Details for Patent: 7,825,137

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Which drugs does patent 7,825,137 protect, and when does it expire?

Patent 7,825,137 protects XALKORI and is included in two NDAs.

This patent has twenty-eight patent family members in twenty-three countries.

Summary for Patent: 7,825,137

Title:	Method of treating abnormal cell growth
Abstract:	The present invention relates to the use of (R)-3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine, a novel c-Met/HGFR inhibitor, for treating abnormal cell growth in mammals. In particular, the invention provides methods of treating mammals suffering from cancer.
Inventor(s):	James Gail Christensen, Yahong Zou
Assignee:	Pfizer Corp SRL
Application Number:	US12/095,114
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 7,825,137: Crizotinib Claims, Patent Scope, Expiration, and Generic Entry Risk

US Patent 7,825,137 covers methods of treating ALK-mediated cancer with crizotinib, including the marketed active ingredient in Xalkori. Its strongest commercial protection is directed to use of the specific crizotinib enantiomer in ALK-driven cancers, particularly genetically altered ALK cancers such as ALK-positive non-small cell lung cancer. The patent does not broadly claim every ALK inhibitor, every crizotinib formulation, or the chemical compound itself.

The patent issued on November 2, 2010. Its 20-year patent term is generally calculated from the relevant nonprovisional or international filing date, with a projected expiration in August 2027. Xalkori received FDA approval on August 26, 2011, and its five-year new chemical entity exclusivity expired in 2016.[1][2]

What drug and active ingredient does US Patent 7,825,137 protect?

US Patent 7,825,137 protects therapeutic use of the compound known as crizotinib.

Field	Details
Active ingredient	Crizotinib
Chemical form in claim 1	(R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine
Brand	Xalkori
Original developer	SUGEN, later acquired by Pfizer
Commercial sponsor	Pfizer
Molecular target	Anaplastic lymphoma kinase, or ALK
Drug class	Small-molecule tyrosine kinase inhibitor
FDA initial approval	August 26, 2011
Primary original indication	ALK-positive metastatic NSCLC
Patent type	Method-of-treatment patent
Patent number	US 7,825,137 B2
Issue date	November 2, 2010
Projected patent expiration	August 2027

Crizotinib inhibits ALK, ROS1, and other kinases. The patent claims, however, are framed around cancer mediated by ALK. The patent does not expressly claim ROS1-driven cancer in the claims provided.

What are the independent and dependent claims in US 7,825,137?

Claim 1 is the controlling independent claim. It requires four principal elements:

1. Administration to a mammal.
2. A therapeutically effective amount of the specified R-enantiomer of crizotinib, or a pharmaceutically acceptable salt.
3. Reversal or inhibition of abnormal cell growth.
4. Cancer mediated by ALK.

The claim is therefore narrower than a composition claim covering all products containing crizotinib. It is also narrower than a compound claim covering the molecule regardless of use.

The dependent claims add patient, target, disease, and formulation limitations.

Claim	Added limitation	Legal significance
1	Administration of crizotinib for ALK-mediated cancer	Core method claim
2	Mammal is a human	Human-treatment limitation
3	Mammal is a dog	Veterinary-treatment limitation
4	ALK is genetically altered	Covers mutation, rearrangement, amplification, or other genetic alteration
5	Cancer is NSCLC, squamous cell carcinoma, hormone-refractory prostate cancer, papillary renal cell carcinoma, colorectal adenocarcinoma, neuroblastoma, ALCL, or gastric cancer	Closed disease list
6	Administration as a pharmaceutical composition with a pharmaceutically acceptable carrier	Formulation-dependent method claim
7	Human patient and genetically altered ALK	Narrow combination of claims 2 and 4

Claim 5 uses “selected from the group consisting of,” which generally creates a closed Markush group. A cancer not listed in claim 5 may fall outside that dependent claim even if it remains within claim 1.

What is the scope of claim 1 of US 7,825,137?

Claim 1 is a use claim directed to the treatment of ALK-mediated cancer with crizotinib. It has both structural and functional limitations.

The structural limitation identifies a specific stereochemical form of crizotinib. The R-configuration matters. A different stereoisomer, racemate, analog, or chemically unrelated ALK inhibitor would not satisfy that limitation solely because it inhibits ALK.

The functional disease limitation requires that the cancer be “mediated by” ALK. A product label or clinical use directed to ALK-positive or ALK-rearranged disease would provide strong evidence that this limitation is met.

The claim does not require:

• A particular dosage.
• A particular dosing schedule.
• A specific route of administration.
• A particular formulation.
• A specific ALK mutation or fusion.
• A response threshold.
• A biomarker testing step.
• Prior failure of another ALK inhibitor.
• Treatment of metastatic disease only.

This breadth gives claim 1 meaningful coverage of physician use, product labeling, and induced-infringement theories involving crizotinib products marketed for ALK-positive cancer.

What cancers are covered by the patent claims?

The claims cover ALK-mediated cancer generally under claim 1. Claim 5 identifies specific cancer types.

Cancer	Expressly listed in claim 5?	Commercial relevance
NSCLC	Yes	Core Xalkori indication
Squamous cell carcinoma	Yes	Covered if ALK-mediated
Hormone-refractory prostate cancer	Yes	Covered if ALK-mediated
Papillary renal cell carcinoma	Yes	Covered if ALK-mediated
Colorectal adenocarcinoma	Yes	Covered if ALK-mediated
Neuroblastoma	Yes	Relevant to pediatric and oncology research
Anaplastic large cell lymphoma	Yes	ALK-positive ALCL is a recognized disease setting
Gastric cancer	Yes	Covered if ALK-mediated
ROS1-positive NSCLC	No express limitation in the listed claims	Not directly identified by claim 5

The patent does not make every cancer listed in claim 5 infringing merely because a patient receives crizotinib. The ALK-mediated limitation remains important. The disease must have a sufficient relationship to ALK.

What does the genetically altered ALK limitation cover?

Claims 4 and 7 require a genetically altered ALK. This language is broader than a single named ALK fusion or mutation.

Potentially relevant alterations include:

• ALK gene rearrangements.
• EML4-ALK fusions.
• Other ALK fusion partners.
• Activating ALK mutations.
• ALK amplification or other activating genetic changes.

The dependent claims do not expressly limit the alteration to EML4-ALK. That breadth is commercially important because the original Xalkori label focused on ALK-positive NSCLC identified through an FDA-approved test, while the claim language can reach a wider range of genetically altered ALK cancers.

What formulation protection does US 7,825,137 provide?

Claim 6 covers a method in which crizotinib is administered in a pharmaceutical composition containing at least one pharmaceutically acceptable carrier.

The formulation claim is limited in several respects:

• It does not identify a particular excipient.
• It does not require a capsule, tablet, solution, suspension, or injectable form.
• It does not require a specific release profile.
• It does not claim a particle size, polymorph, salt form, or manufacturing process.
• It does not independently claim the composition as a product.

As drafted, claim 6 provides method coverage for ordinary pharmaceutical compositions containing crizotinib. It is not a detailed formulation patent of the type that typically protects a specific solid form, excipient system, dissolution profile, or controlled-release technology.

A generic manufacturer could still face claim 6 if it markets a crizotinib composition for an ALK-mediated cancer. The claim would not necessarily reach a composition sold for a non-ALK use unless the ALK-mediated treatment limitation is satisfied.

When does US Patent 7,825,137 lose exclusivity?

The relevant exclusivity dates are different for regulatory exclusivity and patent protection.

Exclusivity right	Date or status
FDA approval	August 26, 2011
Five-year NCE exclusivity	Expired in 2016
Patent term	Projected to expire in August 2027
Patent-linked pediatric exclusivity	May extend regulatory restrictions by six months where applicable
Small-molecule status	No biosimilar pathway applies

The patent’s projected term is more commercially significant than the expired NCE exclusivity. FDA NCE exclusivity prevented submission of an ANDA or 505(b)(2) application for five years, subject to the Paragraph IV exception. After that period, generic applicants could file ANDAs and challenge listed patents.

Patent expiration does not automatically authorize every generic use. A generic applicant may launch under a Paragraph III certification after patent expiration or under a Paragraph IV certification if it defeats the patent or reaches a settlement permitting earlier entry.

What is the Orange Book status of crizotinib?

Xalkori is an FDA-approved small-molecule drug. Its relevant regulatory pathway is an NDA, not a biologics license application.

The Orange Book analysis for crizotinib should distinguish:

• Drug substance patents.
• Method-of-use patents.
• Formulation or solid-form patents.
• Pediatric exclusivity.
• Patent certifications submitted by ANDA applicants.

US 7,825,137 is a method-of-use patent associated with the ALK-directed therapeutic use of crizotinib. Other crizotinib patents may provide separate protection for the compound, compositions, salts, polymorphs, formulations, or additional uses. The existence of this method patent does not establish that it is the only patent listed for Xalkori.

A complete Orange Book determination requires the current FDA patent listing and exclusivity record for the relevant NDA. The patent number, expiration date, and use code should be evaluated against the exact proposed generic labeling.

What other patents are relevant to the crizotinib patent estate?

The crizotinib estate includes more than US 7,825,137. The relevant categories are:

Compound and chemical-entity patents

These patents protect the crizotinib molecule or a broader chemical genus that includes it. They are usually the principal barrier to unrestricted generic launch because they can cover the active ingredient regardless of the selected therapeutic indication.

Method-of-treatment patents

US 7,825,137 is in this category. These patents are narrower than compound claims but can create infringement exposure through product labeling, prescribing instructions, and induced-use theories.

Formulation patents

Potential formulation patents may cover:

• Specific capsule or tablet compositions.
• Salt forms.
• Crystalline forms.
• Particle characteristics.
• Stability systems.
• Release profiles.
• Manufacturing processes.

A generic product that uses the same active ingredient may avoid a particular formulation patent by using different excipients or a different solid form, but it may remain exposed to compound or method claims.

Additional indication patents

Crizotinib has activity against ROS1 and has been used in additional disease settings. A ROS1-specific patent would require separate claim analysis because the claims provided for US 7,825,137 are directed to ALK-mediated cancer.

How strong is the patent estate for crizotinib?

US 7,825,137 has moderate-to-strong practical enforcement value for labeled ALK-positive uses but limited breadth outside those uses.

Strengths

• It identifies the exact marketed R-enantiomer.
• It covers ALK-mediated cancer rather than a single named fusion.
• Claim 1 does not require a specific dose or formulation.
• Claims 2, 4, and 7 align with human treatment and genetically altered ALK disease.
• A generic label for ALK-positive NSCLC would closely track the claim language.

Limitations

• It is not a compound claim.
• It is not a broad claim to all ALK inhibitors.
• It does not expressly cover ROS1-mediated disease.
• Claim 5 is limited to the listed cancers.
• A generic applicant may attempt a skinny label excluding patented ALK indications.
• Infringement depends on the actual use, labeling, marketing, and prescriber behavior.

The patent is strongest when a generic product is labeled for ALK-positive NSCLC or another clearly ALK-mediated cancer. It is weaker as a barrier to a product marketed for a non-ALK indication with a carefully limited label.

Which companies could challenge the crizotinib patents?

Generic companies typically challenge small-molecule oncology patents through ANDA Paragraph IV certifications. The potential challenger must show that the proposed product does not infringe or that the listed patent is invalid or unenforceable.

The main challenge theories are:

• Lack of anticipation.
• Obviousness based on known ALK inhibitors and prior crizotinib disclosures.
• Written-description or enablement challenges.
• Noninfringement based on a carved-out label.
• Noninfringement based on a different indication.
• Invalidity of a formulation or polymorph claim.
• Patent-term or listing challenges.

Publicly reported litigation should be evaluated patent by patent because a challenge to a compound patent has a different commercial effect from a challenge to US 7,825,137. A successful attack on this method patent would not necessarily remove separate compound or formulation patents.

What Paragraph IV risks exist for generic crizotinib?

A Paragraph IV certification asserts that an Orange Book-listed patent is invalid, unenforceable, or will not be infringed by the ANDA product.

For US 7,825,137, the main generic risks are:

1. Induced infringement: The proposed label instructs use of crizotinib for ALK-positive cancer.
2. Method overlap: The label uses language equivalent to “ALK-mediated,” “ALK-positive,” or “genetically altered ALK.”
3. Composition overlap: The generic uses crizotinib with a conventional pharmaceutical carrier.
4. Labeling evidence: Promotional materials or risk-management documents encourage the patented use.
5. Clinical practice: Substantially all foreseeable use is for the patented indication.

A skinny-label strategy can reduce exposure if the generic removes ALK-directed indications and related instructions. That strategy is commercially difficult where ALK-positive cancer is the principal or only commercially meaningful use for the product.

Does crizotinib face biosimilar competition?

No. Crizotinib is a chemically synthesized small molecule, not a biologic. Competitors would file ANDAs or, in some cases, 505(b)(2) applications. The biosimilar pathway under the Public Health Service Act does not apply.

The competitive issue is generic entry, not biosimilar substitution.

How does crizotinib compare with competing ALK inhibitors?

Drug	Company	ALK generation or profile	Key commercial distinction
Crizotinib	Pfizer	First-generation ALK/ROS1 inhibitor	Earlier approval; resistance and CNS limitations
Ceritinib	Novartis	Second-generation ALK inhibitor	Activity after crizotinib resistance; gastrointestinal tolerability concerns
Alectinib	Roche	Second-generation ALK inhibitor	Strong CNS activity and major first-line competitor
Brigatinib	Takeda	Second-generation ALK inhibitor	Broad activity and CNS penetration
Lorlatinib	Pfizer	Third-generation ALK/ROS1 inhibitor	Designed for resistant disease and CNS activity
Ensartinib	Xcovery/partnered commercial interests	Next-generation ALK inhibitor	Competes in ALK-positive NSCLC

The commercial value of US 7,825,137 depends on whether physicians still use crizotinib in first-line treatment, ROS1-positive disease, pediatric disease, or settings where access and tolerability favor it. Later-generation ALK inhibitors reduce the addressable market for a generic crizotinib product but do not remove patent infringement risk for the ALK-labeled use.

What generic launch scenarios are possible?

Launch after patent expiration

The lowest-risk path is launch after expiration of all relevant blocking patents and regulatory exclusivity periods. A generic would still need FDA approval and must comply with any remaining patent-listed restrictions.

Paragraph IV launch

A generic may launch before expiration if it receives approval and successfully defeats the challenged patents, or if the patent holder does not obtain an injunction or other effective relief. This path carries litigation and damages exposure.

Settlement-based launch

A patent settlement may establish an agreed entry date before the latest patent expiration. Settlement terms can include:

• Authorized generic arrangements.
• No-challenge provisions.
• Supply or licensing rights.
• Earlier entry for one applicant.
• Restrictions on launch timing.
• Treatment of pediatric exclusivity.

The commercial entry date cannot be inferred from the expiration date of US 7,825,137 alone.

Skinny-label launch

A generic could omit patented ALK indications if FDA labeling rules and the approved reference labeling permit a lawful carve-out. This strategy is less attractive if ALK-positive cancer represents the principal use of crizotinib.

What geographic coverage does US 7,825,137 provide?

The patent provides rights only in the United States. Equivalent protection may exist in foreign family members, but each jurisdiction has separate:

• Claim scope.
• Patent-term rules.
• Validity standards.
• Supplementary protection certificate or term-extension rules.
• Litigation history.
• Orange Book or national regulatory linkage.

A US patent does not block manufacture, sale, or use outside the United States. It can, however, affect US importation, commercial supply, and manufacturing performed for US distribution.

What manufacturing and IP barriers remain after this patent expires?

Expiration of US 7,825,137 would remove one method-of-use barrier, but generic entry may still depend on:

• Expiration or invalidation of compound patents.
• Crystalline-form or salt patents.
• Formulation patents.
• Manufacturing-process patents.
• FDA approval timing.
• Controlled supply of the active pharmaceutical ingredient.
• Patent rights in export or manufacturing jurisdictions.
• The ability to obtain an acceptable bioequivalence result.

For crizotinib, the central question is whether an applicant can market the active ingredient without infringing separate compound or formulation claims. US 7,825,137 alone does not determine the complete launch date.

What litigation status affects US Patent 7,825,137?

The relevant litigation inquiry is whether an ANDA applicant has:

• Filed a Paragraph IV certification against the patent.
• Triggered the 30-month stay under Hatch-Waxman.
• Reached a settlement with Pfizer.
• Obtained a judgment of invalidity, unenforceability, or noninfringement.
• Received an agreed launch date.

The patent’s commercial status should therefore be determined from the current FDA Orange Book record, ANDA litigation dockets, USPTO records, and any Federal Circuit decisions. A patent number alone does not establish that the patent is enforceable against every generic product or every indication.

Key Takeaways

• US 7,825,137 is a method-of-treatment patent for crizotinib in ALK-mediated cancer.
• Claim 1 covers the specific R-enantiomer of crizotinib, or a pharmaceutically acceptable salt.
• The patent is particularly relevant to ALK-positive and genetically altered ALK cancers.
• Claims 2 and 7 focus on human treatment; claim 3 covers dogs.
• Claim 5 lists eight cancer categories but does not eliminate the ALK-mediated limitation.
• Claim 6 provides broad carrier-based pharmaceutical-composition coverage but is not a detailed formulation claim.
• The patent is not a biosimilar matter because crizotinib is a small molecule.
• NCE exclusivity expired in 2016.
• The projected patent term extends into August 2027.
• Generic risk is highest for an ANDA labeled for ALK-positive NSCLC or another ALK-driven cancer.
• The complete launch analysis requires review of the separate crizotinib compound, formulation, solid-form, and additional-use patents.

FAQs About US Patent 7,825,137 and Crizotinib

Does US 7,825,137 claim crizotinib itself?

No. The claims provided are method claims. They require administering crizotinib to treat ALK-mediated cancer. Separate patents may claim the compound or related chemical forms.

Does the patent cover crizotinib for ROS1-positive cancer?

The provided claims do not expressly recite ROS1-mediated cancer. A separate patent or claim set would be needed to assess ROS1 use.

Can a generic launch before August 2027?

Yes, potentially through a successful Paragraph IV challenge, a settlement with an agreed entry date, or a lawful label carve-out. The patent expiration date alone does not establish the earliest available launch date.

Does claim 5 cover every listed cancer automatically?

No. The cancer must still be mediated by ALK. The dependent claim narrows claim 1 to the specified cancer categories.

Is a crizotinib capsule covered by claim 6?

It can be, if the capsule is administered as part of a method that satisfies the ALK-mediated cancer limitations. Claim 6 does not independently claim every crizotinib capsule as a product.

References

1. U.S. Patent No. 7,825,137 B2. (2010). Methods of treating cancer using (R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2011). FDA approves Xalkori for late-stage lung cancer. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (2023). Xalkori (crizotinib) prescribing information. Pfizer Laboratories.

5. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation resources. USPTO.

6. Pfizer Inc. (2011). Pfizer receives FDA approval for Xalkori (crizotinib) capsules for patients with late-stage ALK-positive lung cancer. Pfizer.

Drugs Protected by US Patent 7,825,137

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pf Prism Cv	XALKORI	crizotinib	CAPSULE, PELLETS;ORAL	217581-001	Sep 7, 2023		RX	Yes	No	7,825,137					TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
Pf Prism Cv	XALKORI	crizotinib	CAPSULE, PELLETS;ORAL	217581-001	Sep 7, 2023		RX	Yes	No	7,825,137					METHOD OF REVERSING OR INHIBITING THE PROGRESS OF UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE IN ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
Pf Prism Cv	XALKORI	crizotinib	CAPSULE, PELLETS;ORAL	217581-001	Sep 7, 2023		RX	Yes	No	7,825,137					TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE

Foreign Priority and PCT Information for Patent: 7,825,137

PCT Information
PCT Filed	November 23, 2006	PCT Application Number:	PCT/IB2006/003397
PCT Publication Date:	June 14, 2007	PCT Publication Number:	WO2007/066187

International Family Members for US Patent 7,825,137

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	056832
Argentina	099982
Austria	E488237