Details for Patent: 10,420,749

Which drugs does patent 10,420,749 protect, and when does it expire?

Patent 10,420,749 protects LORBRENA and is included in one NDA.

This patent has thirty-five patent family members in twenty-two countries.

Summary for Patent: 10,420,749

Title:	Crystalline form of lorlatinib free base
Abstract:	This invention relates to a crystalline form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-5-oxo-10,15,16,17-tetrahydro-2H- -8,4-(metheno)pyrazolo[4,3-h] [2,5,11]benzoxadiazacyclo-tetradecine-3-carbonitrile (lorlatinib) free base (Form 7). This invention also relates to pharmaceutical compositions comprising Form 7, and to methods of using Form 7 and such compositions in the treatment of abnormal cell growth, such as cancer, in a mammal.
Inventor(s):	Pencheva; Klimentina Dimitrova (Sandwich, GB), Birch; Melissa J. (Sandwich, GB)
Assignee:	Pfizer Inc. (New York, NY)
Application Number:	15/743,894
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

United States Patent 10,420,749: A Detailed Analysis of Scope, Claims, and Patent Landscape

Introduction

United States Patent 10,420,749, titled "Crystalline form of lorlatinib free base," is a significant patent in the pharmaceutical industry, particularly in the treatment of certain types of cancer. This patent, owned by Pfizer Inc., pertains to the crystalline forms of lorlatinib, a potent inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1).

Background of Lorlatinib

Lorlatinib, marketed under the brand names Lorbrena and Lorviqua, is approved for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC)[4].

Patent Scope and Claims

Crystalline Forms

The patent describes several novel crystalline forms of lorlatinib, including Form 7, which is a specific anhydrous crystalline form of lorlatinib free base. These forms are characterized by their unique solid-state nuclear magnetic resonance (NMR) spectra and powder X-ray diffraction (XRD) patterns[1][4].

Characterization

• The patent includes detailed descriptions of the NMR spectra, specifically the ({}^{13})C and ({}^{19})F solid-state NMR spectra, which are crucial for identifying the crystalline forms of lorlatinib. For example, the ({}^{13})C solid-state NMR spectrum of Form 7 includes specific resonance values listed in the patent[1].
• The XRD patterns are also provided to distinguish between different crystalline forms.

Pharmaceutical Compositions

The patent covers pharmaceutical compositions comprising lorlatinib free base (Form 7) and a pharmaceutically acceptable carrier or excipient. These compositions are formulated for various routes of administration, ensuring the drug's efficacy and stability[1][4].

Methods of Treatment

Therapeutic Use

The patent outlines methods for treating abnormal cell growth in mammals, including humans, by administering a therapeutically effective amount of lorlatinib free base (Form 7) or a pharmaceutical composition containing it. This is particularly relevant for treating ALK-positive NSCLC and other cancers where ALK or ROS1 mutations are present[1][4].

Patent Landscape

Patent Protection

The patent is one of several filed by Pfizer Inc. to protect lorlatinib. As of the latest updates, none of the patents related to lorlatinib have expired, ensuring continued protection for the drug until the patents' expiration dates[2].

Regulatory Compliance

The patent information must be submitted to the FDA for listing in the Orange Book, which is a critical step for innovator companies to protect their intellectual property and prevent generic versions of the drug from entering the market prematurely. Failure to list the patents in a timely manner can result in the loss of certain legal protections, such as the automatic 30-month stay of a generic drug's application[5].

Patent Claims and Scope Metrics

Claim Language and Scope

The scope of the patent claims is a crucial aspect of patent quality. Metrics such as independent claim length and independent claim count can be used to measure patent scope. Narrower claims, as seen in this patent, are often associated with a higher probability of grant and a shorter examination process[3].

Examination Process

The examination process for this patent likely involved a detailed review of the claim language to ensure clarity and specificity. The patent office tends to narrow the scope of patent claims during the examination process, which can result in more defined and enforceable patents[3].

Industrial and Clinical Significance

Treatment of NSCLC

Lorlatinib's efficacy in treating ALK-positive NSCLC has been clinically validated, making it a significant therapeutic option for patients with this specific mutation. The crystalline forms described in the patent ensure the drug's stability and bioavailability, which are critical for its therapeutic effectiveness[4].

Competitive Landscape

The patent landscape for lorlatinib is complex, with multiple patents protecting different aspects of the drug, including its crystalline forms and pharmaceutical compositions. This extensive patent protection helps Pfizer maintain its market position and prevents early generic competition[2].

Key Takeaways

• Crystalline Forms: The patent describes novel crystalline forms of lorlatinib, including Form 7, characterized by specific NMR spectra and XRD patterns.
• Pharmaceutical Compositions: The patent covers pharmaceutical compositions of lorlatinib free base and its use in treating ALK-positive NSCLC.
• Patent Protection: The patent is part of a broader set of patents protecting lorlatinib, ensuring continued market exclusivity.
• Regulatory Compliance: Timely listing of patent information in the Orange Book is crucial for maintaining legal protections against generic competition.
• Clinical Significance: Lorlatinib is a clinically validated treatment for ALK-positive NSCLC, with the described crystalline forms ensuring its stability and efficacy.

FAQs

What is the primary use of lorlatinib as described in the patent?

Lorlatinib is primarily used for treating abnormal cell growth in mammals, particularly in the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC)[1].

How are the crystalline forms of lorlatinib characterized in the patent?

The crystalline forms are characterized by their ({}^{13})C and ({}^{19})F solid-state NMR spectra and powder X-ray diffraction (XRD) patterns[1].

What is the significance of listing patent information in the Orange Book?

Listing patent information in the Orange Book is crucial for innovator companies to protect their intellectual property and prevent generic versions of the drug from entering the market prematurely. It also allows for an automatic 30-month stay of a generic drug's application if a patent infringement dispute arises[5].

How long is the patent protection for lorlatinib expected to last?

As of the latest updates, none of the patents related to lorlatinib have expired, and they continue to protect the drug until their respective expiration dates[2].

What metrics are used to measure the scope of patent claims?

Metrics such as independent claim length and independent claim count are used to measure patent scope. Narrower claims are often associated with a higher probability of grant and a shorter examination process[3].

Cited Sources:

1. US10420749B2 - Crystalline form of lorlatinib free base - Google Patents
2. Lorbrena patent expiration - Pharsight - GreyB
3. Patent Claims and Patent Scope - Hoover Institution
4. Novel polymorphs of Lorlatinib and their processes for the preparation - Defensive Publications Series
5. In the United States District Court - District of Delaware

Drugs Protected by US Patent 10,420,749

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pfizer	LORBRENA	lorlatinib	TABLET;ORAL	210868-001	Nov 2, 2018		RX	Yes	No			Y	Y		TREATMENT OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER, PROGRESSED ON: CRIZOTINIB + AT LEAST 1 OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB, OR CERITINIB AS FIRST ALK INHIBITOR FOR METASTATIC DISEASE.
Pfizer	LORBRENA	lorlatinib	TABLET;ORAL	210868-001	Nov 2, 2018		RX	Yes	No			Y	Y		TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST
Pfizer	LORBRENA	lorlatinib	TABLET;ORAL	210868-002	Nov 2, 2018		RX	Yes	Yes			Y	Y		TREATMENT OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER, PROGRESSED ON: CRIZOTINIB + AT LEAST 1 OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB, OR CERITINIB AS FIRST ALK INHIBITOR FOR METASTATIC DISEASE.
Pfizer	LORBRENA	lorlatinib	TABLET;ORAL	210868-002	Nov 2, 2018		RX	Yes	Yes			Y	Y		TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST

Foreign Priority and PCT Information for Patent: 10,420,749

PCT Information
PCT Filed	July 27, 2016	PCT Application Number:	PCT/IB2016/054483
PCT Publication Date:	February 09, 2017	PCT Publication Number:	WO2017/021823

International Family Members for US Patent 10,420,749

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	105507
Australia	2016304420
Brazil	112017028604
Canada	2937257
China	107849060