Patent: 10,786,662

Summary for Patent: 10,786,662

Title:	Method of manufacturing microneedle and microneedle manufactured thereby
Abstract:	A method of manufacturing a microneedle according to the present disclosure includes a step of preparing a microneedle; a step of cooling the microneedle; and a step of inducing an endothermic reaction of the cooled microneedle, and coating the cooled microneedle with an active ingredient at least once. In accordance with such a configuration, coatability of the active ingredient can be improved due to an endothermic reaction without a separate drying process, thereby providing superior medication.
Inventor(s):	Baek; Seung Ki (Seoul, KR), Ahn; Myun Hwan (Namyangju-si, KR), Baek; Sun Young (Seoul, KR)
Assignee:	QuadMedicine (Seongnam-si, KR)
Application Number:	15/863,318
Patent Claims:	see list of patent claims

Executive summary US 10,786,662 is a manufacturing process patent aimed at stabilizing and delivering water-soluble actives from water-soluble microneedles by (i) sequential vacuum/dry-air cooling and active-coating under tightly defined low relative humidity windows, (ii) immediate waterproofing using mineral- or lipid-based barrier agents, and (iii) room-temperature drying with no separate post-cooling drying step. The claims are broad at the process-system level (multiple cooling and coating hardware modes, multiple barrier agents, multiple active ingredient classes) but narrow in the critical operational envelope (humidity ranges, sequencing, sealed chamber cooling, no separate drying after cooling, and specific waterproofing-drying conditions). The estate is likely defensible against “make-and-coat” process variants that do not preserve the claimed RH windows and sequence, but it is vulnerable to design-arounds that decouple steps (separate drying), change humidity regime, or substitute non-lipid/mineral waterproof layers outside the enumerated families.

What is US Patent 10,786,662 and what does it claim about microneedle manufacturing?

Answer: US 10,786,662 claims a microneedle manufacturing method that cools a water-soluble microneedle and sequentially coats it with a water-soluble active ingredient, then waterproof-coats it with a mineral- or lipid-based agent, and dries at room temperature, where cooling and coating occur sequentially under vacuum or dry air without separate drying of the cooled microneedle, using defined relative humidity ranges during cooling (1% to 30%) and coating (1% to 20%), with the cooling performed in a sealed chamber and using rapid cooling methods and non-contact/low-heat coating techniques; the active is deposited in multilayer form with same-solubility actives.

Claim 1 as the core: what is actually protected?

Claim 1 is the anchor independent claim. It protects a coupled process chain that requires all of the following elements to be performed in the specified way:

A. Starting structure: “water-soluble microneedle” and no intermediate drying

• The process begins with a “water-soluble microneedle.”
• After cooling, the claim requires coating with a water-soluble active ingredient at least once.
• After the cooled microneedle is coated, the claim requires waterproof-coating with a waterproofing agent including:
  • a mineral-based substance or
  • a lipid-based material.
• Drying occurs at room temperature.
• Key limitation: cooling and coating are sequentially performed under vacuum or dry air conditions without a separate drying process of the cooled microneedle.

This “no separate drying” requirement is a primary patentability-and-infringement fulcrum: it blocks sequences that cool, dry, re-humidify/re-equilibrate, or otherwise insert a drying hold.

B. Operational envelope: sealed chamber cooling and RH windows

• Cooling chamber: the cooling step includes placing the microneedle in a sealed cooling chamber.
• Cooling humidity: relative humidity during cooling is 1% to 30%.
• Coating humidity: relative humidity during coating is 1% to 20%.
• The claim does not specify the absolute temperature, but it requires “rapid cooling” modes and the RH constraints.

These RH windows likely define novelty over conventional microneedle coating processes that tolerate higher humidity or use separate drying.

C. Cooling and coating can be implemented by multiple hardware “routes”

Claim 1 lists at least one of several rapid cooling methods:

• screw method
• piston method
• mono-pump method
• time-pressure method
• valve method
• spray method
• piezo method
• air-solenoid method
• immersing in a cooling substance

Cooling substances can include at least one of:

• liquid nitrogen
• tetrafluoroethane
• Peltier element cooling fan
• dry ice

For coating, Claim 1 likewise enumerates at least one of:

• electro-spinning coating method
• ultrasonic coating
• atomization coating
• non-contact spray coating

Claim 1 thus reads on many equipment choices as long as the process requirements (sequencing, environment, RH, and waterproofing/drying requirements) are met.

D. Active loading: multilayer structure and height limitation

• In Claim 1, the active ingredient coating is described as a multilayer structure using two or more active ingredients having the same solubility (Claim 1 language).
• Claim 8 adds an additional restriction: active ingredient coated up to one fifth or more of the height from the upper end of the microneedle.

This height qualifier supports an infringement argument if the active layer reaches at least that portion of needle height.

E. Waterproofing: mineral- or lipid-based agents, enumerated exemplars

The waterproofing agent includes:

• mineral-based substance, and/or
• lipid-based material.

Claim 1 then provides a detailed list of lipid/mineral candidates. The enumerated lipid family includes common topical barrier fats and waxes, for example:

• beeswax
• oleic acid
• soy fatty acid
• castor oil
• phosphatidylcholine
• vitamin E (d-alpha-tocopherol)
• common edible oils
• hydrogenated vegetable oils
• triglycerides (caprylic/capric derived from coconut or palm seed oil)
• phosphatidylcholine again (as both phospholipid and barrier component)

Claim 1 also restricts waterproofing application methods to at least one of:

• dip-coating
• atomization coating
• electro-spinning coating
• ultrasonic coating

F. “Room temperature drying” is a constraint

Claim 1 requires drying at room temperature after waterproof coating.

This can limit process variants that rely on elevated temperature drying to drive off solvent/water.

What do Claims 2-14 add? (Dependence map)

Dependent claims extend Claim 1 into mold/molding hardware and into specific polymer/additive compositions and specific active ingredient classes.

Claims 2-7: microneedle manufacturing feedstock via mold machining and polymer selection

Claim 2 introduces:

• mold with plurality of tip grooves
• supplying chemical liquid comprising raw material or biodegradable polymer
• removing mold from microneedle

Claim 3 defines example mold compositions:

• PDMS mold with at least one of: polyurethane, metal, biocompatible aluminum material, water-soluble polymer, lipophilic polymer, amphiphilic polymer
• amphiphilic and lipophilic polymer lists are extensive (HPC/HPMC, PCL, PGA, PLA, PLGA, PVP, PEG/PEO/PPO, PVME, PMA, etc.)

Claims 4-6 cover:

• centrifugation and polymer melting after injecting chemical liquid in low/high viscosity
• chemical liquid formed of biocompatible material and water-soluble additive
• biocompatible materials enumerated from cellulose derivatives, polysaccharides, and proteinaceous polymers to chitosan and multiple synthetic polymers

Claim 7 specifies water-soluble additives, again with trehalose/oligosaccharides/disaccharides and multiple polymeric or bioactive additives (including HA and various gels/polysaccharides).

Net effect: these dependent claims can create multiple “fallback” claim scopes for distinct microneedle bodies and casting/molding processes, which can matter for validity if the main claim is deemed too broad.

Claims 8-10: coating depth and coating-agent compositions

• Claim 8: active coating up to at least one fifth of microneedle height.
• Claim 9: a coating agent comprising thickening agent, biodegradable polymer resin, water-soluble substance, and active ingredient.
• Claim 10: thickening agent enumerations include many gums, carbomers, PVP/HPMC/HPC, and other cellulosic and polymeric thickeners.

These claims support infringement theories where the active is delivered as a structured coating formulation, not merely absorbed.

Claim 11-12: active ingredient classes

• Claim 11: active ingredient examples include many biologics and drugs (alpha/beta interferons, interferon gamma, ILs, G-CSF/GM-CSF, hCG, signal transduction proteins, calcitonin, insulin, growth hormone, filgrastim, heparin, etc.).
• Claim 12: water-soluble substance in the coating agent can be drawn from the same broad sugar/polysaccharide list.

This makes the patent’s claim coverage robust across “water soluble biologic/drug” classes, though actual enforcement will hinge on the process steps of Claim 1.

Claim 13: microneedle geometry

• microneedle has multiple tips conical or polygonal pyramid.

Claim 14: optional solvent evaporation

• further includes evaporating a solvent from the coated microneedle.

This can broaden enforcement to processes adding solvent evaporation post-coating, but it must still remain consistent with Claim 1’s “no separate drying of the cooled microneedle.”

How broad are the claims versus typical microneedle process steps, and what design-arounds reduce infringement risk?

Answer: The claim is broad on the “how” of cooling/coating hardware and the identity of waterproof lipids/minerals, but narrow on the sequencing and the specific humidity ranges. Design-arounds are most plausible by changing sequencing (adding a separate drying step), changing atmosphere (escaping the dry-air/vacuum constraint), moving outside RH windows, or switching away from the claimed waterproofing agent family and/or waterproofing method.

Highest-impact infringement levers

1. Sequencing and “no separate drying”
   Any process that cools, then dries (or holds with active drying) before active coating is a direct non-infringement path. Claim 1 is explicit that cooling and coating are sequentially performed under vacuum/dry air without a separate drying process of the cooled microneedle.

2. RH compliance (cooling 1%–30%; coating 1%–20%)
   If an accused process operates above 30% RH in cooling or above 20% RH during coating, it falls outside the claim’s operational definition. This is also a likely litigation flashpoint because RH is measurable if someone logs chamber conditions.

3. Sealed cooling chamber and rapid cooling methods
   Claim 1 requires cooling in a sealed chamber and at least one listed rapid cooling method. A process relying on non-listed refrigeration (e.g., room refrigeration without a “rapid cooling method” apparatus) may argue non-compliance, though equivalents could still be argued.

4. Waterproof coating and room temperature drying
   Replacing the waterproof barrier with a different polymer film system not mineral- or lipid-based (or not within enumerated lipid examples) is a design-around. Removing the waterproof layer or drying above room temperature also risks non-infringement.

Likely design-around categories that can avoid the claim

• Step separation: insert a distinct drying step immediately after cooling (even short).
• Atmosphere shift: conduct active coating in humid air rather than vacuum/dry air.
• RH regime change: run coating above 20% RH.
• Different barrier chemistry: use non-mineral and non-lipid barrier materials (for example, purely polymeric moisture barriers) rather than beeswax/oleic acid/lipid oils/phosphatidylcholine/triglycerides or mineral powders.
• Drying at elevated temperature: replace room temperature drying with controlled heat drying.

Risk remains even if active ingredient differs

Claim 1 is process-centric and lists active ingredient classes broadly elsewhere. If an accused process matches the process envelope, the identity of the active ingredient often becomes a secondary issue.

What microneedle formulations and actives fall within claim coverage?

Answer: The claims cover water-soluble microneedle bodies and water-soluble actives, including many biologics and common drugs, with coating excipients centered on sugars, polysaccharides, cellulose derivatives, cyclodextrins, and polyols as water-soluble stabilizers.

Formulation components anchored in dependent claims

• Biocompatible polymers for microneedle body (Claim 6):
  cellulose derivatives and polysaccharides, HA, chitosan, fibrin/agarose/pullulan, dextrans, and multiple synthetic polymers including PVP/PEG and related families.

• Water-soluble additives (Claim 7):
  trehalose, sucrose, maltose, lactose, cellobiose, oligosaccharides; also HA, alginate, pectin, carrageenan, chondroitin sulfate, dextran sulfate, and cyclodextrin.

• Coating agent thickening systems (Claim 10):
  gums (guar, locust bean), carbomers, PVP, HPMC/HPC, cyclodextrin, and other high-viscosity polymers.

• Actives (Claim 11):
  interferons (alpha and beta related to MS; interferon gamma), ILs, G-CSF/GM-CSF, hCG, salmon calcitonin, insulin, growth hormone, filgrastim, heparin and low-molecular-weight heparin, somatotropin, vaccine and enzyme inhibitor classes, and GNRH antagonists.

Waterproofing compositions anchored in Claim 1

The waterproofing agent includes lipid examples: beeswax, oleic acid, castor oil, phosphatidylcholine, vitamin E, and multiple edible oil and hydrogenated oil entries, plus triglycerides derived from coconut/palm seed oil, and mineral-based substances (not enumerated further).

How does US 10,786,662 compare with other microneedle manufacturing IP families?

Answer: Without the full patent-family record and the cited references from the prosecution history, a complete comparative landscape cannot be stated. However, structurally, this patent sits in a specific IP niche: process-environment controls (vacuum/dry air, RH windows), sequential step integration (cool then coat then waterproof then room-temp dry), and multi-option coating and cooling apparatus. That combination differentiates it from patents that only claim:

• the microneedle material formulation, or
• a general coating method without humidity windows and step sequencing, or
• generic waterproofing layers without the operational constraints.

In other words, the enforceable “handle” in US 10,786,662 is the manufacturing workflow and environmental limits, not a single chemical.

What patents protect the same concept: how many related filings likely exist?

Answer: No complete patent landscape count can be produced from the information provided. The claims alone do not include the patent family identifiers, priority data, assignee, or prosecution citations required to enumerate related US continuations, divisionals, or PCT nationalizations.

What is the Orange Book status, FDA pathway, and regulatory relevance?

Answer: The claims describe a manufacturing process and do not specify a named FDA-approved drug product, active ingredient label, or microneedle product that would allow mapping to an Orange Book listing. Without the patent’s stated assignee/product tie-in, regulatory status (Orange Book listing, exclusivity expirations, or any FDA reference product) cannot be determined.

When does exclusivity end and what launch risk exists for generics/biosimilars?

Answer: A definitive exclusivity timeline cannot be produced from the claim text alone because it does not establish:

• the effective filing date and term calculation inputs for US 10,786,662,
• whether the patent has any patent term adjustment,
• whether it is listed in the Orange Book for a specific NDC/RLD, or
• whether any related regulatory exclusivity (or pediatric extension) applies.

Litigation and Paragraph IV risk: what can be inferred?

Answer: US 10,786,662 reads like a process patent and would typically be asserted against products using the same manufacturing workflow. Paragraph IV is a Hatch-Waxman mechanism tied to ANDAs for small molecules and Orange Book listing. Without an Orange Book mapping, the relevant litigation mechanism (AND A Paragraph IV, 505(b)(2), or state-law process injunction) cannot be tied to this patent with certainty.

Claim strength and likely validity posture

Answer: Claim 1’s breadth is balanced by several narrow process constraints:

• specific RH windows during cooling and coating,
• vacuum/dry-air sequential cooling-to-coating without separate drying,
• sealed cooling chamber rapid cooling,
• waterproofing with lipid/mineral agents and room temperature drying.

That structure often improves validity over broad “coat-and-dry” patents by tying novelty to controlled manufacturing conditions rather than routine processing. At the same time, the large enumerations of polymer excipients, active ingredient types, cooling/coating techniques, and waterproof lipids can increase vulnerability to obviousness if prior art describes:

• sequential cooling and coating in low humidity,
• using lipid waterproof layers around water-soluble matrix microneedles,
• and using common non-contact coating technologies with similar RH control.

What would be the likely prior-art theme?

A typical invalidity theory would argue that:

• cooling and coating under controlled humidity is routine for moisture-sensitive dosage forms,
• water-soluble microneedles coated with drugs and then protected with lipid barriers are known,
• and the enumerated cooling/coating techniques are interchangeable for one of skill in the art.

Against that, the patentee would rely on the combination as claimed: sequential cooling and coating under defined RH windows and “no separate drying after cooling,” plus the specific waterproofing barrier options and room-temperature drying.

Where the claim is most actionable for enforcement

Answer: This is strongest for manufacturing sites that:

• use a sealed chamber to cool water-soluble microneedles rapidly,
• maintain RH within the claimed range during both cooling and coating,
• immediately coat the cooled microneedles with water-soluble actives under vacuum/dry air without drying between steps,
• then apply a lipid/mineral waterproof layer (examples include beeswax, oleic acid, castor oil, phosphatidylcholine, vitamin E, and oils/triglycerides),
• and dry at room temperature.

Key Takeaways

• US 10,786,662 protects a microneedle manufacturing workflow defined by step sequencing (cool then coat then waterproof then room-temperature dry) and tight environmental constraints (sealed chamber cooling; vacuum/dry-air sequencing; RH cooling 1%–30% and coating 1%–20%).
• The claim is broad in equipment implementation (multiple rapid cooling and coating methods) and broad in waterproofing lipid enumerations, but narrow in the operational envelope and the “no separate drying” limitation.
• Design-arounds with the highest likelihood target the claimed sequencing and RH windows, or replace waterproof barrier chemistry and drying conditions outside the claim.
• A complete US patent landscape count, competitor mapping, Orange Book status, exclusivity dates, and litigation/Paragraph IV risk cannot be derived from the claim text alone.

FAQs

1. Does “no separate drying after cooling” require the same chamber for cooling and coating?
2. If a competitor uses a lipid waterproofing agent not listed in Claim 1, does that avoid the patent?
3. How do the RH limits (1%–30% cooling; 1%–20% coating) get evidenced in litigation?
4. Can “rapid cooling” be satisfied by standard refrigeration cycles, or must it match the listed methods?
5. Do dependent claims on mold materials (PDMS and polymer lists) matter if the accused process uses different molds?

References

1. United States Patent No. 10,786,662.

Details for Patent 10,786,662

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974	10,786,662	2038-01-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984	10,786,662	2038-01-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985	10,786,662	2038-01-05

International Patent Family for US Patent 10,786,662

Country	Patent Number	Estimated Expiration
South Korea	101745682
United States of America	2018185625