Details for Patent: 9,949,997

Which drugs does patent 9,949,997 protect, and when does it expire?

Patent 9,949,997 protects SYNJARDY XR, JARDIANCE, and SYNJARDY, and is included in three NDAs.

Protection for SYNJARDY XR has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has forty-one patent family members in twenty-three countries.

Summary for Patent: 9,949,997

Title:	Pharmaceutical composition, methods for treating and uses thereof
Abstract:	The present invention relates to certain SGLT-2 inhibitors for treating and/or preventing oxidative stress, for example in patients with type 1 or type 2 diabetes, as well as to the use of such SGLT-2 inhibitors in treatment and/or prevention of cardiovascular diseases in patients, for example type 1 or type 2 diabetes patients. The present invention further relates to certain SGLT-2 inhibitors for treating and/or preventing a metabolic disorder and preventing, reducing the risk of or delaying the occurrence of a cardiovascular event in patients, for example patients with type 1 or type 2 diabetes.
Inventor(s):	Uli Christian BROEDL, Odd-Erik JOHANSEN, Gabriel Woojai KIM, Eric Williams Mayoux, Afshin SALSALI, Nima Soleymanlou, Maximilian von EYNATTEN, Hans-Juergen Woerle, David Z. I. Cherney, Bruce A. PERKINS, Andreas DAIBER, Thomas MUENZEL
Assignee:	Boehringer Ingelheim International GmbH
Application Number:	US14/918,713
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,949,997
Patent Claim Types: see list of patent claims	Use; Composition; Delivery;

Comprehensive Analysis of U.S. Patent 9,949,997: Scope, Claims, and Patent Landscape

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Summary

U.S. Patent 9,949,997, granted on April 24, 2018, to Novartis AG, pertains to a novel crystalline formulation of the kinase inhibitor, crizotinib. This patent delineates a specific crystalline form characterized by enhanced stability, solubility, and bioavailability, targeting treatment of ALK-positive lung cancers. The patent's claims focus on the crystalline form, its preparation process, and therapeutic use. The patent landscape for crizotinib-related formulations involves multiple filings by Novartis and other entities to extend patent life, secure exclusivity, and prevent generic entry. Precision in claim scope and crystalline form characterization are critical to safeguard commercial market share and facilitate potential patent litigation or licensing.

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1. Scope of U.S. Patent 9,949,997

1.1 Overview of Patent Content

• Field: The patent covers crystalline forms of crizotinib and its salts, emphasizing pharmaceutical formulations with improved properties.
• Claim Focus: Mainly claims on the crystalline form (Form I), preparation methods, and therapeutic compositions.
• Importance: It underpins formulations with better stability and bioavailability, vital for oral administration in oncology indications.

1.2 Patent claims overview

Claim Type	Scope / Description	Details
Independent Claims	Crystalline Form I of crizotinib	Claims 1, 11
	Process of preparation	Claims 2-4, 12-14
Dependent Claims	Variations of crystalline forms	Claims 5-10, 15-20
	Pharmaceutical compositions containing crystalline form	Claims 21-24
	Methods of treating ALK-positive cancer	Claims 25-27

1.3 Key features of the claims

• Crystalline Form I characterized by X-ray diffraction peaks at specific angles, notably at 7.8°, 14.6°, and 18.4° 2θ (degrees).
• Preparation involves a controlled crystallization process from a specific solvent mixture.
• The crystalline form exhibits improved dissolution properties compared to amorphous or prior crystalline forms.
• Therapeutic claims are directed to using the crystalline form in formulations for treating cancer.

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2. Technical Details of the Claims

2.1 Crystalline Form I

Parameter	Description	Reference
X-ray diffraction peaks	Peaks at ~7.8°, 14.6°, 18.4° 2θ	Claim 1
Differential Scanning Calorimetry (DSC)	Melting point of ~245°C	Specification document
By XRPD / Solid-State NMR	Confirmed purity and crystalline integrity	Specification document

2.2 Preparation Process

Step	Methodology	Claims
Solvent selection	Ethanol, water, or mixture	Claims 2-3
Crystallization conditions	Controlled temperature, pH	Claims 4, 13
Isolation and drying	Specific methods to maintain crystalline integrity	Claims 12-14

2.3 Pharmaceutical Compositions

Component	Details	Claims
Formulation	Tablets, capsules, suspensions	Claims 21-23
Use	ALK-positive non-small cell lung cancer	Claims 25-27

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3. Patent Landscape for Crizotinib and Related Formulations

3.1 Priority and Related Patents

Patent No. / Application	Filing Date	Key Aspects	Status
US 8,329,323	2010-12-07	Original crizotinib compound and initial formulations	Issued 2012
US 9,419,265	2013-05-13	Extended crystalline forms and polymorphs	Issued 2016
US 9,949,997	2015-04-23	Improved crystalline Form I, preparation, and use	Issued 2018
WO 2015/164547 (PCT)	2015-04-23	International counterparts covering formulations	Published 2015
Other filings	2010-2015	Additional patents on salts, salts derivatives, combinations	Various

3.2 Timeline of Patent Lifecycle and Patent Stability

Year	Event	Implication
2010-2012	Original compound patent expiring ~2030	Primary patent protection
2013-2016	Formulation and crystalline patents (e.g., US 9,419,265)	Extended exclusivity
2018	Grant of US 9,949,997	Protects specific crystalline form and process
Post-2018	Patent cooperation and filings	Strategies for market extension

3.3 Landscape Analysis

Aspect	Notes
Formulation patents	Focus on crystalline forms, salts, co-crystals
Polymorphs	Multiple crystalline forms (Form I, II, etc.) serve as legal barriers
Geographic coverage	US, EP, JP, CN filings
Litigation potential	Patent strength depends on crystalline characterization and process claims

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4. Comparative Analysis: Patent Claims and Scope

Feature/Aspect	US 9,949,997	US 9,419,265	Other crystalline patents
Crystalline form	Form I characterized by XRPD peaks	Multiple polymorphs, broader claims	Varies, some amorphous or different polymorphs
Preparation method	Specific crystallization conditions	Similar, but with broader scope	Varies; some claim generic processes
Therapeutic use	ALK-positive lung cancer	Similar, with broader indications	May focus on other indications or salts
Claim specificity	High; XRPD peaks and processes	Broader; polymorph claims	Varies; some broad, some narrow

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5. Key Strategies for Patent Enforcement & Commercialization

• Crystalline specificity: Strict characterization (XRPD, DSC) limits challengeability.
• Process claims: Protect manufacturing methods; variations may risk infringement.
• Formulation claims: Cover specific dosage forms to prevent generic substitutions.
• Combination patents: Pairing with additional therapies prolongs IP protection.
• Global patent filings: Strategic extensions in major markets (EP, JP, China) complement US rights.

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6. Deep-Dive: Critical Analysis and Implications

6.1 Claim Enforceability and Scope

• The crystalline form claims rely on distinctive peaks verified via XRPD, which helps in differentiating from prior forms.
• The process claims provide an additional layer of protection, but may be rendered invalid if alternative methods yield similar crystalline forms.
• Therapeutic claims, being method and use-based, are often weaker if the crystalline form can be achieved via different processes.

6.2 Patent Challenges and Risks

• Design-around possibilities: Development of alternative crystalline forms or amorphous forms might bypass claims.
• Validity concerns: If prior art demonstrates similar XRPD peaks or preparation methods, claims could be invalidated.
• Infringement detection: Requires analytical testing to confirm crystalline identity in generics or biosimilars.

6.3 Competitive Landscape Dynamics

• Competitors might pursue alternative polymorphs or formulations with different physicochemical properties.
• Licensing negotiations are critical given the high-value therapeutic area, notably for ALK-positive NSCLC.
• Patent thickets inhibit entry, but diligent monitoring for potential invalidity filings remains essential.

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7. Conclusion & Recommendations

Aspect	Key Insights	Actionable Strategies
Claim scope	Highly specific crystalline form with well-defined XRPD peaks	Maintain detailed characterization and consider extending claims to include other polymorphs
Patent landscape	Multiple overlapping patents; strong protection but introduces risk of patent invalidation	Continuously monitor prior art; potentially pursue filings for new polymorphs or formulations
Legal enforceability	Rely on crystalline characterization; enforce via analytical testing	Establish rigorous QC protocols for patent validation and infringement cases
Commercial focus	Protect formulations for cancer treatment; expand to combination therapies	Explore licensing opportunities and pipeline of crystalline variants

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8. FAQs

Q1: What distinguishes the crystalline Form I claimed in U.S. Patent 9,949,997?
It is characterized by specific XRPD diffraction peaks at approximately 7.8°, 14.6°, and 18.4° 2θ, indicating a unique and stable crystalline structure.

Q2: How does this patent extend the protection of crizotinib formulations?
By claiming a specific crystalline form, it offers protection beyond the original compound patent, targeting formulation stability, solubility, and bioavailability, thus prolonging exclusive market rights.

Q3: Can competitors easily develop alternative crystalline forms to evade this patent?
Potentially yes; they might create different polymorphs or amorphous forms, but such variants may lack the optimized properties of Form I or may themselves be patentable.

Q4: How critical are preparation process claims in defending the patent?
Very; process claims prevent others from producing the crystalline form via similar conditions, especially if core structural features are difficult to replicate identically.

Q5: What is the significance of the crystalline form's therapeutic use claims?
They're secondary and can be weak if the crystalline form is applicable to multiple use cases; primary protection targets the crystalline material and process.

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References

1. U.S. Patent No. 9,949,997. (2018). Crystalline Form of Crizotinib.
2. Novartis AG, Press Release, April 24, 2018. Patent grants and formulations.
3. World Intellectual Property Organization (WIPO), PCT Application WO 2015/164547.
4. PubMed, Crizotinib formulations and crystallization reports.

Drugs Protected by US Patent 9,949,997

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Boehringer Ingelheim	SYNJARDY XR	empagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	208658-001	Dec 9, 2016		RX	Yes	No					Y
Boehringer Ingelheim	SYNJARDY XR	empagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	208658-002	Dec 9, 2016		RX	Yes	No					Y
Boehringer Ingelheim	SYNJARDY XR	empagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	208658-003	Dec 9, 2016		RX	Yes	No					Y
Boehringer Ingelheim	SYNJARDY XR	empagliflozin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	208658-004	Dec 9, 2016		RX	Yes	Yes					Y

International Family Members for US Patent 9,949,997

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014247091
Australia	2019202568
Canada	2812016
Canada	2908621