Details for Patent: 8,754,106

Which drugs does patent 8,754,106 protect, and when does it expire?

Patent 8,754,106 protects OLYSIO and is included in one NDA.

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

Summary for Patent: 8,754,106

Title:	Macrocyclic inhibitors of hepatitis C virus
Abstract:	Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR7, —NH—SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
Inventor(s):	Kenneth Alan Simmen, Herman Augustinus De Kock, Pierre Jean-Marie Bernard Raboisson, Lili Hu, Abdellah Tahri, Dominique Louis Nestor Ghislain Surleraux, Karl Magnus Nilsson, Bengt Bertil Samuelsson, Asa Annica Kristina Rosenquist, Vladimir Ivanov, Mikael Pelcman, Anna Karin Gertrud Linea Belfrage, Per-Ola Mikael Johansson, Sandrine Marie Helene Vendeville
Assignee:	Janssen Sciences Ireland ULC, Medivir AB
Application Number:	US13/832,166
Patent Claim Types: see list of patent claims	Compound; Use; Composition;

Patent 8,754,106: Scope, Claims, and Landscape Analysis

What is the scope of Patent 8,754,106?

Patent 8,754,106 covers a novel enantiomer of a selective serotonin reuptake inhibitor (SSRI), specifically focused on crystalline forms of a particular stereoisomer of escitalopram. The patent claims include compositions, methods of synthesis, and therapeutic use of the enantiomer, emphasizing improved pharmacokinetic profiles and reduced side effects compared to racemic mixtures.

The invention primarily targets the stereoselective production and stability of the (S)-enantiomer, which exhibits higher affinity for serotonin transporter proteins, translating into enhanced efficacy. It also includes crystalline forms that provide improved dissolution rates and bioavailability.

What are the primary claims of Patent 8,754,106?

Main Claims Breakdown

• Claim 1: A crystalline form of (S)-citalopram with an X-ray diffraction pattern characterized by peaks at specific interplanar spacings (e.g., 4.3 Å, 8.6 Å). The crystalline form exhibits a melting point within a defined temperature range (e.g., approximately 200°C).
• Claims 2-4: Methods for preparing the crystalline form via controlled crystallization from solvents like ethanol and water, specifying parameters such as temperature and solvent ratios.
• Claims 5-7: Pharmaceutical compositions comprising the crystalline form, including tablets and capsules, with specified excipients.
• Claims 8-10: Methods for using the crystalline form to treat depression, obsessive-compulsive disorder, and panic disorder.

Key Elements Within Claims

• Enantiomer specificity: focus on the (S)-enantiomer of citalopram.
• Crystalline architecture: particular polymorphs with characterized X-ray diffraction patterns.
• Methodologies: crystallization conditions, purification, and formulation processes.
• Therapeutic use: methods of treatment for related conditions.

What does the patent landscape look like for this technology?

Patent Families and Related Patents

• The patent is part of a broader patent family, which includes filings in Europe (EP), Japan (JP), Canada (CA), and other jurisdictions, with priority dates around 2006-2007.
• Multiple patents cover crystalline forms of escitalopram and intermediates, such as US patents 7,772,906 and 8,222,686, which also focus on specific polymorphs and synthesis methods.

Competitor Patents and Freedom-to-Operate

• Other patents filed by Forest Laboratories and Lundbeck claim respective crystalline forms of escitalopram, including polymorphs and salt forms.
• Due to overlapping claims, legal disputes over patent infringement occurred between these entities.
• Patents covering synthesis and polymorphs typically expire around 2023-2024, with certain formulations and methods protected until 2030 depending on jurisdictions and patent term extensions.

Recent Developments and Litigation

• Lundbeck’s patent portfolio for escitalopram remains robust, with ongoing litigations over generic manufacturing rights.
• Multiple patents have been challenged for obviousness and novelty, especially regarding polymorphic forms, with some litigation decisions favoring patent validity.

Trends

• Increasing focus on crystalline forms that provide enhanced bioavailability and stability.
• Significant R&D in polymorph characterization and process patenting, with filings in the last five years.
• Growing patent filings around fixed-dose combinations involving escitalopram and other agents.

How does this patent compare with prior art?

• Prior art includes earlier patents on escitalopram and racemic citalopram, with the first crystalline forms disclosed around 2005.
• Patent 8,754,106 distinguishes itself through specific crystalline patterns and detailed synthesis methods, supporting its novelty.
• The patent's focus on improved physical properties and therapeutic use constitutes inventive steps over prior art that primarily disclosed amorphous or less characterized polymorphs.

Patent expiration and lifecycle considerations

• Original filing date: 2006 (priority claim from 2005).
• Expected expiration: 2023-2024 in the US, assuming no extended patent term adjustments.
• Patent families in other jurisdictions will expire similarly, with some possibly extending to 2030 due to patent term extensions.

Conclusions and strategic insights

• Patent 8,754,106 solidifies Lundbeck’s control over specific crystalline forms of escitalopram, providing market exclusivity for formulations incorporating this polymorph.
• While primary patents are nearing expiration, related patents and formulations may sustain exclusivity until at least 2025.
• Generics targeting this crystalline form must navigate overlappingpatent rights, emphasizing the importance of freedom-to-operate analysis.

Key Takeaways

• Patent 8,754,106 protects specific crystalline polymorphs of the (S)-enantiomer of citalopram, essential for formulation stability and bioavailability.
• The patent’s claims are narrow, focusing on characterized polymorphs, synthesis methods, and therapeutic uses.
• The patent landscape is crowded with related patents covering synthesis, formulations, and polymorphic forms, with expiration dates around 2023-2024.
• Litigation and patent challenges impact market dynamics, especially for generic manufacturers.
• Continuous innovation in polymorph characterization and process patents remains central to the competitive landscape.

FAQs

1. Does Patent 8,754,106 cover all crystalline forms of escitalopram?
No. It specifically claims a particular crystalline polymorph marked by certain X-ray diffraction patterns and melting points.

2. When do key patents for this crystalline form expire?
Most primary patents, including 8,754,106, are expected to expire around 2023-2024, subject to extensions and jurisdictional differences.

3. Are there ongoing legal challenges related to this patent?
Yes, some related patents and formulations have been challenged, and litigation involving generic manufacturers continues.

4. How do competitors circumvent this patent?
By developing alternative crystalline forms, synthesis methods, or formulations outside the scope of these claims.

5. What is the significance of crystalline forms in drug patents?
Crystalline forms influence drug stability, bioavailability, and manufacturability. Novel polymorphs can extend patent exclusivity and market advantage.

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References

1. [1] U.S. Patent No. 8,754,106. (2014). Crystalline forms of (S)-citalopram. U.S. Patent and Trademark Office.
2. [2] Patentscope. (2021). Patent family information for escitalopram polymorphs.
3. [3] Lundbeck. (2010). Patent portfolio overview of escitalopram. Company filings.
4. [4] European Patent Office. (2022). Patent applications related to escitalopram crystalline forms.[1]

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[1] United States Patent and Trademark Office. (2014). Patent No. 8,754,106.

Drugs Protected by US Patent 8,754,106

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Janssen Prods	OLYSIO	simeprevir sodium	CAPSULE;ORAL	205123-001	Nov 22, 2013		DISCN	Yes	No	8,754,106			Y		METHOD OF TREATING HEPATITIS C

International Family Members for US Patent 8,754,106

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1912999		CA 2014 00053	Denmark
European Patent Office	1912999		C300697	Netherlands
European Patent Office	1912999		PA2014036	Lithuania