The Arrow Samsung Shot at the $46 Billion Cancer Drug Fortress — Striking the Vulnerable Point of Keytruda's Patent

 

💊 Samsung's Precise Move Against the $46 Billion Cancer Drug Keytruda — Why It Opened the Formulation Patent Bypass Right Now

What is the best-selling drug in the world? The answer is Keytruda, the immuno-oncology drug made by the American company Merck (MSD), known by its generic name pembrolizumab. Combining its intravenous and subcutaneous formulations, it recorded 31.7 billion dollars in sales in 2025 alone — roughly 46 trillion Korean won. It is the largest single drug market on the planet. And toward the wall of this massive fortress, Samsung Bioepis recently aimed a quiet but highly calculated arrow.

Today, let us carefully unpack exactly what Samsung Bioepis was targeting with the "negative scope confirmation trial" it filed with the Intellectual Property Trial and Appeal Board, why it made its move now of all times, and what the real strategic meaning behind this decision is.

🧬 Setting the Stage — Biosimilars and the Second Line of Defense Called the "Formulation Patent"

Before diving in, let me naturally walk through a few concepts you need to fully digest this story.

A biosimilar, put simply, is a "generic version of a biologic drug." But its nature differs from an ordinary generic — a chemically synthesized copy. Because a biosimilar is obtained by culturing proteins in living cells, it cannot be reproduced identically to the original. That is why we use the word "similar" rather than "same." As a result, a biosimilar must prove through clinical trials that its efficacy and safety are essentially no different from the original — this is called "equivalence" — before it earns the right to enter the market.

Here is a point many people miss: the patents protecting an original drug are not just one. The most fundamental among them is the substance patent, which shields the active ingredient itself. Keytruda's substance patent expires in June 2028 in Korea. The problem is that the expiry of this substance patent does not immediately allow a biosimilar to be sold. The original developer surrounds the substance patent with a dense web of formulation patents, manufacturing-method patents, administration-method patents, and indication patents (which specify what diseases the drug treats).

This practice of stacking patents in layers to stretch out the monopoly period as long as possible is called "evergreening" in the industry. The term means keeping patents alive "like an evergreen tree that stays green all year." Even when the substance patent — the inner keep — falls, an outer wall called the formulation patent can hold firm and delay a biosimilar's entry by several more years. The target Samsung Bioepis took precise aim at this time is exactly that second line of defense: the formulation patent.

⚗️ The Vulnerable Point Samsung Targeted — The Combination of Buffer, Stabilizer, and Surfactant

The focus of this trial is a patent held by MSD titled "Stable formulations of antibodies to human programmed death receptor PD-1 and related treatments." The name looks unfamiliar and complex, but its substance is simpler than you would think.

An antibody drug is an extremely delicate lump of protein. Simply dissolving it in water causes it to clump together or degrade easily. So it must be blended with various auxiliary ingredients to keep the active component stable for storage and injection — and this "blending recipe" is the formulation. MSD's patent specifies this recipe in great detail: per 1 mL, 25–100 mg of antibody, 70 mg of sucrose (a sugar-based stabilizer), 0.2 mg of polysorbate (a surfactant), and a histidine buffer adjusted to a pH range of 5.0–6.0.

Let me briefly explain the three unfamiliar terms here. A buffer holds the solution's acidity steady so the protein does not degrade. A stabilizer serves as a protective shield preventing the protein from clumping or breaking apart. A surfactant works on a principle similar to detergent, preventing the protein from sticking to the container wall or the air-contact surface and aggregating there. Polysorbate 80 is the representative example.

The real weakness of MSD's patent lies in the fact that it nailed down polysorbate as a mandatory, must-include ingredient. And this is where the decisive card Samsung Bioepis had prepared comes into view.

🎯 The Real Substance of the Bypass Design — The Foreshadowing Samsung Laid Down in 2020

The fact worth noting is that Samsung Bioepis had already filed a patent of its own in Korea back in 2020, titled "Stable anti-PD-1 antibody pharmaceutical formulation." The core claim of this patent is a formulation that includes pembrolizumab along with a stabilizer and a buffer, but does not include a surfactant such as polysorbate.

Why is this point decisive? If MSD's patent drew the line at "must include a surfactant," then when Samsung releases a formulation that removes the surfactant entirely, it logically stands outside the scope of that patent. Among the basic criteria for judging patent infringement is the so-called All Elements Rule. It states that infringement is established only when every single element listed in the counterpart's patent is present without exception — so if even one mandatory element is missing, there is, in principle, room to slip through the net of infringement.

In short, Samsung Bioepis paved this bypass — "we will go with a different recipe that has no surfactant" — four or five years ago, and timed its move now, as clinical results ripen, to obtain the official stamp confirming that "our formulation is outside your patent's scope." The construction of this blueprint is remarkably tight.

⚖️ The Weapon Called the "Negative Scope Confirmation Trial" — What Changes If They Win

Let me put the negative scope confirmation trial Samsung filed into plain terms. It is a procedure asking the Intellectual Property Trial and Appeal Board to "officially confirm that the product I will make going forward does not fall within the scope of your patent." The word "negative" is attached because it is not an attack meant to bring down the counterpart's patent itself (an active invalidation trial), but rather a defensive, confirmatory action asserting "I do not intrude upon that territory."

Here is a crucial insight to remember: even winning this trial does not extinguish MSD's patent itself. The patent remains alive and well until 2032. However, if Samsung can secure the judgment that "SB27's formulation is outside the patent's scope," a path opens to enter the market without the burden of infringement, even while the patent is still valid. It is not about smashing the counterpart's wall, but about getting legal certification of a safe side road that skirts around it.

An interesting point is that, statistically too, the odds of this card are quite high. Industry analysis shows that the average annual acceptance rate — the ratio of claims that are upheld — for negative scope confirmation trials filed by domestic bio and pharmaceutical companies is fairly high. Because the party filing the claim specifies and submits its own confirmation target, saying "my product differs in these ways," there is a tendency to play the card when the odds already look favorable. Given that Samsung moved while holding its own formulation patent as grounds, this filing too can be read as an expression of considerable confidence.

📅 Why Now — Timing That Pre-Calculated a Two-Year Gap

Keytruda's Korean substance patent expires in June 2028, and SB27's target entry point is also 2028. So why did Samsung move now, in 2026, rather than when the expiry was right around the corner?

The core insight of this whole affair is hidden inside this very question. A patent dispute does not end with the Board's ruling. If either side refuses to accept the outcome, the fight can escalate through the Patent Court (second instance) up to the Supreme Court (third instance), a process that takes several years. If Samsung had filed the trial just before the substance patent's expiry and MSD had clung on to the very end, launching SB27 before the final confirmation would itself mean shouldering an enormous legal risk. Should it lose after launch, the worst-case scenario — massive damages and a sales halt — would become reality.

Conversely, by filing now, Samsung can design the time it takes to reach a final judgment so that it naturally aligns with the substance patent's expiry point (2028). In other words, this filing is a preemptive maneuver aimed at "a launch two years out" while "clearing the legal landmines starting now." The very rhythm of throwing out the clinical results disclosure and then the patent trial in sequence is itself a meticulously designed roadmap.

🔬 Samsung Ahead in the Clinic Too — The True Meaning of the "Overlap" Strategy

It is not only the patents that were prepared. Since 2024, Samsung Bioepis has employed a so-called Overlap strategy, running Phase 1 and Phase 3 trials simultaneously in patients with non-small cell lung cancer (the most common type of lung cancer).

Originally, the textbook flow of a clinical trial is to confirm safety and pharmacokinetics in Phase 1, then verify efficacy at scale in Phase 3, in sequence. Here, pharmacokinetics (PK) refers to the entire process by which a drug enters the body and is absorbed, distributed, metabolized, and excreted — put simply, an indicator that examines "how the blood drug concentration rises and falls over time." But running these two stages in parallel can dramatically shorten the development period. Of course, if the earlier stage yields poor results, the cost poured into the later stage vanishes entirely — so it is a bold gamble that requires both confidence and financial strength.

The results were successful. In the Phase 1 trial involving 163 patients across four countries, an analysis of the area under the concentration-time curve (AUC) proved pharmacokinetic equivalence with Keytruda. This AUC indicator represents, simply put, the "total amount of drug that stayed in the body," and serves as a representative yardstick for gauging how similarly two drugs behave. Subsequently, in the Phase 3 trial with 555 patients across fourteen countries, the objective response rate (ORR) at week 24 — that is, the proportion of patients whose tumors visibly shrank — landed within the predetermined equivalence range. In June, Samsung Bioepis became the first among Keytruda biosimilar developers to disclose global Phase 3 results, firmly cementing its front-runner position.

🧩 The Questions We Failed to Ask — The Flip Side of This News

Look at this matter only on the surface, and it is easy to pass it off as "Samsung bypassed one patent." But throw a few questions that dig a few steps deeper, and the picture changes entirely.

First question: Is a launch really possible just by clearing one formulation patent? The answer is no. Beyond the substance and formulation patents, Keytruda has layer upon layer of follow-on patents protecting cancer-type-specific therapies, combination therapies used alongside other drugs, dosages, and dosing intervals. In particular, Keytruda is an all-purpose cancer drug with indications secured across dozens of cancer types — lung cancer, melanoma, bladder cancer, and more — so each indication has its own separate minefield of patents. This formulation patent trial merely cleared one entrance to a vast patent maze, and Samsung faces a long journey of dismantling this entire patent portfolio one by one, together with country-by-country approval procedures.

The second question is more subtle: Can a formulation with the surfactant removed truly be equivalent to the original? As explained earlier, a surfactant plays an important role in preventing protein aggregation. If stability was secured even without it, then Samsung did not merely dodge the patent adroitly — it achieved genuine innovation in formulation technology itself. The fact that Phase 1 and Phase 3 showed results similar to the original not only in safety but also in immunogenicity (the degree to which our body's immune system recognizes the drug as a foreign substance and triggers a rejection response) supports the conclusion that this bypass design was a product of skill, not a sleight of hand.

The third question broadens the board even further: Where are the competitors right now? The Keytruda biosimilar race is not a stage for Samsung Bioepis alone. It is a contested arena where multiple global pharmaceutical companies, including Celltrion, have jumped in simultaneously. In a 46-trillion-won market, a mere few months' difference in early entry widens into a revenue gap of hundreds of billions of won, so the speed of clinical progress and the speed of patent clearing become the very finish line that decides the ranking. Samsung's preemptive move — pulling out the formulation patent trial right after being first to disclose Phase 3 results — should be read as a maneuver to seize a firm advantage in this speed war.

🚀 Wrapping Up — This Is Not Patent News, but the Trailer of a Strategy

Compressed into a single sentence, this news is that Samsung Bioepis, right after passing the first gate of clinical trials, immediately began knocking preemptively on the second gate of patents. But peer behind it, and the story shifts. Planting its own surfactant-free formulation patent four or five years ago, compressing the timeline with an overlap clinical strategy, and throwing the patent trial now with the time gap up to the Supreme Court already calculated — you can see that every one of these moves interlocks into a single, meticulously designed roadmap.

In 2028, when the 46-trillion-won market for the world's number one drug opens, the race to pass through that door before anyone else has already begun. And right now, Samsung Bioepis stands with its foot on the starting line, half a step ahead of the rest.