Details for Patent: 5,972,882
Summary for Patent: 5,972,882
| Title: | Treatment of polycystic kidney disease using vasopressin V2 receptor antagonists | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The present invention is directed to the novel treatment of ARPKD and ADPKD by administering a pharmacologically effective amount of a V2 receptor antagonist. Orally active V2 receptor antagonists such as OPC-31260, OPC-41061, SR121463A and VPA-985 are administered alone, or in combination to mammalian PKD subjects to reduce the cAMP generated by the increased expression of AVP-V2 receptor, AQP2 and AQP3, thereby reducing and/or preventing cyst enlargement. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | II Vincent H. Gattone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | KANSAS MEDICAL CENTER A NON-PROFIT ORGANIZATION, University of , University of Kansas Medical Center | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US09/211,396 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Delivery; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | U.S. Patent 5,972,882: Scope, Claims, Expiration, and Polycystic Kidney Disease Patent LandscapeU.S. Patent No. 5,972,882 covers the use of vasopressin V2 receptor antagonists to treat polycystic kidney disease, reduce azotemia, and slow cyst enlargement. Its claims are method-of-treatment claims rather than compound, formulation, manufacturing, or dosage-form claims. The patent’s nominal U.S. term has expired, meaning it is no longer a current patent barrier to generic or branded development in the United States, subject to any unusual term adjustment or extension recorded in the official patent file.[1] The patent is historically important because it broadly links V2 receptor blockade with autosomal dominant polycystic kidney disease, the indication later commercialized with tolvaptan. It does not, based on the claims provided, specifically claim tolvaptan by name, a commercial tolvaptan formulation, or a manufacturing process. What does U.S. Patent 5,972,882 claim?The patent claims two related therapeutic concepts:
The claims are summarized below.
The supplied text of claim 6 identifies “VPA-9835,” while claims 5 and 9 identify “VPA-985.” That inconsistency is material to claim construction. The issued patent, prosecution history, correction certificates, and applicable file history would control whether the discrepancy is treated as a typographical error, an intentional limitation, or an ambiguity. How broad is claim 1 of U.S. Patent 5,972,882?Claim 1 is the patent’s broadest independent treatment claim. It requires:
The claim does not limit the antagonist to a named molecule. It also does not specify:
That structure gives claim 1 potentially broad literal scope. Its practical enforceability, however, would depend on claim construction, written-description support, enablement, anticipation, obviousness, and whether the accused product is used for the claimed indication. A generic V2 antagonist could potentially fall within claim 1 even if it is not one of the molecules listed in claim 2. Claim 2 narrows the genus to named compounds and peptide antagonists; it does not define the full scope of claim 1. What compounds are expressly identified in the patent claims?The claims identify five categories or compounds: OPC-31260OPC-31260 is a nonpeptide vasopressin V2 receptor antagonist used in preclinical research. Claims 3 and 7 limit the compound to oral administration at about 60 mg/kg/day. OPC-41061OPC-41061 is listed in claim 2 but has no claim-specific dosage or route limitation. The compound is associated with the tolvaptan development program, although the patent claims provided do not name tolvaptan or establish that OPC-41061 and tolvaptan are interchangeable for every legal purpose. SR121463ASR121463A is named in claim 2. Claims 4 and 8 specify oral administration at about 2 mg/kg/day. VPA-985VPA-985 is named in claims 2, 5, and 9. Claims 5 and 9 specify oral administration at about 2 mg/kg/day. Peptide V2 antagonistsThe claims also cover peptide V2 antagonists as a category. That language creates a genus limitation but does not identify particular peptide sequences, structures, formulations, or manufacturing methods. What is the significance of the dose limitations?Claims 3 through 5 and 7 through 9 add specific dose and route limitations to the broader independent claims. The phrase “about” generally creates a range rather than a single mathematically exact dose. The permissible range would depend on the intrinsic evidence, specification, prosecution history, and expert evidence. A product administered at a materially different dose may fall outside a dependent claim while still potentially falling within claim 1 or claim 6. The dose claims are also narrower because they require oral administration. An intravenous, subcutaneous, transdermal, or other nonoral use would not literally satisfy those dependent claims, although it could remain relevant to the broader independent claims. The dose limitations do not claim:
Those omissions leave formulation and dosing-regimen protection to later or separate patents. What disease and treatment outcomes are covered?Claim 1 requires treatment of polycystic kidney disease. Claim 6 is narrower in one respect because it specifies two treatment outcomes:
“Azotemia” generally refers to abnormal accumulation of nitrogenous waste products in blood, often assessed through measures such as blood urea nitrogen or serum creatinine. “Cyst enlargement” relates to the growth of renal cysts associated with polycystic kidney disease. Claim 6 does not expressly require both outcomes to be measured through a particular assay or imaging method. It also does not specify the amount or percentage of attenuation. The claim therefore raises potential issues concerning what constitutes attenuation and how the treatment effect must be demonstrated. Is U.S. Patent 5,972,882 still active?The patent’s nominal term has expired. For a U.S. utility patent filed after June 8, 1995, the standard term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory rules.[2] U.S. Patent 5,972,882 issued in 1999 and has passed the ordinary 20-year term associated with its underlying filing history.
Expiration removes the patent right to exclude future use under the patent. It does not erase historical infringement exposure during the enforceable term, and it does not resolve ownership, inventorship, prosecution-history, or claim-construction disputes that could have mattered before expiration. What is the Orange Book status of U.S. Patent 5,972,882?U.S. Patent 5,972,882 is not, based on the claims and patent identity provided, a product-specific Orange Book patent for the current JYNARQUE or JINARC tolvaptan products. The Orange Book primarily lists patents submitted by approved drug sponsors for approved products and identified as covering the drug substance, drug product, or approved method of use.[3] A historical method patent can be relevant to the same therapeutic field without being listed for a later-approved product. The patent’s claims do not identify:
Accordingly, a developer evaluating tolvaptan should review the current Orange Book entries for the approved product separately from U.S. Patent 5,972,882. How does this patent relate to tolvaptan and JYNARQUE?Tolvaptan is a selective vasopressin V2 receptor antagonist developed by Otsuka. The FDA approved JYNARQUE in 2018 to slow kidney-function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease.[4] The patent is relevant to the scientific and historical development of V2 antagonism in polycystic kidney disease, but it should not be treated as the principal current patent for JYNARQUE. The commercial tolvaptan estate is more likely to involve later patents directed to:
The distinction is important. A broad expired pioneer method patent can establish historical prior art without controlling the current commercial exclusivity position of a later-approved product. What formulation patents are protected by U.S. Patent 5,972,882?None are apparent from the claims provided. The patent does not claim:
Its oral claims establish a route of administration, not a formulation architecture. A competitor could therefore design around the dependent oral-dose claims by using a different formulation or dose, although such a design would not necessarily avoid claim 1 or claim 6. Does the patent cover manufacturing or composition of matter?No, based on the supplied claims. The patent does not claim:
The patent is therefore weak as a manufacturing barrier. Its historical value is concentrated in the method-of-use concept. What Paragraph IV risks exist for generic V2 antagonists?Because the patent has expired, it does not create a current Paragraph IV obstacle. During the enforceable term, an ANDA applicant seeking approval for a product labeled to treat polycystic kidney disease could have faced a potential patent certification issue if the patent had been listed for the relevant reference product. The applicant might have considered:
For current generic development, the principal risk is not U.S. Patent 5,972,882. The relevant risks are later, unexpired patents covering the specific active ingredient, approved indication, dosing regimen, formulation, or product. Which companies are associated with the competitive landscape?The patent claims identify compounds associated with several development programs, but the commercial landscape is narrower.
The patent does not itself establish a license, collaboration, assignment chain, or royalty obligation. Any licensing analysis would require review of assignments, recorded agreements, SEC filings, merger documents, and commercial development agreements. What litigation and settlement issues affect the patent?No litigation or settlement conclusion follows from the claims alone. A complete litigation review would distinguish among:
The patent’s expiration materially reduces its current litigation significance. Litigation concerning JYNARQUE is more likely to focus on later Orange Book-listed patents and later method-of-use or product claims than on this expired patent. Does biosimilar risk apply to this patent?No. Biosimilar concepts do not apply directly because the patent concerns small-molecule vasopressin V2 receptor antagonists and method-of-treatment claims. Tolvaptan is a small molecule regulated through the abbreviated new drug application pathway for generic competition, not through the biosimilar pathway under the Public Health Service Act. A competing biologic V2 antagonist would present a separate regulatory and patent analysis, but the claims provided would not create a conventional biosimilar barrier. How strong is the patent estate for a current tolvaptan competitor?U.S. Patent 5,972,882 alone is weak as a current exclusionary asset because it is expired and does not claim a commercial formulation or tolvaptan-specific product.
The commercial strength of the broader V2 antagonist patent landscape depends on later patents, regulatory exclusivity, approved labeling, and any live claims covering tolvaptan-specific use or formulation. What generic launch scenarios exist?Three scenarios are relevant: Immediate post-expiration developmentA developer can rely on the expiration of U.S. Patent 5,972,882 when assessing this patent. The patent does not require a license for current use if no other enforceable rights apply. Carved-label launchA generic applicant may seek a label excluding a patented method when the FDA pathway and reference labeling permit such a carve-out. This is more relevant to later unexpired method patents than to the expired patent. Full-label launch after later patent expiry or challengeA full-label generic launch depends on the live patent and exclusivity position for the relevant reference product. U.S. Patent 5,972,882 does not determine that date. What are the key geographic limitations?The patent is a U.S. right. Its claims do not control treatment, sale, manufacture, or use outside the United States. International freedom to operate requires separate review of national counterparts and related applications in jurisdictions such as:
A U.S. expiration does not establish foreign expiration. Conversely, a foreign patent does not restore U.S. exclusivity. Key Takeaways
FAQs About U.S. Patent 5,972,882Does U.S. Patent 5,972,882 specifically claim tolvaptan?Not by name in the claims provided. OPC-41061 is listed, but the claim text does not use the generic name tolvaptan or identify the JYNARQUE product. Can a generic manufacturer rely on expiration of this patent?Yes, as to this patent alone. A generic manufacturer must still evaluate later patents, regulatory exclusivity, labeling restrictions, and other intellectual-property rights. Does the patent cover autosomal dominant polycystic kidney disease?The supplied claims say “polycystic kidney disease” and do not expressly limit the claims to autosomal dominant disease. The specification and prosecution history could affect the interpretation. Is the 60 mg/kg/day OPC-31260 dose relevant to approved tolvaptan dosing?No direct equivalence should be assumed. The claimed OPC-31260 dose is a preclinical or compound-specific limitation and does not establish the approved human dosing regimen for tolvaptan. Does the VPA-9835 error invalidate claim 6?Not automatically. The legal effect depends on the issued patent, any certificate of correction, the prosecution history, and whether a court treats the reference as an obvious typographical error or an ambiguous chemical limitation. References
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Drugs Protected by US Patent 5,972,882
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
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| >Applicant | >Tradename | >Generic Name | >Dosage | >NDA | >Approval Date | >TE | >Type | >RLD | >RS | >Patent No. | >Patent Expiration | >Product | >Substance | >Delist Req. | >Patented / Exclusive Use | >Submissiondate |
