US Patent 6,617,317: Scope, Bortezomib Coverage, Expiration and Generic Risk

US Patent 6,617,317 covers injectable compositions containing a broad class of N-substituted dipeptidyl boronic acids, including bortezomib, the active ingredient in Velcade. Claim 12 is the clearest product-specific claim because it expressly recites N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid, the chemical entity generally identified as bortezomib.

The patent is important for three reasons:

It claims bortezomib in an injectable composition intended for intravenous, intramuscular or subcutaneous administration.
It claims broad structural genera around the bortezomib molecule.
It does not primarily claim a manufacturing process, a treatment method, or a particular dosing schedule.

The commercial blocking value of US 6,617,317 therefore depends on whether an accused product contains bortezomib in a covered composition and whether the patent remained enforceable against the relevant generic launch date.

What drug does US Patent 6,617,317 cover?

US 6,617,317 covers boronic acid-containing peptide compositions, with the most commercially significant compound being bortezomib.

Item	Description
Patent	US 6,617,317
Patent type	Pharmaceutical composition and compound genus claims
Principal active compound	Bortezomib
Chemical description	N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid
Brand	Velcade
Sponsor/originator	Millennium Pharmaceuticals, later associated with Takeda
Administration in claims	Intravenous, intramuscular or subcutaneous
Therapeutic class	Proteasome inhibitor
FDA product	Bortezomib for injection
Primary generic pathway	ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act
Biologic status	Not a biologic; biosimilar pathway does not apply

Bortezomib is a small-molecule dipeptidyl boronic acid proteasome inhibitor. Its boronic acid group binds the catalytic site of the 26S proteasome, producing the pharmacologic activity used in multiple myeloma and mantle cell lymphoma.

What are the independent claims of US 6,617,317?

The supplied claim set contains three independent composition claims: claims 1, 12, 13 and 21. Claims 1, 13 and 21 are Markush claims. Claim 12 is a compound-specific composition claim.

Claim 1: Pyrazinyl acyl or sulfonyl genus

Claim 1 covers a composition that forms an injectable solution after combination with physiologically acceptable saline. The compound must have:

P equal to a pyrazinyl carbonyl or pyrazinyl sulfonyl group;
X2 equal to -C(O)-NH-;
two hydroxy groups at Z1 and Z2;
A equal to zero; and
variable peptide-side substituents at R2 and R3.

The claim covers a large family of dipeptidyl boronic acids. It is narrower than claim 13 with respect to P because claim 1 limits P to pyrazinyl derivatives. It is broader than claim 12 because it does not identify a single amino-acid sequence.

Claim 12: Specific bortezomib composition

Claim 12 recites:

A composition ... comprising N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid.

This is the strongest claim in the patent for direct bortezomib analysis. It does not depend on the broader structural definitions in claim 1. An injectable composition containing bortezomib is the principal commercial product target of the claim.

The claim is directed to a composition that becomes suitable for administration when combined with a physiologically acceptable aqueous carrier. The claim does not require a particular vial size, concentration, excipient system, reconstitution volume, container, or dosing regimen.

Claim 13: Expanded heteroaryl genus

Claim 13 broadens P to include carbonyl or sulfonyl groups bearing:

quinolinyl;
pyrazinyl;
pyridyl;
quinoxalinyl;
furyl;
pyrrolyl; or
N-morpholinyl substituents.

This claim reaches compounds beyond bortezomib. It includes bortezomib because the pyrazinyl carbonyl group falls within the defined P group.

Claim 21: Alternative N-substituent genus

Claim 21 changes the P definition to H or an amino-group-protecting moiety and narrows R2 to naphthylmethyl, pyridylmethyl or quinolylmethyl. It therefore covers a different portion of the disclosed compound space and is less directly aligned with the commercial bortezomib structure than claim 12.

What chemical structure does claim 12 cover?

Claim 12 covers the bortezomib structure commonly written as:

N-(2-pyrazinecarbonyl)-L-phenylalanine-L-leucine boronic acid;
also known as a dipeptidyl boronic acid proteasome inhibitor;
commonly supplied as bortezomib for injection.

The structural elements are:

Structural element	Bortezomib feature
N-terminal acyl group	2-pyrazinecarbonyl
First amino-acid residue	L-phenylalanine
Second amino-acid residue	L-leucine
C-terminal functional group	Boronic acid
Stereochemistry	L-amino-acid configuration
Dosage form contemplated	Injectable composition after reconstitution

The claim is composition-based. A product containing bortezomib in a physiologically acceptable aqueous or saline carrier is the most direct infringement risk.

How broad are the Markush claims?

The Markush claims are materially broader than bortezomib. They cover multiple combinations of:

N-terminal heteroaryl carbonyl or sulfonyl groups;
alkyl, cycloalkyl, aryl and heterocyclic side chains;
benzyl, naphthylmethyl, pyridylmethyl and quinolylmethyl substituents;
alkoxy and alkylthio groups;
optional aromatic-ring substitution;
pharmaceutically acceptable salts; and
injectable saline or aqueous compositions.

The claim hierarchy narrows the field progressively.

Claim	Main scope	Commercial relevance
1	Pyrazinyl carbonyl/sulfonyl genus	Broad bortezomib-related genus
2	Claim 1 with specified R and alkyl R3	Narrows alkyl substituents
3	Claim 2 with C4 R3	Reaches isobutyl-type side chains
4	Claim 1 with specified R	Limited narrowing
5	Defined R2/R3/R5 substituent classes	Broader structural subgenus
6-9	Alkyl R3, including C4 and isobutyl	Relevant to leucine-like side chain
10-11	Specified R2 groups, including benzyl and naphthylmethyl	Defines selected peptide-side chains
12	Bortezomib-specific composition	Direct product claim
13	Expanded heteroaryl genus	Broadest major genus
14	Enumerated compounds	Specific exemplified compounds
15-20	Narrower R2/R3 and compound selections	Subgenera and species
21	Alternative P and R2 genus	Separate compound family
22	Claim 21 with isobutyl R3	Narrower alternative genus

Claims 6 through 11 are particularly relevant to bortezomib because they identify an alkyl R3 group, including C4 alkyl and isobutyl. Those limitations correspond closely to the leucine-derived side chain in bortezomib.

What formulations are protected by US 6,617,317?

The patent protects compositions that are suitable for preparing injectable solutions. The relevant carrier language includes:

physiologically acceptable saline;
physiologically acceptable aqueous carriers; and
solutions suitable for intravenous, intramuscular or subcutaneous administration.

The claims do not expressly require:

mannitol;
a specific pH;
a particular buffer;
a particular concentration;
a lyophilized cake;
a prefilled syringe;
a vial;
a preservative-free presentation; or
a particular reconstitution solvent.

Accordingly, the claims are potentially relevant to multiple bortezomib injectable presentations if the active ingredient is present in the claimed chemical form and the composition satisfies the carrier and administration limitations.

The claims are less clearly directed to:

oral tablets or capsules;
transdermal products;
inhaled products;
nonaqueous depot formulations; or
compositions that do not form a suitable injectable solution.

The phrase "upon combination with" is important. It suggests that a composition supplied before reconstitution may fall within the claim if, after combination with saline or an aqueous carrier, it forms the claimed injectable solution. The patent should therefore be analyzed together with the product label, vial contents and reconstitution instructions.

Is US 6,617,317 a formulation patent or a drug-substance patent?

It is primarily a composition patent with both drug-substance and injectable-use characteristics.

It is not a narrowly drafted excipient patent. The claims do not focus on a particular stabilizer, buffer, container, particle-size distribution or lyophilization cycle. Instead, they identify the active boronic acid compound and require a composition capable of forming an injectable solution.

The patent therefore sits between:

a compound patent, because it claims defined boronic acid structures; and
a formulation patent, because the independent claims require an injectable composition or a composition that can form one.

It is not primarily a method-of-use patent. None of the supplied claims expressly recites treating multiple myeloma, mantle cell lymphoma, or another disease.

What is the patent expiration date?

The reported US term for US 6,617,317 extends into December 2022, subject to the official USPTO term calculation and any applicable regulatory exclusivity. The practical commercial significance of the patent ended when the enforceable term expired or when authorized or licensed generic entry occurred, whichever came first.

Milestone	Date or period
Patent issued	September 9, 2003
FDA approval of Velcade	May 2003
Reported patent-term endpoint	December 2022
Relevant product	Bortezomib for injection
Regulatory pathway for generics	ANDA
Biosimilar pathway	Not applicable

The patent term must be separated from FDA exclusivity. Patent expiration and FDA market exclusivity are independent legal protections. An ANDA applicant may submit a Paragraph IV certification before patent expiration, while commercial launch depends on litigation, settlement, the 180-day first-filer period and any agreed entry date.

What was the Orange Book status of US 6,617,317?

US 6,617,317 was associated with the Velcade patent estate and was relevant to FDA-listed patent analysis for bortezomib. Orange Book status should be distinguished from the broader patent family:

an Orange Book listing concerns patents identified by the NDA holder as claiming the approved drug or an approved method of using it;
unlisted family members may still create litigation or freedom-to-operate issues;
a patent can remain visible in the patent estate even after its Orange Book listing ceases to have practical blocking effect;
an expired patent does not create a continuing Orange Book barrier to ANDA approval.

For bortezomib, the key Orange Book question was not whether every compound-family patent covered the product, but whether the listed patent claims covered the approved injectable composition and whether a generic applicant could overcome or await the listed patent term.

Which companies challenged bortezomib patents?

Bortezomib faced generic competition through ANDA filings and Paragraph IV patent challenges. The relevant competitive group included major generic manufacturers such as:

Teva;
Dr. Reddy's Laboratories;
Sandoz;
Fresenius Kabi;
Hikma; and
other ANDA sponsors.

The commercial dispute centered on the Velcade patent estate rather than US 6,617,317 alone. Generic applicants commonly challenged:

validity;
enforceability;
claim construction;
infringement;
patent-term calculations; and
whether the proposed injectable product satisfied the claims.

A Paragraph IV certification is an allegation by the ANDA applicant that the listed patent is invalid, unenforceable or not infringed. It is not itself a court finding. If the NDA holder sues within the statutory period, FDA approval can be delayed under the Hatch-Waxman automatic stay, subject to statutory limits and litigation outcomes.

What patent litigation and settlements affected generic entry?

Bortezomib generic entry was governed by the combined effect of:

the core compound patent estate;
injectable-composition patents;
Paragraph IV litigation;
settlement agreements;
FDA ANDA approval timing; and
commercial launch rights.

Settlements can permit an ANDA applicant to launch before the latest listed patent expiration in exchange for a specified entry date, license terms or other consideration. The existence of a settlement does not establish that every asserted patent is valid or infringed.

For investment and litigation analysis, US 6,617,317 should not be treated as the sole bortezomib barrier. The relevant question is whether a proposed generic product infringes an enforceable claim of this patent or another patent in the Velcade estate. A noninfringing formulation may avoid a composition claim even if it contains the same active ingredient, but changing excipients alone would not avoid claim 12 if the claim is construed to cover the active-containing injectable composition.

What generic launch scenarios existed for bortezomib?

Scenario 1: Launch after patent expiry

A generic could launch after expiration of the relevant enforceable patent term, subject to FDA approval and any remaining exclusivity. This is the lowest litigation-risk pathway.

Scenario 2: Licensed early entry

A settlement or license could permit launch before the nominal expiration date. The commercial launch date would depend on the agreement, regulatory approval and supply readiness.

Scenario 3: Successful Paragraph IV challenge

A generic could launch after prevailing in litigation or obtaining a judgment that the patent is invalid, unenforceable or not infringed.

Scenario 4: Noninfringing product design

An ANDA applicant could argue that its formulation does not meet a required claim limitation. For claim 12, that strategy is difficult if the proposed product contains the recited bortezomib compound in an injectable composition. For broader Markush claims, infringement depends on whether the specific compound and composition fall within every limitation.

How strong is the patent estate?

US 6,617,317 has a mixed strength profile.

Factor	Assessment
Claim 12 chemical specificity	Stronger than the broad genus claims
Breadth of claims 1 and 13	Broad, but exposed to prior-art and written-description challenges
Injectable composition limitation	Narrows the claim to administration-ready or reconstitutable products
Method-of-use coverage	Limited in the supplied claims
Manufacturing protection	Not a principal feature
Direct relevance to bortezomib	High
Post-expiration blocking value	None after enforceable term ends
Biosimilar relevance	None
Generic litigation relevance	High before expiration; limited after expiry

The broad Markush claims may face greater validity risk than claim 12 because they cover many heteroaryl groups and amino-acid substituent combinations. Claim 12 has a narrower chemical target and a clearer product mapping, although it still requires analysis of the claimed composition and carrier limitations.

How does US 6,617,317 compare with a manufacturing patent?

A manufacturing patent would protect a process for producing bortezomib, resolving stereochemistry, controlling impurities, or forming the final injectable product. US 6,617,317 does not principally do that.

Issue	US 6,617,317	Manufacturing patent
Primary subject	Compound-containing injectable composition	Production process
Product claim	Yes	Sometimes
Process claim	Not central to supplied claims	Usually central
Design-around options	Change compound, composition or claim element	Change process steps or reagents
ANDA certification relevance	Product and formulation infringement	Process certification and infringement issues
Supplier risk	High for bortezomib injectable products before expiry	Depends on manufacturing route

A generic manufacturer could avoid a process patent by using a different synthesis route. It could not avoid claim 12 merely by changing the synthetic route if the final product remains the claimed bortezomib composition.

What geographic coverage does the patent have?

US 6,617,317 provides protection only in the United States. Corresponding foreign applications may have produced patents in Europe, Japan, Canada and other jurisdictions, but each foreign right must be analyzed independently.

Differences may include:

claim scope;
patent-term calculation;
supplementary protection certificates;
prosecution amendments;
validity proceedings;
national litigation;
regulatory linkage; and
generic launch rules.

A US freedom-to-operate conclusion does not establish freedom to operate in Europe or other markets.

Key Takeaways

US 6,617,317 covers injectable compositions containing broad classes of peptide boronic acids.
Claim 12 specifically covers a composition comprising bortezomib.
Claims 1 and 13 create broader Markush protection around pyrazinyl and other heteroaryl derivatives.
The claims are composition-focused, not primarily treatment-method or manufacturing claims.
The patent is relevant to intravenous, intramuscular and subcutaneous bortezomib products.
The reported US patent-term endpoint is in December 2022.
Bortezomib is a small molecule, so generic competition proceeds through ANDA litigation rather than biosimilar litigation.
The commercial blocking position depended on the entire Velcade patent estate, Orange Book listings, Paragraph IV certifications and settlement-based entry dates.
After expiration of the enforceable term, US 6,617,317 no longer independently blocks generic bortezomib entry.

FAQs

Does US 6,617,317 claim bortezomib by name?

Yes. Claim 12 expressly recites N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid, the compound generally known as bortezomib.

Can a generic avoid claim 12 by changing the saline carrier?

Changing the carrier may not avoid claim 12 if the final product still contains bortezomib in a composition that forms a suitable injectable solution. The result depends on construction of each carrier and administration limitation.

Does US 6,617,317 cover oral bortezomib?

The supplied claims are directed to compositions that form solutions suitable for intravenous, intramuscular or subcutaneous administration. They do not expressly cover an oral tablet or capsule.

Is a bortezomib generic a biosimilar?

No. Bortezomib is a chemically synthesized small molecule. FDA approval generally proceeds through the ANDA pathway, not the section 351(k) biosimilar pathway.

Does a different bortezomib manufacturing process avoid this patent?

Not necessarily. The supplied claims focus on the compound-containing composition. A different manufacturing route may avoid a process patent but would not by itself avoid a product claim covering the final bortezomib composition.

References

United States Patent and Trademark Office. (2003). US Patent No. 6,617,317: N-substituted amino acid boronic acid compounds and compositions.
U.S. Food and Drug Administration. (2003). Velcade (bortezomib) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications.
U.S. Code, 35 U.S.C. § 154. Patent term.
U.S. Code, 21 U.S.C. § 355. New drug applications and abbreviated applications.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0788360	⤷ Start Trial	91083	Luxembourg	⤷ Start Trial
European Patent Office	0788360	⤷ Start Trial	300151	Netherlands	⤷ Start Trial
European Patent Office	0788360	⤷ Start Trial	CA 2004 00012	Denmark	⤷ Start Trial
European Patent Office	0788360	⤷ Start Trial	SPC/GB04/021	United Kingdom	⤷ Start Trial
European Patent Office	0788360	⤷ Start Trial	SPC008/2004	Ireland	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,617,317

Summary for Patent: 6,617,317