United States Drug Patent RE40812: Scope, Claims, Expiration, and Calcitonin Nasal Spray Patent Landscape

U.S. Patent RE40,812 covers liquid nasal formulations of calcitonin, particularly salmon calcitonin, stabilized and absorption-enhanced with citric acid or citrate at defined concentrations. The patent also covers specified pH, osmolarity, viscosity, preservatives, surfactant, dosage strength, nasal administration methods, and stability or bioavailability improvements.

The patent is expired. Its enforceable term ended in December 2017, based on the priority and original patent dates. RE40,812 therefore does not currently block generic manufacture, marketing, formulation development, or nasal administration of calcitonin products in the United States.

What does U.S. Patent RE40,812 cover?

RE40,812 covers a formulation platform rather than calcitonin as a molecule. The central technical combination is:

Calcitonin or an acid-addition salt;
Citric acid, citrate, or both;
Citric acid or citrate concentration of approximately 10 to 50 mM;
A liquid dosage form suitable for nasal administration.

The patent focuses on improving the stability and nasal bioavailability of calcitonin. The claims narrow the formulation through additional limitations covering pH, osmotic pressure, viscosity, preservative systems, surfactant content, calcitonin potency, and delivery method.

Core claim architecture

Claim group	Subject matter	Commercial relevance
Claims 1-12	Broad and narrower nasal liquid compositions	Covers the formulation platform
Claims 13-17	Low-pH, lower-citrate formulations with excipient limitations	Targets optimized nasal formulations
Claims 18-19	Specific salmon calcitonin formulations	Closest to commercial product formulations
Claims 20-21	Nasal administration methods	Covers use of the claimed composition
Claims 22-23	Stability and bioavailability methods	Covers formulation process and performance claims
Claims 24-29	Narrow dependents to the low-pH formulation	Adds defined excipient, concentration, and physical-property limitations

The patent does not claim every calcitonin nasal spray. A competing product would need to satisfy the elements of at least one claim. Because the patent has expired, the claim analysis now has historical, freedom-to-operate, and litigation significance rather than current exclusionary force.

What are the independent claims in RE40,812?

The principal composition claim is claim 1. It requires a liquid pharmaceutical composition containing calcitonin or an acid-addition salt and citric acid or a citrate salt in a concentration from 10 to approximately 50 mM, with the composition suitable for nasal administration.

Claims 13, 20, 22, and 23 appear to define additional independent subject matter in the issued claim set. The text supplied for claims 13, 14, and 24-29 contains formatting artifacts such as "claim 1 A" and "claim 1 13." Those artifacts should not be treated as substantive claim language. The issued patent document, including its certificate of correction if applicable, controls claim construction.

Claim 1: broad composition coverage

Claim 1 has four principal limitations:

A liquid pharmaceutical composition;
Calcitonin or an acid-addition salt;
Citric acid and/or a citrate salt at 10 to approximately 50 mM;
A form suitable for nasal administration.

The claim does not require:

Salmon calcitonin specifically;
A nasal spray device;
A particular pH;
Saline;
A preservative;
A surfactant;
A particular osmolarity;
A particular calcitonin concentration.

Those features appear in dependent claims or narrower formulation claims.

The broadest practical infringement risk historically applied to liquid nasal calcitonin products using citrate within the claimed concentration range. A product using another absorption enhancer, no citrate, or citrate outside the claimed range could avoid claim 1, subject to the remaining claims and doctrine-of-equivalents analysis.

Claims 2-5: carrier, spray, and viscosity

Claims 2 through 5 narrow claim 1 by adding:

An aqueous liquid nasal carrier;
Aqueous saline;
A nasal spray presentation;
Viscosity below 0.98 cP.

These claims were directed toward conventional liquid nasal spray products rather than dry powder or injectable formulations.

The viscosity limitation is commercially relevant because it may distinguish a high-viscosity mucoadhesive formulation from a low-viscosity aqueous spray. A product with viscosity at or above 0.98 cP would not literally satisfy claim 5, although it could still fall within claim 1 or another composition claim.

Claims 6-7: calcitonin species

Claim 6 identifies:

Salmon calcitonin;
Human calcitonin;
Porcine calcitonin;
1,7-Asu-cyclocalcitonin, identified in the claim text as 1,7-Asu-ccl calcitonin.

Claim 7 narrows the formulation to salmon calcitonin. The salmon calcitonin limitation is commercially significant because Miacalcin and Fortical were salmon calcitonin nasal products.

Claims 8-11: calcitonin potency

The claims create nested potency ranges:

Claim	Calcitonin concentration
Claim 8	Approximately 100-8,000 MRC units/ml
Claim 9	Approximately 500-4,000 MRC units/ml
Claim 10	Approximately 500-3,000 MRC units/ml
Claim 11	Approximately 1,000-2,500 MRC units/ml

A product outside a narrower range may still fall within a broader range. The concentration must be evaluated using the patent's unit conventions and the product's labeled or measured potency.

Claim 12: pH range

Claim 12 requires a pH of approximately 3 to 5. This limitation captures acidic aqueous formulations and excludes neutral or alkaline formulations outside the range.

The commercial formulation significance is high because calcitonin stability and nasal absorption can depend on acidic conditions. The claim does not require the narrower pH range of claims 13 and 14.

What formulations are protected by claims 13-19 and 24-29?

Claims 13-19 and 24-29 target a narrower formulation with low pH and a defined citrate concentration.

The principal limitations are:

Calcitonin for nasal administration;
Citric acid, citrate salt, or both as the bioavailability-enhancing agent;
Combined enhancer concentration of 10-25 mM;
pH of approximately 3.5-3.9;
A preferred pH of approximately 3.7;
Optional or additional saline;
Osmotic pressure of 250-350 mOsm/liter;
Viscosity below 0.98 cP;
Salmon calcitonin;
At least 0.1% polyoxyethylene(20) sorbitan monooleate;
Specified preservatives.

Polyoxyethylene(20) sorbitan monooleate is commonly known as polysorbate 80. The claims identify it by chemical description rather than the commercial name.

Specific formulations in claims 18 and 19

Claim 18 recites a composition containing approximately:

2,200 MRC units of salmon calcitonin;
10 mM citric acid;
0.2% phenylethyl alcohol;
0.5% benzyl alcohol;
0.1% polyoxyethylene(20) sorbitan monooleate.

Claim 19 recites a similar formulation with:

Approximately 2,200 MRC units of salmon calcitonin;
20 mM citric acid;
0.2% phenylethyl alcohol;
0.5% benzyl alcohol;
0.1% polyoxyethylene(20) sorbitan monooleate.

These claims are substantially narrower than claim 1 because they require a defined active, potency, excipient system, and citrate concentration. They would have been most relevant to a product closely matching the claimed formulation.

Claim 22: stability method

Claim 22 covers improving the stability of a liquid calcitonin pharmaceutical composition by adding citric acid or a citrate salt at 10 to approximately 50 mM.

This claim is directed to a formulation method. It does not require nasal administration on its face, unlike claims focused expressly on nasal delivery. Its scope depends on whether the accused activity is characterized as practicing the claimed stability-improvement method rather than merely selling a finished formulation.

Claim 23: bioavailability and plasma concentration method

Claim 23 covers improving calcitonin bioavailability or plasma calcitonin concentration after nasal administration by adding citric acid or a citrate salt at 10 to approximately 50 mM before administration.

This is a method-of-use claim. It requires:

A liquid calcitonin formulation;
Nasal administration;
Citrate addition in the specified concentration;
Improvement in bioavailability or plasma calcitonin concentration.

Claims 20 and 21 separately address administration of the claimed composition, including administration of approximately 200-600 MRC units.

When did U.S. Patent RE40,812 expire?

RE40,812 expired in December 2017. The reissue did not create a new 20-year patent term. Reissue patents generally retain the term of the original patent, subject to the applicable patent-term-adjustment and terminal-disclaimer rules.

Key patent dates

Event	Date
Earliest claimed priority	December 20, 1996
Original U.S. patent filing	December 19, 1997
Original U.S. patent grant	June 15, 1999
Reissue grant	May 5, 2009
End of ordinary 20-year term	December 2017
Current enforceability	Expired

The original patent was U.S. Patent No. 5,912,014. RE40,812 is the reissue patent. The reissue may have modified the claim set, but it did not provide a fresh patent term extending beyond the original patent's statutory expiration.

The expiration date should be confirmed against the USPTO patent-term records for transaction-specific diligence, including any patent-term adjustment or terminal disclaimer. For ordinary competitive assessment, the decisive conclusion is that RE40,812 is no longer an enforceable exclusionary right.

What was the FDA and Orange Book status of RE40,812?

RE40,812 was associated with the patent estate for salmon calcitonin nasal spray products, including the Miacalcin product family. The relevant FDA regulatory framework was a New Drug Application under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act, followed by abbreviated applications for generic products under section 505(j).

MONEY? No current Orange Book listing can create enforceability after patent expiration. A patent listed in the Orange Book remains relevant to historical Paragraph IV litigation and approval timing, but the listing does not extend patent life.

Relevant products

Product	Active ingredient	Dosage form	Regulatory pathway
Miacalcin nasal spray	Salmon calcitonin	Nasal spray	NDA
Fortical nasal spray	Salmon calcitonin	Nasal spray	NDA
Generic calcitonin salmon nasal spray	Salmon calcitonin	Nasal spray	ANDA

FDA-approved calcitonin nasal products have faced market contraction because of safety concerns associated with long-term calcitonin use and changing osteoporosis treatment practice. FDA labeling has included warnings concerning malignancy risk and limitations on chronic use. Those regulatory issues affect commercial demand but do not alter the expired status of RE40,812.[1][2]

Which companies challenged or competed against RE40,812?

The principal competitive field consisted of branded salmon calcitonin nasal spray manufacturers and generic applicants. Miacalcin was associated with Novartis. Fortical was developed and marketed by Upsher-Smith Laboratories. Generic applicants pursued approval through the ANDA pathway.

Publicly reported Paragraph IV disputes involving calcitonin nasal spray products generally concerned Orange Book-listed patents protecting the relevant branded products. The existence, outcome, and scope of any particular Paragraph IV notice must be assessed from the FDA Orange Book, ANDA litigation docket, and settlement documents for the specific product and patent.

Because RE40,812 expired in 2017, any historical Paragraph IV challenge involving this patent no longer presents a current launch-blocking patent risk. A generic applicant today would not need to wait for RE40,812 to expire.

Biosimilar risk versus generic risk

Calcitonin is a peptide hormone, but a nasal calcitonin product is ordinarily assessed as a small-molecule-style drug product for U.S. approval purposes rather than as a biosimilar to a biologic licensed under section 351(k). The relevant competitive pathway is generally an ANDA under section 505(j), subject to FDA's determination of pharmaceutical equivalence, bioequivalence, quality, device performance, and labeling requirements.

The practical risk is therefore generic entry, not biosimilar substitution. A competitor may still face analytical and bioequivalence challenges because nasal delivery can be sensitive to spray pattern, droplet size, device performance, formulation pH, viscosity, and excipient composition.

How strong was the RE40,812 patent estate?

RE40,812 had meaningful historical scope but limited current value because its term has ended.

Historical strengths

Claim 1 covered a technically important combination of calcitonin and citrate at 10-50 mM.
Claims 13-19 covered a commercially realistic acidic nasal formulation.
Claims 18 and 19 claimed specific salmon calcitonin formulations with defined preservatives and surfactant.
Claims 20-23 extended protection to administration, stability, and bioavailability methods.
The claims addressed both composition and use, creating multiple potential infringement theories.

Historical weaknesses

The composition claims required a relatively narrow excipient concept: citric acid or citrate.
Many claims depended on measurable parameters such as pH, viscosity, osmolarity, concentration, and MRC units.
Narrow formulation claims could be avoided through changes to excipients, pH, potency, or delivery format.
Method claims could raise proof issues concerning the purpose of formulation use and measurable improvement.
The reissue did not extend the patent's term.

Current strength

Current enforceability is zero because the patent expired. The patent remains relevant as prior art and as a record of formulation design, but it cannot support a new infringement action for post-expiration commercial activity.

What generic launch scenarios exist for calcitonin nasal spray?

Scenario 1: Conventional generic nasal spray

A generic product can use salmon calcitonin in an aqueous nasal spray with citrate, provided it satisfies current FDA requirements and no unexpired patent blocks approval. RE40,812 does not prevent this scenario.

Scenario 2: Formulation design-around

A manufacturer may use:

A citrate concentration outside 10-50 mM;
A non-citrate absorption enhancer;
A different pH;
A different preservative system;
A different surfactant;
A powder or alternative nasal dosage form;
A different spray-device configuration.

These approaches were historically relevant to avoiding the patent's narrower claims. They remain relevant for product differentiation and regulatory development.

Scenario 3: Authorized generic or branded competition

A rights holder may compete through an authorized generic, licensing arrangement, contract manufacturer, or reformulated nasal product. The commercial barrier would be FDA approval, manufacturing capability, supply economics, and market demand rather than RE40,812.

What manufacturing and intellectual-property barriers remain?

The patent does not currently create a manufacturing barrier. The remaining barriers are operational and regulatory:

Consistent manufacture of a labile peptide;
Control of aggregation and degradation products;
Preservation of a multidose aqueous product;
Device compatibility;
Spray-content uniformity;
Droplet and plume characterization;
Container-closure integrity;
Sterility or microbial-control requirements;
Demonstration of bioequivalence for a nasal product;
Commercial viability in a declining calcitonin market.

Formulation knowledge disclosed in RE40,812 may still be useful, but the disclosed formulation cannot be treated as proprietary merely because it appears in an expired patent.

How does RE40,812 compare with competing calcitonin patent protection?

Issue	RE40,812	General competing calcitonin estate
Core subject	Citrate-containing liquid nasal formulations	Product, formulation, device, process, or use
Active	Calcitonin, especially salmon calcitonin	Usually salmon calcitonin
Key enhancer	Citric acid or citrate	May use citrate or another enhancer
Delivery	Nasal liquid, especially spray	Nasal spray, injectable, or alternative delivery
Main claim types	Composition, method of administration, stability, bioavailability	Composition, device, manufacturing, regulatory use
Status	Expired in December 2017	Must be reviewed patent by patent
Current launch risk	None from RE40,812	Depends on unexpired patents and regulatory exclusivity

A complete current freedom-to-operate opinion requires review of all active U.S. patents, Orange Book entries, terminal disclaimers, FDA exclusivity, and litigation records associated with the specific proposed product. RE40,812 alone is not a current barrier.

Key Takeaways

RE40,812 covers citrate-containing liquid nasal calcitonin formulations.
Claim 1 is the principal broad composition claim, requiring 10-50 mM citric acid or citrate.
Claims 13-19 and 24-29 narrow the invention to acidic, low-viscosity formulations with defined excipients and physical properties.
Claims 20-23 cover nasal administration, stability improvement, and bioavailability or plasma-concentration improvement.
Claims 18 and 19 recite specific salmon calcitonin formulations containing phenylethyl alcohol, benzyl alcohol, and polysorbate 80.
The patent's term ended in December 2017.
RE40,812 cannot currently block generic launch or formulation development.
The relevant U.S. competitive pathway is generally an ANDA, not a biosimilar application.
Current commercial risk depends on FDA requirements, manufacturing performance, device characteristics, market demand, and any separate unexpired patents.

FAQs About U.S. Patent RE40,812

Does RE40,812 cover injectable calcitonin?

No. The principal claims require a liquid composition suitable for nasal administration or expressly address nasal administration. Injectable formulations are outside the ordinary literal scope of the nasal claims.

Does a citrate-free calcitonin nasal spray infringe RE40,812?

A citrate-free product would not literally satisfy the citric acid or citrate limitation in the principal composition claims. Other patents and claim theories would require separate analysis.

Is salmon calcitonin itself patented by RE40,812?

No. RE40,812 does not claim salmon calcitonin as a molecule. It claims formulations and methods using calcitonin with citric acid or citrate under defined conditions.

Can a company rely on claim 18 to block a competing nasal spray?

No. Claim 18 expired with the patent in December 2017. It may remain relevant as prior art or as evidence of historical formulation disclosure, but it cannot support a current infringement injunction.

Are FDA exclusivity and patent expiration the same?

No. FDA regulatory exclusivity and patent term are separate. FDA exclusivity can restrict approval timing even when a patent has expired, while patent expiration does not itself establish that FDA exclusivity has ended. Each must be checked separately in the Orange Book and FDA regulatory records.

References

U.S. Food and Drug Administration. (2014). Miacalcin (calcitonin salmon) nasal spray prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Patent and Trademark Office. (2009). United States Patent RE40,812: Pharmaceutical compositions containing calcitonin. https://patents.google.com/patent/USRE40812E1/en
U.S. Patent and Trademark Office. (1999). United States Patent 5,912,014: Pharmaceutical compositions containing calcitonin. https://patents.google.com/patent/US5912014A/en
U.S. Food and Drug Administration. (2024). Approved drug product list and patent and exclusivity information. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-drug-database/Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	3660401	⤷ Start Trial
Australia	783952	⤷ Start Trial
Canada	2399505	⤷ Start Trial
China	1183965	⤷ Start Trial
China	1422160	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: RE40812