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 .
Status of the Claims
Claims 1 – 6, 8 – 15 and newly added claim 16 are pending.
Claims 1 – 6, 8, 10 – 12 and 16 are rejected.
Claim 9 is objected.
Claims 13 – 15 contain allowable subject matter.
Response to Applicant’s Remarks
Applicant’s amendments filed on December 11, 2025 have been fully considered.
The objections to claims 1, 11 and 13 are withdrawn in view of the amendments to recite proper singular/ plural form in the claims.
The rejection under 35 U.S.C. §112(a) of claims 1 – 6 and 10 – 12 as failing to comply with the written description is withdrawn in view of the amendments to incorporate the limitations of cancelled claim 7 into the independent claim 1.
The rejection under 35 U.S.C. §112(b) of claims 2 – 6, 8 – 9 and 13 – 15 (claim 7 is cancelled) as being indefinite for reciting a broad range together with a narrow range that falls within the broad range (in the same claim) is withdrawn in view of the amendments to delete the narrow limitations from the claims.
The rejection under 35 U.S.C. §103 of claims 1 – 6, 8 and 10 – 15 (claim 7 is cancelled) as being unpatentable over Hoffman et al., bioRxiv August 5, 2020, 42 pages as evidenced by Cell Signaling Technology, Camostat Mesylate #42819, Retrieved on September 4, 2025, https://www.cellsignal.com/ products/activators-inhibitors/camostatmesylate/42819?srsltid= AfmBOooFWq4COfzreoUTt XhzDEZyykNrwF4PsIcGGlDQqNEFXpVIn5q, in view of Okuyama et al. EP 0350840 A2 is withdrawn in view of the amendments to recite the compound of Formula (II), wherein Z is an quaternary ammonium moiety, in claim 1.
On page 10, 2nd paragraph – page 12, 2nd paragraph, Applicant further demonstrate experimental data from a transwell assay using Calu-3 lung epithelial cells. Applicant presents data for permeability assessment of Camostat-Cholin (see, e.g., Figure 1) and TMPRSS2 inhibition profiles of Camostat derivatives (see, e.g., Figure 1) to show that camostat-cholin (which has a quaternary ammonium moiety as group Z and is permanently positively charged under physiological conditions) does not penetrate epithelial cells and ensures (i) high local concentrations beyond the inherent assets of local administration, and (ii) no systemic availability to avoid adverse effects from systemic exposure. Further, Camostat-cholin has a very similar potency in inhibiting TMPRSS2 enzymatic activity as camostat mesylate. Thus, Applicant state the claims are not obvious over the teachings of Hoffman or Okuyama, alone or in combination. However, MPEP §716.01(c)(II) recites (emphasis added):
“The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration (…)”
MPEP §716.01(c)(I) also recites (emphasis added):
“Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.”
Therefore, Applicants’ arguments demonstrating experimental data from a transwell assay using Calu-3 lung epithelial cells are not considered.
Examination: Applicant’s amendments necessitate extending the search. The search has been further extended to include the scope of compound of Formula (II).
Claim Rejections – Improper Markush Group Rejection
Claims 1 – 6, 8, 10 – 12 and 16 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the compound of Formula (II) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Claim 1 is directed to a pharmaceutical composition comprising a serine protease inhibitor for use in a method for the treatment or prevention of viral infections, wherein the pharmaceutical composition is administered topically, and wherein the serine protease inhibitor is a compound of Formula (II):
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, wherein:
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The structures associated with each of the variables (A, B, L3, R1, Y*, L1 and L2) above in the Formula (II) do not share a substantial feature to each other. Besides the general carboxyl moiety (–C(=O)O–) connecting the variables A and B, the compounds of Formula (II) as claimed in claim 1 do not belong to the same art-recognized class or chemical class of compounds because there is no common core structure shared among all of the compounds that would enable them to be categorized the same. For example, in variables A, B, L3, R1, Y*, L1 and L2, the alternatives for “aryl” and “heteroaryl” groups can be classified as phenylenes (e.g., CPC class C07C17), thiophenes (e.g., CPC C07D333 and C07D495), pyrrole (e.g., CPC C07D207 and C07D487), or as selenophenes (e.g., CPC C07D345 and C07D517). Further, the alternatives for “hydrolysable derivative from an acidic functional group” can also be classified in different CPC classes as noted above. The compounds do not belong to the same recognized physical or chemical class or to the same art-recognized class and each compound would possess different physical and chemical properties in view of the functional and cyclic groups such that they would not be expected to have the necessary common use. Thus, the compounds of the Markush grouping cannot be considered to share a “single structural similarity” that is essential from which a common use flows.
In order to overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. For example, the following is a proper Markush group of structure of Formula (III) (see, claim 9):
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or a single grouping of patentably indistinct species such that the variables A, B, L3, Y*, L1 and L2 are conserved across all species of Formula (II).
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.
Claims 1 – 6, 10 – 12 and 16 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 1 recites the limitation “Y* is a hydrolysable derivative from an acidic functional group”. See, page 2, line 16. The claim does not define the term, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “hydrolysable derivative” is a relative term and it is unclear the extent to which the variable Y* can be derivatized and still be considered a hydrolysable derivative in the compound of Formula (II). Thus, the metes and bounds cannot be ascertained and the limitation renders the claims indefinite. Dependent claims 2 – 6, 10 – 12 and 16 do not clarify or cure the deficiencies of the limitations in claim 1.
In order to overcome the rejection, Applicant may amend the limitation as follows: “Y* is
Claims 1 – 6, 10 – 12 and 16 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance,
Claim 1 recites the broad limitation “Y* is a hydrolysable derivative from an acidic functional group” (see, page 2, line 16), and the claim also recites “preferably selected from the group consisting of ester, inverted ester, amide, carbamate, and anhydride” (see, page 2, lines 17), which is the narrower statement of the limitation. The limitations as claimed in claim 1 do not clearly set forth the metes and bounds for the scope of variable Y* in the compound of Formula (II). Dependent claims 2 – 6, 10 – 12 and 16 do not clarify or cure the deficiencies of the limitations in claim 1. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In order to overcome the rejection, Applicant may amend the limitation as follows: “Y* is
Allowable Subject Matter
Claim 9 is 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.
Claims 13 – 15 are allowed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Sagar Patel whose telephone number is (571)272-1317. The examiner can normally be reached Monday - Friday: 9am to 5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sagar Patel/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626