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 .
Amendments Received
Amendments to the claims were received and entered on 04/20/2026.
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Claims 11-17 are under consideration, as claims 1-7, 9-10, and 21-24 are withdrawn.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 05/12/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objections
In view of Applicant’s amendments, objections to the Specification are hereby withdrawn.
It is noted that claim 15
Withdrawn Rejections
In view of Applicant’s amendments, rejections of claims 14 and 17 under 35 USC § 112(b) are hereby withdrawn.
Claim Objections
Claim 17 is objected to because it depends from a rejected base claim.
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).
Examiner’s Note: For examination purposes, the phrase “reduction of functional Cosmc molecular chaperone in the cell and/or reduction of functional T-synthase in the cell” is interpreted under the broadest reasonable interpretation as encompassing any reduction in the functional activity of the respective proteins within the modified cell, and is not limited to reductions in expression level, protein abundance, or complete elimination of activity.
Regarding claim 11, 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). 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 additionally co-expressing His-sCosmc. Aryal et al. teaches that the ability of the CBRT motif to competitively bind COSMC, thereby inhibiting Cosmc-assisted folding of T-synthase (pg. 11635, bottom right column). Aryal et al. further teaches that insertion of the CBRT sequence into β4GalT1 confers Cosmc binding onto the β4GalT1 chimera, thereby producing a β4GalT1 construct capable of interacting with Cosmc through the same recognition motif required for T-synthase maturation.
Under the broadest reasonable interpretation, the claimed reduction of functional Cosmc molecular chaperone activity encompasses a reduction in Cosmc’s ability to perform its molecular chaperone function and is not limited to decreased protein expression or abundance. Because Aryal teaches expression of a β4GalT1 chimera that acquires the CBRT recognition motif and binds Cosmc through that motif, Aryal teaches expression of β1,4-galactosyltransferase in a cell while reducing functional Cosmc molecular chaperone activity, with the corresponding reduction in functional T-synthase activity taught by Aryal as the consequence of impaired Cosmc-assisted folding.
Aryal et al. expressly teaches throughout the reference that functional Cosmc is required for formation of active T-synthase and that disruption of the CBRT-Cosmc interaction results in inactive T-synthase. Accordingly, under the broadest reasonable interpretation, the disclosed β4GalT1-CBRT construct is reasonably interpreted as reducing functional Cosmc and/or functional T-synthase activity. Thus, the Hi-5 cell represented in Figure 6 is a cell modified to express β1,4-galactosyltransferase while simultaneously exhibiting reduced functional Cosmc molecular chaperone activity and/or 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 infected Hi-5 cells express β1,4-galactosyltransferase-CBRT chimeric proteins. The β4GalT1-CBRT protein constitutes a polypeptide product expressed by the modified cell, and Aryal et al. teaches infecting Hi-5 cells with a recombinant baculovirus construct encoding the β1,4-galactosyltransferase-CBRT chimera, whereby the infected cells express the recombinant β1,4-galactosyltransferase-CBRT polypeptide, thereby satisfying the limitation of instant claim 14 (pg. 11631, Experimental Procedures). 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.
Response to Arguments for Prior Art Rejections
In the Response filed on April 20, 2026, Applicant argues that Aryal et al. does not disclose the method recited in claim 11 or each of the claimed features because: (1) Aryal merely identifies and characterizes the interaction between COSMC and T-synthase and does not disclose reducing functional COSMC molecular chaperone activity and/or reducing functional T-synthase activity while overexpressing β1,4-galactosyltransferase in the same modified cell; (2) the experimental procedures of Aryal et al. utilize transformed cells only to express proteins for subsequent biochemical assays and do not disclose a modified cell simultaneously exhibiting the claimed modifications; (3) Figure 6 does not support the Office’s interpretation that expression of the β4GalT1-CBRT chimera reduces functional COSMC or T-synthase activity; (4) the enzyme activity assays were performed using cell lysates rather than living cells; and (5) Aryal et al. does not disclose the combined modifications recited in claim 11. Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below.
First, Applicant argues that Aryal et al. (herein “Aryal) merely identifies and characterizes the interaction between COSMC and T-synthase. However, Aryal teaches more than characterization alone. Aryal expressly teaches that COSMC is required for proper folding and functional activity of T-synthase, identifies the COSMC binding region within T-synthase (CBRT) as the specific recognition motif responsible for COSMC binding, teaches that disruption of the CBRT-mediated interaction results in inactive T-synthase, and further teaches that insertion of the CBRT sequence into β4GalT1 confers COSMC binding onto the β4GalT1 chimera. Thus, Aryal teaches both expression of β1,4-galactosyltransferase and the functional consequences associated with modification of the COSMC/T-synthase interaction.
Second, Applicant argues that Aryal does not disclose simultaneous overexpression of β1,4-galactosyltransferase together with reduced functional COSMC molecular chaperone activity and/or reduced functional T-synthase activity. This argument is not persuasive because the pending claims recite reduction of functional COSMC molecular chaperone activity and/or reduction of functional T-synthase activity, rather than requiring decreased protein expression, reduced protein abundance, or complete elimination of the corresponding proteins. Under the broadest reasonable interpretation, the claimed limitation encompasses any reduction in functional activity of COSMC and/or T-synthase within the modified cell. Aryal teaches expression of a β4GalT1-CBRT chimera in Hi-5 insect cells, wherein the inserted CBRT motif confers COSMC binding onto the β4GalT1 chimera through the same recognition motif required for maturation of active T-synthase. Aryal further teaches that disruption of the CBRT-COSMC interaction results in inactive T-synthase. Accordingly, Aryal teaches the claimed functional relationship.
Applicant further argues that “at no point does Aryal simultaneously co-express defective/non-functional COSMC/T-synthase and β4GalT1 in the cells.” This argument is likewise unpersuasive because the pending claims do not require co-expression of defective or mutant COSMC or T-synthase proteins. Rather, the claims require reduction of functional COSMC molecular chaperone activity and/or reduction of functional T-synthase activity. Under the broadest reasonable interpretation, this limitation encompasses any reduction in functional activity and is not limited to mutations, knockouts, knockdowns, decreased protein expression, or expression of defective proteins. Aryal instead teaches expression of a β4GalT1-CBRT construct that functionally interacts with COSMC through the CBRT recognition motif. Under the broadest reasonable interpretation, the resulting reduction in functional COSMC molecular chaperone activity and corresponding reduction in functional T-synthase activity satisfies the claimed limitation regardless of whether COSMC or T-synthase themselves are mutated or defective proteins.
Third, Applicant argues that Figure 6 does not demonstrate reduced COSMC or T-synthase activity and therefore does not support the Office’s interpretation. The rejection is not predicated solely upon a comparison of individual lanes within Figure 6. Rather, the rejection relies upon the disclosure of Aryal as a whole, including its express teachings that (i) COSMC is required for formation of active T-synthase, (ii) the CBRT motif is the recognition sequence through which COSMC binds T-synthase, (iii) disruption of this interaction results in inactive T-synthase, and (iv) insertion of the CBRT motif into β4GalT1 confers COSMC binding onto the β4GalT1 chimera. These express teachings, considered together, reasonably disclose the claimed reduction of functional COSMC molecular chaperone activity and corresponding reduction of functional T-synthase activity under the broadest reasonable interpretation of the claims.
Fourth, Applicant argues that the enzyme activity assays were performed using cell lysates and therefore do not represent modified cells. This argument is likewise unpersuasive. The pending claims recite modifying a cell. Aryal expressly discloses transforming Hi-5 insect cells with nucleic acid constructs encoding β4GalT1 and β4GalT1-CBRT, thereby producing modified cells expressing the disclosed constructs. The subsequent biochemical assays evaluate the properties and activities of proteins expressed by those modified cells. The fact that enzymatic activity was subsequently analyzed using cell lysates does not negate the disclosure of the preceding cellular modifications.
Finally, Applicant argues that Aryal does not disclose the claimed combination of modifications. As discussed above, Aryal teaches modified Hi-5 cells expressing β4GalT1-CBRT constructs, wherein the inserted CBRT motif confers COSMC binding onto β4GalT1, and further teaches the functional significance of the CBRT-COSMC interaction in producing active T-synthase. Under the broadest reasonable interpretation of the pending claims, Aryal therefore discloses a modified cell expressing β1,4-galactosyltransferase while exhibiting reduced functional COSMC molecular chaperone activity and corresponding reduction of functional T-synthase activity. Accordingly, Applicant’s arguments are not persuasive, and the rejection under 35 U.S.C. § 102 is maintained.
Examiner’s Note: Applicant’s request for withdrawal of the alleged objection to claim 15 is acknowledged. No objection for claim 15 was made in the previous Office action. Rather, the Office merely advised applicant that claim 15 could be objected to as a substantial duplicate of claim 14 should claim 14 ultimately be found allowable. Accordingly, no objection is presently maintained.
Conclusion
No claim is in condition for allowance.
THIS ACTION IS MADE FINAL. 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.
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
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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