Details for Patent: 9,375,405

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Which drugs does patent 9,375,405 protect, and when does it expire?

Patent 9,375,405 protects SENSIPAR and is included in one NDA.

This patent has eighty-one patent family members in twenty-nine countries.

Summary for Patent: 9,375,405

Title:	Rapid dissolution formulation of a calcium receptor-active compound
Abstract:	The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a calcium receptor-active compound and at least one pharmaceutically acceptable excipient, wherein the composition has a controlled dissolution profile. The present invention further relates to a method of manufacturing the pharmaceutical composition, as well as a method of treating a disease using the pharmaceutical composition.
Inventor(s):	Glen Gary Lawrence, Francisco J. Alvarez, Hung-Ren H. Lin, Tzuchi R. Ju
Assignee:	Amgen Inc
Application Number:	US12/942,646
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,375,405
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Compound;

United States Patent 9,375,405: Cinacalcet Hydrochloride Formulation Scope, Claim Analysis, and Patent Landscape

US Patent 9,375,405 protects oral pharmaceutical compositions containing cinacalcet hydrochloride, specific excipient classes, defined weight percentages, and, in several claims, particle and granule-size characteristics. The patent is formulation-focused rather than a basic compound patent. Its principal commercial relevance is the potential to cover generic or follow-on cinacalcet tablets that use conventional wet-granulation excipients and closely resemble the Sensipar formulation.

The strongest claim group is directed to compositions containing 10% to 40% cinacalcet HCl, 45% to 85% diluent, 1% to 5% binder, and 1% to 10% disintegrant. Claims 20 through 23 narrow the invention toward intragranular disintegrant and a specific starch, microcrystalline cellulose, povidone, and crospovidone formulation.

What drug and formulation does US 9,375,405 protect?

US 9,375,405 covers pharmaceutical compositions containing cinacalcet hydrochloride for treating hyperparathyroidism, hypercalcemia, hyperphosphatemia or an elevated calcium-phosphorus product.

The claims are composition claims. They do not require a particular brand name, tablet strength, manufacturing company, or dosage regimen. A product may fall within the claims if its formulation satisfies the listed ingredient, concentration, particle-size and granulation limitations.

Claim architecture

Claim group	Principal limitation	Commercial significance
Claims 1-4	Core formulation with defined active, diluent, binder and disintegrant ranges	Broadest formulation coverage
Claims 5-6	Povidone binder and crospovidone disintegrant	Covers common excipient choices
Claims 7-9	Particle morphology and amorphous/crystalline forms; D50 of 50 micrometers or less	Adds active-particle controls
Claims 10-14	Granule D50 of 50-150 or 80-130 micrometers; crospovidone placement	Targets granulation process outcomes
Claims 15-19	Granules, colloidal silicon dioxide, magnesium stearate, disease and diluent limitations	Captures conventional tablet manufacturing
Claims 20	Core composition with disintegrant present at least intragranularly	Narrows infringement to granulation architecture
Claims 21-23	Specific starch, microcrystalline cellulose, povidone and crospovidone composition	Most formulation-specific claims

How broad are the independent claims?

Claims 1, 20 and 21 are the principal independent claims.

Claim 1

Claim 1 requires:

1. Cinacalcet HCl at 10% to 40% by weight and 20 mg to 100 mg per composition;
2. A listed diluent at 45% to 85%;
3. A listed binder at 1% to 5%;
4. A listed disintegrant at 1% to 10%; and
5. Use for at least one of the listed calcium or parathyroid disorders.

The claim does not require:

• A tablet;
• A specific release profile;
• A particular salt polymorph;
• A specified dissolution result;
• A particular granulation method;
• A coating;
• Magnesium stearate;
• Colloidal silicon dioxide; or
• A specific brand or dosage strength.

The claim therefore reaches a wide range of immediate-release solid oral formulations, provided the formulation falls within the numerical ranges and uses the listed excipient categories.

Claim 20

Claim 20 resembles claim 1 but requires that the disintegrant be present at least intragranularly. This limitation narrows the claim from ingredient identity and concentration to excipient location within the granule structure.

A formulation with crospovidone only outside the granules should not satisfy the express intragranular requirement. A formulation containing both intragranular and extragranular crospovidone would remain within the literal scope if the other limitations are met.

Claim 21

Claim 21 is narrower and more commercially targeted. It requires:

• Cinacalcet HCl at 10% to 40%;
• Starch at 5% to 10%;
• Microcrystalline cellulose at 40% to 75%;
• Povidone at 1% to 5%; and
• Crospovidone at 1% to 10%.

The claim uses a duplicated "(b)" designation for starch and microcrystalline cellulose. That drafting error does not necessarily defeat the claim because the elements are separately described and the intended composition is apparent.

Claim 21 is more vulnerable to design-around than claim 1 because a competitor can potentially move one component outside its stated range or substitute a non-listed excipient. It is also more likely to map directly onto a conventional generic tablet formula.

What excipients are covered by US 9,375,405?

The patent claims specific excipient categories rather than all pharmaceutical excipients.

Diluent coverage

The claimed diluents are:

• Microcrystalline cellulose;
• Starch;
• Dicalcium phosphate;
• Lactose;
• Sorbitol;
• Mannitol;
• Sucrose;
• Methyl dextrins; and
• Mixtures of those materials.

A formulation using a diluent outside this list may avoid literal infringement of the diluent limitation, although the overall formulation and any applicable equivalents analysis would remain relevant.

Claim 19 narrows the diluent to microcrystalline cellulose or starch. Claim 21 requires both starch and microcrystalline cellulose in defined ranges.

Binder coverage

The listed binders are:

• Povidone;
• Hydroxypropyl methylcellulose;
• Hydroxypropyl cellulose;
• Sodium carboxymethylcellulose; and
• Mixtures of those binders.

Claim 5 specifically requires povidone. A formulation using a different binder, such as certain maltodextrins or copolymers, may avoid the literal binder limitation if it does not also include one of the listed binders.

Disintegrant coverage

The listed disintegrants are:

• Crospovidone;
• Sodium starch glycolate;
• Croscarmellose sodium; and
• Mixtures of those materials.

The claim text uses "crospovidine" in several places. Crospovidone is the recognized pharmaceutical excipient name and is the apparent intended subject of those limitations.

Claim 6 requires crospovidone. Claims 12-14 address whether crospovidone is intragranular, extragranular or both.

Which particle and granule characteristics are protected?

Claims 7 through 14 add physical-structure limitations that can materially affect infringement analysis.

Cinacalcet particle form

The claims cover:

• Needle-shaped particles;
• Rod-shaped particles;
• Plate-shaped particles;
• Amorphous powders;
• Crystalline particles; and
• Mixtures of those forms.

Claim 7 applies the morphology limitation to a formulation already containing crospovidone. Claim 8 covers amorphous or crystalline cinacalcet HCl. Claim 9 requires a particle D50 of 50 micrometers or less.

These limitations create analytical issues because particle morphology and particle-size distribution generally require batch-specific testing. The relevant evidence may include:

• Laser diffraction;
• Sieve analysis;
• Microscopy;
• X-ray diffraction;
• Solid-state characterization; and
• Manufacturing specifications.

Granule size

Claims 10 and 11 require a granule D50 measured by sieve analysis of:

• About 50 to 150 micrometers; or
• About 80 to 130 micrometers.

Claim 11 is narrower than claim 10. Claims 12 and 13 distinguish intragranular and extragranular crospovidone. Claim 14 allows either location or a combination, subject to the other requirements.

The granule-size claims can create a significant evidence burden. A generic manufacturer may have a formulation that meets the ingredient ranges but avoids claims 10 and 11 because its granule distribution falls outside the specified range. Conversely, routine manufacturing variation could create batch-to-batch risk if the product specification overlaps the patented range.

What are the likely design-around pathways?

The most practical design-around strategies involve the numerical ranges, excipient selection, particle size, and granulation architecture.

Design-around variable	Potential approach	Risk
Diluent	Use a non-listed diluent or move the listed diluent below 45% or above 85%	May avoid claim 1, subject to total composition constraints
Binder	Use a binder outside the listed group	May avoid the binder limitation
Disintegrant	Use a non-listed disintegrant	May avoid claim 1 if no listed disintegrant is present
Povidone	Replace povidone with another binder	Avoids claims 5 and 21
Crospovidone	Use croscarmellose sodium or sodium starch glycolate	Avoids crospovidone-specific claims
Starch/MCC combination	Change starch below 5%, above 10%, or MCC outside 40%-75%	Targets claim 21
Particle size	Maintain cinacalcet D50 above 50 micrometers	Targets claim 9 and dependent claims
Granule size	Maintain granule D50 outside 50-150 micrometers	Targets claims 10 and 11
Disintegrant location	Place disintegrant only extragranularly	Targets claim 20 and some dependent claims
Dosage amount	Use a strength outside 20-100 mg	May avoid the express amount limitation, but requires a commercially viable product

Design-around analysis must account for claim dependency. Avoiding claim 21 does not avoid claim 1 if the alternative still meets claim 1's broader ranges. A competitor must evaluate all independent claims and the dependent claims that may remain satisfied.

How does US 9,375,405 compare with compound and method-of-use patents?

US 9,375,405 is materially different from a basic cinacalcet compound patent.

Patent type	Typical subject matter	Relevance to generic entry
Compound patent	Cinacalcet molecule or salt	Broad active-ingredient protection; generally expires earlier
Salt or polymorph patent	Cinacalcet HCl form or solid-state characteristics	Can restrict API sourcing or formulation
Formulation patent	Excipients, concentrations, granulation and particle size	Targets the finished dosage form
Method-of-use patent	Treatment of hyperparathyroidism or related disorders	May affect label carve-outs and Paragraph IV strategy
Manufacturing patent	Crystallization, milling, granulation or tableting process	Can create supply-chain or process constraints

The '405 patent is most relevant where the proposed product uses the same broad excipient architecture as the reference product. It is less powerful against a materially different formulation that uses alternative excipients, different concentration ranges, or a different manufacturing structure.

What is the Orange Book relevance of US 9,375,405?

The Orange Book relevance depends on whether the patent is listed for an approved cinacalcet product and whether its claims correspond to the approved labeling. FDA's Orange Book distinguishes patents associated with approved drug products from patents that may exist elsewhere in the patent family or broader patent portfolio.[1]

For a listed formulation patent, an ANDA applicant may need to make one of the following certifications:

• Paragraph I: no relevant patent information is listed;
• Paragraph II: the patent has expired;
• Paragraph III: the applicant will wait until patent expiration; or
• Paragraph IV: the patent is invalid, unenforceable or will not be infringed.

A Paragraph IV certification can trigger patent litigation under 21 U.S.C. § 355(j)(5)(B)(iii). A timely infringement action may produce a statutory 30-month stay, subject to the statute and litigation events.[2]

The claim language indicates that the patent could be relevant to an immediate-release cinacalcet tablet. It does not, by itself, establish the patent's current Orange Book listing, use code, litigation history or enforceability.

When does US 9,375,405 lose exclusivity?

The patent's effective expiration date depends on:

• The earliest effective nonprovisional filing date;
• Any priority claims;
• Patent term adjustment;
• Patent term extension;
• Terminal disclaimers; and
• Whether the relevant claims remain enforceable.

Under 35 U.S.C. § 154, a utility patent generally expires 20 years from the earliest effective nonprovisional filing date, subject to adjustment and extension.[3] The grant date alone is not the expiration date.

The claim text supplied does not include the priority chain, filing date, PTA, PTE or terminal-disclaimer information. An exact expiration date cannot be calculated from the claims alone.

What patent litigation and settlement issues affect generic cinacalcet?

A generic applicant challenging the '405 patent would likely focus on four technical defenses.

Anticipation

The applicant would search for earlier cinacalcet tablet disclosures containing:

• 10% to 40% active;
• 45% to 85% diluent;
• 1% to 5% binder; and
• 1% to 10% disintegrant.

A reference must disclose all limitations, either expressly or inherently, to anticipate claim 1.

Obviousness

The combination of conventional excipients may create an obviousness challenge, particularly if prior art teaches cinacalcet tablets using microcrystalline cellulose, starch, povidone and crospovidone. The patent holder would likely rely on formulation performance, content uniformity, dissolution, manufacturability or stability data to defend the claimed ranges.

Written description and enablement

The broad Markush groups and wide percentage ranges may invite scrutiny of whether the specification supports the full claimed genus and enables the range without undue experimentation. Claims 10-14 may face separate scrutiny if the specification does not adequately connect granule size or disintegrant placement to demonstrated performance.

Infringement proof

A formulation patent case would likely require confidential ANDA and batch information. The relevant evidence may include:

• Master batch records;
• Finished-product specifications;
• API particle-size data;
• Granulation records;
• Excipient percentages;
• Coating composition; and
• Laboratory testing.

Settlement agreements could authorize a generic launch before patent expiration, but the claim text does not identify any settlement date, licensed entrant, launch date or licensee.

How strong is the patent estate around cinacalcet?

The '405 patent has meaningful formulation value but does not provide the same breadth as a compound patent. Its strength is highest when:

• The approved product uses the claimed excipient system;
• Generic ANDA formulations copy the same composition;
• The patent is listed for the relevant product;
• The patent term extends beyond compound exclusivity; and
• The patent holder has supporting dissolution, stability and manufacturability data.

Its strength is lower when a generic applicant can use an alternative disintegrant, binder or diluent, or can demonstrate that its particle and granule distributions fall outside the claimed ranges.

Cinacalcet has no biosimilar pathway risk because it is a small-molecule drug. Competitive entry occurs through the ANDA pathway, not through a 351(k) biosimilar application. FDA approval of generic cinacalcet depends on pharmaceutical equivalence, bioequivalence and applicable patent certifications.[4]

What commercial exposure does the patent create?

The commercial exposure is concentrated in oral cinacalcet tablets used for:

• Secondary hyperparathyroidism in patients with chronic kidney disease on dialysis;
• Hypercalcemia in parathyroid carcinoma; and
• Severe hypercalcemia in primary hyperparathyroidism when surgery is not clinically appropriate.

A generic manufacturer can potentially avoid the patent through a different formulation, but a copycat formulation using microcrystalline cellulose, starch, povidone and crospovidone presents higher Paragraph IV and infringement risk.

Revenue exposure depends on the approved product's sales, generic-entry timing, number of authorized entrants and the ability of competitors to design around the claims. The patent itself does not establish product revenue, market share or the economics of a settlement.

Key Takeaways

• US 9,375,405 is a cinacalcet HCl formulation patent, not a basic compound patent.
• Claims 1, 20 and 21 are the principal claims.
• Claim 1 broadly covers defined ranges of cinacalcet, diluent, binder and disintegrant.
• Claims 9-14 add particle-size, granule-size and disintegrant-location limitations.
• Claim 21 specifically targets starch, microcrystalline cellulose, povidone and crospovidone.
• The most credible design-arounds change excipient identity, move a component outside the claimed range, alter particle or granule size, or place the disintegrant only extragranularly.
• Generic applicants would likely challenge the patent through Paragraph IV certifications based on obviousness, anticipation, written description or enablement.
• Cinacalcet is a small molecule, so biosimilar litigation is not relevant.
• Exact patent expiration, Orange Book listing, litigation and settlement status require the official patent and FDA records, not the claim text alone.

FAQs About US Patent 9,375,405 and Cinacalcet Generic Entry

Does US 9,375,405 cover all cinacalcet tablets?

No. It covers only compositions satisfying the specified active-ingredient, excipient, percentage and, for certain claims, particle or granule limitations.

Can a generic use microcrystalline cellulose and avoid the patent?

Potentially. Use of microcrystalline cellulose alone does not automatically establish infringement. The complete formulation must be compared against the limitations of each asserted claim.

Does a different tablet strength avoid US 9,375,405?

Not necessarily. The independent claims require 20 mg to 100 mg of cinacalcet HCl, so a strength outside that range may avoid the express amount limitation. The formulation must still be assessed against all relevant claims and patent families.

Is crospovidone required in every claim?

No. Claims 1 and 20 allow several disintegrants. Crospovidone is specifically required by claims 6, 7, 12-14 and 21-23.

Does the patent cover a cinacalcet API manufacturing process?

No process limitation appears in the supplied claims. The claims are directed to pharmaceutical compositions and related physical characteristics, not to synthesis or manufacture of cinacalcet HCl API.

References

1. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

2. 21 U.S.C. § 355(j).

3. 35 U.S.C. § 154.

4. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application (ANDA). https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda

Drugs Protected by US Patent 9,375,405

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amgen	SENSIPAR	cinacalcet hydrochloride	TABLET;ORAL	021688-001	Mar 8, 2004		DISCN	Yes	No			Y
Amgen	SENSIPAR	cinacalcet hydrochloride	TABLET;ORAL	021688-002	Mar 8, 2004		DISCN	Yes	No			Y
Amgen	SENSIPAR	cinacalcet hydrochloride	TABLET;ORAL	021688-003	Mar 8, 2004		DISCN	Yes	No			Y

International Family Members for US Patent 9,375,405

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	045637
Australia	2004279318
Brazil	122018013029
Brazil	PI0414254
Canada	2536487