but not the HAT domain, were required for deglycosylation of GFP-Nup62 within cells (FIG. 7A).
Thus, the specification cites Roth (see below for a full citation) for a structural information of the domains. The diagram below copied from a supplemental information linked in Roth shows that the catalytic domain is the fragment starting from amino acid residue 11 to 396. Fig. 6A of the specification also designates catalytic domain from 60 to 366, not 1 to 400.
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Claim Rejections - 35 USC § 102
(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.
Claim(s) 1-5, 7, 8, 10-12, 15-22, 29, and 34 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramirez et al (“Ramirez”) Publication date: 2018/8/19, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Volume, 256.
Ramirez teaches a fusion protein comprising llama nanobodies to OGA O-GlcNAcase removes “Using llama nanobodies to engineer new protein tools for proximity-directed changes in O-GlcNAcylation of a specific protein” and “new flexible fusion proteins as tools that combine enzymes involved in OGlcNAc installation and removal with nanobodies, small ~12 kDa antibody like proteins derived from llamas, for redirection that allow us to specifically increase or decrease the amount of OGlcNAc on a target protein. We demonstrate that the fusion proteins are able to modify OGlcNAc stoichiometry to a variety of different protein targets carrying a short recognition tag, such as transcription factors, epigenetic regulators, and nucleoporins. O-GlcNAc stoichiometry was measured via affinity purification, mass-shift PEG-5Kda labeling, and mass spectrometrybased glycoproteomics experiments. The target proteins interact with our fusion proteins by coimmunoprecipitation and immunofluorescence experiments. Furthermore, the fusion proteins are readily engineered to directly modify an endogenous target protein using the appropriate nanobody. Overall, we have expanded the toolset available for researchers to control O-GlcNAc stoichiometry on target proteins that will accelerate understanding of the role of O-GlcNAc on specific proteins in cellular processes and in disease.
The fusion protein was made from a recombinant engineering using the polynucleotide claimed and host cells hovering the expression vectors.
Claim(s) 1-5, 7, 8, 10-12, 15-22, 29, and 34 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020092355 A2 (“Woo”, IDS item), published 2020-05-07. The copending Application No. 17289613 (PGPUB 2021/0395704 A1) cited below under NSDP is a 371 application.
Woo teaches a fusion protein comprising a nanobody fused to OGA. Note claims 1-7 on page 103.
As for claims 11 and 12, Woo teaches a nanobody targeting a green fluorescent protein (GFP). Note claims 10, 11, 14, and 15.
As for a peptide linker in claim 15, Woo teaches it on [0047] of PGPUB 2021/0395704 A1.
As for claim 15 drawn to a peptide linker, Woo teaches a peptide linker. Note [00128] “Plasmid #1 was a GFP nanobody fusion to full-length OGT”.
As for the rest of claims, note the entire teachings of Woo, especially claim.
Claim(s) 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Roth (IDS).
Roth teach to a split OGA comprising truncated catalytic domain and a truncated stalk domain. Note the diagram copied from Roth’s supplemental information.
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 1-5, 7, 8, 11, 12, 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8, 10, 12, 16, 20-22 of copending Application No. 17289613 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claims are drawn to a fusion protein comprising a single domain fused to OGA. Note claim 1 amended on 4/28/2025 and instant claim 2. The reference application is still being examined and the reference applicant is also rejected under provisional NSDP over the claims in the instant applications. In the reference application, applicant did not argue the respective claims are different inventions. Rather applicant stated (note for example, applicant’s remark on 14-15 filed 4/28/2025) that the reference application was filed earlier than the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Misook Yu whose telephone number is (571)272-0839. The examiner can normally be reached M-Th, 7-5pm.
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/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641