On August 18, 2023, the FDA approved Eylea HD, Regeneron’s 8 mg reformulation of its blockbuster eye drug aflibercept. Nine months later, on May 18, 2024, Regeneron’s regulatory exclusivity on the original 2 mg Eylea expired. Two days after that, the FDA approved the first two aflibercept biosimilars [1][2]. The timing was not a coincidence. It was a company preparing to lose a patent fight and building its own replacement before the loss became official.
That sequence is not unique to Regeneron. It is a pattern that repeats across the biggest biologics in the industry: Amgen and pegfilgrastim, Sanofi and insulin glargine, Merck and pembrolizumab. Each company built a next-generation version of its own drug on a timeline that lines up, almost to the month, with the expiration of the patent protecting the original. The industry calls these products bio-betters. The marketing language calls them innovation. The timing tells a different story.
The Short Answer
A bio-better is a molecularly modified version of an approved biologic, filed through the FDA’s full 351(a) pathway as a new drug rather than the abbreviated 351(k) biosimilar pathway [3]. Because it counts as new, it earns its own 12-year exclusivity period and its own patent estate, regardless of what happens to the original molecule’s patents [3][4]. Companies frame this as lifecycle innovation. But when the timing of a bio-better’s approval consistently clusters within months of the original drug’s patent cliff, the more accurate description is a hedge: an acknowledgment, built years in advance, that the original patent estate will not hold.
What a Bio-Better Actually Is (and Isn’t)
The term “bio-better” has no formal FDA definition. It describes a biologic that has been deliberately engineered to improve on a marketed reference product, through a longer half-life, a different formulation, a new delivery route, or a modified target [4]. This distinguishes it from a biosimilar, which must match its reference product’s structure closely enough to be considered “highly similar,” and from a “follow-on biologic,” an older regulatory category used before the biosimilar pathway existed.
The FDA’s Two Pathways: 351(a) New BLA vs. 351(k) Biosimilar
Under the Public Health Service Act, an applicant can seek approval for a biologic in one of two ways. Section 351(k) is the abbreviated biosimilar pathway created by the Biologics Price Competition and Innovation Act (BPCIA) of 2010. It lets an applicant rely on the reference product sponsor’s existing safety and efficacy data, provided the new product is highly similar with no clinically meaningful differences [3]. Section 351(a) is the standard pathway for any new biologic, biosimilar or not. It requires a full data package: independent Phase 1, 2, and 3 trials establishing safety, purity, and potency for every indication sought [4].
351(a) Requirements
A 351(a) filing for a bio-better typically takes over a decade and costs well into the billions of dollars, because the modified molecule is legally a new drug and gets none of the abbreviated pathway’s shortcuts [4].
351(k) Requirements
A 351(k) biosimilar filing is faster and cheaper precisely because it borrows the reference product’s clinical data. It cannot claim to be better. It can only claim to be equivalent.
Why a Bio-Better Restarts the Exclusivity Clock
This is the commercial logic that makes bio-betters attractive regardless of motive. A biologic approved under 351(a) receives 12 years of BPCIA exclusivity from its own approval date, plus a new composition-of-matter patent estate covering whatever was structurally modified. None of that protection depends on what happens to the original molecule’s patents. If the original drug’s patents collapse the day after the bio-better launches, the bio-better’s protection is untouched.
Bio-Better vs. Biosimilar vs. Follow-On Biologic: A Taxonomy
The Timing Tell: Five Bio-Betters and the Patent Clocks Behind Them
Patent expiration dates and FDA approval dates are both public record. Lining them up produces a pattern that a marketing deck rarely shows: bio-better approvals do not arrive on a random schedule relative to the original drug’s loss of exclusivity. In the cases with the most public documentation, they arrive right before it.
Original drug
Company
Original approval
Bio-better
Bio-better approval
Original patent/exclusivity event
Calculated gap
Neupogen (filgrastim)
Amgen
1991
Neulasta (pegfilgrastim)
2002
Zarxio biosimilar approved 2015 [5]
13 years ahead
Rituxan (rituximab)
Genentech/Roche
1997
Gazyva (obinutuzumab)
Nov. 1, 2013 [6]
EU rituximab patent expired 2013 [7]
Same year
Lantus (insulin glargine U-100)
Sanofi
2000
Toujeo (insulin glargine U-300)
Feb. 25, 2015 [8]
Lantus U.S. patent expired February 2015 [9]
Same month
Eylea (aflibercept 2 mg)
Regeneron
2011
Eylea HD (aflibercept 8 mg)
Aug. 18, 2023 [10]
Regulatory exclusivity expired May 18, 2024 [1]
9 months ahead
Keytruda IV (pembrolizumab)
Merck
2014
Keytruda Qlex (subcutaneous)
Sept. 19, 2025 [11]
Core patent expires 2028 [12]
~3 years ahead
Amgen’s Neupogen-to-Neulasta Playbook (1991-2015)
Amgen approved Neupogen in 1991 for chemotherapy-related neutropenia. It approved Neulasta, a PEGylated version requiring one injection per chemotherapy cycle instead of daily shots, in 2002 [5]. Sandoz did not get FDA approval for Zarxio, the first filgrastim biosimilar and the first biosimilar ever approved in the United States, until 2015 [13]. By then, Neulasta had been on the market for 13 years and had become Amgen’s second-best-selling drug, generating close to $3.9 billion in U.S. sales in a single year even after its own patent had expired without a direct challenger [14].
The 33% Decline That Didn’t Touch Neulasta
Amgen reported a 33% year-over-year decline in U.S. Neupogen sales in 2016, the first full year Zarxio competed against it [15]. Neulasta sales were barely affected, because Zarxio was a biosimilar of Neupogen, not of Neulasta. A pegfilgrastim biosimilar did not reach the U.S. market until 2018, when Mylan’s Fulphila was approved [5].
Regeneron’s Eylea HD: Approved Nine Months Before the Cliff
Eylea generated roughly $6 billion a year in U.S. sales at its peak and became one of the most litigated biologics in the country. Regeneron sued at least six aflibercept biosimilar developers under the BPCIA, including Mylan and Biocon over Yesafili, Samsung Bioepis over Opuviz, Celltrion, Formycon, and Amgen over Pavblu [16][17]. It won preliminary and permanent injunctions against several of them [18]. But Regeneron did not rely on litigation alone.
The Nine-Month Window
Eylea HD, an 8 mg reformulation allowing dosing every 12 to 16 weeks instead of every 4 to 8 weeks, was approved August 18, 2023 [10]. Regeneron’s regulatory exclusivity for the original Eylea expired exactly nine months later, on May 18, 2024, and the first interchangeable biosimilars, Yesafili and Opuviz, were approved two days after that [1][2]. Eylea’s U.S. sales still fell 25% year over year in a recent quarter even with the litigation wins, evidence that a bio-better does not fully insulate a franchise once biosimilars start clearing legal hurdles [19].
Sanofi’s Toujeo: Filed for Litigation and R&D at the Same Time
Sanofi’s Lantus, approved in 2000, became the best-selling insulin in the world. In January 2014, Sanofi sued Eli Lilly and Boehringer Ingelheim over their follow-on insulin glargine product, Basaglar, delaying its U.S. launch [20]. At the same time, Sanofi was finishing development of Toujeo, a three-times-more-concentrated version of insulin glargine that could not be substituted unit-for-unit with Lantus [21][22]. The FDA approved Toujeo on February 25, 2015, the same month Lantus’s core U.S. patent expired [8][23].
Basaglar’s Bumpy Path
Basaglar was not approved through the biosimilar pathway at all. Insulin was not classified as a biologic under the BPCIA until 2020, so Basaglar entered as a “follow-on” product under a hybrid application, and it launched in the U.S. in December 2016, nearly two years after Sanofi’s suit was filed [20][24]. Toujeo had a two-year head start to build prescriber habit before any competitor to Lantus reached pharmacy shelves.
Merck’s Keytruda Qlex: Racing a 2028 Expiration
Keytruda generated more than $29 billion in 2024 and accounts for roughly half of Merck’s total revenue [25][26]. Its core patent is set to expire in 2028 [12][26]. The FDA approved Keytruda Qlex, a subcutaneous formulation combined with Halozyme’s hyaluronidase enzyme technology, on September 19, 2025 [11]. Merck has stated it expects to convert 30% to 40% of Keytruda’s solid-tumor market share to the Qlex formulation before the 2028 cliff arrives [26].
Halozyme’s ENHANZE Technology
The subcutaneous shift itself became a new patent fight. Halozyme has alleged that patents in its modified hyaluronidase portfolio cover Keytruda Qlex, and filed suit in April 2025 in the District of New Jersey, alleging infringement of 15 patents [27]. Merck has responded with post-grant review petitions at the Patent Trial and Appeal Board challenging the validity of Halozyme’s patents [27]. The bio-better did not escape patent litigation. It moved the litigation to a different plaintiff.
The Exception That Proves the Rule: Genentech’s Gazyva
Genentech’s Gazyva, a third-generation anti-CD20 antibody, was approved November 1, 2013, for chronic lymphocytic leukemia, more than 16 years after Rituxan first reached the U.S. market [6][28]. On the surface this looks like early, unhurried lifecycle planning rather than a defensive scramble. But Rituxan’s European patents expired that same year, and EU biosimilars, unavailable to Genentech in the U.S. market but visible as a preview of what U.S. patent expiration would eventually allow, launched there in 2017 [7]. Gazyva’s approval date lines up with the first jurisdiction where Rituxan’s patent wall actually came down, even though the U.S. version of that wall held for several more years through BPCIA litigation that delayed Truxima’s full U.S. launch until November 2019 [29][30].
What the Data Shows: Original Timing Analysis
Methodology
This analysis compares each bio-better’s FDA approval date to the most specific, publicly documented patent or exclusivity event affecting its own reference product: a stated patent expiration date, a stated regulatory exclusivity expiration date, or the first competing biosimilar approval date, whichever was most precisely reported in primary sources or contemporaneous trade press. Where a source reported a patent expiring in a given month, that month was used. Where only a year was available, the analysis notes the gap as approximate. Gaps are calculated in calendar time between the two dates and rounded to the nearest reported unit (month or year). This is DrugPatentWatch’s own calculation from the dates in the table above, not a reported industry statistic, and it covers only the five cases with sufficiently precise public dates; it is not a random or exhaustive sample of every biologic that has ever received a bio-better.
Findings
Two of five cases show a gap of a year or less between the bio-better’s approval and a specific, dated loss of exclusivity affecting the original drug: Sanofi’s Toujeo, same month as Lantus’s patent expiration, and Regeneron’s Eylea HD, nine months ahead of Eylea’s exclusivity expiration. A third, Merck’s Keytruda Qlex, was approved roughly three years ahead of a publicly disclosed 2028 patent cliff, still inside the same product-planning horizon as the other two. Only Amgen’s Neulasta, approved 13 years before any filgrastim biosimilar reached the market, breaks that pattern outright, and even that gap reflects a market where the abbreviated biosimilar pathway did not exist until 2010, six years before Amgen faced its first direct pegfilgrastim competitor.
Ten biosimilars of Humira reached the U.S. market by 2024, with some priced up to 90% below the original list price, yet AbbVie’s newer immunology drugs, not a Humira bio-better, absorbed most of the lost revenue [31][32].
The Legal Machinery That Makes This Possible
The BPCIA Patent Dance, Explained
The BPCIA created a structured information exchange, nicknamed the “patent dance,” between a biosimilar applicant and the reference product sponsor. Under 42 U.S.C. § 262(l), a biosimilar applicant is supposed to share its application and manufacturing information with the sponsor after FDA accepts the application, so the two sides can identify which patents are actually in dispute before litigation begins [33]. None of this applies to a bio-better filed under 351(a), because a bio-better is not a biosimilar application at all. It is a standard new-drug filing that never triggers the dance.
The 180-Day Notice Requirement
Separately, the BPCIA requires a biosimilar applicant to give the reference sponsor 180 days’ notice before commercially launching. For years, sponsors argued this notice could only be given after FDA approval, effectively adding six months of exclusivity beyond a biosimilar’s approval date.
Sandoz v. Amgen (2017): The Supreme Court Weakens the Dance
In a unanimous decision issued June 12, 2017, the Supreme Court ruled in Sandoz Inc. v. Amgen Inc. that a biosimilar applicant may refuse to participate in the patent dance altogether, and that the 180-day notice of commercial marketing can be given before FDA approval, not only after it [34][35]. The Court also held that an injunction is not available under federal law to force compliance with the information-exchange step, leaving that question to state law where it might apply [36].
What the Court Actually Held
The practical effect narrowed the reference sponsor’s ability to force early disclosure of a competitor’s manufacturing details. But it did nothing to touch the sponsor’s own bio-better strategy, which runs entirely outside the BPCIA’s dispute-resolution framework.
Why a New BLA Sidesteps the Fight Entirely
This is the structural reason bio-betters are legally cleaner than patent thickets. A patent thicket, like the more than 130 patents AbbVie built around Humira, has to survive validity challenges, inter partes review, and antitrust scrutiny over settlement agreements [37][38]. A bio-better does not need any of its predecessor’s patents to survive. It stands on its own exclusivity, granted independently of whatever a court eventually decides about the original molecule.
When Bio-Betters Cross Into “Product Hopping”
The Namenda Precedent
In 2014, Forest Laboratories and its acquirer Actavis planned to withdraw the twice-daily Alzheimer’s drug Namenda IR from the market ahead of generic entry, forcing patients onto the once-daily Namenda XR before cheaper generic IR became available [39]. New York’s attorney general sued, and the Second Circuit upheld an injunction against the hard switch, establishing that forcibly discontinuing an older drug to block generic substitution can violate antitrust law [39][40].
How AbbVie’s Skyrizi and Rinvoq Test the Line
AbbVie did not build a molecular bio-better of Humira itself. Instead, it relied on a patent thicket of roughly 130 to 136 granted patents, drawn from more than 200 applications, to hold U.S. biosimilars off the market until January 2023, six years after biosimilars had already launched in Europe [37][41][42]. Once biosimilars arrived, AbbVie shifted prescribers toward two unrelated drugs it already had approved for the same conditions, Skyrizi (risankizumab) and Rinvoq (upadacitinib), which trade press has explicitly labeled a form of product hopping [43][44]. Humira’s global revenue fell from a 2022 peak of roughly $21.2 billion to $4.5 billion in 2025, a decline of nearly 80%, while combined Skyrizi and Rinvoq sales reached $25.9 billion in the same year, already ahead of AbbVie’s own 2027 target [45][46].
IQVIA’s Fill-Volume Data
IQVIA data cited by Center for Biosimilars showed adalimumab biosimilar fill volume growing 400% between March and April 2024, even as total adalimumab volume declined, a pattern attributed to patients and prescribers moving to Skyrizi and Rinvoq instead of to a biosimilar of Humira [43].
What Antitrust Enforcers Have (and Haven’t) Done About It
A federal antitrust suit alleging the Humira patent thicket itself was anticompetitive was dismissed by the Northern District of Illinois in June 2020 and affirmed on appeal by the Seventh Circuit, on the reasoning that obtaining and asserting valid patents, even many of them, is not itself illegal absent additional anticompetitive conduct [47][48][49]. No comparable federal court ruling has yet addressed whether shifting prescribers to Skyrizi and Rinvoq, rather than withdrawing Humira as Actavis did with Namenda IR, crosses the line the Second Circuit drew in the Namenda case. The distinction matters: Humira was never pulled from the market, which is the fact pattern that made Namenda actionable.
Who Is Exposed: The Balance Sheet Evidence
Humira’s Fall and Skyrizi/Rinvoq’s Rise
AbbVie generated roughly $187 billion in cumulative Humira revenue between 2002 and 2023 [42]. U.S. sales fell 32% in 2023, the first year of biosimilar competition, and continued declining through 2025 even as AbbVie’s total company revenue set a new record of $61.2 billion, powered almost entirely by Skyrizi and Rinvoq rather than by any direct Humira successor [46][50].
The Reverse Payment Settlements
Part of the Humira delay came from settlements, not court wins. AbbVie reached agreements with roughly ten biosimilar makers, including Amgen, Samsung Bioepis, and Sandoz, allowing European launches starting in October 2018 while keeping U.S. entry locked until January 2023 [41][51]. One policy estimate put the resulting delay in U.S. savings at $2.2 billion for Medicare alone [51].
Eylea’s Erosion Despite Litigation Wins
Regeneron has won permanent and preliminary injunctions against most aflibercept biosimilar developers, and Amgen still launched its biosimilar Pavblu “at risk” in October 2024 after a federal appeals court declined to block it [18][52]. Eylea’s U.S. sales still fell to $1.1 billion in a single recent quarter, down 25% year over year, showing that even a well-timed bio-better and a favorable litigation record only slow erosion, not stop it [19].
32 Patents, One Injunction
In its suit against Amgen, Regeneron alleged infringement of 32 patents covering Eylea’s manufacturing and use [52], a reminder that Eylea HD’s independent exclusivity did not replace the need to keep litigating the original molecule’s patent estate.
Keytruda’s $29.5 Billion Countdown
Keytruda’s scale makes its 2028 cliff the single largest patent event on the industry’s near-term calendar. Merck’s own conversion target of 30% to 40% of solid-tumor volume moving to Keytruda Qlex before 2028 [26] is itself an admission of how much revenue the company expects the original patent estate to fail to protect.
What This Means for Biosimilar Developers
A bio-better does not block a biosimilar of the original molecule. Sandoz still launched Zarxio against Neupogen regardless of Neulasta’s existence, and Mylan and Biocon still won approval for Yesafili against Eylea regardless of Eylea HD [1][5]. What a bio-better does is shrink the addressable market a biosimilar developer is fighting over, by moving prescribers to a differentiated, still-patented product before the biosimilar even launches. Developers evaluating a biosimilar opportunity should treat a sponsor’s bio-better filing history, not just its patent list, as a signal of how much of the reference market will still exist by the time their own product clears litigation.
What This Means for Brand Manufacturers
The five cases above suggest a bio-better filed within roughly a year of a specific, dated patent or exclusivity event preserves more revenue than one filed a decade in advance with no clear trigger, simply because prescribers have less time to develop loyalty to a molecule under active threat. But timing a 351(a) filing to a patent cliff requires starting clinical development years before the cliff is public knowledge, since Phase 1 through 3 trials for a modified biologic routinely take the better part of a decade [4]. A company only gets the tight nine-month window Regeneron achieved with Eylea HD if it started planning for the loss years before litigation outcomes were known.
What This Means for Payers and Patients
None of the five bio-betters in this analysis launched at a lower price than the product they were replacing. Toujeo, Eylea HD, and Keytruda Qlex all entered the market priced at parity with or above their predecessors, since each carries new exclusivity and no biosimilar competition of its own. A payer expecting a patent cliff to produce savings should confirm whether the manufacturer has an FDA-approved bio-better available for the same indication, since utilization can shift there instead of to the biosimilar the payer was budgeting against.
Why Some Bio-Betters Aren’t a Confession at All
Genuine Clinical Advance vs. Defensive Reformulation
Not every bio-better fits this pattern. Amgen’s Aranesp, a longer-acting version of Epogen, and early PEGylation programs across the industry predate the modern biosimilar threat by years and reflect real, independently valuable clinical advances rather than a reaction to a specific legal deadline [5]. The distinguishing question is not whether a bio-better exists, but whether its approval date correlates with a dated, public patent or exclusivity event for its predecessor.
A Proposed Taxonomy of Bio-Better Motivation
Based on the cases examined here, bio-betters can be grouped into three categories. First, proactive lifecycle innovation, where the bio-better arrives many years ahead of any dated patent event and is driven primarily by unmet clinical need, as with early PEGylation programs. Second, cliff-synchronized defense, where the bio-better’s approval falls within about a year of a specific, publicly dated patent or exclusivity expiration, as with Toujeo and Eylea HD. Third, disclosed-horizon defense, where a company publicly states a patent cliff years in advance and times a bio-better’s development to arrive a few years ahead of it, as with Keytruda Qlex. This is an original classification built from the five cases above, not an established FDA or industry category, and a larger sample would be needed to test how common each category is across the full universe of approved biologics.
The DrugPatentWatch Angle: Tracking the Timing, Not Just the Molecule
Most patent-tracking tools flag when a drug’s listed patents expire. Few flag when a sponsor has quietly filed a 351(a) application for a modified version of the same molecule, which is the earlier and more useful signal for anyone trying to model how much of a franchise’s revenue will actually be exposed on the expiration date. DrugPatentWatch’s value in this analysis was in cross-referencing patent and exclusivity expiration dates against FDA approval records for each bio-better, the same kind of dated comparison a biosimilar developer or a payer contracting team needs before assuming a patent cliff will translate into an open market.
What Happens Next
The 2028 Keytruda Test
Keytruda Qlex is the clearest live test of whether a bio-better filed roughly three years ahead of a known cliff can hold significant volume once 2028 arrives, and whether Halozyme’s litigation over the enabling hyaluronidase technology becomes the new front in a fight that pembrolizumab’s own composition patents were expected to lose [12][27].
The Next Wave: GLP-1s and the Ozempic-to-Wegovy Playbook
Novo Nordisk’s Ozempic (semaglutide, weekly dosing) and Wegovy (semaglutide, higher dose for obesity) already show the same underlying logic applied through indication and dosing strategy rather than molecular change, without requiring a new composition of matter [53]. As semaglutide’s own patents draw closer to expiration, watching whether Novo Nordisk files a genuinely modified successor molecule, rather than another label extension of the same molecule, will show whether the GLP-1 class follows the cliff-synchronized pattern documented here.
FAQ
Does a bio-better delay biosimilar approval of the original drug? No. A bio-better filed under 351(a) has no legal effect on a separate biosimilar application referencing the original molecule. Zarxio’s approval against Neupogen was unaffected by Neulasta’s existence [1][5].
Can a biosimilar be filed against a bio-better itself? Yes, once the bio-better’s own 12-year exclusivity expires and its patents are challenged or expire, it becomes a reference product like any other. No pegfilgrastim biosimilar existed until 2018, 16 years after Neulasta’s approval [5].
Is “biobetter” an FDA-recognized term? No. The FDA does not use “bio-better” in regulation. It is industry shorthand for a modified biologic approved through the standard 351(a) new-drug pathway [3][4].
Why didn’t AbbVie build a Humira bio-better? AbbVie instead relied on a patent thicket of roughly 130 patents to delay biosimilars, then shifted prescribers to two unrelated drugs, Skyrizi and Rinvoq, once biosimilars arrived [37][43].
Does the BPCIA patent dance apply to bio-betters? No. The patent dance under 42 U.S.C. § 262(l) applies only to 351(k) biosimilar applications. A 351(a) bio-better filing never triggers it [33].
What did Sandoz v. Amgen actually decide? The Supreme Court held in 2017 that a biosimilar applicant may skip the patent dance entirely and may give the required 180-day marketing notice before FDA approval, not only after it [34][35].
Is product hopping illegal? It depends on the conduct. Forcibly withdrawing an older drug to block generic substitution, as in the Namenda case, has been found to violate antitrust law. Simply promoting a newer drug alongside an older one facing biosimilar competition, without withdrawing the older product, has not been tested the same way in court [39][47].
How much of Eylea’s exclusivity gap did Eylea HD cover? Eylea HD was approved nine months before Eylea’s regulatory exclusivity expired, giving Regeneron a head start before any biosimilar reached the market [1][10].
Did Toujeo launch cheaper than Lantus? No. Toujeo entered the market at a comparable or higher price point than Lantus, and it carries its own patent protection separate from Lantus’s expired patents [21].
Will Keytruda Qlex fully offset Keytruda’s 2028 patent cliff? Unknown. Merck has stated a target of converting 30% to 40% of solid-tumor volume to the Qlex formulation, which would offset a meaningful share of exposure but not all of it, and Qlex itself is now the subject of separate patent litigation from Halozyme [26][27].
Key Takeaways
Regeneron’s Eylea HD was approved nine months before Eylea’s regulatory exclusivity expired; the first Eylea biosimilars were approved two days after that exclusivity ended [1][10].
Sanofi’s Toujeo was approved the same month Lantus’s core U.S. patent expired [8][23].
Merck’s Keytruda Qlex was approved roughly three years ahead of pembrolizumab’s disclosed 2028 patent cliff, and is itself now facing separate patent litigation from Halozyme over the technology that enables it [12][27].
AbbVie did not build a molecular bio-better of Humira. It used a patent thicket of roughly 130 patents to delay biosimilars until 2023, then shifted revenue to two unrelated drugs, Skyrizi and Rinvoq, which grew to $25.9 billion in combined 2025 sales as Humira fell to $4.5 billion [37][45][46].
A bio-better does not block or delay a biosimilar filed against the original molecule; it only shifts prescriber volume before the biosimilar arrives [1][5].
None of the five bio-betters examined launched at a lower price than the product they succeeded.
References
Goodwin. (2024, June 8). Updates on aflibercept biosimilar approvals and BPCIA litigation. https://www.goodwinlaw.com/en/insights/blogs/2024/06/updates-on-aflibercept-biosimilar-approvals-and-bpcia-litigation
Center for Biosimilars. (2024, May 21). FDA approves first Eylea biosimilars. https://www.centerforbiosimilars.com/view/fda-approves-first-eylea-biosimilars
Sandoz Inc. v. Amgen Inc., 137 S. Ct. 1664 (2017). https://www.supremecourt.gov/opinions/16pdf/15-1039_1b8e.pdf
DrugPatentWatch. (2026, March 3). The future of biologics and bio-betters: A strategic deep dive into next-generation therapies. https://www.drugpatentwatch.com/blog/the-future-of-biologics-bio-betters-and-the-dawn-of-next-generation-therapies/
BioPharma Dive. (2017, December 14). The 2018 biosimilar litigation landscape: A primer. https://www.biopharmadive.com/news/the-2018-biosimilar-litigation-landscape-a-primer/512982/
Pharmacy Times. (2026, June 20). Obinutuzumab (Gazyva). https://www.pharmacytimes.com/view/obinutuzumab-gazyva
pharmaphorum. First Rituxan biosimilar Truxima set to make its debut in US. https://pharmaphorum.com/news/first-rituxan-biosimilar-truxima-set-to-makes-its-debut-in-us
Fierce Pharma. (2015, February 25). Sanofi receives FDA approval of once-daily basal insulin Toujeo. https://www.fiercepharma.com/pharma/sanofi-receives-fda-approval-of-once-daily-basal-insulin-toujeo%C2%AE
AJMC. FDA approves Toujeo, basal insulin seen as successor to Lantus. https://www.ajmc.com/view/fda-approves-toujeo-basal-insulin-seen-as-successor-to-lantus
Regeneron Pharmaceuticals. (2023, August 18). EYLEA HD (aflibercept) Injection 8 mg approved by FDA. https://investor.regeneron.com/news-releases/news-release-details/eylea-hd-aflibercept-injection-8-mg-approved-fda-treatment-wet
Pharmacy Times. The FDA approval of Keytruda Qlex: A subcutaneous version of pembrolizumab. https://www.pharmacytimes.com/view/the-fda-approval-of-keytruda-qlex-a-subcutaneous-version-of-pembrolizumab
Fierce Pharma. (2025, September 20). Merck scores FDA approval for subcutaneous Keytruda, securing potential blockbuster protection. https://www.fiercepharma.com/pharma/merck-scores-fda-approval-subcutaneous-keytruda
Justia. Amgen Inc. v. Sandoz Inc., No. 18-1551 (Fed. Cir. 2019). https://law.justia.com/cases/federal/appellate-courts/cafc/18-1551/18-1551-2019-05-08.html
pharmaphorum. FDA finally approves Sandoz’s Neulasta biosimilar, but will Amgen put up a fight? https://pharmaphorum.com/news/fda-finally-approves-sandozs-neulasta-biosimilar-but-will-amgen-put-up-a-fight
Bloomberg Law. (2017, December 20). Sandoz biosimilar process doesn’t infringe Amgen patent. https://www.bna.com/sandoz-biosimilar-process-n73014473460/
Center for Biosimilars. (2024, May 21). FDA approves first Eylea biosimilars. https://www.centerforbiosimilars.com/view/fda-approves-first-eylea-biosimilars
Loeb & Loeb. (2025, February 19). The landscape of Regeneron’s Eylea litigation after the Federal Circuit affirmed two preliminary injunction orders. https://quicktakes.loeb.com/post/102k069/the-landscape-of-regenerons-eylea-litigation-after-the-federal-circuit-affirmed
Biosimilars Review & Report. (2025, January 3). Amgen wins injunction battle against Regeneron, paving way for aflibercept launch. https://biosimilarsrr.com/2024/10/29/amgen-wins-injunction-battle-against-regeneron-paving-way-for-aflibercept-launch/
Fierce Pharma. (2025, October 22). Regeneron settles Eylea patent dispute with Celltrion, allowing another biosimilar to launch at end of 2026. https://www.fiercepharma.com/pharma/regeneron-settles-eylea-patent-dispute-celltrion-allowing-another-biosimilar-launch-2026
Pharmaceutical Technology. (2017, January 5). The first follow-on biologic insulin is launched in the US. https://www.pharmaceutical-technology.com/research-reports/researchreportthe-first-follow-on-biologic-insulin-is-launched-in-the-us-5710019/
GaBI Online. Biosimilars of insulin glargine. https://www.gabionline.net/biosimilars/general/Biosimilars-of-insulin-glargine
Center for Biosimilars. With Lantus under pressure from follow-on, Sanofi releases Phase 3 results for Toujeo in pediatric population. https://www.centerforbiosimilars.com/view/with-lantus-under-pressure-from-followon-sanofi-releases-phase-3-results-for-toujeo-in-pediatric-population
Drugs.com. Toujeo SoloStar (insulin glargine [rDNA origin]) FDA approval history. https://www.drugs.com/history/toujeo-solostar.html
MedXDRG. Is insulin glargine the same as Lantus? Guide to products. https://medxdrg.com/is-insulin-glargine-the-same-as-lantus-understanding-brand-biosimilar-and-interchangeable-options
DrugPatentWatch. (2026, May 22). Bio-betters are eating biosimilars: The $150B patent strategy reshaping biologic competition. https://www.drugpatentwatch.com/blog/bio-betters-are-eating-biosimilars-the-150b-patent-strategy-reshaping-biologic-competition/
FirstWord Pharma. (2025, December 16). Physician views preview: Tracking early US adoption of subcutaneous Keytruda. https://firstwordpharma.com/story/6745952
Merck & Co. (2025). Form 10-Q, FY2025. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/310158/000162828025021834/mrk-20250331.htm
AHDB Online. (2014, March). Gazyva (obinutuzumab) for chronic lymphocytic leukemia: First FDA-approved breakthrough therapy in oncology. https://www.ahdbonline.com/issues/2014/march-2014-volume-7-special-feature-fifth-annual-payers-guide-to-new-fda-approvals/gazyva-obinutuzumab-for-chronic-lymphocytic-leukemia-first-fda-approved-breakthrough-therapy-in-oncology
Goodwin. (2026, July 9). Celltrion and Teva’s Truxima becomes first interchangeable rituximab biosimilar in U.S. https://www.goodwinlaw.com/en/insights/blogs/2026/07/celltrion-and-tevas-truxima-becomes-first-interchangeable-rituximab-biosimilar-in-us
Big Molecule Watch. (2020, May 4). TRUXIMA launches as first U.S. Rituxan biosimilar approved for RA. https://www.bigmoleculewatch.com/2020/05/04/truxima-launches-as-first-u-s-rituxan-biosimilar-approved-for-ra/
Managed Healthcare Executive. AbbVie plays its ace cards against Humira’s decline. https://www.managedhealthcareexecutive.com/view/abbvie-plays-its-ace-cards-against-humira-s-decline
Center for Biosimilars. (2024, November 6). Skyrizi overtakes Humira: “Product hopping” leaves biosimilar market in limbo. https://www.centerforbiosimilars.com/view/skyrizi-overtakes-humira-product-hopping-leaves-biosimilar-market-in-limbo
K&L Gates. (2019, May 23). Amgen v. Sandoz: New developments in biosimilars litigation. https://www.klgates.com/Amgen-v-Sandoz—New-Developments-in-Biosimilars-Litigation-05-23-2019
Mintz. (2017, June 14). Amgen v. Sandoz: The Supreme Court’s first biosimilars ruling. https://www.mintz.com/insights-center/viewpoints/2017-06-14-amgen-v-sandoz-supreme-courts-first-biosimilars-ruling
National Law Review. Amgen v. Sandoz: The Supreme Court’s first biosimilars ruling. https://natlawreview.com/article/amgen-v-sandoz-supreme-court-s-first-biosimilars-ruling
Food and Drug Law Institute. (2018, February 27). Case note: Sandoz v. Amgen. https://www.fdli.org/2017/08/case-note-sandoz-v-amgen/
Qz. (2022, December 14). How AbbVie denied Americans access to fair competition for Humira. https://qz.com/humira-abbvie-competition-from-cheaper-biosimilars-1849876888
SSRN (Knox, R., & Curfman, G.). (2022, October 11). The Humira patent thicket, the Noerr-Pennington doctrine, and antitrust’s patent problem. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4215822
Forbes. (2024, May 21). How drug companies stifle competition with ‘product hopping.’ https://www.forbes.com/sites/theapothecary/2024/05/21/how-drug-companies-stifle-competition-with-product-hopping/
Haug Partners. (2024, September 26). Pharmaceutical antitrust update: Courts address how and when product hopping may violate the antitrust laws. https://haugpartners.com/article/pharmaceutical-antitrust-update-courts-address-how-and-when-product-hopping-may-violate-the-antitrust-laws/
Lexology/Bristows. (2022, August 8). What’s wrong with having lots of patents? Humira ‘patent thicket’ survives antitrust challenge. https://www.lexology.com/library/detail.aspx?g=80412d04-8389-4dba-9427-efe424a6f794
Center for Biosimilars. (2024, November 6). Skyrizi overtakes Humira: “Product hopping” leaves biosimilar market in limbo. https://www.centerforbiosimilars.com/view/skyrizi-overtakes-humira-product-hopping-leaves-biosimilar-market-in-limbo
AJMC. Humira: The first $20 billion drug. https://www.ajmc.com/view/humira-the-first-20-billion-drug
Fierce Pharma. (2024, February 2). As Humira plummets, AbbVie dials up Rinvoq and Skyrizi estimates to a combined $27B. https://www.fiercepharma.com/pharma/amid-humira-trough-abbvie-dials-rinvoq-and-skyrizi-sales-goals-combined-27b
Markman Advisors. (2020, June 10). Why was the Humira “patent thicket” antitrust case against AbbVie dismissed? https://www.markmanadvisors.com/blog/2020/6/10/why-was-the-humira-patent-thicket-antitrust-case-against-abbvie-dismissed
Bristows. (2022, August 8). What’s wrong with having lots of patents? Humira ‘patent thicket’ survives antitrust challenge. https://www.bristows.com/news/whats-wrong-with-having-lots-of-patents-humira-patent-thicket-survives-antitrust-challenge/
Petrie-Flom Center, Harvard Law School. (2021, January 6). AbbVie Humira antitrust patent thicket. https://petrieflom.law.harvard.edu/2021/01/06/abbvie-humira-antitrust-patent-thicket/
Clinical Trials Arena. (2025, January 16). JP Morgan 2025: AbbVie counts on Skyrizi and Rinvoq to fill Humira-sized hole. https://www.clinicaltrialsarena.com/news/jp-morgan-2025-abbvie-counts-on-skyrizi-and-rinvoq-to-fill-humira-sized-hole/
Arnold Ventures. (2026, May 14). Anticompetitive behaviors policy brief. https://www.arnoldventures.org/resources/anticompetitive-behaviors-policy-brief-sept-18-2024
Big Molecule Watch / BR&R. (2025, January 3). Amgen wins injunction battle against Regeneron, paving way for aflibercept launch. https://biosimilarsrr.com/2024/10/29/amgen-wins-injunction-battle-against-regeneron-paving-way-for-aflibercept-launch/
DrugPatentWatch. (2026, May 22). Bio-betters are eating biosimilars: The $150B patent strategy reshaping biologic competition. https://www.drugpatentwatch.com/blog/bio-betters-are-eating-biosimilars-the-150b-patent-strategy-reshaping-biologic-competition/
