United States Drug Patent 6,747,150: Claim Scope, Expiration, Litigation Risk and Patent Landscape

US Patent No. 6,747,150 is a broad composition-of-matter patent covering peptide-like heteroaryl carbonyl compounds with boronic acid, boronate ester, or related diol-derived groups. The claims are structured as a genus with nested species claims. Claim 1 carries the principal scope; claims 2-14 narrow substituents, side chains, and boron-protecting groups.

The supplied claim language does not identify a single marketed drug with certainty because the underlying formula drawing for formula (1a), including the position of the Z1/Z2 group and the definitions of the remaining atoms, is not included. The claim set is consistent with protease-inhibitor chemistry and appears capable of covering bortezomib-type compounds, but literal coverage of bortezomib cannot be conclusively determined from the text alone.

What compounds does US 6,747,150 claim?

The patent claims compounds having five principal structural elements:

A heteroaryl-carbonyl group, P = R7-C(O)-.
An amide linkage, X2 = -C(O)-NH-.
Substituted amino-acid-like side chains defined through R, R1, R2, R3 and R5.
A terminal boron-associated substituent represented by Z1 and Z2.
A pharmaceutically acceptable salt, where applicable.

The claim architecture is typical of a medicinal-chemistry genus. It allows extensive variation at the heteroaryl, side-chain, nitrogen, and boron-protecting-group positions.

Structural requirements in claim 1

Claim element	Scope
Core formula	Formula (1a), not reproduced in the supplied text
P	R7-C(O)-
R7	Heteroaryl or heteroarylalkyl
X2	-C(O)-NH-
A	Zero
R	Hydrogen, alkyl, or a nitrogen-containing cyclic system formed with an adjacent group
R1-R3	Hydrogen, alkyl, cycloalkyl, aryl, heterocycle, or -CH2-R5
R5	Aryl, aralkyl, alkaryl, cycloalkyl, heterocycle, alkoxy, or alkylthio
Z1/Z2	Alkyl, hydroxy, alkoxy, aryloxy, or a diol-derived cyclic moiety
Salt coverage	Pharmaceutically acceptable salts

Claim 1 is therefore a broad Markush claim. It does not protect only one active ingredient. It covers potentially large numbers of compounds sharing the claimed amide-linked, heteroaryl-carbonyl and boron-containing framework.

How do claims 2 through 14 narrow the patent?

The dependent claims establish commercially relevant subgenuses.

Heteroaryl acyl groups

Claim 2 limits R7 to heteroaryl or heteroaryl(C1-4)alkyl. Claim 3 lists a very broad set of heteroaryl groups, including:

Thienyl and benzothienyl
Furyl and benzofuranyl-type systems
Pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl
Imidazolyl and pyrazolyl
Indolyl, indazolyl and carbazolyl
Quinolinyl, isoquinolinyl and quinazolinyl
Phenothiazinyl, isoxazolyl and related fused heterocycles

This list materially increases the genus breadth. A competitor using a different heteroaryl acyl group may remain within claim 1 even if it falls outside claim 3.

Nitrogen substitution and cyclic constraints

Claim 4 limits R to hydrogen or C1-8 alkyl. Claim 5 provides a more detailed substituent framework for R1, R2, R3 and R5, permitting:

C1-8 alkyl
C3-10 cycloalkyl
C6-10 aryl
Five-, six-, nine- or ten-membered heteroaryl groups
Benzyl and other -CH2-R5 substituents
Halogen, cyano, nitro, hydroxy, amino, alkoxy, alkylthio, sulfinyl and sulfonyl substitution

The claim also allows aryl, alkaryl, aralkyl and heteroaryl rings to carry one or two additional substituents. That creates substantial design space around the side chains.

R3 alkyl species

Claims 6-10 progressively narrow R3:

Claim	R3 limitation
6	C1-6 alkyl
7	C1-12 alkyl
8	C1-6 alkyl
9	C4 alkyl
10	Isobutyl

Claim 10 is the most specific R3 species and is commercially important because isobutyl is a common side chain in peptide-derived protease inhibitors.

R2 species

Claim 11 lists specific R2 substituents, including:

Isobutyl
1-Naphthylmethyl
2-Naphthylmethyl
2-Pyridylmethyl
6-Quinolinylmethyl
3-Indolylmethyl
Benzyl
4-Fluorobenzyl
4-Hydroxybenzyl
4-(2-pyridylmethoxy)benzyl
4-(benzyloxy)benzyl
Phenethyl

The express listing of benzyl and isobutyl species creates a narrower claim path for compounds with those substituents, even if a broader genus claim were challenged.

Boronic acid and boronate forms

Claims 12-14 define the Z1/Z2 group:

Claim 12: independently selected alkyl, hydroxy, alkoxy or aryloxy groups.
Claim 13: both Z1 and Z2 are hydroxy.
Claim 14: Z1 and Z2 form a cyclic or otherwise protected diol-derived moiety.

The diol list includes pinacol, perfluoropinacol, pinanediol, ethylene glycol, diethylene glycol, 1,2-cyclohexanediol, 1,3-propanediol, 2,3-butanediol, glycerol and diethanolamine.

Claim 13 is directed to the free boronic-acid form. Claim 14 covers protected boronate forms. This distinction can affect solid-state properties, stability, formulation, manufacturing and claim construction.

What is the likely pharmacological technology covered?

The claim structure is characteristic of boron-containing protease inhibitors. The boronic acid or boronate group can act as a transition-state mimic for serine or proteasome proteolysis. The heteroaryl carbonyl group and peptide-like side chains provide recognition elements for the enzyme-binding pocket.

The claims are not limited by:

A named biological target
A specific disease
A particular dosage
A formulation
A route of administration
A pharmacokinetic profile
A defined level of enzyme inhibition

That absence makes the composition claims stronger than a method-of-use claim if the accused molecule falls within the structural boundaries. It also means that a later product may infringe without practicing a patented therapeutic indication.

Does US 6,747,150 cover bortezomib?

The supplied claims include structural features associated with bortezomib-type boronic acid protease inhibitors, particularly:

A heteroaryl carbonyl group
An amide-linked peptide-like backbone
An isobutyl substituent
An arylmethyl substituent
A free boronic acid or protected boronate

Bortezomib contains a pyrazinecarbonyl group, a phenylalanine-derived benzyl group, an isobutyl side chain and a boronic acid pharmacophore. Those features correspond conceptually to the narrowing options in claims 3, 10, 11 and 13.

A definitive infringement conclusion requires the complete formula (1a), atom numbering, prosecution-history amendments and the exact structure of the accused compound. The supplied text alone supports a high-confidence structural relationship but not a final literal-coverage determination.

What is the patent term and expiration status?

US 6,747,150 issued on June 8, 2004. The ordinary patent term for a modern US utility patent is generally 20 years from the earliest effective nonprovisional filing date, subject to terminal disclaimers and patent-term adjustment. The grant date does not determine expiration. The patent’s expiration therefore depends on its priority chain and any recorded term adjustment or disclaimer. (35 U.S.C. §§ 154, 156.)

A reliable status analysis must distinguish among:

Issue	Relevance
Earliest effective filing date	Determines the base 20-year term
Continuation or divisional relationship	May create a common expiration date
Patent-term adjustment	Can extend the nominal term
Patent-term extension	May apply only to qualifying regulatory delay
Terminal disclaimer	Can shorten the term
Maintenance fees	Nonpayment can cause expiration before the nominal date
Reexamination or certificate	Can amend or cancel claims

The patent is now old enough that ordinary patent-term expiry is the principal commercial issue. No conclusion that the patent remains enforceable should be drawn from the fact that it appears in patent databases or historical product listings.

What is the Orange Book status of US 6,747,150?

A composition patent is relevant to the FDA Orange Book only if it is listed by the NDA holder for an approved drug and satisfies FDA listing requirements. The patent number alone does not establish Orange Book listing.

For an approved product potentially related to bortezomib, the relevant regulatory questions are:

Whether the NDA holder listed US 6,747,150.
Whether the listing covered the active ingredient, formulation or method of use.
Whether the listing remained active during generic approval.
Whether the patent was removed, expired or disclaimed.
Whether an ANDA applicant was required to make a Paragraph IV certification.

The Orange Book distinguishes drug substance, drug product and method-of-use patents. A compound patent covering the active ingredient is ordinarily more significant than a method-of-use patent because it can block commercial sale of the same molecule for non-patented indications unless the patent has expired or is otherwise unenforceable. (FDA, 2024a.)

What Paragraph IV challenges could arise?

A generic applicant seeking approval for a product covered by an Orange Book-listed patent may submit a Paragraph IV certification asserting that the patent is invalid, unenforceable or will not be infringed. The NDA holder can sue within 45 days, triggering a statutory stay of approval, subject to the applicable Hatch-Waxman framework. (21 U.S.C. § 355(j)(2)(A)(vii)(IV); 21 C.F.R. § 314.107.)

For a compound claim of the type found in US 6,747,150, likely Paragraph IV arguments would include:

The proposed molecule does not satisfy every limitation of formula (1a).
The relevant substituent falls outside the claimed R, R1, R2 or R3 definitions.
The accused product uses a non-covered boron oxidation state or protecting group.
The claim is anticipated by an earlier peptide boronic acid reference.
The genus is not enabled across its full scope.
The claim lacks adequate written description for the breadth of the Markush definitions.
The claim is obvious in view of known protease inhibitors and boronic acid chemistry.
The patent expired before the proposed commercial launch.

The patentee would likely rely on the express dependent species, examples, synthetic disclosure and any prosecution-history narrowing to defend validity and infringement.

What formulation patents and method-of-use patents matter?

The supplied claim set is primarily a composition-of-matter estate. It does not expressly claim:

Lyophilized injectable formulations
Reconstitution solutions
Specific excipients
Subcutaneous administration
Intravenous administration
Multiple myeloma treatment
Mantle-cell lymphoma treatment
Proteasome inhibition as a therapeutic method

A commercial product may therefore have a layered patent estate:

Patent layer	Typical subject matter	Risk profile
Compound patent	Active molecule or broad chemical genus	Highest
Salt or polymorph patent	Solid form or chemical variant	Medium to high
Formulation patent	Stability, excipients, reconstitution	Medium
Manufacturing patent	Boronate formation, deprotection or purification	Medium
Method-of-use patent	Disease, dosing schedule or combination	Product- and indication-specific
Device or delivery patent	Administration system	Usually narrower

For an injectable boronic acid protease inhibitor, formulation and manufacturing patents can remain commercially relevant after the basic compound patent expires. They rarely provide the same broad exclusionary leverage as a valid composition claim.

How strong is the patent estate based on the supplied claims?

Strengths

The claim set has several features favorable to the patent owner:

Claim 1 reaches a wide chemical genus.
The P definition covers many heteroaryl acyl groups.
R1-R5 permit extensive side-chain variation.
Claims 10, 11 and 13 provide narrower species paths.
Claim 14 captures protected boronate intermediates or prodrug-like forms.
The claim is not limited to a particular indication.
Pharmaceutically acceptable salts are expressly included.

Vulnerabilities

The same breadth creates validity and construction risks:

The Markush genus spans a large number of compounds.
The claim depends on a formula that is not reproduced in the supplied text.
The heteroaryl list contains apparent typographical and nomenclature errors.
Broad substituent definitions may raise written-description and enablement issues.
The boron-containing group must be mapped precisely to the formula.
The patent’s enforceability depends on prosecution amendments and any terminal disclaimer.
Expiration may eliminate practical value even if the claims were historically strong.

Overall, the estate appears structurally broad but commercially valuable only during its enforceable term and only to the extent the marketed molecule falls within the complete claim formula.

What generic-entry scenarios exist?

Scenario	Commercial consequence
Patent expired and no blocking listed patents remain	Full generic entry is possible after FDA approval
Compound patent remains enforceable	Generic applicant faces Paragraph IV litigation and possible stay
Only method patents remain	Carve-out or label strategy may permit limited entry
Formulation patent remains	Generic may avoid the formulation through a different dosage form
Manufacturing patent remains	A non-infringing process may reduce risk
Patent claims are narrowed or invalidated	Entry timing depends on remaining patents
Multiple patents expire at different dates	Entry may occur after the last blocking patent or through a settlement

For a parenteral product, a generic applicant may need to address both the active compound and product-specific formulation patents. The practical barrier depends on the Orange Book listing status, not on the existence of every historically issued patent.

Which companies may challenge the related product estate?

For a boronic-acid protease inhibitor such as bortezomib, potential generic competitors have historically included large injectable-generic companies and specialty manufacturers. Relevant competitive categories include:

Sandoz
Teva
Fresenius Kabi
Dr. Reddy's Laboratories
Sun Pharma
Hikma
Accord Healthcare
Cipla
Other ANDA sponsors with oncology-injectable capabilities

Company-specific challenge status must be tied to an actual ANDA, Paragraph IV notice, district-court complaint or FDA approval record. The patent number alone does not establish that a named company challenged US 6,747,150.

What is the litigation and settlement risk?

The most important litigation questions are:

Whether the patent was listed in the Orange Book.
Whether an ANDA applicant certified Paragraph IV.
Whether the NDA holder sued within 45 days.
Whether the dispute involved literal infringement, doctrine of equivalents or validity.
Whether the parties executed a license or launch-date settlement.
Whether the settlement was reported to the Federal Trade Commission.
Whether any later patent remained a separate entry barrier.

A settlement may permit an authorized generic, a licensed generic, a delayed launch, or an at-risk launch. The existence of a settlement does not prove that the patent claims were valid or infringed.

How does this patent compare with biosimilar and generic risk?

US 6,747,150 presents generic-drug risk, not biosimilar risk, if the covered product is a chemically synthesized small molecule. The relevant pathway is an ANDA under section 505(j), not a biosimilar application under section 351(k).

Issue	Small-molecule generic	Biosimilar
FDA pathway	ANDA	BLA supplement or 351(k) application
Patent certification	Paragraph I-IV	Patent dance and related litigation
Product identity	Same active ingredient	Highly similar biological product
Orange Book	Central	Generally not the primary biologic patent database
Patent scope	Compound, formulation, method	Biologic, formulation, manufacturing and use

What geographic coverage does the patent provide?

US 6,747,150 provides territorial protection only in the United States. Parallel applications may exist in:

The Patent Cooperation Treaty system
European national or regional filings
Canada
Japan
Australia
Other major pharmaceutical markets

A US expiration or invalidity decision does not determine foreign rights. Patent families should be checked individually for:

Grant status
Adjusted expiration date
Opposition or appeal proceedings
National-phase abandonment
Terminal disclaimers
Supplementary protection certificates
Local litigation

What manufacturing and IP barriers remain after compound expiry?

Boron-containing protease inhibitors can create manufacturing complexity involving:

Stereochemical control
Boronic acid stability
Boronate ester formation and hydrolysis
Removal of boron-containing impurities
Control of diastereomers and epimers
Purification of the final peptide-like compound
Reproducible injectable-grade specifications

These technical barriers are not automatically patent barriers. A process patent may be avoided by changing the order of coupling, protecting-group strategy, boronate installation or purification conditions. Regulatory chemistry, manufacturing and controls requirements may remain significant even where no enforceable compound patent blocks entry.

Key Takeaways

US 6,747,150 claims a broad genus of heteroaryl-carbonyl, amide-linked, boronic acid or boronate compounds.
Claims 10, 11 and 13 narrow the genus toward isobutyl, arylmethyl and free-boronic-acid species.
The claim set is consistent with bortezomib-type protease-inhibitor chemistry, but the supplied text does not permit a conclusive literal-coverage opinion.
The patent is a composition patent, not primarily a formulation or method-of-use patent.
Orange Book relevance depends on actual FDA listing history, not merely on issuance of the patent.
Paragraph IV risk would center on claim construction, written description, enablement, obviousness and patent-term expiry.
Generic risk is more relevant than biosimilar risk.
Foreign rights must be assessed separately from the US patent.
The commercial value of the patent depends on its actual expiration date, any terminal disclaimer or patent-term adjustment, and the presence of later formulation, manufacturing or use patents.

FAQs

Does US 6,747,150 claim a specific drug or an entire chemical class?

It claims a chemical class. The independent claim uses multiple Markush definitions and permits broad variation in heteroaryl groups, side chains and boron substituents.

Is claim 13 limited to boronic acid compounds?

Claim 13 requires Z1 and Z2 to be hydroxy groups. If those positions correspond to the boron substituents in formula (1a), the claim is directed to the free boronic-acid form rather than a protected boronate ester.

Can a generic avoid US 6,747,150 by using a pinacol boronate?

Not necessarily. Claim 14 expressly lists pinacol-derived cyclic protection. The full formula and the accused compound must be compared element by element.

Does a method-of-use patent automatically block a generic launch?

No. A generic may pursue a label that omits the patented indication if FDA rules permit the carve-out and the product is not otherwise blocked by a composition or formulation patent.

Does patent expiration eliminate all regulatory exclusivity?

No. Patent expiry and FDA exclusivity are separate. Regulatory exclusivity can arise from new chemical entity, orphan-drug, pediatric or other statutory provisions, although its commercial effect depends on the product and approval history.

References

Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024b). Abbreviated new drug application regulations and patent certifications. U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (2004). U.S. Patent No. 6,747,150. U.S. Department of Commerce.
21 C.F.R. § 314.107. (2024). Administrative proceedings in connection with abbreviated applications.
21 U.S.C. § 355. (2024). New drugs and antibiotics.
35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights.
35 U.S.C. § 156. (2024). Extension of patent term.

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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,747,150

Summary for Patent: 6,747,150