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 .
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.
Claim Status
Applicant’s amendment of 04/20/2026 is acknowledged. Claims 1-2, 4-5, and 13-14 are amended, and claim 3 is cancelled. Claims 1-2 and 4-17 are currently pending.
Election/Restrictions
An election of invention/species was required in the instant application as detailed in the Office action dated 06/25/2025. The election is maintained and claims 6-12 and 15-17 remain withdrawn. Accordingly, claims 1-2, 4-5, and 13-14 are examined on the merits herein.
Priority
The instant application is a 371 of PCT/IB2021/053152 filed on 04/16/2021 and claims foreign priority to IN202041016518 filed on 04/16/2020 as reflected in the filing receipt dated on 04/26/2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Previous Rejections/Objections
Applicant’s arguments filed 04/20/2026 have been fully considered. Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied as necessitated by Applicant’s amendment to the claims. They constitute the complete set of rejections and/or objections presently being applied to the instant application. Applicant’s arguments insofar as they pertain to the present grounds of rejections and/or objections are addressed herein.
Claim Objections
Claim 2 is objected to because of the following informalities:
Claim 2 recites the limitation “Sapogenin” in line 1, which is inappropriately capitalized and should read “sapogenin”.
Appropriate correction is required.
Drawings
The drawings are objected to because the percentage values labeled on/above the first two bars of the graph presented in FIG. 2 are illegible. More specifically, the white text color is difficult to read against the light gray background. Further, the figure is pixelated, making all percentage values difficult to decipher.
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.
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.
Claims 1-3, 5, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (RSC Adv., 5, 74828–74834; published: 08/27/2015; PTO-892 of 11/18/2025) in view of Gao (MOJ Bioequiv Availab., 5(3), 125‒128; published: 05/02/2018; PTO-892 of 11/18/2025).
Li teaches an amphiphilic polymer-drug conjugate poly(ethylene glycol) (PEG)-diosgenin, wherein the PEG and diosgenin segments are linked via an ester bond between a -COOH carboxylic acid linker (attached to PEG) and diosgenin (Li, Page 74828, R. Col. and Scheme 1A). Diosgenin reads on the sapogenin of claims 1 and 2, and PEG reads on the same recited in claim 1.
While Li teaches a carboxylic acid linker, Li does not teach wherein the carboxylic acid is succinate, adipate, glutarate, pimelate, malonate, or sebecate as recited in claim 1.
Gao teaches that PEG polymers are routinely modified with anhydrides such as succinic anhydride, which provides a free -COOH group for bioconjugation and acts as a spacer between the polymer and drug in order to control the site and rate of drug release (Gao, Page 127, R. Col.).
Regarding claims 1, 2, and 5, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the PEG of Li with alternative carboxylic acid linkers, such as the succinyl group of Gao, which results in the instantly claimed succinate linker, in order to optimize the drug release kinetics of the PEG-diosgenin carrier as desired by Li (Li, Page 74829, L. Col.). The PEG-succinate-diosgenin conjugate taught by the combination of Li and Gao reads on Applicant’s elected species of claimed compound, diosgenin polyethylene glycol succinate, as recited in claim 5.
Regarding claim 13, Li teaches nanoparticles comprising PEG-diosgenin conjugate loaded with anticancer drug HCPT (Li, Page 74829, Section 2.5), which reads on the instantly claimed composition comprising the compound of instant claim 1 and an active ingredient, wherein the active ingredient is an active pharmaceutical ingredient. It would have been prima facie obvious to load the PEG-succinate-diosgenin conjugate taught by the combination of Li and Gao with the anticancer drug of Li according to known methods to yield the predictable result of a drug-loaded nanoparticles with optimized drug release kinetics. The Examiner notes that the instant claim language does not require that the composition further include an excipient. Thus, the drug-loaded nanoparticles taught by the prior art combination meets all limitations of claim 13.
Regarding claim 14, Li teaches that the drug-loaded nanoparticles are prepared by dissolving 10 mg HCPT active ingredient and 20 mg of PEG-diosgenin conjugate compound in distilled water (Li, Page 74829, R. Col.), resulting in a 1:2 ratio of the active ingredient to the conjugate, which lies within and thus reads the instantly claimed range. It would have been prima facie obvious to formulate the drug-loaded nanoparticles taught by the combination of Li and Gao using the same ratio of active ingredient to conjugate as described in Li because this ratio is known to provide a sufficient therapeutic effect.
One of ordinary skill in the art would reasonably expect success in modifying the PEG-diosgenin conjugate of Li with the teachings of Gao as proposed because the combined references teach that the proposed synthetic methods are well known in the art to be useful in developing new drug delivery systems with improved pharmacokinetic and pharmacodynamic profiles (Gao, Page 125, L. Col.).
Claims 1-2, 4-5, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (RSC Adv., 5, 74828–74834; published: 08/27/2015; PTO-892) in view of in view of Gao (MOJ Bioequiv Availab., 5(3), 125‒128; published: 05/02/2018; PTO-892), as applied to claims 1-2, 5, and 13-14 above, and further in view of Gursahani et al. (J. Pharm. Sci., 98(8), 2847-2856; published: 04/30/2009; PTO-892).
The combination of Li and Gao teaches the invention(s) of claims 1-2, 5, and 13-14 as discussed in detail above and further incorporated herein.
While the prior art combination teaches a PEG polymer, the combination does not expressly teach wherein the PEG is PEG 200, PEG 400, PEG 600, PEG 800, PEG 1000, or PEG 2000.
Gursahani teaches that PEG size plays a dominant role in controlling the rate and mechanism of PEG-conjugate absorption and permeability across the pulmonary epithelium (Gursahani, Page 2848, L. Col.), noting that the permeability of the pulmonary epithelium to PEG is effectively linear for PEG sizes of 550, 1000, 2000, and 3400, whereas larger PEG sizes of 5000 and greater exhibited a significantly slower rate of elimination from the tissue (Gursahani, Page 2851, L. Col.).
Regarding claim 4, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the PEG-succinate-diosgenin taught by the combination of Li and Gao by substituting the PEG, which has a molecular weight of 5000 (Li, Page 74829, L. Col.), with a lower molecular weight PEG, such as the PEG 1000 or PEG 2000 of Gursahani, which read on PEG species recited in claim 4, in order to improve the permeability and drug release rate of the PEG-diosgenin conjugate according to therapeutic need.
One of ordinary skill in the art would reasonably expect success in modifying the PEG-succinate-diosgenin conjugate taught by Li and Gao, which is implemented in the treatment of lung tumors (Li, Page 74832, R. Col.), with the teachings of Gursahani as proposed because the combined references teach that modulating the molecular weight of PEG in bioconjugates is useful strategy for altering the diffusion rate of the polymer-drug conjugate across the pulmonary epithelium (Gursahani, Page 2853, L. Col.).
Response to Arguments
Applicant’s arguments submitted on 04/20/2026 with respect to rejections under 35 U.S.C. 103 have been fully considered in so far as they apply to the new or modified rejections of the instant Office action, but were not found to be persuasive.
Applicant’s arguments related to the withdrawn rejections under 102 are addressed herein to the extent that they apply to the 103 rejections of record. Applicant argues that Li does not disclose, teach, or suggest insertion of a linker positioned between sapogenin and PEG as described in amended claim 1. This argument was not found to be persuasive. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The deficiencies of Li are cured by Gao, which teaches that succinylation of PEG, wherein the free -COOH of the succinyl group is conjugated (i.e., linked) with other molecules, is a routine approach used to develop new drug delivery systems with improved pharmacokinetic and pharmacodynamic profiles by reducing steric hindrance. A skilled artisan looking to improve upon the work of Li would be reasonably motivated to include such a linker in order to optimize the drug release kinetics of the PEG-diosgenin carrier using a known technique, wherein improved pharmacokinetics is expressly desired by Li (Li, Page 74829, L. Col.; previously cited).
Applicant additionally argues that Li does not disclose the genus of sapogenins as described in the instant claims. The Examiner respectfully disagrees as Li expressly teaches diosgenin, which is clearly named by Applicant as a suitable sapogenin in claim 2. Note: MPEP 2131.02. "A generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus." The species in that case will anticipate the genus. In re Slayter, 276 F.2d 408, 411, 125 USPQ 345, 347 (CCPA 1960); In re Gosteli, 872 F.2d 1008, 10 USPQ2d 1614 (Fed. Cir. 1989).
Applicant further argues that Gao does not disclose sapogenins or the particular linkers described in amended claim 1. Applicant then references Gao’s Table 1 to assert that there is no mention of any of the specific linker moieties described in amended claim 1. This argument was not found to be persuasive. Again, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In the passage of Gao cited by the Examiner (Gao, Page 127, R. Col.), the reference expressly teaches use of a succinate linker for the purpose of PEG bioconjugation, wherein the free -COOH of the succinylated PEG is then available to form an ester bond conjugate with another molecule, such as the diosgenin of Li. Ester bond conjugation is the same mechanism used to join PEG and diosgenin in the work of Li (see Scheme 1A of Li; previously cited) and thus an ordinarily skilled artisan would reasonably expect success in synthesizing the proposed conjugate. Because the prior art provides both a motivation to modify the PEG-diosgenin conjugate and a reasonable expectation of success in doing so, all features of the instantly claimed invention are rendered prima facie obvious.
Applicant further argues that Gursahani is directly solely to pharmacokinetics and pulmonary absorption of free PEG polymers of varying molecular weights and does not disclose or suggest a compound including sapogenins, selective linker moiety, and PEG. This argument was not found to be persuasive. Again, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Gursahani expressly teaches that PEG conjugation of molecules can slow absorption from the pulmonary epithelium to the systemic circulation (Gursahani, Page 2848, L. Col.; previously cited). Therefore, the work of Gursahani is directly related to optimizing the pharmacokinetics and pulmonary absorption of PEG conjugates and—contrary to Applicant’s assertion that the reference only examines free PEG—uses PEG-FITC conjugates as a model for evaluating the effect of PEG size on drug delivery. Therefore, an ordinarily skilled artisan looking to improve the permeability and drug release rate the PEG-succinate-diosgenin conjugate taught by the combination of Li and Gao would certainly look to the teachings of Gursahani to optimize the PEG component with a reasonable expectation of success. Together, the prior art combination renders obvious all features of the instantly claimed invention.
In view of the foregoing, the prior art rejections of record are maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated any 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 SARAH CLINKSCALES WISTNER whose telephone number is (571)270-7715. The examiner can normally be reached Monday - Thursday 8:00 AM - 5:00 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached at (571)272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH C WISTNER/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616
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