US 8,067,427 protects a narrowly defined oral pharmaceutical formulation containing vandetanib, also known as ZD6474, together with two classes of insoluble diluents: a brittle diluent and a ductile-compression diluent. The broadest claim covers listed calcium-based or magnesium-based brittle diluents paired with microcrystalline cellulose, starch, ethylcellulose, or carboxymethylcellulose. Claim 6 is the commercially most relevant limitation because it narrows the formulation to dibasic calcium phosphate and microcrystalline cellulose. The patent does not claim vandetanib as a molecule, its kinase-inhibition mechanism, or every vandetanib tablet.

US 8,067,427 Patent Scope, Claims, Expiration, and Vandetanib Formulation Landscape

What does US 8,067,427 protect?

US 8,067,427 protects a pharmaceutical composition containing three required components:

Vandetanib, identified in the patent as ZD6474, or a pharmaceutically acceptable salt.
A brittle diluent selected from:
- Dibasic calcium phosphate
- Tribasic calcium phosphate
- Calcium phosphate anhydrous
- Calcium carbonate
- Calcium sulphate
- Magnesium oxide
A second diluent that is practically insoluble and has ductile compression properties, selected from:
- Microcrystalline cellulose
- Starch
- Ethylcellulose
- Carboxymethylcellulose

The independent claim is composition-based. It does not require a particular tablet shape, coating, dissolution profile, manufacturing process, dosage strength, or therapeutic indication. The claim is directed to the excipient architecture surrounding vandetanib rather than to the active pharmaceutical ingredient itself. [1]

The claim structure is:

Claim	Scope
1	Vandetanib or salt plus one listed brittle diluent and one listed ductile diluent
2	Claim 1 limited to dibasic calcium phosphate
3	Claim 1 or 2 limited to microcrystalline cellulose
4	Claim 1 with broad weight ranges totaling 100 parts
5	Claim 1 with narrower weight ranges totaling 100 parts
6	Claim 4 or 5 limited to dibasic calcium phosphate and microcrystalline cellulose

How broad is claim 1 of US 8,067,427?

Claim 1 is broader than the commercially typical dibasic-calcium-phosphate/microcrystalline-cellulose formulation because it contains two separate Markush groups. A formulation may fall within claim 1 if it uses any one member from each group, provided the active ingredient is vandetanib or a covered salt.

The claim does not require:

A specific ratio of the two diluents.
A specific vandetanib concentration.
A tablet dosage form.
A particular compression force.
A disintegrant, lubricant, binder, glidant, coating, or capsule shell.
A specific polymorph or particle size.
A specific release profile.
A particular salt, provided the salt is pharmaceutically acceptable.

The functional language concerning a diluent that is "practically insoluble" and has "ductile compression properties" creates an additional claim-construction issue. The listed excipients provide the principal scope, but a dispute could concern whether a particular grade or material satisfies those functional descriptions. Microcrystalline cellulose is the clearest example of the ductile-compression component.

What formulations are protected by claims 2, 3, and 6?

Claims 2, 3, and 6 progressively narrow the formulation.

Claim 2: dibasic calcium phosphate

Claim 2 covers the use of dibasic calcium phosphate as the brittle diluent. It does not require microcrystalline cellulose because claim 2 depends only on claim 1.

A product using dibasic calcium phosphate with starch, ethylcellulose, or carboxymethylcellulose could remain within claim 2 if the other requirements of claim 1 are met.

Claim 3: microcrystalline cellulose

Claim 3 requires microcrystalline cellulose as the second diluent. It does not independently require dibasic calcium phosphate because it depends alternatively on claim 1 or claim 2.

A formulation using microcrystalline cellulose with calcium carbonate, tribasic calcium phosphate, or another listed brittle diluent may therefore fall within claim 3.

Claim 6: the commercially important combination

Claim 6 requires:

Vandetanib or a pharmaceutically acceptable salt.
Dibasic calcium phosphate.
Microcrystalline cellulose.
The weight ranges from claim 4 or claim 5.

Claim 6 is narrower than claim 1 and presents a more defined target for design-around work. A generic sponsor that uses the same two excipients but changes their proportions must assess both the broad ranges in claim 4 and the narrower ranges in claim 5.

What are the weight-range limitations in claims 4 and 5?

Claims 4 and 5 use parts by weight, with the three components totaling 100 parts.

Claim	Vandetanib	Brittle diluent	Ductile diluent
4	1 to 70 parts	1 to 96 parts	0.1 to 20 parts
5	5 to 50 parts	10 to 70 parts	1 to 15 parts

Claim 5 is narrower in every component range except that the ranges must still be read together with the 100-part total.

A formulation can fall outside claim 5 but remain within claim 4. For example, a formulation with 3 parts vandetanib would not satisfy claim 5 but could satisfy claim 4 if the diluent quantities meet the other limitations.

The parts are not the same as a tablet's labeled milligram strength. They describe the relative composition of the claimed three-component system. Other ingredients may be present unless excluded by the patent's claim language or an applicable claim-construction ruling.

Does US 8,067,427 cover Caprelsa tablets?

Caprelsa is the branded vandetanib product marketed by AstraZeneca. FDA approved Caprelsa tablets in 2011 for symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. The approved strengths are 100 mg and 300 mg. [2]

The supplied claims are consistent with protection for a compressed oral tablet formulation containing vandetanib and selected diluents. The claims do not, by themselves, establish that every commercial Caprelsa tablet has exactly the claimed excipient quantities. That determination requires comparison with the approved product's formulation and the patent's examples or regulatory disclosures.

The relevant infringement question is not whether a generic contains vandetanib. It is whether its formulation contains all limitations of at least one unexpired claim, either literally or under the doctrine of equivalents.

When does US 8,067,427 lose exclusivity?

Patent expiration must be determined from the patent's effective filing date, continuity data, terminal disclaimers, patent-term adjustment, and any patent-term extension. The issue date of December 6, 2011 does not establish the expiration date. [1, 3]

The relevant term analysis is:

Exclusivity right	Relevance to this patent
Patent term	Depends on the effective U.S. filing date and any PTA or terminal disclaimer
Patent-term extension	Must be checked against the USPTO and FDA extension records
New chemical entity exclusivity	Applies to the drug approval, not automatically to this formulation patent
Orphan-drug exclusivity	Applies to the approved indication and product, not as a general formulation patent right
Pediatric exclusivity	Adds six months to qualifying listed exclusivities when granted

The FDA Orange Book should be used to confirm whether US 8,067,427 remains listed for Caprelsa, the listed expiration date, and any patent-use code. [4] A patent may remain enforceable after FDA marketing exclusivity ends, but a formulation patent cannot block a product that does not practice an unexpired claim.

Is US 8,067,427 an Orange Book patent?

The patent's Orange Book relevance depends on whether AstraZeneca submitted it for listing against Caprelsa and whether FDA accepted the listing under the statutory and regulatory criteria. Orange Book listing is separate from validity and infringement. FDA does not determine whether the claims are valid or infringed when it publishes a patent listing. [4, 5]

For a generic applicant, the operative questions are:

Is US 8,067,427 currently listed for vandetanib tablets?
What expiration date appears in the Orange Book?
Is a use code associated with the patent?
Does the proposed generic formulation practice the listed claims?
Has the patent holder received a Paragraph IV notice?
Has litigation triggered a 30-month stay?

A formulation patent may be listed even though it does not claim the active ingredient itself. Under the Hatch-Waxman framework, a listed patent can require a certification in an abbreviated new drug application. [5]

What Paragraph IV risks arise from these claims?

A generic applicant can challenge the patent through a Paragraph IV certification alleging that the patent is invalid, unenforceable, or will not be infringed. The principal technical pathways are:

Non-infringement

The applicant may design its formulation to avoid at least one required element, such as:

Using only one diluent class.
Replacing dibasic calcium phosphate with an unlisted excipient.
Using a ductile excipient not included in the claim.
Selecting quantities outside the claimed ranges.
Demonstrating that the relevant excipient does not possess the required functional characteristics.

A formulation containing vandetanib alone with a soluble filler would generally present a stronger non-infringement position against claim 1 than a formulation containing both dibasic calcium phosphate and microcrystalline cellulose.

Invalidity based on anticipation

An earlier publication, patent, regulatory filing, or product disclosure would need to disclose every element of the asserted claim in a single reference. For claim 1, the reference would need to disclose vandetanib or a covered salt together with one qualifying brittle diluent and one qualifying ductile diluent.

Invalidity based on obviousness

An obviousness challenge would focus on whether a skilled formulator would have selected the claimed combination to address known problems such as poor flow, compactability, tablet strength, dissolution, or content uniformity. The narrow selection of excipients and the functional compression properties are likely to be central to that analysis. [1, 6]

Written description and definiteness

The terms "practically insoluble" and "ductile compression properties" may receive scrutiny if the patent specification does not provide adequate technical boundaries or reproducible testing criteria. The risk is fact-dependent and turns on the specification, prosecution history, and expert evidence.

What patent landscape surrounds vandetanib?

US 8,067,427 should be separated from the broader vandetanib patent estate.

Patent category	Typical subject matter	Relationship to US 8,067,427
Compound patents	Vandetanib and related quinazoline compounds	Separate from the formulation claims
Salt or solid-form patents	Salts, polymorphs, crystallinity, or stability	May create additional product risks
Formulation patents	Excipients, tablet structure, dissolution, or stability	US 8,067,427 belongs to this category
Method-of-use patents	Treatment of medullary thyroid cancer or other cancers	Separate infringement analysis
Manufacturing patents	Synthesis, intermediates, purification, or crystallization	Relevant to API supply rather than tablet composition
Regulatory exclusivity	NCE, orphan, or pediatric protection	Separate from patent rights

The patent does not claim a method of treating cancer. A generic product could face separate method-of-use issues even if it avoids US 8,067,427. Conversely, a product could avoid method-of-use infringement while still practicing the formulation claims.

How strong is the patent estate for this formulation?

The claim estate is strongest against a product that reproduces the apparent commercial formulation: vandetanib, dibasic calcium phosphate, and microcrystalline cellulose within the claimed ranges.

Its practical strength decreases where a competitor:

Uses a different filler system.
Removes either the brittle or ductile diluent.
Uses a formulation outside the claim 4 and claim 5 ranges.
Uses a non-tablet dosage form that does not otherwise satisfy the composition claim.
Demonstrates that a selected substitute does not meet the claim's functional language.

The claims have meaningful formulation specificity but limited reach beyond the listed excipient combinations. They do not provide a general monopoly over all vandetanib oral dosage forms.

What litigation and settlement issues affect US 8,067,427?

The claim text alone does not establish whether AstraZeneca has asserted US 8,067,427 against a particular generic applicant, whether a Paragraph IV notice has been served, or whether a settlement agreement contains a restricted-entry date.

The relevant public records are:

USPTO Patent Center for prosecution history and continuity.
FDA Orange Book for listing and expiration data.
Federal district court dockets for infringement complaints.
Federal Circuit decisions for claim construction and validity rulings.
SEC filings for disclosed generic challenges and settlements.

Any settlement date must be distinguished from the patent expiration date. A settlement may permit an agreed launch before patent expiration, while a patent may remain legally enforceable until its statutory term ends.

What manufacturing and geographic barriers remain?

US 8,067,427 is a United States composition patent. Its direct exclusionary effect is limited to the United States. Corresponding family members may create separate rights in Europe, Japan, Canada, or other jurisdictions, but foreign scope, validity, and expiration must be assessed independently.

The patent does not necessarily block manufacture outside the United States. It may still affect:

Importation of covered tablets into the United States.
Contract manufacturing for U.S. distribution.
U.S. commercial packaging or tableting.
ANDA approval and launch strategy.
Supply-chain selection for a U.S. generic.

The patent also does not necessarily block manufacture of vandetanib API. Its claims focus on the finished composition.

What is the commercial exposure from this patent?

The commercial exposure is tied to U.S. vandetanib tablet sales and the extent to which a generic must use the claimed excipient system to achieve acceptable tablet performance.

Risk is highest when:

The generic copies the reference-listed drug's excipient profile.
Dibasic calcium phosphate and microcrystalline cellulose are both used.
The relative amounts fall within claim 4 or claim 5.
The patent remains listed and unexpired.
The generic applicant files a Paragraph IV certification.

Risk is lower when a generic can establish a robust alternative formulation without the claimed pair of diluent classes. The availability of a technically acceptable alternative is therefore more important than the breadth of the active-ingredient limitation, which is relatively narrow because it is limited to vandetanib.

Key Takeaways

US 8,067,427 is a formulation patent, not a basic vandetanib compound patent.
Claim 1 requires vandetanib, one listed brittle diluent, and one listed ductile-compression diluent.
Claim 6 is the narrowest commercially important claim and focuses on dibasic calcium phosphate plus microcrystalline cellulose.
Claims 4 and 5 impose parts-by-weight ranges that must total 100 parts.
The patent does not require a particular dose, tablet coating, dissolution profile, manufacturing process, or therapeutic use.
A generic can pursue design-around strategies by changing the diluent system or moving outside the claimed ranges.
Orange Book listing and patent enforceability must be analyzed separately.
Exact patent expiration requires review of the patent's continuity, PTA, terminal-disclaimer, and FDA extension records.
The patent's strongest commercial position is against a Caprelsa-like tablet formulation.
Separate compound, method-of-use, solid-form, manufacturing, and regulatory exclusivities may affect vandetanib launch timing.

FAQs About US 8,067,427 and Vandetanib

Does US 8,067,427 cover all vandetanib tablets?

No. It covers only compositions containing vandetanib or a covered salt together with the specified brittle and ductile diluent categories.

Can a generic use microcrystalline cellulose and avoid the patent?

Possibly, but not automatically. The generic must also avoid the claimed brittle-diluent requirement and the applicable weight-range limitations.

Does a formulation outside claim 5 automatically avoid infringement?

No. It may still fall within the broader ranges of claim 4 or within claim 1, which has no express weight percentages.

Is US 8,067,427 a method-of-treatment patent?

No. The supplied claims are composition claims. They do not recite administering vandetanib to a patient or treating a disease.

Does FDA approval prove that a generic does not infringe US 8,067,427?

No. FDA approval and patent infringement are separate determinations. A generic may obtain approval while patent litigation or a launch restriction remains in place.

References

United States Patent No. 8,067,427. (2011). Pharmaceutical composition comprising ZD6474. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2011). Caprelsa (vandetanib) prescribing information. FDA.
United States Patent and Trademark Office. (2024). Manual of patent examining procedure: Patent term adjustment and patent term extension. USPTO.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.
United States Patent and Trademark Office. (2024). MPEP Chapter 2100: Patentability. USPTO.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Genzyme Corp	CAPRELSA	vandetanib	TABLET;ORAL	022405-001	Apr 6, 2011		RX	Yes	No	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Genzyme Corp	CAPRELSA	vandetanib	TABLET;ORAL	022405-002	Apr 6, 2011		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0411378.3	May 21, 2004

PCT Information
PCT Filed	May 18, 2005	PCT Application Number:	PCT/GB2005/001931
PCT Publication Date:	December 01, 2005	PCT Publication Number:	WO2005/112934

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	049059	⤷ Start Trial
Argentina	110045	⤷ Start Trial
Austria	E439841	⤷ Start Trial
Australia	2005244650	⤷ Start Trial
Brazil	PI0511253	⤷ Start Trial
Canada	2565513	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,067,427

Which drugs does patent 8,067,427 protect, and when does it expire?

Summary for Patent: 8,067,427