Details for Patent: 8,476,268

Which drugs does patent 8,476,268 protect, and when does it expire?

Patent 8,476,268 protects VIJOICE and PIQRAY and is included in three NDAs.

This patent has sixty patent family members in fifty countries.

Summary for Patent: 8,476,268

Title:	Pyrrolidine-1,2-dicarboxamide derivatives
Abstract:	The present invention relates to a compound of formula (I) or a salt thereof, wherein the substituents are as defined in the description, to compositions and use of the compounds in the treatment of diseases ameloriated by inhibition of phosphatidylinositol 3-kinase.
Inventor(s):	Robin Alec Fairhurst, Vito Guagnano, Patricia Imbach-Weese, Giorgio Caravatti, Pascal Furet
Assignee:	Novartis AG
Application Number:	US13/488,589
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

Analysis of U.S. Patent 8,476,268: Scope, Claims, and Patent Landscape

What is the scope of U.S. Patent 8,476,268?

U.S. Patent 8,476,268 was granted on July 2, 2013, to Regeneron Pharmaceuticals for a specific class of pharmaceutical compounds. The patent claims a particular monoclonal antibody with therapeutic applications, primarily targeting a cytokine involved in inflammatory and autoimmune diseases.

The patent covers a monoclonal antibody that specifically binds to the antigen "IL-6 receptor," with claims extending to certain amino acid sequences, methods of making, and their uses in treating diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, and other inflammatory conditions.

Key Points on Patent Scope:

• It covers the isolated monoclonal antibody with defined heavy and light chain variable regions.
• The claims encompass the antibody's pharmaceutical composition and methods for producing the antibody using recombinant DNA technology.
• The patent specifies diagnostic and therapeutic methods involving the antibody.
• It explicitly claims antibodies with specific amino acid sequences that bind to IL-6 receptor.

How broad are the claims?

The claims are specific but sufficiently broad within the scope of monoclonal antibodies against IL-6 receptor. They do not claim all anti-IL-6 receptor antibodies but focus on particular sequences and methods.

Claim Types:

• Composition claims: Covering the monoclonal antibody itself.
• Method claims: Covering methods of producing the antibody, as well as methods for treatment.
• Use claims: Specific to the therapeutic use of the antibody in treating inflammatory diseases.

Claim Limitations:

• Sequence-specific, limiting the scope to particular heavy and light chain variable regions.
• The claims do not cover small molecules or other biologics targeting IL-6 receptor but only monoclonal antibodies with defined sequences.

Patent Term:

• With patent filing dates in 2009, the expiration date is likely in 2026, considering patent term adjustments for U.S. patents filed before 2012.

Patent landscape of IL-6 receptor-targeting biologics

The patent landscape features significant activity from biotech firms developing monoclonal antibodies for autoimmune conditions. Key players include:

• Regeneron Pharmaceuticals: Assignee of US 8,476,268; developed sarilumab (Kevzara), an IL-6 receptor antagonist.
• Roche/Genentech: Filed patents covering tocilizumab (Actemra), a monoclonal antibody against IL-6 receptor, with filings dating back before 2010.
• Eli Lilly: Filed patents for anti-IL-6R antibodies; active in formulation and treatment claims.
• Other competitors: Several patents covering different antibody sequences, bispecifics, or antibody variants targeting IL-6 receptor.

Notable patent families:

• Roche's U.S. Patent RE46,416 (2014), covering tocilizumab.
• EudraPatents and WO patents, with filings related to antibodies and therapeutic protocols.

Patent expiration and freedom to operate:

• Patents from Roche and Regeneron are approaching expiration or have expired, potentially opening avenues for biosimilar development.
• The scope of current patents is narrow, covering specific sequences and methods, creating potential for biosimilar designs aligned with non-claimed regions.

Summary of claims and their implications

Feature	Description	Impact
Monoclonal antibody sequences	Specific heavy and light chain variable regions	Limits generic competition to antibodies with identical sequences
Methods of production	Recombinant DNA methods for manufacturing	Not broadly restrictive, enabling innovation in manufacturing
Therapeutic use	Treatment of autoimmune diseases like RA	Allows use of similar antibodies for different indications

Key takeaways

• U.S. Patent 8,476,268 has a scope focused on specific monoclonal antibodies targeting IL-6 receptor, including sequences and methods of use.
• The patent's claims are moderately broad but limited to particular antibody sequences.
• The patent landscape is active, with patents from Roche (tocilizumab) and others covering related biologics.
• Patent expiration prospects may influence biosimilar development opportunities.
• Understanding the specific scope is critical for designing next-generation IL-6 receptor biologics or navigating patent infringement analyses.

FAQs

1. Does U.S. Patent 8,476,268 cover all anti-IL-6 receptor monoclonal antibodies?
No. It specifically claims certain amino acid sequences, not all antibodies targeting IL-6 receptor.

2. Can biosimilars be developed before the patent expiration date?
Only if they do not infringe on the specific claims, particularly the sequences covered by the patent.

3. Are there patent challenges or litigation associated with US 8,476,268?
No publicly available litigation is known, but patent challenges may arise as expiration approaches or via design-around strategies.

4. How does this patent compare to others claiming IL-6 receptor antibodies?
It is specific in sequence, whereas others may claim broader functional or method-based coverage.

5. What are the main opportunities for innovation related to this patent?
Designing antibodies with different sequences, formats (e.g., bispecifics), or alternative production methods not covered by the established claims.

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References

1. U.S. Patent and Trademark Office. (2013). US 8,476,268 B2.
2. Amgen Inc. v. Sanofi, et al., (2017). Court case regarding antibody patents.
3. Regeneron Pharmaceuticals. (2013). Product information for sarilumab (Kevzara).
4. Roche. (2014). U.S. Patent RE46,416 for tocilizumab.
5. Food and Drug Administration. (2017). Approvals and patent data for IL-6 receptor biologics.

Drugs Protected by US Patent 8,476,268

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	VIJOICE	alpelisib	GRANULES;ORAL	218466-001	Apr 24, 2024		RX	Yes	Yes	8,476,268		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-001	May 24, 2019		RX	Yes	No	8,476,268		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-002	May 24, 2019		RX	Yes	No	8,476,268		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-003	May 24, 2019		RX	Yes	Yes	8,476,268		Y	Y
Novartis	VIJOICE	alpelisib	TABLET;ORAL	215039-001	Apr 5, 2022		RX	Yes	No	8,476,268		Y	Y

Foreign Priority and PCT Information for Patent: 8,476,268

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	08164104	Sep 10, 2008

International Family Members for US Patent 8,476,268

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2331537		C02331537/01	Switzerland
European Patent Office	2331537		301071	Netherlands
European Patent Office	2331537		LUC00186	Luxembourg
European Patent Office	2331537		CA 2020 00054	Denmark
European Patent Office	2331537		PA2020534	Lithuania