United States Patent 10,668,072: Scope, Claims, and US Patent Landscape for a pH-Buffered Oral Liquid of Formula (I)
US Patent 10,668,072 protects an oral liquid formulation containing (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (“compound of formula (I)”), optionally as a pharmaceutically acceptable salt or combination, with a specific acidic pH window, high drug loading (20 to 30 mg/mL), and a defined cyclodextrin/citrate/sweetener system.
What is claimed? (Core formulation definition)
The independent claim 1 defines a liquid formulation with five hard constraints:
- Active: compound of formula (I) or pharmaceutically acceptable salt
- Excipients: hydroxypropyl-β-cyclodextrin and sodium citrate and a sweetener
- pH window: about 2.5 to about 5.5
- Drug concentration: about 20 mg/mL to about 30 mg/mL
- Combination nature: includes salt forms and mixtures, not only free base
Claims 2 to 22 then narrow or add specific compositions (salt form, wt.% of excipients, preservative system, bitterness masking, and specific sweetener/flavor packages).
How broad is the claim scope?
Claim 1: Broadest independent claim (composition and functional limits)
Claim 1 is broad because it is open on several axes:
- Salt flexibility: “pharmaceutically acceptable salt” is expressly allowed, and claim 2 later narrows to hydrogen sulfate.
- Sodium citrate flexibility: claim 1 permits “sodium citrate” generally; claims 5 to 8 narrow to dihydrate levels.
- Sweetener flexibility: claim 1 requires only “a sweetener,” leaving selection open until claims 9 to 13 and 17.
- Concentration and pH: claim 1 anchors the formulation to two numeric ranges that strongly constrain formulation design.
Net effect: Claim 1 captures any oral liquid meeting:
- pH 2.5 to 5.5
- drug (formula I) at 20 to 30 mg/mL
- hydroxypropyl-β-cyclodextrin + sodium citrate + sweetener in the liquid
Dependent claims: Where scope narrows sharply
Dependent claims create multiple “design islands” that are easier to design around but also easier to detect for infringement if marketed formulations match the exact ranges.
Key narrowing features include:
- Salt form (claim 2): hydrogen sulfate salt as the source of formula (I)
- Hydroxypropyl-β-cyclodextrin wt.% (claims 3-4): 13 to 17 wt.% (or specifically 15 wt.%)
- Sodium citrate dihydrate (claims 6-8): 0.7 to 1.5 wt.% (or about 1.1 wt.%)
- Sweetener package (claims 9-13): sucrose + glycerin + sorbitol + flavoring; sweetener buffered with citric acid and sodium phosphate; preserved with methylparaben and potassium sorbate; sweetener total 45 to 55 wt.% (or about 50 wt.%)
- Bitterness masking (claims 14-16): 0.2 to 0.5 wt.% (or about 0.4 wt.%)
- Sweetener alternative (claim 17): “sweetener includes sucralose”
- Flavor specifications (claims 18-20): flavoring agent as berry flavoring; 0.01 to 0.1 wt.%
- Alternative dependent claim structures (claims 21-22): require specific subcombinations that essentially read like narrower embodiments
What does each claim add (element-by-element scope map)?
Claims 1-2: Salt source and formulation base
Landscape implication: A product using a different salt form can avoid claim 2 while still risking claim 1 if pH/excipient/drug concentration constraints are met.
Claims 3-4: Hydroxypropyl-β-cyclodextrin amount
- Claim 3: hydroxypropyl-β-cyclodextrin is 13 to 17 wt.%
- Claim 4: specifically about 15 wt.%
Landscape implication: Even if a product uses hydroxypropyl-β-cyclodextrin, moving outside 13 to 17 wt.% can reduce risk for these dependent claims; however, it does not eliminate claim 1 coverage.
Claims 5-8: Sodium citrate hydrate form and level
- Claim 5: sodium citrate includes sodium citrate monohydrate and/or sodium citrate dihydrate
- Claim 6: sodium citrate includes sodium citrate dihydrate
- Claim 7: sodium citrate dihydrate at 0.7 to 1.5 wt.%
- Claim 8: specifically about 1.1 wt.%
Landscape implication: Claim 1 only needs “sodium citrate,” while claims 7-8 require dihydrate and exact wt.% banding.
Claims 9-13: Sweetener system with buffers and preservatives
- Claim 9: sweetener includes sucrose, glycerin, sorbitol, and flavoring
- Claim 10: sweetener further includes citric acid and sodium phosphate
- Claim 11: sweetener further includes methylparaben and potassium sorbate
- Claim 12: sweetener present at 45 to 55 wt.%
- Claim 13: sweetener present at about 50 wt.%
Landscape implication: These claims read like a complete flavor-preservation-buffering system. A challenger can often avoid these dependent claims by changing preservatives, buffering salts, or reducing sweetener wt.% below the band. But again, the independent claim 1 still requires only “a sweetener.”
Claims 14-16: Bitterness masking agent
- Claim 14: includes bitterness masking agent
- Claim 15: bitterness masking agent at 0.2 to 0.5 wt.%
- Claim 16: about 0.4 wt.%
Landscape implication: If a marketed oral liquid avoids a bitterness mask or uses a different ingredient profile outside these bands, the dependent coverage can fail while claim 1 may still apply.
Claims 17-20: Sucralose and berry flavor embodiment
- Claim 17: sweetener includes sucralose
- Claim 18: further includes a flavoring agent
- Claim 19: flavoring agent is berry flavoring
- Claim 20: berry flavoring agent at 0.01 to 0.1 wt.%
Landscape implication: This defines an alternate “sweetener/flavor” island. It does not replace claim 1; it adds a distinct embodiment.
Claims 21-22: Two narrower packaged embodiments
Claim 21 requires:
- hydroxypropyl-β-cyclodextrin 13 to 17 wt.%
- sodium citrate dihydrate 0.7 to 1.5 wt.%
- sweetener includes sucrose + glycerin + sorbitol + flavoring
- sweetener buffered with citric acid + sodium phosphate
- preserved with methylparaben + potassium sorbate
- sweetener at 45 to 55 wt.%
- bitterness masking agent 0.2 to 0.5 wt.%
- pH 2.5 to 5.5
- drug concentration 20 to 30 mg/mL
Claim 22 requires:
- hydroxypropyl-β-cyclodextrin 13 to 17 wt.%
- sodium citrate dihydrate 0.7 to 1.5 wt.%
- sweetener includes sucrose (only as stated)
- flavoring agent 0.01 to 0.1 wt.%
- pH 2.5 to 5.5
- drug concentration 20 to 30 mg/mL
Where is infringement most likely in the real world?
The high-risk product profile
Infringement risk concentrates on liquid products that simultaneously meet:
- pH: 2.5 to 5.5
- drug concentration: 20 to 30 mg/mL
- complexation system: hydroxypropyl-β-cyclodextrin
- buffering system: sodium citrate
- taste system: includes some sweetener
- plus, for dependent claim alignment, one or more of:
- hydroxypropyl-β-cyclodextrin at 13 to 17 wt.%
- sodium citrate dihydrate at 0.7 to 1.5 wt.%
- hydrogen sulfate salt source
- preservative suite (methylparaben + potassium sorbate)
- total sweetener around 45 to 55 wt.%
- bitterness masking at 0.2 to 0.5 wt.%
Practical read-across: “design around” levers
From a formulation strategy perspective, the claim set creates multiple levers, but the independent claim 1 reduces the effectiveness of partial changes:
- Moving pH outside 2.5 to 5.5 is the cleanest way to avoid claim 1.
- Moving drug concentration outside 20 to 30 mg/mL avoids claim 1.
- Removing hydroxypropyl-β-cyclodextrin or sodium citrate avoids claim 1.
- Changing the “sweetener” concept may be enough to avoid claim 1 if the product is not “a sweetener” within claim meaning, but many oral liquids will still use a sweetening system.
Dependent claims provide extra leverage, but only if the product also remains within claim 1’s avoided parameters.
US patent landscape: what can be concluded from this filing alone?
No external bibliographic data, prosecution history, assignees, related applications, continuation families, or citing/cited documents were provided for US Patent 10,668,072. With only the claims text, a complete and accurate cross-patent landscape cannot be constructed.
What can be stated strictly from the claim language is the technical scope that defines the likely claim family boundary:
- The patent is aimed at oral liquid formulation engineering for the same compound of formula (I), not at new chemical entities (the active is defined by formula (I)).
- The protected inventions are formulation constraints: acidic pH, cyclodextrin complexation level banding, citrate dihydrate salt-basis, and taste/preservative/bitterness package.
Landscape inference limited to claim scope: Any other US patents that cover this product class will likely also be formulation patents around:
- alternative buffers (other citrate forms or different acid systems)
- different cyclodextrin derivatives or ratios
- salt form changes (e.g., hydrogen sulfate vs. other pharmaceutically acceptable salts)
- taste systems (sweetener substitutes, reduced sweetener wt.%, different preservatives)
But a defensible landscape requires specific, citable US documents, which are not included in the prompt.
Claim-to-coverage matrix (for quick freedom-to-operate screening)
| Feature |
Claim 1 required? |
Dependent claim alignment (examples) |
Typical “avoidance” lever |
| Compound of formula (I) or salt |
Yes |
Claim 2 restricts salt source (hydrogen sulfate) |
Use different salt source to avoid claim 2 (claim 1 may remain) |
| Hydroxypropyl-β-cyclodextrin present |
Yes |
Claims 3-4 require 13 to 17 wt.% (or ~15%) |
Remove or replace to avoid claim 1; shift wt.% to avoid dependent claims |
| Sodium citrate present |
Yes |
Claims 5-8 require dihydrate and 0.7 to 1.5 wt.% |
Remove/replace; shift hydrate form/level |
| Sweetener present |
Yes |
Claims 9-13 require specific sweetener components and preservatives and 45 to 55 wt.% |
Remove sweetener or use different system to avoid dependent claims; claim 1 is broad |
| pH 2.5 to 5.5 |
Yes |
Applies across claims |
Adjust pH outside band to avoid claim 1 |
| Drug concentration 20 to 30 mg/mL |
Yes |
Applies across claims |
Adjust concentration outside band to avoid claim 1 |
| Hydrogen sulfate salt prepared from |
No |
Claim 2 |
Use non-hydrogen sulfate salt source |
| Bitterness masking agent |
No |
Claims 14-16 at 0.2 to 0.5 wt.% |
Omit or change outside band |
| Preservative suite |
No |
Claims 10-11, 21 |
Remove methylparaben/potassium sorbate or change package |
| Berry flavor |
No |
Claims 18-20 |
Use different flavor system or outside 0.01 to 0.1 wt.% |
Key Takeaways
- US 10,668,072 protects a defined oral liquid formulation of compound of formula (I) with pH 2.5 to 5.5 and 20 to 30 mg/mL drug concentration, plus required presence of hydroxypropyl-β-cyclodextrin, sodium citrate, and a sweetener (claim 1).
- Dependent claims lock in specific embodiments: hydrogen sulfate salt (claim 2), hydroxypropyl-β-cyclodextrin 13 to 17 wt.% (claims 3-4), sodium citrate dihydrate 0.7 to 1.5 wt.% (claims 7-8), and a complete sweetener preservation/buffering system using citric acid + sodium phosphate and preservatives methylparaben + potassium sorbate (claims 10-13).
- The best path to non-infringement is to change at least one of the claim 1 anchors: pH band or drug concentration band, or remove required excipients (hydroxypropyl-β-cyclodextrin, sodium citrate, sweetener). Avoiding only dependent features may still leave claim 1 exposure.
- A full US “patent landscape” across other related or opposing US patents cannot be produced from the provided claims text alone.
FAQs
1) Does claim 1 require hydroxypropyl-β-cyclodextrin at a specific wt.%?
No. Claim 1 requires it to be present, while wt.% limits appear in dependent claims 3-4.
2) What are the two numeric anchors that most strongly constrain product design?
The formulation pH (about 2.5 to about 5.5) and the drug concentration (about 20 mg/mL to about 30 mg/mL).
3) Can a hydrogen sulfate salt product avoid claim 2 but still infringe claim 1?
Yes. Claim 2 narrows to formulations prepared from hydrogen sulfate, but claim 1 still covers the salt generally if other requirements are met.
4) How do preservatives affect infringement risk?
Preservative selection (methylparaben and potassium sorbate) is required only in specific dependent embodiments (claims 10-13 and 21), not in claim 1.
5) What is the role of bitterness masking?
Bitterness masking is optional under claim 1 and becomes required only under dependent claims 14-16, with specific wt.% limits.
References
[1] US Patent 10,668,072 (claims as provided).
