Bifunctional proteins combining checkpoint blockade for targeted therapy

This patent covers a bifunctional fusion protein that combines PD-L1 checkpoint blockade with VEGF inhibition in a single molecule. Reading claim 1 in plain English: it claims a fusion protein built around an antibody (or antigen-binding fragment) whose binding domain targets programmed cell death protein 1 ligand (PD-L1), with that domain defined by specific complementarity-determining regions — a heavy chain variable region (CDR1/2/3 from SEQ ID NO: 4) and a light chain variable region (CDRs from amino acids 1-111 of SEQ ID NO: 3) — fused to a VEGF-inhibiting domain comprising the amino acid sequence of SEQ ID NO: 9. The dependent claims (e.g., claim 2) add architectural detail such as an Fc domain and an Fab fragment connected to the Fc N-terminus. The abstract broadens the disclosure to bispecific proteins and to antibody-drug conjugates that link a therapeutic agent to the PD-L1/VEGF binding entity via a covalent linker. The claim scope is anchored to defined sequences, which makes this a sequence-specific molecule claim rather than a broad mechanism claim — a narrower but more defensible posture.

The assignee is AP Biosciences Inc, with named inventors Her Jeng-Horng, You Jhong-Jhe, Hsu Ching-Hsuan, and Huang Po-Lin. The patent was granted in 2023 (US-11780922-B2). It sits in a family of 24 members spanning 14 countries, which signals aggressive international prosecution — a notably large footprint for a company of AP Biosciences' size and consistent with intent to protect a lead clinical asset across major pharmaceutical markets. Its primary CPC classifications (C07K peptides/proteins, A61P therapeutic activity, A61K pharmaceutical preparations, G01N analysis) are exactly what you would expect for a biologic therapeutic.

Where this patent stands: Its forward-citation count is 0, but that is uninformative here — the patent was granted in 2023 and almost every on-point neighbor is itself from 2023–2025, so there has been no time for citations to accumulate. The zero count reflects recency and publication lag, not lack of significance; treat this as strategic IP that citation-weighted ranking under-rewards. Functionally, this is a focused, sequence-specific anchor filing for a single PD-L1×VEGF bifunctional molecule — almost certainly the IP backbone for an AP Biosciences clinical or pipeline candidate, given the 24-member family. It is not a foundational mechanism patent (the PD-L1/VEGF combination concept predates it, as shown by the Genentech neighbor below); rather it is a defined-molecule claim staking out one specific antibody-plus-VEGF-trap construct within a now-crowded class.

The surrounding space is densely clustered and unusually concentrated around antibody/protein chemistry: Peptides & Proteins (C07K) appears in 49 of the patents at 52× the corpus baseline, with Pharmaceutical Preparations (A61K, 19.5×) and Therapeutic Drug Activity (A61P, 22.4×) close behind — unambiguous evidence this is a tight therapeutic-biologic niche, not a diffuse field. The citation-impact chart is led by older foundational immuno-oncology assignees — Medarex (3221 citations across 2 patents), the University of Texas System, Abbott, Genentech, Regeneron, and Roche entities (Roche Glycart, Hoffmann-La Roche) — reflecting historic checkpoint and antibody-engineering work rather than the specific PD-L1×VEGF bifunctional sub-cluster. In that nearest sub-cluster, a wave of Chinese biopharma players (Huabo, Biotheus, WuXi Biologics, Akeso, Beijing Hanmi, Anhui Biox) dominates the most on-point filings, though none of them appears on the TOP_ASSIGNEES citation list — they are recent enough that their citation counts haven't built up.

Closest related patents:

• US-12269885-B2 — Anti-PD-L1/VEGF bifunctional antibody and use thereof (Huabo Biopharm (Shanghai) · 0 citations · 12-member family). A direct functional analog: same dual PD-L1/VEGF targeting concept, distinguished by its own sequences. A 2025 grant — strategic IP the citation-weighted score under-rewards.
• US-12325759-B2 — Anti-VEGF-anti-PD-L1 bispecific antibody (Biotheus · 0 citations · 12-member family). Another near-identical mechanistic neighbor from 2025, competing in the same molecular class.
• US-9895441-B2 — Methods of treating cancer using PD-L1 axis binding antagonists and VEGF antagonists (Genentech · 2 citations · 42-member family). This is the conceptual predecessor — a 2018 grant claiming the combination of PD-L1 and VEGF blockade as a treatment method, with a large 42-member family signaling broad prosecution. It frames the therapeutic rationale that the subject patent embodies in a single fusion protein.
• US-12195527-B2 — Anti-PD-1/VEGFA bifunctional antibody (Akeso Biopharma · 0 citations · 34-member family). A closely related bifunctional construct (PD-1 rather than PD-L1 arm) with a large 34