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 .
Response to Arguments
Applicant's arguments, filed August 11, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 7, and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Barnett et al. (US 2011 0104052; cited on IDS filed October 24, 2023).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed May 11, 2026 and those set forth herein.
Applicant argues that Barnett fails to disclose all limitations of claim 1 within a single embodiment. Applicant argues that Barnett’s claim 13 does not teach introducing a loading complex into a pre-formed hydrogel microsphere containing pH gradient liposomes prior to loading. Applicant argues that Barnett’s BMEDA disclosure is restricted to PEGDA-encapsulated ammonium-gradient liposomes as a radiolabeling technique, and that Barnett’s use of ionophores involves removal rather than retention in the liposome. Applicant argues that ¶ 24 of Barnett does not map to a loading complex retained within as claim 1 requires.
This argument is unpersuasive. Under MPEP § 2131.02, a reference disclosure can anticipate a claim when the reference describes the limitations but ‘d[oes] not expressly spell out’ the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination. Barnett’s disclosure does not present an improper mosaic of unrelated teachings. Rather, Barnett’s generic disclosure in claim 13 provides an overarching inventive concept, a method of producing a therapeutic polymer matrix comprising nanoparticles loaded with one or more bioactive agents comprising incubating nanoparticles and polymer matrix after polymerization with bioactive agents. The individual limitations identified by the examiner such as hydrogel, liposomes with pH gradient, and BMEDA-complexed agents represent a limited, well-defined set of preferred alternatives provided within single specification of Barnett. Because Barnett provides a concise set of explicit choices for each structural component, a POSITA reading Barnett would at once envisage the specific combination recited in instant claim 1. Therefore, because the species can be immediately and clearly conceived from the disclosure, the generic disclosure in prior art can anticipate as claimed species. Barnett’s claim 13 explicitly teaches a method of loading a pre-formed, post-polymerization structure which reads on post-manufacture loading, manufactured prior to loading, and pre-formed microsphere of instant claim. While Barnett discusses ionophore removal in certain alternative embodiments, the examiner specifically relied on the BMEDA loading complex mechanism. Applicant’s narrow reading of Barnett is misplaced. Barnett’s disclosure of BMEDA-mediated loading is not isolated, rather it serves as a representative loading mechanism for the gradient liposomes disclosed throughout Barnett. Selecting a preferred loading complex (BMEDA) discloses in Barnett to load gradient liposomes embedded in a post-polymerization matrix does not require inventive leap or modification, it is an arrangement directly envisaged from Barnett’s explicit teachings. The recitation of ¶ 24 is for demonstrating that Barnett teaches that a bioactive agent can be an agent listed in instant claim 7. The claimed structure already is already taught or directly envisaged by Barnett’s disclosures as discussed above.
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 1-5, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Xiong et al. (US 2014 0127287; cited on IDS filed October 24, 2023) in view of Barnett et al. (US 2011 0104052; cited on IDS filed October 24, 2023).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed May, 11, 2026 and those set forth herein.
Applicant argues that Xiong teaches an inverse architecture compared to claim 1 and that teaches away from radioembolization microsphere. Applicant argues that there is no motivation to combine Xiong and Barnett absent hindsight reconstruction.
This argument is unpersuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Applicant’s focus on Xiong alone is misplaced because the rejection is based on the combination of Xiong and Barnett. Modifying Xiong’s polymer/liposome delivery system to incorporate a plurality of liposomes within a hydrogel microsphere, as taught by Barnett, is a design choice involving known structural elements performing their established functions. The law does not require the primary reference alone to teach every structural feature of the claim that is the very premise of a 35 U.S.C. 103 combination. Under MPEP § 2143.01, a reference does not teach away merely because it discloses a different preferred embodiment or scale, unless it explicitly criticizes, discredits, or discourages the claimed combination. Xiong’s disclosure of 100-400 nm lipogels does not criticize larger microsphere dimensions nor state that hydrogel-liposome matrices cannot be sized for embolization. Furthermore, scaling a polymer matrix size to fit a targeted anatomical site is a matter of routine optimization within the skill of a POSITA.
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. 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. Xiong and Barnett belong to the same field of endeavor, hydrogel-liposome hybrid drug delivery systems. A POSITA seeking to improve the versatility, entrapment efficiency, and radiotherapeutic application of Xiong’s system would naturally look to Barnett’s explicit teachings as discussed in the Office Action mailed May 11, 2026. The motivation to combine Xiong and Barnett is supported by the teachings if the prior art and the knowledge generally available to a POSITA. Such a combination is grounded in objective evidence rather than impermissible hindsight reasoning. Combining these known elements yields the predictable result of a delivery system as claimed. Such a combination is well within the ordinary capabilities of a POSITA.
Applicant argues that Example 1 demonstrates unexpected superior results and offers to submit a Declaration.
This argument is unpersuasive. Applicant’s assertions of unexpected results fail to satisfy the requisite legal criteria established under MPEP § 716.02. Objective evidence of unexpected results must be supported by an appropriate evidentiary showing, direct comparative data, and must be commensurate in scope with the claims. Applicant has failed to meet this burden based on the following criteria.
First, the alleged results are predictable, not truly unexpected. To establish unexpected results, the improvement or enhancement must significantly exceed what a person having ordinary skill in the art would have reasonably anticipated by the prior art. The alleged improvements in radiolabeling efficiency and embolization performance are predictable outcomes stemming from the known properties of the combined components. As discussed above, Barnett explicitly teaches that incorporating pH-gradient liposomes into hydrogels for efficient active agent entrapment and retention. Achieving higher loading efficiency upon adding gradient liposomes to an alginate matrix represents a predictable trend and expected difference in degree, not an unexpected difference in kind.
Second, Applicant fails to provide a direct comparison with the closest prior art (Barnett and Xiong individually or in a baseline combination). The evidence of unexpected results must involve a direct, side-by-side comparison between the claimed invention and the closest prior art. Without a direct comparison showing that the actual performance of the claimed composition is significantly better than what would be predicted from the prior art, the showing is insufficient to rebut the prima facie case of obviousness. Applicant cannot establish unexpected results merely by comparing the claimed formulation against inferior or no-prior art control formulations. An empty alginate sphere is an improper control because it lacks the hybrid liposome-hydrogel architecture taught by Barnett and Xiong.
Third, the results are not commensurate in scope of the claims. To effectively rebut a rejection of obviousness, the disclosure or evidence of unexpected results must be commensurate in scope with the claims to which the evidence is applied. Claim 1 broadly encompasses any pH-gradient liposomes, and any therapeutic/diagnostic agent or any combination thereof. However, Applicant’s arguments rely on a narrow, specific example such as Re-186/Tc-99m-BMEDA complex. Applicant fails to provide examples of more combinations across different amounts of different liposomes, hydrogel, active agent, and loading agents. The limited experimental data does not establish that the entire claimed genus would exhibit the same allegedly unexpected properties.
Further, arguments or conclusory statements in the remarks section of a response do not take the place of evidence in the record. Allegations of unexpected results must be explicitly set forth in the originally filed specification or presented in a formal, signed declaration/affidavit accompanied by actual data. Absent the submission of such proper objective evidence, Applicant’s remarks remain mere unsubstantiated allegations that cannot overcome the rejection. Attorney arguments cannot serve as a substitute for comparative test data showing unexpected results.
Accordingly, because the combination of teachings would have been obvious to one of ordinary skill in the art, and because the Applicant has not provided sufficient objective evidence to demonstrate unexpected results, the rejection is maintained.
Conclusion
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 JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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