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 .
Status of Claims and Response to Amendments
The amendments filed October 14, 2025 have been acknowledged and entered. Claims 1-3, 5-6, 10-18, 20-21, 24-25, 27-28, 30-33 and 45-46 are pending.
Election/Restriction
Examination of the instant application is based Applicant’s election of species corresponding to compound 68 (pictured below).
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Applicant has not overcome the previous art rejections set forth in the office action mailed April 14, 2025. The search has therefore been limited to the subgenus of Formula I wherein X is O; R1 is H; R2 is OH; R3 is NHC(O) (CH2)nR5 wherein n is 0 or 1 and R5 is C1-C10 alkyl; and R4 is -NHC(O)R6 wherein R6 is C1-C10 alkyl.
Claims 12-15, 21, and 24-25 (in full) and claims 1-3, 5-6, 10-11, 16-17, 18, 20, 27-28, 30-33, and 45-46 (all in part, other than the above indicated subgenus of compounds of Formula (I) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this Office Action has been withdrawn or rendered moot in view of Applicant’s amendments and/or
remarks.
Maintained Rejections
Claim Rejections - 35 USC § 103
Claim(s) 1-3, 5-6, 10-11, 16-17, 18, 20, 27-28, 30-31, and 45-46 are rejected under 35 U.S.C. 103 as being unpatentable over Magesh et al. (Bioorganic & Medicinal Chemistry Letters, 2008, 18, 532-537) (hereinafter “Magesh”) in view of Nan et al. (Journal of Leukocyte Biology 2007, 81, 284-296) (hereinafter “Nan”).
The reasons for this rejection were set forth in the previous Office Action mailed April 14, 2025 and are incorporated herein by reference.
Response to Arguments
Applicant’s arguments filed October 14, 2025 have been fully considered but they are not persuasive.
Applicant argues Magesh fails to teach, suggest, or disclose independent claim 1 (page 17 of remarks). Applicant further argues the cited reference Nan fails to cure the deficiencies of Magesh. Specifically, Nan relates to a study of endogenous sialidase activity of freshly isolated human T lymphocytes and its role in production of cytokines (page 17 of remarks). Applicant argues Nan merely postulates that Neul and/or Neu3 may have a role in other immune functions of human lymphocytes, without providing any evidence of such activity. Nowhere in Nan is there any demonstration of the effect of inhibition of Neul and/orNeu3 on such other immune functions, let alone the beneficial effect of selective inhibition as taught and claimed in the present application.
These arguments are not found persuasive for the reason that the rejection is based on a combination of the references. Magesh clearly teaches the claimed compounds were known inhibitors of Neu1 and makes note that sialidases (Neuraminidases) are involved in a variety of cellular processes (e.g. proliferation, differentiation) and are associated with pathological conditions (Introduction, columns 1-2). Nan demonstrates that the art was aware that inflammation could potentially be treated by inhibition of Neu1. The person of ordinary skill in the art seeking to treat inflammation would have been motivated to use the claimed compounds because they were known inhibitors of Neu1 and therefore may have use in treating the condition.
Applicant argues that Nan fails to provide any evidence (page 17 of remarks, paragraphs 2-3) and that there would be no reasonable expectation of success in combining the references to treat inflammation as claimed (page 18 of remarks). Examiner respectfully disagrees for the reason that Nan specifically states inhibition of sialidase (i.e. Neu1, Neu 3; see page 293 col 2: sialidase activity (Neu1 and Neu3)) activity results in a significant reduction of the proinflammatory cytokine IFN ɣ (IFN gamma) (see page 293, col 2, final paragraph. “The proinflammatory cytokine IFN…inhibition of sialidase activity result in a significant reduction in the synthesis of IFN…”). As evidenced by Ghosh et al. (Gut 2006 55, 1071-1073), inhibition of IFN gamma was known to be of therapeutic use in the in the treatment of inflammatory conditions before the effective filing date of the invention (“In inflammatory bowel disease, both Crohn’s disease (CD) and ulcerative colitis (UC), plasma and tissue concentrations of proinflammatory cytokines such as.. IFN ɣ… are increased (page 1071, col 1); “the early experience of anti- IFN ɣ antibody in active CD has been reported…In a phase I/II dose ranging (0.1, 1.0, and 4.0 mg/kg) evaluation in active CD, fontolizumab, a humanized anti- IFN ɣ antibody was reasonably well tolerated… At day 29, evidence of biological efficacy was also noted with a significant decrease in CRP from baseline in the 1.0 and 4.0 mg/kg intravenous cohort” (col 3 of page 1071 to col 1 of page 1072).
Thus, a person skilled in the art could have reasonably expected that administration of the claimed compounds would have the effect of treating inflammation, at least for the reason that the art was aware inhibition of sialidase activity (e.g. Neu1) reduced proinflammatory cytokine IFN gamma and reduction in IFN gamma was already known in the art to have therapeutic use in treating inflammatory disease.
The rejection is still deemed proper and thus maintained.
Claim(s) 1 and 32-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Magesh et al. (Bioorganic & Medicinal Chemistry Letters, 2008, 18, 532-537) (hereinafter “Magesh”) in view of Nan et al. (Journal of Leukocyte Biology 2007, 81, 284-296) (hereinafter “Nan”) as applied to claim 1 above, and further in view of Li et al. (Frontiers in Immunology 2017, Vol 8, Article 744) (hereinafter “Li”).
Response to Arguments
Applicant’s arguments filed October 14, 2025 have been fully considered but they are not persuasive.
Applicant argues Magesh and/or Nan fail to teach, suggest, or disclose independent claim
1, and the claims that depend therefrom, under 35 U.S.C. § 103 (page 18 of remarks). Examiner disagrees for the reasons set forth above.
Applicant further argues Li fails to cure the deficiencies of Magesh and/or Nan and states the cited reference Li is silent regarding any teaching of the role of any of Neul, Neu3 or Neu4 in inflammation or regarding the use of a specific or a bispecific neul, neu3, and/or neu4 inhibitor compound in a "method of treating immune thrombocytopenia or inflammation," as recited in independent claim 1.
This argument is not found persuasive because, as noted above, the rejection is based on a combination of the references. Li simply provides immune thrombocytopenia is an inflammatory condition and thus in view of the combined references the claimed method would have been obvious for the reasons set forth in the rejection (see pages 6-7 of the previous Office Action). In further support of this argument, Ni et al. (Am. J. Hematol. 2015 E94-5) teaches that before the effective filing date of the instant application the art was well aware that sialidase inhibition had the effect of increasing platelet counts and therefore may be a new treatment for immune thrombocytopenia (Title, col 1 of page 1). Given that the claimed compounds were known to be potent sialidase inhibitors (Magesh) and that sialidase inhibitors were believed to a possible treatment of inflammatory conditions (Nan), including immune thromobocytopenia (Li), it would have been reasonable to expect that administration of the claimed compounds may have use in treating the condition as claimed.
The rejection is still deemed proper and thus maintained
35 USC § 112b
Claim(s) 1-3, 5-6, 10-11, 16-17, 18, 20, 27-28, 30-33, and 45-46 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.
The claims recite “the inhibitor is an ester” (see claim 1, final two lines) or “pharmaceutically acceptable ester (e.g. see claim 2, 27...). The limitation “ester” is indefinite because applicant has provided no definition of this limitation and therefore a person skilled in the art could not say which esters are included in the scope of the instant claims. Is there an additional substituent not included in Formula (I), such as -O-C(O)-CH3 or -C(O)O-CH3 intended somewhere on the compound to make the compound an ester? Where is this group substituted and what does it look like?
Response to Arguments
Applicant’s arguments filed October 14, 2025 have been fully considered but they are not persuasive.
Applicant argues independent claim 1 is being amended to specify that R1 is H. With this amendment, the compound of Formula I includes a carboxylic acid at the Cl position. As would be readily
understood by a person having ordinary skill in the art, an ester of the compound of Formula I is obtained by esterification such that the hydroxy group of the carboxylic acid is replace with an O-R'. Since the limitation "the inhibitor compound is an ester" of independent claim I is definite in accordance with 35 U.S.C. § l 12(b), independent claim 1, and the claims that depend therefrom, are definite in accordance with 35 U.S.C. § l 12(b).
Examiner disagrees for the reason that the specification fails to provide adequate definition of what Applicant regards as an “ester” of Formula (I). “Esters” are defined at pages 31-32; however, this definition includes a massive number of distinct compounds. Furthermore, this definition fails to provide any indication of the structure of the “ester” of the claims. The limitation “ester” is indefinite at each occurrence throughout the claims because the number of possible compounds defined by this Markush grouping is massive and one skilled in the art cannot possibly envision all compounds considered in the scope of the invention. “[A] Markush group may be so expansive that persons skilled in the art cannot determine the metes and bounds of the claimed invention. For example, if a claim defines a chemical compound using one or more Markush groups, and that claim encompasses a massive number of distinct alternative members, the claim may be indefinite under 35 U.S.C. 112(b) if one skilled in the art cannot determine its metes and bounds due to an inability to envision all of the compounds defined by the Markush group(s). In such a circumstance, a rejection of the claim for indefiniteness under 35 U.S.C. 112(b) is appropriate.” See MPEP 2173.05(h). This is exactly the case here. A person skilled in the art cannot ascertain the metes and bounds of the invention.
The rejection is still deemed proper and thus maintained. Examiner suggests deleting the limitation “ester”.
Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 112
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 1-3, 5-6, 10-11, 16-17, 18, 20, 27-28, 30-33, and 45-46 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.
The claims recite or require the transitional phrase “comprises” (see e.g. lines 6-7 of claim 1; see line 2 of the claims 45-46: “inhibitor compound comprises the structure ”). “Comprises” renders the claims indefinite because the term “comprises” is open ended (see MPEP 2111.03 Transitional Phrases) and therefor the structure of the inhibitor, and thus scope of the claim, is unclear. Examiner suggests amending the claim to recite the “inhibitor compound has the structure of Formula I or Compound 5c”, or similar definite language, to clarify the scope of the claim.
Conclusion
No claim is allowed.
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.
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November 16, 2025
/K.S.M./Examiner, Art Unit 1624
/BRUCK KIFLE/Primary Examiner, Art Unit 1624