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 .
Claim Status
The claim set and Applicant’s remarks filed November 06, 2025 have been entered. Claims 23, 30-33 and 38-41 are canceled. Claims 4-5, 10-12, 14-22, 28-29 and 36-37 are withdrawn from further consideration as being drawn to either a nonelected invention or a nonelected species as discussed in the Election/Restrictions section within the non-final office action mailed July 07, 2025.
Thus, claims 1-3, 6-9, 13, 24-27, 34-35 and 42 as amended are examined on the merits herein.
Drawings
The drawings are objected to because Figure 7 does not recite a title for the Y-axis. The Examiner respectfully notes within the specification on pg. 5, Figure 7 represents the mean plasma concentration as a function of time, see pg. 5, paragraph 2.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) 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. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency.
Additional replacement sheets may be necessary to show the renumbering of the remaining figures. 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.
Response to Arguments
The rejection of claims 1-3, 6-9, 13, 24-27, 34-35 and 42 under 35 U.S.C. 103 is maintained.
Applicant argues:
(A) The Office’s conclusion of obviousness is based on improper hindsight rationale, see Applicant’s arguments, pg. 22, paragraph 1.
(B) The Office’s reconstruction of the instant elected species here is improper because one of ordinary skill in the art would not have been motivated to begin with and perform specific modifications to the compound of Schinazi, see Applicant’s arguments, pg. 22, paragraph 1.
(C) The Office relies on EFdA which is a compound outside the scope of the compounds of Schinazi for the first modification of substituting a hydrogen for the hydroxyl on the tetrahydrofuran nucleus, see Applicant’s arguments, pg. 22, paragraph 2.
(D) Schinazi provides laundry lists within its disclosure to arrive at the second and third modifications, see Applicant’s arguments, pg. 22, paragraph 2.
(E) The experimental data (or a lack thereof) of Schinazi provide no motivation for the skilled artisan to select the reference compound as the lead compound for further modification, see Applicant’s arguments, pg. 22, paragraph 2.
(F) Antiviral potency values for the reference compound of Schinazi are absent, Applicant’s arguments, pg. 22, paragraph 3.
(G) The compound with the lowest (i.e. best) antiviral potency values was EFdA, which is outside the scope of the compounds of Schinazi, and from this the skilled artisan might have selected EFdA as the lead compound, but certainly not the reference compound of Schinazi for which no antiviral potency data was provided, see Applicant’s arguments, pg. 22, paragraph 3.
(H) The skilled artisan would not have been motivated to further modify EFdA based on the teachings of Schinazi because all of the tested compounds within the scope of Schinazi’s teachings had higher (i.e. worse) antiviral potency values. Thus, the Office operated with impermissible hindsight by using the present application as a roadmap, identifying features in various parts of the disclosure of Schinazi and transposing them onto the reference compound, for which antiviral potency data was not even provided, see Applicant’s arguments, pg. 22, paragraph 3.
(I) One skilled in the art would have been motivated to further substitute the phenyl group and C22 alkyl chain to arrive at the elected species, with no reason to do so, see Applicant’s arguments, pg. 23, paragraph 1.
(J) Table 5A of Schinazi shows a compound with the same 5’-position substitution as the reference compound (page 97, last compound), having much less potency against HIV in PBM cells that both EFdA (outside the scope of Schinazi) and EFrA (within the scope of Schinazi) indicate the results are anything but predictable, and thus Applicant concludes the Examiner’s argument of combining prior art elements according to known compounds/compositions yields predictable results is entirely based on impermissible hindsight, see Applicant’s arguments, pg. 23, paragraph 1.
With respect to Applicant’s arguments (A)-(J), the Examiner respectfully notes Schinazi teaches compounds and compositions for treating or preventing HIV, specifically the compounds used include specific nucleoside inhibitors described by Schinazi. Schinazi exemplifies a specific nucleoside compound having the following structure,
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. Although, Schinazi does not exemplify the elected species of formula (I) as discussed in the Election/Restrictions section above.
Specifically, the compound of Schinazi depicted above shows:
(i) an hydroxyl on the tetrahydrofuran nucleus, whereas in the elected species above depicts a hydrogen at that position;
(ii) a C1-alkyl, corresponding to R2 of formula (I), whereas in the elected species above depicts a C1-alkyl-C6-aryl at that position; and
(iii) a C3-alkyl, corresponding to R3 of formula (I), whereas in the elected species above depicts a C22-alkyl at that position.
Firstly, with respect to limitations (ii) and (iii), Schinazi teaches Formula (A) wherein R4 is a P(O)R6R7; wherein R6 and R7 are independently selected from the group consisting of and including (a) OR15, wherein R15 is a benzyl (e.g. R1 is C6-aryl, required in the elected species above); and (b) the ester of an L-amino acid depicted as,
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, wherein R17 is restricted to those occurring in natural L-amino acids.
Schinazi teaches R17 can be selected from the group consisting of and including an optionally substituted C1-6-alkyl-aryl; wherein Schinazi defines aryl to include phenyl (e.g. a C1-alkyl-C6-aryl required in the elected species corresponding to R2).
Schinazi teaches R18 is a C1-20-alkyl optionally substituted with a C1-6-alkyl, therefore when R18 is a C20-alkyl that is optionally substituted with a C2-alkyl, the Examiner respectfully noted it will meet the structural limitation of a C22-alkyl corresponding to R3 of the elected species above, see pg. 13, second full paragraph.
Accordingly, the teachings of Schinazi suggest limitations (ii) and (iii) of formula (A) of Schinazi and wherein the Examiner respectfully notes encompasses the exemplified nucleoside compound of Schinazi as depicted above.
Thus, one of ordinary skill in the art would have been motivated and would have had a reasonable expectation of success to have made modifications (ii) and (iii) to the exemplified nucleoside compound of Schinazi, as Schinazi explicitly discloses said modifications are within the scope of formula (A) of Schinazi, and wherein the Examiner reiterates the exemplified nucleoside compound of Schinazi is encompassed by the scope of formula (A) of Schinazi.
Secondly, with respect to limitation (i), the Examiner respectfully noted Schinazi further taught the compound EFdA which can be used in combination therapy. Schinazi demonstrates EFda has activity against HIV as discussed in Table 5 of Schinazi.
Schinazi also teaches the compound known as EFdA has the following structure,
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.
The Examiner respectfully notes two differences between the exemplified nucleoside compound of Schinazi and the EFdA compound. The first is the 5’-OH of the tetrahydrofuran ring of the exemplified nucleoside compound is modified as depicted above. The second is the 2’-carbon of the tetrahydrofuran ring of the exemplified nucleoside compound depicts an -OH group, resulting in a ribose sugar core. The Examiner additionally respectfully notes the 2’-carbon of the tetrahydrofuran ring of EFdA depicts a hydrogen atom (-H), resulting in a deoxyribose sugar core.
The Examiner further respectfully notes within Table 5 of Schinazi, said table depicts the median effective concentration (EC50) of compounds against HIV in PBM cells and macrophages, see Schinazi, pp. 96-97, table 5.
The Examiner notes two drugs screened in said HIV assay were EFdA as depicted above; and EFrA, depicted as
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, see Schinazi, pg. 97, first recited compound.
The Examiner respectfully notes the only difference between the structures of EFdA and EFrA as depicted above are the type of sugar core of the nucleoside.
The Examiner also specifically notes said difference is the presence of an -OH group at the 2’-carbon of the tetrahydrofuran ring, resulting in a ribose sugar core with respect to EFrA; and as previously explained above a hydrogen atom (-H) at the 2’-carbon of the tetrahydrofuran ring, resulting in deoxyribose sugar core with respect to EFdA as discussed above.
The Examiner also respectfully notes Table 5 of Schinazi shows significantly improved EC50 in both PBM cells and macrophages of EFdA when compared to EFrA.
Moreover, the Examiner respectfully notes within Table 5A of Schinazi referenced within Applicant’s argument (J) discussed above, a significantly improved EC50 in both PBM cells and macrophages in antiviral potency of EFdA is shown when compared to EFrA.
Accordingly, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the teachings of Schinazi as a whole, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the Examiner respectfully reiterates the teachings of Schinazi as discussed above suggest limitations (ii) and (iii) within formula (A) of Schinazi and wherein the Examiner also respectfully notes the exemplified nucleoside compound of Schinazi as depicted above is encompassed by formula (A) of Schinazi.
Furthermore, with respect to limitation (i) as discussed above, the Examiner respectfully notes Schinazi’s teachings suggest that changing the sugar core from a ribose as suggested by EFrA into a deoxyribose as suggested by EFdA is a known consideration in the prior art; and wherein Schinazi substantiates such a modification as discussed above by showing experimental data that modifying a ribose sugar core into a deoxyribose sugar core improves the median effective concentration and antiviral potency when targeting HIV in both PBM cells and macrophages.
Therefore, the teachings of Schinazi provide a clear and particular motivation to incorporate limitation (i) into the exemplified nucleoside compound of Schinazi, as Schinazi teaches compounds for treating or preventing HIV.
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).
Thus, 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.
Claims 1-3, 6-9, 13, 24-27, 34-35 and 42 remain rejected under 35 U.S.C. 103 as being unpatentable over Schinazi et al. (Published 04 July 2019, WO-2019133712-A1, IDS filed 09/15/2022).
Regarding claims 1-3, 6-9, 13, 24-27, 34-35 and 42, Schinazi teaches compounds and compositions for treating or preventing HIV, see abstract. Schinazi teaches the compounds used include specific nucleoside inhibitors described herein, see pg. 3, paragraph 3, lines 1-2. Schinazi teaches the compounds encompass stereoisomeric forms, see pg. 40, iii stereoisomerism and polymorphism.
Schinazi teaches pharmaceutical compositions including one or more of the compounds in combination with a pharmaceutically acceptable carrier or excipient (e.g. the pharmaceutical composition required in claim 24), see pg. 3, paragraph 3, lines 7-9.
Schinazi teaches administration parenterally (e.g. required in claim 25) and in liquid or solid form, see pg. 52, viii. pharmaceutical compositions. Schinazi teaches they can be compressed into tablets (e.g. tablet form, required in claim 26), see pg. 53, paragraph 1, lines 2-3. Schinazi teaches solutions or suspensions used for parenteral application can include a sterile diluent such as water for injection (e.g. parenteral injection, required in claim 27), see pg. 53, paragraph 4, lines 4-6.
Schinazi teaches the compositions can include a combination of one or more compounds with other antiviral compounds including anti-HIV compounds (e.g. the combination required in claims 34-35), see pg. 3, paragraph 3, lines 13-15.
Schinazi exemplifies a specific nucleoside compound having the following structure,
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, see pg. 17, left column, second recited compound.
Although, Schinazi does not exemplify the elected species of formula (I) as discussed in the Election/Restrictions section above. Specifically, the compound of Schinazi discussed above shows (i) an hydroxyl on the tetrahydrofuran nucleus, whereas in the elected species above there is a hydrogen at that position; (ii) a C1-alkyl, corresponding to R2 of formula (I), whereas in the elected species above there is a C1-alkyl-C6-aryl at that position; and (iii) a C3-alkyl, corresponding to R3 of formula (I), whereas in the elected species above there is a C22-alkyl at that position.
However, in the same field of endeavor of compounds and compositions for treating or preventing HIV, with respect to limitation (i), Schinazi further teaches the compound EFdA which can be used in combination therapy, see pg. 51, last paragraph. Schinazi teaches EFdA as having the following structure,
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, and demonstrates EFda as having activity against HIV, see pg. 96, Table 5, EFdA. The Examiner respectfully notes that the structure of EFdA is structurally similar to the compound exemplified by Schinazi above, however, EFdA contains a hydrogen atom on the tetrahydrofuran nucleus, which the Examiner notes corresponds to the identical position of the hydroxyl on the tetrahydrofuran nucleus of the exemplified compound of Schinazi above.
With respect to limitations (ii) and (iii), Schinazi teaches Formula (A), see pg. 10, ii active compounds, formula (A); wherein R4 is a P(O)R6R7, see pg. 11, paragraph 6, R4; wherein R6 and R7 are independently selected from the group consisting of and including (a) OR15, wherein R15 is a benzyl (e.g. R1 is C6-aryl, required in the elected species above), see pg. 12, paragraph 3 – line 1, paragraph 4, line 3; and (b) the ester of an L-amino acid depicted as,
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, wherein R17 is restricted to those occurring in natural L-amino acids, see pg. 13, second full paragraph. Schinazi teaches R17 can be selected from the group consisting of and including an optionally substituted C1-6-alkyl-aryl, see pg. 34, paragraph 3, R17; wherein Schinazi defines aryl to include phenyl (e.g. a C1-alkyl-C6-aryl required in the elected species corresponding to R2), see pg. 7, paragraph 1, line 3. Schinazi teaches R18 is a C1-20-alkyl optionally substituted with a C1-6-alkyl, thus when R18 is a C20-alkyl that is optionally substituted with a C2-alkyl it will meet the structural limitation of a C22-alkyl corresponding to R3 of the elected species above, see pg. 13, second full paragraph.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have included limitations (i)-(iii) as discussed above into the exemplified compound of Schinazi as depicted above as within the scope of the artisan as combining prior art elements according to known compounds/compositions to yield predictable results, as these limitations are taught by Schinazi as known modifications to nucleoside containing HIV inhibiting compounds, specifically EFdA as discussed above with respect to limitation (i); or as potential modifications of formula (A) which the exemplified compound of Schinazi depicted above is included within with respect to limitations (ii) and (iii). One of ordinary skill in the art would have had a reasonable expectation of success to have made these modifications to the exemplified compound of Schinazi depicted above, as Schinazi discloses all of these modifications can be a part of a nucleoside compound with anti-HIV activity as discussed above.
With respect to the limitation “is formulated as a long acting parenteral injection” required in claim 27, the Examiner is reasonably interpreting this limitation as a physical limitation of the resulting pharmaceutical composition. In addition, since the pharmaceutical composition of claim 27 only requires a compound of claim 1 and a pharmaceutically acceptable excipient; and given Schinazi teaches a pharmaceutical composition comprising a compound of claim 1 and a sterile diluent such as water (e.g. the pharmaceutically acceptable excipient) for injection parenterally; the physical limitation of the parenteral infection being “long acting” is met as all structural limitations required in claim 27 for formulating the pharmaceutical composition are met. Thus, the Examiner reasonably interprets the pharmaceutical composition of Schinazi is formulated as a long acting parenteral injection as required in claim 27.
It would have been prima facie obvious to one of ordinary skill in art before the invention was filed to have included limitations (i)-(iii) within the exemplified compound of Schinazi depicted above as within the scope of the artisan as combining prior art elements according to known compounds/compositions to yield predictable results. One of ordinary skill in the art would have been motivated to make these modifications to create compounds and compositions for treating or preventing HIV as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated limitations (i)-(iii) into the exemplified compound of Schinazi depicted above, as Schinazi teaches limitations (i)-(iii) as known modifications of nucleoside compounds for use in treating or preventing HIV as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the 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.
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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