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 .
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 07/27/2026 has been considered by the Examiner inasmuch as foreign documents have been submitted into the file wrapper in English.
Claim Status
The claim set and Applicant remarks filed July 27, 2026 have been entered.
Claims 3-4, 14, 19, 23 and 25-31 are canceled.
Claims 22 and 32-34 continue to be withdrawn from further consideration as being drawn to a nonelected species or invention(s) as discussed in the non-final office action mailed February 27, 2026.
Thus, claims 1-2, 5-13, 15-18, 20-21 and 24 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action February 27, 2026:
(I) The objection to claim 18 is withdrawn in view of Applicant’s amendment to this claim.
(II) The rejection of claims 1-2, 5-13, 15-18, 20-21 and 24 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to claim 1.
Response to Arguments
The Examiner has reviewed and considered Applicant’s claim amendments and remarks which are found persuasive to overcome the 103-rejection written in the non-final rejection mailed February 27, 2026, as discussed above.
However, upon further consideration of the prior art, particularly the combination of the Bhargava, Marciani and Hubbell references, said combination teach the newly added limitation recited in claim 1, line 4. Accordingly, the Examiner has written a new 103 rejection which is discussed in further detail below.
Moreover, the Examiner respectfully notes the newly written 103 rejection renders moot Applicant’s arguments I-III and V as written in Applicant’s remarks, as discussed above on pp. 21-23.
Furthermore, the Examiner respectfully disagrees with Applicant’s argument IV written on pg. 23 of Applicant’s remarks for at least the following reasons discussed below.
Applicant argues:
There is no reasonable expectation of success as the modification at the 3-O-glucuronic acid residue would significantly impact solubility, membrane interaction and biological activity; and Hubbell provides only a generic disclosure of bifunctional linkers without teaching compatibility with complex saponin structures or preservation of biological activity, see Applicant’s remarks, pg. 23, section IV.
With respect to Applicant’s argument the Examiner notes the derivatized SO1861 of the combined teachings of Bhargava, Marciani and Hubbell result in a derivatized SO1861 that is less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin as taught by Marciani and is particularly useful in the method of Bhargava as said method already administers SO1861 as an adjuvant to treat pancreatic cancer which is discussed in greater detail below.
Thus, Applicant’s argument has been fully considered but is not found persuasive.
New Claim Rejections
The following is a new ground rejection necessitated by Applicant's amendment, filed on July 27, 2026, where the limitations in pending claims 1-2, 5-13, 15-18, 20-21 and 24 as amended now have been changed.
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 1-2, 5-13, 15-18, 20-21 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Bhargava et al. (Published 29 July 2017, Molecular Oncology, Vol. 11, Issue 11, pp. 1527-1543, IDS filed 12/04/2023) in view of Marciani (Published 02 November 1999, US-5977081-A, IDS filed 12/04/2023) and Hubbell et al. (Published 04 April 2017, WO-2017058996-A1, PTO-892 mailed 02/27/2026).
Regarding claims 1-2, 5-13, 15-18, 20-21 and 24, Bhargava teaches targeted dianthin to treat pancreatic carcinoma when applied in combination with the glycosylated triterpene SO1861, see pg. 1527, title.
Bhargava teaches a fusion protein of the ribosome-inactivating protein dianthin and human epidermal growth factor in combination with a glycosylated triterpene (SO1861) which serves as an endosomal escape enhancer, as a combined therapy resulting in more than a 13-fold better efficacy with complete regression in 80% of cases when administered to BxPC-3 xenografts in CD-1 nude mice, see pg. 1527, abstract.
Bhargava teaches SO1861 was isolated from Saponaria officinalis L., see pg. 1529, right column, 2.2. isolation of SO1861.
Bargava teaches the dosage of SO1861 was fixed at 30 µg per treatment diluted in 100 µL Dulbecco’s PBS without Ca2+ and Mg2+ (PAA, Linz, Austria) which was applied subcutaneously into the neck (e.g. the pharmaceutical composition, required in claim 24), see pg. 1531, right column, paragraph 1.
Although, Bhargava does not teach SO1861 has a first saccharide chain comprising a carboxyl group of a glucuronic acid moiety which has been derivatized as required in claim 1, lines 10-12; and wherein said SO1861 has been derivatized with N-(2-aminoethyl)maleimide (AEM) to create the corresponding AEM amide as exemplified and elected in molecule 18 as discussed on pg. 2 of the non-final rejection as discussed above.
However, in the same field of endeavor of a glycosylated triterpene that has adjuvant activity, Marciani teaches triterpene saponin analogs having adjuvant and immunostimulatory activity, see title.
Marciani teaches novel chemical compounds in which a lipophilic moiety such as and including a terpene is covalently attached to an exemplified non-acylated or deacylated triterpene saponin via a carboxyl group present on the 3-O-glucuronic acid of the triterpene saponin (e.g. the carboxyl group of a glucuronic acid moiety, required in claim 1, lines 10-12), see abstract.
Marciani teaches the attachment of a lipophilic moiety to the 3-O-glucuronic acid (e.g. 3-O-glcA) of a saponin such as and including a saponin from Saponaria enhances their adjuvant effects on humoral and cell mediated immunity, see abstract.
Marciani teaches the attachment of a lipophile moiety to the 3-O-glucuronic acid residue of the exemplified non- or des-acyl saponin yields a saponin analog that is easier to purify, less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin, see abstract.
Marciani teaches a bifunctional linker can be employed to conjugate the lipophile to the 3-O-glcA residue of the saponin, see Col. 8, lines 4-6.
Marciani teaches non-limiting examples of the linker which can be used to link the saponin and lipophilic moiety are alkylene diamines (NH2-CH2)n-NH2), where n is from 2 to 12, see Col. 8, lines 60-63; and further exemplifies non-limiting bifunctional linkers comprising a free amino group (derived from an alkylene diamine) can also comprise a maleimido group exemplified in sulfosuccinimidyl 4-(N-maleimidocyclohexane)-1-carboxylate, see Col. 14, lines 44-50.
Marciani teaches pharmaceutical compositions comprising one or more of the saponin-lipophile conjugates and one or more pharmaceutically acceptable diluents, carriers, or excipients (e.g. the pharmaceutical composition, see Col. 6, lines 8-11.
Marciani teaches vaccines comprising one or more antigens and a saponin-lipophile conjugate, see Col. 6, lines 13-15; and that said compositions are useful as vaccines to induce active immunity toward antigens in subjects, see Col. 22, lines 42-43.
Marciani exemplifies the antigen can be proteins, peptides and mixtures thereof, and may comprise a protein fragment comprising one or more immunogenic regions of the molecule, see Col. 23, lines 35-41.
Marciani teaches because of their stimulation of humoral and T-cell immunity, as well as negligible toxicity, the saponin-lipophile conjugates of the present invention are suitable for the preparation of cancer vaccines, see Col. 31, lines 50-55.
Although Marciani does not exemplify N-(2-aminoethyl)maleimide (AEM) as the linker as required in the elected species above.
However, in the same field of endeavor of cancer vaccines, Hubbell exemplifies polymer-conjugate vaccines, see title. Hubbell teaches using compounds for inducing the immune system, particularly in treating cancer in humans, by administering said polymer-conjugates, see paragraph [0125].
Hubbell teaches a bifunctional linker can be used as a latent spacer between a therapeutic moiety and a polymer, see paragraph [0091].
Hubbell teaches exemplary compounds used as bifunctional linkers in the preparation of polymeric vaccines can include N-(2-aminoethyl)maleimide trifluoroacetate salt (e.g. the N-(2-aminoethyl)maleimide, required in claim 15, pg. 10, lines 6-7; claim 18, pg. 13, lines 3-5; claim 20, pg. 18, lines 9-10; and claim 21, lines 4-5), see paragraph [0091], pg. 30, line 5-10; which the Examiner respectfully notes is the identical compound as disclosed and evidenced by the specification to introduce a N-(2-aminoethyl)maleimide into the elected compound as discussed above (see pg. 120, line 21).
The Examiner also respectfully notes when the teachings of both Marciani and Hubbell are incorporated into the SO1861 as taught by Bhargava above it will result in the creation of the elected species as discussed above, where the SO1861 as taught by Bhargava is modified with the bifunctional linker N-(2-aminoethyl)maleimide as taught by Hubbell and where said bifunctional linker is specifically incorporated at the 3-O-glcA residue of the saponin to link said SO10861 of Bhargava to the lipophile as taught by Marciani above.
The Examiner further respectfully notes Marciani teaches by incorporating said bifunctional linker as discussed above, the resulting lipophile-saponin conjugate connected via said bifunctional linker possesses equal or better adjuvant properties than the original saponin as taught by Marciani above.
With particular respect to the structural limitations as recited within claims 1-2, 5-13, 15-18 and 20-21, the Examiner reasonably interprets all of the required structural limitations of the claims listed above are taught by the combined teachings of Bhargava, Marciani and Hubbell; as Bhargava teaches the SO1861 saponin; Marciani teaches said 3-O-glcA residue of the saponin is derivatized with a bifunctional linker, which may include alkylene diamines (NH2-CH2)n-NH2), where n is 2 and may also comprise an maleimido group; and Hubbell teaches the bifunctional linker known as N-(2-aminoethyl)maleimide as an exemplified linker used in polymer conjugate vaccines to treat cancer in humans as discussed above, and therefore consequently corresponds to Applicant’s election of SO1861-Glu-AEM (molecule 18) as discussed above as evidenced by the specification which discloses the structure of SO1861-Glu-AEM (molecule 18) (see pg. 133, lines 10-15; Figure 11 of the Drawings filed 12/23/2022; and the elected species as depicted on pg. 2 of the non-final rejection discussed above).
Thus, in view of the teachings above, the Examiner reasonably interprets all structural limitations required in claims 1-2, 5-13, 15-18 and 20-21 as elected by Applicant within molecule 18 as discussed above are met by the combined teachings of Bhargava, Marciani, and Hubbell as discussed above.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have derivatized the saponin as taught by Bhargava above based on the teachings of Marciani to create lipophile-saponin conjugates that possesses equal or better adjuvant properties than the original saponin as taught by Marciani above as within the scope of the artisan as combining prior art elements according to known compounds to yield predictable results; and to have used the N-(2-aminoethyl)maleimide as taught by Hubbell as the bifunctional linker which links the saponin and lipophilic moiety of Marciani, as Marciani teaches nonlimiting examples of the linker include alkylene diamines (NH2-CH2)n-NH2), where n is 2, and may comprise an maleimdo group which the Examiner notes are all structural limitations which encompass the N-(2-aminoethyl)maleimide as taught by Hubbell above.
One of ordinary skill in the art would have had a reasonable expectation of success to have derivatized the SO1861 of Bhargava using the teachings of Marciani and Hubbell as discussed above, because Marciani teaches their saponin-lipophile conjugates are suitable for the preparation of cancer vaccines; Hubbell uses the N-(2-aminoethyl)maleimide linker as a latent spacer between a therapeutic moiety and a polymer in Hubbell’s polymer conjugate vaccines which can be used to treat cancer in humans; and Bhargava is drawn to using a combination comprising a drug-antigen conjugate and SO1861 as an adjuvant to treat pancreatic cancer as discussed above.
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have derivatized the SO1861 of Bhargava using the teachings of Marciani and Hubbell as discussed above for the reasons already stated above as within the scope of the artisan as combining prior art elements according to known compounds to yield predictable results.
One of ordinary skill in the art would have been motivated to have made the derivatized SO1861 as discussed above and therefore would have arrived at SO1861-Glu-AEM (molecule 18) as elected by Applicant above in order to create a starting compound of a saponin comprising a 3-O-glcA residue comprising a carboxyl group which is derivatized with a bifunctional linker to allow for the linking of a lipophile to create a lipophile-saponin conjugate that is easier to purify, less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin as taught by Marciani above.
One of ordinary skill in the art would have had a reasonable expectation of success to have made the derivatized SO1861 of Bhargava because the resulting lipophile-saponin conjugates taught by Bhargava, Marciani, and Hubbell are particularly useful in the method of Bhargava as said method already administers SO1861 as an adjuvant to treat pancreatic cancer as discussed above.
Thus, the claimed invention would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
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 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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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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