US Patent 6,974,861: Claim Scope, Expiration, and Patent Landscape for BNP-32/Nesiritide
US Patent 6,974,861 covers pharmaceutical compositions and therapeutic use of a specific 32-amino-acid B-type natriuretic peptide, commonly identified as BNP-32 or nesiritide. The patent claims the peptide itself only when present in a pharmaceutical composition, plus administration of the peptide to induce natriuresis, diuresis, vasodilation, or treatment of congestive heart failure.
The patent does not broadly claim all natriuretic peptides, BNP analogues, formulations, manufacturing processes, or combination therapies. Its commercial significance is tied to whether the claimed BNP-32 sequence is present in an accused product and whether the patent remains enforceable. By 2025, the patent’s statutory term had ended or was no longer a practical barrier to generic entry.
What peptide does US Patent 6,974,861 protect?
The claimed peptide is the 32-residue mature human B-type natriuretic peptide sequence:
Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-Lys-Val-Leu-Arg-Arg-His
The sequence is commonly written using one-letter notation as:
SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH
This is BNP-32, the active peptide associated with nesiritide, marketed in the United States as Natrecor by Scios and later Johnson & Johnson entities.
The supplied claims use “Cis” at two positions. “Cis” is not a standard three-letter amino-acid abbreviation. The biologically recognized residues in BNP-32 are cysteines, abbreviated “Cys.” The controlling document for infringement analysis is the issued patent and its official sequence listing, not a transcribed claim excerpt.
Core technical identity
| Attribute |
Scope |
| Active peptide |
Human BNP-32 |
| Common drug name |
Nesiritide |
| Therapeutic class |
B-type natriuretic peptide |
| Molecular form claimed |
Peptide or C-terminal amide |
| Claimed biological effects |
Natriuresis, diuresis, vasodilation |
| Claimed disease |
Congestive heart failure |
| Administration route stated in claims |
Not limited |
| Dose stated in claims |
Not limited |
| Formulation stated in claims |
Pharmaceutical composition with suitable excipient |
What does claim 1 of US 6,974,861 cover?
Claim 1 is a pharmaceutical-composition claim. It requires:
- An effective amount of the specified BNP-32 peptide or its amide; and
- A suitable pharmaceutical excipient.
The claim is sequence-specific. A composition containing a different BNP fragment, a modified BNP analogue, or a different natriuretic peptide would not literally satisfy the peptide limitation.
The phrase “or the amide thereof” most naturally covers the C-terminal amide form of the claimed peptide. It does not automatically cover every chemical modification, PEGylated form, lipid conjugate, salt, ester, substituted residue, or sequence variant.
Scope of the formulation language
The excipient limitation is broad. It can encompass conventional pharmaceutical vehicles, buffers, stabilizers, tonicity agents, preservatives, carriers, and other formulation components. The claim does not specify:
- Intravenous administration
- Bolus or infusion dosing
- A particular concentration
- A specific pH
- A particular container
- A lyophilized product
- A prefilled syringe
- A pump-compatible formulation
- A defined stability profile
The broad excipient language expands the range of potentially covered dosage forms, but the claim remains dependent on the presence of the exact BNP-32 peptide or its amide.
What do claims 2 and 3 cover?
Claims 2 and 3 are method-of-use claims.
Claim 2: natriuresis, diuresis, and vasodilation
Claim 2 covers administering the claimed peptide, its amide, or a pharmaceutical composition containing it to a subject in need of treatment to induce:
- Natriuresis
- Diuresis
- Vasodilation
- Any combination of those effects
The use of “and/or” makes the claim potentially applicable where the intended therapeutic effect is one, two, or all three of those physiological outcomes.
The claim does not specify:
- A particular cardiac diagnosis
- A specific patient population
- A route of administration
- A dose
- A treatment duration
- A biomarker threshold
- A required clinical endpoint
The “subject in need” limitation remains important. Routine administration to a person without a recognized need for treatment would present a different infringement analysis.
Claim 3: congestive heart failure
Claim 3 covers administration of the same peptide or composition to treat congestive heart failure.
This claim is narrower in disease scope than claim 2 but may be commercially more important because it is aligned with the approved therapeutic use of nesiritide. The claim does not appear limited to acute decompensated heart failure, New York Heart Association class, ejection fraction, hospitalization status, or a defined severity level.
The absence of dose and route limitations increases the claim’s potential reach. It also creates potential validity and construction issues if prior art disclosed the use of BNP-32 across a similarly broad range of heart-failure treatments.
How many independent claim concepts does US 6,974,861 contain?
The three claims represent three distinct protection categories:
| Claim |
Claim type |
Required subject matter |
Commercial relevance |
| 1 |
Composition |
BNP-32 or amide plus pharmaceutical excipient |
Product and formulation coverage |
| 2 |
Method of treatment |
Administration to induce natriuresis, diuresis, or vasodilation |
Physiological-use coverage |
| 3 |
Method of treatment |
Administration to treat congestive heart failure |
Disease-use coverage |
The claims do not independently claim:
- The isolated peptide as a composition of matter
- A nucleic acid encoding BNP-32
- A host cell producing BNP-32
- A recombinant manufacturing method
- A purification process
- A specific dosing regimen
- A combination with diuretics or vasodilators
- A delivery device
- A sustained-release formulation
- A biomarker-guided treatment protocol
What patents protect nesiritide and BNP-32?
The relevant patent estate is broader than US 6,974,861 and historically included several categories of rights:
| Patent category |
Subject matter |
Relationship to US 6,974,861 |
| Natriuretic peptide composition patents |
BNP, ANP, CNP, fragments, and related sequences |
May cover the peptide or broader peptide families |
| Method-of-use patents |
Treatment of heart failure, hypertension, fluid overload, or renal conditions |
May overlap claims 2 and 3 |
| Formulation patents |
Stabilized peptide preparations and injectable products |
Potentially relevant to commercial product manufacture |
| Manufacturing patents |
Recombinant expression, refolding, purification, or peptide processing |
Can create process barriers independent of product claims |
| Regulatory exclusivity |
FDA exclusivity linked to the approved product |
Separate from patent rights |
| Trademark rights |
Natrecor and related branding |
Not a patent barrier to generic entry |
US 6,974,861 is best characterized as a sequence-specific composition and use patent. It is not a complete product estate for every commercial version of nesiritide.
When did US Patent 6,974,861 lose exclusivity?
The patent was issued on December 13, 2005. Under the modern patent-term framework, the relevant term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable extension. The issuance date does not determine expiration. [1]
By 2025, US 6,974,861 was no longer an active exclusivity barrier. Any analysis of a current generic or follow-on product should therefore focus on:
- Whether related continuation or divisional patents remain active
- Whether separate formulation patents remain enforceable
- Whether manufacturing patents remain active
- Whether FDA regulatory exclusivity applies
- Whether the proposed product is therapeutically equivalent to the reference product
The patent’s expiration does not eliminate historical infringement exposure for conduct occurring before expiration.
Patent-term considerations
| Issue |
Effect |
| Patent term |
Generally tied to the earliest effective nonprovisional filing date |
| Patent-term adjustment |
Could extend the nominal term |
| Patent-term extension |
Requires a qualifying regulatory review and FDA certificate |
| Terminal disclaimer |
Can shorten the term to match another patent |
| Post-expiration status |
No prospective exclusion right, but past damages may remain relevant |
What is the Orange Book status of US 6,974,861?
The Orange Book lists patents submitted by applicants for approved small-molecule drug applications, subject to FDA listing rules. [2] The presence of a patent in the Orange Book depends on the NDA holder’s submission and FDA’s listing determination. Patent rights and Orange Book listing are separate questions.
Nesiritide was approved by FDA under NDA 020920 as Natrecor. [3] The approved product is a recombinant peptide administered intravenously for the treatment of patients hospitalized for acute decompensated heart failure.
US 6,974,861 should not be treated as an Orange Book barrier merely because it covers the active peptide or an approved use. A current regulatory analysis must distinguish:
- Whether the patent was submitted for Orange Book listing
- Whether it was listed for the drug product, a method of use, or both
- Whether the listing remained active during the relevant generic filing period
- Whether the patent’s expiration date passed before an ANDA filing
The expiration of the patent would remove any current Paragraph IV litigation leverage based solely on this patent.
Are Paragraph IV challenges and generic entry risks significant?
A Paragraph IV certification alleges that a listed patent is invalid, unenforceable, or will not be infringed. Under the Hatch-Waxman framework, a Paragraph IV notice can trigger patent litigation and, if timely sued upon, a 30-month stay of approval. [4]
For a nesiritide product, the principal generic-entry risks would be:
- Exact-sequence infringement. A product containing BNP-32 would create the highest literal infringement risk during the patent term.
- Amide-form coverage. A C-terminally amidated version could fall within the express “amide thereof” language.
- Formulation overlap. A generic injectable product could implicate separate formulation claims.
- Method-of-use exposure. Labeling for heart failure or natriuretic treatment could raise method-claim issues.
- Non-infringing design-around. A materially different peptide sequence or formulation could avoid literal infringement but may not be therapeutically interchangeable.
- Regulatory labeling constraints. A generic applicant may need a carve-out for patented uses if unpatented indications remain available.
Because US 6,974,861 had expired by 2025, it would not ordinarily support a new Paragraph IV enforcement action. Any current challenge would more likely concern another patent in the nesiritide estate or a different reference-product strategy.
How strong is the patent estate?
The claim estate was moderate for the exact peptide and weaker for broader platform protection.
Strengths
- The sequence is precisely defined.
- Claim 1 reaches pharmaceutical compositions containing the peptide.
- Claims 2 and 3 cover broad therapeutic administration concepts.
- The claims do not impose narrow dose or route limitations.
- The peptide is associated with a well-defined approved therapeutic product.
Limitations
- The claims do not cover all natriuretic peptides.
- They do not claim the peptide independent of a pharmaceutical composition.
- They do not expressly cover analogues, fragments, conjugates, or chemically modified variants.
- Expired claims cannot block current manufacture, sale, or use.
- The method claims may face prior-art issues if BNP-32 use for fluid regulation or heart failure was already disclosed.
- The formulation claim may be avoided by a product that does not contain the claimed sequence or uses a distinct active moiety.
The practical strength was therefore highest during the patent term against a product using unmodified BNP-32 or its amide in a conventional pharmaceutical formulation.
What manufacturing and IP barriers remain after patent expiration?
Patent expiration does not remove all market-entry barriers. Nesiritide is a peptide product, and a follow-on manufacturer may still face:
- Recombinant expression and recovery challenges
- Correct disulfide-bond formation
- Control of oxidation and aggregation
- Potency and impurity specifications
- Sterility and endotoxin controls
- Comparability of intravenous formulation
- Reference-product sourcing
- Clinical pharmacology requirements
- FDA product-quality review
A peptide product may be regulated through an abbreviated drug pathway or another FDA route depending on the reference product, product characterization, and applicable statutory framework. FDA approval requirements are separate from patent rights. [3]
Which companies have competed with nesiritide?
Nesiritide competes within the broader natriuretic-peptide and acute-heart-failure field rather than through direct substitution by identical products.
| Product or program |
Active peptide or class |
Competitive relationship |
| Natrecor |
Nesiritide, recombinant BNP-32 |
Reference product |
| Ularitide |
Urodilatin-related natriuretic peptide |
Clinical alternative and development competitor |
| Carperitide |
Atrial natriuretic peptide |
Regional alternative, particularly Japan |
| Cenderitide |
Designer natriuretic peptide |
Investigational analog |
| Standard acute-heart-failure drugs |
Diuretics, vasodilators, inotropes |
Pharmacologic alternatives |
Most competing products do not practice claims requiring the exact BNP-32 sequence. Their patent analysis must be conducted separately based on their own sequences, formulations, and indications.
What patent litigation affects US 6,974,861?
The supplied claim text does not establish a litigation history. Patent litigation cannot be inferred from the claims alone. The relevant legal issues would include:
- Whether the patent was listed against Natrecor
- Whether an ANDA filer issued a Paragraph IV notice
- Whether Scios or Johnson & Johnson filed an infringement action
- Whether any settlement imposed a delayed generic-entry date
- Whether a court construed “amide thereof,” “effective amount,” or “subject in need”
- Whether the patent was challenged for anticipation, obviousness, written description, enablement, or indefiniteness
For current commercial purposes, the patent’s expiration is more important than historical litigation because an expired patent no longer provides prospective exclusion.
Key Takeaways
- US 6,974,861 targets BNP-32, the 32-amino-acid peptide associated with nesiritide.
- Claim 1 covers a pharmaceutical composition containing BNP-32 or its C-terminal amide and a suitable excipient.
- Claim 2 covers administration to induce natriuresis, diuresis, or vasodilation.
- Claim 3 covers administration to treat congestive heart failure.
- The patent does not broadly cover all natriuretic peptides, BNP analogues, manufacturing processes, or delivery systems.
- The “Cis” references in the supplied text are likely transcription errors for “Cys”; the official sequence listing controls.
- By 2025, the patent was no longer a prospective exclusivity barrier.
- Current market-entry analysis should focus on related patents, Orange Book records, FDA requirements, formulation comparability, and manufacturing capability.
- A product using a different peptide sequence may avoid literal infringement, but it may not qualify as an equivalent generic product.
FAQs
Is US 6,974,861 a composition-of-matter patent for nesiritide?
No. Claim 1 is a pharmaceutical-composition claim. It requires BNP-32 or its amide to be present with a suitable pharmaceutical excipient. It does not claim the isolated peptide in every form.
Does US 6,974,861 cover intravenous nesiritide?
Potentially, if the intravenous product contains the claimed BNP-32 peptide or its amide and satisfies the pharmaceutical-composition limitations. The claim itself does not expressly require intravenous administration.
Does the patent cover BNP analogues?
Not expressly. A modified BNP sequence would need to be analyzed for literal infringement and equivalents. The issued claims are directed to the specified sequence or its amide.
Can a generic manufacturer avoid claim 3 by removing heart-failure language from its label?
Potentially, but the answer depends on the approved indication, labeling strategy, induced infringement theory, and other active patents. Labeling cannot be assessed in isolation from the regulatory product pathway.
Does expiration of US 6,974,861 guarantee immediate generic approval?
No. Expiration removes this patent as a prospective exclusion right. FDA approval, product quality, formulation comparability, manufacturing validation, regulatory exclusivity, and other patents can still affect launch timing.
References
- United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension. https://www.uspto.gov/patents/laws/patent-term-calculator
- U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
- U.S. Food and Drug Administration. (2001). Natrecor (nesiritide) prescribing information and approval materials. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/
- U.S. Food and Drug Administration. (n.d.). Patent certification and the 30-month stay under the Hatch-Waxman Act. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/abbreviated-new-drug-application-anda-forms-and-guidances
