Advancements in Bispecific Antibody Development

A comprehensive review: Bispecific antibodies: advancing precision oncology Bispecific antibodies (bsAbs) offer a novel approach to anticancer therapy by targeting different antigens via a range of mechanisms of action. Manipulating bsAb structures allows generation of multiple formats to optimize molecular function for specific clinical contexts. Thus far, a total of seven bsAbs have received regulatory approval for use in hematological malignancies and four in select solid tumors, with notable clinical efficacy. The toxicities associated with the use of bsAbs need bespoke management strategies and expertise in clinical use. Understanding mechanisms of resistance to bsAbs is crucial to rational combination regimens or sequencing with other therapeutics to improve patient outcomes. Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is determined by the bsAb molecular targets and structure (or format), which can be manipulated to create variable and novel functionalities, including linking immune cells with tumor cells, or dual signaling pathway blockade. Several bsAbs have already changed the treatment landscape of hematological malignancies and select solid cancers. However, the mechanisms of resistance to these agents are understudied and the management of toxicities remains challenging. Herein, we review the principles in bsAb engineering, current understanding of mechanisms of action and resistance, data for clinical application, and provide a perspective on ongoing challenges and future developments in this field. https://lnkd.in/edZExrpd

What’s going on with Bispecific Antibodies? And not just one program - but across the board. Over just the last 4–6 weeks, this field has gone from “interesting” to industry-shaping: 🧬 Bristol Myers Squibb + BioNTech: $11.1B alliance ($1.5B upfront) to co-develop BNT327 (PD-L1 × VEGF), already in 20 trials, including two at Phase 3 🧬 Pfizer + 3SBio Inc.: $1.25B upfront for ex-China rights to SSGJ-707 (PD-1 × VEGF), launching Phase 3 later this year 🧬 Johnson & Johnson: Trispecific JNJ-5322 (BCMA × GPRC5D × CD3) hit 86% ORR in heavily pre-treated myeloma; 100% in antigen-naïve patients 🧬 Amgen’s tarlatamab cut SCLC mortality by 40% vs chemotherapy in a recent Phase 3 readout 🧬 Innovent Biologics’s IBI363 (PD-1 × IL-2 bias) showed durable responses in IO-resistant NSCLC and “cold” melanoma 🧬 IGM Biosciences, Inc., Xilio Therapeutics, Inc., and Bright Peak Therapeutics are pushing novel formats - from IgM-scaffold BsAbs to tumor-activated immune engagers and cytokine fusions 🧬 CDMOs like AGC Biologics, Celonic Group, KBI Biopharma, Northway Biotech, ExcellGene SA, evitria AG, and mAbxience are scaling capabilities across North America and Europe to support complex BsAb and bsADC pipelines 🧬 Regeneron ↔ FUJIFILM diosynth biotechnologies Diosynth: $3B+ manufacturing deal to expand BsAb capacity in the U.S. 🧬 Roche is building a $283M Shanghai facility focused on bispecifics like Vabysmo There's an awful lot of progress going on... So, what’s behind it? ✅ Dual & tri-specific formats are breaking resistance - solid tumors are finally in play ✅ Platform manufacturing has caught up: automated, modular suites now exist ✅ Commercial validation from Epkinly and Vabysmo proves the model works ✅ And Big Pharma just placed serious bets - not exploratory ones Signals to watch: ➡️ PD-(L)1 × VEGF bispecifics heading into late-stage trials ➡️ CDMOs pouring capital into flexible BsAb production ➡️ Modality expanding beyond oncology - including autoimmunity and inflammation Anyone building in biotech should be watching this space closely - not just for the deals, but for what it signals: ✅ BsAbs are moving beyond hematologic cancers ✅ They’re fast becoming a preferred modality for next-gen immune-oncology ✅ And the next 12–24 months could be transformative for both platform innovation and manufacturing models BsAbs were already clinically validated - but until recently, they were mostly confined to blood cancers and a few commercial formats. Now, we’re seeing something different: ➡️ Expansion into solid tumors ➡️ Rise of trispecifics and novel combinations ➡️ Big Pharma doubling down across platforms, trials, and capacity This is not just "some pipeline noise" - to me, this looks like a structural shift in how immunotherapy is being designed. Have I missed any emerging BsAb players or late-breaking updates worth tracking? 👇 #biotech #oncology #bispecificantibodies #immunotherapy #drugdevelopment

Numab Therapeutics AG just cracked one of the hardest problems in multispecific antibodies: immunogenicity at scale. As bispecifics and trispecifics move from novelty to standard of care, one issue compounds fast: every added scFv increases the risk of anti-drug antibodies (ADAs). 🔹The insight: Many approved and clinical antibodies contain T-cell epitopes in light-chain CDR2 (CDR2L) — a region historically overlooked in immunogenicity design. The mistake everyone makes: Replacing the entire CDR2L with germline sequences. ✔ immunogenicity drops ✖ binding and stability collapse 🔹Numab’s breakthrough: Instead of redesigning everything, they identified two non-essential positions in CDR2L (AHo67–AHo68) and replaced them with glycine–glycine (67G-68G). 🔹Why this matters Preserves binding, stability, and expression ▪ Eliminates treatment-emergent ADA signals in patient sera ▪ Works across >80% of approved / clinical antibody sequences (in silico) Scales cleanly to trispecific antibodies 🔹Most important signal: This is not a one-off fix. It’s a plug-and-play de-immunization rule for complex antibody architectures. As multispecifics become more modular, generalizable immunogenicity solutions will matter more than clever individual designs. 🔹The real question: Will CDR-level “universal fixes” like 67G-68G become standard in antibody engineering — the way humanization once did? Reference: "Structure-guided design of antibody CDRs to reduce their reactivity to treatment-emergent anti-drug antibodies." mAbs. Vol. 18. No. 1. Taylor & Francis, 2026. (Open source publication) #biotech #antibodies #immunogenicity #drugdevelopment #proteinengineering #multispecific #Numab

Bispecific Antibodies Enter a New Era With growing traction in both immune-mediated diseases and solid tumors, bispecifics are fast becoming a cornerstone of modern therapeutic strategy. While combinations like PD-(L)1 × VEGF are gaining attention, they're just one piece of the puzzle. We're also seeing momentum across formats targeting co-stimulatory receptors (e.g., CD28, 4-1BB), cytokine modulators, and tumor antigens combined with immune checkpoints. The versatility of bispecifics is enabling more refined control of immune activation, better tumor selectivity, and novel approaches to treating hard-to-target diseases. And the momentum isn’t slowing down 👇 🔹 Harbour BioMed signs global strategic deal with Otsuka Pharmaceutical Companies (U.S.) to advance a BCMA×CD3 T cell engager for autoimmune disease 🔹 Cullinan Therapeutics licenses a clinical-stage BCMA bispecific from Genrix Bio for autoimmune programs 🔹 BioNTech & BMS enter a co-development and commercialization deal on BNT327 for solid tumors 🔹 Boehringer Ingelheim x Cue Biopharma partner on next-gen bispecifics for autoimmune and inflammatory diseases. With over 3,500 #multispecifics now in development, the space is evolving fast, driven by growing clinical confidence, engineering ingenuity, and a renewed push to solve the next generation of challenges. This wave of activity highlights just how far bispecifics have come since their early days in the 1960s. From unstable, hard-to-manufacture prototypes to modular, multifunctional formats tackling immune evasion, #toxicity, tumor penetration, and more. That said, key hurdles remain. #Immunotoxicity, particularly in T-cell #engagers, still limits therapeutic windows. Tumor specificity and trafficking remain challenging in solid cancers. And with the explosion of formats, developers now face growing complexity in manufacturing, regulatory pathways, and differentiating clinical value in an increasingly crowded field. More information on the evolution of the T-Cell Engager space: https://lnkd.in/ecz9fPG7 👉 Curious about how the T-cell engager space has evolved? 🔗 More on the evolution of T-cell engagers #Immunotherapy #AntibodyTherapeutics #BispecificAntibodies #TCellEngagers #CancerImmunotherapy

🧬✨ 𝗛𝗼𝘄 𝗯𝗶𝘀𝗽𝗲𝗰𝗶𝗳𝗶𝗰 𝗮𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗮𝗿𝗰𝗵𝗶𝘁𝗲𝗰𝘁𝘂𝗿𝗲 𝘀𝗵𝗮𝗽𝗲𝘀 𝗺𝗮𝗻𝘂𝗳𝗮𝗰𝘁𝘂𝗿𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗮𝗻𝗱 𝗯𝗶𝗻𝗱𝗶𝗻𝗴 ✨🧬 Bispecific antibodies (BsAbs) unlock therapeutic mechanisms unreachable with conventional mAbs, but their architecture deeply influences both production and function. Selecting a format is rarely just a binding question — it is also a CMC question. In a recent publication by Rivera-Castro et al. in 𝘑𝘰𝘶𝘳𝘯𝘢𝘭 𝘰𝘧 𝘉𝘪𝘰𝘵𝘦𝘤𝘩𝘯𝘰𝘭𝘰𝘨𝘺, five BsAb formats targeting a viral epitope (Zika/dengue EDE) and the transferrin receptor (TfR, for BBB shuttling) were compared head-to-head, using stable CHO cell pools and identical binding sequences. 🔬 𝗙𝗼𝗿𝗺𝗮𝘁𝘀 𝗲𝘃𝗮𝗹𝘂𝗮𝘁𝗲𝗱: • Asymmetric knobs-into-holes with C-terminal scFv • DVD-Ig (dual-variable domain) • LC-scFv (scFv fused to light chain C-terminus) • HC-scFv and attenuated AHC-scFv (scFv fused to heavy chain C-terminus) ⚙️ 𝗠𝗮𝗻𝘂𝗳𝗮𝗰𝘁𝘂𝗿𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗳𝗶𝗻𝗱𝗶𝗻𝗴𝘀: • Light-chain modification and asymmetric assembly reduced viability, growth, and productivity by up to 70% vs. the parental IgG • Asymmetric format suffered from imbalanced chain expression, knob-HC proteolysis, and half-antibody/homodimer byproducts — purity dropped to ~68% after Protein A • Symmetric HC-scFv and AHC-scFv preserved growth kinetics, productivity, and purity (>95%), behaving like the parental mAb 🧪 𝗕𝗶𝗻𝗱𝗶𝗻𝗴 𝗼𝘂𝘁𝗰𝗼𝗺𝗲𝘀 (𝗘𝗟𝗜𝗦𝗔): • Fab-region modifications altered apparent affinity to Zika virus • DVD showed the highest anti-ZIKV binding (flexible linker effect) • Bivalent HC-scFv gave the strongest apparent TfR binding; monovalent formats (LC-scFv, asymmetric) were weaker 🎯 𝗞𝗲𝘆 𝘁𝗮𝗸𝗲-𝗮𝘄𝗮𝘆𝘀: • BsAb architecture directly governs manufacturability, product quality, and apparent binding • Avoid LC modification and asymmetric assembly when scalable production is a priority • C-terminal HC-scFv fusions are the most robust compromise between developability and dual binding • Protein A purification remains effective for symmetric formats; asymmetric designs need additional polishing 💡 𝗪𝗵𝗮𝘁 𝗱𝗼𝗲𝘀 𝗶𝘁 𝗯𝗿𝗶𝗻𝗴 𝘁𝗼 𝘁𝗵𝗲 𝗳𝗶𝗲𝗹𝗱? By comparing five formats with identical binding domains in stable CHO pools, this study isolates architecture as the variable — providing a rare, controlled benchmark to guide early format selection in BsAb development. #Bispecifics #Biomanufacturing #AntibodyEngineering Juan Carlos Rivera Castro, Octavio Ramírez & Laura A. Palomares / Instituto de Biotecnología UNAM

𝗜𝗳 𝘆𝗼𝘂 𝘄𝗮𝗻𝘁 𝘁𝗼 𝗕𝗶𝘀𝗽𝗲𝗰𝗶𝗳𝗶𝗰: The Curious Challenge of Antibody Engineering Antibodies stick to things. They have two identical binding regions — one on each fork of the Y-shaped molecule — that latch onto the same target. For decades, bioengineers wondered: what if you repurposed this structure to bind two different things? Could you bring distinct targets into close proximity and trigger a therapeutic effect? Over time, the idea of bispecific antibodies — designed to engage two targets at once — moved from curiosity to clinical reality. But the road was anything but smooth. 𝗧𝗵𝗲 𝗳𝗶𝗿𝘀𝘁 𝗯𝗶𝘀𝗽𝗲𝗰𝗶𝗳𝗶𝗰 𝗮𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗮𝗽𝗽𝗿𝗼𝘃𝗲𝗱 𝗶𝗻 𝘁𝗵𝗲 𝗰𝗹𝗶𝗻𝗶𝗰, 𝗖𝗮𝘁𝘂𝗺𝗮𝘅𝗼𝗺𝗮𝗯 (2009, Europe), was designed to do something bold: One arm would bind EpCAM on tumor cells The other, CD3 on T cells Its purpose? Bring immune killers into direct contact with cancer. But Catumaxomab had a major design complexity: It required four unique protein chains — two heavy chains, two light chains — each needing to pair with the correct partner. Inside the producer cell, all four chains were expressed at once. With no built-in control, they assembled randomly — creating a zoo of mismatched, nonfunctional, or even toxic variants. This issue, known as chain mispairing, had been theorized for years. 𝗖𝗮𝘁𝘂𝗺𝗮𝘅𝗼𝗺𝗮𝗯 𝗺𝗮𝗱𝗲 𝘁𝗵𝗲 𝗰𝗵𝗮𝗹𝗹𝗲𝗻𝗴𝗲 𝗶𝗺𝗺𝗲𝗱𝗶𝗮𝘁𝗲 𝗮𝗻𝗱 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 — 𝗮𝗻𝗱 𝘀𝗽𝗮𝗿𝗸𝗲𝗱 𝘁𝗵𝗲 𝗽𝘂𝘀𝗵 𝘁𝗼 𝗶𝗻𝘃𝗲𝘀𝘁 𝗶𝗻 𝗲𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗶𝗻𝗴 𝘀𝗼𝗹𝘂𝘁𝗶𝗼𝗻𝘀. 1️⃣ Knobs-into-Holes (Genentech, late 1990s) 🔬 A “knob” is added to one heavy chain, and a “hole” to the other ➡️ This structural pairing forces correct assembly, blocking mismatches ✅ Used in: Emicizumab (approved 2017) → The first bispecific to replace standard clotting factors — a breakthrough in hemophilia A 2️⃣ CrossMab (Roche, ~2010) 🔬 Domains are swapped between light and heavy chains on one side ➡️ Asymmetry ensures each chain pairs only with its match ✅ Used in: Faricimab (approved 2022) → The first dual-acting antibody for eye disease — targeting both VEGF and Ang-2 in one shot 3️⃣ DuoBody® Platform (Genmab, ~2013) 🔬 Two full antibodies are produced separately, then reassembled in vitro via redox chemistry ➡️ Cleanly avoids mispairing by building the bispecific outside the cell ✅ Used in: Teclistamab and Epcoritamab (2022–2023) → Brought off-the-shelf T-cell engagers to market — unlocking new options in multiple myeloma 𝗖𝗮𝘁𝘂𝗺𝗮𝘅𝗼𝗺𝗮𝗯 𝗱𝗶𝗱𝗻’𝘁 𝗿𝗲𝘃𝗲𝗮𝗹 𝗻𝗲𝘄 𝗽𝗿𝗼𝗯𝗹𝗲𝗺𝘀 — 𝗶𝘁 𝗰𝗼𝗻𝗳𝗶𝗿𝗺𝗲𝗱 𝘁𝗵𝗲𝗺. It showed that bispecifics could work — but only if we rewrote the rules of antibody assembly. And once that happened, the floodgates opened. Today, we have 19 approved bispecifics globally and over 150 in clinical trials. As biology shifts from a science problem to an engineering challenge — bispecifics may just be its most elegant blueprint.

In a paper newly published in mAbs, Merck- and University of Natural Resources and Life Sciences, Vienna (BOKU)-based authors reveal details of a novel biochemically stable multispecific IgA-based format derived from strand-exchanged engineered domain (SEED) technology. From the abstract: Immunoglobulin (Ig) A has attracted interest as a proposed therapeutic agent due to its ability to engage cell groups differently compared to an IgG scaffold and elicit tumor eradication. Further, its multimeric forms enable increased flexibility in the design of available paratopes. The latter is particularly advantageous for bi- and multispecific antibody formats, which are unparalleled in their enhanced selectivity and unique biological functions. We engineered bispecific heterodimeric IgA-based antibodies using the strand-exchanged engineered domain (SEED) technology, which relies on intertwined segments of IgA and IgG in the CH3 domain, and applied mutagenesis to introduce two additional binding sites to enable the interaction of IgA-Fc with the myeloid cell-activating receptor CD89 (FcαR). These antibodies exhibited good biophysical properties and thermostability similar to the parental SEED molecule. Binding capacity to both antigens recognized by variable domains, epidermal growth factor receptor (EGFR) and receptor tyrosine kinase like orphan receptor 1 (ROR1), was not impaired, and in contrast to the original SEED-IgA, trispecific mutants could bind to CD89-expressing cells, mediate tumor cell-effector cell clustering, and induce neutrophil-mediated specific lysis of tumor cells. Trispecific design was applicable to both SEED-IgA1 and -IgA2 scaffolds. Interestingly, HEK-expressed mutants featured a CH2-linked N-glycan pattern more similar to wild-type IgA, with reduced core fucosylation in comparison with IgA-SEED. Collectively, the presented format combines the mobilization of CD89-positive effector cells with the flexibility of incorporating antigen specificities of choice into the variable domains, and thus is a promising basis for biochemically stable multispecific IgA with high therapeutic potential. https://lnkd.in/eJWJ5dRq

🚀 How can we design smarter, more versatile #biparatopic #antibodies? A recent post by Vishal Kamat (link in the comments) revisits the fundamentals of biparatopic antibody design — highlighting their role in target #clustering, #internalization, and degradation. But in today’s world of #multispecifics, we should ask: 👉 Can biparatopic antibodies be designed to do more — like trigger #allostery? 👉 And can we intentionally decouple one mechanism of action (#MOA) from another? A fascinating study from #Merck Germany, led by Stefan Zielonka, explored exactly this. By combining #AlphaFold3 with a simplified, structure-informed allostery-predicting model, they identified novel VHH combinations that induced allosteric signaling changes in EGFR — a conformationally regulated receptor. 🔍 What stood out in their approach: ✅ Using AF3 cautiously — defining complex ranking thresholds, and not over-interpreting atomistic details (especially flexible CDR loops). ✅ Repurposing a coarse-grained, physics-informed model (originally developed for small-molecule allosteric prediction)— to predict energetic consequences of single and dual epitope engagement. ✅ Tackling paratope uncertainty — by averaging energy predictions across multiple conformers per VHH. 💡 The outcome? They identified #epitope combinations that strongly inhibited signaling without promoting internalization — highlighting that internalization and signaling inhibition can be decoupled depending the type of epitope being engaged. In summary: ➡️ Combining two #antibodies doesn’t guarantee additive internalization. ➡️ Instead, their combination can trigger entirely different MOAs — like allostery. 🔬 Why is this important? This study shows how combining #AI-based structural models with mechanistic energy calculations, early in #antibody #discovery can unlock new #MOAs and optimize epitope targeting in ways we didn’t anticipate. ❓ Where could this approach shine next? I see potential in targeting complex systems like #GPCRs, #ion channels, or dysregulated #enzymes. However, one thing to note that the success of the work, hugely dependent on the vast availability of structural information on EGFR:EGF interaction as well as epitope information from well-validated clinical antibodies. But as models are being improved and refined, like #Chai-2, there is a future where such methods can be implemented without the need of extensive structural data. Link to the paper: https://lnkd.in/eVd_Q4r6 #AntibodyDiscovery #Allostery #Multispecifics #ProteinEngineering #AIInBiotech

🚀 NK Cell Engagers: The Next Disruptive Wave in Cancer Immunotherapy ?? 🚀 Move over T-cell engagers. The innate immune system is having its moment, and Natural Killer Cell Engagers (NKCEs) are poised to redefine the landscape of solid tumor treatment. For investors and biz dev leaders in biopharma, here’s why this space is heating up. The Bottom Line Up Front: NKCEs offer a potentially superior safety and efficacy profile compared to T-cell redirecting therapies, especially for solid tumors. Recent technological breakthroughs have overcome key historical limitations, creating fertile ground for value creation and M&A. Here are the critical insights driving our bullish outlook: 1. It’s All About Multi-Specificity. The first-gen bispecifics are giving way to trispecific formats. Why? Because co-engaging receptors like CD16 + NKG2D or NKp46 isn't just additive, it creates synergistic nanoscale clustering that supercharges the immune synapse. This means more potent signaling and tumor cell killing, a fundamental step-change in potency. 2. The "CD16 Problem" is Solved. A major hurdle for CD16-targeted therapies was neutralization by circulating IgG. Breakthrough antibody engineering has yielded novel, high-affinity clones that are selective for CD16a, avoiding off-target binding and working effectively in human serum. This dramatically widens the therapeutic window. 3. Beyond Engagement: "Smart" Platforms Are Emerging. The most sophisticated platforms now integrate activation with other functions. Think nanoengineered NKCEs that co-activate CD16 and 4-1BB (for persistence) AND deliver chemo payloads directly to tumors. This isn't just an engager; it's a targeted combination therapy in a single molecule. 4. The Solid Tumor Opportunity is Real. While hematological malignancies are the low-hanging fruit, the primary multi-billion-dollar addressable market is in solid tumors. Next-gen NKCEs are specifically designed to overcome the immunosuppressive tumor microenvironment, making this goal increasingly attainable. Implications: Near-term: Watch for clinical proof-of-concept data in solid tumors from companies like StarMab, Inc. , BeOne Medicines or GT Biopharma, Inc. Positive readouts will be major catalysts. Platforms are Key: Value resides in companies with robust, modular platforms for multi-specific engagers, not just single assets. The NKCE space is transitioning from promising biology to clinical assets with blockbuster potential. The companies that solve the complexity of multi-specific engineering and demonstrate clinical efficacy will define the next chapter of immuno-oncology. What’s your take? Are NKCEs the logical successor to T-cell engagers? #Biotech #ImmunoOncology #NKCell #DrugDiscovery #VC #LifeSciences #Investing #BusinessDevelopment #Pharma #Innovation

What’s the best antibody engineering invention of the last decade? I’m happy to debate this but two years ago I saw a poster on Genmab’s Hexcyte technology. It blew my mind. So here’s how they got there and why it’s so cool. IgG hexamerizes on the cell surface and enables efficient interaction with C1q, itself a hexamer, and initiates the complement pathway and ultimately cell killing. Antibody engineers have sought to enhance this hexamerization to develop more potent therapeutics. The first report (2011) involved fusion of the IgM tailpiece to the IgG Fc domain. This generated IgG hexamers in solution and very potent ADCC and CDC. However, solution hexamers are a manufacturing challenge and possible safety risk due to the high effector function. The better approach would be to mimic nature and only hexamerize when engaged with antigen on the cell surface (on-target hexamerization). IgG hexamerizes through Fc-Fc interactions located at the CH2-CH3 boundary. Researchers sought to enhance this process by introducing mutations that promote self-association. Some mutations resulted in solution hexamers but others remained monomeric in solution and drove enhanced hexamerization on the cell surface. I believe Genmab were first to demonstrate this with their Hexabody technology but others have since followed with alternative mutations. The Genmab team then combined their hexamerization technology with their Duobody technology for bispecifics. The result is a highly potent bispecifc (or biparatopic) that hexamerizes – they call this Duohexabody. One of the challenges of drug development in general is avoiding off target toxicity. It’s rare that antigens are truly specific to a cancer cell, so there is the risk of collateral damage. What if we created logic gated bispecifics? A bispecific that only kills when two specific antigens are present. Each individual antigen alone may be expressed on many healthy cell types but are only found in combination on certain cancers. The Genmab team put their thinking caps on. They came up with a different set of mutations that minimizes homo-hexamers and promotes hetero-hexamerization. They then modulated Fcγ receptor and C1q binding such that the antibodies were effectively silent as monomers but gave potent CDC only as bispecific hexamers on the cell surface. So truly selective cell killing! They call it HexElect. Although first published in 2022 it is the culmination of 20 years work starting with what seemed like an obscure interest in IgG4 that led to the unveiling of Fab-arm exchange, the development of a novel bispecific technology (Duobody) and then onwards to combining that knowledge with hexamerization. See first comment for links to papers. ----- I'm Ian, I post about antibody engineering, recombinant proteins and my journey to bootstrap Gamma Proteins into a leading supplier of Fc receptors. If you like my content please reshare with your network and follow me to see more.