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 arguments, see pg. 10, paragraph 2; pg. 11, last paragraph of the page; pg. 12, paragraph 3; pg. 12, paragraph 4; pg. 12, last paragraph of the page – pg. 13, paragraph 1; and pg. 13, the first two paragraphs from the bottom of the page of Applicant's remarks, filed March 10, 2026, with respect to Applicant’s election of (3S,4R,5S,6R)-6-(acetoxymethyl)-3-(cyclobutanecarboxarnido)tetrahydro-2H-pyran-2,4,5-triyl triacetate / Acetyl 3,4,6-tri-O-acetyl-2-cyclobutanecarboxamido-2-deoxy-α/β-D-rnanno-hexopyranoside, recited in lines 2-4 of instant claim 1, wherein the compound is also known as compound (i) within claim 1, have been fully considered and are persuasive.
The application has been examined on the merits to the extent readable on the elected compound and is hereby expanded to include the species grouping of compounds (i)-(iv), recited in claim 1, lines 2-13.
Furthermore, with respect to Applicant’s argument the claims now possess unity of invention due to the deletion of compound (xii) recited in claim 1, pg. 3, lines 13-15, see Applicant’s remarks, pg. 8, A. The Claims Posses Unity of Invention, paragraph 1; the Examiner notes Yarema teaches (3S,4R,5S,6R)-6-(acetoxymethyl)-3-(cyclohexanecarboxamido)tetrahydro-2H-pyran-2,4,5-triyl triacetate / Acetyl 3,4,6-tri-O-acetyl-2-cyclohexanecarboxamido-2-deoxy-α/β-D-manno-hexopyranoside, i.e. compound (iii), as recited in claim 1, lines 8-10, and is explained in further detail in the maintained 103 rejection below.
Thus, since the teachings of Yarema correspond to compound (iii) as recited in claim 1, lines 8-10, the Examiner reasonably determines the claims as amended by Applicant as discussed above do not possess unity of invention.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 03/10/2026 has been considered by the Examiner inasmuch as foreign documents have been submitted into the file wrapper in English.
Claim Status
The claim set and Applicant’s remarks filed March 10, 2026 have been entered. Claims 14-16 are canceled. Claims 9-13 and 17-18 are withdrawn from further consideration as being drawn to a nonelected invention.
Thus, claims 1-8 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on December 10, 2025:
(I) The objection to claims 1 and 7 is withdrawn in view of Applicant’s amendments to claims 1 and 7.
(II) The rejection of claim 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment to claim 8.
Response to Arguments
The rejection of claims 1-6 under 35 U.S.C. 103 is maintained.
Applicant argues:
(A) Yarema discloses an extraordinarily broad Markush genus with numerous independently-variable substituents, resulting in multitudes of possible combinations but no guidance toward specific structural features of compound 1, see Applicant’s remarks, pg. 9, D. The Claims are Patentable over Yarema, paragraph 3.
(B) Yarema’s working examples and preferred embodiments focus on aromatic N-acyl substitutents, particularly Ac4Glc2Bz and Ac4Gal2Bz. The only non-aromatic cycloalkyl specifically mentioned is cyclohexyl (a 6-membered ring) (present within the exemplified compound known as Ac4GlcNCyx of Yarema), and there is no disclosure of cyclobutyl, cyclopentyl or any small-ring cycloalkyl carboxamide; therefore, a person of ordinary skill in the art following Yarema’s teachings would be led toward benzamide-type compounds, not toward small saturated cycloalkyl rings, see Applicant’s remarks, pg. 9, D. The Claims are Patentable over Yarema, paragraph 3 – pg. 10, paragraph 1.
(C) Therefore, Yarema provides no teaching or suggestion that would direct a skilled person to select the specific combination of
(i) a ManNAc scaffold,
(ii) an N-cycloalkyl (e.g., cyclobutanoyl) acyl at C-2; and
(iii) the specific stereochemistry of the elected compound, among the myriad theoretical possibilities encompassed by Yarema’s broad Markush list, and therefore it appears by only impermissible hindsight of Applicant’s claimed compound 1 could the person “combine elements to yield predictable results”, see Applicant’s remarks, pg. 10, paragraph 1.
With respect to Applicant’s arguments (A)-(C), the Examiner notes the election of species has been expanded to include the first four compounds recited within claim 1 corresponding to compounds (i)-(iv) recited in claim 1, lines 2-13 as discussed above; which the Examiner respectfully notes are peracetylated mannosamines where the -NH-C(O)- connected to the mannopyranoside core is substituted with a cycloalkyl having between 4 and 7 carbon atoms.
The Examiner also notes Yarema teaches the exemplified compound known as Ac4Man2Bz; and notes the only structural difference between Ac4Man2Bz of Yarema and the compound known as compound (iii) as recited in claim 1, lines 8-10, is the presence of a benzyol at C-2 of the Ac4Man2Bz of Yarema vs the cyclohexanoyl at C2 on the mannosamine on compound (iii) as recited in claim 1, lines 8-10.
The Examiner also notes Yarema explicitly teaches the compounds may have other substituents instead of the benzamide group on the N-acetyl group of the hexosamine, and explicitly teaches a cyclohexane, see Yarema, paragraph [0118]; additionally, the Examiner also notes in the 103 rejection below, Yarema further explicitly teachings that all such isomeric forms of these compounds are expressly included in the present invention as discussed in the maintained 103 rejection below.
Therefore, the Examiner notes the teachings of Yarema as discussed in the preceding two paragraphs as written above correspond to the recited compound (iii) in claim 1, lines 8-10.
Thus, in view of the teachings of Yarema as discussed above, Yarema’s teachings provide guidance to arrive at a compound with:
(i) a ManNAc scaffold,
(ii) an N-cycloalkyl (e.g., cyclohexanoyl) acyl at C-2; and
(iii) the specific stereochemistry disclosed in compound (iii) as recited in claim 1, lines 8-10, and discussed in greater detail within the maintained 103 rejection below.
Finally, in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
(D) Applicant refers to paragraph [000193] of the specification which discusses comparative analysis in Figure 9A of compound 1b (known as Ac4ManMCb or MA-3), and wherein the Examiner also notes corresponds to the elected compound recited in claim 1, lines 2-4, see paragraphs [0047] and [0257], wherein Figure 9A demonstrates compound 1b increases flux of sialic acid biosynthesis when compared to the corresponding five carbon straight chain N-pentanoyl analogue of compound 1g, wherein compound 1g did not show any effect, and where Applicant suggests that steric effects played a prominent role, Applicant’s remarks, see pg. 10, paragraph 2.
With respect to Applicant’s argument (D), the Examiner notes the cyclopropanoyl glucopyranoside analogue 2a also shown within Figure 9A does not appear to show an increased flux of sialic acid biosynthesis, whereas its cyclopropanoyl mannopyranoside analogue 1a does increase flux of sialic acid biosynthesis within Figure 9A.
Therefore, based on Applicant’s results it appears that steric effects, for example the inclusion of N-cycloalkyl (e.g. cyclobutanoyl-cycloheptanoyl) acyls at C-2, as well as specific stereochemical configurations of the hexosamine, for example the cyclopropanoyl mannopyranoside analogue 1a is an α-D-mannopyranose; while the cyclopropanoyl glucopyranoside analogue 2a is a β-D-glucopyranose; might both play a role in the effect of modulating flux of sialic acid biosynthesis.
Accordingly, based on the experimental data provided by the cyclopropanoyl glucopyranoside analogue compound 2a above, Applicant’s argument of the effect of increasing flux of sialic acid biosynthesis is openly questionable to other sugar scaffolds such as glucopyranosides and/or potentially with regard to the specific stereochemistry of the hexosamine used, for example the α/β designation of the C1 hydroxyl of the manno-hexopyranoside; as the Examiner particularly notes compounds (i)-(iv) recited in claim 1, lines 2-13, encompass both α/β-D-manno-hexopyranosides.
The Examiner also particularly notes it appears Applicant does not test any cycloalkyl analogues other than the cyclopropanoyl or the cyclobutanoyl analogue of mannopyranoside, which is in addition to the cyclopropyl glucopyranoside analogue discussed above; and therefore this is particularly noteworthy as claim 1, lines 2-13, recites N-cycloalkyl (e.g. cyclobutanoyl-cycloheptanoyl) acyl analogues of α/β-D-mannopyranoside; and thus the Examiner notes the evidence as discussed within Applicant’s argument (D) does not appear to be commensurate in scope with the grouping of compounds (i)-(iv) as recited within claim 1, lines 2-13 as discussed above.
(E) The specification provides extensive comparative data demonstrating the N-cyclobutanoyl ManNAc analogue (e.g. compound 1b above) exhibits unexpected and superior biological activity, by discussing in paragraph [000194] and in Figure 8b the elected compound 1b showed a four-fold increase in sLeX expression, which is the maximum among the analogues, see Applicant’s remarks, pg. 11, last paragraph of the page.
(F) The specification further demonstrates a differential property of N-cyclobutanoyl analogue compound 1b which was not captured by the N-cyclopropyl compound 1a, thus highlighting the significance of ManNAc analogue-structure dependent biological outcomes, Applicant’s remarks, pg. 12, paragraph 3.
(G) The specification provides flow cytometry results revealing a robust and significant increase of 2.3-fold in cells treated with compound 1b (50µM, 72h) with respect to untreated cells; and the controls treated with compound 1a showed no significant change with respect to untreated cells, and therefore critically the cyclopropanoyl analogue compound 1a showed no significant change in E-selectin binding compared to untreated cells, while the cyclobutanoyl analogue compound 1b showed a robust 2.3-fold increase, see Applicant’s remarks, pg. 12, paragraph 4.
(H) The specification discloses it is seen that HL-60 cells pre-incubated with the cyclobutanoyl analogue compound 1b exhibited about 40% increase in the numbers of adhered cells on mCD62E coated surface compared to all other conditions, and these results established that treatment with compound 1b, but not controls, resulted in increased binding to CSLEX1, mCD62E, and MAL-II, and in turn exhibited improved adherent properties to E-selectin coated surfaces in a static adhesion model, see Applicant’s remarks, pg. 12, last paragraph of the page – pg. 13, paragraph 1.
With respect to Applicant’s arguments (E)-(H), the Examiner reiterates the argument that it appears Applicant does not test any cycloalkyl analogues other than the cyclopropanoyl or the cyclobutanoyl mannopyranoside analogue, which again the Examiner respectfully reiterates appears to not be commensurate in scope with the grouping of compounds (i)-(iv) as recited within claim 1, lines 2-13 as discussed above.
(I) The scope of Yarema and the present instant application are fundamentally different, as Yarema is directed to compounds as UAP inhibitors which function by reducing glucose flux through the hexosamine biosynthetic pathway, in order to suppress an abnormal glycolysis pathway, see Applicant’s remarks, pg. 13, second paragraph from the bottom of the page.
(J) The present invention is directed to peracetylated hexosamine substrates that are actively fed into cellular metabolic pathways to modulate glycan biosynthesis; and as disclosed in Example 2, paragraph [00158], and Figure 1, of the present application, the claimed compounds are designated for metabolic incorporation and reprogramming of cell-surface sialoglycans, thereby modulating cell-cell, cell-matrix, and cell-pathogen interactions, as well as cell migration, see Applicant’s remarks, pg. 13, last paragraph of the page.
With respect to Applicant’s arguments (I)-(J), the Examiner notes the specification in paragraph [000100] discloses a compound selected from a compound of Formula II where the compound inhibits, modulates, alters, or enhances cell-cell interactions, cell-pathogen interactions, or cell-extracellular matrix interactions.
Furthermore, paragraph [0009] in the specification discloses Formula II which encompasses compound (iii) as recited in claim 1, lines 8-10, when R1 and R’1 are all -C(O)C1 alkyl, R2 is hydrogen, m is 0, and n is 4.
Therefore, compound (iii) as recited in claim 1, lines 8-10 is disclosed by Applicant’s specification to be a compound that includes either inhibiting, modulating, altering, or enhancing cell-cell interactions, cell-pathogen interactions, or cell-extracellular matrix interactions.
Consequently, Applicant’s arguments (A)-(J) have been fully considered but are not found persuasive.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention 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 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6 remain rejected under 35 U.S.C. 103 as being unpatentable over Yarema et al. (Published 31 May 2018, filed 14 August 2015, US-20180148468-A1, PTO-892 mailed 12/10/2025).
Yarema teaches UAP inhibitors to inhibit glucose flux in the hexosamine biosynthetic pathway, see abstract.
Yarema teaches a pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt, wherein said compound or said salt thereof is depicted as
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, wherein X is selected from and including CO, see paragraph [0028].
Yarema teaches R6, R7, R8 and R9 are each independently selected from and including CO(CH2)nCH3, see paragraph [0029]; wherein n is 0-16, see paragraph [0031]; and R is selected from the group consisting of and including
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, see paragraph [0031]; wherein i is 0 to 16 and k is 0 to 10, see paragraph [0033].
Yarema teaches all such isomeric forms of these compounds are expressly included in the present invention, see paragraph [0192].
Yarema teaches the pharmaceutical composition comprises a pharmaceutically acceptable carrier, see paragraph [0217]; and exemplifies said carrier can be an excipient, see paragraph [0218].
Yarema exemplifies the compound known as Ac4Man2Bz which has the following structure,
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, see pg. 10, first row, second recited structure.
Although, Yarema does not exemplify the compound is (3S,4R,5S,6R)-6-(acetoxymethyl)-3-(cyclohexanecarboxamido)tetrahydro-2H-pyran-2,4,5-triyl triacetate / Acetyl 3,4,6-tri-O-acetyl-2-cyclohexanecarboxamido-2-deoxy-α/β-D-manno-hexopyranoside, i.e. compound (iii) as recited in claim 1, lines 8-10, as discussed in the Election/Restriction section above and required in claims 1-6.
Additionally, the Examiner notes the exemplified compound of Ac4Man2Bz as shown above depicts an -NH-benzoyl at the C-2 position.
However, the Examiner respectfully notes when R is
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and i is 0 and k is 4 as taught in the general formula of Yarema above; the compound of Yarema as exemplified above would exhibit an -NH-cyclohexanoyl at the C-2 position on the core structure of the exemplified compound Ac4Man2Bz as shown above.
The Examiner also notes Yarema explicitly teaches the compounds may have other substituents instead of the benzamide group on the N-acetyl group of the hexosamine, and explicitly teaches a cyclohexane, see Yarema, paragraph [0118].
Therefore, the teachings of Yarema as discussed in the preceding four paragraphs as written above correspond to the recited compound (iii) in claim 1, lines 8-10 as discussed above.
Additionally, the Examiner reasonably interprets the wavy line (e.g. squiggly line) within Ac4Man2BZ of Yarema above denotes a substituent that can be either axial or equatorial; which is further supported in view of Yarema’s teaching that all such isomeric forms of these compounds are expressly included as discussed above.
The Examiner also respectfully notes when the substituent -NH-X-R of Yarema above is axially (upwardly) oriented and when the substituent -OR7 of Yarema is equatorially (downwardly) oriented it would correspond to the manno-configuration core as required within compound (iii) of claim 1, lines 8-10, as discussed above and is further supported by the exemplary compound Ac4Man2Bz of Yarema shown above.
Therefore, based on the teachings of Yarema and the interpretations of the Examiner as discussed above the Examiner respectfully notes the teachings of Yarema teach compound (iii) of claim 1, lines 8-10, which is known as (3S,4R,5S,6R)-6-(acetoxymethyl)-3-(cyclohexanecarboxamido)tetrahydro-2H-pyran-2,4,5-triyl triacetate / Acetyl 3,4,6-tri-O-acetyl-2-cyclohexanecarboxamido-2-deoxy-α/β-D-manno-hexopyranoside as discussed above.
Furthermore, with respect to the limitations of:
(A) the compound has a glycomimetic structure, both directly and via metabolic processing, for modifying sialoglycans, mucin-type O-glycans (MTOG), selectins, siglecs, B-O-GlcNAc-ylation, or combinations thereof, as required in claim 2;
(B) wherein the compound modifies the interactions as required in claims 3-4; and
(C) the compound is an adjunct in combinatorial cancer chemotherapy or an adjunct in combinatory cancer immunotherapy, required in claim 5; the Examiner reasonably interprets these limitations to either be (1) a physical characteristic of the selected compound of claim 1 when referring to the limitation “a glycomimetic structure” of limitation (A) or an adjunct of limitation (C); or (2) a functional characteristic of the selected compound of claim 1 for example modifying the siaglycans within limitation (A) or modifying the interactions within limitation (B). Since Yarema teaches all structural elements of compound (iii) of claim 1, recited in lines 8-10, which is known as (3S,4R,5S,6R)-6-(acetoxymethyl)-3-(cyclohexanecarboxamido)tetrahydro-2H-pyran-2,4,5-triyl triacetate / Acetyl 3,4,6-tri-O-acetyl-2-cyclohexanecarboxamido-2-deoxy-α/β-D-manno-hexopyranoside as written above; the Examiner reasonably interprets the teachings of Yarema would exhibit all physical and functional characteristics as recited in limitations (A)-(C) as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have chosen from the specific limitations as taught by Yarema above in order to arrive at compound (iii) known as (3S,4R,5S,6R)-6-(acetoxymethyl)-3-(cyclohexanecarboxamido)tetrahydro-2H-pyran-2,4,5-triyl triacetate / Acetyl 3,4,6-tri-O-acetyl-2-cyclohexanecarboxamido-2-deoxy-α/β-D-manno-hexopyranoside as recited in claim 1, lines 8-10, as within the scope of the artisan as combining prior art elements according to known compounds to yield predictable results; as the Examiner respectfully notes that Yarema explicitly teaches each structural element recited within compound (iii) of claim 1, lines 8-10, when in view of the combined teachings of Yarema and the exemplification of Ac4Man2Bz of Yarema as discussed above.
One of ordinary skill in the art would have been motivated to arrive at compound (iii) of claim 1, lines 8-10, in order to create the compound of Yarema above as a UAP inhibitor as taught by Yarema above. One of ordinary skill in the art would have had a reasonable expectation of success to arrive at compound (iii) of claim 1, lines 8-10, because Yarema explicitly teaches each structural element required of compound (iii) of claim 1, lines 8-10, when in view of the combined teachings of Yarema and the exemplification of Ac4Man2Bz of Yarema as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the teachings of the prior art.
Allowable Subject Matter
Claims 7-8 are 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.
Conclusion
No claims are allowed in this action.
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 JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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