Patent: 10,144,776

Summary for Patent: 10,144,776

Title:	Treatment of central nervous system disorders by intranasal administration of immunoglobulin G
Abstract:	The present invention provides, among other aspects, methods and compositions for treating a central nervous system (CNS) disorder by delivering a therapeutically effective amount of a composition of pooled human immunoglobulin G (IgG) to the brain via intranasal administration of the composition directly to the olfactory epithelium of the nasal cavity. In particular, methods and compositions for treating Alzheimer\'s disease are provided.
Inventor(s):	Frey; William H. (White Bear Lake, MN), Hanson; Leah Ranae Bresin (Vadnais Heights, MN), Pokropinski; Sharon (Schaumburg, IL), Rausa; Francisco M. (Vernon Hills, IL)
Assignee:	Baxalta Incorporated (Bannockburn, IL) Baxalta GmbH (Zug, CH)
Application Number:	15/335,027
Patent Claims:	see list of patent claims

United States Patent 10,144,776 (Pooled Human IgG Intranasal Delivery to Upper Third of Nasal Cavity): Claim Scope, Patent Landscape, Expiration and Challenge Risk

United States Patent 10,144,776 claims a CNS-treatment method using intranasal administration of pooled human IgG with a quantified deposition requirement: at least 40% of administered IgG contacts nasal epithelium in the upper third of the nasal cavity. Dependent claims narrow to specific CNS indications (including Alzheimer’s and Parkinson’s), delivery mechanics (drop, directed liquid aerosol, directed powder aerosol), deposition thresholds (50% to 70%), and product/formulation parameters (glycine-containing aqueous solutions, pH windows, and dry powder preparations). The enforceable value is driven by the deposition metric, the upper-third targeting limitation, and the combination of (i) IgG as the active modality, (ii) pooled-human IgG, and (iii) intranasal route with an anatomic deposition constraint.

What is US Patent 10,144,776 claiming in pooled human IgG intranasal CNS therapy?

Answer: A method claim that requires intranasal dosing of pooled human IgG with a defined deposition into the upper third nasal epithelium to treat CNS disorders.

Independent claim 1: the “anatomic deposition” novelty lever

Claim 1 requires all elements:

• Treat a subject with a CNS disorder.
• Deliver a therapeutically effective amount of a composition comprising pooled human IgG to the brain.
• Delivery to the brain occurs by intranasal administration to the upper third of the nasal cavity.
• Quantified deposition: at least 40% of pooled human IgG administered contacts nasal epithelium in the upper third of the nasal cavity.

This type of claim is typically harder to design around than route-only claims because it adds a measurable distribution requirement tied to the upper-third anatomic region.

Dependent claims 2–5: indication scope

• Claim 2 includes broad CNS disorder classes: neurodegenerative, demyelinating, movement/extrapyramidal, psychiatric syndromes, etc.
• Claim 3 narrows to a list including Alzheimer’s, Parkinson’s, multiple sclerosis, ALS, Huntington’s, cerebral palsy, bipolar disorder, schizophrenia, and PANS.
• Claim 4 narrows further to Alzheimer’s, multiple sclerosis, Parkinson’s.
• Claim 5 narrows further to Alzheimer’s.

From a risk perspective, this creates a stacked indication ladder. Any product-development targeting one of these listed conditions can remain inside the claim family even if clinical positioning uses different ICD-style descriptors.

Dependent claims 6–7: delivery mechanics

• Claim 6: intranasal administration via a liquid drop directly onto nasal epithelium.
• Claim 7: directed administration of a liquid aerosol to nasal epithelium in the upper third.

These are mechanistic constraints that can matter for both infringement (how the dosing device directs deposition) and design-around (changing droplet/aerosol physics while keeping the same actives and dosing objectives).

Dependent claims 8–10: deposition thresholds

Claim 7’s directed liquid aerosol is then restricted by deposition:

• Claim 8: at least 50%
• Claim 9: at least 60%
• Claim 10: at least 70%

This suggests the patent is built around a dose-to-region deposition performance envelope.

Dependent claims 11–14: powder aerosol pathway

• Claim 11: directed powder aerosol to the upper third.
• Claims 12–14: deposition thresholds at 50% / 60% / 70%.

This expands device-mode coverage across both liquid and dry-powder delivery platforms.

Dependent claim 15–16: deposition thresholds under claim 1

• Claim 15: at least 50% contacts upper-third epithelium.
• Claim 16: at least 60%.

These claims further tighten claim 1’s baseline ≥40% requirement for additional patent positions.

Dependent claims 17–23: formulation and composition boundaries

Claim 17 specifies the composition consisting essentially of:

• pooled human IgG plus glycine, histidine, or proline (selected amino acid).

Claims 18–20 define aqueous composition with both IgG concentration and glycine concentration, plus pH windows:

• pooled human IgG: 10 mg/mL to 250 mg/mL
• glycine: 50 mM to 500 mM
• pH: either 4.0 to 6.0 or 6.0 to 7.5 (two alternate ranges)

Claims 21–23 define a dry powder composition prepared from an aqueous solution having the same IgG and glycine concentration bands and pH ranges.

This matters because it gives the patentee multiple layers of fallback: if deposition can be challenged, formulation constraints still provide independent infringement theories where product composition overlaps.

Dependent claims 24–27: dosing amount, frequency

• Claim 24: 0.08 mg to 100 mg IgG/kg
• Claim 25: fixed dose 50 mg to 10 g
• Claim 26: at least twice monthly
• Claim 27 repeats the ≥70% deposition requirement

In infringement assessment, the dosing-frequency and dose-range claims support multiple “entry points” if clinical protocols vary by investigator/site.

Which CNS disorders does US 10,144,776 cover and how broad is the indication strategy?

Answer: It covers a wide CNS disorder taxonomy, with explicit fallback lists that include Alzheimer’s and Parkinson’s.

Broad claim 2 categories

Claim 2 lists disorder groupings spanning:

• neurodegenerative disorders,
• systemic atrophy primarily affecting CNS,
• extrapyramidal/movement disorders,
• demyelinating disorders,
• episodic/paroxysmal disorders,
• paralytic syndromes,
• nerve/nerve root/plexus disorders,
• organic mental disorders and psychoactive-substance induced mental/behavioral disorders,
• schizophrenia spectrum,
• mood/affective and related neurotic/stress-related/somatoform disorders,
• behavioral syndrome and adult personality/behavior disorders,
• psychological development disorders,
• child onset behavioral/emotional disorders.

This breadth increases litigation surface if an accused therapy is clinically described under any of these categories.

Narrow list claim 3 is where commercial risk concentrates

Claim 3’s list is commercially aligned with high-interest neurodegenerative and neuropsychiatric programs: Alzheimer’s, Parkinson’s, MS, ALS, Huntington’s, schizophrenia, and PANS.

Claim 4–5 create focused high-value positions

Claim 4 focuses on Alzheimer’s/MS/Parkinson’s. Claim 5 further focuses on Alzheimer’s. If a competitor pursues any of these lead indications, the patent family offers multiple parallel claim positions.

What delivery system limitations create the key design-around barriers?

Answer: Upper-third targeting plus quantitative IgG deposition (≥40% and dependent ≥50/60/70%) and specific delivery modalities (drop, directed liquid aerosol, directed powder aerosol).

Upper third anatomic limitation

The core limitation is anatomic: delivery to the upper third of the nasal cavity and deposition into upper-third nasal epithelium. Many intranasal approaches claim “intranasal” or “nasal mucosa” more generally. A competitor that cannot credibly shift dosing away from upper-third contact while still reaching brain targets faces infringement risk.

Quantified deposition thresholds

• Baseline: ≥40% contacts upper-third epithelium (claim 1)
• Higher fallbacks: ≥50%, ≥60%, ≥70% (claims 8–10, 12–14, 15–16, 27)

These thresholds are performance-based. They can be tested by labeled IgG deposition studies. In litigation, the deposition metric becomes the focal factual and expert issue.

Device mode variants

The claim family covers:

• liquid drop (claim 6),
• directed liquid aerosol (claims 7–10),
• directed powder aerosol (claims 11–14).

A competitor may attempt a different device physics approach, but the patent’s coverage is broad across the principal intranasal delivery modes.

What formulations are protected by US 10,144,776 and what parameters matter most?

Answer: Glycine-containing pooled human IgG aqueous formulations with defined concentration/pH windows and dry powder preparations from those aqueous solutions.

Composition consisting essentially of IgG + amino acid

Claim 17 limits the “consists essentially of” boundary to pooled human IgG plus one amino acid selected from glycine, histidine, proline. This can constrain formulations that add extra excipients if those excipients are not compatible with “consisting essentially of.”

Concentration ranges and pH windows

The core parameter set (claim 18 and dependent claims) includes:

• pooled human IgG: 10–250 mg/mL
• glycine: 50–500 mM
• pH: 4.0–6.0 OR 6.0–7.5

Dry powder claims reuse these same solution-origin conditions (claims 21–23), so a competitor cannot simply change dosage form without keeping the originating formulation in-range.

Why this is commercially important

If a competitor uses:

• different stabilizers (other amino acids or buffering systems),
• different IgG concentration bands,
• pH outside the windows,
• or a dry-powder pathway not derived from the in-range aqueous solution conditions,

then formulation infringement theories may narrow. If deposition performance still overlaps, infringement risk can still persist under method-of-treatment claims that do not require the exact formulation limits. But the formulation-dependent claims offer additional coverage layers.

What dose ranges and dosing frequency are within the claim?

Answer: Broad but defined dosing parameters, including per-kg ranges and fixed dose bands, plus at-least-twice-monthly scheduling.

• 0.08 mg to 100 mg IgG/kg (claim 24)
• 50 mg to 10 g fixed dose (claim 25)
• at least twice monthly (claim 26)
• plus deposition thresholds (claim 27 with ≥70% in a dependent context)

These constraints can interact with real-world protocols. Many clinical studies titrate dose across cohorts; the presence of wide numeric ranges increases the chance that at least one administered cohort aligns with claim scope.

How strong is the patent estate strength implied by this claim design?

Answer: The estate strength is driven by claim architecture that stacks (i) anatomic deposition, (ii) deposition fraction, (iii) delivery modality, and (iv) formulation windows.

This claim set is built like an infringement lattice:

1. Performance-based deposition: quantified % IgG contacting upper-third nasal epithelium.
2. Route + anatomy + modality: intranasal delivery to upper third, via drop/aerosol/powder aerosol.
3. Fallback numeric thresholds: 40% baseline, with 50/60/70% dependent sub-claims.
4. Composition fallbacks: glycine-containing formulations and dry powder derivations.
5. Indication ladder: broad CNS disorder taxonomy down to specific disease names like Alzheimer’s.

That combination increases the probability that an accused regimen will land inside at least one claim pathway unless the competitor changes fundamentals: active type (pooled human IgG), delivery anatomy (upper-third contact), delivery method type, deposition performance, or the formulation origin conditions.

What generic entry risks exist for CNS intranasal IgG approaches?

Answer: Typical small-molecule “generic” pathways do not map cleanly onto pooled human IgG products; the risk is more about biosimilar/biologic follow-on and method-of-use/process barriers for any IgG intranasal CNS therapy.

For intranasal IgG CNS products, “entry risk” usually arises via:

• follow-on biologics/biosimilars (where feasible),
• alternative product forms that attempt to move outside deposition or formulation boundaries,
• method-of-use and formulation carve-outs.

The patent’s deposition and anatomic targeting can function as a “process-of-delivery” gate even if the active biologic is the same.

What would infringement analysis likely focus on for US 10,144,776?

Answer: Whether the administered IgG contacts upper-third nasal epithelium at the claimed fractions, and whether the intranasal dosing method falls within the covered delivery modes.

Key infringement questions

• Does the dosing deliver pooled human IgG intranasally to the upper third?
• What fraction of IgG contacts upper-third nasal epithelium (≥40% / ≥50% / ≥60% / ≥70%)?
• Is the delivery via liquid drop, directed liquid aerosol, or directed powder aerosol to the upper third?
• Does the formulation fall within the amino-acid selection and the IgG/glycine concentration and pH windows, and is a dry powder derived from those in-range aqueous solutions?

Evidentiary battleground

The deposition threshold likely drives the expert dispute. In litigation, deposition quantification and nasal deposition mapping become the central factual issue because it directly tracks claim limitations.

Key Takeaways

• US 10,144,776 is anchored to a deposition metric: at least 40% of administered pooled human IgG must contact upper-third nasal epithelium after intranasal administration to reach the brain.
• Design-around is harder than route-only intranasal claims because the patent requires both anatomic targeting and quantified deposition; it also includes dependent fallbacks at 50/60/70%.
• Indication coverage ranges from broad CNS disorders to disease-specific lists, with commercial hotspots including Alzheimer’s and Parkinson’s.
• Delivery modalities are explicitly covered: liquid drop, directed liquid aerosol, and directed powder aerosol.
• Formulation claims add extra layers via glycine-containing pooled IgG aqueous ranges, pH windows, amino-acid selection in “consists essentially of” form, and dry powder derivation from those solutions.
• Litigation and entry risk will center on deposition studies and delivery-device performance that maps the delivered IgG to the upper-third epithelium.

FAQs

1. Can a competitor avoid infringement by changing intranasal deposition from the upper third to a different nasal region?
   If the design reduces IgG contact with upper-third epithelium below the claimed fractions, it can potentially avoid the anatomic deposition limitation, which is central to claim 1.

2. Does using the same pooled human IgG but changing the formulation buffer outside glycine/pH windows avoid US 10,144,776?
   It may avoid formulation-dependent dependent claims, but method claim 1 can still apply if deposition and delivery mechanics remain within the covered limitations.

3. Are liquid aerosols and powder aerosols equally covered under the claims?
   Yes. The claim set includes directed liquid aerosol and directed powder aerosol pathways with deposition-threshold dependent claims.

4. How do the deposition thresholds (40% vs 70%) affect launch timing and litigation risk?
   Higher thresholds in dependent claims can increase the range of infringement theories if the product performs well in deposition, making it more difficult for an accused product to fall outside the claim set.

5. Does the wide dosing range (mg/kg and fixed dose) make it harder to design a non-infringing regimen?
   Yes. Wide numeric ranges increase the likelihood that clinical dosing schedules overlap at least one claimed dose tier.

References

1. United States Patent 10,144,776, “Method for treating central nervous system disorders using intranasal delivery of pooled human IgG to the brain,” claims text as provided.

Details for Patent 10,144,776

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Csl Behring Ag	CARIMUNE, CARIMUNE NF, PANGLOBULIN, SANDOGLOBULIN	immune globulin intravenous (human)	For Injection	102367	July 27, 2000	10,144,776	2036-10-26
Csl Behring Ag	PRIVIGEN	immune globulin intravenous (human), 10% liquid	Injection	125201	July 26, 2007	10,144,776	2036-10-26
Csl Behring Ag	PRIVIGEN	immune globulin intravenous (human), 10% liquid	Injection	125201	October 02, 2009	10,144,776	2036-10-26
Csl Behring Ag	PRIVIGEN	immune globulin intravenous (human), 10% liquid	Injection	125201	February 07, 2013	10,144,776	2036-10-26
Bio Products Laboratory	GAMMAPLEX	immune globulin intravenous (human)	Injection	125329	September 17, 2009	10,144,776	2036-10-26
Bio Products Laboratory	GAMMAPLEX	immune globulin intravenous (human)	Injection	125329	February 07, 2014	10,144,776	2036-10-26