Targeted protein degradation (TPD) has moved from promising concept to near-commercial reality in under a decade. By hijacking the cell’s ubiquitin-proteasome system, TPD therapies eliminate disease-driving proteins entirely rather than merely inhibiting them. This approach is particularly powerful against “undruggable” targets that lack deep binding pockets. PROTACs (proteolysis-targeting chimeras) and molecular glues remain the most clinically advanced modalities, but LYTACs (lysosome-targeting chimeras), AUTACs (autophagy-targeting chimeras), DUBTACs (deubiquitinase-targeting chimeras), and degrader-antibody conjugates (DACs) are advancing rapidly.
Parallel to the scientific maturation, patent filings, including those covering E3 ligase binders, bifunctional scaffolds, linkers, and mechanisms of degradation, have expanded significantly, creating a layered and increasingly competitive patent environment.
We previously examined targeted protein degradation (TPD) as an emerging frontier in precision medicine. Since then, the field has materially accelerated as large-pharma collaborations have expanded in scale, late-stage assets shift commercialization strategies, and M&A activity reflects that protein degraders are now core pipeline priorities.
Here we provide updates on patent activity, recent transactions, clinical developments across PROTACs and molecular glues, and evolving partnership and IP considerations shaping the TPD landscape in early 2026.
The IP landscape surrounding targeted protein degradation has evolved as rapidly as the science. Early patent activity in the field focused on foundational platform IP, including bifunctional molecule scaffolds, E3 ligase recruiting ligands (e.g., cereblon, VHL, IAP), linker chemistry, and general methods of inducing ubiquitination and proteasomal degradation. Those early filings now form the backbone of a dense and increasingly overlapping patent landscape.
As clinical assets advance, the focus for IP filers has shifted toward layered protection strategies including:
- Composition-of-matter claims directed to specific degrader molecules and defined linkers.
- Genus claims covering structurally-related degraders targeting the same protein.
- Target-specific degradation methods tied to defined E3 ligases.
- Formulation, dosing, and combination therapy claims designed to extend lifecycle protection.
- Platform claims directed to screening technologies, proteomics approaches, and induced-proximity mechanisms.
Patent filings in the TPD space have grown steadily over the past decade, with published U.S. and PCT applications increasing materially year-over-year between 2020 and 2025, with no signs of slowing in early 2026.[1] In fact, there are already more application publications in the first quarter of 2026 than the total number of publications in 2020.[2] Landscape analyses have identified hundreds of patent families directed to PROTACs and bifunctional degraders alone, underscoring the breadth of active assignees and the competitive intensity of this area.
As a snapshot, the assignees with the most published patent families in the TPD space since 2024 are shown below:[3]
For molecular glues, the IP analysis presents distinct challenges. Many next-generation cereblon modulators must be differentiated from legacy immunomodulatory imide drug (IMiD) estates, which can require careful claim drafting. Functional claiming tied to induced proximity also raises enablement and written description considerations, as courts increasingly scrutinize broad genus claims, even in the small-molecule context.
The result is a patent environment that is no longer driven mainly by invention, but also by freedom-to-operate concerns. To succeed, companies must evaluate:
- The breadth and enforceability of early foundational patent families;
- Competing linker and scaffold coverage;
- Target-specific degradation claims filed by early movers;
- Potential post-grant challenges to broad foundational filings, particularly broad functionally-claimed molecules; and
- Jurisdiction-specific differences in claim interpretation and exclusivities.
Accordingly, IP strategy in TPD has shifted from offensive filing to proactive portfolio management, e.g., by integrating offensive and defensive prosecution strategies, transaction structuring including licensing and acquisitions, proactive patent challenges, and litigation readiness into core development planning.
In the last year, new PROTACs and molecular glues have entered development and there have been several updates to those already in development.
PROTACs
As for new PROTACs in development, Amgen acquired Dark Blue Therapeutics Ltd., adding the MLLT1/3 degrader to Amgen’s portfolio. According to Jay Bradner, M.D., executive vice president of Research and Development at Amgen, “[t]his acquisition complements and extends our research in targeted protein degradation and leukemia therapeutics, advancing our strategy to invest early in rising medicines for novel therapeutic targets. The adjacency of this program to our considered expertise in cancer biology will propel MLLT1/3-targeting medicines to clinical investigation for patients facing the challenging diagnosis of AML.”[4]
Beyond pipeline expansion, acquisitions of first-in-class degraders may secure control over composition-of-matter claims and target-specific degradation patent estates, which can define exclusivity boundaries for follow-on entrants targeting the same protein.
While many of the clinical trials are still active and ongoing, others are now complete. An updated version of PROTACs in development are listed below:
Molecular Glues
The majority of clinical trials for molecular glues remain active. In addition, SEED Therapeutics has entered clinical trials with its molecular glue and announced, “the dosing of the first patient in its Phase 1a dose-escalation study of ST-01156, an oral RMB39 degrader, in patients with advanced solid tumors.”[21]
As next-generation molecular glues advance, patent strategy increasingly turns on differentiation from legacy patent estates, such as those directed to cereblon-modulation. Structural changes, altered substrate specificity, or new mechanistic distinctions are central both to patentability and freedom-to-operate analyses.
An updated table of examples of molecular glues that are FDA-approved or in development is shown below:
Biotechnology and pharmaceutical companies continue to actively pursue TPD therapies. Companies with notable programs in the TPD field are provided in the updated table below.
As we outlined in our prior post on TPD, because TPD is an innovative therapeutic approach, numerous strategic partnerships and licensing agreements are aimed at advancing TPD technologies. Below we discuss (a) updates to existing deals and collaborations, (b) new licensing deals and collaborations, (c) upcoming milestones in existing collaborations, and (d) licensing deals and collaborations with no significant updates. Many of these agreements reflect not just scientific collaboration, but access to platform intellectual property, field-of-use exclusivity, and risk allocation tied to patent term and portfolio strength.
Updates to Existing Deals and Collaborations
In September 2025, Arvinas and Pfizer provided an update on their collaboration for the development of vepdegestrant, an oral PROTAC estrogen receptor protein degrader. Specifically, the collaborators agreed to out-license the vepdegestrant commercialization rights to a third party. Arvinas and Pfizer seek a party “with the capabilities and expertise to maximize the commercial potential of vepdegestrant, if approved, for patients with ESR1-mutant, ER+/HER2-advanced or metastatic breast cancer and potentially develop vepdegestrant in new settings.”[53]
Also in September 2025, Monte Rosa and Novartis announced their collaboration on a second deal for accelerating the development of molecular glue degrader for immune-mediated diseases.[54]
New Licensing Deals
A few new deals have recently been announced. In June 2025, Gilead Sciences and Kymera Therapeutics entered into an exclusive option and license agreement for the development and acceleration of a novel molecular glue degrader targeting cyclin-dependent kinase 2 (CDK2) with the potential for broad oncology treatment including in breast cancer and other solid tumors.[59]
Although not a formal licensing deal, the UK’s Institute of Cancer Research (ICR) Centre for Protein Degradation and NEOsphere Biotechnologies announced a research collaboration on October 2, 2025, aimed at accelerating molecular glue degrader discovery.[60]
Upcoming Milestones in Existing Licensing Deals
The C4 Therapeutics and Betta Pharmaceuticals deal has not yet had significant updates, but CFT8919, the EGFR degrader for non-small-cell lung cancer, is set to use data from the Phase 1 trial to inform potential ex-China clinical development by the end of Q1 2026.[63]
No Significant Updates to Licensing Deals and Collaborations
Deals involving (a) Nurix Therapeutics and Sanofi, (b) Arvinas and Novartis, (c) Kymera and Vertex, (d) Vividion and Roche, (e) C4 Therapeutics and Merck, (f) Gilead and Nurix, and (g) Seagen (now Pfizer) and Nurix have not announced significant updates, but there is no indication that the deals have ceased.
As first-generation degraders approach late-stage development, companies are increasingly focused on exclusivity duration. Follow-on degraders with modified ligase recruiters, optimized linkers, alternative binding epitopes, improved oral bioavailability, or enhanced CNS penetration may support new composition-of-matter protection and extend effective exclusivity horizons. Simultaneously, combination approaches, including degrader-antibody conjugates and multi-modal constructs, likewise create opportunities for secondary filings that augment core platform patents and extend exclusivity.
Targeted protein degradation (TPD) continues to redefine the boundaries of drug discovery, offering transformative solutions for previously intractable diseases. With PROTACs, molecular glues, and emerging modalities like DUBTACs and LYTACs driving clinical successes, the TPD market is on track to explode higher. Yet, this promise comes with challenges: navigating a dense patent landscape, securing freedom to operate, and overcoming scientific and regulatory hurdles require strategic precision. As the TPD field accelerates, partnering with the patent counsel with subject matter expertise is critical to staying ahead.
[1] Search of Derwent database March 2026 (INPADOC family count and publication year results generated using the keyword query: (CTB=((protein ADJ degrad*) OR (PROTAC OR proteolysis ADJ target* ADJ chimera) OR “molecular glue” OR (LYTAC OR lysosome ADJ target* ADJ chimera) OR (AUTAC OR autophagy ADJ target* ADJ chimera) OR (ATTEC OR autophagy ADJ teth* ADJ compound))) AND (AD>=(20200101)) AND (CC=(US OR WO)).
[2] Id.
[3] Search of Derwent database March 2026 (INPADOC family count and publication year results generated using the keyword query: (CTB=((protein ADJ degrad*) OR (PROTAC OR proteolysis ADJ target* ADJ chimera) OR “molecular glue” OR (LYTAC OR lysosome ADJ target* ADJ chimera) OR (AUTAC OR autophagy ADJ target* ADJ chimera) OR (ATTEC OR autophagy ADJ teth* ADJ compound))) AND (AD>=(20240101)) AND (CC=(US OR WO)); sorted by Optimized Assignee.
[4] Id.
[5] Tan, Xueqiang, et al. “Molecular glue-mediated targeted protein degradation: A novel strategy in small-molecule drug development.” Iscience (2024).
[6] https://clinicaltrials.gov/study/NCT05654623?cond=NCT05654623&rank=1
[7] Tan et al.
[8] https://clinicaltrials.gov/study/NCT03888612
[9] Tan et al.
[10] https://clinicaltrials.gov/study/NCT05067140
[11] Danilov, Alexey, et al. “A first-in-Human phase 1 trial of NX-2127, a first-in-class Bruton’s Tyrosine Kinase (BTK) dual-targeted protein degrader with immunomodulatory activity, in patients with relapsed/refractory B cell malignancies.” Blood 142 (2023): 4463.
[12] https://clinicaltrials.gov/study/NCT04830137
[13] Tan et al.
[14] https://clinicaltrials.gov/study/NCT05225584
[15] Tan et al.
[16] https://clinicaltrials.gov/study/NCT04861779
[17] https://www.darkbluetx.com/our-science#pipeline
[18] https://clinicaltrials.gov/study/NCT06764485
[19] https://clinicaltrials.gov/study/NCT05006716
[20] https://clinicaltrials.gov/study/NCT06964009
[21] https://www.seedtherapeutics.com/media/seed-therapeutics-doses-first-patient-in-phase-1-trial-of-st-01156-a-molecular-glue-degrader-targeting-rbm39-2
[22] Hansen, Joshua D., et al. “CC-90009: a cereblon E3 ligase modulating drug that promotes selective degradation of GSPT1 for the treatment of acute myeloid leukemia.” Journal of medicinal chemistry 64.4 (2021): 1835-1843.
[23] Liu, Lei, et al. “Targeted BRD4 protein degradation by dBET1 ameliorates acute ischemic brain injury and improves functional outcomes associated with reduced neuroinflammation and oxidative stress and preservation of blood–brain barrier integrity.” Journal of neuroinflammation 19.1 (2022): 168.
[24] Yamanaka, Satoshi, et al. “Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation.” Nature communications 14.1 (2023): 4683.
[25] Oleinikovas, Vladas, et al. “From thalidomide to rational molecular glue design for targeted protein degradation.” Annual review of pharmacology and toxicology 64.1 (2024): 291-312.
[26] Sasso, Janet M., et al. “Molecular glues: the adhesive connecting targeted protein degradation to the clinic.” Biochemistry 62.3 (2022): 601-623.
[27] Id.
[28] Id.
[29] https://clinicaltrials.gov/study/NCT04975997
[30] Sasso et al.
[31] https://clinicaltrials.gov/study/NCT03930953
[32] Hansen, Joshua D., et al. “Discovery of CRBN E3 ligase modulator CC-92480 for the treatment of relapsed and refractory multiple myeloma.” Journal of medicinal chemistry 63.13 (2020): 6648-6676.
[33] https://www.bmsclinicaltrials.com/us/en/clinical-trials/NCT03989414
[34] Hansen et al.
[35] https://clinicaltrials.gov/study/NCT03891953
[36] https://ir.arvinas.com/news-releases/news-release-details/arvinas-enters-transaction-novartis-including-global-license
[37] https://www.pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizer-announce-global-collaboration-develop
[38] https://foghorntx.com/wp-content/uploads/2023/04/Netherton_DDC_2023_presentation.pdf
[39] https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-announces-global-license-agreement; https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-announces-collaboration-novartis
[40] https://ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-outlines-2025-goals-and-objectives
[41] https://ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-announces-extension-strategic-collaboration-0
[42] https://ir.nurixtx.com/news-releases/news-release-details/nurix-announces-strategic-collaboration-seagen-combining
[43] https://investors.kymeratx.com/news-releases/news-release-details/kymera-announces-expansion-kt-474-sar444656-hs-and-ad-phase-2
[44] https://investors.vrtx.com/news-releases/news-release-details/vertex-and-kymera-therapeutics-establish-strategic-collaboration
[45] https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-announces-delivery-second-development-candidate
[46] https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-announces-strategic-discovery-research
[47] https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-and-betta-pharmaceuticals-announce-exclusive
[48] https://news.bms.com/news/details/2019/Bristol-Myers-Squibb-to-Acquire-Celgene-to-Create-a-Premier-Innovative-Biopharma-Company/default.aspx
[49] https://www.biospace.com/novartis-strikes-1-3-billion-deal-with-protein-degradation-startup-dunad-therapeutics
[50] https://www.seedtherapeutics.com/media/seed-therapeutics-completes-30-million-series-a-3-financing; https://beyondspringpharma.com/beyondspring-subsidiary-seed-therapeutics-announces-research-collaboration-and-license-agreement-with-lilly/
[51] https://www.fiercebiotech.com/biotech/jj-gv-line-back-protein-degradation-biotech-epibiologics-107m-series-b
[52] https://www.amgen.com/newsroom/press-releases/2026/01/amgen-acquires-dark-blue-therapeutics-bolstering-oncology-pipeline.
[53] https://ir.arvinas.com/news-releases/news-release-details/arvinas-provides-update-collaboration-pfizer-and-announces
[54] https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-announces-collaboration-novartis
[55] https://www.pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizer-announce-global-collaboration-develop
[56] https://ir.arvinas.com/news-releases/news-release-details/arvinas-provides-update-collaboration-pfizer-and-announces
[57] https://ir.arvinas.com/news-releases/news-release-details/arvinas-announces-fda-acceptance-new-drug-application
[58] https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-announces-closing-global-license
[59] https://investors.kymeratx.com/news-releases/news-release-details/gilead-sciences-and-kymera-therapeutics-enter-exclusive-option
[60] https://www.icr.ac.uk/about-us/icr-news/detail/icr-centre-for-protein-degradation-and-neosphere-biotechnologies-announce-research-collaboration–to-discover-new-molecular-glue-degrader-therapeutics
[61] https://investors.kymeratx.com/news-releases/news-release-details/gilead-sciences-and-kymera-therapeutics-enter-exclusive-option
[62] https://www.icr.ac.uk/about-us/icr-news/detail/icr-centre-for-protein-degradation-and-neosphere-biotechnologies-announce-research-collaboration–to-discover-new-molecular-glue-degrader-therapeutics
[63] https://www.biospace.com/press-releases/c4-therapeutics-reports-fourth-quarter-and-full-year-2025-financial-results-and-recent-business-highlights
[64] https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-and-betta-pharmaceuticals-announce-exclusive
[65] https://ir.nurixtx.com/news-releases/news-release-details/nurix-licenses-drug-discovery-program-sanofi-targeting-novel
[66] https://ir.arvinas.com/news-releases/news-release-details/arvinas-enters-transaction-novartis-including-global-license
[67] https://investors.vrtx.com/news-releases/news-release-details/vertex-and-kymera-therapeutics-establish-strategic-collaboration
[68] https://vividion.com/news/vividion-therapeutics-announces-drug-discovery-collaboration-with-roche-focused-on-novel-e3-ligases/
[69] https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-announces-strategic-discovery-research
[70] https://ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-announces-extension-strategic-collaboration
[71] https://ir.nurixtx.com/news-releases/news-release-details/nurix-announces-strategic-collaboration-seagen-combining