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 .
Priority
This application has a provisional application 63/309,117 02/11/2022.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/309,117, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The application does not have support for R1 is O-acetyl, X1 is H, R2 is H or acetyl, X2 is H, R3 is H, acetyl or COCH2CX3, X3 is H, R4 is H or a C1-C6 alkyl group, X4 is H and wherein the sialidase inhibitor is not 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, required in claim 2; the sialidase inhibitor of the formula claimed in claim 3, required in claim 3; R1 is O-acetyl, X1 is H, R2 is H or acetyl, X2 is H, R3 is acetyl or COCH2CX3, X3 is H, R4 is H or a C1-C6 alkyl group, and X4 is H, required in claim 14; the sialidase inhibitor of the formula claimed in claim 20, required in claim 20; the recitations of R2, R3, or R4 or combinations thereof, required in claims 21-28; or wherein R1 is O-acetyl, required in claims 29 and 30.
Thus, claims 2-9, 14 and 20-30 are interpreted to have a priority date of 02/13/2023.
Claim Status
Applicant’s remarks filed on April 01, 2026 have been entered.
Claims 1, 10-13 and 15-19 are canceled.
Therefore, claims 2-9, 14 and 20-30 are examined on the merits herein.
Response to Arguments
The rejection of claims 2-9, 14, and 20-30 under 35 U.S.C. 103 is maintained.
Applicant argues:
(A) The results are unpredictable and the proposed modification would impermissibly alter Cross’ principle of operation, see Applicant’s remarks, pg. 6, third paragraph.
(B) Modifying Cross’ compound to be membrane-permeable would impermissibly change Cross’ cell surface-based principle of operation, see Applicant’s remarks, pg. 7, first full paragraph.
With respect to Applicant’s arguments (A)-(B), the Examiner notes in Cross on pp. 5-6, paragraph [15], it teaches a method of inhibiting a sialidase comprising contacting the sialidase with at least one compound of the recited formula which includes both DANA and the modification which changes R8 from acetyl to hydrogen; and further teaches the sialidase is encoded by a neuraminidase gene such as neu 1.
Furthermore, as evidenced by Yang et al. (Published 17 February 2023, iScience, Vol. 26, Issue 2, pp. 1-20, PTO-892), Yang discloses Neu1 is an intracellular sialidase, see pg. 1, title; and on pg. 11, Figure 7 visually depicts the proposed inhibition of sialidase by a cytosolic sialidase inhibitor by illustrating DANA crossing the cell membrane and entering the cytosol to inhibit an intracellular sialidase.
Therefore, the Examiner reasonably interprets the compounds of Cross which include DANA and its analogues are membrane-permeable cytosolic sialidase inhibitors and thus the modification of DANA taught by Cross does not impermissibly alter Cross’ principle of operation as argued by Applicant.
(C) The use of the membrane-permeable, cytosolic sialidase inhibitors of the present disclosure provides a technical benefit over DANA as illustrated in the specification, and this benefit would not have been expected from the disclosure of Cross, see Applicant’s remarks, pg. 7, first full paragraph.
With respect to Applicant’s argument (C), the Examiner notes general formula (I) recited in claim 1 encompasses the compound known as Neu5Ac2en9N3, which is structurally similar to DANA, the difference is the C9 position of Neu5Ac2en9N3 is substituted with an azide (N3), while the C9 position of DANA is substituted with a hydroxyl (OH).
The Examiner notes Neu5Ac2en9N3 corresponds to general formula (I) when R1 is N3, R2 is acetyl, R3 is H, and R4 is H.
Moreover, as evidenced by Yang as discussed above, Yang discloses Neu5Ac2en9N3 is a cell surface sialidase inhibitor, see pg. 4, sialidase inhibitors library screening, paragraph 1.
(D) The Office’s rationale requires making specific selections for A, R1, R2, R3, R3’, R4, R5, R6 and Y with respect Von Izstein, see Applicant’s remarks, pg. 7, second full paragraph.
(E) The preferences provide no motivation to make the specific selections alleged in the office action; and accordingly, the Office’s rationale is clearly predicated on impermissible hindsight, see Applicant’s arguments, pg. 7, second full paragraph.
(F) The substitution relying on Brown which only occurs under the Office’s rationale after Cross has already been modified by the teachings of Von Izstein, and thus there is no mere simple substitution of the primary reference Cross to which the Office also improperly ignores the degree of unpredictability in the field of the application, see Applicant’s remarks, pg. 7, last full paragraph.
With respect to Applicant’s arguments (D)-(F), the Examiner notes both Cross and Von Izstein are drawn to derivatives of DANA.
Von Izstein is relied upon to substitute two positions of Cross in order to arrive at the recited compounds of general formula (I) in claim 14, e.g. (i) where R1 is an O-acteyl and (ii) R3 acetyl.
Additionally, the Examiner notes Von Izstein teaches these structural substitutions as discussed within the applicable prior art rejection(s) below.
Moreover, Brown is relied upon to substitute the hydrogen atom of the COOH group of the DANA compound taught by Cross and/or Von Izstein with a methyl group which corresponds to and is recited in R4 of instant claims 3, 20, 23 and 25-28; as Brown teaches a hydrogen atom and a methyl group are known bioisosteres used in medicinal chemistry as discussed in within the applicable 103 rejection(s) below.
Furthermore, the Examiner also noted within the applicable prior art rejections the motivation to combine the teachings of Cross and Von Izstein was to create derivatives and analogues of DANA as the least one sialic acid compound which included both DANA and the like which affects the actions of endogenous sialidases as taught by Cross.
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).
Therefore, in view of the foregoing reasons, Applicant’s arguments (A)-(F) 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.
(I) Claims 2, 4-8, 21 and 29 remain rejected under 35 U.S.C. 103 as being unpatentable over Cross et al. (Published 06-23-2005, WO 2005056047 A1, PTO-892 mailed 05/01/2024).
Cross teaches methods of treating, preventing, inhibiting, or modulating a viral disease or infection that comprises administering to the subject a therapeutically effective amount of at least one compound inhibiting a sialidase, see abstract; wherein the virus is a coronavirus, see pg. 41, paragraph #12. Cross teaches pharmaceutical compositions comprising the compounds, see abstract. Cross teaches to prolong the activity of sialic acid and its analogues and to increase its bioavailability, the molecule may be coupled to another carrier molecule, see pg. 37, paragraph [103]; and provides an example of a pharmaceutically acceptable carrier, see pg.43, paragraph #20.
Cross teaches the compounds may be administered by mouth (i.e. p.o.), see pg. 37, paragraph [104]. Cross teaches the compounds may be administered by subcutaneous injection, see pg. 37, paragraph [104]. Cross teaches the active agents may be administered into the peritoneal cavity, see pg. 37, paragraph [104]. Cross teaches that sialic acid or its analogues may be given intravenously, see pg. 37, paragraph [104].
Cross teaches sialic acid compounds which have the following structural formula,
PNG
media_image1.png
155
279
media_image1.png
Greyscale
, wherein in preferred embodiments the compound is 2,3-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA), see pg. 4, paragraph [14]. As evidenced by Cross, the structure of DANA is as follows,
PNG
media_image2.png
312
431
media_image2.png
Greyscale
see pg. 12, paragraph [35], DANA.
Cross teaches in preferred embodiments the disease or the infection is caused by and includes HIV and corona viruses; and in preferred embodiments the sialic acid compound is and includes both DANA and TamifluTM and the like that affect the action of endogenous sialidases, see paragraph [108].
Cross teaches sialic acid compounds are a phylogenetically conserved family and are potent modulators of biological behavior, see paragraph [06]. Cross teaches sialic acid compounds have the ability to prevent hyposialyation of cells by competitive inhibition of the endogenous sialidase(s); wherein desialyation of cells is shown to increase adhesive properties of the cells and to render cells more susceptible to invasion by infectious organisms such as HIV, see paragraph [32].
Although, Cross does not exemplify wherein the compound is not DANA, required in claim 2.
However, in the same field of endeavor of treating a viral infection, Cross teaches that R8, which corresponds to COCH3 (acetyl) in DANA, can be either CORa, wherein Ra is a C1-4 alkyl (i.e. wherein C1 is an acetyl as exemplified by DANA and C2 is a propionyl) or an H atom, see pg. 4, paragraph [14], lines 5-6.
Cross teaches a method of inhibiting a sialidase which comprises contacting the sialidase with at least one compound having the structural formula which comprises R8 which is either CORa, wherein Ra is a C1-4 alkyl; or an H atom, see pp. 5, paragraph [15] – pg. 6, paragraph 1.
Cross also teaches the sialidase is encoded by a neuraminidase gene, such as neu 1, neu 2, neu 3, neu 4, and the like, see pg. 6, paragraph 1.
The Examiner notes when R8 is an H atom, the resulting compound is not 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, required in claim 2 and wherein R1 is O-acetyl, required in claim 29. Additionally, the Examiner notes when Ra is CORa, wherein Ra is a C2-alkyl, it corresponds to a COCH2X2, wherein X2 is a C1-alkyl as recited in formula (I) of claim 2 (i.e. R2 is not H, required in claim 21).
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have substituted the COCH3 group as exemplified by DANA for a hydrogen atom as taught by Cross above as within the scope of the artisan as combining prior art elements according to known compositions and methods to yield predictable results. One of ordinary skill in the art would have been motivated to treat the coronavirus infection of Cross by administering a compound inhibiting a sialidase as taught by Cross with at least one sialic acid compound including both DANA and the like that affect the action of endogenous sialidases as taught by Cross above. One of ordinary skill in the art would have had a reasonable expectation of success to have modified the structural formula of Cross with the modifications as stated above, as Cross teaches R8 can be both H or a CORa, wherein Ra is a C1 alkyl (i.e. an acetyl) as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claim 9 remains rejected under 35 U.S.C. 103 as being unpatentable over Cross et al. (Published 06-23-2005, WO 2005056047 A1, PTO-892 mailed 05/01/2024) as applied to claims 2, 4-8, 21 and 29 above, and further in view of Harless (Published 09-23-2021, WO 2021184123 A1, PTO-892 mailed 05/01/2024).
Cross addresses claims 2, 4-8, 21 and 29 as written above. Although, Cross does not teach wherein the coronavirus infection is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
However, in the same field of endeavor of treating coronavirus infections, Harless teaches DANA and DANA analogues as sialidase inhibitors, see paragraph [0010], in treating COVID-19 (SARS-CoV-2), see abstract.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included the SARS-CoV-2 infection as recited in instant claim 9 as the coronavirus infection as taught by Cross above as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to treat the coronavirus infection as taught by Cross above. One of ordinary skill in the art would have had a reasonable expectation of success to have included the limitation as discussed above, as both Cross and Harless are directed to treating coronavirus infections with DANA or DANA analogs as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(III) Claims 14, 22, 24 and 30 remain rejected under 35 U.S.C. 103 as being unpatentable over Cross et al. (Published 06-23-2005, WO 2005056047 A1, PTO-892 mailed 05/01/2024) as applied to claims 2, 4-8, 21 and 29 above, and further in view of Von Izstein et al. (Published 01 November 1994, US-5360817-A, PTO-892 mailed 10/01/2025).
Cross addresses claims 2, 4-8, 21 and 29 as written above. Although, Cross does not teach a compound of general formula (I) wherein R1 is O-acetyl and R3 is acetyl as required in claim 14.
However, in the same field of endeavor of antiviral compositions, Von Izstein teaches derivatives and analogues of 2-deoxy-2,3-didehydro-N-acetyl neuraminic acid and their use as antiviral agents, see Col. 1, lines 1-5.
Von Izstein teaches 2-deoxy-2,3-didehydro-N-acetyl neuraminic acid is DANA, see Col. 1, 30-35.
Von Izstein teaches compounds of formula (I) depicted as,
PNG
media_image3.png
124
152
media_image3.png
Greyscale
, see col. 2, lines 50-55, wherein R3 and R3’ are different and each denotes H or OR6, see col. 3, lines 9-10; and R5 denotes CHYR6CHYR6CH2YR6, wherein Y is O, see col.3, lines 24-25; and R6 is an acyl group having 1 to 4 carbon atoms, see col. 3, lines 3-5. The Examiner notes the recitations above correspond to formula (I) of the instant claims when R1 is O-acetyl and R3 is acetyl as required in instant claim 14, instant claim 22 and instant claim 24; additionally, when R1 is O-acetyl as required in instant claim 30.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included the teachings of Von Izstein into the compounds of Cross as within the scope of the artisan as simple substitutions by combining prior art elements according to known compositions to obtain predictable results. One of ordinary skill in the art would have been motivated to carry out these substitutions in order to create the derivatives and analogues of DANA as taught by Von Izstein as the at least one sialic acid compound which includes both DANA and the like that affect the action of endogenous sialidases as taught by Cross above. One of ordinary skill in the art would have had a reasonable expectation of success as both Cross and Von Izstein are drawn to compounds comprising DANA analogs for use as antiviral agents.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(IV) Claims 3, 20, 23 and 25-28 remain rejected under 35 U.S.C. 103 as being unpatentable over Cross et al. (Published 06-23-2005, WO 2005056047 A1, PTO-892 mailed 05/01/2024) and Von Izstein et al. (Published 01 November 1994, US-5360817-A, PTO-892 mailed 10/01/2025) as applied to claims 2, 4-8, 14, 21-22, 24 and 29-30 above, and further in view of Brown ("Bioisosterism in Medicinal Chemistry" in: Brown, N., Bioisoteres in Medicinal Chemistry (Weinheim, Wiley-VCH Verlag & Co. KGaA, 2012), pp. 3-14, PTO-892 mailed 10/01/2025).
Cross and Von Izstein address claims 2, 4-8, 14, 21-22, 24 and 29-30 as written above. The Examiner reiterates both Cross and Von Izstein teach compounds above where the compounds contain a hydrogen (H) atom located at the position corresponding to R4 of formula (I) as recited in instant claim 2 and instant claim 14.
Although, Cross and Von Izstein do not teach wherein R4 as recited in general formula (I) is a methyl group, as required in instant claims 3, 20, 23 and 25-28.
However, in the same field of endeavor of derivatives and analogs of DANA, Brown teaches bioisosterism in medicinal chemistry, see pg. 3, title. Brown teaches some examples of classical bioisosteres where groups in each row are equivalent; Brown exemplifies a CH3 (methyl) group is equivalent for H (a hydrogen atom), see pg. 7, table 1.3, monovalent bioisosteres.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have substituted the hydrogen atom as taught by the compounds of Cross and/or Von Izstein for the methyl group as taught by Brown above as a simple substitution as combining prior art elements according to known compositions to yield predictable results. One of ordinary skill in the art would have been motivated to have made the substitution as discussed above in order to create the derivatives and analogues of 2-deoxy-2,3-didehydro-N-acetyl neuraminic acid for use as antiviral agents as taught by Von Izstein above; and to have used said derivatives and analogues as the at least one sialic acid compound which includes both DANA and the like that affect the action of endogenous sialidases as taught by Cross above. One of ordinary skill in the art would have had a reasonable expectation of success to have made the substitution as discussed above, as both Cross and Von Izstein are drawn to DANA analogs, both Cross and Von Izstein recite a hydrogen atom corresponding to R4 of general formula (I) of the instant claims; and Brown teaches that CH3 (methyl) and a hydrogen atom are equivalent monovalent classical bioisosteres in medicinal chemistry as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
Prosecution Insights