DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 15 October 2025 has been entered.
Election/Restrictions
Claim 172 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 13 June 2022.
Drawings
The drawings were received on 23 March 2023. These drawings are acceptable.
Claim Rejections - 35 USC § 103
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 173 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Rao et al. (2010) (WO 2010/037001 A2) in view of Sletten et al. (2009 Sep. 1) (Bioorthogonal chemistry: fishing for selectivity in a sea of functionality, Angew Chem Int Ed. 2009;48(38):6974-98. doi: 10.1002 /anie.200900942).
The teachings of Rao et al., (2010) (WO 2010/037001 A2) have been documented in the Examiner’s Answer mailed on 04/24/2024.
Rao et al. (2010) do not teach modification of the glucose portion of a uridine diphosphoglucose (UDP-Glu) molecule with azide or thio moiety recited in amended claim 173 field on 10/15/2025.
Sletten et al. (2009) teach:
The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules. (See Abstract).
Sletten et al. (2009) teach:
“4.3 - Reactions of Azides and Alkynes: An alternate mode of reactivity for the azide is its participation as a 1,3-dipole in a [3+2] cycloaddition with alkenes and alkynes. This reaction, first reported at the end of the 19th century, has been proposed to proceed by a concerted cycloaddition since the 1950s, when Rolf Huisgen introduced the concept of 1,3-dipolar cycloadditions. However, the high temperatures or pressures required to promote the cycloaddition of azides and most dipolarophiles are not compatible with living systems. Nevertheless, the potential of this transformation, especially the cycloaddition of azides and alkynes to form aromatic triazole products (ΔG° ≈ -61 kcal mol-1), was too great for it to be overlooked”. (See bridging paragraph, pages 6985-6986).
Sletten et al. (2009) further teach:
Azides and other unnatural groups have also been incorporated into cell-surface sialic acid residues by using the sialic acid analogues directly. Modification of the 5-N-acyl and 9-OH positions of sialic acid are well tolerated, and numerous unnatural groups have been introduced therein to study sialic acid binding events. Alkyl and aryl azides have been incorporated into cell-surface glycans through sialic acid precursors modified at the 5- and 9-positions (56–58). Photo-cross-linking of sialic acid 58 was used to study the glycan ligands for CD22. Tanaka and Kohler have performed similar photo-cross-linking studies using a diazirine- containing ManNAc derivative, 60 (ManNDAz).[296] Luchansky et al. employed sialic acids 56, 57, and 59 along with their corresponding ManNAc precursors 53, 61, and 51 to show that bypassing the first step of the sialic acid biosynthetic pathway often increases the yield of cell-surface glycans. Notably, the sialic acid biosynthetic pathway proved to be just as efficient as the salvage pathway for the incorporation of azides into sialic acid residues when ManNAz (53) and the corresponding azidosialic acid 56 were employed as substrates.
Fucosylated glycans have been labeled with 6-azidofucose 62; however, fucose 62 was found to be toxic in many mammalian cell lines and has not been extended into living animals. Wong and co-workers reported the use of 6-alkynyl fucose 63, which was less toxic than the azido analogue. The Wong research group also successfully labeled cell surface sialic acids with alkynyl ManNAc precursor 64, and Wu and co-workers used the same metabolite to label cell surface glycans in mice. The degree of sialic acid metabolic labeling with alkynyl ManNAc is superior to that of ManNAz; however, the alkyne must be detected by using CuAAC, which is not ideal for the detection of glycans in a living system, because of the toxicity of copper(I). Yarema and co-workers reported the metabolic labeling of sialic acids on stem cells with thio-ManNAc analogue 65 (ManNTGc) and showed that this unnatural glycan influenced their differentiation.
(See last paragraph page 6991, bridging to first paragraph page 6992).
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Scheme 19. Unnatural carbohydrate metabolites for use in metabolic oligosaccharide engineering. A) N-Acetylmannosamine (ManNAc) metabolites. B) Sialic acid (Sia) metabolites. C) N-Acetylgalactosamine (GalNAc) metabolites. D) N-Acetylglucosamine (GlcNAc) metabolite. E) Fucose (Fuc) metabolites. (Page 6991)
It would have been prima facie obvious for a skilled artisan to modify the glucose portion of a uridine diphosphoglucose (UDP-Glu) molecule with azide or thio moiety following the teachings of Sletten et al. in the “Unnatural carbohydrate metabolites for use in metabolic oligosaccharide engineering” shown demonstrated in Scheme 19.
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In view of the above presentation and in the absence of convincing evidence to the contrary, claim 173 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Rao et al. (2010) (WO 2010/037001 A2) in view of Sletten et al. (2009 Sep. 1) (Bioorthogonal chemistry: fishing for selectivity in a sea of functionality, Angew Chem Int Ed. 2009;48(38):6974-98. doi: 10.1002 /anie.200900942)
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 173 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 6, 8, and 9 of U.S. Patent No. 8,741,567 (Date of Patent 06/03/2014, US application 13/095,505) in view of Sletten et al. (2009 Sep. 1) (Bioorthogonal chemistry: fishing for selectivity in a sea of functionality, Angew Chem Int Ed. 2009;48(38):6974-98. doi: 10.1002 /anie.200900942)
The teachings of Rao et al., (2010) (WO 2010/037001 A2) have been documented in the Examiner’s Answer mailed on 04/24/2024.
The teachings of Sletten et al. (2009 Sep. 1) have been documented in the 35 USC 103(a) rejection set forth above in this Office action.
While the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘567 patent are drawn to a method, which in claim 1, comprises
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As seen in dependent claims 3, 5, 6, 8, and 9:
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While claim 1 of the ‘567 patent is to “a method for distinguishing” and not “a method for detecting”, it is noted that the patented method of distinguishing is to result in detection of 5-hydroxymethylcytosine which has a “modified glucose molecule” which, as seen in claims 5 and 6 comprises an azide linker or a thiol linker. It is further noted that claim 15 of the ‘567 patent requires “sequencing”, which is deemed to be required of “detecting” the modified nucleotide of the claimed method.
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682