Prosecution Insights
Last updated: April 19, 2026
Application No. 18/002,681

COMPOSITIONS AND METHODS OF USING A PLA2-RESPONSIVE DRUG DELIVERY SYSTEM

Final Rejection §103
Filed
Dec 21, 2022
Examiner
MEJIAS, SAMANTHA LEE
Art Unit
1618
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Trustees of the University of Pennsylvania
OA Round
2 (Final)
50%
Grant Probability
Moderate
3-4
OA Rounds
3y 6m
To Grant
99%
With Interview

Examiner Intelligence

Grants 50% of resolved cases
50%
Career Allow Rate
8 granted / 16 resolved
-10.0% vs TC avg
Strong +57% interview lift
Without
With
+57.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
61 currently pending
Career history
77
Total Applications
across all art units

Statute-Specific Performance

§101
1.2%
-38.8% vs TC avg
§103
48.3%
+8.3% vs TC avg
§102
21.7%
-18.3% vs TC avg
§112
18.0%
-22.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 16 resolved cases

Office Action

§103
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 . Claims 1-5, 13-17, 19-20, 22, 26, 28-29, 35, 42 and 47-48 are pending. Claims 13-17, 19-20, 22, 26, 28-29 and 35 are withdrawn. Claims 6-12, 18, 21, 23-25, 27, 30-34, 36-41, 43-46 are cancelled. Claims 47-48 are added. Claims 1, 2, 4, 5, and 42 are amended. Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Claim Rejections - 35 USC § 103 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. 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, 42, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over GAO (PLA2-responsive and SPIO-loaded phospholipid micelles. Chem Commun. 2015.) in view of THOMAS (US 2019/0142835 A1). Regarding claim 1, GAO teaches a micelle that is loaded with phospholipids which are further conjugated to an active agent, such as a dye (abstract and scheme 1). The active agent is released from the phospholipid when hydrolyzed by phospholipase A2 (abstract). Regarding claim 2, GAO teaches the active agent is released from the phospholipid when hydrolyzed by phospholipase A2 (abstract). Regarding claim 4, GAO teaches the drug delivery system is a micelle (abstract). Regarding claim 5, GAO teaches that the micelle comprises a fluorescent dye (page 2, paragraph 4). Regarding claim 42, GAO teaches a micelle that is loaded with phospholipids which are further conjugated to an active agent, such as a dye (abstract and scheme 1). Additional disclosures: GAO teaches the phospholipids give the delivery system biocompatibility (page 2, paragraph 2). GAO further teaches that elevated levels of PLA2 are associated with cancer, such as in prostate cancer PLA2 levels have been found to be up to 22-fold higher than physiological levels (page 1, paragraph 1). Furthermore, this study is designed for future research to create a PLA2-responsive phospholipid micelles loaded with nanoparticles that could provide drug release specifically in response to PLA2 activity, and also enable non-invasive magnetic resonance (MR) imaging (page 2, paragraph 2). The system was set up to mimic a PLA2-responsvie prodrug (page 2, paragraph 3). GAO does not teach that the active agent is a phospholipase A2 (PLA2) enzyme inhibitor. Regarding claim 1, THOMAS teaches treating cancer using a PLA2 inhibitor (claim 1), such as varespladib (claim 3 and figures 5H-J). Varespladib increases cell apoptosis for cancer cells (page 13, paragraph 0179), which decreases tumor growth (page 1, paragraph 0009). Regarding claims 47-48, THOMAS teaches treating cancer using a PLA2 inhibitor (claim 1), such as varespladib (claim 3 and figures 5H-J). It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using varespladib as the drug. The person of ordinary skill in the art would have been motivated to make those modifications, because varespladib increases cell apoptosis for cancer cells, which leads to decreased tumor growth. Furthermore, PLA2 levels are increased in cancer areas of the body and this would allow the cancer drug to be accurately released in cancer areas and reasonably would have expected success because the references are in the same field of endeavor, such as cancer therapeutics involving PLA2. Further, the delivery system in GAO is designed to be later used as a delivery system for providing drug release specifically in response to PLA2 activity, and also enable non-invasive magnetic resonance (MR) imaging. The reference does not specifically teach the weight percent of phospholipid as claimed by the Applicant. The weight percent of phospholipid is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal weight percent of phospholipid in order to best achieve desired results, such as having enough phospholipids to achieve biocompatibility and to attach the desired amount of active agents. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the weight percent of phospholipid would have been obvious at the time of Applicant’s invention. Response to Arguments Applicant’s arguments with respect to claim(s) 1-5, 42 and 46-47 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Conclusion No claims are allowable. 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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F. 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, MICHAEL 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. 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. /S.L.M./Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
Read full office action

Prosecution Timeline

Dec 21, 2022
Application Filed
Nov 03, 2025
Non-Final Rejection — §103
Feb 05, 2026
Response Filed
Apr 06, 2026
Final Rejection — §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
50%
Grant Probability
99%
With Interview (+57.1%)
3y 6m
Median Time to Grant
Moderate
PTA Risk
Based on 16 resolved cases by this examiner. Grant probability derived from career allow rate.

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