DETAILED ACTION
The amendment submitted on August 4, 2026 has been entered. Claims 2-3, 6, 8, 12-13, 15, and 18-20 are pending in the application. Claims 2-3, 6, 12-13, and 19 are allowed. Claims 8, 15, 18, and 20 are rejected for the reasons set forth below.
Allowable Subject Matter
Claims 2-3, 6, 12-13, and 19 are allowed.
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.
Withdrawn Rejections
The rejection of claim 3 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of applicant’s corrective amendment.
The rejection of claims 2-3, 6, 8, 12-13, 15, and 18-20 under 35 U.S.C. 103 as being unpatentable over Yoshiaki, Blumberg, Lee, Shah, and Cheng is withdrawn because the limita-tions of claim 17, which was not rejected on this basis, have been incorporated into independent claim 6.
Response to Arguments
Applicant argues that the claimed subject matter is “not disclosed in the prior art in an enabling manner.” See applicant’s Remarks, submitted August 4, 2026, p. 6. In applicant’s view, “each specific prodrug compound requires its own unique synthesis to be created and each compound further reacts and functions in a different way, depending on the underlying struc-ture, chemical bonds, and mechanism of action.” Remarks at p. 10. Applicant further “asserts that there is not a finite number of predictable solutions in the context of the present invention” and “there are a multitude of infinite possibilities of nanocarriers that can be co-formulated with specific TLR prodrugs that could be synthesized that make the instant claims nonobvious and not a reasonable predictable outcome.” Remarks at p. 10. Applicant’s argument about enablement, however, is not supported by any specific evidence. “Arguments presented by applicant cannot take the place of evidence in the record.” See MPEP 2145(I) (argument does not replace evidence where evidence is necessary). In fact, the evidence of record contradicts applicant’s position. The examiner is required to take the teachings of the cited references at face value. “When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability.” See MPEP 2121(I) (prior art is presumed to be operable/enabling). The cited references teach or suggest that their methods and tech-niques are broadly useful. For example, Yoshiaki discloses the synthesis of a wide range of compounds (see, generally, the machine translation of Yoshiaki at pp. 29-55). Blumberg specifi-cally teaches that prodrug techniques can be applied to “broad classes of compounds” (para. 0047). Shah similarly discloses detailed instructions for the preparation of solid lipid nanoparti-cles (pp. 61-65). Applicant has not presented specific evidence that the inventors have overcome a particular problem or otherwise advanced the useful arts. The examiner maintains that the claims at issue are readily predictable from the teachings of the cited references.
Applicant also argues that “there is no support either in Yoshiaki or Blumberg of the specifically claims compounds.” Remarks at p. 8. In applicant’s view, the examiner only arrives as the claimed subject matter by making an improper “hindsight leap.” Remarks at p. 9. In support of this argument, applicant notes that the cited references disclose “an exhaustive set of potential compounds.” Remarks at pp. 9-10. Any judgment on obviousness “is in a sense neces-sarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” See MPEP 2145(X)(A) (impermissible hindsight). All of the limitations of the claimed invention were known in the prior art, and there is motivation to combine them to arrive at the subject matter of the instant claims. The examiner therefore maintains that the rejection is proper.
Finally, applicant further asserts a showing of “‘unexpected results’ that further reinforce the fact that the claims are not obvious.” Remarks at p. 7. Applicant asserts “both synergism as well as superiority of properties.” Referring to Figs. 33, 35-37, and 46-48 in the drawings, applicant asserts a “synergistic effect of … co-formulated SLNPs in multiple Xenograft models.” Referring to Figs. 21-23, applicant asserts a “specific mechanistic validation of the claimed TLR prodrug in view of other TLR prodrugs.” Based on this information, applicant concludes that “not all TLR prodrugs act the same or function the same way.” Remarks at pp. 11-12. “Any differences between the claimed invention and the prior art may be expected to result in some differences in properties.” The issue is whether the properties differ to such an extent that the difference is really unexpected.” See MPEP 716.02 (allegations of unexpected results). It is important to compare the claimed invention to the closest prior art. See MPEP 716.02(e) (comparison with closest prior art). It is not reasonable to conclude that something is unexpected before a baseline is first established of what would, in fact, be expected. The data referred to in applicant’s draw-ings (Figs. 21-23, 33, 35-37, and so forth) appear to describe the characteristics of a composition referred to as “SLNP-TR12,” but what is this composition compared to?
Applicant’s arguments have been fully considered but are not persuasive. The rejection below is therefore maintained.
Maintained Rejections 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 8, 15, 18, and 20, as amended, remain rejected under 35 U.S.C. 103 as being unpatentable over Yoshiaki (WO 2008/114817 A1) in view of Blumberg (US 2013/0184265 A1), Lee (Acc. Chem. Res. 2020, 53, 2081-93), and Shah (J. Physical Science 2014;25,159-75).
Yoshiaki (cited in the prior action) teaches a compound of the structure
PNG
media_image1.png
89
179
media_image1.png
Greyscale
(see p. 84 of the original Japanese-language document at para. 0118) as a pharmaceutical prod-uct (p. 1, abstract). Yoshiaki further discloses that the compound “activates a Toll-like receptor (TLR), more particularly TLR7” (see the machine translation mailed on June 2, 2025 at para. 0041).
The difference between the prior art and the claims at issue is that Yoshiaki does not disclose that the compound is in the form of stearic acid prodrug with a hydroxymethylcarbamate linker or that it is in the form of a nanocarrier composition having the Zav size and Zeta potential limitations of the instant claims.
Blumberg (cited in the prior action), however, discloses prodrugs of secondary amine compounds comprising a stearic acid moiety with a hydroxymethylcarbamate linker having the following structure:
PNG
media_image2.png
124
258
media_image2.png
Greyscale
See Table 1 at para. 0079 in Blumberg. This lipid-containing moiety can be used to make prodrugs of a wide range of different drugs (para. 0047-78). Optimization of drug pharmacology in this manner “has many potential benefits,” such as “less frequent dosing” and “extending the period through which the drug is released,” among other things (para. 0007).
Lee (cited in the prior action) teaches that conjugation of a C18 chain to a TLR agonists generates lipidated prodrugs which, owing to their hydrophobicity, show lesser side effects due to lower serum concentration and system circulation (see “Hydrophobic or Macromolecule Conjugation” at p. 2085). This “not only immobilizes the [TLR] agonists but also transforms them into particulate formulas” (p. 2085). Another benefit is that such prodrugs are activated in the tumor environment thereby reducing undesirable side-effects arising from TLR agonist-mediated immune responses (p. 2084).
It would have been prima facie obvious to one of skill in the art as of the effective filing date to use the prodrug techniques of Blumberg and modify the drug of Yoshiaki to arrive at the chemical structure illustrated in the claims. Motivation for doing so would have come from Lee, from which the skilled artisan would have understood that TLR agonist lipid-conjugates and prodrugs have greater lipophilicity and lesser side effects. One would have had a reasonable expectation of success because Blumberg teaches that these prodrug techniques may be used on a wide variety of different drugs, so surely it would also be useful in making a prodrug deriva-tive of the compounds of Yoshiaki.
While Lee mentions “particulate formulas” (p. 2085), it does not specifically disclose a solid-lipid nanoparticle (SLNP) having a Zav size of 93.37 nm or a Zeta potential of -12.8 mV (see instant claim 15). One would therefore look to the prior art for information about the “particu-late formulas” referred to in Lee, and Shah provides an answer to this question.
Shah (cited in the prior action) reviews the properties of particle size and Zeta potential and how they correlated to particle stability in solid-lipid nanoparticles. This reference discloses that SLNPs are a well-tolerated lipid carrier system (see Abstract). They provide numerous benefits, such as the ability to encapsulate and protect labile drugs from degradation, improved bioavailability, drug targeting, and excellent physical stability, among other things (p. 60). They comprise “particles typically in the size range of 50-1000 nm (p. 60). Typical Zeta potential meas-urements are “in the range of -11 to -17 mV” (p. 66). Note that these ranges generally encompass the Zav size and Zeta potential limitations of claim 15.
It would have been prima facie obvious to one of skill in the art as of the effective filing date to formulate the prodrug suggested by Yoshiaki, Blumberg, and Lee using the solid-lipid nanoparticles discussed in Shah and thereby arrive at subject matter within the scope of the instant claims. One would have been motivated to do so in order to take advantage of the numerous benefits described in Shah. Furthermore, Lee acknowledges “particulate formulas,” but does not provide specific information about them. One would therefore look to Shah for this missing information. Finally, note that the Zav size and Zeta potential limitations of instant claim 15 are within the general ranges taught by Shah. One would therefore have viewed the Zav size of 93.37 nm or a Zeta potential of -12.8 mV in claim 15 as being a matter of routine optimization within the general conditions taught by the prior art. See MPEP 2144.05.
Finally, any written instructions associated with the kit of claims 18 and 20 have not been accorded patentable weight for the reasons discussed in MPEP 2111.04.
Conclusion
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 Theodore R. Howell whose telephone number is (571)270-5993. The exam-iner can normally be reached Monday - Thursday, 8:00 am - 7:00 pm (Eastern Time). 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, 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.
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.
THEODORE R. HOWELL
Primary Examiner
Art Unit 1628
/THEODORE R. HOWELL/ Primary Examiner, Art Unit 1628
October 14, 2026
