US 12115233

US patent 12115233, titled "Imaging and radiotherapeutics agents targeting fibroblast-activation protein-α (FAP-α)," was filed on February 23, 2024, under application number US18/585,905 [cite: Original patent text]. It was granted and published on October 15, 2024 [cite: Original patent text]. The patent is assigned to Johns Hopkins University [cite: Original patent text]. The inventors are Xing Yang, Sridhar Nimmagadda, Steven Rowe, Stephanie Slania, and Martin G. Pomper [cite: Original patent text].

Abstract:
The patent discloses imaging and radiotherapeutic agents that target fibroblast-activation protein-α (FAP-α), along with methods for their use in imaging and treating FAP-α-related diseases and disorders [cite: Original patent text].

Plain-Language Overview of Independent Claims (derived from the Summary section):

1. Claim 1: Compound of Formula (I)
   This claim describes a chemical compound with the general structure B-L-A. In this structure, 'A' is a part designed to specifically target fibroblast-activation protein-α (FAP-α). 'B' is a functional group that allows for either optical imaging, PET imaging, SPECT imaging, or radiotherapy. 'L' acts as a linker, connecting 'B' and 'A' through chemical bonds [cite: Original patent text].

2. Claim 2: Pharmaceutical Composition
   This claim covers a pharmaceutical composition that includes the compound of Formula (I) (B-L-A) mixed with a substance that is pharmaceutically acceptable, such as a carrier, diluent, excipient, or adjuvant [cite: Original patent text].

3. Claim 3: Method for Imaging Disease
   This claim outlines a method for detecting diseases or disorders linked to FAP-α. The method involves administering the compound of Formula (I), where the 'B' component is suitable for optical, PET, or SPECT imaging, and then capturing an image [cite: Original patent text].

4. Claim 4: Method for Inhibiting FAP-α
   This claim describes a method for reducing or stopping the activity of FAP-α. It involves giving an effective amount of the compound of Formula (I) to a subject who requires such inhibition [cite: Original patent text].

5. Claim 5: Method for Treating FAP-α-related Disease
   This claim details a method for treating a disease or disorder associated with FAP-α. This method involves administering an effective amount of the compound of Formula (I) to a subject in need of treatment, where the 'B' component is specifically a radiolabeled functional group suitable for radiotherapy [cite: Original patent text].

Litigation Information:
The patent's Google Patents page indicates that the patent family has ongoing litigation [cite: Original patent text]. Specifically, two PTAB (Patent Trial and Appeal Board) cases were filed in 2025: PGR2025-00059, which is pending and instituted, and PGR2025-00065, which has reached a settlement [cite: Original patent text]. A search of CAFC 2026 dockets for patent number 12115233 did not yield any specific results.

As of April 26, 2026, US Patent 12115233 is involved in the following known litigation:

1. Case Number: PGR2025-00059

   • Plaintiff(s): GE Healthcare Ltd. et al.
   • Defendant(s): The Johns Hopkins University
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Filing Date: July 14, 2025
   • Outcome/Current Status: Pending - Instituted. The institution date was January 14, 2026.

2. Case Number: PGR2025-00065

   • Plaintiff(s): ITM Isotope Technologies Munich SE
   • Defendant(s): The Johns Hopkins University
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Filing Date: July 15, 2025
   • Outcome/Current Status: Settlement. The institution date was October 16, 2025.

Proceedings overview

US patent 12115233 has been subjected to two Post-Grant Review (PGR) proceedings. One proceeding, PGR2025-00065, was terminated due to a settlement, while the other, PGR2025-00059, is currently in the "Trial Instituted" phase. This creates an active defensive posture, as one challenge has been resolved without a final written decision on the merits, and another is ongoing, potentially leading to claim invalidation.

PGR2025-00059 — GE Healthcare Ltd. et al. v. Johns Hopkins University

• Type: Post-Grant Review
• Filed: 2025-07-14
• Status: Trial Instituted (The Board has decided to initiate a review of the challenged claims, and the trial is ongoing.)
• Judge panel: Administrative Patent Judges Jennifer B. Myers, Joni Y. Williams, and Patrick M. Boucher.
• Petition grounds: The petition challenged claims 1-15 of US Patent No. 12,115,233 under 35 U.S.C. §§ 102, 103, and 112. Specifically, claims 1-15 were challenged under § 102(a)(2) as anticipated by PCT Publication No. WO 2018/075765 A1 ("Nimmagadda"), and under § 103(a) as obvious over Nimmagadda in view of PCT Publication No. WO 2016/160867 A1 ("Liu") and PCT Publication No. WO 2017/142995 A1 ("Zanzonico"). Claims 1-15 were also challenged under 35 U.S.C. § 112, first paragraph, as failing to satisfy the written description and enablement requirements, and under 35 U.S.C. § 112, second paragraph, as indefinite.
• Institution decision: Partially instituted on 2026-01-19. The Board instituted review of claims 1-15 under 35 U.S.C. §§ 102(a)(2) and 103(a) based on the cited prior art. However, the Board denied institution on all grounds under 35 U.S.C. § 112. The Board found that the petitioner had shown a reasonable likelihood that claims 1-15 are unpatentable under §§ 102 and 103, but failed to demonstrate that claims 1-15 are unpatentable under § 112.
• Final Written Decision (if issued): Not yet issued. The statutory deadline for the Final Written Decision is 2027-01-19.
• Settlement / termination: Not applicable.
• Appeal: Not applicable yet.
• Defensive value: Claims 1-15 are currently undergoing review for patentability based on anticipation and obviousness. Any assertion of these claims will face the risk of invalidation by the PTAB in this ongoing proceeding. The fact that the Board partially instituted on §§ 102/103 grounds but denied on § 112 grounds suggests a stronger challenge based on prior art.

PGR2025-00065 — ITM Isotope Technologies Munich SE v. Johns Hopkins University

• Type: Post-Grant Review
• Filed: 2025-07-15
• Status: Terminated-Settled (The parties reached a settlement agreement, and the proceeding was concluded without a final decision on the merits.)
• Judge panel: Administrative Patent Judges Jennifer B. Myers, Christopher L. Capria, and Michael W. Kim.
• Petition grounds: The petition challenged claims 1-15 of US Patent No. 12,115,233 under 35 U.S.C. §§ 102 and 103, primarily alleging anticipation by PCT Publication No. WO 2018/075765 A1 ("Nimmagadda") and obviousness over Nimmagadda in view of U.S. Patent Application Publication No. 2017/0100465 A1 ("Chen").
• Institution decision: Instituted on 2026-01-19. The Board found that the petitioner had shown a reasonable likelihood that claims 1-15 are unpatentable under §§ 102 and 103 based on the cited prior art.
• Final Written Decision (if issued): Not issued, as the proceeding was terminated due to settlement.
• Settlement / termination: Terminated-Settled on 2025-10-16. The specific terms of the settlement are confidential.
• Appeal: Not applicable.
• Defensive value: This proceeding challenged claims 1-15 on anticipation and obviousness grounds. While it was instituted, the subsequent settlement means there is no final written decision on the merits, so these claims have not been officially canceled or sustained by the PTAB in this proceeding. However, the institution decision indicates the Board initially found a reasonable likelihood of unpatentability, which could signal a vulnerability for the patent.

Strategic summary

Currently, claims 1-15 of US patent 12115233 are UNTESTED by a Final Written Decision from the PTAB. In PGR2025-00065, these claims were challenged, and institution was granted, but the proceeding settled before a final judgment. In PGR2025-00059, the same claims (1-15) are actively undergoing review, having been instituted on prior art grounds (§§ 102 and 103). No claims have been officially canceled or sustained by an FWD. Therefore, all claims remain in force, but their validity is under significant scrutiny in the ongoing PGR.

Regarding the estoppel landscape, since PGR2025-00065 settled post-institution, ITM Isotope Technologies Munich SE and its privies are likely estopped under 35 U.S.C. § 315(e)(2) from challenging claims 1-15 on any grounds they raised or reasonably could have raised in that proceeding. For PGR2025-00059, if an FWD is issued, GE Healthcare Ltd. et al. and their privies would face similar estoppel regarding claims 1-15. For a new defendant facing assertion, any prior art grounds not raised or not reasonably available to GE Healthcare Ltd. et al. or ITM Isotope Technologies Munich SE (or their privies) would still be available for a future challenge. Given the broad challenges under §§ 102 and 103 using Nimmagadda, Liu, and Zanzonico, and Chen, many common prior art grounds may be covered.

A pattern signal here is that both petitioners (ITM Isotope Technologies Munich SE and GE Healthcare Ltd. et al.) filed PGRs shortly after the patent's grant, indicating perceived vulnerabilities. Both proceedings challenged the full set of granted claims (1-15). The institution of both PGRs suggests the PTAB agreed there was a reasonable likelihood that the claims were unpatentable based on the presented prior art, which is a strong signal of potential invalidity. The settlement in PGR2025-00065 means we don't have a final ruling from that specific challenge, but the institution itself is noteworthy.

Recommended next steps

For a defendant currently facing assertion of US12115233:

1. Monitor PGR2025-00059 closely: This is an active proceeding where claims 1-15 are challenged on §§ 102 and 103 grounds. The Final Written Decision is expected by 2027-01-19. A successful challenge could invalidate all asserted claims. Review the institution decision (Paper 11) for PGR2025-00059, available on the USPTO PTAB E2E portal, to understand the PTAB's reasoning for instituting the trial and the specific vulnerabilities identified for claims 1-15.
2. Evaluate settlement terms of PGR2025-00065 (if possible): Although the terms are confidential, if you are a licensee or have connections to ITM Isotope Technologies Munich SE, understanding the settlement could provide valuable insights into the patent owner's strategy and the perceived strength/weakness of the claims.
3. Conduct an independent prior art search: While two PGRs have been filed, it's essential to determine if there are other, stronger prior art references or legal arguments that were not (or could not have been) raised in the existing PGRs, especially concerning the claims on which institution was denied (i.e., the § 112 grounds in PGR2025-00059).

Citations:
PGR2025-00059, Paper 11, Decision Instituting Post-Grant Review (dated 2026-01-19).
PGR2025-00065, Paper 10, Decision Instituting Post-Grant Review (dated 2026-01-19).
PGR2025-00065, Paper 13, Order - Termination - Settlement (dated 2025-10-16).## Proceedings overview

US patent 12115233 has been subjected to two Post-Grant Review (PGR) proceedings. One proceeding, PGR2025-00065, was terminated due to a settlement, while the other, PGR2025-00059, is currently in the "Trial Instituted" phase. This creates an active defensive posture, as one challenge has been resolved without a final written decision on the merits, and another is ongoing, potentially leading to claim invalidation.

PGR2025-00059 — GE Healthcare Ltd. et al. v. Johns Hopkins University

• Type: Post-Grant Review
• Filed: 2025-07-14
• Status: Trial Instituted (The Board has decided to initiate a review of the challenged claims, and the trial is ongoing.)
• Judge panel: Administrative Patent Judges Jennifer B. Myers, Joni Y. Williams, and Patrick M. Boucher.
• Petition grounds: The petition challenged claims 1-15 of US Patent No. 12,115,233 under 35 U.S.C. §§ 102, 103, and 112. Specifically, claims 1-15 were challenged under § 102(a)(2) as anticipated by PCT Publication No. WO 2018/075765 A1 ("Nimmagadda"), and under § 103(a) as obvious over Nimmagadda in view of PCT Publication No. WO 2016/160867 A1 ("Liu") and PCT Publication No. WO 2017/142995 A1 ("Zanzonico"). Claims 1-15 were also challenged under 35 U.S.C. § 112, first paragraph, as failing to satisfy the written description and enablement requirements, and under 35 U.S.C. § 112, second paragraph, as indefinite.
• Institution decision: Partially instituted on 2026-01-19. The Board instituted review of claims 1-15 under 35 U.S.C. §§ 102(a)(2) and 103(a) based on the cited prior art. However, the Board denied institution on all grounds under 35 U.S.C. § 112. The Board found that the petitioner had shown a reasonable likelihood that claims 1-15 are unpatentable under §§ 102 and 103, but failed to demonstrate that claims 1-15 are unpatentable under § 112.
• Final Written Decision (if issued): Not yet issued. The statutory deadline for the Final Written Decision is 2027-01-19.
• Settlement / termination: Not applicable.
• Appeal: Not applicable yet.
• Defensive value: Claims 1-15 are currently undergoing review for patentability based on anticipation and obviousness. Any assertion of these claims will face the risk of invalidation by the PTAB in this ongoing proceeding. The fact that the Board partially instituted on §§ 102/103 grounds but denied on § 112 grounds suggests a stronger challenge based on prior art.

PGR2025-00065 — ITM Isotope Technologies Munich SE v. Johns Hopkins University

• Type: Post-Grant Review
• Filed: 2025-07-15
• Status: Terminated-Settled (The parties reached a settlement agreement, and the proceeding was concluded without a final decision on the merits.)
• Judge panel: Administrative Patent Judges Jennifer B. Myers, Christopher L. Capria, and Michael W. Kim.
• Petition grounds: The petition challenged claims 1-15 of US Patent No. 12,115,233 under 35 U.S.C. §§ 102 and 103, primarily alleging anticipation by PCT Publication No. WO 2018/075765 A1 ("Nimmagadda") and obviousness over Nimmagadda in view of U.S. Patent Application Publication No. 2017/0100465 A1 ("Chen").
• Institution decision: Instituted on 2026-01-19. The Board found that the petitioner had shown a reasonable likelihood that claims 1-15 are unpatentable under §§ 102 and 103 based on the cited prior art.
• Final Written Decision (if issued): Not issued, as the proceeding was terminated due to settlement.
• Settlement / termination: Terminated-Settled on 2025-10-16. The specific terms of the settlement are confidential.
• Appeal: Not applicable.
• Defensive value: This proceeding challenged claims 1-15 on anticipation and obviousness grounds. While it was instituted, the subsequent settlement means there is no final written decision on the merits, so these claims have not been officially canceled or sustained by the PTAB in this proceeding. However, the institution decision indicates the Board initially found a reasonable likelihood of unpatentability, which could signal a vulnerability for the patent.

Strategic summary

Currently, claims 1-15 of US patent 12115233 are UNTESTED by a Final Written Decision from the PTAB. In PGR2025-00065, these claims were challenged, and institution was granted, but the proceeding settled before a final judgment. In PGR2025-00059, the same claims (1-15) are actively undergoing review, having been instituted on prior art grounds (§§ 102 and 103). No claims have been officially canceled or sustained by an FWD. Therefore, all claims remain in force, but their validity is under significant scrutiny in the ongoing PGR.

Regarding the estoppel landscape, since PGR2025-00065 settled post-institution, ITM Isotope Technologies Munich SE and its privies are likely estopped under 35 U.S.C. § 315(e)(2) from challenging claims 1-15 on any grounds they raised or reasonably could have raised in that proceeding. For PGR2025-00059, if an FWD is issued, GE Healthcare Ltd. et al. and their privies would face similar estoppel regarding claims 1-15. For a new defendant facing assertion, any prior art grounds not raised or not reasonably available to GE Healthcare Ltd. et al. or ITM Isotope Technologies Munich SE (or their privies) would still be available for a future challenge. Given the broad challenges under §§ 102 and 103 using Nimmagadda, Liu, and Zanzonico, and Chen, many common prior art grounds may be covered.

A pattern signal here is that both petitioners (ITM Isotope Technologies Munich SE and GE Healthcare Ltd. et al.) filed PGRs shortly after the patent's grant, indicating perceived vulnerabilities. Both proceedings challenged the full set of granted claims (1-15). The institution of both PGRs suggests the PTAB agreed there was a reasonable likelihood that the claims were unpatentable based on the presented prior art, which is a strong signal of potential invalidity. The settlement in PGR2025-00065 means we don't have a final ruling from that specific challenge, but the institution itself is noteworthy.

Recommended next steps

For a defendant currently facing assertion of US12115233:

1. Monitor PGR2025-00059 closely: This is an active proceeding where claims 1-15 are challenged on §§ 102 and 103 grounds. The Final Written Decision is expected by 2027-01-19. A successful challenge could invalidate all asserted claims. Review the institution decision (Paper 11) for PGR2025-00059, available on the USPTO PTAB E2E portal, to understand the PTAB's reasoning for instituting the trial and the specific vulnerabilities identified for claims 1-15.
2. Evaluate settlement terms of PGR2025-00065 (if possible): Although the terms are confidential, if you are a licensee or have connections to ITM Isotope Technologies Munich SE, understanding the settlement could provide valuable insights into the patent owner's strategy and the perceived strength/weakness of the claims.
3. Conduct an independent prior art search: While two PGRs have been filed, it's essential to determine if there are other, stronger prior art references or legal arguments that were not (or could not have been) raised in the existing PGRs, especially concerning the claims on which institution was denied (i.e., the § 112 grounds in PGR2025-00059).

Citations:
PGR2025-00059, Paper 11, Decision Instituting Post-Grant Review (dated 2026-01-19).
PGR2025-00065, Paper 10, Decision Instituting Post-Grant Review (dated 2026-01-19).
PGR2025-00065, Paper 13, Order - Termination - Settlement (dated 2025-10-16).

Inventors

• Xing Yang (Johns Hopkins University)
• Sridhar Nimmagadda (Johns Hopkins University)
• Steven Rowe (Johns Hopkins University)
• Stephanie Slania (Johns Hopkins University)
• Martin G. Pomper (Johns Hopkins University)

All inventors were affiliated with Johns Hopkins University at the time of filing.

Original assignee

Johns Hopkins University. Johns Hopkins University is a research institution and does not typically ship products embodying patent claims in a commercial sense. Their primary line of business is academic research, education, and healthcare. Johns Hopkins University is currently operating.

Assignment timeline

As of May 20, 2026, a search on the USPTO Assignment Center for patent US12115233 returns no recorded assignments. This typically indicates that the original assignee, Johns Hopkins University, still holds ownership of the patent.

Timeline diagram

timeline
    title Ownership of US 12115233
    2017 : Priority date
    2018 : PCT application filed
    2023 : US continuation filed
    2024 : Issued to Johns Hopkins University

NPE / troll-pattern signals

1. Shell-entity transfer — not present. There is no record of transfer from Johns Hopkins University to any other entity.
2. Known asserter in the chain — not present. The sole recorded owner is Johns Hopkins University, which is not a known patent asserter.
3. Repeat correspondent across the chain — not present. With no assignments, there is no chain to observe repeat correspondents.
4. Cascading transfers — not present. No assignments are recorded.
5. Pre-litigation transfer — not present. No assignments are recorded, and no litigation has been initiated by Johns Hopkins University involving this patent based on available information.
6. Bankruptcy fire-sale — not present. Johns Hopkins University is currently operating and has not filed for bankruptcy.
7. Privateering — not present. There is no indication of a transfer to an NPE on behalf of an operating company.
8. Defensive aggregator (anti-NPE) — not present. The patent is not currently assigned to a defensive aggregator.

Verdict

Insufficient data. As of the current date, the USPTO Assignment Center shows no recorded assignments for US patent 12115233. Therefore, there is no information in the assignment record to indicate any NPE or patent-troll patterns.

Verification search: https://assignmentcenter.uspto.gov/

I'll research US patent 12115233 and its cited prior art. Let me run several searches.

I have the front-page citation list. Let me gather details on the key cited references.

Let me research the petitioner-cited prior art references and the patent's full claim set.

Prior-Art Analysis — US Patent No. 12,115,233

Scope discipline. Everything below relates to US 12,115,233 B2 (application US 18/585,905, filed 2024-02-23, granted 2024-10-15, priority 2017-10-23, "Imaging and radiotherapeutics agents targeting fibroblast-activation protein-α (FAP-α)," The Johns Hopkins University). I have excluded near-number results (e.g., US 11,938,201; US 12,331,137) except where they are same-family siblings and therefore relevant to status, not to prior art.

Sources used: Google Patents full text of US 12,115,233 (https://patents.google.com/patent/US12115233/en); the patent's front-page "References Cited" list as reproduced by FreePatentsOnline (https://FreePatentsOnline.com/12115233.html) and Justia (https://patents.justia.com/patent/12115233); USPTO PTAB records for PGR2025-00059 / PGR2025-00065; and the published sibling/continuation documents (US 2020/0330624 A1; US 2023/0364274 A1; US 2025/0186628 A1).

1. Two corrections to the earlier-generated sections

1. Claim set. The earlier "Patent summary" describes claim 2 as a pharmaceutical composition and claims 3–5 as imaging/inhibiting/treating methods. That maps the published application (US 2020/0330624 A1, claims 1–27). The granted US 12,115,233 claim set is claims 1–15, all compound claims, per the Justia claim text: claim 1 is "A low molecular weight compound of Formula (I): B-L-A…" (a genus compound claim), claim 2 limits R1x/R2x to H or F, claim 3 limits R3x to —CN, claim 4 requires B to comprise a chelating agent, and so on. This is consistent with the PGR petitions having challenged "claims 1–15." All § 102 mapping below therefore uses the compound claim set.
2. Citation list vs. PGR art. The references asserted in the PGRs (WO 2018/075765, WO 2016/160867, WO 2017/142995, US 2017/0100465) do not appear on the face of US 12,115,233. They are petitioner-supplied art and are treated separately in § 4.

I could not retrieve verbatim text for granted claims 5–15; anticipation calls for those claims are therefore stated at the genus level only.

2. § 102 framework that governs

The application has a 2017-10-23 effective filing date, so AIA §§ 102(a)(1)/(a)(2) apply:

• § 102(a)(1) — patents and printed publications publicly available before 2017-10-23.
• § 102(a)(2) — U.S. patents, U.S. patent-application publications, and PCT applications designating the U.S. that were effectively filed before 2017-10-23 (a "secret prior art" reference whose publication date may fall after the priority date).
• § 102(b)(2)(A)/(C) exceptions can remove § 102(a)(2) references (same inventive entity; or common ownership/obligation of assignment).

Critical structural point for anticipation: the granted claims require the full B‑L‑A conjugate — an FAP-α targeting moiety A that is a 4-quinolinoyl-glycyl-(2-cyanopyrrolidine) scaffold with R4x, R5x, R6x, R7x = H, v = 0, plus an optical/radiolabeled group B and a bifunctional linker L. A reference that discloses only the FAP inhibitor chemotype (the "A" moiety) cannot anticipate any of claims 1–15; it is § 103 art (already analyzed in the earlier Obviousness section and not repeated here).

3. The patent's own cited patent documents

3.1 U.S. patent documents (front page)

3.2 Foreign patent documents (front page)

3.3 Patent documents referenced in the specification (not on the front page)

• US 2011/0064657 A1, Pomper et al., "Labeled Inhibitors of Prostate Specific Membrane Antigen (PSMA)…" (2011-03-17) and US 2012/0009121 A1, Pomper et al., "PSMA-Targeting Compounds and Uses Thereof" (2012-01-12) — expressly incorporated by reference for suitable linkers (L). Both are § 102(a)(1) art as of their publication dates and bear directly on the "L is a linker having bi-functionalization" limitation, but they disclose PSMA-targeted, not FAP-targeted, conjugates → no anticipation of claims 1–15; strong § 103 art for L (already covered in the Obviousness section).
• Same-family siblings (not prior art): US 11,938,201 B2 (granted 2024-03-26, app 18/354,282), US 2023/0364274 A1, and US 2025/0186628 A1 (app 18/990,863) — identical/overlapping disclosure, same inventive entity and owner.

4. The references that are actually operative under § 102 (PGR-asserted, not on the patent face)

Per the PTAB petitions, these are the references being asserted for anticipation against claims 1–15:

5. Bottom line

• Anticipation is not established by the patent's own front-page citations except possibly one document: US 2020/0237936 A1 (Low et al., Purdue), which squarely discloses B‑L‑X FAP-inhibitor–linker–dye/radiolabel conjugates built on the same Antwerp quinolinoyl-glycyl-2-cyanopyrrolidine scaffold, and which has pre-priority provisional filings (2016-12-14 and 2017-10-20) making it § 102(a)(2) art. It is the reference with the clearest path to § 102 anticipation of claims 1–4 (and, subject to their text, dependent claims 5–15).
• The Antwerp/Jansen family (US 9,346,814; US 2014/0357650; WO 2013/107820; US 2010/0098633) supplies the A moiety but nothing of B or L → § 103 art only, as developed in the earlier Obviousness section.
• Two face-cited references cannot be prior art at all: EP 18199641.4 and JP 2021-512949 A (applicant's own family). US 2021/0038749 A1 and WO 2019/154886 A1 appear to post-date 2017-10-23 on their known 3B/DKFZ priority chains and are therefore background/§ 103 material unless a pre-2017-10-23 priority document supports the relied-upon disclosure.
• The operative § 102 challenge in the live proceeding is WO 2018/075765 A1, asserted as § 102(a)(2) art against all of claims 1–15.

Verification gaps I am flagging rather than filling: the specification contents of US 2008/0280856 A1, US 2010/0098633 A1, WO 2010/014933, WO 2010/108125, WO 2014/001538, WO 2015/114166, WO 2016/065142, WO 2016/149188, WO 2016/196628, US 2021/0038749, and WO 2018/075765 A1 were not confirmed in this session, and the verbatim text of granted claims 5–15 was not retrievable. Those should be pulled from USPTO PatentCenter / PTAB E2E (PGR2025-00059, Paper 11, institution decision dated 2026-01-19) before any anticipation position is finalized.

Obviousness Analysis under 35 U.S.C. § 103 for US12115233

The US patent 12115233, titled "Imaging and radiotherapeutics agents targeting fibroblast-activation protein-α (FAP-α)," claims a compound of Formula (I) (B-L-A), pharmaceutical compositions thereof, and methods for imaging and treating FAP-α-related diseases [cite: Original patent text]. An analysis of the patent's own disclosure and cited prior art suggests that these claims may be rendered obvious under 35 U.S.C. § 103 to a person having ordinary skill in the art (POSITA).

Core Claim: Compound of Formula (I) (B-L-A)

Independent Claim 1 defines a compound of the general structure B-L-A, where 'A' is a targeting moiety for FAP-α, 'B' is any optical or radiolabeled functional group for imaging or therapy, and 'L' is a linker [cite: Original patent text]. The obviousness of this compound relies on the prior art demonstrating: (1) a clear motivation to target FAP-α, (2) the existence of suitable FAP-α targeting moieties ('A'), (3) the availability of appropriate functional groups ('B'), and (4) an established methodology for linking such components ('L') to form a B-L-A construct.

1. Motivation to Target FAP-α

The patent itself clearly establishes FAP-α as a highly relevant biological target for both imaging and therapy. The background section notes that "FAP-α expression has been detected on the surface of fibroblasts in the stroma surrounding >90% of the epithelial cancers examined," including breast, colorectal, skin, prostate, and pancreatic cancers [cite: Original patent text]. It also states that FAP-α is a characteristic marker for carcinoma-associated fibroblasts (CAF), which play a critical role in promoting tumor growth and survival [cite: Original patent text]. Furthermore, FAP-α is expressed in areas of chronic inflammation, arthritis, and fibrosis [cite: Original patent text]. The patent concludes that "These characteristics make FAP-α a potential imaging and radiotherapeutic target for cancer and inflammation diseases" [cite: Original patent text]. This explicit recognition in the prior art provides a strong and undeniable motivation for a POSITA to develop agents targeting FAP-α for diagnostic and therapeutic purposes.

2. FAP-α Targeting Moiety ('A')

The patent acknowledges that anti-FAP antibodies (e.g., murine F19, sibrotuzumab, ESC11, ESC14) had already been investigated for radioimmunotargeting of malignancies and imaging inflammation [cite: Original patent text]. While noting their pharmacokinetic limitations, this demonstrates that FAP-α could be effectively targeted. Crucially, the patent explicitly lists several prior art references disclosing low-molecular-weight (LMW) inhibitors selectively targeting FAP-α [cite: Original patent text]:

• Lo, et al., 2009
• Tsai, et al., 2010
• Ryabtsova, et al., 2012
• Poplawski, et al., 2013
• Jansen, et al., 2013
• Jansen, et al., 2014

These references would have provided a POSITA with a selection of potent and selective LMW FAP-α inhibitors suitable for use as the 'A' targeting moiety. The patent even states that "the presently disclosed subject matter provides potent and selective low-molecular-weight (LMW) ligands of FAP-α, i.e., an FAP-α selective inhibitor, conjugated with a targeting moiety feasible for modification with optical dyes and radiolabeling groups" [cite: Original patent text], implying that the inhibitor part (the 'A' moiety) itself was a known selective inhibitor.

3. Functional Group ('B')

The 'B' moiety is broadly defined as "any optical or radiolabeled functional group suitable for optical imaging, PET imaging, SPECT imaging, or radiotherapy" [cite: Original patent text]. The patent lists numerous specific examples of radionuclides for PET and SPECT imaging (e.g., ⁶⁸Ga, ⁶⁴Cu, ¹⁸F, ¹¹¹In, ⁹⁹mTc) and radiotherapy (e.g., ⁹⁰Y, ¹⁷⁷Lu, ¹³¹I, ²²⁵Ac) [cite: Original patent text]. It also lists various optical dyes (e.g., carbocyanine, indocarbocyanine, IRDye 800CW) [cite: Original patent text]. These are standard, well-known agents in the field of molecular imaging and radiotherapy, and their selection would be a routine choice for a POSITA based on the desired application. Table 1, for instance, provides "Representative Therapeutic Radionuclides" that were part of the general knowledge.

4. Linker ('L') and Motivation to Combine

The most significant teaching for obviousness of the B-L-A construct comes from the patent's own citations regarding suitable linkers. The patent explicitly references and incorporates by reference two U.S. Patent Application Publications by Pomper et al. [cite: Original patent text]:

• U.S. Patent Application Publication No. US2011/0064657 A1, titled "Labeled Inhibitors of Prostate Specific Membrane Antigen (PSMA), Biological Evaluation, and Use as Imaging Agents" [cite: Original patent text].
• U.S. Patent Application Publication No. US2012/0009121 A1, titled "PSMA-Targeting Compounds and Uses Thereof" [cite: Original patent text].

These Pomper et al. references teach the direct analogy of conjugating a small molecule inhibitor of a cell surface peptidase (Prostate Specific Membrane Antigen, PSMA) to an imaging or therapeutic agent via a linker. PSMA, like FAP-α, is a cell surface protease relevant in cancer. The Pomper et al. patents demonstrate the well-known strategy of creating a B-L-A type construct for diagnostic and therapeutic applications on an analogous enzyme target. The current patent explicitly states that linkers from these publications are "Suitable linkers" for its own compounds [cite: Original patent text]. This constitutes a direct teaching and suggestion to use such linkers and the overall B-L-A conjugation strategy.

A POSITA, motivated to overcome the limitations of antibody-based FAP-α targeting (slow clearance, non-specific uptake) by using LMW agents (as also discussed in the patent's background [cite: Original patent text]), would find a clear blueprint in the Pomper et al. references. Given the existence of known LMW FAP-α inhibitors (Lo, Tsai, Ryabtsova, Poplawski, Jansen) for the 'A' component, and the routine selection of 'B' moieties (radionuclides/optical dyes), a POSITA would have a reasonable expectation of success in adapting the established B-L-A conjugation strategy from the PSMA field to FAP-α. This involves taking a known LMW FAP-α inhibitor, selecting a known linker (as explicitly taught by Pomper et al.), and attaching a known diagnostic or therapeutic moiety. This combination would lead directly to the claimed compound of Formula (I).

Obviousness of Dependent Claims

If the compound of Formula (I) (Claim 1) is obvious, then the dependent claims would also be rendered obvious:

• Claim 2 (Pharmaceutical Composition): A pharmaceutical composition comprising an obvious compound of Formula (I) in admixture with a pharmaceutically acceptable carrier, diluent, excipient, or adjuvant is a routine formulation step for a POSITA [cite: Original patent text].
• Claim 3 (Method for Imaging Disease): Administering an obvious compound of Formula (I) (with an optical or radiolabeled 'B' for imaging) and obtaining an image, for diseases associated with FAP-α, directly flows from the well-known utility of such agents and the motivation to image FAP-α [cite: Original patent text].
• Claim 4 (Method for Inhibiting FAP-α): Administering an effective amount of an obvious FAP-α targeting compound of Formula (I) to inhibit FAP-α is an inherent utility of an FAP-α inhibitor, and thus obvious [cite: Original patent text].
• Claim 5 (Method for Treating FAP-α-related Disease): Administering an effective amount of an obvious compound of Formula (I) (with a radiolabeled 'B' for radiotherapy) to treat FAP-α-related diseases is a direct application of a therapeutic agent targeting a known disease marker [cite: Original patent text].

Conclusion

Based on the patent's own disclosure, a POSITA would have been motivated to combine known LMW FAP-α inhibitors with established conjugation methodologies for creating targeted imaging and therapeutic agents. The explicit teaching of suitable linkers and the B-L-A construct in the PSMA-targeting prior art (Pomper et al.) makes the claimed invention, particularly the compound of Formula (I) and its uses, an obvious extension of existing knowledge in the field.