Details for Patent: 10,213,487

Which drugs does patent 10,213,487 protect, and when does it expire?

Patent 10,213,487 protects BAQSIMI and is included in one NDA.

This patent has fifty-four patent family members in forty countries.

Summary for Patent: 10,213,487

Title:	Nasal powder formulation for treatment of hypoglycemia
Abstract:	The present invention provides a powder formulation containing glucagon or a glucagon analog for nasal administration, useful in the treatment of hypoglycemia, and in particular the treatment of severe hypoglycemia. The present invention also provides a method of making this powder formulation, and to devices and methods for using the powder formulation.
Inventor(s):	Sankaram Mantripragada, Claude A. Piche, Jo Jan Filip Van Betsbrugge
Assignee:	Amphastar Pharmaceuticals Inc
Application Number:	US15/545,332
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 10,213,487: Glucagon Nasal Powder Claims, Scope and Patent Landscape

US Patent 10,213,487 protects a specific glucagon nasal-powder platform centered on a 1:1:8 weight ratio of glucagon, phospholipid and beta-cyclodextrin. The patent reaches the composition itself, selected phospholipids, nasal applicators containing the powder, manufacturing processes, and treatment of hypoglycemia through intranasal administration. Its strongest infringement position is against products that reproduce the claimed excipient system and ratio. Its weakest areas are products using materially different excipients, ratios, delivery routes or manufacturing conditions.

What does US Patent 10,213,487 protect?

The patent protects five related subject-matter categories:

Claim category	Claims	Protected subject matter
Core composition	1-7	Glucagon, a defined phospholipid and beta-cyclodextrin in a 1:1:8 weight ratio
Closed composition	8	Glucagon, dodecylphosphocholine and beta-cyclodextrin only, in a 1:1:8 ratio
Optional excipients	9-12	Sodium citrate, citric acid and limited residual water
Nasal device	13	Applicator reservoir containing the claim 1 powder
Manufacturing	14-17	Aqueous mixing, phospholipid concentration at or above critical micelle concentration, drying and powder processing
Therapeutic use	18-19	Intranasal treatment of hypoglycemia, including administration to one nostril

The patent is directed to a dry glucagon formulation rather than to glucagon as a molecule. A competing product containing glucagon can avoid the composition claims if it does not use the claimed phospholipid and beta-cyclodextrin combination in the claimed ratio.

How should the independent claims be construed?

Claim 1: open composition claim

Claim 1 requires:

1. Glucagon corresponding to SEQ ID NO: 1;
2. A phospholipid;
3. Beta-cyclodextrin; and
4. A 1:1:8 weight ratio of glucagon to phospholipid to beta-cyclodextrin.

The term "comprising" makes claim 1 open-ended. An accused product may contain additional excipients and still fall within claim 1 if the three required components and the ratio are present.

The ratio is a material limitation. A formulation using 1:1:7 or 1:2:8 would present a non-infringement position, subject to claim construction, measurement methodology and possible doctrine-of-equivalents arguments. The relevant issue is whether the ratio applies to the components as incorporated into the finished powder or to the formulation before drying. The specification and prosecution history would control that analysis.

Claim 8: narrower closed composition

Claim 8 is materially narrower because it uses "consisting of." It covers a powder composed of:

• Glucagon;
• Dodecylphosphocholine; and
• Beta-cyclodextrin;

in a 1:1:8 weight ratio.

A product containing sodium citrate, citric acid, a buffer, a stabilizer or another formulation excipient may fall outside claim 8 even if it remains within claim 1. Claim 8 therefore provides a clean fallback claim for the specific dodecylphosphocholine formulation but has a more limited infringement perimeter.

Which phospholipids are covered?

Claims 2 through 7 identify five phospholipid alternatives:

Phospholipid	Claim
Dodecylphosphocholine	3
Didecylphosphatidylcholine	4
Lysolauroylphosphatidylcholine	5
Dioctanoylphosphatidylcholine	6
Dilauroylphosphatidylglycerol	7

Claim 2 is a Markush claim. It covers at least one member of the listed group or mixtures of those members. The dependent claims isolate each listed option.

The claim set does not expressly cover every phospholipid. A formulation using phosphatidylcholine, phosphatidylglycerol or another lipid outside the recited group would require a separate infringement theory under claim 1, including analysis of whether the generic term "phospholipid" covers that material. Claims 3 through 7 are narrower and do not expand the scope of claim 1.

What formulations are protected by US 10,213,487?

The most commercially relevant protected formulation is a dry nasal powder containing glucagon, dodecylphosphocholine and beta-cyclodextrin at 1:1:8 by weight.

Claims 9 through 12 add formulation detail:

• Sodium citrate or citric acid may be present.
• The citrate or citric acid content may be up to 10% by weight.
• Water may be present.
• Water content must be below 5% by weight.

These claims create additional protection around residual moisture and buffering. They do not require the formulation to be completely anhydrous. A powder with 0.5%, 2% or 4.9% water can fall within claim 12 if the other limitations are satisfied. Water at 5% or more would not literally satisfy the stated limitation.

The claims do not specify a particular particle-size distribution, emitted dose, nasal deposition profile, container geometry or glucagon concentration per device. Those features may be covered by other patents or regulatory specifications, but they are not express limitations of the supplied claims.

Does the patent cover Baqsimi?

The claim set is closely aligned with the technical architecture of Baqsimi, Eli Lilly's glucagon nasal powder. Baqsimi was approved by the FDA on July 24, 2019, for the emergency treatment of severe hypoglycemia in adults and children with diabetes aged four years and older at the time of approval.[2]

Baqsimi uses glucagon nasal powder delivered through a single-use nasal device. The composition and device concepts in claims 1, 8 and 13 are therefore commercially relevant to Baqsimi.

A product-by-product infringement conclusion requires comparison of the accused product's actual formulation, excipient quantities, water content, device configuration and manufacturing process. FDA labeling alone generally does not disclose every quantitative formulation parameter needed to establish infringement.

What manufacturing processes are protected?

Claims 14 through 17 protect a process with four principal stages:

1. Forming an aqueous solution containing glucagon and phospholipid;
2. Using phospholipid at or above its critical micelle concentration;
3. Adding beta-cyclodextrin;
4. Drying and processing the resulting solid into a uniform powder.

Claims 14 and 15 differ in the final product limitation. Claim 14 requires at least part of the powder to contain a phase characterized by an XRPD mesopeak. Claim 15 does not include that mesopeak limitation.

Claims 16 and 17 specify freeze drying or spray drying. Those are dependent process claims and do not necessarily exclude other drying techniques from the broader claims 14 and 15.

XRPD mesopeak limitation

The XRPD mesopeak requirement is a technical product-by-process limitation in claim 14. It may create evidentiary complexity because infringement depends on:

• The XRPD test method;
• Instrument parameters;
• Sample preparation;
• The location and definition of the mesopeak;
• Whether the feature is reproducibly present in commercial batches.

Claim 15 is potentially more enforceable against a process that uses the claimed order of addition and critical micelle concentration but produces a powder without the claimed XRPD mesopeak.

What nasal applicator is covered?

Claim 13 covers a nasal applicator with:

• A powder formulation reservoir; and
• A powder formulation contained in that reservoir;

where the formulation is the composition of claim 1.

The device claim is narrower than a general nasal-delivery claim because it incorporates the claim 1 formulation. A nasal device containing a different glucagon powder would not literally satisfy claim 13.

The claim does not expressly require a particular actuator, plunger, nozzle, metering structure or dose volume. Those elements may be relevant to infringement only if they appear in other claims or patents.

What method of use is protected?

Claim 18 covers treating hypoglycemia by administering the claimed composition as a powder to the nasal mucosa in a therapeutically effective amount. Claim 19 narrows that method to administration into only one nostril.

The method claims require the claimed composition. Intranasal administration of glucagon in a formulation lacking the specified glucagon-phospholipid-beta-cyclodextrin combination would not literally infringe claims 18 or 19.

The one-nostril limitation reflects the practical design of single-use nasal glucagon products. It may be difficult to use claim 19 against a product label that permits administration without expressly requiring one-nostril delivery. Claim 18 is commercially broader because it does not include that restriction.

When does US Patent 10,213,487 lose exclusivity?

US Patent 10,213,487 issued on February 26, 2019. Its patent term is calculated from the relevant nonprovisional application or international application date, not from the grant date. The nominal expiration is in 2034 based on the family filing chronology, subject to any patent-term adjustment, terminal disclaimer or patent-term extension reflected in USPTO records.[1]

Event	Date or status
Patent grant	February 26, 2019
Patent term basis	Twenty years from the applicable nonprovisional/PCT filing date
Nominal term endpoint	2034 family expiration period
Patent-term adjustment	Must be determined from the USPTO patent term data
Patent-term extension	No extension is established by the supplied claim record
FDA approval of Baqsimi	July 24, 2019

Patent expiration does not automatically mean immediate generic competition. FDA regulatory exclusivity, listed patents, litigation stays and settlement terms can affect the earliest commercial launch date.

What is the Orange Book status of this patent?

Baqsimi is an FDA-approved small-molecule or peptide drug product regulated through the NDA framework, and its relevant patents are evaluated through the Orange Book rather than the Purple Book. The Orange Book records patent listings submitted by the NDA holder, including formulation, method-of-use and other patents that may be relevant to an ANDA applicant.[3]

US 10,213,487 is relevant to Orange Book analysis because its claims cover the approved dosage form and its administration method. The practical effect depends on:

• Whether the patent is listed against the Baqsimi NDA;
• Which claims are identified in the FDA patent-use code;
• Whether an ANDA applicant certifies to the patent;
• Whether the NDA holder brings a timely infringement action.

A generic applicant may file a Paragraph IV certification asserting that the patent is invalid, unenforceable or not infringed. A timely patent action can trigger a statutory stay of ANDA approval for up to 30 months under the Hatch-Waxman framework.[4]

Which companies are challenging Baqsimi exclusivity?

The supplied claim record does not identify a Paragraph IV filer, ANDA applicant, litigation complaint or settlement agreement. The principal competitive threat is therefore best analyzed by product pathway rather than by a confirmed challenger.

Potential entrants would generally use one of three strategies:

Strategy	Regulatory route	Relevance to this patent
Same or substantially similar nasal powder	ANDA, if FDA determines sameness and bioequivalence can be shown	Highest direct patent exposure
Different nasal powder formulation	ANDA or other FDA pathway depending on product differences	May avoid exact ratio and excipient claims
Injectable glucagon product	ANDA or separate application pathway	Does not practice the intranasal composition or device claims

A glucagon product is not a biosimilar merely because glucagon is a peptide. Biosimilar status under section 351(k) applies to biological products licensed under the Public Health Service Act. A conventional generic glucagon product is generally analyzed through the applicable abbreviated drug-approval pathway, not the Purple Book biosimilar pathway.[5]

How strong is the patent estate?

The patent has meaningful but concentrated strength.

Strongest protection

The strongest positions are:

• Exact 1:1:8 ratio;
• Dodecylphosphocholine formulation under claims 1 and 8;
• The combination of formulation and nasal delivery;
• The manufacturing sequence requiring phospholipid at or above critical micelle concentration;
• Claim 15, which omits the XRPD mesopeak limitation.

These limitations are technically specific and can be compared against a competitor's batch records, development reports and manufacturing instructions.

Weakest protection

The weaker positions are:

• Claim 13, because it depends on the claim 1 composition;
• Claim 19, because it requires one-nostril administration;
• Claim 14, because XRPD mesopeak testing may create proof and reproducibility issues;
• The exact ratio limitation, if a competitor can develop a clinically equivalent formulation outside the literal range;
• Claims directed to the listed phospholipid alternatives, if the market product uses a different lipid.

The patent does not independently block all nasal glucagon products. It blocks products that combine the specific formulation architecture with the claimed ratios, components or process steps.

How does Baqsimi compare with competing glucagon products?

Product	Company	Route	Product type	Direct exposure to US 10,213,487
Baqsimi	Eli Lilly	Intranasal	Dry glucagon powder	High, based on formulation and device alignment
Gvoke	Xeris Pharmaceuticals	Subcutaneous injection	Ready-to-use liquid glucagon	Low for the intranasal claims
Zegalogue	Zealand Pharma	Subcutaneous injection	Dasiglucagon injection	Low for the claimed glucagon powder
Traditional emergency glucagon kits	Multiple companies	Injection	Reconstituted powder or liquid injection	Low unless a product adopts the claimed nasal formulation

Baqsimi has the closest technical relationship to the patent. Gvoke and Zegalogue compete commercially in severe hypoglycemia but use different routes and formulation platforms. Their products do not, on the supplied claim language, practice the claimed nasal powder system.

What generic launch risks exist?

A generic nasal glucagon applicant faces four principal risks:

1. Composition risk. The applicant may reproduce the 1:1:8 glucagon-phospholipid-beta-cyclodextrin ratio.
2. Device risk. The applicant may use a reservoir-based nasal applicator containing the claimed powder.
3. Process risk. The manufacturing process may use the claimed order of addition, critical micelle concentration and drying steps.
4. Method-of-use risk. The approved labeling may direct treatment of hypoglycemia through the nasal mucosa.

A design-around could use another absorption enhancer, another cyclodextrin, a different ratio, a different delivery device or a materially different drying process. Regulatory equivalence and clinical performance may make those alternatives commercially difficult even where they reduce patent exposure.

What geographic coverage does the patent provide?

US 10,213,487 provides protection only in the United States. International protection would depend on corresponding national patents in the PCT family and their individual prosecution outcomes, claim scope and expiration dates.

A company commercializing the same formulation outside the United States must separately evaluate Canadian, European, Japanese, Australian and other national rights. Patent term, supplementary protection certificates, opposition proceedings and national claim amendments can materially change the international risk profile.

Key Takeaways

• US 10,213,487 is a formulation-and-use patent directed to intranasal glucagon powder.
• The central limitation is a 1:1:8 weight ratio of glucagon, phospholipid and beta-cyclodextrin.
• Dodecylphosphocholine is the commercially most important listed phospholipid.
• Claim 1 is open-ended; claim 8 is closed and excludes additional composition components.
• Claims 14 through 17 protect aqueous preparation, micelle-level phospholipid concentration, drying and powder processing.
• Claim 14 requires an XRPD mesopeak; claim 15 does not.
• The patent aligns closely with the technical platform used by Baqsimi.
• Injectable glucagon competitors such as Gvoke and Zegalogue have limited direct exposure to these claims.
• Generic nasal glucagon products face composition, device, manufacturing and method-of-use risks.
• The nominal patent term extends into the 2034 period, subject to USPTO term calculations and any applicable regulatory or patent-term adjustments.
• No Paragraph IV challenger, litigation outcome or settlement agreement is identified in the supplied record.

FAQs

Is beta-cyclodextrin required for infringement?

Yes. Claims 1 through 19 require beta-cyclodextrin directly or through dependency. A glucagon nasal powder without beta-cyclodextrin would not literally satisfy these claims.

Can a formulation with a different phospholipid avoid the patent?

It may avoid claims 2 through 7 if the phospholipid is outside the listed group. Claim 1 still requires analysis because it recites the broader term "a phospholipid."

Does a 1:1:8 ratio mean the formulation must contain equal glucagon and phospholipid amounts?

Yes, by weight, the claim requires one part glucagon, one part phospholipid and eight parts beta-cyclodextrin. The relevant basis for measuring the ratio must be determined from the patent specification and prosecution history.

Is a nasal glucagon product automatically a biosimilar?

No. Biosimilar classification depends on the statutory product category and regulatory pathway. Nasal glucagon competition would generally involve generic or other drug-approval analysis rather than an automatic 351(k) biosimilar pathway.

Can a competitor avoid the patent by using two nostrils?

Using two nostrils may avoid claim 19's one-nostril limitation, but it would not avoid claims 1 through 18 if the product and treatment method satisfy those broader claims.

References

1. United States Patent and Trademark Office. (2019). United States Patent No. 10,213,487, Glucagon formulations and methods of use.
2. U.S. Food and Drug Administration. (2019, July 24). FDA approves first generic glucagon nasal powder for treatment of severe hypoglycemia.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (n.d.). Hatch-Waxman amendments and abbreviated new drug applications.
5. U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products.

Drugs Protected by US Patent 10,213,487

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amphastar Pharms Inc	BAQSIMI	glucagon	POWDER;NASAL	210134-001	Jul 24, 2019		RX	Yes	Yes			Y			TREATMENT OF SEVERE HYPOGLYCEMIA IN PATIENTS WITH DIABETES

Foreign Priority and PCT Information for Patent: 10,213,487

PCT Information
PCT Filed	February 16, 2016	PCT Application Number:	PCT/US2016/018003
PCT Publication Date:	August 25, 2016	PCT Publication Number:	WO2016/133863

International Family Members for US Patent 10,213,487

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016220235
Australia	2021203035
Brazil	112017014994
Canada	2975562
Chile	2017002031
China	107278154
Colombia	2017008148