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 II in the reply filed on 08/22/2025 is acknowledged. The traversal is on the ground(s) that the claims are directed to the categories of a product, a process for manufacturing the product, and the use of the product, thereby having unity of invention. Additionally, Applicant alleges that Aryal et al. does not teach or suggest a cell modified to overexpress β1,4- galactosyltransferase in the cell, enhance β1,4 galactosylation of a polypeptide product, and reduce O-GaINAc galactosylation activity in the cell, all at the same time. Applicant’s arguments were not found to be persuasive.
Regarding applicant’s arguments that the claims of Groups I-V possess unity of invention because they are directed to a product and processes of making and using said product, while claims may indeed fall into such categories, unity of invention further requires that the groups’ shared common technical feature makes a special technical contribution over the prior art. Merely reciting claims to a product, a process for making the product, and a use of the product does not, standing alone, establish unity. However, upon further review, the examiner has determined that Groups II and III should be combined and examined together. Therefore, claims 15-17 will be examined along with claims 11-14.
Regarding applicant’s argument that Aryal et al. does not teach or suggest a cell modified to overexpress β1,4- galactosyltransferase in the cell, enhance β1,4 galactosylation of a polypeptide product, and reduce O-GaINAc galactosylation activity in the cell, all at the same time, Applicant is reminded that the shared technical feature among the group of inventions is a modified cell, comprising (1) reduction of functional COSMC molecular chaperone and/or reduction of function T-synthase, and (2) overexpression of β1,4 galactosyltransferase. Enhancing β1,4 galactosylation of a polypeptide product is not a shared feature, as it is not a recited limitation of the cell, as currently presented in claim 1. Furthermore, it is noted that overexpressing β1,4 galactosyltransferase in the cell, does not necessarily equate to enhanced β1,4 galactosylation in the cell. The claim requires expression of the enzyme, but does not necessarily require that said enzyme is catalytically active. Reduction of O-GaINAc galactosylation activity in the cell, while recited in claim 1, is treated as an intended use/result of the modified cell, and is thus not given patentable weight (see MPEP 2111.02 II). Thus, Aryal et al. does disclose a modified cell (Hi-5 insect cells) engineered to overexpress β1,4 galactosyltransferase and have reduced functional COSMC chaperone and/or T-synthase activity, through introduction of a β4GalT1-CBRT chimera and co-expression of COSMC in said cell (see Fig. 6C-D, lane 8), rendering the COSMC functionally inactive as a molecular chaperone for T-synthase (described in further detail in art rejections below).
Therefore, the requirement, with the exception of combining Groups II and III, is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1-7, 9-17, and 21-24 are currently pending.
Claims 11-17 are under consideration, as claims 1-7, 9-10, and 21-24 are withdrawn.
Priority
The present application claims status as a 371 (National Stage) of PCT/EP2021/072287 filed on 08/10/2021 and claims priority to a foreign (United Kingdom of Great Britain and Northern Ireland) application GB2012512.6, filed on 08/11/2020. Acknowledgment is made of applicant' s claim for foreign priority and papers submitted under 35 U.S.C. 119 (a)-(d). In future actions, the effective filing date may change due to amendments or further review of priority documents.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/31/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., pg. 4 lines 21, 23, and 29; pg. 6 line 1, etc.). 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.
Claim Objections/Warnings
Applicant is advised that should claim 14 be found allowable, claim 15 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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.
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.
Claims 14 and 17 are 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 14 recites “the method according to claim 11, wherein the method further comprises modifying the cell to express a polypeptide product. The claim is indefinite as it is unclear what modification is required by “modifying the cell to express a polypeptide product”. It is not clear whether the claim requires, for example, introduction of a heterologous nucleic acid encoding a polypeptide of interest, modification of endogenous gene regulatory elements, or some other unspecified modification. In the interest of compact prosecution, the examiner is interpreting “modifying the cell to express a polypeptide product” as encompassing the introduction of a heterologous nucleic acid encoding a recombinant protein, into the cell.
Clarification is required.
Claim 17 is indefinite and unclear due to the recitation of “…a UMG feeding strategy comprising or consisting of…”, which introduces an internal inconsistency as to whether additional components may be present in the recited feeding strategy, thereby rendering the scope of the claim uncertain.
Clarification is required.
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.
Claims 11-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Aryal et al. (Identification of a novel protein binding motif within the T-synthase for the molecular chaperone Cosmc. J Biol Chem. 2014 Apr 25;289(17):11630-11641, cited in the IDS).
Aryal et al. teaches that Cosmc is required for T-synthase folding, activity and synthesis of O-glycans, and discloses the region of the T-synthase that is essential for binding to Cosmc (Cosmc binding region within T-synthase, or CBRT). Aryal et al. further teaches that mutations within CBRT result in the formation of inactive T-synthase (Abstract and Fig. 1).
Regarding claim 11, Aryal et al. discloses insect Hi-5 cells expressing wild-type and chimeric β1,4-glycosyltransferase-CBRT constructs as shown in Figure 6. Specifically, lanes 7 and 8 of Figure 6 correspond to cells expressing a β1,4-galactosyltransferase-COSMC binding region T-synthase (β4GalT1-CBRT) chimera, with lane 8 further including co-expression of COSMC. Aryal et al. expressly contemplated the ability of the CBRT motif to competitively bind COSMC, thereby inhibiting Cosmc-assisted folding of T-synthase (pg. 11635, bottom right column). Accordingly, expression of the β4GalT1-CBRT chimera in COSMC-containing cells (i.e., Fig. 6 - lane 8) inherently reduces the functional availability of COSMC as a molecular chaperone, necessarily reducing T-synthase activity, as the CBRT sequence occupies the COSMC-binding interface required for T-synthase maturation. As demonstrated in Figure 6C, lanes 7 and 8 exhibit expression of β1,4-galactosyltransferase activity attributable to the chimera. Simultaneously, Figure 6D shows that T-synthase activity in lane 8 is further reduced relative to lane 6 (wild-type β4GalT1 + COSMC), confirming that COSMC function is competitively sequestered by the CBRT-containing construct and therefore unavailable to chaperone T-synthase. The functional consequence of this sequestration is an effective reduction of both COSMC and T-synthase activity within the same cell. Thus, the Hi-5 cell represented in lane 8 of Aryal et al. is a cell modified to express β1,4-galactosyltransferase while simultaneously exhibiting reduced functional COSMC molecular chaperone activity and reduced T-synthase activity, satisfying the limitations of the instant claim. It is noted that the claim preamble recites “to enhance β1,4-galactosylation of a polypeptide product”, which is being treated as an intended use and/or intended result, thus not given patentable weight. It is further noted that the recitation of “reducing O-GalNac galactosylation activity in the cell” merely describes an intended result of the recited modifications (i.e., reduction of functional COSMC and/or T-synthase) and does not introduce an additional manipulative step. Accordingly, the phrase is treated as an intended result for examination purposes, and is interpreted as describing the inherent functional consequence of the recited modifications.
Regarding claim 12, as described above, Aryal et al. discloses preparation of a nucleic-acid construct encoding human-soluble β-1,4-galactosyltransferase I and its chimeric form HPC-4-s-β-4-GalT1-CBRT, as synthesized by GeneScript and cloned by the Emory DNA Core Facility (pg. 11631, Experimental Procedures, “Preparation of Expression Constructs and Peptides,”). Aryal further teaches infection of insect Hi-5 cells with baculoviruses carrying these constructs for expression (pg. 11631, “Pull-down and T-synthase activity assay”). The delivery of said constructs into cells via recombinant baculovirus constitutes transformation of the cells with nucleic acid encoding β-1,4-galactosyltransferase as required by instant claim 12.
Regarding claim 13, as described above, Aryal et al. teaches modifying the gene encoding COSNC and/or T-synthase through construction of multiple truncation mutants (pg. 11631, right column, “Preparation of Expression Constructs and Peptides”) and a chimeric fusion protein comprising β1,4-galactosyltransferase fused to the COSMC binding region of T-synthase (CBRT). Aryal et al. demonstrates direct modification of the gene encoding T-synthase to produce the variants and chimeric derivatives, which inherently disrupt or abolish the native expression of functional T-synthase.
Regarding claim 14, as described above, Aryal et al. teaches that the transfected Hi-5 cells express β1,4-galactosyltransferase-CBRT chimeric proteins. The β4GalT1-CBRT protein constitutes a polypeptide product expressed by the modified cell, satisfying the limitation of instant claim 14. It is noted that no requirement exists that the expressed product differ from the glycosyltransferase encoded by the transformation construct; thus, the polypeptide product of Aryal et al. meets the recited condition.
Regarding claim 15, Aryal et al. describe incubating (correlates to culturing) the transfected insect cells prior to enzymatic assays, which constitutes incubating the modified cells for expression of the recombinant β4GalT1-CBRT polypeptide product (pg. 11631-11632). Accordingly, the steps of claim 15 are explicitly met by the experimental procedures disclosed in Aryal et al.
Regarding claim 16, the limitation “wherein the polypeptide is produced to have at least 0.5 fold increased β1,4-galactosylation and/or 0.5 fold increased bi-galactosylation” is considered an intended result of the method of claim 15, upon which claim 16 depends. Since Aryal et al. explicitly teaches a polypeptide produced by the method of claim 15, a 0.5 fold increase in β1,4-galactosylation thereby represents an inherent result of the disclosed method.
Thus, the subject matter of instant claims 11-16 are anticipated by the teachings of Aryal et al.
Conclusion
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAGHMEH NINA MOAZZAMI whose telephone number is (703)756-4770. The examiner can normally be reached Monday-Friday, 9:00-5:00.
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/NAGHMEH NINA MOAZZAMI/Examiner, Art Unit 1652
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652