US Patent 6,939,539: Claim Scope, Expiration, Orange Book Status, and Glatiramer Acetate Patent Landscape

US Patent 6,939,539 protects a molecular-weight-defined form of copolymer-1, the active pharmaceutical ingredient in glatiramer acetate products such as Copaxone. Its claims cover a non-uniform mixture of glutamic acid, lysine, alanine, and tyrosine polypeptides with an average molecular weight generally between 4 and 9 kilodaltons, together with pharmaceutical compositions and multiple-sclerosis treatment methods.

The patent was granted on September 6, 2005, and its ordinary patent term expired on December 11, 2021. It therefore no longer provides enforceable US patent exclusivity. Its commercial importance was concentrated in the pre-2022 period, when generic manufacturers sought approval for glatiramer acetate products and Teva relied on the patent in Hatch-Waxman litigation and Orange Book listings.

What does US Patent 6,939,539 cover?

The patent covers three related claim categories:

Claim category	Claims	Principal limitation
Copolymer-1 composition	1-11	Non-uniform glutamic acid, lysine, alanine, and tyrosine polypeptide mixture with specified molecular-weight characteristics
Pharmaceutical composition	12-22	The copolymer-1 composition combined with a pharmaceutically acceptable excipient
Treatment method	23-33	Administration of the pharmaceutical composition to a patient with multiple sclerosis

The patent does not claim a single defined peptide sequence. It claims a heterogeneous mixture of polypeptides, which is characteristic of glatiramer acetate. The scope is therefore determined by compositional identity and molecular-weight distribution rather than by a discrete amino-acid sequence.

What active ingredient is covered?

The claimed material is copolymer-1, commonly known as glatiramer acetate. It is composed of polypeptide chains containing four amino acids:

L-glutamic acid
L-lysine
L-alanine
L-tyrosine

The claim language uses “copolymer-1 composition,” while commercial products generally use the term glatiramer acetate. The patent is directed to the polypeptide mixture and its molecular-weight profile, not to a conventional small-molecule active ingredient.

Is the composition uniform or sequence-defined?

No. Claims 1 and 12 expressly require that the mixture be “non-uniform with respect to molecular weight and sequence.” That limitation distinguishes the claimed product from a single peptide, a uniform polymer, or a composition consisting of one defined sequence.

This feature also reflects the manufacturing reality of glatiramer acetate. The product is a distribution of related polypeptide chains rather than a single molecular entity.

How do the molecular-weight limitations define claim scope?

The core technical limitation is the molecular-weight distribution. The claims use several overlapping boundaries.

Limitation	Claims
Average molecular weight of about 4 to about 9 kDa	1, 12
More than 75% of polypeptides between about 2 and 20 kDa	2, 4, 9, 13, 15, 20
Less than 5% above 40 kDa	3, 4, 14, 15
Average molecular weight of 6.25 to 8.4 kDa	5, 10, 16, 21
Average molecular weight of about 4 to about 8.6 kDa	6, 17
Average molecular weight of about 5 to about 9 kDa	7, 18
Less than 2.5% above 40 kDa	8-10, 19-21
Distribution substantially corresponding to Figure 1 or Figure 2, with average molecular weight of about 7.7 kDa	11, 22

The dependent claims create nested fallbacks. A composition may fall within claim 1 but outside claim 5, for example, if its average molecular weight is 8.7 kDa. Conversely, a product satisfying claim 10 would also need to satisfy the limitations inherited from claims 8 and 9.

What is the strongest composition claim?

Claim 10 is among the narrowest composition claims. It requires:

A non-uniform copolymer-1 mixture;
An average molecular weight within 6.25 to 8.4 kDa;
Less than 2.5% of the polypeptides above 40 kDa; and
More than 75% of the polypeptides between 2 and 20 kDa.

Claim 11 takes a different approach by referring to molecular-weight distribution curves in the patent figures and an average molecular weight of about 7.7 kDa. That claim can raise technical questions about how closely an accused product must match the disclosed curves.

What do the pharmaceutical-composition claims add?

Claims 12-22 largely repeat claims 1-11 but add a pharmaceutically acceptable excipient and a therapeutically effective dose for treating multiple sclerosis.

The added excipient limitation may include conventional formulation components such as:

Water for injection
Tonicity agents
Stabilizers
Buffers
Preservatives, if used
Other formulation components compatible with parenteral administration

The claims do not identify a specific excipient, concentration, syringe configuration, injection volume, or dosing frequency. Their principal value comes from tying the molecular-weight-defined copolymer-1 mixture to a pharmaceutical product.

A product containing the claimed copolymer mixture but lacking a pharmaceutically acceptable excipient would implicate the composition claims in claims 1-11, but not necessarily claims 12-22.

What do the method-of-use claims cover?

Claims 23-33 require administering one of the pharmaceutical compositions to a patient suffering from multiple sclerosis.

These claims are dependent method claims. They inherit the composition limitations from claims 12-22, including the molecular-weight and distribution requirements. They do not specify:

A particular multiple-sclerosis subtype
Relapsing-remitting versus progressive disease
A dose amount
A dosing interval
Subcutaneous versus another administration route
A treatment duration
A clinical endpoint

The broad method language increases potential claim scope, but infringement still depends on whether the administered product satisfies the inherited composition limitations.

When did US Patent 6,939,539 expire?

US Patent 6,939,539 expired on December 11, 2021, based on the patent’s effective filing and priority history. The patent was granted on September 6, 2005.

Event	Date
Effective priority or filing basis	December 11, 2000
US patent grant	September 6, 2005
Standard 20-year patent-term endpoint	December 11, 2021
Current enforceability	Expired

The patent did not create current US exclusivity for glatiramer acetate. Any patent-term adjustment, patent-term extension, or terminal-disclaimer issue would need to be checked against the USPTO patent file and Orange Book record, but the commercially relevant listed expiration date was December 11, 2021.

What was the Orange Book status of US Patent 6,939,539?

The patent was listed in the FDA Orange Book for glatiramer acetate products associated with Copaxone. Its listing supported Hatch-Waxman patent certifications by ANDA applicants.

The patent’s Orange Book significance was primarily tied to product composition and molecular-weight distribution. It was not principally a regimen patent. Later patents in the Copaxone estate addressed dosing schedules and other product or formulation aspects, especially the 40 mg three-times-weekly product.

The Orange Book listing did not itself establish validity or infringement. It supplied the regulatory mechanism through which an ANDA applicant could make a Paragraph IV certification and trigger patent litigation.

Which companies challenged the Copaxone patent estate?

The principal competitive challengers in the US glatiramer acetate market included Sandoz, Mylan, and other generic or follow-on manufacturers. The challenges targeted multiple patents in Teva’s Copaxone estate, not necessarily US 6,939,539 alone.

The principal challenge mechanisms were:

Paragraph IV certifications alleging invalidity, unenforceability, or non-infringement;
Declaratory and infringement litigation under the Hatch-Waxman framework;
FDA ANDA review for generic glatiramer acetate;
Commercial launch after patent expiry, litigation resolution, or settlement.

The most important commercial disputes involved the broader Copaxone patent portfolio, including patents covering molecular-weight characteristics, dosing regimens, and the 40 mg formulation or administration schedule.

What Paragraph IV risks did US Patent 6,939,539 create?

An ANDA applicant seeking approval for a glatiramer acetate product could make a Paragraph IV certification asserting that the patent was:

Invalid;
Unenforceable; or
Not infringed by the proposed product.

For this patent, the principal technical dispute points were likely to include:

The meaning of “average molecular weight”;
The analytical method used to measure molecular weight;
Whether the claimed percentages are calculated on a molar-fraction basis;
Whether the proposed product contains less than 5% or less than 2.5% above 40 kDa;
Whether the product distribution is substantially similar to the curves in Figures 1 and 2;
Whether “copolymer-1” is sufficiently defined;
Whether the claims are enabled across the claimed molecular-weight ranges;
Whether the prior art disclosed the claimed distribution.

A generic applicant could avoid literal infringement by manufacturing a distribution outside one or more claimed numerical boundaries. The practical difficulty is that glatiramer acetate products may have overlapping distributions even where their manufacturing processes differ.

What litigation affected US Patent 6,939,539?

The patent was part of Teva’s broader US litigation strategy against generic glatiramer acetate applicants. The most significant appellate decisions concerning Copaxone involved related Teva patents and addressed claim construction, obviousness, infringement, and the scope of protection available for later Copaxone products.

The litigation environment had several recurring issues:

Claim construction

The interpretation of “average molecular weight” was central. Different analytical approaches, including number-average, weight-average, and distribution-based measurements, can produce materially different results for a heterogeneous polypeptide mixture.

Indefiniteness and measurement reproducibility

Because the claimed product is defined by statistical distribution, an accused party could challenge whether the claims identify a sufficiently objective boundary. The relevant question is whether a skilled person can determine, using accepted analytical methods, whether a product meets the claimed percentage and average-molecular-weight limitations.

Anticipation and obviousness

Earlier copolymer-1 disclosures created potential prior-art issues. The patent’s defensibility depended on whether the prior art disclosed the claimed molecular-weight distribution and whether the claimed range would have been an obvious manufacturing target.

Infringement testing

Testing would likely require multiple analytical measurements, batch sampling, and a defined method for converting molecular-weight data into molar fractions. A single certificate of analysis would not necessarily resolve all infringement questions.

How strong was the patent estate for Copaxone?

The estate was commercially strong before the December 2021 expiration of US 6,939,539, but its protection was distributed across several patents rather than concentrated in one claim set.

Protection type	Representative subject matter	Strategic role
Original copolymer-1 patents	Basic glatiramer composition and use	Foundational protection; largely expired before the later estate
US 6,939,539	Molecular-weight distribution and composition	Product-quality and composition barrier
Later Copaxone patents	40 mg dosing and administration schedules	Delayed generic competition for the higher-strength product
Formulation and device patents	Syringe, packaging, delivery, or formulation features	Potential product-specific barriers
Manufacturing know-how	Reaction conditions, purification, molecular-weight control	Non-patent barrier and quality-control advantage

The 6,939,539 patent was stronger against products that closely matched the claimed molecular-weight distribution. It was weaker against products designed around the numerical boundaries or products supported by a different analytical characterization.

How did the patent compare with the 40 mg Copaxone patent strategy?

The 20 mg and 40 mg products presented different exclusivity profiles.

Issue	20 mg glatiramer acetate	40 mg glatiramer acetate
Typical dosing	Daily injection	Three times weekly
Relevance of US 6,939,539	Direct composition relevance	Direct composition relevance
Main later patent risk	Composition and product patents	Regimen and product-specific patents
Generic approval pathway	ANDA	ANDA, with additional patent certifications
Main commercial barrier	Molecular-weight and product characterization	Dosing-regimen and later Orange Book patents

US 6,939,539 did not independently protect the three-times-weekly regimen. A competitor using the same molecular-weight-defined glatiramer acetate could still face separate patents directed to the 40 mg dosing schedule.

Did this patent create biosimilar risk or generic risk?

The principal risk was generic, not biosimilar.

Glatiramer acetate is a synthetic polypeptide mixture regulated through the small-molecule drug framework for ANDA purposes. FDA approved generic glatiramer acetate products through abbreviated new drug applications. The products were not approved as biosimilars under the Public Health Service Act.

The relevant competitive risks were:

ANDA approval;
Paragraph IV patent litigation;
Product-by-product analytical characterization;
Substitution under state pharmacy laws;
Price competition after market entry;
Manufacturing consistency across commercial batches.

What manufacturing and intellectual-property barriers remain?

After patent expiry, manufacturing barriers remain important even when the composition patent no longer applies.

Molecular-weight control

The manufacturer must control polymerization and hydrolysis conditions sufficiently to produce a reproducible distribution. Excess high-molecular-weight material may affect both product quality and historical patent boundaries.

Batch consistency

Because glatiramer acetate is a heterogeneous mixture, release specifications require more extensive characterization than a single-molecule drug. Variability in chain length, amino-acid composition, and distribution can complicate comparability.

Analytical methods

The method used to measure average molecular weight and the percentage above 40 kDa can affect regulatory and litigation conclusions. Analytical validation, reference standards, and method comparability are central technical issues.

Process know-how

Patents may expire while manufacturing know-how remains protected as confidential information. Process optimization, raw-material control, purification, and analytical release testing can continue to limit the number of credible commercial suppliers.

What generic launch scenarios existed after expiration?

After the December 2021 expiration of US 6,939,539, the patent itself no longer blocked launch. Remaining launch constraints could still arise from:

Other unexpired Orange Book patents;
Patent litigation involving later Copaxone strengths or regimens;
FDA review of the ANDA;
Manufacturing readiness;
State substitution rules;
Commercial supply and reimbursement agreements.

A generic product that avoided or defeated other listed patents could launch after approval without relying on US 6,939,539 as a continuing barrier.

What was the revenue exposure for Teva?

Copaxone was one of Teva’s largest products before generic competition. Global Copaxone revenue was measured in the billions of dollars annually at its peak, with US revenue representing a major share. Revenue declined materially after generic glatiramer acetate products entered the US market and after the 40 mg product faced competition.

The patent’s economic value was therefore front-loaded. Its principal value was the ability to delay or complicate generic entry before December 2021, rather than to sustain exclusivity after that date.

What geographic coverage did the patent provide?

US 6,939,539 provided protection only in the United States. Corresponding foreign applications or patents may have protected related glatiramer acetate compositions in other jurisdictions, but foreign rights required separate analysis by country.

The US expiration date did not automatically determine:

European Patent Office expiration;
Canadian expiration;
Japanese expiration;
Australian expiration;
Patent status in emerging markets;
Regulatory exclusivity in any non-US jurisdiction.

Patent term, supplementary protection certificates, prosecution history, opposition proceedings, and national validation differ by jurisdiction.

Key Takeaways

US 6,939,539 covers a non-uniform glatiramer acetate polypeptide mixture composed of glutamic acid, lysine, alanine, and tyrosine.
The central limitations are average molecular weight and the percentage of material within or above specified molecular-weight ranges.
Claims 1-11 cover the composition itself.
Claims 12-22 cover pharmaceutical compositions containing the copolymer and an excipient.
Claims 23-33 cover treatment of multiple sclerosis using those pharmaceutical compositions.
The patent does not claim a single peptide sequence or a defined dosing schedule.
Its commercially relevant expiration date was December 11, 2021.
Generic, not biosimilar, competition was the principal threat.
The patent was one component of Teva’s broader Copaxone estate, which also included later patents directed to dosing regimens, formulations, devices, and product-specific protections.
Current US exclusivity cannot be based on US 6,939,539 because the patent has expired.

FAQs About US Patent 6,939,539

Does US Patent 6,939,539 cover all glatiramer acetate products?

No. It covers products meeting the claimed amino-acid composition and molecular-weight limitations. A product may be glatiramer acetate but fall outside one or more claimed distribution requirements.

Is US Patent 6,939,539 still enforceable?

No. The patent expired on December 11, 2021, and does not provide current US patent exclusivity.

Does the patent cover Copaxone 40 mg three-times-weekly dosing?

The patent covers the molecular-weight-defined copolymer composition and related pharmaceutical composition. It does not independently require the 40 mg three-times-weekly regimen. Separate Copaxone patents addressed regimen-specific protection.

Can a generic manufacturer avoid this patent by using a different average molecular weight?

A product outside the claimed ranges may avoid literal infringement, but the complete molecular-weight distribution and all inherited claim limitations must be assessed. Altering only the reported average may not avoid infringement if other claim elements remain satisfied.

Are glatiramer acetate generics biosimilars?

No. FDA-approved glatiramer acetate competitors were generally approved through the ANDA pathway as generic drugs, not through the biosimilar pathway.

References

U.S. Patent No. 6,939,539. (2005). Copolymer-1 compositions and methods of use. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2021). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (2017). FDA approves first generic version of widely used multiple sclerosis drug. FDA.
U.S. Patent and Trademark Office. (2024). Patent term calculator and patent term adjustment information. United States Department of Commerce.
Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., 789 F.3d 1335 (Fed. Cir. 2015).
Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., 809 F.3d 1286 (Fed. Cir. 2015).
Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., 876 F.3d 1359 (Fed. Cir. 2017).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0762888	⤷ Start Trial	90987	Luxembourg	⤷ Start Trial
European Patent Office	0762888	⤷ Start Trial	C300096	Netherlands	⤷ Start Trial
European Patent Office	0762888	⤷ Start Trial	C300251	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,939,539