DETAILED ACTION
The present application is a national stage entry of PCT/EP2022/051981, filed 28 January 2022, which claims foreign priority to EP21305131.1, filed 29 January 2021.
The preliminary amendment filed 27 July 2023 is acknowledged. Claims 19-36 are pending in the current application. Claims 33-36 are withdrawn as being drawn to a non-elected invention, see below.
The Declaration of Dr. Emeline Richard, submitted by Applicant on 27 March 2026 under 37 CFR §1.132 are acknowledged and will be further discussed below.
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 I, claims 19-32 in the reply filed on 27 March 2026 is acknowledged. The traversal is on the ground(s) that the product is the subject matter of Group I, and the process of use is the subject matter of Group II, thus, unity of invention exists. This is not found persuasive because the shared technical feature does not make a contribution over the prior art with respect to an inventive step in view of Samain et al.
Samain et al. (US Patent No. 8,507,227, cited in previous Office Action) teaches a sialylated tetrasaccharide: Neu5Acα-3Galβ-4GlcNAcβ-4GlcNAc (col.3:12-20). Samain et al. also teach a heptasaccharide prepared by sialylating a chitooligosaccharide: Neu5Acα-3Galβ-4[GlcNAcβ-4]4GlcNAc (col.20:9-24). The sialylated tetrasaccharide of Samain et al. is a positional isomer of the present compound of Formula (I), difference highlighted in bold. While the tetrasaccharide of Samain et al. has an α-2,3-linked Neu5Ac, the present claims have an α-2,6-linked Neu5Ac. Samain et al. also teach an α-2,6-sialyltransferase could be used instead of α-2,3-sialyltransferase (col.7:28-38).
While the compound of Formula (I) is novel, it is not considered an inventive step, because the claimed compound is a positional isomer of a known compound, and the prior art expressly teach both isomers for that position are acceptable. Accordingly, it would have been obvious to substitute Neu5Ac-α-2,3 with Neu5Ac-α-2,6. As such, the shared technical feature does not make a contribution over the prior art with respect to an inventive step in view of Samain et al. Consequently, the product lacks a special technical feature as defined by PCT Rule 13.2 as it does not possess an inventive step over the teachings of the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 33-36 are 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 27 March 2026.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: For example, while figure 5 is described in the Specification, figures 5A-D are not (check other reference characters, e.g. 6A, etc). Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 19-32 are objected to because of the following informalities: Independent claims should begin with “A”, while dependent claims should begin with “The” to clearly refer back to the independent claim. For example, claim 19 should recite “A synthetic sialoside”, and claim 20 should recite “The synthetic sialoside according to claim 19”, etc. 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.
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.
Claim 25 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 recitation “Synthetic sialoside according to Claim 19 presenting the formula (II):” in claim 25 renders the claim herein indefinite. Claim 19 is directed towards a compound of formula (I). Claim 25 can be interpreted to include a compound of formula (I) and formula (II). Claim 25 could be rewritten as an independent claim.
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 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.
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.
Claim(s) 19-24 are rejected under 35 U.S.C. 103 as being unpatentable over Samain (US Patent No. 8,507,227, cited in previous Office Action).
Samain teaches a sialylated tetrasaccharide: Neu5Acα-3Galβ-4GlcNAcβGlcNAc (col.3:12-20). Samain also teach a heptasaccharide prepared by sialylating a chitooligosaccharide: Neu5Ac-3Galβ-4[GlcNAcβ-4]4GlcNAc (col.20:9-24). The sialylated tetrasaccharide and heptasaccharide are positional isomers of the present compound of Formula (I), with the differences highlighted in bold. While the tetra-/hepta-saccharide contain a terminal 2,3-linked Neu5Ac, the present claims contain a terminal 2,6-linked Neu5Ac. Samain et al. teach an α-2,6-sialyltransferase could be used instead of α-2,3-sialyltransferase (col.7:28-38; also see claim 16).
Samain teaches “N-acetylneuraminic acid (Neu5Ac) is the most common member of the sialic acid family of aminosugars. Neu5Ac is frequently found as a terminal sugar in cell surface complex carbohydrates and plays a major role in many biological processes such as cellular adhesion and binding of toxins and virus (Varki, 1993)” (col.1:21-29).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the terminal Neu5Ac-2,3-linkage with Neu5Ac-2,6-, because they are positional isomers of each other, and Samain et al. expressly teach α-2,6-sialyltransferase could be used instead of α-2,3-sialyltransferase in the design and synthesis of the sialylated oligosaccharides. Thus, one having ordinary skill in the art would have had a reasonable expectation of success in making the positional isomer.
See MPEP 2144.09(II), “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.”.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 26, 27 and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Samain et al. (US Patent No. 8,507,227, cited in previous Office Action) as applied to claims 19-24 above, and further in view of Sasisekharan et al. (US Patent No. 8,815,522, cited in PTO-892).
Samain et al. teach as discussed above.
Samain et al. do not expressly disclose multivalent sialoside (present claim 26).
Sasisekharan et al. teach the preparation of glycans that bind to influenza hemagglutinin (HA), including multivalent structures (col.1:1-49; col.68:18-34; fig. 18; col.61:47-48). Glycan structures include Neu5Acα2-6-Sug1-Sug2-Sug3 (claim 16). Sasisekharan et al. teach the glycan structures can be fixed to a support, e.g. agarose beads (col.37:48-50; col. 38:41). Dosage forms include inhalants (col.51:11-15; col.52:43-46). Sasisekharan et al. teach “the present invention encompasses the recognition that high affinity binding to long α2-6 glycans, which are extensively expressed in the upper respiratory tissues, is a determinant not only for HA human adaptation, but also for influenza virus transmission in general” (col. 73:24-28).
According to Sasisekharan et al., avian hemagglutinin (HA), H5 HAs show the most diverse binding to Neu5Ac-α-2,3 linkages including sulfated and fucosylated α2-3 (col.61:29-52). The human adapted H1 and H3 HAs bind to long α2-6. Wild type and mutant H5N1 Has is, however, not supported by long α2-6, although it is supported by both α2-3 and short α2-6 classifiers. Figure 15 of Sasisekharan et al. shows human H1 HA has a narrow specificity, while the H3 HA (Mos99) can bind to diverse sialylated glycans. Sasisekharan et al. teach multivalency enabled binding to HA units (fig. 18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a multivalent sialoside having Neu5Ac-6Galβ-4[GlcNAcβ-4]4GlcNAc.
In addition to the reasons discussed above, the skilled artisan would have been motivated to substitute Neu5Ac-3Galβ-4[GlcNAcβ-4]4GlcNAc with Neu5Ac-6 to give Neu5Ac-6Galβ-4[GlcNAcβ-4]4GlcNAc, because in the same field of endeavor of preparing sialylated oligosaccharides for binding to cells, bacteria and viruses, Sasisekharan et al. teach Neu5Ac-2,6 terminated oligosaccharides bind to human influenza viruses. Sasisekharan et al. generally teach Neu5Acα2-6-Sug1-Sug2-Sug3, which encompasses the sialyloligosaccharide of Samain et al.
One having ordinary skill in the art would have been motivated to prepare a multivalent glycan, because they generate a higher binding affinity than monovalent antigens. Additionally, converting a monovalent glycan to a multivalent glycan was a known strategy, including for sialyl oligosaccharide based glycans, terminated in Neu5Ac-2,6 residues. The ordinary artisan would have had a reasonable expectation of success because Sasisekharan et al. expressly prepared multivalent sialyl oligosaccharides, for binding to influenza viruses.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Samain et al. and Sasisekharan et al. as applied to claims 19-24, 26, 27 and 30-32 above, and further in view of Roy et al. (J. Chem. Soc. Chem. Commun., 1993, pp. 264-265, cited in PTO-892).
Samain et al. teach as discussed above.
Samain et al. do not expressly disclose a poly-lysine support (present claim 28), or a grafting rate of the sialyl oligosaccharide and support (present claim 29).
Sasisekharan et al. teach as discussed above.
Roy et al. is concerned with the preparation of sialyl oligosaccharides that bind to influenza HA, wherein the sialyl oligosaccharide is bound to a poly-lysine support (title). Roy et al. teach preparing conjugates having 1 molar ratio of sialic acid to 17 free lysine groups, i.e. 4-5 mol% (p.264, fourth and fifth para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conjugate a multivalent sialoside having Neu5Ac-6Galβ-4[GlcNAcβ-4]4GlcNAc to poly-lysine, because it is a known support for sialosides, including those used for targeting viral receptors, like influenza HA. While Roy et al. teach grafting 4-5 mol% sialoside per poly-lysine, the ordinary artisan would have routinely optimized the molar ratio of sialoside to support.
See MPEP 2144.05, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Response to Arguments
Applicant's arguments filed 27 March 2026 have been fully considered but they are not persuasive.
Applicant contends Samain does not describe or suggest a compound of formula (I), having a Neu5Ac-α-2,6-linkage. Applicant contends Samain does not describe or suggest the compounds as claimed are capable of binding to the influenza virus.
Applicant argues the examples provided in the Specification demonstrate the claimed compounds advantageously enable inhibition of hemagglutination and possess therapeutic properties – see examples 7-13.
The examples provided in the Specification, and the data provided in Table 3 of the Declaration, have been fully considered, but are not found persuasive, because the results provided therein are not commensurate in scope with the present claims.
The data presented in the Specification are limited in structure to multivalent sialosides, having a grafting ratio of 23%-77% (present claim 19 is directed to a monovalent sialoside); linked to poly-L-lysine (present claims 26 and 27 include any support).
The data presented in the Specification is limited to human influenza strains (please note withdrawn claim 35 is drawn to human, equine, porcine, and avian influenza viruses).
The data presented in the Specification are limited to a single sialoside structure: Neu5Acα2-6Galβ1-4[GlcNAcβ1-4]4GlcNAc, while present claim 19 recites “R1 is a glycan structure comprising one or more galactose (Gal)”. Claim 19 encompasses an endless number of glycans, provided there is at least one galactose moiety. However, the compounds tested only contain a single galactose, unsubstituted, and linked only in a β1-4 manner. Claim 19 defines “n is superior or equal to 1”. Thus, the upper limit is endless. However, the compounds tested are defined where n is 4.
ER15, ER59, ER60 and ER61 have a grafting ratio of 77%, 65%, 43% and 23%, respectively.
ER84, a multivalent compound was prepared having the oligosaccharide: Neu5Ac-α-2,3-Galβ1-4[GlcNAcβ1-4]4GlcNAc, which represents the closest prior art structure, as taught by Samain et al.
Table 3 shows that while ER84 did not bind to influenza types H1N1, H3N2 or B, multivalent sialosides ER15, ER59, ER60 and ER61 did bind, especially to H1N1.
Table 3 shows ER100, which differs from ER15 by the number of repeating units of GlcNAcβ1-4 (2 vs 4) had mostly no inhibitory activity, particularly in comparison to ER15. Thus, the data shows the criticality of the definition of ‘n’ in the present claims.
Table 3 also shows ER101, which differs from ER15 by the number of repeating units of GlcNAcβ1-4 (3 vs 4) had mostly no inhibitory activity, particularly in comparison to ER15. Thus, the data shows the criticality of the definition of ‘n’ in the present claims.
With respect to H3N2, only ER60 and ER61, having a grafting ratio of 43% and 23% sialoside, had some inhibitory activity towards influenza types H1N1 and B.
According to Sasisekharan et al. (US Patent No. 8,815,522, cited in PTO-892), avian hemagglutinin (HA), H5 HAs show the most diverse binding to Neu5Ac-α-2,3 linkages including sulfated and fucosylated α2-3 (col.61:29-52). The human adapted H1 and H3 HAs bind to long α2-6. Wild type and mutant H5N1 HAs is, however, not supported by long α2-6, although it is supported by both α2-3 and short α2-6 classifiers. Figure 15 of Sasisekharan et al. shows human H1 HA has a narrow specificity, while the H3 HA (Mos99) can bind to diverse sialylated glycans.
Thus, from Sasisekharan et al. and the Declaration, binding to different human influenza strains is not completely predictable. High affinity binding appears to vary depending on whether an oligosaccharide is terminated in α-2,6 linkages vs α-2,3 linkages, as well as the length of the sialyl oligosaccharide. While Sasisekharan et al. showed a diverse array of oligosaccharides could bind strongly to H3N2 (particularly in comparison to H1N1), the Declaration of Dr. Richard provided on 27 July 2023 showed binding to H3N2 was less favorable than H1N1, and/or depended on the sialoside:lysine grafting ratio.
However, the results provided in the Declaration are limited to a specific heptasaccharide, as discussed above.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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