Keytruda sold $31.68 billion in 2025. That was 48.7% of Merck’s total sales of $65.01 billion. [1] Merck lists the main US patent for Keytruda as expiring in 2028. [1] Since July 2025, Merck has announced three acquisitions with a combined equity value of about $25.9 billion. [3][4][5] This article shows how strategy teams move from a patent date to a named partnership target, and what the public record says about each step.
We use primary documents where they exist: SEC filings, company press releases, FDA pages, and tribunal decisions. We label every calculation as analysis. DrugPatentWatch, the patent and regulatory database affiliated with DrugChatter, supplies the patent records that teams use to start this work. It does not replace the primary documents.
The Short Answer: How Do Strategy Teams Turn a Patent Expiration Into a Partnership Target?
Strategy teams turn a patent expiration into a partnership target in six steps. They list the revenue tied to each expiry date. They measure the time left. They classify the revenue gap and pick a deal type. They price the risk. They test the target’s own patents. They then track the docket after signing.
The Five Findings That Matter
Keytruda and Keytruda Qlex together made $31.68 billion in 2025, or 48.7% of Merck’s sales. This is a calculation from Merck’s 10-K. [1]
Merck’s 10-K gives Keytruda different expiry years by region: 2028 in the US and China, 2031 in the EU, and 2032 to 2033 in Japan. [1]
Merck’s three announced deals since July 2025 total about $25.9 billion in equity value. That equals 0.82 times Keytruda’s 2025 sales. This is a calculation. The deals buy different assets at different stages, so the ratio is a scale check and not a replacement forecast. [3][4][5]
The share of a licensing deal paid at signing ranges from 4.0% to 20.7% in the three China-sourced licensing deals we examined. Acquisitions pay the full price in cash. These are calculations from deal press releases. [6][7][8]
AbbVie’s Humira fell 78.6% from $21.237 billion in 2022 to $4.540 billion in 2025. Skyrizi and Rinvoq together grew from $7.687 billion to $25.866 billion in the same period. This is a calculation from AbbVie’s results. [24][25]
GlobalData estimates that the US pharmaceutical market will lose more than $230 billion in revenue between 2025 and 2030 because of loss of exclusivity. [2]
What Is a Patent Expiration Partnership Target?
A patent expiration partnership target is an asset, company, or technology that a brand manufacturer licenses, acquires, or co-develops to replace or protect revenue that will fall when a patent or exclusivity period ends. The term is ours. It is a working definition for this article and not an industry standard.
Definitions Used in This Article
Loss of exclusivity (LOE)
LOE is the date when a brand product no longer has legal protection from generic or biosimilar competition. The date depends on patents and on FDA exclusivity periods. The two can end on different days.
Patent cliff
A patent cliff is a period in which many LOE dates fall close together, or in which one product with very large sales loses protection. Keytruda is the second type at Merck.
Deal vehicle
A deal vehicle is the legal structure of a transaction. Examples are a full acquisition, a single-asset license, a multi-program license with options, and a technology license.
What Is the Difference Between a Patent and Exclusivity?
A patent is granted by the USPTO. Exclusivity is a marketing right granted by FDA when it approves a drug. FDA states that exclusivity is ‘exclusive marketing rights granted by the FDA upon approval of a drug.’ [10] The two can overlap, and a drug can have several patents. [10]
FDA lists these exclusivity periods: 5 years for a new chemical entity, 7 years for an orphan drug, and 6 months added to existing patents and exclusivity for pediatric studies. [10] For biologics, a biosimilar application cannot be submitted until 4 years after first licensure, and approval cannot take effect until 12 years after first licensure. [12]
How Big Is the Patent Cliff? Why Do Estimates Differ?
Published estimates range from more than $230 billion to about $400 billion. The numbers differ because each source counts a different thing.
Cliff Estimates Compared
Source
Figure
Scope
Period
Ref.
GlobalData
More than $230 billion
US market revenue lost to LOE
2025 to 2030
[2]
Pharmaceutical Executive
About $400 billion
Revenue of about 200 drugs with patents or exclusivity ending
2026 to 2030
[9]
The first figure counts revenue that the US market is expected to lose. The second counts the total revenue of drugs whose protection ends. Revenue exposed is not revenue lost. A team cannot add or compare the two numbers directly. This is our analysis of the scope of each source.
Keytruda: One Product Is 48.7% of Merck’s Sales
Merck’s 10-K reports Keytruda and Keytruda Qlex sales of $31,680 million in 2025 and $29,482 million in 2024. [1] Total Merck sales were $65,011 million in 2025 and $64,168 million in 2024. [1]
From these figures, Keytruda was 48.7% of sales in 2025 and 45.9% in 2024. Keytruda sales grew 7.5% year over year. These are our calculations. The share rose as the expiry date came closer.
Why concentration matters more than total size
A company with ten products that each make 10% of sales can absorb one expiry. A company with one product at 48.7% cannot. Strategy teams therefore rank exposure by the share of company sales, and then by the dollar amount.
Which Other Companies Face a Dated Exposure?
GlobalData expects Bristol Myers Squibb to lose US exclusivity for Opdivo and Eliquis around 2028. [21] GlobalData also says Johnson & Johnson’s Darzalex has US exclusivity ending by 2029. [2] Bristol Myers Squibb closed more than $30 billion in deals over two years, according to the same trade report. [21]
Methodology: How We Built the Deal Comparison
What Data We Used
We used nine deals announced between December 2023 and January 2026. They are Pfizer and Seagen, Bristol Myers Squibb and Karuna, Johnson & Johnson and Intra-Cellular, Merck and Verona, Merck and Cidara, Merck and Terns, Pfizer and 3SBio, GSK and Hengrui, and AstraZeneca and CSPC.
How We Selected Records
A deal was included if three conditions held. A company press release, SEC filing, or named trade report gave the price and structure. The buyer stated or was widely reported to have a patent-expiry or revenue-gap motive. The deal had one clear lead asset or program set. We did not include every large deal. The set is a purposive sample and does not represent the whole market.
How We Calculated Derived Figures
Share of sales equals product sales divided by total company sales, both from the same 10-K. [1]
Months to LOE equals days from announcement to December 31 of the stated US expiry year, divided by 30.4375. We use year-end because Merck’s 10-K gives a year and not a day. [1]
Upfront ratio equals upfront payment divided by the sum of upfront payment and stated milestones. Equity investments and royalties are excluded.
Deal values are equity values as stated by each source. Some include contingent value rights or cash that the target holds, so values are not fully comparable.
Limits of This Analysis
Headline licensing values include milestones that buyers may never pay. Press releases do not state every term. Patent expiry years from a 10-K can change after litigation or a settlement. Sales forecasts from analysts are estimates. We mark each one.
Step 1: How Do Strategy Teams Build an Exposure Ledger?
An exposure ledger lists every product, its sales, and the date it loses protection in each major market. The ledger comes before any search for deals, because it sets how large the gap is and how soon it opens.
Where Do the Expiry Dates Come From?
Company 10-K patent tables
Merck’s 10-K lists Keytruda expiry by region. The US date is 2028, with two further patents expiring in 2029 because of patent term adjustment. The EU date is 2031. The Japan date is 2032 to 2033. The China date is 2028. [1]
Orange Book and Purple Book
FDA must list in the Orange Book the patent number and expiry date of each patent that claims a drug or a method of using it. [10] The Purple Book lists licensed biologics with their reference product exclusivity. [12] Teams read both to check what the sponsor has declared.
Commercial patent databases
DrugPatentWatch’s Keytruda record, updated October 14, 2026, lists seven patents from company disclosures. Their expiry dates run from November 13, 2037 to September 2, 2041. [14] The record reports the central US patent, 8,354,509, as generally expiring in 2028 after adjustments. [14] The record does not state what each later patent claims. A team must read the claims to learn whether a later patent blocks a competitor.
What Do the Regional Gaps Show?
Keytruda’s EU expiry year is three years after the US year. Its Japan expiry is four to five years after the US year. These are calculations from the 10-K years. [1] A company with large ex-US sales can hold part of its revenue longer than the US date suggests. A team therefore models each region on its own date.
How Do Exclusivity Layers Change the Date?
Patent term extension
Patent term extension under 35 U.S.C. 156 restores part of the time a patent owner lost during FDA review. The extension may not exceed five years. The total of the remaining patent term and the extension may not exceed fourteen years from approval. [13]
New chemical entity exclusivity and the NCE-1 date
For a small-molecule drug, an ANDA with a Paragraph IV certification can be submitted at the ‘NCE-1’ date, which is year 4 after approval. [11] A Paragraph IV certification is an assertion that a patent is invalid, unenforceable, or not infringed. [11]
The 30-month stay and 180-day exclusivity
When an NCE applies, FDA says the 30-month stay is extended so that 7.5 years pass from the date of NDA approval. [11] The first applicant to submit a substantially complete ANDA with a Paragraph IV challenge earns 180-day exclusivity. [11] Each of these events moves a date on the ledger.
Biologic exclusivity
Keytruda was first approved in September 2014. [14] Twelve years from September 2014 is September 2026. This is our calculation, and it matches the DrugPatentWatch statement that the period has expired. [14] The consequence is that biosimilar timing for Keytruda now depends on patents and litigation and not on the 12-year bar. [12] This is our analysis.
Step 2: How Much Time Is Left Before the Patent Clock Runs Out?
The next step is to count the months between today and the expiry date. The count decides which deal stages can still pay off before the date.
Keytruda Patent Timeline
Date
Event
Type
Ref.
September 2014
First FDA approval of Keytruda
Regulatory
[14]
November 2024
MSD files the first post-grant review petition against a Halozyme patent
Litigation
[16]
April 24, 2025
Halozyme files suit in the District of New Jersey, alleging that Keytruda Qlex infringes 15 patents
Litigation
[16]
June 2025
PTAB institutes the first review
Litigation
[16]
September 2025
FDA approves subcutaneous Keytruda (Keytruda Qlex) for solid tumor indications
Regulatory
[15]
May 12, 2026
PTAB final written decision holds claims of US 11,952,600 unpatentable
Litigation
[16]
September 2026
12-year biologic exclusivity period ends (calculated)
Analysis
[12][14]
October 7, 2026
Dutch court order reported, barring Keytruda SC in eight European markets
Litigation
[17]
November 19, 2026
Hearing set on Merck’s appeal of the German preliminary injunction
Litigation (scheduled)
[17]
2028
US and China expiry of the main Keytruda patents
Patent
[1]
2029
Two further US patents expire after patent term adjustment
Patent
[1]
2031
EU expiry
Patent
[1]
2032 to 2033
Japan expiry
Patent
[1]
How Many Months Remain on the Keytruda Clock?
From October 15, 2026 to December 31, 2028 is 808 days, or about 26.5 months. This is our calculation. It is an upper bound for the 2028 date, because the 10-K gives a year and not a day. [1]
Months between announcement and the 2028 expiry year
Merck announced Verona on July 9, 2025, which was about 41.8 months before the end of 2028. It announced Cidara on November 14, 2025, about 37.6 months before. It announced Terns on March 25, 2026, about 33.2 months before. These are calculations from the announcement dates in the sources. [3][4][5]
Step 3: Which Deal Vehicle Fits the Gap? A Four-Type Taxonomy
We group partnership targets into four types: Bridge, Defend, Seed, and Option. The taxonomy is our own framework. It is built from documented deal facts, and it is not an industry standard. The type depends on when the target can book revenue and on how much risk the buyer keeps.
What Is a Bridge Target?
A Bridge target is a marketed product or a product with a near-term FDA decision. It adds revenue before the expiry date.
Bristol Myers Squibb agreed to buy Karuna on December 22, 2023, at $330 per share. The equity value was about $14.0 billion, or $12.7 billion net of cash. [19] Karuna’s NDA for KarXT in schizophrenia was accepted, with a PDUFA date of September 26, 2024. [19] From the announcement to the PDUFA date was 279 days. This is our calculation.
Chief executive Christopher Boerner said KarXT should enhance growth ‘through the late 2020s and into the next decade.’ [19]
Johnson & Johnson agreed on January 13, 2025 to buy Intra-Cellular Therapies at $132 per share, an equity value of about $14.6 billion. [20] Caplyta was approved for schizophrenia and for bipolar depression. [20] J&J stated that Caplyta had potential for more than $5 billion in peak-year sales. That is a company projection and it is not risk-adjusted. [20] Caplyta sales were $240 million in the third quarter of 2025, as Stelara sales fell. [23]
Merck’s purchase of Verona belongs here. Verona’s Ohtuvayre (ensifentrine) was cleared by FDA in June 2024 for COPD maintenance treatment. Verona reported $71.3 million in sales in the first quarter of 2025. [3] Merck announced the deal on July 9, 2025 at $107 per ADS, for about $10 billion. [3]
What Is a Defend Target?
A Defend target protects the existing product. It does not add a new product. The usual form is a new formulation or delivery route with its own patents.
Keytruda Qlex and Opdivo Qvantig
Merck’s Keytruda Qlex is a subcutaneous fixed combination of pembrolizumab and berahyaluronidase alfa. [1] FDA approved it for the solid tumor indications of intravenous Keytruda. [15] Bristol Myers Squibb’s Opdivo Qvantig combines nivolumab with hyaluronidase-nvhy and Halozyme’s ENHANZE technology. FDA approved it on December 27, 2024. [22]
From approval to December 31, 2028 is about 48.1 months for Opdivo Qvantig and about 39.4 months for Keytruda Qlex. These are calculations that use the approval dates in the sources and the year-level expiry assumption. [15][22]
What Is a Seed Target?
A Seed target is an asset in clinical development that will not earn revenue until after the expiry date, or that has revenue plans far out. It builds the next product line. It carries the highest scientific risk.
Pfizer agreed on March 13, 2023 to buy Seagen at $229 per share, at an enterprise value of about $43 billion. Pfizer financed the deal mainly with $31 billion of new long-term debt. [18] Pfizer stated that Seagen could contribute more than $10 billion in risk-adjusted revenues in 2030. [18] From signing to 2030 is seven years. This is our calculation.
Merck’s Cidara deal is a Seed deal in Phase 3. Merck agreed on November 14, 2025 to buy Cidara at $221.50 per share, for about $9.2 billion. The lead asset, CD388, is an investigational long-acting antiviral to prevent influenza. It is in the Phase 3 ANCHOR study and holds Breakthrough Therapy Designation. [4] Merck’s chairman and chief executive Robert Davis said CD388 ‘has the potential to be another important driver of growth through the next decade.’ [4]
Merck’s Terns deal is an earlier Seed deal. Merck announced it on March 25, 2026 at $53 per share, for about $6.7 billion, or $5.7 billion net of acquired cash. [5] TERN-701 is an oral allosteric BCR::ABL1 tyrosine kinase inhibitor for chronic myeloid leukemia. It is in a Phase 1/2 trial and holds Orphan Drug Designation. [5] Merck expected a charge of about $5.8 billion in its second quarter and full-year 2026 results. [5]
What Is an Option Target?
An Option target is a license, usually with a low payment at signing and large milestones later. The buyer pays more only if programs succeed. Option deals often cover several programs, so the buyer can drop the weak ones.
Pfizer and 3SBio
Pfizer announced on May 19, 2025 an exclusive license to SSGJ-707, a bispecific antibody that targets PD-1 and VEGF. The terms were $1.25 billion upfront, up to $4.8 billion in milestones, tiered double-digit royalties, and a $100 million equity investment. Pfizer received global rights outside China and an option for China. [6]
GSK and Hengrui
GSK announced on July 28, 2025 agreements for up to 12 programs. The upfront payment was $500 million, and the milestones were about $12 billion. The first program, HRS-9821, is a PDE3/4 inhibitor in development for COPD. [7] GSK’s chief scientific officer Tony Wood said the agreements ‘complement our already-extensive pipeline.’ [7]
AstraZeneca and CSPC
Pharmaceutical Executive reports a January 2026 AstraZeneca and CSPC agreement with $1.2 billion upfront and $17.3 billion in potential milestones, a total of about $18.5 billion. [8] The report says the deal advances eight programs. [8]
Nine Deals Compared: Reference Table
Buyer / Target
Announced
Headline value
Lead asset and stage at signing
Type (our framework)
Ref.
Pfizer / Seagen
Mar 13, 2023
$229 per share; about $43 billion enterprise value
Oncology company; more than $10 billion risk-adjusted revenue expected in 2030
Seed
[18]
Bristol Myers Squibb / Karuna
Dec 22, 2023
$330 per share; about $14.0 billion
KarXT; NDA accepted, PDUFA Sept 26, 2024
Bridge
[19]
Johnson & Johnson / Intra-Cellular
Jan 13, 2025
$132 per share; about $14.6 billion
Caplyta; marketed
Bridge
[20]
Merck / Verona
Jul 9, 2025
$107 per ADS; about $10 billion
Ohtuvayre; marketed since 2024
Bridge
[3]
Merck / Cidara
Nov 14, 2025
$221.50 per share; about $9.2 billion
CD388; Phase 3
Seed
[4]
Merck / Terns
Mar 25, 2026
$53 per share; about $6.7 billion
TERN-701; Phase 1/2
Seed
[5]
Pfizer / 3SBio
May 19, 2025
$1.25 billion upfront; up to $4.8 billion milestones
SSGJ-707; clinical trials in China
Option
[6]
GSK / Hengrui
Jul 28, 2025
$500 million upfront; about $12 billion milestones
Up to 12 programs; HRS-9821 first
Option
[7]
AstraZeneca / CSPC
Jan 2026
$1.2 billion upfront; $17.3 billion milestones
Eight programs
Option
[8]
What Does the Table Show About Stage at Signing?
Three of the nine deals bought a marketed product or a product with an FDA decision date. Three bought assets in clinical development with revenue years away. Three were licenses with low upfront shares. Merck’s three deals fall into two types, Bridge and Seed. This count is our classification of the documented facts.
Step 4: How Do Buyers Price the Risk? Upfront Ratios in Licensing Deals
An acquisition pays the full price at closing. A license splits the price between a payment now and payments later. The upfront ratio shows how much risk the licensor carries.
Upfront Ratios in Three China-Sourced Licensing Deals
Deal
Upfront
Milestones
Upfront ratio (calculated)
Ref.
Pfizer / 3SBio (one asset)
$1.25 billion
Up to $4.8 billion
20.7%
[6]
GSK / Hengrui (up to 12 programs)
$500 million
About $12 billion
4.0%
[7]
AstraZeneca / CSPC (eight programs)
$1.2 billion
$17.3 billion
6.5%
[8]
The single-asset deal has the highest upfront ratio. The two multi-program deals have ratios below 7%. Three deals are too few to set a rule. The pattern fits a simple reading: a buyer pays more at signing when it takes one asset and fewer dollars per program when it holds options on many. This is our interpretation.
Why Are China-Sourced Assets a Larger Share of Licensing?
A Jefferies research report, covered by Fierce Biotech in July 2025, put China’s share of out-licensing deal value at 32% in the first quarter of 2025. [27] The same report said upfront payments for China-sourced assets run about 60% to 70% below those of global peers, and total deal sizes run about 40% to 50% below. [27] The report named drug pricing pressure and patent expirations as main drivers of the rise in deals. [27]
What buyers should check in a China-sourced license
A buyer checks four items: the territory split, the scope of ex-China rights, the party that controls the filings, and the status of the licensor’s patents in the US and EU. The Pfizer and 3SBio terms show the split. Pfizer received global rights outside China and an option for China. [6]
Step 5: What Happens if the Target’s Own Patents Fail? The Keytruda Qlex and Halozyme Case
A Defend deal can fail on the target’s side. The Keytruda Qlex dispute shows how. Merck’s subcutaneous product depends on an enzyme and a formulation, and a third party claims patents on the enzyme.
Litigation Breakdown: Halozyme v. Merck
The claim
Halozyme alleges that Keytruda Qlex infringes its modified hyaluronidase patents. [15] The Qlex enzyme, berahyaluronidase alfa, is from Alteogen. [15] Halozyme filed suit in the District of New Jersey on April 24, 2025, and alleged infringement of 15 patents. [16]
The US challenge
Merck, through MSD, filed post-grant review petitions at the PTAB. The PTAB instituted 13 petitions. [16] On May 12, 2026, in PGR2025-00003, it held claims 1 to 4 and 8 to 21 of US 11,952,600 unpatentable for lack of enablement and for failure to meet the written description requirement. Halozyme had disclaimed claims 5 to 7. [16] Three further inter partes review petitions filed on March 23, 2026 are pending. [16]
The European injunctions
A specialized Dutch patent court in The Hague barred MSD BV from making, marketing, or stocking Keytruda SC in eight markets: Belgium, Denmark, France, Ireland, Italy, Sweden, Switzerland, and the Netherlands. The order concerns European patent EP 2,797,622, and the court rejected Merck’s invalidity arguments. [17] Merck has appealed a German preliminary injunction, with a hearing set for November 19, 2026. [17] Halozyme says the order does not affect intravenous Keytruda. [17]
What Does the Qlex Case Mean for Defend Deals?
The case shows that a Defend deal has its own patent clock. A subcutaneous product can win FDA approval and still face injunctions in some jurisdictions. A US tribunal and a European court can reach different results on related patents. This is our analysis of the record in [16] and [17].
Keytruda vs. Opdivo: how do the two subcutaneous plans compare?
Both are PD-1 products. Both use hyaluronidase. Bristol Myers Squibb’s version uses Halozyme’s own ENHANZE technology, and Halozyme states that its enforcement does not affect partners that use ENHANZE. [17][22] Merck’s version uses an Alteogen enzyme, and Halozyme disputes it. [15][17] The public record shows no Halozyme dispute over Opdivo Qvantig in the sources we reviewed. We did not search for other disputes, and a reader should check the docket.
What Happens After Loss of Exclusivity? Three Documented Outcomes
AbbVie: Humira Down 78.6%, Immunology Franchise Up
AbbVie reported 2022 global net revenues of $21.237 billion for Humira, $5.165 billion for Skyrizi, and $2.522 billion for Rinvoq. [24] For 2025 it reported $4.540 billion for Humira, $17.562 billion for Skyrizi, and $8.304 billion for Rinvoq. [25]
Product
2022 ($ million)
2025 ($ million)
Change (calculated)
Ref.
Humira
21,237
4,540
-78.6%
[24][25]
Skyrizi
5,165
17,562
+240%
[24][25]
Rinvoq
2,522
8,304
+229%
[24][25]
Three products combined
28,924
30,406
+5.1%
[24][25]
The three products made 49.8% of AbbVie’s net revenues in 2022 and 49.7% in 2025. These are our calculations from AbbVie’s reported totals of $58.054 billion and $61.160 billion. [24][25] The result is a case in which a replaced franchise held its share of company revenue. It is one company. It is not a forecast for any other.
Johnson & Johnson: Stelara Down 40% in Nine Months
Stelara reached peak sales of $10.9 billion in 2023. Its sales fell 40% over the first nine months of 2025. [23] Darzalex made $10.4 billion in the first nine months of 2025, and oncology made $18.5 billion. [23] Global innovative medicine revenue still grew 5%. [23]
Novartis: Entresto Under Generic Pressure
Novartis reported third-quarter 2025 sales of $13.9 billion, up 7%. Kisqali rose 68% to $1.3 billion. Entresto sales were almost $1.9 billion, as generics reached the US market in the summer. [26]
What Do the Three Cases Have in Common?
In each case the company had other products growing fast enough to cover most or all of the loss. This is our reading of [23], [25], and [26]. The sources do not say the growth products were chosen in advance as replacements. A team should not assume that any one deal will do the same.
Scenario Analysis: What if Keytruda Sales Fall by 10%, 25%, or 49.5%?
The table below is illustrative arithmetic. It applies three assumed erosion rates to Keytruda’s 2025 sales of $31.68 billion. [1] The 49.5% rate is the reported 2025 decline of Humira. [25] It is not a forecast for Keytruda.
Assumed erosion
Revenue removed (calculated)
Merck’s three deals as a multiple of revenue removed
10%
$3.17 billion
8.2 times
25%
$7.92 billion
3.3 times
49.5%
$15.68 billion
1.7 times
The multiple uses the $25.9 billion combined equity value of Verona, Cidara, and Terns. [3][4][5] It compares what Merck paid with one year of lost sales. It does not say how much revenue the three assets will earn. Their peak sales are not known. BMO estimated 2025 sales of about $400 million and peak sales of about $3.4 billion for Ohtuvayre. That is an analyst estimate. [3]
Step 6: How Do Teams Check the Target’s Patents and Track the Docket After Signing?
The last step has two parts. Before signing, the team reads the target’s own patents and any third-party claims. After signing, it tracks every date that can move the ledger.
What Should a Freedom-to-Operate Check Cover?
Enabling technology
The Keytruda Qlex case shows why. The product’s enzyme is under dispute, and the dispute reached a district court, the PTAB, and courts in two European countries. [15][16][17]
Territory and licence scope
A license that excludes China, as in the Pfizer and GSK deals, leaves the licensor with those rights. [6][7] A team confirms that its own patent ledger and the licensor’s ledger use the same territories.
Patent term adjustments
Merck’s 10-K lists two Keytruda patents that expire in 2029 because of patent term adjustment. [1] A team that reads only the headline year of 2028 misses them. We do not know from the 10-K what those patents claim.
Which Dates Should a Team Track After Signing?
Date
Event to track
Status
Ref.
November 19, 2026
Hearing on Merck’s appeal of the German preliminary injunction
Scheduled
[17]
Pending
Three inter partes review petitions filed March 23, 2026
Pending
[16]
2028
US and China expiry of the main Keytruda patents
Stated in 10-K
[1]
2029
Expiry of two further US Keytruda patents
Stated in 10-K
[1]
2031
EU expiry
Stated in 10-K
[1]
How Do Teams Use DrugPatentWatch in This Process?
Teams use DrugPatentWatch to build the first draft of the ledger. A record such as the Keytruda page gives patent expiry dates, exclusivity periods, and litigation entries in one place. [14] The team then checks each date against the primary document, such as the 10-K, the Orange Book, the Purple Book, or the court docket. We do not treat the database as proof of a date. [14]
DrugPatentWatch published a related article in October 2026. It covers 2026 deal totals, upfront ratios, and a seven-step framework. [28] This article uses a different classification and a different set of deals.
What This Means for Brand Manufacturers, Licensors, and Biosimilar Developers
What This Means for Brand Manufacturers
A brand manufacturer should rank its products by share of company sales and by months to expiry. Merck’s Keytruda is at 48.7% of sales with a US date in 2028. [1] A product at that share needs several deals of different types. Merck’s three deals include two Bridge and Seed types. [3][4][5] A Defend deal protects the base while the other deals mature.
What This Means for Biotech Licensors
A licensor sees the buyer’s clock. A buyer with a dated expiry has a reason to move quickly, and a reason to prefer assets that can earn revenue in time. The Verona deal shows the premium on a marketed product. Merck agreed to pay about $10 billion for a drug with $71.3 million in first-quarter 2025 sales. [3] A licensor with an earlier-stage asset can offer more programs and accept a lower upfront share, as Hengrui and CSPC did. [7][8]
What This Means for Generic and Biosimilar Developers
A biosimilar developer for Keytruda faces a protected date that is set by patents and not by the 12-year bar. [1][12] The developer’s ledger should include the main 2028 patents, the two 2029 patents, and any later patents on the subcutaneous product. The DrugPatentWatch record lists patents with expiry dates from 2037 to 2041. A developer must read their claims to learn whether they apply to its product. [14]
Events to Watch Through 2028
The German appeal hearing on November 19, 2026. [17]
The outcome of the three pending inter partes review petitions at the PTAB. [16]
Phase 3 results and approval timing for CD388, which Merck acquired from Cidara. [4]
Phase 1/2 data for TERN-701 in chronic myeloid leukemia. [5]
The dates in the 10-K for US, China, EU, and Japan expiry of Keytruda. [1]
These are scheduled or stated events. We do not forecast the outcomes.
Key Takeaways
Keytruda was 48.7% of Merck’s 2025 sales, and Merck lists its main US patent expiry as 2028. [1]
Keytruda’s expiry year differs by region: 2028 in the US and China, 2031 in the EU, and 2032 to 2033 in Japan. [1]
Merck’s Verona, Cidara, and Terns deals total about $25.9 billion, which is 0.82 times Keytruda’s 2025 sales. [3][4][5]
Our four-type taxonomy sorts nine deals as three Bridge, three Seed, and three Option. [3][4][5][6][7][8][18][19][20]
The upfront share of the three China-sourced licenses ranges from 4.0% to 20.7%. [6][7][8]
PTAB held claims of Halozyme’s US 11,952,600 unpatentable on May 12, 2026, while a Dutch court barred Keytruda SC in eight European markets on a different patent. [16][17]
AbbVie’s Humira fell 78.6% from 2022 to 2025, and the three-product immunology group grew 5.1%. [24][25]
Published cliff estimates use different scopes, so a team should not compare $230 billion of US revenue loss with $400 billion of exposed revenue. [2][9]
FAQ: Patent Expirations and Partnership Targets
What is the difference between loss of exclusivity and patent expiration?
Loss of exclusivity is the date when competition can enter. Patent expiration is one input to that date. FDA exclusivity periods can end earlier or later than the patents. [10]
When does Keytruda lose US patent protection?
Merck’s 10-K gives 2028 for the US, with two further patents expiring in 2029 after patent term adjustment. [1]
Does 12-year biologic exclusivity still protect Keytruda?
No. FDA bars approval of a biosimilar until 12 years after first licensure. [12] Keytruda was first approved in September 2014, so the period ended in September 2026. This is our calculation. [14]
Which other companies face large expiries around 2028?
GlobalData expects Bristol Myers Squibb to lose US exclusivity for Opdivo and Eliquis around 2028. [21] GlobalData also lists Johnson & Johnson’s Darzalex with US exclusivity ending by 2029. [2]
What is an upfront ratio?
It is the upfront payment divided by the sum of the upfront payment and stated milestones. A low ratio means the buyer pays most of the price only if programs succeed. The GSK and Hengrui ratio is 4.0%. [7]
What is a Paragraph IV certification?
It is an assertion by an ANDA applicant that a patent is invalid, unenforceable, or will not be infringed. [11] The first applicant to file a substantially complete ANDA with such a challenge earns 180-day exclusivity. [11]
How long can a patent term extension last?
The extension may not exceed five years. The total of the remaining patent term and the extension may not exceed fourteen years from approval. [13]
Why do large companies license from China?
A Jefferies report cited drug pricing pressure and patent expirations as main drivers. It also reported that upfront payments for China-sourced assets run about 60% to 70% below those of global peers. [27]
Can a US PTAB ruling stop a European injunction?
The sources we reviewed do not show that it can. The PTAB decision concerns US 11,952,600. The Dutch order concerns European patent EP 2,797,622. They are separate patents in separate jurisdictions. [16][17]
Can the expiry years in a 10-K change?
Yes. A 10-K states a date at the time of filing. Patent term adjustment already moves some dates, as Merck’s footnote on two 2029 patents shows. [1] Litigation or settlement can also change dates. Teams re-check each date against the docket.
References
Merck & Co., Inc. (2026). Form 10-K for the fiscal year ended December 31, 2025. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/310158/000031015826000063/mrk-20251231.htm
GlobalData, via Trade and Industry Development. (2025, July 7). Big Pharma prepares for ‘patent cliff’ as blockbuster drug revenue losses loom. https://www.tradeandindustrydev.com/industry/bio-pharmaceuticals/big-pharma-prepares-patent-cliff-blockbuster-drug-34694
BioSpace. (2025, July 9). Merck makes big respiratory play with $10B acquisition of Verona. https://www.biospace.com/deals/merck-makes-big-respiratory-play-with-10b-acquisition-of-verona
Merck & Co., Inc. (2025, November 14). Merck to acquire Cidara Therapeutics, Inc., diversifying its portfolio to include late-phase antiviral agent [Press release]. Business Wire. https://www.businesswire.com/news/home/20251114185276/en
Terns Pharmaceuticals, Inc. (2026, March 25). Merck to acquire Terns Pharmaceuticals [Press release, Form 8-K Exhibit 99.1]. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/1831363/000119312526122785/d86253dex991.htm
Pfizer Inc. (2025, May 19). Pfizer enters into exclusive licensing agreement with 3SBio [Press release]. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-enters-exclusive-licensing-agreement-3sbio
GSK plc. (2025, July 28). GSK and Hengrui Pharma enter agreements to develop up to 12 innovative medicines [Press release]. https://www.gsk.com/media/1v0m0glr/gsk-and-hengrui-pharma-enter-agreements-to-develop-up-to-12-innovative-medicines.pdf
Pharmaceutical Executive. (2026). Deepening ties: Why China is becoming big pharma’s most essential R&D partner. https://www.pharmexec.com/view/deepening-ties-why-china-becoming-big-pharma-most-essential-rd-partner
Hollan, M. (2026). Patent cliff explained: What it is and how companies navigate it. Pharmaceutical Executive. https://www.pharmexec.com/view/patent-cliff-explained-what-how-companies-navigate
U.S. Food and Drug Administration. (n.d.). How can I better understand patents and exclusivity? https://www.fda.gov/industry/fda-basics-industry/how-can-i-better-understand-patents-and-exclusivity
Patel, R. (n.d.). Exclusivity: Which one is for me? U.S. Food and Drug Administration, Office of Generic Drugs. https://fda.gov/media/135234/download
U.S. Food and Drug Administration. (2020, August 3). Background information: List of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations (Purple Book). https://www.fda.gov/drugs/biosimilars/background-information-list-licensed-biological-products-reference-product-exclusivity-and
U.S. Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, section 2758: Calculation of patent term extension. https://www.uspto.gov/web/offices/pac/mpep/s2758.html
DrugPatentWatch. (2026, October 14). Keytruda (pembrolizumab) biologic drug record. https://www.drugpatentwatch.com/p/biologics/tradename/KEYTRUDA
Fierce Pharma. (2025, September 19). Merck scores FDA approval for subcutaneous Keytruda, securing potential blockbuster protection. https://fiercepharma.com/pharma/merck-scores-fda-approval-subcutaneous-keytruda
Pearce IP. (2026, May 12). MSD invalidates US Halozyme patent in SC pembrolizumab dispute. https://www.pearceip.law/2026/05/12/msd-invalidates-us-halozyme-patent-in-sc-pembrolizumab-dispute/
AllSci. (2026, October 7). Halozyme wins Dutch court order barring Merck’s Keytruda SC from eight European markets. https://allsci.com/news/patents/keytruda-sc-halozyme-wins-dutch-court-order/
Pfizer Inc. (2023, March 13). Pfizer invests $43 billion to battle cancer [Press release, Form 8-K Exhibit 99.1]. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/78003/000119312523068538/d408093dex991.htm
Bristol Myers Squibb Company. (2023, December 22). Bristol Myers Squibb strengthens neuroscience portfolio with acquisition of Karuna Therapeutics [Press release, Form 8-K Exhibit 99.1]. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/14272/000114036123059159/ef20017313_ex99-1.htm
Johnson & Johnson. (2025, January 13). Johnson & Johnson to acquire Intra-Cellular Therapies [Press release, filed as Exhibit 99.1 by Intra-Cellular Therapies]. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/1567514/000119312525004990/d910241dex991.htm
Pharmaceutical Technology. (2026, January 13). JPM26: BMS places confidence in core pipeline to weather 2030 patent cliff. https://www.pharmaceutical-technology.com/news/jpm26-bms-places-confidence-in-core-pipeline-to-weather-2030-patent-cliff/
American Journal of Managed Care. (2025, January 2). FDA approves first subcutaneous nivolumab injection in most solid tumors. https://ajmc.com/view/fda-approves-first-subcutaneous-nivolumab-injection-in-most-solid-tumors
BioSpace. (2025, October 22). How J&J kept growing amid the erosion of cornerstone drug Stelara. https://www.biospace.com/business/how-j-j-kept-growing-amid-the-erosion-of-cornerstone-drug-stelara
AbbVie Inc. (2023). AbbVie reports full-year and fourth-quarter 2022 financial results [Press release]. Reproduced by BioSpace. https://www.biospace.com/abbvie-reports-full-year-and-fourth-quarter-2022-financial-results
AbbVie Inc. (2026, February 4). AbbVie reports full-year and fourth-quarter 2025 financial results [Press release]. https://news.abbvie.com/2026-02-04-AbbVie-Reports-Full-Year-and-Fourth-Quarter-2025-Financial-Results
pharmaphorum. (2025, October 28). Novartis’ new drugs outweigh Entresto decline in Q3. https://pharmaphorum.com/news/novartis-new-drugs-outweigh-entresto-decline-q3
Masson, G. (2025, July 14). China biotechs ‘reshaping’ US biopharma as outlicensing deals rise 11%: Jefferies report. Fierce Biotech. https://www.fiercepharma.com/biotech/china-biotechs-reshaping-us-biopharma-outlicensing-deals-rise-11-jefferies-report
DrugPatentWatch. (2026, October). From patent cliff to partnership pipeline: A 7-step framework built on 2026 deal data. https://www.drugpatentwatch.com/blog/from-patent-cliff-to-partnership-pipeline-a-7-step-framework-built-on-2026-deal-data/
