DETAILED ACTION
Status of Application
The amendments and response filed 16 July 2026 are acknowledged and have been considered in their entireties. Claims 3, 5, 9-13, 15-18, 20-22, 24-25, 28, 30-38, 40-43, 45, 47, 49-50 are canceled, claims 51-56 are new and dependent upon previously examined claim 6. Thus, claims 1-2, 4, 6-8, 14, 19, 23, 26-27, 29, 39, 44, 46, 48 and 51-56 are pending; Claims 27, 29, 39, 44, 46 and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.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, claims 1-2, 4, 6-8, 14, 19, 23, 26 and 51-56 are subject to examination on the merits.
Withdrawal of Previous Objections/Rejections
The rejection of claims 1-2, 6-8, 14, 23 and 26 under 35 U.S.C. 101 is withdrawn in view of the amendments to incorporate the limitations of claim 3 into claim 1, e.g. the signal peptide is removed and replaced by an initiator methionine.
The rejection of claim(s) 1-2, 14, 19 and 23 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ruddock, L. (US 9238817 – cited previous PTO-892) is withdrawn in view of the amendments to incorporate the limitations of claim 3 into claim 1, e.g. the signal peptide is removed and replaced by an initiator methionine.
The rejection of claim(s) 1-2, 6, 14, 19, 23 and 26 under 35 U.S.C. 102(a)(1) as being anticipated by Hirrano et al. (Eur. J. Biochem., 1995 – cited previous PTO-892) as evidenced by Zhu et al. (Reproduction, 2010 – cited previous PTO-892) is withdrawn in view of the amendments to incorporate the limitations of claim 3 into claim 1, e.g. the signal peptide is removed and replaced by an initiator methionine.
The rejection of claim(s) 1-4, 7, 14, 19, 23 and 26 under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (J. Thromb. And Heam., 2019 – cited previous PTO-892; hereafter Wang 2019) as evidenced by Wang et al. (Antioxidants & Redox Signaling, 2013 – cited previous PTO-892; hereafter Wang 2013) and Galligan et al. (Human Genomics, 2012 – cited previous PTO-892) is withdrawn. As Applicant’s point out, hPDI is expressed from p4hb.
New Objections/Rejections – Necessitated by Claim Amendments
Claim Objections
Claim 51 is objected to because of the following informalities: the PDI gene P4HB is repeated twice in the claim (lines 3 and 4). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 8 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.
The claim states that one of the human PDI gene family members is “GR2”. However, there is no “GR2” protein disulfide isomerase that exists. Rather, there is an “AGR2”. For examination purposes, “GR2” will be interpreted to be “AGR2” which is consistent with the specification.
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) 1-2, 4, 7-8, 14, 19, 23 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nguyen et al. (Acta Cryst F, 2018 – cited herein).
Nguyen et al. teach:
Regarding claims 1, 2, 4, 7 and 8, the human disulfide isomerase anterior gradient protein 3 (AGR3), which has the first 23 amino acids, which is the ER signal peptide, removed to produce the mature form of the enzyme, wherein said mature enzyme further comprises an N-terminal initiator methionine and an epitope tag of Hisx6 (MHHHHHHM) – See Abstract and Section 2.1. It is noted, His6x is defined as an epitope tag in the instant specification (see paragraph 0080, PG-Pub).
Regarding claims 14, 19 and 23, the construct was cloned into an expression vector pVD1 and introduced/expressed in the host cell E. coli. – Section 2.1, first paragraph:
The gene for mature human AGR3(Ile24–Leu166; UniProt Q8TD06) was amplified by PCR from IMAGE clone 4694757 using a forward primer that contained an NdeI restriction site and a reverse primer that contained a BamHI restriction site (Table 1). The gene was cloned into a derivative of pET-23b (Novagen), which results in expression from a T7 promoter of a protein with a noncleavable N-terminal His tag with the sequence MHHHHHHM. The plasmid generated (pVD1) was sequenced to ensure there were no errors in the cloned gene. pVD1 was transformed into the expression strain Escherichia coli BL21(DE3)pLysS using the calcium chloride heat shock method. An isogenic expression strain was saved as duplicate glycerol stocks and stored at 70C.
Regarding claim 26, the ARG3 purified protein was formulated into 20 mM Tris buffer at pH 6.8 which is a pharmaceutically acceptable carrier (See last paragraph of Section 2.1)
Claim(s) 1-2, 4, 6-7, 14, 19, 23, 26 and 52-56 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kozlov et al. (Structure, 2004 – cited herein) as evidenced by Zhu et al. (Reproduction, 2010 – cited previous PTO-892) and as evidenced by GeneScript pGEX-6P-1 sequence map (cited herein).
Kozlov et al. teach:
Regarding claims 1-2, 4, 6-7, 14, 19, 23, 26 and 52-56, the human protein disulfide isomerase GRP58/ERp57 comprising an N-terminal deletion of amino acids 1-23 which is the N-terminal ER signal sequence. Said protein was expressed as a fusion protein with the epitope tag GST (see instant paragraph 0080, PG-PUB) and produced in the expression vector pGEX-6P-1 and produced in E. coli host cells. (See Experimental Procedure: Protein Expression, Preparation, and Purification, p. 1337). Said protein was further purified and was in a pharmaceutically acceptable GST buffer. The GeneScript vector/plasmid information for pGEX-6P-1 evidences that the GST epitope tag/protein begins with an N-terminal initiator methionine. Thus, effectively, the ER signal sequence is removed and replaced with an initiator methionine containing GST epitope/protein.
Regarding claims 6, 52-56, Zhu evidences GRP58/ERp57 comprises a nuclear localization signal at the C-terminus – See Figure 1 (reproduced herein).
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Conclusion
1-2, 4, 6-8, 14, 19, 23, 26 and 52-56 are rejected. Claim 51 is objected to for a minor formality and is also 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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 23 September 2026
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