Scope, Claims, and US Patent Landscape for RE43580
US RE43580 is a US reissue patent that centers on nasal liquid formulations of calcitonin using citric acid (and/or citric acid salts) as the bioavailability-enhancing agent, with tightly bounded concentration, pH, and tonicity (osmotic pressure) parameters, and with optional inclusion of viscosity control, surfactant, and preservatives. The claims also include methods for improving stability and plasma exposure after nasal administration.
What is the claim core (what the patent actually protects)?
1) Composition claim nucleus
The independent composition language is built around the following constraint set:
- Drug component: calcitonin (or acid addition salt), including specific species:
- salmon calcitonin
- human calcitonin
- porcine calcitonin
- 1,7-Asu-eel calcitonin
- Absorption/performance agent: citric acid and/or its salts
- Citric acid (bioavailability enhancer) concentration: 10 to about 50 mM
- Dosage form: liquid suitable for nasal administration, including nasal spray
- pH window:
- about 3 to about 5
- dependent narrowing: about 3.5 to about 3.9
- further narrowing: about 3.7
This forms a “fence” around a specific formulation chemistry: calcitonin + citric acid at defined mM + nasal-appropriate liquid + acidic pH.
2) “Locked” performance parameters in later claim sets
The claims then add a stricter sub-scope (claim set keyed to “claim 15” / “claim 31” language) with additional performance descriptors:
- Total bioavailability enhancing agent concentration: 10 to 25 mM (in claim 15 framework)
- Citric acid concentration: 20 mM (explicit in claim 15 framework)
- pH: 3.5 to 3.9
- Osmotic pressure: 250 to about 350 mOsm/liter
- Liquid nasal carrier may be aqueous saline
- Viscosity target: less than 0.98 cP (dependent from claim 4/5/15/24/25 style)
3) Optional but practically significant excipient constraints
The formulation is not limited to just citric acid and calcitonin. Several dependent claims add excipient boundaries that can materially affect design-around.
- Surfactant / wetting agent: polyoxyethylene(20) sorbitan monooleate (also indicated as polysorbate monooleate-type surfactant naming)
- threshold: at least 0.1% by weight
- explicit exemplar: 0.1%
- Preservatives (examples):
- benzyl alcohol
- phenylethyl alcohol
- methyl paraben
- ethyl paraben
- propyl paraben
- butyl paraben
- threshold: at least one preservative
- explicit exemplar in claim 18/19/34:
- phenylethyl alcohol 0.2%
- benzyl alcohol 0.5%
- Specific exemplar compositions appear in claims 18 and 19
- claim 18: ~2,200 MRC units salmon calcitonin, 10 mM citric acid, 0.2% phenylethyl alcohol, 0.5% benzyl alcohol, 0.1% polyoxyethylene(20) sorbitan monooleate
- claim 19: ~2,200 MIC units salmon calcitonin, 20 mM citric acid, same excipient set
These exemplars matter because they can become anchors for claim interpretation and prosecution history estoppel arguments in enforcement scenarios.
What are the actual claim boundaries (ranges and “switches”)?
A. Citric acid concentration
Two key windows appear across the claim set:
- 10 to about 50 mM citric acid/citric acid salt (core claims 1 and also as a method parameter in claims 22-23)
- 10-25 mM total bioavailability enhancer in the tighter framed claims (claim 15; also claim 20 method)
- A further explicit fixed target in claim 15:
- Claim 31 uses:
- 10-50 mM combined bioavailability enhancer concentration (broader than claim 15 but paired with osmotic pressure bounds)
Practical reading: there is a broader “10-50 mM” conceptual invention, then a narrower “10-25 mM with citric acid at 20 mM and osmotic pressure 250-350 mOsm/l” pocket.
B. pH
Multiple boundaries stack:
- about 3 to about 5 (claim 12)
- about 3.5 to about 3.9 (claim 13)
- about 3.7 (claim 14)
- In the performance-driven claims: pH 3.5-3.9 (claims 15 and 31)
Practical reading: pH is a central differentiator for both novelty and efficacy framing. Deviations outside 3.5-3.9 are meaningful to non-infringement arguments for the tighter dependent claims.
C. Osmotic pressure (tonicity)
Only the tighter framed claim set explicitly locks tonicity:
- 250 to about 350 mOsm/liter (claim 15 framework and claim 31)
Practical reading: changing tonicity can be a clean design-around if the rest of the formulation stays within the claim core.
D. Viscosity
Only tied to the nasal spray / viscosity claim elements:
- viscosity < 0.98 cP (claim 5)
- later dependent claims incorporate the “claim 15” composition with carrier and viscosity (claim 25 ties to claim 15 via “wherein said composition has a viscosity of less than 0.98 cP”)
Practical reading: viscosity is not universally required in every independent composition, but it becomes required in the dependent claim path.
E. Calcitonin identity and unit measurement
Claim 6 explicitly lists calcitonin types, with claim 7 narrowing to salmon calcitonin.
Unit ranges appear in MRC-unit frameworks:
- 100 to about 8,000 MRC units/ml (claim 8)
- 500 to about 4,000 MRC units/ml (claim 9)
- 500 to about 3,000 MRC units/ml (claim 10)
- 1,000 to about 2,500 MRC units/ml (claim 11)
The exemplar claims use ~2,200 MRC units and ~2,200 MIC units. This unit switching can matter during claim construction if MIC and MRC are defined differently in the patent/specification.
How broad are the claims as a whole (scope map)?
1) Broadest composition layer
- Liquid nasal calcitonin composition with:
- citric acid/citric acid salt 10-50 mM
- pH 3-5
- “suitable for nasal administration”
- calcitonin identity includes multiple species
This is the broadest conceptual scope (claims 1, 12, 6).
2) Mid-scope performance constrained layer
- Adds:
- aqueous nasal carrier
- nasal spray form
- viscosity <0.98 cP (dependent)
- pH 3.5-3.9 or about 3.7
- calcitonin amount windows
This tightens both the physical form and operating conditions (claims 2-5, 13-14, 8-11).
3) Narrowest pocket: citric acid fixed at 20 mM + osmotic pressure window
A highly structured combination appears in claim 15:
- calcitonin + citric acid as enhancer
- total enhancer 10-25 mM
- citric acid concentration 20 mM
- osmotic pressure 250-350 mOsm/liter
- pH 3.5-3.9
- optionally:
- polyoxyethylene(20) sorbitan monooleate ≥0.1%
- preservatives selected from the stated list
Claim 31 expands osmotic-pressure framing while allowing combined enhancer 10-50 mM, but keeps:
- pH 3.5-3.9
- osmotic pressure 250-350 mOsm/liter
Net effect: the enforcement “sweet spot” is the intersection of:
- citric acid/citric acid salt in the locked mM band
- pH in 3.5-3.9
- osmotic pressure 250-350 mOsm/liter
- and, if the formulation includes them, required excipients (surfactant/preservatives) per the dependent paths.
What methods are covered (use and improvement claims)?
1) Method of administering calcitonin via nasal route
Claims 20, 29, 35, 36 cover administering a therapeutically effective amount of the claimed compositions via nasal route, with dependencies:
- claim 20: method tied to claim 1 and citric acid enhancer at 10-25 mM with pH 3.5-3.9
- claim 21: method calcitonin dose 200 to 600 MRC units
- claim 29: method of administering therapeutically effective amount of claim 15 composition
- claim 35 and 36: methods tied to claim 31 and claim 34 compositions respectively
Practical reading: if a competitor product matches the composition elements, method claims can be asserted even if the manufacturer sells via the nasal indication.
2) Improvement methods (stability and bioavailability)
- claim 22: improving stability by adding citric acid (10-50 mM) to a calcitonin liquid composition
- claim 23: improving bioavailability / plasma calcitonin concentration after nasal administration by adding citric acid (10-50 mM) prior to administration
These are “process-of-formulation” and “use” hooks around citric acid addition at the defined mM.
Which design-arounds are implied by the claim structure? (Not hypothetical, direct claim-deltas)
A competitor intent typically targets one or more required elements. Based strictly on these claims, meaningful delta points are:
- Move citric acid concentration outside 10-50 mM (for claim 1/22/23) or outside 10-25 mM (for claim 15 path).
- Change pH outside 3.5-3.9 (for claims 15/31/13-14 dependent islands).
- Change osmotic pressure outside 250-350 mOsm/liter (for claim 15 and claim 31).
- Replace or remove polyoxyethylene(20) sorbitan monooleate at ≥0.1% (for dependent paths 16, 26, 34).
- Remove preservatives from the specified list (for dependent paths 17, 27, 32, 34).
How does this fit into the US calcitonin nasal formulation patent landscape?
Landscape characteristics relevant to RE43580
Without a full bibliographic pull of the underlying issued family and prosecution history, the best defensible landscape framing is at the level of claim architecture, because RE43580’s claims indicate where the patent system expects infringement fights:
- Formulation acidity and tonicity windows are treated as patentable control points.
- Citric acid concentration in mM is treated as the central active excipient parameter.
- Specific excipients (notably a polyoxyethylene(20) sorbitan monooleate class) and preservative packages are included as dependent claim gates.
- Salmon calcitonin is a key embodiment (claim 7, and exemplar 18-19).
What this implies for freedom-to-operate (FTO)
For FTO, the practical question is not “Does the product use citric acid?” but whether it matches the stacked constraints:
- If a product is a nasal liquid/spray calcitonin formulation using citric acid at 10-50 mM, acidic pH 3-5, it is in the general claim zone (claim 1).
- If the product further nails pH 3.5-3.9 plus osmotic pressure 250-350 mOsm/liter and uses citric acid 20 mM in the claimed 15 framework, the probability of matching dependent claim paths increases sharply (claims 15, 24, 25, 26, 27, 28, 31-34).
- If the product includes the same surfactant level and preservative system present in the exemplars, dependent claim exposure rises (claims 16-19, 26-28, 32-34).
Claim-by-claim scope matrix (what each claim adds)
| Claim |
What it adds beyond the base concept |
| 1 |
Calcitonin (various), citric acid/citric salt 10-50 mM, nasal-suitable liquid |
| 2 |
Requires aqueous liquid nasal carrier |
| 3 |
Carrier comprises aqueous saline |
| 4 |
Nasal spray form |
| 5 |
Viscosity <0.98 cP |
| 6 |
Lists calcitonin species (including salmon, human, porcine, 1,7-Asu-eel) |
| 7 |
Calcitonin is salmon calcitonin |
| 8 |
Calcitonin amount 100-8,000 MRC units/ml |
| 9 |
Calcitonin amount 500-4,000 MRC units/ml |
| 10 |
Calcitonin amount 500-3,000 MRC units/ml |
| 11 |
Calcitonin amount 1,000-2,500 MRC units/ml |
| 12 |
pH 3-5 |
| 13 |
pH 3.5-3.9 |
| 14 |
pH about 3.7 |
| 15 |
Adds: citric acid enhancer 10-25 mM total, citric acid 20 mM, osmotic pressure 250-350 mOsm/l, pH 3.5-3.9 |
| 16 |
Surfactant: polyoxyethylene(20) sorbitan monooleate ≥0.1% w/w |
| 17 |
Preservatives: one or more from listed set |
| 18 |
Example: ~2,200 MRC salmon calcitonin + 10 mM citric acid + 0.2% phenylethyl alcohol + 0.5% benzyl alcohol + 0.1% surfactant |
| 19 |
Example: ~2,200 MIC salmon calcitonin + 20 mM citric acid + same excipients |
| 20 |
Method: administer composition of claim 1 with enhancer 10-25 mM total and pH 3.5-3.9 |
| 21 |
Method calcitonin dose 200-600 MRC units |
| 22 |
Method: improve stability by adding citric acid 10-50 mM |
| 23 |
Method: improve bioavailability/plasma concentration by adding citric acid 10-50 mM |
| 24 |
Claim 15 includes aqueous saline |
| 25 |
Claim 15 has viscosity <0.98 cP |
| 26 |
Claim 15 includes surfactant ≥0.1% |
| 27 |
Claim 15 includes at least one preservative from the listed set |
| 28 |
Claim 15 calcitonin is salmon |
| 29 |
Method administering therapeutically effective amount of claim 15 composition |
| 30 |
Method of claim 20 where calcitonin is salmon |
| 31 |
Aqueous nasal composition with: salmon calcitonin + enhancer 10-50 mM, pH 3.5-3.9, osmotic pressure 250-350 mOsm/l |
| 32 |
Claim 31 includes preservatives from listed set |
| 33 |
Enhancer total is 20 mM (within claim 31 framework) |
| 34 |
Adds explicit excipients: 0.2% phenylethyl alcohol, 0.5% benzyl alcohol, 0.1% surfactant |
| 35 |
Method administering therapeutically effective amount of claim 31 composition |
| 36 |
Method administering therapeutically effective amount of claim 34 composition |
How to use this to map enforcement risk for competing nasal calcitonin sprays
Risk tiers based on element matching
- High-risk match: nasal spray calcitonin liquid using citric acid in mM, pH 3.5-3.9, and osmotic pressure 250-350 mOsm/liter, with any overlap to 20 mM citric acid (claim 15 framework) or total enhancer 20 mM (claim 33 framework).
- Moderate-risk match: nasal liquid calcitonin with citric acid 10-50 mM and pH 3-5, even if osmotic pressure differs, because claim 1 remains broad.
- Narrow-risk match: only partial overlaps, such as citric acid present but outside defined mM/pH/tonicity, or excipient set differs such that dependent claims are avoided.
Key Takeaways
- RE43580’s scope is built around citric acid-controlled nasal calcitonin liquids with acidic pH and, in narrower claim sets, osmotic pressure 250-350 mOsm/l.
- The tightest enforcement pocket is claim 15 and claim 31, where pH 3.5-3.9 combines with osmotic pressure 250-350 mOsm/l and mM enhancer constraints (including citric acid 20 mM in claim 15).
- Dependent claims add material “gates” for viscosity (<0.98 cP), polyoxyethylene(20) sorbitan monooleate (≥0.1%), and specific preservative packages.
- For competing formulations, the most direct non-infringement levers are moving pH, citric acid concentration, and osmotic pressure outside the specified bands, or excluding the enumerated excipients where dependent claims would otherwise be met.
FAQs
-
What parameter is most central to RE43580’s novelty?
Citric acid (and/or salt) as the bioavailability-enhancing agent at defined mM concentrations, paired with acidic pH for nasal calcitonin.
-
Which claims most strongly constrain product tonicity?
The claims tied to the performance pockets, including claim 15 and claim 31, require osmotic pressure 250-350 mOsm/liter.
-
Is salmon calcitonin required for all claim scope?
No. The broad composition claims list multiple calcitonin species, but salmon calcitonin is explicitly required in some dependent paths and in claim 31.
-
Do the claims require a specific preservative?
They require that a composition contains at least one preservative from a specified list only in certain dependent claims; the base claim set does not universally impose the preservative requirement.
-
What is the most practical design-around strategy implied by the claims?
Adjust the formulation so that it misses at least one stacked requirement in the dependent pockets, typically pH, citric acid mM, and/or osmotic pressure.
References
[1] US RE43580 (reissue patent). Claim set as provided in the prompt (claims 1-36).
